Biological parameters extracted from electrical signals from various body parts have been used for many years to analyze the human body and its behavior. In addition, electrical signals from cancer cell lines, normal cells, and viruses, among others, have been widely used for the detection of various diseases. Single-cell parameters such as cell and cytoplasmic conductivity, relaxation frequency, and membrane capacitance are important. There are many techniques available to characterize biomaterials, such as scanning tunneling microscopy (STM), nanotechnology, microstrip cavity resonance measurement, dielectric impedance measurement (DEPIM), etc. This article reviews the single cell isolation and sorting techniques, summarizes the common single cell operations such as impedance flow cytometry, cell electrical impedance, electrical impedance sensing, and summarizes the current single cell analysis techniques and their applications.

The accurate classification of landfill waste diversion plays a critical role in efficient waste management practices. Traditional approaches, such as visual inspection, weighing and volume measurement, and manual sorting, have been widely used but suffer from subjectivity, scalability, and labour requirements. In contrast, machine learning approaches, particularly Convolutional Neural Networks (CNN), have emerged as powerful deep learning models for waste detection and classification. This paper analyses VGG-16, InceptionResNetV2, DenseNet121, Inception V3, and MobileNetV2 models to classify real-life waste when trained on pristine and unadulterated materials, versus samples collected at a landfill site. When training on DiversionNet, the unadulterated material dataset with labels required for landfill modelling, classification accuracy was limited to 49.69% in the real environment. Using real-world samples in the newly formed RealWaste dataset showed that practical applications for deep learning in waste classification is possible, with Inception V3 reaching 89.19% classification accuracy on the full spectrum of labels required for accurate modelling.

Marine sand, in addition to oil and gas resources, is the second largest marine mineral resource. The rational development and utilization of marine sand resources are conducive to the growth of the marine economy. Marine sand can be categorized into surface marine sand and buried marine sand. Buried marine sand deposits are buried beneath the sea floor, making it challenging to locate them due to their thin distribution. Consequently, there exist numerous technical difficulties associated with marine sand exploration. In this study, various geophysical methods such as sub-bottom profile survey and single-channel seismic survey were employed in the northern offshore waters of the South China Sea along with offshore engineering geological drilling. As a result, two distinct marine sand bodies were delineated within the study area. Additionally, five reflective interfaces (R0, R1, R2, R3 and R4) were identified from top to bottom. These interfaces can be divided into five seismic sequences: A2, B2, C2, D2 and E2 respectively. Three sets of strata were recognized: the Quaternary Holocene Marine sedimentary layer (Q4m), the Upper Pleistocene alluvial layer, and the diluvial sedimentary layer (Q3al+pl) as well as the Upper Pleistocene Marine sedimentary layer (Q3m). Sequence A2 and B2 corresponded to Quaternary Holocene Formation (Q4m) within the study area while sequence C2 corresponded to B2 as well as upper Pleistocene alluvial and alluvial deposits (Q3al+pl), which represent one of the main occurring layers of sand in this region. Lastly, E2 represents a layer composed mainly of silty clay and round gravel known as upper Pleistocene marine sediment layer (Q3m). In total, two ore bodies containing marine sand have been discovered during this study. The estimated total resource amounts approximately 46 million m³ with an average thickness around 11 meters.

In order to explore the effect of Wickerhamomyces on the production of flavor compounds in Xiaoqu Baijiu, this study examined the correlation between the fungal communities in Xiaoqu and ester compounds. It was hypothesized that Wickerhamomyces contributes to the aroma of Xiaoqu. Enhanced fermentation methods were used to validate the role of Wickerhamomyces in Xiaoqu Baijiu brewing. Compared to traditional Xiaoqu, enhanced fermentation significantly increased the acidity of fermented grains and starch utilization rate (P<0.05). The fungal communities in fermented grains were analyzed by high-throughput sequencing technology. The dominant fungi in both control and test groups were Saccharomyces, Cyberlindnera, Rhizopus, and Meyerozyma, with Wickerhamomyces replacing Saccharomymycopsis in the enhanced group. Flavor compounds in the fermentation experiments were analyzed, revealing that ethyl acetate content in Xiaoqu Baijiu increased by 949.94 mg/L in the test group, while isoamyl alcohol decreased by 23.62 mg/L and isobutanol decreased by 34.81 mg/L. Functional prediction analysis using PICRUSt2 confirmed a higher relative abundance of enzymes involved in ethyl acetate metabolism and a lower relative abundance of enzymes involved in higher alcohol metabolism in the test group. These findings demonstrate that Wickerhamomyces enhances ethyl acetate production and reduces higher alcohols during Xiaoqu Baijiu brewing, offering a theoretical foundation for enhancing the quality of Xiaoqu Baijiu.

In this paper, a novel microwave catalyst Ni@SiC/CNFs (NSC), C/Ni (NC), and C/SiC (SC) were successfully synthesized by electrostatic spinning method, and proved to degrade methylene blue with high efficiency under microwave irradiation. The results imply that the catalyst Ni@SiC/CNFs with double shell structure gave a 99.99 % removal rate in 90 s for the degradation of methylene blue under microwave irradiation, outperformed the C/Ni and C/SiC and most other reported catalysts in similar studies. On the one hand, the possible mechanism of the methylene blue degradation should be ascribed to that double shell structure increases the polarization source of the material, resulting in excellent microwave absorption properties; and on the other, the in-situ generation of active species OH• and O2 - under microwave radiation and the synergistic coupling effect of metal plasma greatly improved the degradation efficiency of methylene blue. The findings of this study could provide a valuable reference for the green degradation of industrial dye wastewater and its sustainable development process.

Acid-producing bacteria in pit mud play a crucial role in the fermentation of Chinese liquor, significantly influencing its flavor, taste, and overall quality. This study investigates three strains of anaerobic acid-producing bacteria from pit mud to optimize both single and combined bacterial fermentations for enhanced acid production. Acid production levels were quantitatively measured using gas chromatography-mass spectrometry. The Design Expert software was employed to identify significant nutritional factors affecting the production of hexanoic and butyric acids. These factors were optimized through climbing tests and response surface analysis. The Box-Behnken Design (BBD) experimental design and variance analysis were used to determine the optimal levels of each significant factor. The SJ-1/SJ-3/SJ-8/enriched solution exhibited the highest acid production, with a total acid production of 2216.07±0.10 mg/100 ml. The yields of caproic acid and butyric acid were 801.94±0.11 mg/100 ml and 1167.33±0.14 mg/100 ml, respectively. The optimized fermentation medium for caproic and butyric acid production consisted of 5.1 g/L peptone, 5.04 g/L sodium acetate, and 4.45 g/L sodium butyrate, with a pH of 6.4. Under these conditions, the production of caproic acid and butyric acid reached 1172.73 mg/100 ml and 2382.45 mg/100 ml, respectively. These values represent significant increases (P<0.05) of approximately 46.24% for caproic acid and 104.09% for butyric acid compared to initial levels. The model predicts caproic and butyric acid production to be 1184.21 mg/100 ml and 2387.84 mg/100 ml, respectively, which closely aligns with experimental results. This indicates the model’s effectiveness and provides valuable insights for enhancing acidity in liquor production.

The neuronal etiology of obesity is centered around diet-induced inflammatory state in the arcuate nucleus of the hypothalamus which impairs the functionality of pro-opiomelanocortine neurons (POMCs) responsible for whole-body energy homeostasis and feeding behavior. Intriguingly, systemic salt inducible kinase 2 (SIK2) knockout mouse demonstrated reduced food intake and energy expenditure along with modestly dysregulated metabolic parameters suggesting a causal link between the absence of SIK2 activity in POMCs and the observed phenotype. To test this hypothesis, we conducted a comparative secretomics study from POMC neurons following pharmacologically induced endoplasmic reticulum (ER) stress induction, a hallmark of metabolic inflammation and POMC dysregulation in diet induced obese (DIO) mice. Our data provide significant in vitro evidence for the POMC specific SIK2 activity in controlling the energy metabolism and feeding in DIO mice by regulating the nature of related POMC secretome. Our data also suggests that under physiological stress conditions SIK2 may act as a gatekeeper for the secreted inflammatory factors and signaling molecules critical for cellular survival and energy homeostasis. On the other hand, in the absence of SIK2 gate opens leading to surge of inflammatory cytokines and apoptotic cues concomitant with the dysregulation of POMC neurons.

Nose mask is a fomite and its usage was mandatory during the COVID-19 outbreak. Its effectiveness has been established; however, as a fomite, it can harbor opportunistic respiratory pathogens such as Streptococcus spp., which could complicate COVID-19 infections. This study profiled Streptococcus species resident on nose masks obtained from consenting participants. Phenotypic assays and 16S rRNA sequencing were used to identify Streptococcus spp. resident on the interior and exterior of 100 nose masks analyzed. Antibiotic resistance (AMR) was determined with disc diffusion and broth microdilution assays. AMR and virulence makers were profiled with primer-specific PCR amplification. 23% of the analyzed samples had Streptococcus isolates. The isolates were highly resistant to the antimicrobials, including conventional, last-resort antibiotics, disinfectants and antiseptics. All the isolates are multidrug resistant with 80-100% levels of AMR to the 16 antibiotics tested with a Multiple-Antibiotic Resistance index greater than 0.2, indicative of potential pathogens. The isolates harbored tetB, ermB, pbp2B, pbp2b1 (resistance) and lytA, lytA1, ply1, cbpA, lytA, pavA (virulence) markers, which might constitute a serious public health risk. Overall, the study emphasizes the need to assess mask usage and the risks associated with opportunistic pathogens that are resident on frequently used nose masks in the COVID-19 era.

Acute and chronic graft versus host disease (a/cGVHD) are major complications of allogeneic stem cell transplantation and a frequent cause of non relapse-mortality. The treatment of a/cGVHD consists of steroid administration at full dose. In the case of aGVHD, around 60 % of patients with grade III/IV fails to respond (steroid-resistant, SR), requiring a second line therapy. Extracorporeal photopheresis (ECP) represents a good option for second line treatment, leading to multiorgan response in several patients. Here, we have evaluated the performances of a cytofluorimetric quality control of the first ECP procedure in 29 patients with severe SR aGVHD who underwent ECP. The quality control represents a check control of in vitro cell apoptosis/death induction in collected and irradiated CD3+ cells by ECP. Our analysis shows that in more than 70 % quality controls a relevant apoptotosis/death of CD3+ cells was observed after cell irradiation, as compared to non-irradiated controls. Albeit observed in a small patients’ series, the occurrence of relevant in vitro effect after ECP relates to less procedures and/or to a better survival on ECP. Age, disease, gender, aGVHD grade and time from transplant to the first ECP had not impact on ECP efficacy in this patients’ series.

