Abstract: Kiwifruit, a perennial horticultural crop known for its nutritional value, faces significant challenges due to biotic and abiotic stresses, affecting its yield and quality. Leucine-rich repeat receptor-like proteins (LRR-RLPs), a major group of receptor-like proteins in plants, have diverse functions in plant physiology, including growth, development, signal transduction, and stress responses. Despite their importance, the specific roles of kiwifruit LRR-RLPs in response to biotic and abiotic stresses remain poorly understood. In this study, we investigated the expression patterns of kiwifruit LRR-RLPs under various stress conditions, including pathogen stress, heat stress, waterlogging stress, and copper stress. Through genome and transcriptome analyses, we identified a total of 101, 164, and 105 LRR-RLPs in Actinidia Chinensis 'Hongyang', Actinidia eriantha 'Huate', and Actinidia chinensis 'Red5' kiwifruit, respectively, classified into 9 subgroups based on phylogenetic relationships. Synteny analysis revealed that the expansion of kiwifruit LRR-RLPs was primarily attributed to segmental duplication events. Using RNA-seq data from pathogen-infected kiwifruits, we identified specific LRR-RLP genes potentially involved in different stages of pathogen infection. Additionally, we observed the potential involvement of kiwifruit LRR-RLPs in abiotic stress responses, with upstream transcription factors possibly regulating their expression. Furthermore, protein interaction network analysis unveiled the participation of kiwifruit LRR-RLP genes in the regulatory network of abiotic stress responses. These findings highlight the crucial roles of LRR-RLPs in mediating both biotic and abiotic stress responses in kiwifruit, offering valuable insights for the breeding of stress-resistant kiwifruit varieties.

Off-grid electrification planning increasingly recognizes the importance of productive use of electricity (PUE) to promote community value creation and (financial) project sustainability. To ensure a sustainable and efficient integration in the community and energy system, PUE assets must carefully be evaluated to match both the community needs and the residential electricity demand patterns. We propose a novel methodology interlinking qualitative interviews, statistical analysis, and energy system modelling to optimize decision-making for PUE integration in off-grid energy systems in rural Madagascar by aligning relevant PUE effectively with anticipated residential electricity demand patterns based on socio-economic determinants of the community. We find that a possible contribution of the PUE to reducing the electricity costs depends signifi-cantly on three factors: 1. the residential electricity consumption patterns that are influenced by the socio-economic composition of the community, 2. the degree of flexibility of i) PUE assets and ii) operational preferences of the PUE user, and 3. the capacity of community members to finance and operate PUE assets. Our study demonstrates that significant cost reductions for PUE-integrated off-grid energy systems can be achieved by applying our proposed methodology. When matching PUE and residential consumption patterns, the integration of PUE assets in residential community energy system can reduce the financial risk of operators, provided the PUE enterprise operates reliably and sustainably. We highlight that the consideration of local value chains and co-creation approaches are essential to ensure the energy system is addressing the community’s needs, creates value for the community, enhances the project´s financial sustainability, and is achieving the overall objectives of decentralized energy system planning.

This paper investigates the efficacy of YOLOv8 variants for vehicle detection and license plate detection within smart parking applications, emphasizing performance under varying ambient lighting conditions. The proposed system is to seize full video frames, extracts regions of interest containing vehicles, and feeds them into separate, pre-trained YOLOv8 models – one dedicated to vehicle detection and another for license plate detection. Four YOLOv8 variants, nano, small, medium, and large, are evaluated. As a pre-processing step, the images are processed with the help of OpenCV and Pillow libraries to adjust the luminosity and increase the images’ DPI so that they would be easy to perceive by the Tesseract OCR engine. Sixteen potential combinations arise from pairing the four YOLOv8 models for vehicle and license plate detection tasks. To identify the most suitable combinations, we employ the Multi-Criteria Decision-Making method, specifically Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) analysis. This analysis considers 4 critical metrics: Precision, mean average precision at 95% Intersection of Union threshold, Recall and Total Inference Time. The objective is to achieve an optimal balance between high accuracy and real-time processing. Following the selection of optimal YOLOv8 combinations through TOPSIS analysis, we assess their performance under varying ambient light intensity (measured in lux). This evaluation aims to identify the most robust model combinations that ensure accurate vehicle and license plate recognition across the diverse lighting conditions encountered in real-world environment.

The study comprehensively evaluated the prognostic roles of PLR, NLR, MLR, BLR, and ELR in patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD). 619 patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics containing laboratory findings of the AECOPD patients and the blood cell counts (CBCs) of the healthy volunteers were collected. Compared with the healthy volunteers, PLR, NLR, and MLR were elevated in COPD patients in stable condition, and were further ele-vated during exacerbation. ELR showed the opposite trend. PLR, NLR, and MLR were all posi-tively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more serious airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while Elevated ELR was associated with decreased in-hospital mortality in AECOPD. A nomogram was construct to predict in-hospital mortality in AECOPD. The nomo-gram had a C-index of 0.850 (95% CI: 0.799 – 0.901) with good predictive value and clinical ap-plicability. In summary, PLR, NLR, MLR, and ELR served as predictors for clinical outcomes in patients with AECOPD.

Background: Psoriasis is a chronic immune-mediated skin disease in which systemic inflammation plays an important role in the pathogenesis. In recent years, neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-monocyte ratio (NMR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) have been shown to be important indicators of inflammation. In this study, our aim is to investigate NLR, NMR, PLR, and SII levels in psoriasis patients treated with biologic agents. Method: Clinical and biochemical data of 209 patients who received systemic therapy for psoriasis were obtained by retrospectively reviewing their medical records. NLR, NMR, PLR, and SII values were calculated from the hemogram values of the patients. Results: In the third month of follow-up, the mean CRP, NLR, NMR, PLR, and SII values were significantly decreased compared to the baseline values. SII values showed strong positive correlations with NLR, NMR and PLR. Adalimumab, etanercept, and infliximab, which are TNF-α blockers, were observed to be more effective on PLR and NLR and especially NMR. Conclusion: NLR, NMR, PLR, and SII, which are data obtained from routine blood tests, can be used in the monitoring of treatment of psoriasis, especially with TNF- α blockers.

The search of DNA polymorphisms useful for the genetic improvement of dairy farm animals lasts more than 40 years with relevant findings in cattle for milk traits, where the best combination of alleles for dairy processing have been found in casein genes and in the DGAT1. Nowadays, similar results are not reached yet in river buffaloes despite advanced genomic technologies and accurate phenotype records are available. The aim of the present study was to investigate and validate in a larger buffalo population the effect on six milk traits of four single nucleotide polymorphisms (SNP) in the CSN1S1, CSN3, SCD and LPL genes, previously reported to be associated with or affect dairy traits in smaller populations often belonging to one farm. A total of 800 buffaloes were genotyped. Daily milk yield (dMY, kg), protein yield (dPY, kg) and fat yields (dFY, kg), fat and protein contents (dFP, % and dPP, %), somatic cell count (SCC, 103cell/ml) and urea (mg/dl) were individually recorded in each month for the whole lactation from 2010 to 2021. A total of 15,742 individual milk test day records (2,496 lactations) were available on 680 buffalo cows with 3.6±1.7 parity (from 1 to 13) and 6.1±1.2 test day records per lactation on average. Three out four SNP in CSN1S1, CSN3 and LPL were associated with at least one of analyzed traits. In particular, the CSN1S1 (AJ005430:c.578C>T) gave favorable associations with all yield traits (dMY, p=0.022; dPY, p=0.014 ; dFY, p=0.029) and SCS (p=0.032), whereas the CSN3 (HQ677596: c.536C>T) positively associated with SCS (p=0.005) and milk urea (p=0.04). Favorable effect on dMY (p=0.028), dFP (p=0.027) and dPP (p=0.050) were observed for the LPL. Conversely, SCD did not show any association with milk traits. This is the first example of confirmation study carried out in the Mediterranean river buffalo for genes of economic interest in dairy field and it represents a very important indication for the preselection of young bulls destined to breeding programs in the view of a more sustainable dairy production.

The realization of a perfect absorber A = 1 with transmittance and reflectance T=R=0 by a thin metasurface is one of the hot topics in recent nanophotonics prompted by energy harvesting and sensor applications (A + R + T =1 is the energy conservation). Here we tested optical properties of over 400 structures of metal-insulator-metal (MIM) metasurfaces for a range of variation in thickness of insulator, the diameter of a disc and intra-disc distance experimentally and numerically. Conditions of a near-perfect absorption A > 95% with simultaneously occurring anti-reflection property (R < 5%) were experimentally determined. Differences between the bulk vs. nano-thin film properties at mid-IR of the used materials can be of interest for plasmonic multi-metal alloys and high entropy metals.

Dipeptidyl peptidase 9 (DPP9) is a multifunctional intracellular protease with roles in tumour growth, inflammation and mitochondrial function. We developed a hepatocyte-specific DPP9 knockout mouse (DPP9-KO) to explore DPP9 in a mouse model of hepatocellular carcinoma (HCC). DPP9-KO mice were generated by crossing Albumin-Cre mice (Wt/Wt Cre+/+) with DPP9 floxed mice (Fl/Fl Cre-/-). Mice were treated with Diethylnitrosamine and Thioacetamide then an atherogenic High Fat Diet until 28 weeks of age. DPP9-KO mice had reduced liver and subcuta-neous adipose tissue mass and lower fasting plasma glucose, fewer small macroscopic liver nod-ules compared to DPP9-WT mice. However, there were no differences in the total number of mac-roscopic liver nodules, tumour burden, inflammation score and steatosis score. Consistent with the known ability of DPP9 to suppress NLRP1 activation, activated caspase-1 protein was ele-vated in DPP9-KO mouse liver. Additionally, Nfkbib, Cxcl10 and Ccl5 mRNA and protein levels of autophagy marker beclin1 and tumour suppressor p53 were increased. In conclusion, DPP9 de-pletion in hepatocytes may reduce liver cancer initiation, via mechanisms that may include in-creased autophagy and innate tumour suppression in this experimental model. Finally, the data supports DPP9 having a role in glucose regulation by the liver.

Accurate determination of the concentration of alcohols and their metabolites is important in forensics and in several life science areas. A new method has been developed to quantify alcohols and their oxidative products using a headspace gas chromatography- mass spectrometer and isotope-labelled internal standards. This work demonstrates the application of this method, specifically in quantifying the concentration of oxidative products of alcohol and other minor alcohols found in hand sanitizers, which have become an essential household item since the COVID-19 pandemic. Apart from the major component, the minor alcohols found in hand sanitizers include methanol, isopropanol, and n-propanol. In ethanol-based hand sanitizers, a significant amount of acetaldehyde was observed as an oxidation product, while in isopropanol-based hand sanitizers, acetone was observed. The concentration of acetaldehyde in ethanol-based hand sanitizers significantly increased with storage time and temperature, whereas no such increase of acetone concentration was observed in isopropanol-based hand sanitizers with storage time and temperature.

This study uses a mass-spring-damping system to simulate the repeated strain of liquefaction cyclic triaxial tests. The two results are compared in this paper to understand the feasibility of the mass-spring-damping system developed in this paper and the feasibility of future research on this related topic and development potential. The main factors affecting this mode's repeated strain are the spring coefficient k and the external force Q0. The spring coefficient has an inverse relationship but does not increase in multiples. The external force has a direct proportional relationship but does not increase the result- a non-multiple increase. When the pore water pressure of the liquefied cyclic triaxial test specimen rises, it will cause the specimen to liquefy, decreasing effective stress, shear modulus G, and damping ratio D, causing an increase in strain. The shear modulus and damping ratio are related to the spring coefficients k and c. Both are variables that change with time. This article takes an original thin-tube specimen at point A in the Yunlin area in Taiwan as a testing example. Through Mathematica software, it can be obtained that the mass m=1kg, the spring coefficient k=244e-0.1t kgf/cm, and the damping coefficient c=0.739e-0.257t kgf-s/cm and external force Q0=10.1sin2πt kg; Finally, this study selected the original thin-tube specimens from four locations in the Yunlin area, and simulated the repeated strain amount of the cyclic triaxial test specimens through a spring-damping system. The results show that the spring-damping system is feasible for simulated cyclic triaxial tests because the model is simple and the parameters are easy to understand and obtain, which also shows the extensibility of this model. Preliminary results of the research show that this model can further simulate the repeated strain obtained by cyclic triaxial tests without considering the increased trend in pore water pressure and the decrease in effective stress during cyclic loading.

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents. In this review, we summarize the latest advancements in ABCs. More importantly, we provide an overview and outlook on novel antibacterial agent-loaded bone cements, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides, etc. Offering novel perspectives for designing ABCs and treating bone infections.

To facilitate the computation of the uniaxial compressive strength value of the cemented paste backfill under the condition of high sand-cement ratio, and to analyze the size effect of the cemented paste backfill with high sand-cement ratio under varied aspect ratios, the cemented paste backfill specimens with sand-cement ratios of 8:1-24:1 and aspect ratios of 0.5, 1, and 2 were prepared. Through response surface experiments and finite element analysis, the influence of three aspect ratios on the cemented paste backfill strength was explored, and the failure characteristics and size effect mechanisms of cemented paste backfill with various aspect ratios were analyzed. The model of strength conversion between cemented paste backfill with different aspect ratios was established. The results show that the compressive strength of the cemented paste backfill decreases with the increase of the aspect ratio under the same mass concentration and sand-cement ratio. When the aspect ratio is 0.5 and 1, the splitting failure is the main factor; when the aspect ratio is 2, the shearing failure is the main factor. The three-dimensional stress caused by the end effect of the cemented paste backfill is the main reason for the high strength when the aspect ratio is 0.5. Due to the one-dimensional stress zone generated in the middle of the cemented paste backfill with an aspect ratio of 2 in the laboratory, its strength value is closer to the actual uniaxial compressive strength value of the cemented paste backfill. The strength values of the cemented paste backfill with aspect ratios of 0.5 and 1 were higher than the actual uniaxial compressive strength values in the laboratory. The rationality of the theoretical analysis was verified by the ABAQUS analysis results. According to the experimental results, a strength conversion model between different aspect ratios is established, which can provide a reference for the design of the uniaxial compressive strength of the cemented paste backfill.