Shigella and Salmonella have been implicated in neonatal sepsis, food poisoning, and bacteremia. Their increasing resistance to antibiotics has undermined treatment options, constituting a public health crisis. Also, the scarcity of new antibiotics in the development pipeline compounds multidrug-resistance (MDR). Hence, there is a need to potentiate antibiotics to mitigate resistance. This study leveraged riboflavin to re-sensitize fluoroquinolones and carbapenems against MDR Shigella and Salmonella spp. Disk diffusion, microbroth-dilution, chequerboard, and time-kill assays were used to determine resistance profiles and riboflavin-antibiotic activity. Biofilm-formation and bacterial viability (after riboflavin-antibiotic challenge) was determined with crystal-violet and Macrophage infection assays, respectively. Strains exhibited &gt;80% resistance to fluoroquinolones and carbapenems, with 160–320 µg MIC ranges and 0.5–2 FIC, indicating no synergy. At 40–80 µg riboflavin, there was two-fold reduction in bacterial survival, with meropenem-riboflavin exhibiting significant reduction and FIC of 0.075 indicating high synergistic activity. Biofilm-formation was altered (from strong to weak phenotype) with 40 µg riboflavin-antibiotic treatment. There was a 40–70% reduction in bacterial survival in THP-1 cells treated with meropenem-riboflavin after 3 hours, and complete clearance between 24-48 hpi. Riboflavin potentiated fluoroquinolones and meropenem, leading to modulation of the host immune response for the clearance of the strains.

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and the most common form of head and neck cancer, posing significant challenges for disease management. Single-cell RNA sequencing (sc-RNAseq) has emerged as a valuable tool for addressing these challenges by enabling detailed characterization of the tumor microenvironment (TME) at the cellular level. This review assesses the utility of sc-RNAseq in HNSCC research, compiling current strategies employing single-cell technologies. For HNSCC etiology, sc-RNAseq allows for the construction of cellular atlases, characterization of different cell types, and investigation of key genes and processes involved in cancer initiation, development, and progression within the TME. In terms of HNSCC diagnosis and prognosis, the high resolution offered by sc-RNAseq enables the identification of cell type-specific signatures, enhancing prognostic models and disease stratifiers for more accurate patient outcome assessments. Regarding HNSCC treatment, sc-RNAseq provides insights into cellular responses to various treatments, including radiotherapy, chemotherapy, and immunotherapy, contributing to improved patient stratification and personalized treatment strategies. This review highlights the unique contributions of sc-RNAseq to HNSCC research, addressing its cellular and biological complexity, and emphasizes its potential for advancing research and clinical practice in other cancer types.

Frontal Polymerization (FP) is recognized as a polymer synthesis method capable of generating a highly localized and self-propagating exothermic front, considered a more rapid and energy-efficient manufacturing scheme for polymer-based fiber-reinforced composite materials. This study conducts a numerical investigation based on the Finite Element Method into the initiation and propagation of frontal polymerization of acrylamide. Utilizing Differential Scanning Calorimetry (DSC) experiments, the study phenomenologically tests the curing kinetics reactions of acrylamide (AM) in deep eutectic solvent (DES)-based polymerizable systems, thereby establishing a curing kinetics model for the autocatalytic reaction of polyacrylamide. By coupling the heat conduction diffusion equation of the frontal polymerization reaction, the Finite Element Method is employed to solve the reaction-diffusion model, aiming to explore the evolution of temperature and degree of curing during the manufacturing process. The results demonstrate the reliability and accuracy of the nth-order autocatalytic model in the study of curing kinetics for DES-based synthesis, indicating that the front propagation speed of the AM-based FP reaction is influenced by the activation temperature, duration of activation temperature, and initial temperature of the solution. Experimental validation of the polyacrylamide manufacturing through frontal polymerization corroborates the accuracy and reliability of the model predictions, providing a reference for the numerical model study and temperature control in the synthesis of acrylamide composite hydrogels via FP.

This study presents the first genome assembly of the freshwater saprobe fungus Neonectria lugdunensis and a comprehensive phylogenomics analysis of the Nectriaceae family, examining genomic traits according to fungal lifestyles. The Nectriaceae family, one of the largest in Hypocreales, includes fungi with significant ecological roles and economic importance as plant pathogens, endophytes, and saprobes. The phylogenomics analysis identified 2684 single-copy orthologs, providing a robust evolutionary framework for the Nectriaceae family. We analyzed the genomic characteristics of 17 Nectriaceae genomes, focusing on their carbohydrate-active enzymes (CAZymes), biosynthetic gene clusters (BGCs), and adaptations to environmental temperatures. Our results highlight the adaptation mechanisms of N. lugdunensis, emphasizing its capabilities for plant-litter degradation and enzyme activity in varying temperatures. Comparative genomics of different Nectriaceae lifestyles revealed significant differences in genome size, gene content, repetitive elements, and secondary metabolite production. Endophytes exhibited larger genomes, more effector proteins, and BGCs, while plant pathogens had higher thermo-adapted protein counts, suggesting greater resilience to global warming. In contrast, the freshwater saprobe shows less adaptation to warmer temperatures and is important for conservation goals. This study underscores the importance of understanding fungal genomic adaptations to predict ecosystem impacts and conservation targets in the face of climate change.

Plant cells' ability to withstand abiotic stress is strongly linked to modifications in their mechanical characteristics. Nevertheless, the lack of a workable method for consistently tracking plant cell mechanical properties severely restricts our comprehension of the mechanical alterations in plant cells under stress. With Polyethylene Glycol (PEG6000), we created a drought-like environment, and we used the Double Resonator Piezoelectric Cytometry (DRPC) method to dynamically and non-invasively track changes in the stress (ΔS) created and viscoelasticity (storage modulus G' and loss modulus G") of protoplasts and suspension cells of rice during drought stress. The findings demonstrate that, rice suspension cells and protoplasts react mechanically differently to 5%–15% PEG6000 stress, implying distinct resistance mechanisms. However, neither of them can withstand 25% PEG6000 stress, they respond mechanically similarly to 25% PEG6000 stress. The results of DRPC are further corroborated by the morphological alterations of rice cells and protoplasts observed under an optical microscope. To sum up, the DRPC technique functions as a precise cellular mechanical sensor and offers novel research tools for the evaluation of plant cell adversity and differentiating between the mechanical reactions of cells and protoplasts under abiotic stress.

Ten new Schiff bases, including thiocarbohydrazone derivatives (1–10), were synthesized using an efficient, uncomplicated, and environmentally friendly approach using the reaction of alkyl-substituted aldehydes. The thiocarbohydrazones that were obtained were derived from o-phthalaldehyde. The chemical structures of the compounds were identified by the utilization of UV-Vis spectroscopy, Fourier transform infrared (FT-IR), ¹H nuclear magnetic resonance (¹H NMR), ¹³C nuclear magnetic resonance (¹³C NMR), and elemental analysis methods. The thermal stability of thiocarbohydrazones was examined using thermogravimetric analysis (TGA-DSC). Investigations were conducted on urease inhibition tests, pharmacokinetic property research, and molecular docking. The collection of samples with the urease enzyme revealed significant molecular docking findings, with MolDock scores ranging from -153 to -189. The compounds have the potential to be effective drug candidates for treating certain diseases, as indicated by the consistent results of molecular docking, urease inhibition tests, and pharmacokinetic characteristics investigations.

The power of movement in plants” by Charles Darwin details many examples of oscillatory growth exemplified more recently at the single cell level by pollen tube tip oscillations and associated ion fluxes, particularly Ca²⁺and H⁺. That implies an underlying growth oscillator based on the recent discovery that classical AGPs bind Ca²⁺ at the cell surface. The juxtaposition of AGPs with three other components embedded in the plasma membrane is evidence of a Ca²⁺ cycle that generates cytosolic Ca²⁺. It involves Ca²⁺ channels, auxin efflux “PIN” proteins and an auxin-activated proton pump that dissociates AGP-Ca²⁺ on demand. While the apparent simplicity of this system satisfies Occam’s Razor its hypothetical role as a global growth oscillator demands rigorous experimental appraisal. The wide ramifications extend from pollen tubes to stomatal guard cells. Stomata act as crucial components of a water hypercycle that contributes to homeostasis of a warming planet by regulating evaporative cooling, reflective cloud cover generated by vast forests and the high albedo of snow-capped mountains including polar ice-caps . The Gaia hypothesis of James Lovelock and Lynn Margulis is a brilliant metaphor.

Cell-culture meat is a novel concept to replace traditional meat produced from animals, and to satisfy rising food demands due to the world population growth. It is still a young field and requires to solve technical issues including cell sources and types, efficient culture for large scale production, taste and texture for customer satisfaction. The current review summarized traditional beef meat production and evaluation methods for customer satisfaction. In particular, serum biomarkers for beef meat evaluation are discussed, which can be applicated for cell-culture meat production.

Spermatogenesis is critical for insect reproduction and is regulated by many different genes. In this study, we found that Forkhead transcription factor Fd59a functions as a key factor in spermatogenesis of Drosophila melanogaster. Fd59a contains a conversed Forkhead domain, and it is clustered to the FoxD subfamily with other FoxD members from some insect and vertebrate species. Mutation in Fd59a caused swelling in the apical region of the testis. More importantly, only a few mature sperm were present in the seminal vesicle of Fd59a mutant flies compared to the control flies, and the fertility of Fd59a2/2 mutant males was significantly lower than that of the control flies. Immunofluorescence staining showed that the homeostasis of testis stem cell niche in Fd59a2/2 mutant and Fd59a RNAi flies was disrupted, and apoptosis of sperm bundles was increased. Furthermore, results from RNA-sequencing and qRT-PCR suggest that Fd59a can regulate expression of genes related to reproductive process and cell death. Taken together, our results indicated that Fd59a plays a key role in the spermatogenesis of Drosophila.

Reconstructing the Tree of Life remains a central goal in biology. Early methods, relying on small numbers of morphological or genetic characters, often yielded conflicting evolutionary histories, undermining confidence in the results. Investigations based on phylogenomics, which use hundreds to thousands of loci for phylogenetic inquiry, have provided a clearer picture of life's history, but certain branches remain problematic. To resolve difficult nodes on the Tree of Life, two recent studies tested the utility of synteny, the conserved collinearity of orthologous genetic loci in two or more organisms, for phylogenetics. Synteny exhibits compelling phylogenomic potential while also raising new challenges. We identify and discuss specific opportunities and challenges that bear on the value of synteny data and other rare genomic changes for phylogenomic studies. Synteny-based analyses of highly contiguous genome assemblies mark a new chapter in the phylogenomic era and the quest to reconstruct the Tree of Life.

This study focuses on the potential medicinal properties of Campsis radicans L. extracts and its aim is to investigate the antioxidant and antiproliferative effects of these extracts on the human colon adenocarcinoma cell line (HT-29). Cytotoxic activity in the HT-29 cell line was evaluated, and the 3-dimensional structures of phenolic compounds were obtained using the GC-MS method. Docking simulations were performed with AutoDock Vina, targeting proteins that are crucial in the apoptotic pathway (Bax, Bcl-2, and Caspase-3). Drug similarities and ADMET estimates of the phenolic compounds were obtained from databases. The highest antioxidant activity of Campsis radicans L. plant was observed in ethanol and water extracts, with notable inhibition capacities. While the total phenolic content was highest in ethanol, water, and ether extracts respectively the total flavonoid content was highest in ethanol, then ether, and water extracts. Certain elements were undetectable in mineral determination, and others exceeded the toxic doses for plants. The water extract exhibited dose-dependent cytotoxic activity in the HT-29 cell line, with an IC50 value of 4.47 mg/mL. Molecular docking results revealed the binding of phenolic molecules to the active sites of apoptotic pathway proteins. The findings suggest that Campsis radicans L. plant possesses cytotoxic properties, significant phenolic and flavonoid content, and a high antioxidant capacity. These properties make it a potential candidate for treatment use, emphasizing its potential therapeutic value in the HT-29 cell line. Further research and exploration on the identified phenolic compounds could contribute to the development of novel therapeutic agents.