In order to improve contrast and restore color for underwater image captured by camera sensors without suffering from insufficient details and color cast, a fusion algorithm for image enhancement in different color spaces based on contrast limited adaptive histogram equalization (CLAHE) is proposed in this article. The original color image is first converted from RGB color space to two different special color spaces: YIQ and HSI. The color space conversion from RGB to YIQ is a linear transformation, while the RGB to HSI conversion is nonlinear. Then, the algorithm separately operates CLAHE in YIQ and HSI color spaces to obtain two different enhancement images. The luminance component (Y) in the YIQ color space and the intensity component (I) in the HSI color space are enhanced with CLAHE algorithm. The CLAHE has two key parameters: Block Size and Clip Limit, which mainly control the quality of CLAHE enhancement image. After that, the YIQ and HSI enhancement images are respectively converted backward to RGB color. When the three components of red, green, and blue are not coherent in the YIQ-RGB or HSI-RGB images, the three components will have to be harmonized with the CLAHE algorithm in RGB space. Finally, with 4 direction Sobel edge detector in the bounded general logarithm ratio operation, a self-adaptive weight selection nonlinear image enhancement is carried out to fuse YIQ-RGB and HSI-RGB images together to achieve the final fused image. The enhancement fusion algorithm has two key factors: average of Sobel edge detector and fusion coefficient, and these two factors determine the effects of enhancement fusion algorithm. A series of evaluate metrics such as mean, contrast, entropy, colorfulness metric (CM), mean square error (MSE) and peak signal to noise ratio (PSNR) are used to assess the proposed enhancement algorithm. The experiments results showed that the proposed algorithm provides more detail enhancement and higher values of colorfulness restoration as compared to other existing image enhancement algorithms. The proposed algorithm can suppress effectively noise interference, improve the image quality for underwater image availably.

The altered nature of archaeological metals means they deteriorate at conditions where metals would be stable. The study of deterioration for such materials is hampered by their complexity, variability and difficulties in measuring deterioration. Placing an object in a sealed container, controlling the RH and pollutant gases and measuring any decrease in oxygen concentration is an accessible method to measure deterioration rate. It has been used for research into suitable environmental conditions to manage deterioration rates of such artefacts including differences in response for artefacts from different excavation sites. Some objects need careful control of RH to low values, this is expensive to maintain and poses risks to other artefacts displayed together. Many objects are actually stable up to quite high RH values and oxygen depletion testing has been used to identify those that can be safely displayed with minimal environmental control. The accelerated corrosion, ‘Oddy’ test is frequently used to sift out unsuitable display materials. The visual assessment is widely recognized to be subjective. The test container has been modified and oxygen depletion appears to give good quantitative measurements of corrosion that correspond with both visual comparison and corrosion quantification for copper, lead and steel, but not for silver.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

Aiming to improve medical diagnosis and treatment, artificial intelligence (AI) has emerged as a transformational force in the healthcare industry. In this article, we examine how AI is increasingly being used to improve healthcare, with an emphasis on how it is changing medical diagnosis and treatment. We explore the opportunities, threats, and ethical concerns of incorporating AI into healthcare practice. In addition, we feature important AI applications in radiology, pathology, cardiology, and cancer. AI has great potential to improve patient outcomes, diagnostic accuracy, and the ability to provide individualized treatment plans in the future if it is used and refined with care.

Biochar is a carbonaceous material derived from the thermochemical conversion of biomass under oxygen-lean conditions. Its properties render it many applications in agriculture, environmental remediation, and catalysis. Commonly produced by pyrolysis under a nitrogen atmosphere, the biochar composition is influenced mainly by residence time, heating rate, and process temperature. The existing literature primarily assesses biochar properties, such as ultimate, proximate, calorific, porosity, and combustibility, generated under various thermo-conversion conditions. However, there is a notable lack of sufficient investigation and attention given to the practical application of biochar. This article seeks to bridge that gap by enhancing the comprehension of the necessary experimental assessment for specific biochar applications and proposing process optimization methods using Multi-Criteria Decision Analysis (MCDA). By delving into these aspects, the study offers a concise overview of biochar production and presents a comprehensive panorama based on articles and patents. Additionally, the research explores the physicochemical characterization techniques associated with biochar and its various applications in conjunction with MCDA. This comprehensive approach aims to uncover valuable insights that could further advance the practical and sustainable utilization of biochar in a wide range of fields.

Rheumatoid arthritis (RA) is an autoimmune disease in which joints are gradually de-stroyed, and early diagnosis and treatment before joint deformation or destruction is im-portant. The detection of novel RA biomarkers in saliva may facilitate the early detection of RA before the onset of disease. In this study, we conducted a comprehensive proteomic analysis of salivary proteins from RA model mice. Proteins were identified by Western blotting and enzyme-linked immunosorbent assay in serum, saliva, and ankle joints from DBA/1JJmsSlc mice, a model of rheumatoid arthritis. Ankle joints and submandibular glands were hematoxylin and eosin stained and immunostained, and the results were compared with those of control mice. Citrullinated α1 antitrypsin (A1AT, 46 kDa) was commonly detected in saliva, serum, and ankle joints of severe RA model mice, and was confirmed by proteome analysis. Western blotting detected a band corresponding to 46 kDa in serum, saliva and ankle joints, and immunostaining of ankle joints with A1AT an-tibody showed a strong positive signal in the synovium. In DBA/1JJmsSlc mice, not only cyclic citrullinated peptide antibodies but also A1AT may be involved in protein citrulli-nation and contribute to the development and severity of RA.

Nutrient depletion in Tanzanian sisal production has led to yield decreases over time. We use nutrient mass balances embedded within a life cycle assessment to quantify the extent of nutrient depletion for different production systems, then used circular economy principles to identify potential cosubstrates from within the Tanzanian economy to anaerobically digest with sisal wastes. The biogas produced is then used to generate bioelectricity and the digestate residual can be used as a fertilizer to address the nutrient depletion. If no current beneficial use of the cosubstrate was assumed, then beef manure and marine fish processing waste were the best cosubstrates. If agricultural wastes were assumed to have a current beneficial use as fertilizer, then marine fish processing waste and human urine were the best cosubstrates. The largest reduction in environmental impacts resulted from bioelectricity replacing electricity from fossil fuels in the national electricity grid and improved onsite waste management practices. There is significant potential to revitalize Tanzanian sisal production by applying circular economy principles to sisal waste management and bioenergy production.

In this study, the impact of the addition of high-aspect-ratio nano-ettringite to photocurable epoxy acrylate resin was explored, with a specific focus on the changes observed in viscosity, shrinkage, tensile strength, and elongation at the break of composites formed. Herein, the nano-ettringite samples were modified using KH-570. The 3 wt% or 6 wt% KH-570-modified and unmodified nano-ettringite were dispersed into the resin by ultrasonic treatment in conjunction with mechanical stirring. The grafting effects of nano-ettringite onto KH-570 were analyzed through scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric (TG) analysis, and Fourier transform infrared spectroscopy (FTIR). The results demonstrate that increased dosages of unmodified and modified nano-ettringite led to increased viscosity of the composite while reducing shrinkage. At the same dosage, the photocurable resin with modified nano-ettringite demonstrated a lower shrinkage and a higher tensile strength. Notably, when the amount of modified nano-ettringite was 3 wt%, the highest tensile strength of the composite was 64.61 MPa, presenting a 72.57% increase compared to the blank sample. Furthermore, the incorporation of modified nano-ettringite as a filler provides a new perspective for improving the performance of photocurable epoxy acrylate resin composites.

Currently, obesity is a critical global public health burden. Numerous studies have demonstrated the regulation of the pathogenesis of obesity and metabolic abnormalities by the gut microbiota and microbial factors; however, their involvement in the various degrees of obesity is not yet understood well. Previously, obesity has been shown to be associated with decreased levels of vitamin B12. Considering exclusive microbial production of vitamin B12, we hypothesised that a decrease in cobalamin levels in obese individuals may be at least partially caused by its depleted production in the intestinal tract by the commensal microbiota. In the present study, our aim was to estimate the abundance of enzymes and metabolic pathways for vitamin B12 synthesis in the gut microbiota of mouse models of alimentary and genetically determined obesity, to evaluate the contribution of the obesogenic microbiome to vitamin B12 synthesis in the gut. We have defined a significantly lower representation of enzymes and metabolic pathways for vitamin B12 biosynthesis in obese mice compared to non-obese mice, wherein enzyme depletion was more pronounced in lepr(-/-) (db/db) mice, which developed severe obesity. The representation of enzymes involved in cobalamin synthesis is strongly correlated with representation of several microbes in high-fat diet fed mice, whereas there were almost no correlations in db/db mice. Therefore, the degree of obesity and the composition of the correspondent microbiota are the main contributors to the representation of genes and pathways for cobalamin biosynthesis in the mouse gut.

: Inflammation may mediate the association of mitral valve prolapse (MVP) with ventricular scarring and arrhythmia. The purpose of this study is to investigate the association of neutrophil- and platelet-to-lymphocyte ratios (NLR, PLR) with ventricular arrhythmia in MVP. Clinical and demographic data were extracted from electronic medical records for all patients aged 18-90 years with MVP on echocardiography between 2016-19 at our institution. We studied 65 patients who had a differential blood count within six months prior to ambulatory ECG (A- ECG) (medi-an age [IQR] 70 [61-77] years; 62% female; 12% African American). Patients with surgery or in-fection within six months prior to CBC were excluded. Complex or frequent ventricular ectopy (cfVE) was defined as the presence of two or more premature ventricular contractions (PVCs) on a 10-second ECG tracing or greater than 1% PVC burden or NSVT on ambulatory ECG monitoring. Logistic and bivariate regression was used to analyze clinical, electrocardiographic and echo-cardiographic factors associated with NLR and PLR. Factors associated with higher NLR were congestive heart failure (p=0.005), male sex (p=0.01), age (p=0.003), and bileaflet MVP (p=0.04). NLR was associated with higher absolute PVC burden (rs=0.28, p=0.03) and cfVE (median NLR [IQR] 3.0 [1.6 – 6.3]) with cfVE versus (2.4 [1.4-3.4], p=0.04) without cfVE. An NLR of 5.6 yielded 50% sensitivity and 90% specificity for PVC burden >1% (AUC 0.69). No significant association was found between PLR and PVC burden or cfVE. NLR is associated with PVC burden and com-plex ventricular ectopy in MVP, suggesting that inflammation is a significant factor in the patho-genesis of ventricular arrhythmia in this condition.

For a hierarchy of large scale structures, like galaxies, galaxy clusters, super-clusters, etc. the requirement that their gravitational (binding) self-energy density must at least equal or exceed the background repulsive dark energy density implies a universal mass-radius relation given by M/R² ~ 1g/cm². Here we point out that this mass-radius relation also holds for important individual biological structures, and even various organisms as a whole such as humans, trees, and to behemoths like whales, even though the physics is different. Here we try to understand this universality from two different physical considerations. We also point out the coincidence that the densities of most biological entities are close to that of water, and that the average density of main-sequence stars and giant planets are close to this density. We give a physical basis for the same.

This research introduces a pioneering solution to the challenges posed by gastrointestinal tract (GI) cancer in radiation therapy, focusing on the imperative task of precise organ segmentation for minimizing radiation-induced damage. GI imaging has historically used manual demarcation, which is laborious and uncomfortable for patients. We address this by introducing the ResECA-U-Net deep learning model, a novel combination of the UNet and ResNet34 architectures. Furthermore, we further augment its functionality by incorporating the Efficient Channel Attention (ECA-Net) methodology. By utilizing data from the UW-Madison Carbone Cancer Centre, we carefully investigate several image processing techniques designed to capture critical local characteristics. With its foundation in computer vision concepts, the ResECA-U-Net model is excellent at extracting fine details from GI images. Sophisticated metrics such as intersection over union (IoU) and the dice coefficient are used to evaluate performance. Our study's outcomes demonstrate the effectiveness of the suggested method, yielding an impressive 96.27% Dice coefficient and 91.48% IoU. These results highlight the significant contribution that our strategy has made to the advancement of cancer therapy. Beyond its scientific merits, this work has the potential to significantly enhance cancer patients' quality of life and provide better long-term outcomes. Our work is a significant step towards automating and optimizing the segmentation process, which can potentially change how GI cancer is treated completely.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

DNA double-strand breakage is the most lethal damage to chromosomal DNA. It activates a series of cellular DNA damage response pathways, including DNA damage sensing, control of cell cycle arrest and apoptosis, and DNA repair. DNA damage response pathways are regulated by complex signaling machineries. Of the intracellular signaling cascades, diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to generate phosphatidic acid (PA). Because both DG and PA serve as second messengers, DGK activity induces a shift of signaling pathways from DG-mediated to PA-mediated cascades, thereby implicating DGK in the regulation of widely various functions. Reportedly, one member of the DGK family, DGKζ, is intimately involved in the regulation of stress responses through p53 and NF-κB. Stresses such as ischemia and infarction cause DGKζ downregulation. Experimental DGKζ depletion renders cells and mice vulnerable to various stressors such as chemotherapeutic agents and ionizing irradiation. Nevertheless, how DGKζ is involved in DNA repair, a critical event of DNA damage response for survival remains unknown. For this study, we examined how DGKζ depletion affects DNA repair mechanisms. We demonstrated that DGKζ depletion causes attenuation of Akt activation and DNA-PK protein expression upon DNA damage, which might engender downregulated BRCA1 protein synthesis and stability. Results suggest that DGKζ depletion attenuates BRCA1-mediated DNA repair machinery, thereby conferring vulnerability to DNA damage.

A multiscale model that enables quantitative understanding and prediction of the size effect on scattering properties of micro- and nanostructures is crucial for the design of LED surface textures optimized for high light extraction efficiency (LEE). In this paper, a hybrid process for combining full-wave finite-difference time-domain simulation and a ray-tracing technique based on a bidirectional scattering distribution function model is proposed. We apply this method to study the influence of different pattern sizes of a patterned sapphire substrate on GaN-based LED light extraction from the microscale to the nanoscale. The results show that near-wavelength–scaled patterns with strong diffraction are not expected to enhance LEE. By contrast, microscaled patterns with optical diffusion behavior have the highest LEE at a specific aspect ratio, and subwavelength-scaled patterns that have antireflection properties show marked enhancement of LEE for a wide range of aspect ratios.

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

This study addresses the critical challenge of Speech Enhancement (SE) in noisy environments, where the deployment of Deep Neural Networksolutions on microcontrollers is hindered by their extensive computational demands. Focusing on this gap, our research introduces a novel SE method optimized for MCUs, employing a 2-layer GRU model that capitalizes on perceptual speech properties and innovative training methodologies. By incorporating self-reference signals and a dual strategy of compression and recovery based on the Mel scale, we develop an efficient model tailored for low-latency applications. Our GRU-2L-128 model demonstrates a significant reduction in size and computational requirements, achieving a 14.2× decrease in model size and a 409.1× reduction in operations compared to traditional DNN methods like DCCRN, without compromising performance. This advancement offers a promising solution for enhancing speech intelligibility in resource-constrained devices, marking a pivotal step in SE research and application.

Introduction: The identification of some prognostic markers in head and neck cancers (HNC) is necessary for the stratification of the therapeutic approach with benefits in increasing treatment response rates and limiting the toxic side effects of treatments. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and pallets-to-lymphocyte ratio (PLR) are currently validated as cheap and accessible biomarkers in different types of solid tumors. The purpose of the study was to evaluate the possible biomarker value of NLR, PLR and MLR recorded pre-treatment (radiotherapy/chemotherapy) for prognostic purposes in HNC. Materials and methods: The study included 190 patients with HNC included in the oncology record in the oncology outpatient clinic of the Craiova County Emergency Hospital starting from January 2002 and deceased until December 2022. Among them, 40 patients treated multimodally in the Clinic were included in the study of Oncology of the Craiova County Emergency Hospital for which the pre-treatment value (chemotherapy/radiotherapy) of NLR, PLR and MLR could be calculated. Overall survival (OS) values were correlated with NLR, PLR and MLR. Results: Median values for NLR, PLR and MLR were 6.15 (1.24-69), 200.79 (61.3- 1775.0) and 0.53 (0.12-5.5) respectively. In the study, the mean values for NLR, PLR and MLR of 2.88, 142.97 and 0.36 respectively were obtained. Median OS in the study group was 11 months (1-120). Although a negative Pearson`s correlation, the relationship between your variables was only weak, values R =.07, p=.67; R=.02, p=.31 and R=07, p=.62 being related with NLR, PLR and MLR respectively correlation with overall survival (OS). The median values of NLR, PLR and MLR were calculated (1.53, 90.32 and 0.18 respectively) for HNC cases with pre-treatment values of NLR <2 and for HNC cases with NLR values ≥6 (23.5, 232.78 and 0.79 respectively). Median OS for cases with NLR<2 and NLR≥6 were 17.4 and 13 months, respectively. Conclusions: The negative correlations of NLR, PLR and MLR with OS reported in the study are in accordance with the data reported in the literature for locally advanced recurrent and metastatic HNSCC cases. The comparative analysis of the data in the group with NLR<2 and NLR≥6 highlights an advantage of 4.4 months in median OS in favor of the group with low values of NLR. Being cheap and accessible, these markers could change the therapeutic approach even in centers with limited resources. The role of borderline NLR values as a prognostic factor in HNSCC must also be defined. PLR and MLR are less evaluated as biomarkers but the study demonstrates their potential to be used as prognostic biomarkers, it remains to be clarified if their inclusion in multivariable models along with NLR would bring a benefit

This study aimed to use remote sensing and GIS to detect changes in surface water and wetlands in the Kumasi Metropolis over a period of 20 years (2002-2022). Landsat images were processed using the QGIS software, and the Maximum Likelihood Algorithm was used to perform supervised classification of land use land cover, while raster calculator aided in detecting wetlands by calculation for NDWI, MNDWI, and AWEI. The results showed that the majority of the landscape in the Kumasi metropolis was made up of built-up areas (79.4%), followed by agricultural lands (13.3%) and wetlands (7.3%). Over the 20-year period, built-up areas had gained 20.7% of the total landscape, while agricultural lands and wetlands had lost 16.7% and 4.0%, respectively. All water index methods recorded an increase in non-water cover and a loss of water cover over the period, with surface water decreasing by 5% and non-water land cover increasing by 5%. The study concludes that there have been significant changes in wetlands and surface water land use and land cover within the Kumasi Metropolis over the past 20 years, and recommends the enforcement of legislation on surface water protection in the area to protect wetlands

In agriculture, soil-borne fungal pathogens, especially Fusarium oxysporum strains, are posing a serious threat to efforts to achieve global food security. In the search for safer agrochemicals, silica nanoparticles (SiO2NPs) have recently been proposed as a new tool to alleviate pathogen damage including Fusarium wilt. Hollow mesoporous silica nanoparticles (HMSNs), a unique class of SiO2NPs, have been widely accepted as a desired pesticide carrier. However, their role in enhancing the disease resistance and the specific mechanism remain unknown. In this study, three sizes of HMSNs (19, 96 and 406 nm as HMSNs–19, HMSNs–96 and HMSNs–406, respectively) were synthesized and characterized to determine their effects on seed germination, seedling growth, and Fusarium oxysporum f. sp. phaseolus (FOP) suppression in cowpea roots by foliar spray using phenotypes, fresh biomass and disease progression as indicators. The results revealed that three HMSNs exhibited no adverse impacts on seed germination and tended to improve plant growth. Also, they exert their FOP suppression with a size- and concentration-dependent manner. HMSNs–406 possessed the best control effect at a concentration of 1000 mg/L showing an upto 40.00% decline in the disease severity. The Si(OH)4 control was also effective on FOP suppression at a lower concentration of 100 mg/L, whereas its higher concentrations exhibited obviously adverse impacts on FOP control, seed germination and plant growth. Moreover, we conformed that HMSNs posed their Fusarium wilt suppression in cowpea plant by activating SA (salicylic acid)-dependent SAR (systemic acquired resistance) responses rather than directly suppressing FOP. A higher level of SA content and elevated expression of its maker genes of PR-1 and PR-5 in HMSNs–406 treated cowpea roots provided substantial evidences of this mode of action. Other resistance-related genes, as well as defense-responsive enzymes, were also involved in the HMSNs-activated SAR pathway. Overall, for the first time, our results extended a new role of HMSNs as a potent elicitor to serve as a versatile alternative for plant disease protection of low cost, highly efficiency and sustainability.

The central nervous system (CNS) is an essential hub for neuronal communication. As a major component of the CNS, glial cells are vital in the maintenance and regulation of neuronal network dynamics. Research on microglia, the resident innate immune cells of the CNS, has advanced considerably in recent years, and our understanding of their diverse functions continues to grow. Microglia play critical roles in the formation and regulation of neuronal synapses, myelination, responses to injury, neurogenesis, inflammation and many other physiological processes. In parallel with advances in microglial biology, cutting-edge techniques for the characterization of microglial properties have emerged with increasing depth and precision. Labeling tools and reporter models are important for the study of microglial morphology, ultrastructure and dynamics, but also for microglial isolation, which is required to glean key phenotypic information through single-cell transcriptomics and other emerging approaches. Strategies for selective microglial depletion and modulation can provide novel insights into microglia-targeted treatment strategies in models of neuropsychiatric and neurodegenerative conditions, cancer and autoimmunity. Finally, fate mapping has emerged as an important tool to answer fundamental questions about microglial biology, including their origin, migration and proliferation throughout the lifetime of an organism. This review aims to provide a comprehensive discussion of these emerging techniques, with applications to the study of microglia in development, homeostasis and CNS pathologies.

The 70/30 copper–nickel alloy is mainly used in critical parts with more demanding conditions in marine settings. There is a need for innovative methods that offer fast production and cost-effectiveness to supplement current copper–nickel alloy manufacturing processes. In this study, we employ wire-arc additive manufacturing (WAAM) to fabricate the 70/30 copper–nickel alloy. The as-built microstructure is characterized by columnar grains with prominent dendrites and chemical segregation in the inter-dendritic area. The aspect ratio of the columnar grain increases with increasing travel speed (TS) at the same wire feed speed (WFS). This is in contrast to an equiaxed grain structure with a more random orientation of conventional sample. The sample built with a WFS of 8 m/min, TS of 1000 mm/min, and a track distance of 3.85 mm exhibits superior corrosion properties in the 3.5 wt% NaCl solution compared to the conventional one, as evidenced by a higher film resistance and breakdown potential, along with a lower passive current density of the WAAM sample. The corrosion morphology reveals the critical roles played by the nickel element unevenly distributed between the dendrite core and inter-dendritic area.

The objective of this study is to investigate the effect of the premixed ethanol ratio based on the same total heating value in-cylinder on the equivalence ratio distributions and the injected fuel droplet behavior in the cylinder of the RCCI engine. The spray simulation was conducted by dividing two-part. First, the spray validation simulations progressed to find the spray-influenced factor of the test injector. Next, the engine simulations were performed with the spray-influenced factor obtained from spray validation simulations to investigate the effect of the premixed ethanol ratio based on the same total heating value in-cylinder on the injected fuel atomization and the equivalence ratio distributions. The introduced total heating value was fixed at 595J based on the lower heating value of diesel 14mg. The heating value of the premixed ethanol ratio varied from 0% to 40% based on the same total heating value in-cylinder in steps of 10%. It was revealed that when the premixed ethanol ratio based on the same total heating value in-cylinder was increased, the spray tip penetration value was reduced from the time after 4deg of diesel injection start because of the short injection duration by the small amount of diesel fuel. The SMD value was also more enormous up to 32.58% with increasing the premixed ethanol ratio because of the low kinetic energy of the injected fuel by the short injection duration and the slow evaporation of the injected fuel by the low cylinder temperature.

Inorganic nanoparticles are utilized for therapeutic, diagnostic, or in combination, theranostic purposes. The latter involves simultaneous sensing, imaging, or tracking of drug delivery. Furthermore, these nanoparticles can differ in their morphologies, which affect outcomes such as the effectiveness of hyperthermia, induction, drug loading, circulation time by escaping the body's immune system, imaging modality clarity, and biosensing. However, design of these theranostics is limited by the lack of a method to predict their therapeutic efficacy. Herein, we report a simple and novel computational approach via algebraic and geometric calculations of surface area (SA) to volume (V) ratios (SA:V) which can help predict the efficacy of the inorganic nanoparticles of the investigated morphologies. The approach comprises a coding platform for the program and uses Python 3 on a Windows 10 operating system. Analyses of 29 polyhedral morphologies that inorganic nanoparticles could assume ex silico showed that only particular concave and convex morphologies in this size regime are more productive over the standard sizes as well as a few noted in literature for baseline comparison. Our results provide a method that can aid in predicting the efficacy of inorganic nanoparticles with certain morphology giving rise to their fundamental basis and eventual implementation ex silico.

Aquaculture contributes to the sustainable development of food security, marine resource conservation, and economy. Shifting aquaculture feed from fish meal and oil to terrestrial plant-derivatives may result in cost savings. However, many carnivorous fish cannot be sustained on plant-derived materials, necessitating the need for the identification of important factors for farmed fish growth and to investigate whether components derived from terrestrial plants can be used in feed. Herein, we focused on the carnivorous fish leopard coral grouper (P. leopardus) to identify the essential growth factors and clarify their intake timing from feeds. Furthermore, we evaluated the functionality of starch, which are easily produced by terrestrial plants. Results reveal that carbohydrates, which are not considered essential for carnivorous fish, can be introduced as a major part of artificial diet. The development of artificial feed using starch offers the possibility of increasing the growth of carnivorous fish in aquaculture.

Lead-acid batteries utilised in electrical substations release hydrogen and oxygen when these are charged. These gases could be dangerous and cause a risk of fire if they are not properly ventilated. Therefore, this research seeks to design and implement a network control panel for heating, ventilation, and air-conditioning systems (HVACS). This is done using a specific range of controllers, which have more than thirty loops of proportional, integral and derivative (PID) control to achieve a cost-effective design. It performs the required function of extracting hydrogen, oxygen, and maintaining the desired temperature of the battery storage room within the recommended limits (i.e. 25°C ±1°C tolerance) without compromising quality as set out in the user requirement specification in Appendix-A. The system control panel allows the user to access control parameters such as changing temperature set-points, fan-speed, sensor database amongst others. The hardware is configured to detect extreme hydrogen and oxygen gas content in the battery room and ensure that the HVACS extract the gas content to the outside environment. The results of the system show that the network control panel effectively operates as per the recommended system requirements. Therefore, the effective operation of the HVACS ensures sufficient gas ventilation, thus mitigating the risk of fire in a typical battery storage room. Furthermore, the effective operation of HVACS enhances battery lifespan because of regulated operating temperature, which is conducive to minimise the effect of sulfation in lead acid Batteries (LABs).