Mesenchymal stem cells (MSCs) hold immense therapeutic potential due to their regenerative and immunomodulatory properties. However, to utilize this potential, it is crucial to optimize their in vitro cultivation conditions. Three-dimensional (3D) culture methods using cell-laden hydrogels aim to mimic the physiological microenvironment in vitro, thus preserving MSC biological functionalities. Cellulosic hydrogels are particularly promising due to their biocompatibility, sustainability, and tunability in terms of chemical, morphological, and mechanical properties. This study investigated the impact of (1) two physical crosslinking scenarios for hydrogels derived from anionic cellulose nanofibers (CNF) used to encapsulate adipose-derived MSCs (adMSCs) and (2) physiological culture conditions on the in vitro proliferation, differentiation, and extracellular vesicle (EV) production of these adMSCs. Our results revealed that additional Ca2+-mediated crosslinking, intended to complement self-assembly and gelation of aqueous to-CNF in the adMSC cultivation medium, adversely affected both the mechanical properties of the hydrogel spheres and the growth of the encapsulated cells. However, cultivation under dynamic and hypoxic conditions significantly improved the proliferation and differentiation of the encapsulated adMSCs. Furthermore, we demonstrated that adMSCs in CNF hydrogel spheres exhibited potential for scalable EV production with potent immunosuppressive capacities in a bioreactor system. These findings underscore the importance of physiological culture conditions and the suitability of cellulosic materials for enhancing the therapeutic potential of MSCs. Overall, our study provides valuable insights for optimizing the in vitro cultivation of MSCs for various applications, including tissue engineering, drug testing, and EV-based therapies.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

We have designed cell penetrating peptides that target the leucine zipper transcription factors ATF5, CE-BPB and CEBPD and that promote apoptotic death of a wide range of cancer cell types, but not normal cells, in vitro and in vivo. While such peptides have the potential for clinical application, their mechanisms of action are not fully understood. Here, we show that one such peptide, Dpep, compromises glucose uptake and glycolysis in a cell-context-dependent manner (in about 2/3 of cancer lines assessed). These actions are dependent on induction of tumor suppressor TXNIP (thioredoxin interacting protein) mRNA and protein. Knockdown studies show that TXNIP significantly contributes to apoptotic death in those cancer cells in which it is induced by Dpep. The metabolic actions of Dpep on glycolysis led us to explore combinations of Dpep with clinically approved drugs metformin and atovaquone that inhibit oxidative phosphorylation and that are in trials for cancer treatment. Dpep showed additive to synergistic activities in all lines tested. In summary, we find that Dpep induces TXNIP in a cell-context-dependent manner that in turn sup-presses glucose uptake and glycolysis and contributes to apoptotic death of a range of cancer cells.

This study investigates the adoption of ecological innovations and management of occupational health hazards among Nigerian paddy rice farmers in response to field contamination and climate risks. Conducted across four major rice-producing states—Ekiti, Kwara, Edo, and Ogun—the research employed a semi-structured questionnaire developed from a comprehensive literature review and validated through peer review. Data were collected from 192 farmers through face-to-face interviews and guided dialogues, focusing on ecological innovations, vulnerability assessments, satisfaction with implemented methods, occupational health hazards, and perceptions of sustainable rice cultivation. Findings reveal that only 29.69% of farmers have adopted new measures to address contamination and climate risks, while 70.31% have not. Work-related injuries, such as cuts and abrasions, affected 28% of farmers, with minimal participation (3.1%) in safety training and support from agricultural or government agencies (1%). Correlation analysis demonstrated weak relationships among variables such as farmers' education, adoption of ecological innovations, satisfaction with results, and use of personal protective equipment (PPE). Importantly, farmers who adopted ecological innovations expressed significantly higher satisfaction (odds ratio = 11.613), as did those with prior exposure to pesticides and chemicals (odds ratio = 4.084) regarding safety practices. The study emphasizes the critical need for increased awareness, training, and support to promote sustainable farming practices and improve occupational health outcomes among paddy rice farmers in Nigeria.

The prospect of drinking water serving as a conduit for gut bacteria, artificially selected by disinfection strategies and lack of monitoring at the point of use, is concerning. Certain opportunistic pathogens, notably some nontuberculous mycobacteria (NTM), often exceed coliform bacteria levels in drinking water, posing safety risks. NTM and other microbiota resist chlorination and thrive in plumbing systems. When inhaled, opportunistic NTM can infect the lungs of immunocompromised or chronically ill patients, and the elderly, primarily postmenopausal women. When ingested with drinking water, NTM often survive stomach acidity, reach the intestines, migrate to other organs using immune cells as vehicles, potentially colonizing tumor tissue, including in breast cancer. The link between the microbiome and cancer is not new, yet the recognition of intratumoral microbiomes is a recent development. Breast cancer risk rises with age, and NTM infections emerged as a concern among breast cancer patients. In addition to studies hinting at a potential association between chronic NTM infections and lung cancer, NTM have also been detected in breast tumors at levels higher than normal adjacent tissue. Evaluating the risks of continued ingestion of contaminated drinking water is paramount, especially given the ability of various bacteria to migrate from the gut to breast tissue via entero-mammary pathways. This underscores a pressing need to revise water safety monitoring guidelines and delve into hormonal factors, which includes addressing the disproportionate impact of NTM infections and breast cancer on women and examining the potential health risks posed by the cryptic and unchecked microbiota from drinking water.

Optical tweezers offer a non-contact method for selecting single cells and translocating them from one microenvironment to another. We have characterized the optical tweezing of yeast S. cerevisiae and can manipulate single cells at velocities up to 0.77 mm/s using laser powers of 40 mW from a 785 nm diode laser. We have fabricated and tested three cell isolation devices; a micropipette, a PDMS chip and laser machined fused silica chip and we have isolated single bacteria, yeast and cyanobacteria cells. The most effective isolation was achieved in PDMS chip, where single yeast cells were grown and observed for 18 hours without contamination. The duration of budding in S. cerevisiae was not affected by the laser parameters used, but the time from tweezing until the first budding event began increased with increase laser energy (laser power x time). Cells tweezed using 25 mW for 1 minute were viable after isolation. We have constructed a micro-consortium of yeast cells, and a co-culture of yeast and bacteria, using optical tweezers in combination with the PDMS network of channels and isolation chambers, which may impact on both industrial biotechnology and understanding pathogen dynamics.

Background: Despite advances in the treatment of hepatocellular carcinoma (HCC) over the last few decades, treatment opportunities for patients with HCC remain limited. HCC is the most common form of liver cancer, accounting for approximately 90% of all cases worldwide. Moreover, apart from the current pharmacological interventions, hepatic resection and liver transplantation are the mainstay curative approaches for patients with HCC. Methods: This systematic review included phase I, II, III, and IV clinical trials (CTs) and randomized controlled trials (RCTs) on current treatments for patients with HCC in an Asian population (2013–2023). A total of 427 articles were screened, and 184 non-duplicate publications were identified. After screening titles and abstracts, 96 publications were excluded, and another 28 were excluded after full-text screening. The remaining 60 eligible RCTs/CTs were finally included. Results: Sixty clinical trials fulfilled our inclusion criteria and screened 36 drugs as monotherapy or combination therapy for HCC. Most studies used sorafenib alone or in combination with any of the treatment regimens. Lenvatinib or atezolizumab with bevacizumab was used for HCC after initial sorafenib treatment. Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. Conclusion: This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicated that sorafenib alone or in combination with atezolizumab and bevacizumab has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in an Asian population

The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting "nodes" in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour, before considering future directions in the field.

Mitochondria are dynamic organelles that can adjust and respond to different stimuli within a cell. This plastic ability allows them to effectively coordinate several cellular functions in cells and becomes particularly relevant in highly complex cells such as neurons. An imbalance in mitochondrial dynamics can disrupt mitochondrial function, leading to abnormal cellular function and ultimately to a range of diseases, including neurodegenerative disorders. Regulation of mRNA transport and local translation inside neurons is crucial for maintaining the proteome of distal mitochondria, which is vital for energy production and synaptic function. A significant portion of the axonal transcriptome is dedicated to mRNAs for mitochondrial proteins, emphasizing the importance of local translation in sustaining mitochondrial function in areas far from the cell body. In neurons, local translation and the regulation of mRNAs encoding mitochondrial-shaping proteins could be essential for synaptic plasticity and neuronal health. The dynamics of these mRNAs, including their transport and local translation, may influence the morphology and function of mitochondria, thereby affecting the overall energy status and responsiveness of synapses. Comprehending the mitochondria-related mRNAs regulation and local translation, as well as its influence on mitochondrial morphology near the synapses will help to better understand neuronal physiology and neurological diseases where mitochondrial dysfunction and impaired synaptic plasticity play a central role.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising chemotherapeutic agent because of its selective apoptotic action on cancer cells. However, resistance to TRAIL-induced apoptosis remains a challenge in many cancers. The gintonin-enriched Panax ginseng extract fraction (GEF) has diverse pharmacological benefits. We explored the combined efficacy of GEF and TRAIL in inducing apoptosis in human renal cell carcinoma (RCC) cells. The effect of GEF treatment on viability, clonogenic potential, wound healing, and TRAIL-induced apoptotic signaling of RCC cells was studied in vitro. Our investigation revealed that GEF pre-treatment sensitized RCC cells to TRAIL-induced apoptosis, as evidenced by DNA fragmentation and cell proliferation, colony formation, and migration inhibition. This sensitization was linked to the upregulation of death receptors 4 and 5 and alterations in apoptotic protein expression; notably, decreased expression of Mu-2-related death-inducing gene, a novel anti-apoptotic protein. Our findings underscore the necessity of caspase activation for GEF/TRAIL-induced apoptosis using the pan-caspase inhibitor Z-VAD-FMK. It demonstrates that GEF sensitizes human RCC cells to TRAIL-induced apoptosis by upregulating DR4/5 and modulating apoptotic protein expression. These findings suggest a promising strategy for overcoming TRAIL resistance in cancer therapy and highlight the potential of GEF as a valuable adjunct to TRAIL-based treatments.

During the last few years, advancement in the area of biochemistry, science of the material world, engineering and computer-aided testing has directed towards advancement of high-throughput tools for the sake of profiling information encoded in a gene. Single-cell RNA-sequencing (scRNA-seq) tools capable to examine the sequence data from each individual cells and it shows within population variety and permit exploring of cell conditions and transformation by extreme resolution, possibly give out cell sub-types or gene expression fluctuations that are shaded in mass sequencing processes, which shows population-averaged evaluations. Yet, the major disadvantage for this tool is the lack of success to pick out location related details of the RNA transcriptome, as this needs tissue detachment and cell isolation. Location based transcript determination is among the advancements in the area of medical biotechnology as this can find out the molecules like RNA dataset in their intact physical placement in tissue segment with spatial context at the scale of a single-cell, which is very advantageous as compare to single-cell sequencing techniques. These approaches give key observation in the areas of biomedical field sub-disciplines like neurology, embryology, carcinoma study, immune cell investigation and histological activities. Generally, this review mainly focused towards single-cell sequencing methods, technology development, its challenges observed, different expression data analysis mechanisms and their applications in different areas, such as in cancer research, microbes, central nervous system, sex organs and immune-biology, intensifying the essentiality of sequencing tools at single-cell level for the characterization of extremely dynamic individual cells.