Lifespan extension was recently achieved in Caenorhabditis elegans nematodes by mitochondrial stress and mitophagy, triggered via iron depletion. Conversely in man, deficient mitophagy due to Pink1/Parkin mutations triggers iron accumulation in patient brain and limits survival. We now aimed to identify murine fibroblast factors, which adapt their mRNA expression to acute iron manipulation, relate to mitochondrial dysfunction and may influence survival. After iron depletion, expression of the plasma membrane receptor Tfrc with its activator Ireb2, the mitochondrial membrane transporter Abcb10, the heme-release factor Pgrmc1, the heme-degradation enzyme Hmox1, the heme-binding cholesterol metabolizer Cyp46a1, as well as the mitophagy regulators Pink1 and Parkin showed a negative correlation to iron levels. After iron overload, these factors did not change expression. Conversely, a positive correlation of mRNA levels with both conditions of iron availability was observed for the endosomal factors Slc11a2 and Steap2, as well as for the iron-sulfur-cluster (ISC)-containing factors Ppat, Bdh2 and Nthl1. Positive correlation only after iron depletion was observed for the iron export factor Slc40a1, mitochondrial iron transporters Slc25a28, Abcb7 and Abcb8, mitochondrial ISC-containing factors Glrx5, Nfu1, Bola1 and Abce1, cytosolic Aco1 and Tyw5, as well as nuclear Dna2, Elp3, Pold1 and Prim2. The latter are regulators of nucleotide synthesis and DNA quality control, which have known importance for growth and lifespan. The only Pink1-/- triggered transcript modulation was the reduced expression of the ISC-containing ribosomal factor Abce1. These mammalian findings support previous fly data that Pink1 influences co-translational quality control via Abce1, as well as mitophagy. Our findings provide the first systematic survey how iron dosage triggers homeostatic transcriptional regulations and elucidate how iron deprivation results in mitophagy.

Abstract: Important variables that affect the quality and functionality of sperm and may affect male reproductive health and fertility include telomere length, mitochondrial content, and the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA). The purpose of this study was to look at the connections between these three sperm characteristics and how they might affect a woman's ability to conceive. Methods: Data were collected from 82 men who underwent IVF/ICSI at the University Hospital of Ioannina's IVF Unit in the Obstetrics and Gynecology Department. Evaluations included sperm morphology, sperm count, sperm motility, and participant history. To address this, males of reproductive age who were categorized into three body mass index (ΒΜΙ) groups—normal, overweight, and obese—had their sperm samples tested. Results: Our findings indicate a negative correlation between relative telomere length and ΒΜΙ for both the normal and overweight groups. Conversely, a positive correlation was observed for the obese group, indicating a possible relationship between mitochondrial health and telomere maintenance. The results were statistically significant only for the obese group. Furthermore, a negative correlation was observed between telomere length and mitochondrial content in both the normal and overweight groups, indicating that a lower mitochondrial content may be linked to longer telomeres. Nonetheless, there was a positive correlation for the group that was obese. For all three groups, the data did not reach statistical significance. Given that mitochondrial con-centration and telomere length are both markers of cellular integrity and health, these correla-tions may have an impact on the quality of sperm. Furthermore, the relative telomere length of the normal and overweight groups had a negative correlation with the ratio of mtDNA to nDNA, though the obese group showed a positive correlation. The findings were not statistical-ly significant in any of the groups under investigation. According to this, male fertility may be negatively impacted by an imbalance in the copy number of the mitochondrial genome com-pared to the nuclear DNA in sperm. Conclusions: Our research, in essence, emphasizes the interaction among human sperm telo-mere length, mitochondrial concentration, and the mtDNA to nDNA ratio. Gaining knowledge of these correlations could help explain the reasons behind male infertility and open up new treatment options for reproductive health problems. The functional importance of these correla-tions and possible uses in therapeutic contexts require more investigation.

The concept of {\it quantum ratio} emerged in the recent efforts to understand how Newton's equations appear for the center of mass (CM) of an isolated macroscopic body at finite body-temperatures, as the first approximation to quantum-mechanical equations. It is defined as $Q\equiv R_q/L_0$, where the quantum fluctuation range $R_q$ is the spatial extension of the pure-state CM wave function, whereas $L_0$ stands for the body's linear size (the space support of the internal, bound-state wave function). The two cases $R_q /L_0 \lesssim 1$ or $R_q/ L_0 \gg 1$, roughly correspond to the body's CM behaving classically or quantum mechanically, respectively. In the present note we elaborate more on this concept, illustrating it in several examples. An important notion following from introduction of the quantum ratio is that the elementary particles (thus the electron and the photon) are quantum mechanical, even when the environment-induced decoherence turns them into a mixed state. Decoherence and classical state should not be identified. This simple observation, further illustrationed by the consideration of a few atomic or molecular processes, may have significant implications on the way quantum mechanics works in biological systems.

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently SARS-CoV-2, al-ready four other coronaviruses have been circulating in the human population. The alpha coronaviruses NL63 and 229E and the beta coronaviruses OC34 and HKU1. These circulating coronaviruses all cause mild respiratory illness during the winter seasons and most people are already infected in early life. Could antibodies and/or T cells, es-pecially against the beta coronaviruses have offered some form of protection against SARS-CoV-2? Related is the question whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2. More importantly, would humoral and cellular immunological memory, generated during the SARS-CoV-2 pandemic, ei-ther by infection or vaccination offer protection against future coronaviruses? Or rather than protection, could antibody dependent enhancement have taken place, a mecha-nism by which circulating corona antibodies enhance the severity of COVID-19? An-other related phenomenon, the original antigen sin, would also predict that the effec-tivity of the immune response to future coronaviruses would be impaired because of reactivation of memory against irrelevant epitopes. Current available evidence indicates that latter scenarios are highly unlikely and that especially cytotoxic memory T cells directed against conserved epitopes of human coronaviruses could at least offer partial protection against future coronaviruses.

The drastically increasing amount of plastic waste is causing an environmental crisis that requires innovative technologies for recycling post-consumer plastics to achieve waste valorization while meeting environmental quality goals. Biocatalytic depolymerization mediated by enzymes has emerged as an efficient and sustainable alternative for plastic treatment and recycling. A variety of plastic- degrading enzymes have been discovered from microbial sources. Meanwhile, protein engineering has been exploited to modify and optimize plastic-degrading enzymes. This review highlights the recent trends and up-to-date advances in mining novel plastic-degrading enzymes through state-of-the-art omics-based techniques and improving the enzyme catalytic efficiency and stability via various protein engineering strategies. Future research prospects and challenges are also discussed

Achieving the thermal conductivity required for efficient heat management in semiconductors and other devices requires the integration of thermally conductive ceramic fillers at concentrations of 60 vol% or higher. However, the increased filler content often negatively affects the mechanical properties of the composite matrix, limiting its practical applicability. To address this issue, in this paper, we present a new strategy to reduce the required ceramic filler content: the use of a thermally conductive ceramic composite filler with carbon nanotubes (CNT) grown on aluminum nitride (AlN). We have combined catalyst coating technology with vacuum filtration to ensure that the catalyst is uniformly applied to micrometer-sized AlN particles, followed by efficient and uniform synthesis of CNTs using a water-assisted process in a vertical furnace. By carefully controlling the number of vacuum filtration cycles and the growth time of the CNTs, we demonstrate precise control over the number and length of the CNT layers, thereby adjusting the properties of the composite to the intended specifications. When AlN/CNT hybrid fillers are incorporated into silicone rubber, while maintaining the mechanical properties of rubber, the thermal diffusivity achieved at reduced filler levels exceeds that of composites using AlN-only or simultaneous AlN and CNTs formulations. This demonstrates the critical role of CNTs on AlN surfaces. Our study represents a significant advancement in the design of thermally conductive materials with potential implications for a wide range of applications.

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative motor neuron disease and remains misunderstood with difficult diagnosis and prognosis. The implication of the immune system is recognized in ALS pathophysiology, hence the interest in leucocytes count as lymphocytes and neutrophils. The neutrophil to lymphocyte ratio (NLR) has recently been used as a prognosis factor to assess the progression of ALS. Thus, the aim of this study was to analyze the evolution of the NLR during disease evolution in a French cohort of ALS patients and its relation with survival. Clinical parameters and NLR were collected in ALS patients followed at the University Hospital of Tours (France). ALS patients were subdivided into three groups in regard to their NLR value at inclusion: group 1 (NLR < 2); group 2 (NLR: 2-3); group 3 (NLR > 3). Comparison of qualitative and quantitative clinical and biological variables between NLR groups was performed. Then Cox-regressions were carried out to determine the association of NLR with survival. We observed a significant correlation of NLR with ALSFRS-r score (p<0.0001) and with vital forced capacity (p=0.0004) at inclusion. We observed that increased NLR at diagnosis is associated with decreased ALS patients’ survival.

We aimed to evaluate the magnesium content in human cirrhotic liver and its correlation with serum AST levels, expression of hepatocellular injury, and MELDNa prognostic score. In liver biopsies obtained at liver transplantation we measured the magnesium content in liver tissue in 27 cirrhotic patients (CIRs) and 16 deceased donors with healthy liver (CTRLs) by atomic absorption spectrometry and within hepatocytes in 15 CIRs using synchrotron-based X-ray Fluorescence Microscopy. In 31 CIRs and 10 CTRLs we evaluated the immunohistochemical expression in hepatocytes of the transient receptor potential melastatin 7 (TRPM7), a magnesium influx chanzyme also involved in inflammation. CIRs showed a lower hepatic magnesium content [117.2 (IQR 110.5-132.9) vs 162.8 (IQR 155.9-169.8) μg/g; p&lt;0.001] and a higher percentage of TRPM7 positive hepatocytes [53.0 (IQR 36.8-62.0) vs 20.7 (10.7-32.8) %; p&lt;0.001) than CTRLs. In CIRs, MELDNa and serum AST at transplant correlated: a) inversely with the magnesium content both in liver tissue and hepatocytes; b) directly with the percentage of hepatocytes stained intensely for TRPM7. The latter also directly correlated with worsening of MELDNa at transplant compared to waitlisting. Magnesium depletion and overexpression of its influx chanzyme TRPM7 in hepatocytes are associated with severity of hepatocyte injury and prognosis in cirrhosis. These data represent the pathophysiological basis for a possible beneficial effect of magnesium supplementation in cirrhotic patients.

Prolonged exercise induces acute renal injury; however, the precise mechanism remains unclear. We investigated the effects of neutrophil depletion in male C57BL/6J mice. Male C57BL/6J mice were divided into four groups: sedentary with control antibody, sedentary with antineutrophil antibody, exhaustive exercise with control antibody, and exhaustive exercise with antineutrophil antibody. Antineutrophil (1A8) or control antibody was administered intraperitoneally to the mice prior to their running on a treadmill. Renal histology was assessed 24 h after exhaustive exercise, and the concentration of kidney injury molecule (KIM)-1 was measured using enzyme-linked immunosorbent assay. The expression levels of inflammatory cytokines were measured using quantitative reverse transcriptase-polymerase chain reaction. Furthermore, nicotinamide adenine dinucleotide phosphate oxidase activity and hydrogen peroxide concentration in the kidneys were measured. The pathologic changes were manifested as congested and swollen glomeruli, tubular dilatation, and nuclear infiltration after exhaustive exercise. These changes were suppressed by the administration of the 1A8 antibodies. KIM-1 concentration increased after exhaustive exercise but were reduced by the 1A8 antibodies. Treatment with the 1A8 antibody also decreased exhaustive exercise-induced inflammation and reactive oxygen species levels in the kidney. These results suggest that neutrophils contribute to exercise-induced acute renal injury by regulating inflammation and reactive oxygen species levels.

Regulatory T cells (Tregs) are major drivers behind immunosuppressive mechanisms and present a major hurdle for cancer therapy. Tregs are characterized by high expression of CD25, which is a potentially valuable target for Treg depletion to alleviate immune suppression. The preclinical anti-CD25 (αCD25) antibody, clone PC-61, has met with modest anti-tumor activity, due to its capacity to clear Tregs from circulation and lymph nodes but not those that reside in the tumor. Optimization of the Fc domain of this antibody clone has been shown to enhance intratumoral Treg depletion capacity. Here, we generated a stable cell line that produces optimized recombinant Treg depleting antibodies. A genome engineering strategy in which CRISPR-Cas9 was combined with homology directed repair (CRISPR-HDR) was utilized to optimize the Fc domain of the hybridoma PC-61 for effector functions by switching it from the original rat IgG1 to a mouse IgG2a isotype. In a syngeneic tumor mouse model the resulting αCD25-m2a antibody mediated effective depletion of tumor resident Tregs leading to a high effector T cell (Teff) to Treg ratio. Moreover, combination of the αCD25-m2a with αPD-L1 treatment augmented tumor eradication in mice, demonstrating the potential for αCD25 as a cancer immunotherapy.