The snATAC + snRNA platform allows epigenomic profiling of open chromatin and gene expression with single-cell resolution. The most critical assay step is to isolate high-quality nuclei to proceed with droplet-base single nuclei isolation and barcoding. With the increasing popularity of multiomic profiling in various fields, there is a need for optimized and reliable nuclei isolation methods, mainly for human tissue samples. Herein we compared different nuclei isolation methods for cell suspensions, such as peripheral blood mononuclear cells (PBMC, n=18) and a solid tumor type, ovarian cancer (OC) (n=18), derived from debulking surgery. Nuclei morphology and sequencing output parameters were used to evaluate the quality of preparation. Our results show that NP-40 detergent-based nuclei isolation yields better sequencing results than collagenase tissue dissociation for OC, significantly impacting cell identification and analysis. Given the utility of applying such techniques to frozen samples, we also tested frozen preparation and digestion (n=6). A paired comparison between frozen and fresh samples validated the quality of both specimens. Finally, we demonstrate the reproducibility of scRNA and snATAC + snRNA platform, by comparing the gene expression profiling of PBMC. Our results highlight how the choice of nuclei isolation methods is critical for obtaining quality data in multiomic assays. It also shows that the measurement of expression between scRNA and snRNA is comparable and effective for cell type identification.

The anatomy of mature vertebrate hearts is marked by a looped design, which is roughly characterized by two components: (1), s-shaped (sigmoid) routing of the cardiac flow path(s), and (2,) bilaterally asymmetric (chiral) routing of the cardiac flow path(s). The looped heart design is regarded as a phylogenetically conserved feature among vertebrates and is thought to represent a significant determinant of the cardiac pumping function. It evolves during the embryonic period of development by a morphogenetic process called “cardiac looping”. During the past decades, remarkable progress has been made in the uncovering of the genetic, molecular, and biophysical factors contributing to cardiac looping. Thereby, a special focus was directed on the evolution of a bilaterally asymmetric (chiral) heart configuration, which is said to play a central role in the determination of the alignments and separations of the pulmonary and systemic flow paths in the multi-chambered hearts of tetrapods. In contrast to the recent progress made in uncovering of the biological driver of cardiac looping, our present knowledge about the functional consequences of cardiac looping is at an immature state. This article provides an overview and discussion of the currently available information about the looped design of vertebrate hearts and its functional implications.

Taiwan’s auditors have suffered from processing excessive audit data, including drawing audit evidence. This study advances sampling techniques by integrating machine learning with sampling. This machine learning integration helps avoid sampling bias, keep randomness and variability, and target the risker samples. We first apply a Naive Bayes classifier to classify data into some classes. Next, a user-based, item-based, or hybrid approach is employed to draw audit evidence. The representativeness index is the primary metric for measuring the representativeness of audit evidence. The user-based approach denotes the selection of samples between two percentiles in a class as audit evidence. It may be equivalent to a combination of monetary and variable sampling methods. The item-based approach represents the choice of risky samples as audit evidence. It may be identical to a combination of non-statistical and monetary sampling methods. Auditors can hybridize those user-based and item-based approaches to balance representativeness and riskiness in selecting audit evidence. Three experiments show that sampling using machine learning integration has the benefits of drawing unbiased samples, handling complex patterns, correlations, and unstructured data, and improving efficiency in sampling big data. However, the limitations are the classification accuracy output by machine learning algorithms and the range of prior probabilities.

JAK2 V617F is a somatic mutation associated with myeloproliferative neoplasm (MPN): polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In MPNs this mutation is associated with the germline GGCC (46/1) haplotype. Most studies consider the association of the JAK2 haplotypeGGCC_46/1 with some MPNs clinical parameters but no one analyzed the association between JAK2 haplotypeGGCC_46/1 and the onset of onco-drug resistance. Thus, we assessed for JAK2 46/1 haplotype correlation with therapy response in JAK2 V617F positive patients. Patients with MPN, selected by the Hematology Laboratory of “V. Fazzi” Hospital (LE), were analyzed with RLFP-PCR assay with rs10974944 SNP. Most of them had PV (63%) or PMF (61%). Among patients that developed onco-drug resistance, 58% had C/G genotype and only 11% had the G/G allele. No correlation between onco-drug resistance and JAK2 haplotype 46/1 variants emerged. Nevertheless, we observed that G/G allele seems to be related to MPNs evolution to myelofibrosis and to the development of onco-drug resistance clinical parameters (p-value= 0.002449; odd ratio of 3.701209). Thus, although other analyses are required, due to the narrow cardinality of sample, our findings suggest how the G/G allele could be useful for MPNs diagnosis and for the prediction of the disease outcome.

Single-cell RNA sequencing (scRNA-seq) technique has enabled detailed analysis of gene expression at the single cell level, enhancing the understanding of subtle mechanisms that underly pathologies and drug resistance. To derive such biological meaning from sequencing data in oncology, some critical processing must be performed, including identification of the tumor cells by markers and algorithms that infer copy number variations (CNVs). We compared the performance of sciCNV, InferCNV, CopyKAT and SCEVAN tools that identify tumour cells by inferring CNVs from scRNA-seq data. Sequencing data from Pancreatic Ductal Adenocarcinoma (PDAC) patients, adjacent and healthy tissues were analysed, and the predicted tumor cells were compared to those identified by well-assessed PDAC markers. Results from InferCNV, CopyKAT and SCEVAN overlapped by less than 30% with InferCNV showing the highest sensitivity (0.72) and SCEVAN the highest specificity (0.75). We show that the predictions are highly dependent on the sample and the software used, and that they return so many false positives hence are of little use in verifying or filtering predictions made via tumor biomarkers. We highlight how critical this processing can be, warn against the blind use of these software and point out the great need for more reliable algorithms.

The identification and molecular characterization of cellular hierarchies in complex tissues is key to understanding both normal cellular homeostasis and tumorigenesis. The mammary epithelium is a heterogeneous tissue consisting of two main cellular compartments, an outer basal layer containing myoepithelial cells and an inner luminal layer consisting of estrogen receptor-negative (ER⁻) ductal cells and secretory alveolar cells (in the fully functional differentiated tissue) and hormone-responsive estrogen receptor-positive (ER⁺) cells. Recent publications have used single-cell RNA-sequencing (scRNA-seq) analysis to decipher epithelial cell differentiation hierarchies in human and murine mammary glands, and reported the identification of new cell types and states based on the expression of the luminal progenitor cell marker KIT (c-Kit). These studies allow for comprehensive and unbiased analysis of the different cell types that constitute a heterogeneous tissue. Here we discuss scRNA-seq studies in the context of previous research in which mammary epithelial cell populations were molecularly and functionally characterized, and identified c-Kit⁺ progenitors and cell states analogous to those reported in the recent scRNA-seq studies.

The COVID-19 pandemic has significantly impacted human health and daily life. Meteorological factors play a crucial role in virus transmission. Understanding these factors is critical for pandemic control, yet debates continue due to variations in research methods and data. This study uses a global dataset and focuses on administrative units smaller than 10,000 km². The relationship between daily COVID-19 incidence rates and meteorological factors—including temperature, relative humidity (RH), ultraviolet radiation (UVR), and diurnal temperature range (DTR)—was analyzed across 173 units in 62 countries. The results revealed significant nonlinear responses and lag effects between incidence rates and the meteorological factors. Key inflection points were observed at 0°C and 24°C for temperature, 63% for RH, 102 KJ/m² for UVR, and 15°C for DTR. Below 0°C, infection risk increased with rising temperatures; from 0°C to 24°C, risk decreased; and above 24°C, risk escalated rapidly. RH below 63% correlated inversely with infection risk, while above 63%, the correlation was positive. Infection risk decreased with UVR below 102 KJ/m² but increased beyond this threshold. These nonlinear responses are primarily driven by the differential effects of these factors on virus survival, transmission, and human immunity. Conditions around 24°C, 63% RH, 102 KJ/m² UVR, and DTR below 15°C appear optimal for human immunity, correlating with lower infection risk. High temperature and low UVR prompted immediate infection responses, while low temperatures, high UVR, and larger DTR showed delayed effects. These findings provide new, more reliable evidence for understanding the mechanisms driving COVID-19 pandemic dynamics and for preventing the future normalization of the epidemic.

Cholesterol homeostasis is pivotal for cellular function. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), also abbreviated as SOAT1, is an enzyme catalyzing the storage of excess cholesterol to cholesteryl esters. ACAT1 is an emerging target to treat diverse diseases including atherosclerosis, cancer, and neurodegenerative diseases. F12511 is a high affinity ACAT1 inhibitor. Previously, we developed a stealth liposome-based nanoparticle to encapsulate F12511 to enhance its delivery to the brain and showed its efficacy in treating a mouse model for Alzheimer’s disease (AD). In this study, we introduce F26, a close derivative of F12511 metabolite in rats. F26 was encapsulated in the same DSPE-PEG2000/phosphatidylcholine (PC) liposome-based nanoparticle system. We employed various in vitro and in vivo methodologies to assess F26's efficacy and toxicity compared to F12511. Results demonstrate that F26 is more effective and durable than F12511 in inhibiting ACAT1, in both mouse embryonic fibroblasts (MEFs) and in multiple mouse tissues including the brain tissues, without exhibiting any overt systemic or neurotoxic effects. This study demonstrates the superior pharmacokinetic and safety profile of F26 in wild-type mice, and suggests its therapeutic potential against various neurodegenerative diseases including AD.

This study employs the reflection symmetry decomposition (RSD) method to extract polarization scattering features from ground object images, aiming to determine the optimal data input scheme for deep learning networks in polarimetric synthetic aperture radar classification. Eight distinct polarizing feature combinations are designed, and the classification accuracy of various approaches is evaluated using the classic convolutional neural networks(CNNs) AlexNet and VGG16. The findings reveal that the commonly employed 6-parameter input scheme, favored by many researchers, lacks the comprehensive utilization of polarization information and warrants attention. Intriguingly, leveraging the complete 9-parameter input scheme based on the polarization coherence matrix results in improved classification accuracy. Furthermore, the input scheme incorporating all 21 parameters from the RSD and polarization coherence matrix notably enhances overall accuracy and the Kappa coefficient compared to the other 7 schemes. This comprehensive approach maximizes the utilization of polarization scattering information from ground objects, emerging as the most effective CNN input data scheme in this study. Additionally, the classification performance using the second and third component total power values (P2 and P3) from the RSD surpasses the approach utilizing surface scattering power value (PS) and secondary scattering power value (PD) from the same decomposition.

Abstract Octreotide is the first synthetic peptide hormone, consisted of eight amino acids, that mimics the activity of somatostatin, a natural hormone in the body. During the past decades, advanced instrumentation and crystallographic software established X-ray Powder Diffraction (XRPD) as a valuable tool for extracting structural information of biological macromolecules. The latter was demonstrated by the successful structural determination of octreotide at a remarkably high d-spacing resolution (1.87 Å) (PDB code: 6vc1). This study focuses on the response of octreotide to different humidity levels and temperatures, with a particular focus on the stability of the polycrystalline sample. XRPD measurements were accomplished employing an Anton Paar MHC-trans humidity-temperature chamber installed within a laboratory X’Pert Pro diffractometer (Malvern Panalytical). The chamber is employed to control and maintain precise humidity and temperature levels of samples during XRPD data collection. Pawley analysis of the collected data sets revealed that the octreotide polycrystalline sample is remarkably stable and no structural transitions were observed. The compound retains its orthorhombic symmetry (space group: P212121, a = 18.57744(4) Å, b = 30.17338(6) Å, c = 39.70590(9) Å, d~ 2.35 Å). However, a characteristic structural evolution in terms of lattice parameters and volume of the unit-cell is reported mainly upon controlled relative humidity variation. In addition, an improvement of signal-to-noise ratio in the XRPD data under a cycle of dehydration/rehydration is reported. These results underline the importance of considering the impact of environmental factors, as humidity and temperature, in the context of structure-based drug design, thereby contributing to the development of more effective and stable pharmaceutical products.

In this study, the microbial strain was isolated from the humus soil to ferment Sophora flavescens and Eleutherococcus sessiliflorus extracts. The isolated microbial was identified as Bacillus genus by 16S rRNA sequence analysis. The fermented plant extracts exhibited the antifungal effects against four types of the plant pathogens such as P. carotorum, B. cinerea, C. fructicola Sau-3, and C. gloeosporioides according to incubation time. Especially, the fermented plant extracts showed the most active activities for Colletotrichum genus to inhibit mycelium growth. Metabolite changes in fermented S. flavescens and E. sessiliflorus extracts were confirmed through LC-Q-TOF/MS. Flavonoid and peptide derivatives were improved in fermented S. flavescens and E. sessiliflorus extracts compared to their unfermented one, respectively. This study suggested that the isolated Bacillus microbial fermentation could be a valuable tool in improving the bioactivity of S. flavescens and E. sessiliflorus extracts to have potential with more environmentally-friendly antifungal agents.

Many of the fundamental molecules of life share extraordinary pigment-like optical properties in the long-wavelength UV-C spectral region. These include strong photon absorption and rapid (sub pico-second) dissipation of the induced electronic excitation energy into heat through peaked conical intersections. These properties have been attributed to a ``natural selection'' of molecules resistant to the dangerous UV-C light incident on Earth's surface during the Archean. In contrast, the ``thermodynamic dissipation theory for the origin of life'' argues that, far from being detrimental, UV-C light was, in fact, the thermodynamic potential driving the dissipative structuring of life at its origin. The optical properties were thus the thermodynamic ``design goals'' of microscopic dissipative structuring of organic UV-C pigments, today known as the ``fundamental molecules of life'', from common precursors under this light. This ``UV-C Pigment World'' evolved towards greater solar photon dissipation through more complex dissipative structuring pathways, eventually producing visible pigments to dissipate less energetic, but higher intensity, visible photons, up to wavelengths of the ``red-edge''. The propagation and dispersal of organic pigments, catalyzed by animals, and their coupling with abiotic dissipative processes, such as the water cycle, culminated in the apex photon dissipative structure, today's biosphere.

Every individual at some point encounters the progressive biological process of aging which is considered one of the major risk factors for common diseases. The main drivers of aging are oxi-dative stress, senescence, and Reactive oxygen species (ROS). The renin-angiotensin-aldosterone system (RAAS) includes several systematic processes for the regulation of blood pressure which is caused by an imbalance of electrolytes. During activation of RAAS, binding of angiotensin II (ANG II) to angiotensin II type I receptor (AGTR1) activates intracellular NADPH oxidase to generate superoxide anions and promote uncoupling of endothelial NO synthase, which in turn decreases NO availability and increases ROS production. Promoting oxidative stress and DNA damage mediated by ANG II is tightly regulated. Individuals with sodium deficiency-associated diseases such as Gitelman syndrome (GS) and Bartter syndrome (BS) show down-regulation of inflammation-related processes and have reduced oxidative stress and ROS. Additionally, the histone deacetylase-Sirtuin-1(SIRT1) has a significant impact on the aging process with reduced activity with age. However, GS/BS patients generally sustain higher levels of SIRT1 activity than aged-matched healthy individuals. In this review, we highlight the importance of the hallmarks of aging, inflammation, and the RAAS system in GS/BS patients and how this might impact healthy aging. We further propose fu-ture research directions for studying the etiology of GS/BS at the molecular level using pa-tient-derived renal stem cells and induced pluripotent stem cells.

This research investigates precision enhancement in regional quasi-geoid refinement through ADS80 tri-linear array scanning stereoscopic imagery for aerial triangulation, coupled with GNSS gravity-potential modeling. Acquiring stereoscopic imagery and analyzing triangulation accuracy with the ADS80 camera, we performed this study over the Qinghai-Tibet Plateau's elevated, desolate terrain, collecting 593 GNSS points following high-precision stereoscopic imagery model. Utilizing 12 gravity satellite models, we computed geoid heights and China 1985 Yellow Sea elevations for 28 benchmarks and GNSS points, thereby refining the Qinghai Province Quasi-Geoid Model (QPQM) using geometric techniques. The findings reveal that POS-assisted ADS80 stereoscopic imagery yields high-precision triangulation with maximal horizontal and elevation accuracies of 0.083/0.116 cm and 0.053/0.09 cm, respectively, across five control point arrangements. The RMSE of normal heights for 1985, processed via these GNSS points, achieved decimeter precision. By applying error corrections from benchmarks to the 1985 elevation data from gravity satellites and performing weighted averaging, the precision of EGM2008, SGG-UGM-2, and SGG-UGM-1 models improved to 8.61 cm, 9.09 cm, and 9.38 cm, respectively, surpassing the QPQM by 9.22 cm to 9.99 cm. This research demonstrates that the proposed methods can significantly enhance the precision of regional quasi-geoid surfaces. Additionally, these methods offer a novel approach for rapidly establishing regional quasi-geoid models in the uninhabited areas of the Qinghai-Tibet Plateau.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

Microwave technology has a potential application in the extraction of zinc from sulphide ores, knowledge of the dielectric properties of these ores plays a major role in the microwave design and simulation for any process. The dielectric properties of zinc sulfide concentrate for two different apparent densities—1.54 and 1.63 g/cm³—have been measured by using the resonance cavity perturbation technique at 915 and 2450 MHz during the roasting process for the temperature ranging from room temperature to 850 °C. The variations of dielectric constant, the dielectric loss factor, the dielectric loss tangent and the penetration depth with the temperature, frequency and apparent density have been investigated numerically. The results indicate that the dielectric constant increases as the temperature increases and temperature has a pivotal effect on the dielectric constant, while the dielectric loss factor has a complicated change and all of the temperature, frequency and apparent density have a significant impact to dielectric loss factor. Zinc sulfide concentrate is high loss material from 450 to 800 °C on the basis of theoretical analyses of dielectric loss tangent and penetration depth, its ability of absorbing microwave energy would be enhanced by increasing the apparent density as well. The experimental results also have proved that zinc sulfide concentrate is easy to be heated by microwave energy from 450 to 800 °C. In addition, the experimental date of dielectric constant and loss factor can be fitted perfectly by Boltzmann model and Gauss model, respectively.

This study provides a comprehensive analysis of the conformational dynamics of pseudo-endocannabinoid receptors (p-CBRs) CB₁ and CB₂ in response to ligand binding. The ligands studied include N-arachidonoyl dopamine (NADA), Cannabidiol (CBD), known agonists (FUB-MDMB and E3R), and inverse agonists (Taranabant and AM630). Using homology models based on crystal structures (PDB ID: 5U09 for CB₁ and 5ZTY for CB₂), molecular docking, and molecular dynamics (MD) simulations, the research validates the structural integrity and dynamic behaviours of these pseudo-receptors. Induced-fit docking revealed NADA as having the highest binding affinity for both receptors, with docking scores of −13.92 kcal/mol for CB₁ and −13.32 kcal/mol for CB₂, facilitated by key hydrogen bond interactions. MD simulations over 250 ns at ~298 K showed successful equilibration, indicating the most stable interaction for NADA, thereby further validating the models. CB₁ and CB₂ exhibited distinct conformational responses to ligands, with Cα RMSD and Cα RMSF analyses suggesting a more rigid binding pocket for CB₁ and a flexible binding pocket for CB₂. These findings highlight the significance of receptor behaviour and dynamics in the development of cannabinoid-based therapeutics, supporting the potential of CBD and NADA as modulators for CB₁ and CB₂, respectively.

During choriogenesis in insects, chorion (eggshell) is formed by surrounding follicular epithelial cells in ovarioles. However, the regulatory endocrine factor(s) activating choriogenesis and the chemical components on eggshell deserve further exploration. In two representative Coleopterans, a Coccinellid Henosepilachna vigintioctopunctata and a Chrysomelid Leptinotarsa decemlineata, genes encoding the 20-hydroxyecdysone (20E) receptor heterodimer, ecdysone receptor (EcR) and ultraspiracle (USP), and two chitin biosynthesis enzymes UDP-N-acetylglucosamine pyrophosphorylase (UAP) and chitin synthase (ChS1), were highly expressed in ovaries of the young females. RNA interference (RNAi)-aided knockdown of either HvEcR or Hvusp in H. vigintioctopunctata inhibited oviposition, suppressed the expression of HvChS1, and lessened the positive signal of Calcofluor staining on the chorions, which suggests the reduction of a chitin-like substance (CLS) deposited on eggshells. Similarly, RNAi of LdEcR or Ldusp in L. decemlineata constrained oviposition, decreased the expression of LdUAP1 and LdChS1, and declined CLS contents in the resultant ovaries. Knockdown of LdUAP1 or LdChS1 caused similar defective phenotypes, i.e., reduced oviposition and CLS contents in the L. decemlineata ovaries. These results, for the first time, indicate that 20E signaling activates choriogenesis in two Coleopteran species. Moreover, our findings propose the deposition of a CLS on the chorions.

Given the accelerating scientific, clinical and consumer interest in highly-prevalent functional gastrointestinal disorders, appropriate therapeutic strategies are needed to address the many aspects of digestive dysfunction. Accumulating evidence for the crucifer-derived bioactive molecule, sulforaphane in upstream cellular defence mechanisms highlights its potential as a therapeutic candidate in targeting functional gastrointestinal conditions together with systemic disorders. This article catalogues the evolution of and rationale for a hypothesis that utilises multifunctional sulforaphane as the initial step in restoring the ecology of the gut ecosystem; it does this primarily by targeting the functions of intestinal epithelial cells. A growing body of work has identified the colonocyte as the driver of dysbiosis, so that targeting gut epithelial function could provide an alternative to targeting the microbes themselves for remediation of microbial dysbiosis. The hypothesis discussed herein has evolved over several years and is supported by case studies showing the application of sulforaphane in gastrointestinal disorders, related food intolerance and several systemic conditions. To our knowledge, this is the first time the effects of sulforaphane have been reported in a clinical environment where several of its key properties within the gut ecosystem appear to be related to its nutrigenomic effects on gene expression.