Protein import into the endoplasmic reticulum (ER) is the first step in the biogenesis of about 10,000 different soluble and membrane proteins in humans. It involves co- or post-translational targeting of precursor polypeptides to the ER and their subsequent membrane insertion or translocation. So far, three pathways for ER targeting of precursor polypeptides plus four pathways for ER targeting of mRNAs were described. Typically, these pathways deliver their substrates to the Sec61 polypeptide-conducting channel in the ER membrane. Next, the precursor polypeptides are inserted into the ER membrane or translocated into the ER lumen, which may involve auxiliary translocation components, such as the TRAP and Sec62/Sec63 complexes, or auxiliary membrane protein insertases, such as EMC and the TMCO1 complex. Recently, the PEX19/PEX3-dependent pathway, which has a well-known function in targeting and inserting various peroxisomal membrane proteins into pre-existent peroxisomal membranes, was also found to act in targeting and, putatively, inserting monotopic hairpin proteins into the ER. These either remain in the ER as resident ER membrane proteins or are pinched off from the ER as components of new lipid droplets. Therefore, the question arose if this pathway may play a more general role in ER protein targeting, i.e. represents a fourth pathway for ER targeting of precursor polypeptides. Thus, we addressed the client spectrum of the PEX19/PEX3-dependent pathway in both PEX3-depleted HeLa cells and PEX3-deficient Zellweger patient fibroblasts by an established approach, which involves label-free quantitative mass spectrometry of the total proteome of depleted or deficient cells and differential protein abundance analysis. The negatively affected proteins included twelve peroxisomal proteins and two hairpin proteins of the ER, thus confirming two previously identified classes of putative PEX19/PEX3-clients in human cells. Interestingly, fourteen collagen-related proteins with signal peptides or N-terminal transmembrane helices and belonging to the secretory pathway were also negatively affected by PEX3-deficiency, which may suggest compromised collagen biogenesis as a hitherto unknown contributor to organ failures in the respective Zellweger patients.

Acoustic Radiation Forced Impulse (ARFI) is an ultrasound integrated method, measuring stiff-ness by point shear wave elastography. To evaluate the diagnostic performance of ARFI of the liver and of the spleen, combined with spleen dimension and platelet count, in predicting clinical events in cirrhosis, a prospective and cross-sectional study was conducted between February 2017 and February 2021. The following ratio scores with ARFI measurements were performed: ALSDP (ARFI Liver-Spleen Diameter-to-Platelets ratio score), ASSDP (ARFI Spleen-Spleen Diam-eter-to-Platelets ratio score), ASSAP (ARFI Spleen-Spleen Area-to-Platelets ratio score), ALSAP (ARFI Liver-Spleen Area-to-Platelets ratio score). In 100 enrolled subjects, spleen ARFI, ASSDP, ASSAP, were significantly associated with high-risk oesophageal varices (HRVs) in the prospec-tive short- and long-term follow-up and in the cross-sectional study (p 0.7). ARFI-ratio scores can predict, in cirrhotic patients, the risk of developing HVRs in short and long-term period.

The precipitation, flocculation, and deposition of asphaltene cause severe formation damage within a reservoir and shorten a well’s productive life. Pressure depletion is one factor that contributes to asphaltene precipitation during production; therefore, the first step in managing asphaltene is to determine the onset pressure of the precipitation. While there are numerous equation of state models that can be used to predict the onset pressure, these models are complex and heavily reliant on tuning parameters. Using multivariate linear regression, this work attempts to develop a simple and accurate thermodynamic model for predicting the upper precipitation onset pressure under pressure depletion above the bubble point pressure (Pb) at various temperatures. A total of 94 experimental data points from 37 published crude oil data sets were compiled from the literature. To develop the model, 59 experimental data points were used as training data and 35 experimental data points as testing data. According to the results of the multicollinearity test, the bubble point pressure, temperature, resins, and saturate-to-aromatic ratio were chosen as predictors. The upper onset pressure data with comparable trends were clustered, and unsupervised recognition of three distinct cluster groups was performed. For each cluster identified, a multivariate linear regression model was developed. The model was chosen based on Mallow’s coefficient of determination (Cp), adjusted R² (statistical measure of fit), and S (standard error of the regression slope). The developed model was tested using a data set, and the results showed an adjusted R² of 96.25%, with a mean absolute error of 4.1%. The model was randomly applied to 15 data points to compare it to perturbed-chain statistical associated fluid theory (PC SAFT) and the Peng-Robinson equation of state models and to the multivariate regression models of Fahim (2007) and Ameli et al. (2016). The results showed that the mean absolute error for predicting the asphaltene precipitation onset pressure was 2.82% using Peng-Robinson, 2.36% using the PC SAFT equation of state, 23.96% using the Fahim model, 24.80% using the model reported by Ameli et al., and 2.39% using the newly developed multivariate regression model. The developed multivariate model appears to be as accurate as the PC SAFT equation of state modeling with tuning parameters. The primary advantage of multivariate regression is that, unlike the PC SAFT equation of state model, it does not require saturates, aromatics, resins, and asphaltenes (SARA)-based characterization methodologies or rigorous parameter tuning. It is simple to use, quick, and it produces results in a short period of time.

With covid infection having a periodic occurrence and each wave affecting millions of people, there is an urgent need for healthcare providers to develop readily available biological markers to predict the severity and mortality of COVID-19 infection at an early stage of the disease to predict the most optimal management. The Neutrophil – lymphocyte Ratio (NLR) and Platelet-lymphocyte ratio (PLR), are novel inflammatory markers suggested to predict the severity of illness in COVID -19 patients. We evaluated a retrospective cohort of 224 patients with covid 19 illnesses from August 2020 to October 2020. We categorized the patients into 'mild' and 'moderate to severe as per the severity of their illnesses. The optimal cut-off values of the continuous NLR, PLR, and Age were calculated by applying the receiver operating characteristic (ROC) curve analysis. Sensitivity, specificity, and likelihood ratios were calculated from ROC analysis. The results showed that Age, Hb, and NLR are significant predictors of the severity of illness. So we quantified the predictive contribution of those variables by its Z- score and showed that NLR is the strongest predictor followed by Age.ROC curve analysis revealed NLR to be an excellent predictor of disease severity (sensitivity 88.30% and specificity 82.60%) at a cut-off of > 4.24. A cut-off of 165.63 was obtained for PLR, which showed good predictive value for the severity of illness. A NLR > 6 was used as a predictor for mortality due to covid illness with good sensitivity and specificity. Conclusion: NLR and PLR can be used as prognostic markers to identify the severity of covid illness and the probability of mortality in the future in low-resource settings. Given its low cost, easily available, accessible, and reproducible data, it can be used as a useful marker to assist the physician in early referral and treatment of covid 19 infected patients.

The golden ratio, also known as Phi (ϕ ≈ 1.618034), attracted the interest of mathematicians, artists, and intellectuals for many centuries, probably from when it was discovered in human anthropometry. Even in recent times, researchers found the presence of golden ratio in Renaissance paintings and aesthetic preferences. The reasons behind the fascination with the golden ratio remain unclear, but it has been suggested that stimuli containing this proportion are often perceived as beautiful. However, evidence is conflicting, and the literature struggles to establish the existence of individual preferences for golden ratio. To gain new insights into the nature of these preferences, one hundred participants completed an implicit association task, with either golden ratio or random stimuli presented with positive or negative words. Participants initially categorized the stimuli based on their assigned categories. Then, we assessed their explicit preferences by asking to rate the stimuli in terms of pleasantness and by completing a line bisection task and the Ultimate Game. The results revealed the typical effects observed in implicit association tasks, with improved response times and accuracy when golden ratio stimuli were associated with positive word categories. In contrast, explicit ratings yielded mixed results. We discuss our findings in relation to previous studies that have explored this issue, highlighting the ongoing debate surrounding preferences for the golden ratio.

Limited knowledge is available about the association between autistic spectrum disorder (ASD) and precocious puberty. Our study examined the association between the two medical conditions, and the effect modification by sex and neuropsychiatric comorbidities in a nationwide population. To compare the risk of precocious puberty between ASD and non-ASD cases, we conducted Cox regression analysis, using ASD as exposure and time-to-precocious puberty as outcome. We adjusted for sex, attention-deficit/hyperactivity disorder (ADHD), tics disorder, obsessive–compulsive disorder (OCD), anxiety disorder, intellectual disability, and epilepsy. We performed a moderation analysis to examine the potential moderating effects by sex or comorbidities. Patients with ASD were prone to have precocious puberty, with an adjusted hazard ratio (aHR) of 1.80 (95% CI: 1.61-2.01). For the effect modification, sex, specifically females, moderated the association between ASD and precocious puberty, with relative excess risk due to interaction (RERI) 7.35 (95% CI 4.90-9.80). No significant effect modification was found for any of the comorbidities within the scope of additive effect modification. We found that patients with ASD were prone to precocious puberty, regardless of sex or comorbid neuropsychiatric disorders. Girls with ASD are at particularly higher risk to develop precocious puberty.

The rapid evolution of technology has given rise to a connected world, where billions of devices interact seamlessly, forming what is known as the Internet of Things (IoT). While IoT offers incredible convenience and efficiency, it presents a significant challenge in cybersecurity and is characterized by various power, capacity, and computational process limitations. Machine learning techniques are employed within Intrusion Detection Systems (IDS) to enhance their capabilities in identifying and responding to security threats. The key features selected to improve IDS efficiency and reduce dataset size, thereby decreasing the time required for attack detection, are drawn from the extensive network dataset. This paper introduces an enhanced feature selection method designed to reduce the computational overhead on IoT resources while simultaneously strengthening intrusion detection capabilities within the IoT environment. Experimental results based on the InSDN dataset demonstrate that our proposed methodology achieves the highest accuracy with the fewest number of features and low computational cost. Specifically, we attain a 99.99% accuracy with 11 features and a computational time of 0.8599 seconds.

HIV treatment strategies against viral enzymes are continuously hampered by viral drug resistance. Recent findings show that viral substrate Gag contributes to HIV-1 Protease Inhibitor (PI) resistance, leading to demands for new strategies in HIV treatment where Gag is recognized as a drug target. To successfully target Gag, there is a need of in-depth understanding of the Gag polyprotein and the effects of Gag mutations. Here, we propose new strategies in designing novel Gag inhibitors against existing and novel emerging Gag mutations via a structural understanding of the Gag-Protease relationship in PI resistance. In this review, we discuss the role of both novel and previously reported mutations, revealing insights to how they aid in PI resistance, and how new Gag inhibitors can be designed.

The high mutation rate of human immunodeficiency virus type 1 (HIV-1) plays a major role in treatment resistance from the development of vaccines to long-lasting drugs. In addressing the crux of the issue, various attempts to estimate the mutation rate of HIV-1 resulted in a large range of 10-5 - 10-3 errors/bp/cycle due to the use of different types of investigation methods. In this review, we discuss the different assay methods, their findings on the mutation rates of HIV-1 and how the location of these mutations can be further analyzed for their potential allosteric effects to reveal potentially new inhibitors with different pharmacodynamics that can be used to circumvent fast occurring HIV drug resistance. Given that HIV is one of the fastest mutating viruses, it is a good model for comprehensive study of its mutations that can give rise to much horizontal understanding towards overall viral drug resistance as well as emerging viral diseases.

Therapeutics antibodies have increasingly shifted the paradigm of disease treatments, from small molecules to biologics, especially in cancer therapy. Despite the increasing number of antibody candidates, much remains unknown about the antibody and how its various regions interact. In fact, the constant region can govern effects that might be useful in reducing the unwanted consequences resulted from systemic circulation. For this reason, apart from the commonly used IgG isotypes, IgA antibodies are promising therapeutics drugs, given its localized mucosal effects. While the antibody Fc effector cell activity has been well explored, recent research has shown evidences that the constant region of the antibody can also influence antigen binding, challenging the conventional idea of region-specific antibody functions. To further investigate this, we analyzed the IgA antibody constant and its allosteric effects onto the antigen binding regions, using recombinant Pertuzumab IgA1 and IgA2 variants. We found mutations in the C-region to reduce Her2 binding, and our computational structural analysis showed that such allosteric communications were highly dependent on the antibody hinge, providing the evidence to consider antibodies as a whole protein rather than a sum of functional regions.

Objectives: The purpose of this study is to determine the association between umbilical venous blood flow (UVBF) to placental pulsatility index (PPI) ratio and gestational age (GA) in women undergoing prenatal assessments and adverse pregnancy outcome (APO) screening Methods: Between January and December 2022, sonographic examinations were conducted to assess the fetal umbilical cord insertion site in singleton fetuses, and hemodynamic indices of the umbilical artery, umbilical vein, and uterine artery were computed. Through regression analysis, we derived the optimal regression equation to elucidate the UVBF/PPI ratio parameters based on GA. Results: Among 492 singleton fetuses between 21+0 and 40+6 weeks of gestation in the final study. The average fetal UVBF/PPI ratio was 180.45±119.32. Correlation analysis revealed a positive relationship between the UVBF/PPI ratio and GA(p = .000). Using regression analysis, the best-fit regression equation was the linear function model, which explains the value of UVBF/PPI ratio parameters based on GA. Lower UVBF/PPI ratio revealed a positive relationship in the low birth weight fetuses (p=0.021) and higher preterm delivery rate (p=0.034). Cerebroplacental ratio (CPR) showed a high correlation with the UVBF/PPI ratio (r=0.471, p=0.000). Conclusions: The findings of our analyses revealed that contribute to our understanding of fetal hemodynamics and highlight the potential of UVBF/PPI ratio as a predictive marker for adverse pregnancy outcomes, such as preterm birth, low birth weight, or potential fetal hypoxemia. It might be useful for prenatal counseling and clinical purposes.