COVID-19 was an inflammatory pneumonia caused by a respiratory infection with a coronavirus named SARS-CoV-2. Severely ill COVID-19 patients could die of acute pulmonary and systemic inflammation. Thus, there was a theory that long COVID-19 shared many similarities with systemic autoimmune diseases. There was also a theory that the SARS-CoV-2 virus could infect many cell- and tissue-types distributed throughout multiple organ systems of the body. I aim to review the above theories using unbiased high-throughput datasets cataloguing gene expression. Studies reviewed used the technology of next generation sequencing, either as bulk tissue RNA sequencing, or as single-cell RNAs sequencing; ingenious methods for signal deconvolution were then used to identify individual cell types. Datasets reviewed suggested that severe COVID-19 induced expression of genes associated with pro-inflammatory signaling, tissue development or remodeling, scarring, or cell death. The datasets also provided evidence for several inflammatory syndromes associated with COVID-19, such as neuronal COVID, acute respiratory disease syndrome, vascular inflammation, or multisystem inflammatory syndrome. Indeed, inflammatory signal during severe COVID-19 was reported in many cell types, for example in structural cells, in infiltrating immune cells, in the vascular system, or in circulating cells in the blood. There was also frequently a change in proportions of immune cell-types in the blood, epithelial cells in the lungs, or among infiltrating immune cells.

Muon tomography leverages cosmic muons’ exceptional penetration capabilities to reconstruct detailed tomographic images via multiple Coulomb scattering interactions, making it invaluable for detecting High-Z materials critical to homeland security. This study introduces the Slope Intercept (SI) algorithm, a novel approach for rapid and precise tomographic image reconstruction. Implemented using Geant4 simulations in a standard-sized container tomography station, SI demonstrates superior performance in speed and simplicity compared to traditional methods. While the imaging results of SI and the Point of Closest Approach (POCA) algorithm are nearly identical, the SI algorithm is simpler to implement, requires shorter CPU time, and exhibits a smaller margin of error. Its computational efficiency and simplicity make it a robust alternative to the POCA algorithm. These findings highlight SI’s suitability for applications demanding robust imaging and efficient data processing, which are crucial for advancing security measures and scientific research.

Introduction: Chronic wounds caused by diabetes or lower-extremity artery disease are intractable because the wound healing mechanism is no longer effective due to the poor environment of the wound bed. Biosheet obtained using in-body tissue architecture (iBTA) is a collagen-based membranous tissue that is created within the body and autologously contains various growth factors and somatic stem cells including pluripotent stem cells. When applied to a wound, granulation formation can be promoted and even epithelialization may be achieved. Hearin, we report our clinical treatment experience with seven cases of intractable diabetic foot ulcers. Cases: From 46- to 93-year-old 7 patients had large foot ulcers including heel area, which was failed to heal with standard wound treatment. Methods: Two or four Biosheet-forming molds were implanted subcutaneously in the chest or abdomen, and after 3 to 6 weeks, the molds were removed. Biosheets that formed inside the mold were obtained and applied directly to the wound surface. Results: In all cases, there were no problems with the mold embedding and removal procedures, and Biosheets were formed without any infection or inflammation during the implantation period. The Biosheets were simply applied to the wounds, and in all cases, they adhered within one week, did not fall of, and became integrated with the wound surface Complete wound closure was achieved within 8 weeks in two cases and within 5 months in two cases. One patient was lost due to infective endocarditis from septic colitis. One case required lower leg amputation due to the wound recurrence, and one case achieved wound reduction and wound healing in approximately 9 months. Conclusion: Biotube obtained via iBTA promoted wound healing and were extremely useful for intractable diabetic foot ulcers involving heel area.

Mast cells are tissue-resident immune cells distributed in all tissues and strategically located close to blood and lymphatic vessels and nerves. Thanks to the expression of a wide array of receptors, mast cells act as tissue sentinels, able to detect the presence of bacteria and parasites and to respond to different environmental stimuli. Mast cells originate from bone marrow progenitors that enter the circulation and mature in peripheral organs under the influence of microenvironment factors, thus differentiating in heterogeneous tissue-specific subsets. Even though mast cell activation has been traditionally linked to IgE-mediated allergic reactions, a role for these cells in other pathological conditions including tumor progression has recently emerged. However, several aspects of mast cell biology remain to be clarified. The advent of single-cell RNA sequencing platforms has provided the opportunity to understand mast cell origin and differentiation as well as the phenotype and functions within different tissues, including the gut. This review recapitulates how single cell transcriptomic studies provided insight into mast cell development as well as into the functional role of intestinal MC subsets in health and disease.

Proper blood-brain barrier (BBB) function is essential to maintain homeostasis keeping the central nervous system healthy. Disruption of the BBB has been described in nearly all neurological disease and injury contexts. Given the various physical and metabolic roles of the BBB and gliovascular unit (GVU), dysfunction should be assessed across multiple levels to pinpoint the exact nature of the impairment. Here we describe imaging techniques for evaluating various aspects of BBB and GVU integrity and function, tailored for use in mouse models with protocols for quantitative image analysis. These imaging techniques complement classical dye tracer experiments and reveal underlying molecular causes of BBB dysfunction.

Certain species of Mucorales have been identified as causative agents of mucormycosis, a rare yet often lethal fungal infection. Notably, these fungi exhibit intrinsic resistance to common azole drugs, which target lipids. Given the pivotal role of lipids in drug resistance and their contribution to the innate resistance to azoles, this study provides a comprehensive overview of key lipid classes, including sphingolipids (SLs), glycerophospholipids(GPLs), and sterols, in Rhizopus delemar 99-880, a well-characterized reference strain among Mucorales. Through high-throughput analysis involving the identification and quantification of intermediates, we have elucidated the biosynthetic pathways of SLs, PGLs, and sterols. Notably, the acidic SLs were not found probably because the acidic branch of the SL biosynthesis pathway terminates at α-hydroxy phytoceramides as evident by their high abundance. Intermediates in the neutral SL pathway incorporated higher levels of 16:0 fatty acid compared to other pathogenic fungi. A strikingly high phosphatidylethanolamine (PE)/phosphatidylcholine (PC) ratio was observed among GPLs. Ergosterol remains the major sterol, similar to other fungi, and our analysis confirms the existence of alternate ergosterol biosynthesis pathways. The total lipidomic profile of R. delemar 99-880 offers insights into its lipid metabolism and potential implications for studying pathogenesis and drug resistance mechanisms.

[Objective] To investigate the expression of ALDH2 in hepatocellular carcinoma and its correlation with macrophage infiltration and with the activation of specific subtypes of macrophages. [Methods] Transcriptome and clinical data from patients with hepatocellular carcinoma were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases and analyzed and collated using R and Perl software. In the TCGA hepatocellular carcinoma dataset, the Wilcoxon test was used to identify macrophage activation-related gene sets that show differential expression between hepatocellular carcinoma and normal tissues. Single-cell sequencing combined with bulk data was used to analyze macrophage infiltration of hepatocellular carcinoma immune cells and the activation and recruitment of different subtypes of macrophages. Single-factor Cox regression and minimum absolute convergence and selection operator (Lasso) were used to identify survival-related genes and construct prognostic models of HCC. The patients were divided into two groups based on their model scores. The Wilcoxon test was used to identify differentially expressed genes (DEGs) between the two groups, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of the DEGs were performed. Single-sample gene set enrichment analysis (ssGSEA) was performed to explore the possible mechanism underlying the differences in prognosis. The reliability of the model was verified using the ICGC hepatocellular carcinoma dataset. A Kaplan‒Meier curve was constructed and used to analyze the influence of macrophage activation-related gene expression on survival and prognosis in patients with hepatocellular carcinoma. The log-rank test and the independent t test were used to analyze survival time data and to compare immune cell infiltration in the two groups. [Results] In a comparison of hepatocellular carcinoma and paracancerous tissues, the expression of six of 137 macrophage activation-related genes (ALDH2, CCNB2, CYP2C9, CYP3A4, F9 and KLKB1) was found to be significantly correlated with overall survival time (OS) in patients with hepatocellular carcinoma. Based on this finding, a prognosis assessment model for hepatocellular carcinoma was constructed. The OS of the patients in the high-scoring group was significantly shorter than the OS of the patients in the low-scoring group (P<0.05), and the model predicted the prognosis of patients with hepatocellular carcinoma independently of sex, age, tumor grade and stage. The area under the receiver operating characteristic (ROC) curve of the model used to predict 1-, 2-, and 3-year survival was greater than 0.7 in both the test set and the validation set. GO enrichment of DEGs between the high- and low-scoring groups of the model suggested that the DEGs are mainly related to immune function. GSEA suggested that the tumor-infiltrating immune cells in the high-scoring group were macrophages, Th2 cells and Treg cells and showed that the number of tumor-infiltrating immune cells, including NK cells, was lower in the high-scoring group than in the low-scoring group. With respect to immune function, the immune checkpoint of the high-scoring group was higher than that of the low-scoring group. Single-cell sequencing data indicated the recruitment of B cells, M0 cells, M1 cells and M2 cells to the hepatocellular carcinoma microenvironment and suggested that ALDH2 regulates related signaling pathways in a way that promotes the differentiation of macrophages into M2-type macrophages. [Conclusion] M2-type macrophages are the dominant type of macrophages associated with immune infiltration in hepatocellular carcinoma. The macrophage-associated activation gene ALDH2 activates the macrophage polarization signaling pathway and negatively regulates the differentiation of macrophages into M2-type macrophages.

Several studies have shown promising treatments for type 1 diabetes mellitus (T1DM) using developing gene therapy methods. This review article focuses on summarizing possible new treatment options and outlining their pros and cons, since there is no cure for T1DM as of yet. New treatments involve islet and stem cell transplantation, genetic vaccination, and immunological precursor cell-mediated therapy. Since most of these methods are still in their early stages, efficacy in human trials of this type of treatment is still largely unknown, however, researchers are hopeful after numerous successes in trials with non-obese diabetic (NOD) mice.

Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than pancreatic ductal adenocarcinoma. We retrospectively evaluated the clinical and molecular features of ACC patients who underwent germline and/or somatic molecular testing at The University of Texas MD Anderson Cancer Center from 2008 to 2022. Patient information was extracted from our institutional database with the approval of Institutional Review Board. We identified 16 patients with available molecular testing results. Fourteen patients had metastatic disease, 1 had borderline resectable disease, and 1 had localized resectable disease at diagnosis. Fifteen patients were wild type for KRAS (1 patient had unknown KRAS status). Somatic/germline mutations of DNA damage repair genes (BRCA1/2, PALB2, and ATM) were present in 5 of 12 patients tested for these genes. One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months. The median overall survival (OS) was 24 months for patients with metastatic disease. One of the additional two cases which had BostonGene tests was found to have NTRK1 fusion. RNA and TME analysis by BostonGene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74 and MMP1 and higher CDH6 compared with PDAC.