Demographic and socio-economic developments couple with other requirements to satisfy human needs result in rapid urban expansion sometimes with increasing rate of surface extent greater than the rate of growth of population, that result in continuous sealing of ground surface thereby affecting ecosystem services. This study applied remote sensing toward achieving the progress of SDGs and stage to determine the ratio of the rate of land consumption to the rate of population growth of Gombe metropolis. QGIS 2.18 was used for the image processing and classification analysis for the key Landsat ETM+ (Enhanced Thematic Mapper), Impervious Surface Indices and population data to inform on the urban trend and LCR/PGR for the periods 2000-2005, 2005-2010, and 2010-2015. The result appears that the LCR/PGR for the periods of study show split trends. During 2000-2005 the result shows that the study area expanded outward with LCR/PGR of 1.2. The result also indicate that during 2005-2010, the study area densified with little expansion with the LCR/PGR of 0.8. The result further reveals that during 2010-2015 the LCR/PGR reached 1.8. Pointing that the study area expanded outward with the rate of ground sealing getting high.

Background: Since the previous study dealing with the case fatality ratio and infection fatality ratio caused by COVID-19, the author has received many comments that prompted the question: "Why did an optimistic prognosis fail?" To answer this question, a more detailed and expanded analysis was carried out in a new study. Objective: To evaluate the dynamics of monthly numbers of cases, deaths, tests and CFR worldwide during three phases of the COVID-19 pandemic. Material and Methods: Twenty three sets of databases, dated the 22nd of each month from January 2020 to November 2021, for 213 countries were collected from the Worldometer website. The number of cases, deaths, tests, CFR, IFR, etc. were counted for various periods of time for each of the 213 countries, then results related to different periods of time were compared. Results: The analysis of the main epidemiological parameters led to the division of three phases of the global pandemic evolution. The first phase (23.01.20-22.07.20), the second phase (23.07.20-22.01.21) and the third phase (23.01.21-22.07.21) were different in terms of the number of tests performed, new cases, and mortality due to COVID-19. By the end of the second phase, the worldwide statistics indicated the imminent end of the pandemic, but the third phase was characterized by a sudden rise in the number of new cases and deaths that could not be explained rationally. The most dramatic evolution of the epidemic curve occurred in the countries where doctors had successfully battled COVID-19 during the first two phases of the pandemic. Conclusions: Despite the decrease in overall death numbers during the latest months analyzed, additional study is necessary to identify the cause for the increase in the number of new cases and deaths during the third phase of the pandemic. Only complete information regarding the positive and negative impact of medical and non-medical methods of diagnostics and prophylaxis of COVID-19 can help to organize effective measures to end the current pandemic and prevent a similar one from occurring in the future. Presumably, there are several causes of the negative evolution of the current pandemic, including the overreliance on PCR tests, application of non-specialized premises for quarantine and treatment, decrease in herd and individual immunity, inadequate change of therapeutic protocols, and ignoring prophylactic treatment. It can be suggested that the use of immunemodulatory drugs, for example, thymus extract or thymic peptides, in groups of people with compromised immunity is necessary, and prophylactic and therapeutic protocols should be changed from the 'standard' types to 'personalized' ones.

Climate change and over-exploitation are imposing unprecedented threats to the groundwater resource. Globally, groundwater reserves have depleted to the extent that well yield have decreased, pumping cost have risen, and land have irreversibly subsided. In Malawi, groundwater quantity is a national problem, specifically in Mzimba district due to severe droughts. In this study, the spatial and temporal trends of groundwater depletion was assessed using Gravity Recovery and Climate Experiment (GRACE) data and Land Surface Models (LSM) from Global Land Data Assimilation System (GLDAS) and Global Surface Water Explorer (GSWE). The results show that 1. Groundwater storage is depleting at an average rate of-1.0 ± 0.06 cm yr-1(0.1043 km3yr-1) in the study area with high rate of up to -1.2 cm yr-1(0.12516 km3 yr-1) in the western side and as low as –0.4 cm yr-1(0.04172 km3 yr-1) in the eastern part. 2. Groundwater storage increases from -13 cm in November up to 15 cm between May and April. 3. Drought is the primary cause of such depletion trends with correlation between active evapotranspiration and groundwater depletion, and downward surface shortwave radiation and groundwater depletion, at -0.577 and -0.678 respectively. The results from the study reveals the need for the scientific community and the general public to consider groundwater recharge strategies specifically by mitigating climate change to reduce prolonged droughts. The study suggests the need to establish a stand-alone groundwater assessment and monitoring authority for enhanced conservation efforts of the water resource in the country.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

Poly(dA:dT) tracts cause nucleosome depletion in many species, e.g., at promoters and replication origins. Their intrinsic biophysical sequence properties make them stiff and unfavorable for nucleosome assembly, as probed by in vitro nucleosome reconstitution. The mere correlation between nucleosome depletion over poly(dA:dT) tracts in vitro and in vivo inspired an intrinsic nucleosome exclusion mechanism in vivo. However, we compile here published and new evidence that this correlation does not reflect mechanistic causation. 1) Nucleosome depletion over poly(dA:dT) in vivo is not universal, e.g., very weak in S. pombe. 2) The energy penalty for incorporating poly(dA:dT) tracts into nucleosomes is modest (<10%) relative to ATP hydrolysis energy abundantly invested by chromatin remodelers. 3) Nucleosome depletion over poly(dA:dT) is much stronger in vivo than in vitro if monitored without MNase and 4) actively maintained in vivo. 5) S. cerevisiae promoters evolved a biased poly(dA) versus poly(dT) distribution. 6) Nucleosome depletion over poly(dA) is directional in vivo. 7) The ATP dependent chromatin remodeler RSC preferentially and directionally displaces nucleosomes towards 5’ of poly(dA). Especially bias and directionality would not be expected for an intrinsic mechanism. Together, this argues for a mechanism where active and species-specific read out of intrinsic sequence properties, e.g., by remodelers, shapes nucleosome occupancy.

Solar Energy has enormous potential to fulfill the energy requirements of the world and can be extracted using solar cells. However, the solar cells are affected by poor efficiency and further affected by wind speed, orientation of the panel, temperature and dust deposition. There are different cleaning technologies devised by many industry experts to clean the solar panels. However, they are facing drawbacks when deployed in the solar farm. An efficient cleaning system, along with an added cooling system must be devised, so that the solar panels must be cleaned and cooled often to maximize the energy production. This paper presents a low-cost, energy-efficient, smart and innovative dust cleaning and cooling system for Photovoltaic (PV) Panels. The system is designed, fabricated, fully-automated using Programmable Logic Controller (PLC) and tested successfully. A battery-charging kiosk, capable of charging two, 24V Lead Acid Batteries embedded within this prototype, shall provide clean-energy in a sustainable manner to the rural communities of the developing nations. The user can check the status of the battery such as battery voltage, battery temperature, and state of charge on the Human Machine Interface (HMI) panel while charging the batteries

Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses concerning SARS-CoV-2 infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear IgG B-cell epitopes in its Spike glycoprotein with a SPOT synthesis peptide array probed with a pool of serum from hospitalized COVID-19 patients. Bioinformatics showed a restricted set of epitopes unique to SARS-CoV-2 compared to other coronavirus family members. Potential crosstalk was also detected with Dengue virus (DENV), confirmed by screening individuals infected with DENV before the COVID-19 pandemic in a commercial ELISA assay for anti-SARS-CoV-2 antibodies. Higher reactivity indices were often measured in individuals with a pre-pandemic dengue infection than those with COVID-19. A high-resolution evaluation of antibody reactivity against peptides representing epitopes in the spike protein identified ten sequences in the NTD, RBD, and S2 domains. Functionally, antibody-dependent enhancement (ADE) in SARS-CoV-2 infection of monocytes was observed with pre-pandemic dengue-positive sera. A significant increase in viral load was measured compared to controls, with no detectable neutralization or considerable cell death, suggesting its role in viral entry. This study highlights the importance of identifying the epitopes generated during the humoral response to a pathogenic infection to understand the potential interplay of previous and future conditions on disease. Vaccine development and optimization strategies should be mindful of the potential for A.D.E. that could differ geographically due to endemic biological risks.

The development of technology that combines supercapacitors and lithium-ion batteries by externally connecting them in parallel is ongoing. This study examines the correlation between the volume ratio and electrical characteristics of a cell made by internally connecting a battery capacitor with Li4Ti5O12 as the anode active material and a supercapacitor in parallel. It was found that increasing the volume occupied by the battery capacitor in the cell led to increased cell energy and resistance, resulting in decreased output characteristics. Conversely, increasing the volume occupied by the supercapacitor in the cell led to a decrease in the IR drop during discharge and cell temperature when evaluating cycle characteristics with a current of 20C. The study also examined the behavior of the current distributed during the charging and discharging process based on the volume ratio of the supercapacitor and the battery capacitor. Analyzing the correlation between the volume ratio and electrical characteristics of supercapacitors and battery capacitors could potentially lead to the development of a new type of energy storage device.

Background: Cutaneous Melanoma (SKCM) is characterized by significant heterogeneity in its molecular, genomic, and immunologic characteristics. Methods: Whole transcriptome RNAseq data from The Cancer Genome Atlas of SKCM (n=328) was utilized. The immune microenvironment was characterized using CIBERSORTX to identify immune cell type composition. Unsupervised hierarchical clustering was performed based on immune cell type content. Samples were separated into those obtained from the primary tumor site and regional skin or soft tissue (locoregional), or distant metastasis and regional lymph node (metastatic). Analysis of overall survival (OS) was performed using Kaplan-Meier estimates and Cox-regression multivariable analyses. Results: Four immune clusters were identified, largely defined by lymphocyte:monocyte (L:M) ratio, monocyte-enrichment, and M0-macrophage-enrichment (L:MLow, MonocyteHigh, M0High; L:MLow, MonocyteMid, M0Low; L:MMid, MonocyteLow, M0Low; L:MHigh, MonocyteLow, M0Low). The L:MLow, MonocyteHigh, M0High cluster demonstrated significantly worse OS than clusters 2-4 in the locoregional group (HR 2.804, 95% CI 1.262–6.234, p=0.0114). Membership in the L:MLow, MonocyteHigh, M0High cluster was an independently poor prognostic factor for survival (HR 3.03, 95% CI 1.12–8.20, p=0.029). The L:MLow, MonocyteHigh, M0High cluster correlated with higher rates of metastasis and decreased predicted response to immune checkpoint blockade compared to the other clusters as determined by the Tumor Immune Dysfunction and Exclusion tool (TIDE). Conclusion: Distinct tumor immune clusters with a M0-macrophage-enriched, L:M ratio low phenotype in the primary melanoma tumor site independently characterize an aggressive phenotype that may differentially respond to treatment.

Renal cell carcinoma (RCC) accounts for approximately 90-95% of all kidney cancers in adults, with the clear cell RCC (ccRCC) the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of polymorphisms in genes HVEM and CD160 on susceptibility to ccRCC and patient overall survival (OS) with over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, and two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within additional HVEM SNPs, rs8725 and rs1886730, is associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of the disease. Moreover, the rs1886730 SNP was found to be associated with patients' OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as patient’s OS.

Stress has been identified as a prominent contributor to the development and advancement of bowel cancer, however its specific involvement is intricate and diverse. This abstract tries to offer a concise summary of the correlation between stress and bowel cancer, consolidating significant discoveries from several research fields. The investigation commences by studying the molecular pathways by which chronic stress impacts the development of colon cancer. Chronic stress causes disruption in the functioning of neuroendocrine, immunological, and inflammatory pathways, leading to the development of a microenvironment within the gastrointestinal system that promotes the growth of tumours. Furthermore, changes in the composition of gut microbiota, variations in epigenetics, and alterations in immune function caused by stress also have a role in increasing the risk and advancing the advancement of cancer. Psychological aspects, including how one perceives stress, the tactics they use to cope with it, and the level of psychosocial support they receive, are crucial in determining a person's susceptibility to bowel cancer and impacting the effectiveness of treatment. Stress management therapies, such as cognitive-behavioral therapy and mindfulness-based stress reduction, have demonstrated potential in enhancing patient well-being and promoting adherence to treatment. Moreover, epidemiological studies and clinical trials offer vital knowledge regarding the correlation between stress and the risk, prognosis, and treatment results of bowel cancer. Although the evidence is inconclusive, it is essential to continue researching the intricate relationship between stress and bowel cancer. This will help us understand the connection better and create specific strategies to reduce its impact on patient outcomes.

According to architectural standards, the common proportion of a rectangular-shaped classroom is the shallow proportion, which has a longer external room facade versus the perpendicular internal sides. Even in the Kingdom of Saudi Arabia (KSA), the same proportion is used in school projects. Environmentally, this proportion is logical when considering the role of adequate natural lighting for classroom visual functions, which could be more easily achieved if its longest side is the external one. But, the environmental efficiency of any architectural space cannot be only judged according to a single human comfort achievement, especially with the diverse environmental characteristics of places around the world. This diversity can show a defect in other human comfort achievements or other environmental issues in different ways when achieving a certain function in a unified way. A holistic study should be done for any common architectural shape or proportion to ensure their priority among other options in achieving maximum green architectural principles for a specific location before confirming and using it. The manuscript compares a rectangular classroom of different external/internal wall proportions to search for their preference to be used in Taif city schools in KSA. The compared case studies have different window variations and similarities to include their effect too. According to the overall green principles assessment, the results showed that the common proportion of classrooms didn’t give the higher green credits, which alerts us that the traditional rectangular classroom proportion is not always optimum for all regions including Taif city in KSA.

Sickle cell disease (SCD) is an inherited disorder of major health challenge in Nigeria. Micronutrients deficiencies often associated with the disorder may cause inflammation and abnormal metabolisms in the body. The copper-to-zinc ratio is a more important assessment than the concentrations of either of the metals in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and copper-to-zinc ratio and to correlate copper-to-zinc ratio with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age and sex matched subjects with normal haemoglobin. Serum copper and zinc were assayed by colorimetric method using reagents supplied by Centronic, Germany while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper to zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using Students t-test and Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and copper-to-zinc ratio were significantly higher (p < 0.001) while zinc level was lower in SCD patients than controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and Copper-to-zinc ratio (r = 0.312; p < 0.002) but the correlation between CRP and fibrinogen was not significant. Inflammatory condition may modulate copper and zinc homeostasis and copper-to-zinc ratio may be used as marker of nutritional deficiency and inflammation in SCD patients.

The pro-protein convertase FURIN (PCSK3) is implicated in a wide range of normal and pathological biological processes such as infectious disease, cancer and cardiovascular disease. Previously, we performed a systemic inhibition of FURIN in a mouse model of atherosclerosis and demonstrated significant plaque reduction and alterations in macrophage function. To understand the cellular mechanisms affected by FURIN inhibition in myeloid cells, we optimized a CRISPR-mediated gene deletion protocol for successfully deriving hemizygous (HZ) and nullizygous (NZ) FURIN knockout clones in U937 monocytic cells using lipotransfection based procedures and a dual guide RNA delivery strategy. We observed differences in monocyte and macrophage functions involving phagocytosis, lipid accumulation, cell migration, inflammatory gene expression, cytokine release patterns, secreted proteomics (cytokines) and whole-genome transcriptomics between wild-type, HZ and NZ FURIN clones. These studies provide a mechanistic basis on the possible roles of myeloid cell FURIN in cardiovascular disorders.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

Capsule endoscopy, which uses a wireless camera to take images of the digestive tract, is emerging as an alternative to traditional colonoscopy. The diagnostic values of these images depend on the quality of revealed underlying tissue surfaces. In this paper, we consider the problem of enhancing the visibility of detail and shadowed tissue surfaces for capsule endoscopy images. Using concentric circles at each pixel for random walks combined with stochastic sampling, the proposed method enhances the details of vessel and tissue surfaces. The framework decomposes the image into two detail layers that contain shadowed tissue surfaces and detail features. The target pixel value is recalculated for the smooth layer using similarity of the target pixel to neighboring pixels by weighting against the total gradient variation and intensity differences. In order to evaluate the diagnostic image quality of the proposed method, we used clinical subjective evaluation with a rank order on selected KID image database and compared to state of the art enhancement methods. The result showed that the proposed method provides a better result in terms of diagnostic image quality and objective quality contrast metrics and structural similarity index.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

One of the industries with the fastest rate of growth is healthcare, and this industry's enormous data requires extensive cloud storage. The cloud may offer some protection, but there is no assurance that data owners can rely on it for refuge and privacy amenities. Therefore, it is essential to offer security and privacy protection. Increased customer satisfaction with security and privacy preservation is crucial since healthcare big data and its sources are stored in the cloud and contain increasingly private and sensitive information. However, maintaining privacy and security in an untrusted green cloud environment is difficult, thus the data owner should have complete data control. A new work SecPri-BGMPOP(security and privacy of Boost graph Convolutional Network -Pinpointing-Optimization Performance) is suggested that can offer a solution that involves several different steps in order to handle the numerous problems relating to security and protecting privacy. Initially Boost Graph Convolutional Network Clustering (BGCNC) algorithm, which reduces computational complexity in terms of time and memory measurements, is first applied to the input dataset to begin the clustering process. Second, enlarge by employing a piece of the magnifying bit string to generate a safe key, pinpointing based encryption avoids amplify leakage even if a rival or attacker decrypts the key or asymmetric encryption. Finally, to determine the accuracy of the method, an optimal key was created using a meta-heuristic algorithmic framework called Hybrid fragment horde bland lobo Optimization (HFHBLO). Our proposed method currently kept in a cloud environment, allowing analytics users to utilize it without risking their privacy or security.

The world is currently going through a serious pandemic of viral infection with SARS-CoV-2, a new isolate of coronavirus, resembling and surpassing the crisis that occurred in 2002 and 2013 with SARS and MERS, respectively. SARS-CoV-2 has currently infected more than 142,000 people, causing 5,000 deaths and reaching more than 130 countries worldwide. The very large spreading capacity of the virus clearly demonstrates the potential threat of respiratory viruses to human health, alarming governments around the world that preventive health policies and scientific research are pivotal to overcoming the crisis. Coronavirus disease 2019 (COVID-19) causes flu-like symptoms in most cases. However, approximately 15% of patients will need hospitalization, and 5% require assisted ventilation, depending on the cohorts studied. What is intriguing, however, is the higher susceptibility of elderly individuals, especially those who are more than 60 years old and have comorbidities, including hypertension, diabetes and heart disease. In fact, the death rate in this group may be up to 10-12%. Interestingly, children are somehow protected and not included as a risk group.Thus, here, we discuss some possibilities of molecular and cellular mechanisms by which elderly subjects may be more susceptible to severe COVID-19. In this sense, we raise two main points: i) increased ACE-2 expression in pulmonary and heart tissue of chronic angiotensin 1 receptor (AT1R) blocker users and hypertensive individuals and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. We believe these are pivotal points for a better understanding of the pathogenesis of severe COVID-19 and must be addressed with attention by physicians and scientists in the field.

The licensing of new reactors implies the use of verified and validated neutronics codes. Numerical validation can rely on sensitivity and uncertainty studies but they require repeated execution of time-consuming neutron flux and depletion calculations. The computational costs can be shortened by using perturbation theories. However, Depletion Perturbation Theory is restricted to single integral values such as a nuclide density. Relying on reduced basis approaches, which reconstruct the whole nuclide densities at once, is one way to get around this restriction. Furthermore, the adjoint-based reduced-order model uses the direct and adjoint equations for the projection. For diffusion or transport calculations, Exact-to-Precision Generalized Perturbation Theory has been developed. Still, no models for depletion calculations are readily available. Therefore, this paper describes a novel adjoint-based reduced order model for the Bateman equation. It uses a range-finding algorithm to create the basis and the Depletion Perturbation Theory for the reconstruction of the nuclide densities at first order. Our paper shows that for several perturbed cases, the depletion reduced-order model successfully reconstructs the nuclide densities. As a result, this serves as a proof of concept for our adjoint-based reduced order model which can perform sensitivity and uncertainty burn-up analysis in a shorter time.

Chronic hepatitis B infection remains a significant worldwide health burden, placing persons at risk for hepatocellular cancer and hepatic fibrosis. Chronic hepatitis B virus (CHB) infection is characterized by elevated levels of immunosuppressive regulatory T cells (Tregs), which can inhibit the function of effector T cells and lead to an insufficient immune clearance response against HBV in the host. Theoretically, suppression of Treg functionality and percentage could increase anti-HBV reactivity in CHB-infected patients, although this has not yet been explored. We attempted to enhance our previously established anti-CHB protocol utilizing the GM-CSF+IFN-α+rHBVvac regimen (GMI-HBVac) by incorporating Mafosfamide (MAF), which has been utilized in anticancer therapy in the past. Intravenous administration of MAF to rAAV8-1.3HBV-infected mice resulted in a dose-dependent reduction of Tregs in the blood, rebounding to pretreatment levels 10 days later. To determine the efficacy of anti-CHB, 2ug/ml MAF was combined with the GMI-HBVac in an HBV-infected animal model as an anti-Treg treatment. When rAAV8-1.3HBV-infected mice were immunized with MAF+GMI-HBVac, peripheral blood Tregs decreased significantly, leading to dendritic cell activation, HBV-specific T cell proliferation, and upregulation of IFN-gamma producing CD8+T cells. In addition, MAF+GMI-HBVac vaccination stimulates T cell infiltration in HBV-infected liver. These conditions may contribute to an enhanced immune response and the clearance of HBV-associated antigens, including serum HBsAg, serum HBcAg, and HBcAg+ hepatocytes. Overall, this is the first indication that MAF was utilized as an adjuvant to deplete Tregs and paired with GMI-HBVac as a unique therapeutic vaccine regimen against established CHB mice to produce a functional cure, as seen by the remarkable clearance of HBsAg.

The emerging new Coronaviridae member, nCoV 19, outbreak announced a pandemic by WHO with an increased morbidity and mortality rate worldwide. nCoV 19 known as the third highly pathogen coronavirus in the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), the nCoV 19. The renin-angiotensin (RAS) signaling pathway, oxidative stress and cell death, cytokines storm and endothelial dysfunction are four major pathways involved in the pathogenesis of nCoV 19. Acute respiratory distress syndrome (ARDS) generally develops with a massive oxidative/nitrosative stress following virus entry and RAS activation. The DNA damage subsequent to oxidative burst activates poly-ADP ribose polymerase-1 (PARP-1), viral macrodomain (NSP3) poly (ADP-ribose) glycohydrolase (PARG) and transient receptor potential channel, melastatin 2 (TRPM2) in a sequential manner ultimately leading to apoptosis and necrosis due to NAD and ATP depletion. Regarding the molecular mechanisms involved in nCoV 19 pathogenesis, angiotensin II receptor blockers and/or PARP, PARG and TRPM2 blockers could be engaged as therapeutic candidates for inhibition of RAS and quenching oxidative stress, respectively. In this review, the molecular aspects of nCoV 19 pathogenesis would be studied precisely and possible therapeutic targets would be proposed. It is recommended to evaluate the proposed drugs and supplements via registered clinical trials along with conventional guideline-based multi-drug regimen.

The generation of platform chemicals and hydrochar is of great interest because they reduce dependence on fossil resources and contribute to climate change mitigation by reducing carbon emissions. The main objective of this study was to evaluate the effect of biomass particle size and biomass water ratio in a hydrothermal conversion system for the generation of value-added products obtained from sugarcane bagasse. Biomass characterization was performed using proximal, elemental, and structural analysis; hydrothermal carbonization was carried out at 220 to 260 °C for one hour; and conversion was monitored using pH, conductivity, and IR spectroscopy. Platform chemicals were quantified by HPLC-IR. Hydrochars were characterized by scanning electron microscopy and energy dispersive spectroscopy. The results show that with a biomass:water ratio of 1:50 and a particle size of 212 μm at 220 °C, a yield of 31.07 % of platform chemicals was obtained on a dry basis. Likewise, the hydrochar with the highest carbon content and a higher porosity appearance was obtained with a biomass-to-water ratio of 1:50 and a particle size of 600 μm at 260 °C.

The invasion of ship domain stands out as a significant factor contributing to the risk of collisions during vessel navigation. However, there is a lack of research on the mechanisms underlying collision risks specifically related to merchant and fishing vessels in coastal waters. This study proposes an assessment method for collision risks between merchant and fishing vessels in coastal waters and validated through a comparative analysis through visualization. First of all, the operational status of fishing vessels is identified. Collaboratively working fishing vessels are treated as a unified entity, expanding their ship domain during operation to assess collision risks. Secondly, to quantify the collision risk between ships, a collision risk index (CRI) is proposed and visualized based on the severity of collision risk. Finally, taking the high risk area of merchant and fishing vessels collision in the Minjiang River Estuary as an example, this paper conduct the analysis involves classifying ship collision scenarios, extracting risk data under different collision scenarios, and visually analyzing areas prone to danger. The results indicate that this method effectively evaluates the severity of collision risk, and the identified high-risk areas resulting from the analysis is verified by accidents occurred in the recent three years.

Guided image filter implicitly balances noise and details based on local variance, achieving noise suppression while preserving prominent edges. However, we have observed limitations in using variance to distinguish between noise and image details, resulting in the suppression of fine structures alongside noise. Furthermore, the goal of enhancing image details, which is crucial in image filtering, has not been adequately addressed in edge-preserving filter design. In this paper, we approach image filtering as a problem of spectral energy reconfiguration, where the gain of each spectral band is adaptively regulated to achieve simultaneous noise suppression and detail enhancement. Instead of relying on variance, we employ a linear noise estimator to obtain the Signal-to-Noise Ratio (SNR) measurement necessary for dynamic gain regulation. Similar to the guided image filter, we determine the filter coefficients by solving the closed-form solution of the optimizer. We demonstrate that the proposed extended guided filter effectively integrates information from multiple spectral bands locally, allowing for the joint enhancement of meaningful details while simultaneously smoothing noise.

Endoscopic medical images can suffer from uneven illumination, low contrast, and lack of texture information due to the use of point directional light sources and the presence of narrow tissue structures, posing diagnostic difficulties for physicians. In this paper, a deep learning-based su-pervised illumination enhancement network is designed for low-light endoscopic images, aiming to improve both global illumination and local details. Initially, a global illumination enhancement module is formulated utilizing a higher-order curve function to improve global illumination. Sec-ondly, a local feature extraction module incorporating dual attention is designed to capture local detailed features. Considering the significance of color fidelity in biomedical scenarios, the designed loss function prioritizes introducing color loss to alleviate image color distortion. Compared with seven state-of-the-art enhancement algorithms on Endo4IE endoscopic datasets, experimental re-sults show that the proposed method can better enhance low-light endoscopic images and avoid image color distortion. It provides an efficient method to enhance images captured by endoscopes which can effectively assist clinical diagnosis and treatment.

In this study organic bulk heterojunction (BHJ) solar cell along with the spiro OMeTAD as a hole transport layer (HTL) and the PDINO as an electron transport layer (ETL) was simulated through the Solar Capacitance Simulator, one dimensional (SCAPS-1D) software to examine the performance of this type of polymer thin film organic solar cells. As an active layer the blend of polymer donor PBDB-T and non-fullerene acceptor ITIC-OE was used. Numerical simulation was performed by varying the thickness of HTL and active layer. Firstly, the HTL layer thickness was optimized to 50 nm, after that the active layer thickness varied up to 80 nm. These results of simulation demonstrated that the HTL thickness has rather little impact on efficiency while in the case of active layer thickness improves efficiency significantly. The temperature effect on the performance of solar cells was considered, by the simulation performed for temperature from 300 K up to 400 K and the efficiency of solar cell decreases with increasing temperature. Generally, polymer films usually are full of traps and defects, the density of defects (Nt) value was also introduced to the simulation, and it was confirmed that with the increasing of defect density (Nt), the efficiency of solar cell decreases. After thickness, temperature and defect density optimization, the reflection coating was also applied on it. It turned out that by introducing the reflection coating on the back side of solar cell, the efficiency increases by 2.5 %. Additionally, the positive effect of HTL and ETL doping on efficiency of this type of solar cells was demonstrated.

Hyperspectral imaging data holds great potential for the different stages of the mining life cycle in active and post-mining environments. However, the technology has yet to reach the stage of large-scale industrial implementation and acceptance. While hyperspectral satellite imagery can achieve high spectral resolution, signal-to-noise ratio (SNR) and global availability with break-through satellite systems like EnMAP, EMIT and PRISMA, limited spatial resolution poses chal-lenges for sectors like mining, which require decimetre to centimetre scale resolution for applica-tions such as reconciliation, ore/waste estimates, geotechnical assessments and environmental monitoring. Hyperspectral imaging from drones (referred to herein as Uncrewed Aerial Systems; UASs) offers high spatial resolution data relevant to the camp/ mine scale, with the capability for frequent, user-defined re-visit times. This has been made possible by the miniaturization of hy-perspectral imaging systems. Collection of data in the visible to near and shortwave infrared (VNIR-SWIR) wavelength regions enables the detection of different minerals and surface altera-tion patterns potentially revealing crucial information for exploration, extraction, re-mining, waste remediation, and rehabilitation. In this paper, we provide a review of relevant studies de-ploying hyperspectral imaging in or applicable to the mining sector, especially for the use of hy-perspectral VNIR-SWIR Uncrewed Aerial Systems. Where required, we draw on previous in-sights derived from satellite or ground-based systems. We also discuss UAS survey planning, and sampling considerations for validation and interpretation.

SOC stock (SOCS) changes caused by land use changes are still unclear, and understanding this response is essential for many environmental policies and land management practices. In this study, we investigated the temporal-spatial and vertical distribution characteristics of SOCS on the Western Sichuan Plateau (WSP) using the sparrow search algorithm-random forest regression (SSA-RFR) models with excellent model applicability and accuracy. The temporal-spatial varia-tions in the SOCS were modeled using 1080 soil samples and a set of nine environmental covariates. We analyzed the effect of land use changes on the SOCS on the WSP. The total SOCS increased by 18.03 Tg C from 1990 to 2020. The results of this study confirmed that the SOCS in the study area has increased significantly since 2010, with an increase of 27.88 Tg C compared to the total SOCS in 2010. We found that the spatial distribution of the SOCS increased from southeast to northwest, and the vertical distribution of the SOCS in the study area decreased with increasing soil depth. Forest and grassland are the main sources of SOCS, the total SOCS in the forest and grassland accounted for 37.53 and 59.39% of the total SOC pool in 2020, respectively. Expansion of the wetlands, forest, and grassland areas could increase SOCS in the study area.

Maternal intake of the polyunsaturated fatty acids omega-3 (n-3 PUFA) and omega-6 (n-6 PUFA) impacts hippocampal neurogenesis during development, an effect that may extend to adulthood by altering adult hippocampal neurogenesis (AHN). n-3 PUFA and n-6 PUFA are precursors of inflammatory regulators that potentially affect AHN and glia. Additionally, n-3 PUFA dietary supplementation may present a sexually dimorphic action in the brain. Therefore, we postulated that dietary n-6/n-3 PUFA balance shapes the adult DG in a sex-dependent manner influencing AHN and glia. We test our hypothesis by feeding adult female and male mice with n-3 PUFA balanced or deficient diets. To analyze the immunomodulatory potential of the diets, we injected mice with the bacterial endotoxin lipopolysaccharide (LPS). LPS reduced neuroblast number, and its effect was exacerbated by the n-3 PUFA deficient diet. The n-3 PUFA deficient diet reduced the DG volume, AHN, microglia number and surveilled volume. Diet effect on most mature neuroblasts was exclusively significant in female mice. Colocalization and multivariate analysis revealed an association between microglia and AHN, and the sexual dimorphic effect of diet. Our study reveals that female mice are more susceptible than males to the effect of dietary n-6/n-3 PUFA ratio on AHN and microglia.

We consider the financial planning problem of a retiree wishing to enter a retirement village at a future uncertain date. The date of entry is determined by the retiree's utility and bequest maximisation problem within the context of uncertain future health states. In addition, the retiree must choose optimal consumption, investment, bequest and purchase of insurance products prior to her full annuitisation on entry to the retirement village. A hyperbolic absolute risk-aversion (HARA) utility function is used to allow necessary consumption for basic living and medical costs. The retirement village will typically require an initial deposit upon entry. This threshold wealth requirement leads to exercising the replication of an American put option at the uncertain stopping time. From our numerical results, active insurance and annuity markets are shown to be a critical aspect in retirement planning.

The ratio of males to females with ASD is generally quoted as 4:1 though it is believed that there are biases preventing females being diagnosed and that the true ratio is lower. These biases have not been clearly identified or quantified. Starting with a clinical dataset of 1711 children <18 years old four different methods were employed in an inductive study to identify and quantify the biases and calculate the proportion of females missed. A mathematical model was constructed to compare the findings with current published data. The true male to female ratio appears to be 3:4. Eighty per cent of females remain undiagnosed at age 18 which has serious consequences for the mental health of young women.

Vibrational overtones in deeply bound molecules are sensitive probes for variation of the proton-to-electron mass ratio μ. In nonpolar molecules, these overtones may be driven as two-photon transitions. Here, we present procedures for experiments with O₂⁺, including state-preparation through photoionization, a two-photon probe, and detection. We calculate transition dipole moments between all X²П_g vibrational levels and those of the A²П_u excited electronic state. Using these dipole moments, we calculate two-photon transition rates and AC-Stark-shift systematics for the overtones. We estimate other systematic effects and statistical precision. Two-photon vibrational transitions in O₂⁺ provide multiple routes to improved searches for μ variation.

Open-vocabulary learning has recently gained prominence as a means to enable image segmentation for arbitrary categories based on textual descriptions. This advancement has extended the applicability of segmentation systems to a broader range of generally purpose scenarios. However, current methods often revolve around specialized architectures and parameters tailored to specific segmentation tasks, resulting in a fragmented landscape of segmentation models. In response to these challenges, we introduce OVAMTSeg, a versatile framework designed for Open-Vocabulary and Multitask Image Segmentation. OVAMTSeg harnesses adaptive prompt learning to empower the model to capture category-sensitive concepts, enhancing its robustness across diverse multi-task and scenario contexts. Text prompts are employed to effectively capture semantic and contextual features of the text, while cross-attention and cross-modal interactions enable the fusion of image and text features. Furthermore, a transformer-based decoder is incorporated for dense prediction. Extensive experimental results underscore the effectiveness of OVAMTSeg, showcasing its state-of-the-art performance and superior generalization capabilities across three segmentation tasks. Notable achievements include a 47.5 mIoU in referring expression segmentation, 51.6 mIoU on Pascal-VOC with four unseen classes, 46.6 mIoU on Pascal-Context in zero-shot segmentation, 65.9 mIoU on Pascal-5i, and 35.7 mIoU on COCO-20i datasets for one-shot segmentation.

This paper describes the optimal design of a miniature fiber-optic linear displacement sensor. It is characterized by its ability to measure displacements along a millimetric range with sub-micrometric resolution. The sensor consists of a triangular reflective grating and two fiber-optic probes. The measurement principle of the sensor is presented. The design of the sensor's triangular grating has been geometrically optimized by considering the step angle of the grating to enhance the sensor's resolution. The optimization method revealed a global optimum at which the highest resolution is obtained

The low water solubility of any pharmacoactive molecules limits their pharmacological potential but the solubility parameter cannot compromise, so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, the oral dosage forms cover more than 50 %, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry screening programs identified that around 40% of new chemical entities (N.C.E.s) face various difficulties at the formulation and development step. These pharmaceuticals are attributed to their less solubility and bioavailability. The bioavailability and drug solubility enhancement are significant challenges in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibits poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of the poorly water-soluble drug, for example, complexation of active molecules, utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelles preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, by some appropriate research reports.

Kynurenic acid (KYNA) is an endogenous tryptophan (Trp) metabolite known to possess neuroprotective property. KYNA plays critical roles in nociception, neurodegeneration, and neuroinflammation. A lower level of KYNA is observed in patients with neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases or psychiatric disorders such as depression and autism spectrum disorders, whereas a higher level of KYNA is associated with the pathogenesis of schizophrenia. Little is known about the optimal concentration for neuroprotection and the threshold for neurotoxicity. In this study the effects of KYNA on memory functions were investigated by passive avoidance test in mice. Six different doses of KYNA were administered intracerebroventricularly to previously trained CFLP mice and they were observed following 24 hours. High doses of KYNA (i.e., 20-40 μg/2 μl) significantly decreased the avoidance latency, whereas a low dose of KYNA (0.5 μg/2 μl) significantly elevated it compared with controls, suggesting that the low dose of KYNA enhanced memory function. Furthermore, six different receptor blockers were applied to reveal the mechanisms underlying the memory enhancement induced by KYNA. The series of tests revealed the possible involvement of the serotonergic, dopaminergic, α and β adrenergic, and opiate systems in the nootropic effect. The study confirmed that a low dose of KYNA improved a memory component of cognitive domain, which was mediated by, at least in part, four systems of neurotransmission in an animal model of learning and memory.

At present, aeroponic control is mainly regulated according to the environmental factors of aeroponics, such as the temperature, humidity, light intensity, carbon dioxide concentration, pH, and electrical conductivity (EC) of the nutrient solution. There is a lack of knowledge available in the literature for an aeroponic control system for plant growth information as the primary feedback signal. Therefore, a fuzzy logic-controlled aeroponics system was developed for the growth of lettuce as a feedback signal. After designing, the effectiveness test of system was performed with experiment having three treatments T1 (180C), T2 (220C) and without control (CK). The results show an increasing trend in shoot length, root length, and shoot area over time in all treatments. In terms of shoot area, the maximum of 345 cm² was observed in the T1 treatment, while the CK treatment had a minimum of 241.8 cm². Statistical analysis indicated that the T1 and T2 treatments were not significantly different, but both were significantly different from the CK treatment. The study demonstrates the effectiveness of the fuzzy logic control system and an 18°C nutrient solution temperature, resulting in improved lettuce growth and reduced root-to-shoot ratio. The findings suggest the potential of using fuzzy logic control in aeroponics for optimized cultivation outcomes.

Lignocellulosic biomass, an abundant and renewable resource, serves as a crucial raw material for the production of biofuels, biochemicals, and various value-added products. This paper aims to develop and optimize a mild alkaline treatment of sawdust assisted by ultrasound, along with enzymatic hydrolysis of the pretreated material. The sonochemical pretreatment with alkali emerged as the optimal approach to enhance the susceptibility of cellulose to subsequent enzymatic hydrolysis, thereby increasing the yield of reducing sugars. A comparative study was performed using various ultrasonic applicators (horn and bath) and conventional assisted alkaline pretreatment. The ultrasonic assisted pretreatment revealed a higher delignification as 68% (horn) and 57% (bath) comparing with conventional pretreatment. Processes were optimized using a statistical analysis based on a 23 factorial design. The ratio between sawdust and alkanine solution (RSL = 0.5–1.5 g/100 mL), US amplitude (A = 20–60%), and working temperature (t = 30–50 °C) were selected as process factors. The optimal operating conditions to maximize the reducing sugar yield (138.15 mg GE /gsubstrate) were found as following: solid/liquid ratio RSL,opt = 1.25 g/100 mL, US amplitude Aopt = 60%, and and pretreatment temperature topt = 50 °C. The overall outcomes clearly confirmed the intensification of delignification by ultrasound assisted alkaline pretreatment

Chitosan's favourable characteristics, such as biocompatibility, biodegradability, and bioactivity, have made it a popular biomaterial and the subject of numerous studies over the last years. This study investigates the enhancement of mechanical properties of chitosan fibres through wet impregnation using tripolyphosphate (TPP) as cross-linker. A 1% w/v solution of TPP was prepared and five separate chitosan fibre specimens were immersed individually in TPP solution for varying times (1, 2, 4, 6, and 8 hours). The specimens were then characterized using FTIR, SEM, and dynamometry to evaluate their physical, chemical, and mechanical properties. The FTIR results indicated successful interaction between the protonated amine groups of chitosan and TPP ions, with the crosslinking reaction reaching completion after 2 hours of immersion. SEM images showed that the surface of the fibres became rougher after the crosslinking reaction, suggesting the formation of new chemical bonds. Mechanical testing revealed a significant improvement in tensile strength for the treated samples compared to untreated ones, indicating successful strengthening through crosslinking. The fibres demonstrate significant potential for use in wound healing dressings.