Barth Syndrome, a rare X-linked disorder affecting 1:300,000 live births, results from defects in Tafazzin, an acyltransferase that remodels cardiolipin and is essential for mitochondrial respiration. Barth Syndrome patients develop cardiomyopathy, muscular hypotonia and cyclic neutropenia during childhood, rarely surviving to middle age. At present, no effective therapy exists and downstream transcriptional effects of Tafazzin dysfunction are incompletely understood. To identify novel, cell-specific, pathological pathways that mediate heart dysfunction, we performed single-nucleus RNA-sequencing (snRNA-seq) on wild-type (WT) and Tafazzin-knockout (Taz-KO) mouse hearts. We determined differentially expressed genes (DEGs) and inferred predicted cell-cell communication networks from these data. Surprisingly, DEGs were distributed heterogeneously across the cell types, with fibroblasts, cardiomyocytes, endothelial cells, macrophages, adipocytes and pericytes exhibiting the greatest number of DEGs between genotypes. One differentially expressed gene was detected for the lymphatic endothelial and mesothelial cell types, while no significant DEGs were found in the lymphocytes. A Gene Ontology (GO) analysis of these DEGs showed cell-specific effects on biological processes such as fatty acid metabolism in adipocytes and cardiomyocytes, increased translation in cardiomyocytes, endothelial cells and fibroblasts, in addition to other cell-specific processes. Analysis of ligand-receptor pair expression, to infer intercellular communication patterns, revealed the strongest dysregulated communication involved adipocytes and cardiomyocytes. For the knockout hearts, there was a strong loss of ligand-receptor pair expression involving adipocytes, and cardiomyocyte expression of ligand-receptor pairs underwent reorganization. These findings suggest that adipocyte and cardiomyocyte mitochondria may be most sensitive to mitochondrial Tafazzin deficiency and that rescuing adipocyte mitochondrial dysfunction, in addition to cardiomyocyte mitochondrial dysfunction, may provide therapeutic benefit in Barth Syndrome patients.

Conventional traceability systems in Cambodian agriculture, such as Rubber Supply Chain Management (RSCM), often struggle to provide timely data and fair market prices, leading to mistrust among stakeholders, exploitation by intermediaries, and hindering progress towards ethical sourcing and sustainable practices. This research aims to showcase the potential of integrating blockchain technology, the Internet of Things (IoT), the InterPlanetary File System (IPFS), and Differential Privacy (DP) methods to empower Cambodian rubber farmers. By enhancing transparency, facilitating fair pricing, and promoting sustainable methods in the rubber industry, this integrated approach leverages Hyperledger Fabric (HLF) to create a decentralized and secure system for tracking rubber from its source to the end consumer. Integration with IPFS ensures secure and easily accessible data storage, further enhancing the system’s reliability. Additionally, the implementation of differential privacy techniques safeguards confidential data during information sharing among farmers and supply chain stakeholders, minimizing potential privacy concerns. This comprehensive system encourages consumers to make ethical and sustainable alternative options by providing accessible information on harvesting methods, processing procedures, labor conditions, and environmental impacts. The potential benefits extend beyond Cambodia, serving as a model for other developing countries aiming to modernize and enhance the agricultural distribution networks. Our results show that transaction send rates (TPS) and throughput in systems with and without differential privacy grow with increased transaction volumes. However, the system without differential privacy achieves greater scalability and efficiency above a certain threshold. However, it offers a slightly reduced latency, reflecting a trade-off between privacy and performance efficiency in blockchain-based agricultural traceability systems.

Survival of Medulloblastoma (MB) depends on various factors, including the gene expression profiles of MB tumor tissues. In this study, we identified 967 MB survival related genes (SRBs) using the gene expression dataset of Cavalli et al. (2017) and the Cox proportional hazards regression model. Notably, the SRGs were over-represented on chromosomes 6 and 17, known for the abnormalities monosomy 6 and isochromosome 17 in MB. The most significant SRG was HMGA1 (high mobility group AT-hook 1), which is a known oncogene and a histone H1 competitor. High expression of HMGA1 was associated with worse survival, primarily in the Group 3γ subtype. The high expression of HMGA1 was unrelated to any known somatic copy number alteration. Most SRGs on chromosome 17p were associated with low expression in Group 4β, the MB subtype with 93% deletion of 17p and 98% copy gain of 17q. Pathway analysis showed that both chromosomes 6 and 17 included SRGs related to telomere maintenance and provide a rationale for testing telomerase inhibitors in Group 3 MBs. We conclude that HMGA1, along with other SRGs on chromosome 6 and 17 warrant further investigation as potential therapeutic targets in selected subgroups or subtypes of MB.

Under physiological conditions the blood-brain barrier (BBB) is required for regulating the passage of substances between the bloodstream and the brain. To date, disruption of the BBB has been associated with nearly all neurological diseases. Dye and tracer experiments have been used to assess BBB integrity for decades, yet quantitative assessment of these experiments has only recently been implemented. Further, interpretation of these results requires the consideration of tracer-specific properties. Here, we describe a protocol for evaluating BBB leakage using the small molecule cadaverine in quantitative way. We also cover advantages/disadvantages of using some reagents and highlight limitations in data interpretations based on assays used to assess BBB permeability.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, with a highly variable expression of phenotypes (restricted interest or activity and repetitive behavior in communication and social interactions), genes (mutation), markers (alteration of transcription) and pathways. Loss of function of the CC2D1A gene appears to primarily affect the brain, leading to a range of behavioral problems in humans. In our study published in 2020; we found that the expressions of miR-19a-3p, miR-361-5p, miR-150-5p, miR-3613-3p, miR-126-3p and miR-499a-5p were downregulated in the serum samples of autistic patients and their families. Here, acquired non-Mendelian hereditary character in a genetically defined mouse model of autism (Cc2d1a +/-) correlates with the transcriptional alteration of five miRNAs. We seek to test the hypothesis that miRNA levels are varying by changes in RNA/DNA structure during development, thereby creating transcription alteration. Behavioral tests were conducted on the offspring of Cc2d1a +/- mutant and control mice, such as novel object, social interaction, marble burying and tail suspension behavior. Two RNA fractions were isolated from mouse hippocampal tissues and sperm cells by standard TRIzol extraction: total RNA and fraction of RNA bound to DNA in the form of a DNA/RNA hybrid (R-loop). The expression levels of miR-19a-3p, miR-361-5p, miR-150-5p, miR-126-3p and miR-499a-5p were investigated by quantitative real-time RT-PCR. We report differences in the distribution of five miRNAs in the hippocampus between male and female mice in RNA fractions, particularly in colonies of Cc2d1a +/- mice. Furthermore, the number of miRNAs engaged in the DNA/RNA hybrid fraction is generally higher in the mutant pedigree than in the control group. On the other hand, in sperm both fractions are at lower levels than in controls. R-loops contribute to the physiology and pathology of organisms including human disease. Here we report a variation in five miRNA levels between gender and tissue. Our results suggest that the transcription levels of these five miRNAs are directly regulated by their RNA.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

Proteins need to be located in appropriate spatiotemporal contexts to carry out their diverse biological functions. Mislocalized proteins may lead to a broad range of diseases, such as cancer and Alzheimer’s disease. Knowing where a target protein resides within a cell will give insights into tailored drug design for a disease. As the gold validation standard, the conventional wet lab uses fluorescent microscopy imaging, immunoelectron microscopy, and fluorescent biomarker tags for protein subcellular location identification. However, the booming era of proteomics and high-throughput sequencing generates tons of newly discovered proteins, making protein subcel-lular localization by wet-lab experiments a mission impossible. To tackle this concern, in the past decades, artificial intelligence (AI) and machine learning (ML), especially deep learning methods, have made significant progress in this research area. In this article, we review the latest advances in AI-based method development in three typical types of approaches, including sequence-based, knowledge-based, and image-based methods. We also elaborately discuss existing challenges and future directions in AI-based method development in this research field.

Knowledge is not merely the characteristic of certain pieces of information being deemed true, believed and justifiable, but rather a process. The sentences that reaches the status of knowledge forms a universe that provides an interpretation of the reality one aims to describe. Language exchanges information through communication and the justification, if concludes successfully with respect to a sentence, it elevates the information to the status of knowledge. We provide a model where we define the fundamental elements of communication and grammar. As a result, knowledge must be \open\ (everyone must be able to acquire it), \free\ (everyone must be able to justifiy) and \tidy\ (everyone must be able to retrace the justification process in all its parts recursively). Ultimately, the development of knowledge processing, referred to as \emph{knowmatic}, represents the evolution of the information technologies (\it).

Robotic systems have been widely used in various industries, so the security of communication between robots and their components has become an issue that needs to be focused on. As a framework for developing robotic systems, the security of ROS2 can directly affect the security of the upper-level robotic systems. Therefore, it is a worthwhile research topic to detect and analyze the security of ROS2. In this paper, we adopt a formal approach to analyze the security of the communication mechanism of ROS2. First, we use a state transition system to model the potential vulnerabilities of ROS2 based on the ROS2 communication mechanism and the basic process of penetration testing. Secondly, we introduce the CIA model on the basis of the established vulnerability model and use LTL to define its security properties. Then, we design and implement a vulnerability detection tool for ROS2 applications based on the vulnerability model and security properties. Finally, we experimentally test some ROS2-based applications, and the results show that ROS2 has vulnerabilities without additional protection safeguards.

Atypical hemolytic uremic syndrome (aHUS) is a rare and life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, necessitating differentiation from other thrombotic microangiopathy disorders. Definitive biomarkers for disease diagnosis and activity are currently lacking, and identifying molecular markers is essential. We conducted single-cell sequencing on peripheral blood mononuclear cells from 13 aHUS patients, 3 aHUS family members, and 4 healthy controls. Analysis included clustering, cell type annotation, pseudotime estimation, and cell-cell communication. Immune cell populations differ among aHUS, aHUS families, and healthy controls. Disease activity and treatment influence T, NK, B, and monocyte subpopulations, with increased intermediate monocyte levels distinguishing aHUS from controls and aHUS groups with varying disease activity. Subclustering revealed differential gene expression in patients compared to controls; higher expression of mitochondria-related genes suggests cell metabolism may influence clinical course. Pseudotime trajectory analysis demonstrated unique immune cell differentiation, and cell-cell interaction analysis identified distinct signaling pathways among patients, family members, and controls. This single-cell sequencing study is the first to confirm immune cell dysregulation in aHUS pathogenesis, offering valuable insights into molecular mechanisms and potential new diagnostic and disease activity markers.

African yam bean (Sphenostylis stenocarpa Hochst, Ex. A. Rich. Harms) is an important grain legume in sub-Saharan Africa because of its nutritional value and adaptability to various agroecological zones. To foster the varietal development of improved African yam bean (AYB) genotypes with economic traits, it is necessary to validate parental polymorphism for key markers in selecting progenies from crosses between desired parents. The study aims to analyze the genetic fidelity between parents and F1 progenies in African yam bean through putative cowpea Simple sequence repeat (SSR) markers. Hence, a total of seventy-seven progenies were derived from four sets of biparental crossings using drought-susceptible (TSs-96, TSs-363, and TSs-274) and drought-tolerant (TSs-417, TSs-111, and TSs-78) AYB accessions. These were validated using 120 cowpea primers targeting SSR under optimal PCR conditions, and the size of the PCR-amplified DNA fragments was checked using gel electrophoresis. Twenty primers exhibited polymorphism in the parental lines, while ten displayed higher levels of the same polymorphism. The average polymorphism level for the surveyed SSR markers was 0.36. Given these findings, our study demonstrates that cowpea SSR markers are a reliable method for regular testing and clear identification of AYB crosses, indicating potential AYB improvements.

Pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R) has a higher affinity for pituitary adenylate cyclase- activating polypeptide (PACAP) than for vasoactive intestinal peptide (VIP). PACAP exerts its neuroprotective effects through PAC1-R. PAC1-R has become a target for drug development, and we targeted PAC1-R to screen small positive allosteric modulator 1 (SPAM1). SPAM1 has a neuroprotective effects, and in the D-galactose (D-gal) mouse model, SPAM1 improved the structure of the hippocampal dentate gyrus and restored the number of neurons. Compared with D-gal model mice, SPAM1 treatment upregulated the expression of Sirtuin 6 (SIRT6) and Lamin B1, and downregulated the expression of YinYang 1 (YY1) and p16. Consistent with this, the same results were obtained in senescent RGC-5 cells. Meanwhile, SPAM1 was also found to up-regulate SIRT6 and down-regulate YY1 expression in normal RGC-5 cells. Then, we further explored the mechanism of SPAM1 neuroprotection by whole transcriptome sequencing and proteomic analysis, and found that SPAM is involved in the longevity regulating pathway, and confirmed the up-regulation of neurofilament light polypeptide and neurofilament medium polypeptide by western blot, thus laying a pharmacological foundation for SPAM1 as a therapeutic agent for neurodegenerative diseases. polypeptide and neurofilament medium polypeptide. Thus, it lays a pharmacological foundation for SPAM1 as a therapeutic drug for neurodegenerative diseases.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

It is important for food recognition to separate each ingredient within a food image at the pixel level. In this paper, we propose a new approach to segment ingredients by utilizing a CNN-based Single-Ingredient Classification Model. In detail, we firstly introduce a standardized biological-based hierarchical ingredient structure and construct a single-ingredient image dataset based on this structure. Then, we build a single-ingredient classification model based on a novel convolutional neural network (CNN) architecture that utilizes an attention mechanism. Afterwards, we propose a new framework for segmentation using the above single-ingredient classification model as the backbone. In this framework, two methods are involved in segmenting ingredients in the food images. We introduce five evaluation metrics (IoU, Dice, Purity, Entirety, Loss of GTs) to assess the performance of ingredient segmentation in terms of ingredient classification. Extensive experiments demonstrate the effectiveness of the proposed method, achieving an maximal mIoU of 0.65, mDice of 0.77, mPurity of 0.83, mEntirety of 0.80, and mLoGTs of 0.06 on the FoodSeg103 dataset. The results confirm that our CNN-based architecture achieves higher segmentation performance compared to ResNet18 and EfficientNet-B0 when used as the backbone for ingredient segmentation. We believe that our ingredient segmentation approach lays the foundation for subsequent ingredient recognition.

In recent years, graphene has received so much attention because of its superlative properties and its potential to revolutionize electronics especially in VLSI. This study analyzes the effect of single event upset (SEU) in SRAM cell which employs metal-oxide semiconductor type graphene nano-ribbon field effect transistor (MOS-GNRFET) and compares the results respectively with another SRAM cell designed in PTM 10nm FinFET node. Our simulation show there is a change in data stored in the SRAM after heavy ion strike. However, it recovers from radiation effects after 0.46 ns for GNRFET and 0.51 ns for FinFET. Since the degradation observed in Q and Qb of GNRFET SRAM are 2.7X and 2.16X as compared to PTM nano-MOSFET, we can conclude that GNRFET is less robust to single effect upset. In addition, the stability of SRAM can be improved by increasing the supply voltage VDD.

Background: Biological processes are based on complex networks of cells and molecules. Single cell multi-OMICs is a new tool aiming to provide new incites in the complex network of events controlling the functionality of the cell.; Methods: Since single cell technologies provide many sample measurements, they are the ideal environment for the application of deep learning and machine learning approaches. An autoencoder (AE) is composed of an encoder and a decoder sub-model. AE are very powerful in data compression and noise removal. However, the decoder model remains a black box from which is impossible to depict the contribution of the single input elements. We have recently developed a new class of autoencoders, called Sparsely Connected Autoencoders (SCA), which have the advantage of providing a controlled association among the input layer and the decoder module. This new architecture has the benefit that the decoder model is no anymore a black box and it can be used to depict new biologically interesting features from single cell data; Results: In this paper, we show that SCA hidden layer can grab new information usually hidden in single cell data, like as providing clustering on meta-features difficult, i.e. transcription factors expression, or impossible, miRNA expression, to depict in single cell RNAseq data. Furthermore, a SCA representation of cell clusters has the advantage of simulating a conventional bulk RNAseq, which is a data transformation allowing the identification of similarity among independent experiments; Conclusions: In our opinion, SCA represent the bioinformatics version of a “Swiss Army knife” for the extraction of hidden knowledgeable features from single cell OMICs data.

Single cell proteins are the dead dried cells of microorganisms or purified protein isolated from microorganism’s cell culture, used as a food supplement to humans’ food and animals feed. World suffer from malnutrition particularly developing countries, due to rapid increase in population, increased the demand for protein and nutrients requirement. Bacteria is potential microorganism for SCP production due to high protein content, fast generation time, bio-active secondary metabolites production and can grow on various substrates. Actinobacteria species and strain have capability to produce biological active compounds, produced about two-thirds of antibiotics available in the market, actively used as antibiotics, antiprotozoal, antifungal, antiviral, anticancer, anticholesterol, antihelminth and immunosuppressant. Actinomycetes can be used as probiotic as well as single cell protein that will deal with antibiotic as well as protein source.

Plant cells are omnipotent and breeding of new varieties can be achieved by protoplast fusion. Such fusions can be achieved by treatment with poly(ethylene glycol) or by applying an electric field. Microfluidic devices allow for controlled conditions and targeted manipulation of small batches of cells down to single cell analysis. To provide controlled conditions for protoplast fusions and achieve high reproducibility, we developed and characterized a microfluidic device to reliably trap few of Arabidopsis thaliana protoplasts and induced a cell fusion by controlled addition of poly(ethylene glycol) (PEG, with a molecular weight of 6000). Experiments were conducted to determine the survival rate of isolated protoplasts in our microfluidic system. Afterwards, PEG induced fusion was studied. Our results indicate that the following fusion parameters had significant impact on the fusion efficiency and duration: PEG concentration, osmolarity of solution, and flow velocity. PEG concentration below 10% led to only partial fusion. Osmolarity of the PEG fusion solution was found to strongly impact the fusion process; complete fusion of two source cells sufficiently took part in slightly hyper osmotic solutions, whereas iso-osmotic solutions led to only partial fusion at 20% PEG concentration. We observed accelerated fusion for higher fluid velocities. Up to this study, it was common sense that fusion is one directional, i.e. once two cells were fused into one cell they stay fused. Here, we present for the first time reversible fusion of protoplasts. Our microfluidic device paves the way to a deeper understanding on the kinetics and processes of cell fusion.

In bacteria, enzymes usually comprise of enzymatic domains only. In eukaryotes/mammals, and here particularly in context of signal transduction, proteins with enzymatic functions contain additional modules promoting interactions with cooperating signaling proteins. Often such protein-protein interaction domains, such as SH2- and SH3-domains, help to localize the enzymatic function (e.g. kinase, phosphatase) to another protein, cellular compartment, or membrane nanodomain. In such cases, the interaction domain(s) serve(s) the enzymatic function. However, there are molecular situations in which an interaction domain fulfills its task completely independent of the protein´s enzymatic function and in this review, we call such function the adapter function of an enzyme. Though many stories can be told, we will concentrate on several proteins playing crucial roles in cells of the immune system, such as BTK, PI3K, and SHIP1, as well as in cancer cells, such as proteins of the RAS/ERK MAPK pathway. We will also discuss how these adaptor functions of enzymes determine or even undermine the efficacy of targeted therapy compounds, such as ATP-competitive kinase inhibitors, thereby highlighting the need to develop pharmacological approaches, such as PROTACs, that eliminate the entire protein. We also review how genetic kock-out and knock-in approaches can be leveraged to identify adaptor functions of signaling proteins.

Background: As cancer progresses, cells acquire traits that allow them to disperse and disseminate to distant locations in the body – a process known as metastasis. While in the vasculature, these cells are referred to as circulating tumour cells (CTCs) and can manifest either as single cells or clusters of cells (i.e., CTC clusters), with the latter being the most aggressive. The increased metastatic potential of CTC clusters is generally associated with cooperative group benefits in terms of survival, such as increased resistance to shear stress, anoikis, immune attacks and drugs. However, the adoption of a group phenotype poses a challenge when exiting the vasculature (extravasation) as the large size can hinder the passage through vessel walls. Despite their significant role in the metastatic process, the mechanisms through which CTC clusters extravasate remain largely unknown. Based on the observed in vivo association between CTC clusters and platelets, we hypothesized that cancer cells take advantage of the platelet-derived Transforming Growth Factor Beta 1 (TGF-β1) – a signalling factor that has been widely implicated in many aspects of cancer, to facilitate their own dissemination. To address this possibility, we evaluated the effect of exogenous TGF-β1 on an experimentally evolved non-small lung cancer cell line that we previously developed and used to investigate the biology of CTC clusters. Results: We found that exogenous TGF-β1 induced the dissociation of clusters into adherent single cells. Once adhered, cells released their own TGF-β1 and were able to individually migrate and invade in the absence of exogenous TGF-β1. Based on these findings we developed a model that involves a TGF-β1-mediated plastic switch between a cooperative phenotype and a single-celled stage that enables the extravasation of CTC clusters. Conclusions: This model allows for the possibility that therapies can be developed against TGF-β1 signalling components and/or TGF-β1 target genes to suppress the metastatic potential of CTC clusters. Considering the negative impact that metastasis has on cancer prognosis and the lack of therapies against this process, interfering with the ability of CTC clusters to switch between cooperative and individual behaviours could provide new strategies to improve patient survival.

Starting from the model of a slow-rolling missile with six degrees of freedom (6 DOF) in the body frame, a 6 DOF model in the Resal frame is obtained, which is used to linearize the coupled commanded motion. Based on the linearized model, we obtain the structural scheme of the commanded object and define the quality parameters. The obtained parameters have a complex representation (with real and imaginary parts) due to the coupling between longitudinal channels. Then, the kinematic guidance equations, the seeker equations and the actuator specific to the slow-rolling single-channel missile are defined using a switching function. The guidance kinematic equations, the seeker equations and the actuator model are linearized in the Resal frame, and the structural diagram of the homing missile is constructed. Starting from this, the characteristic polynomial having complex coefficients is determined and then analyzed with the Frank-Wall stability criterion. Based on the analysis, a stability range is determined for the navigation constant and a minimum and possibly a maximum limit for the time to hit the target is obtained. The stability range defined for the navigation constant on the linear model is finally validated on the nonlinear model in the body frame.

Conventional plaque assays rely on the use of overlays to restrict viral infection allowing the formation of distinct foci that grow in time as the replication cycle continues leading to counta-ble plaques that are visualized with standard techniques such as crystal violet, neutral red or immunolabeling. This classical approach takes several days until large enough plaques can be visualized and counted with some variation due to subjectivity in plaque recognition. Since plaques are clonal lesions produced by virus-induced cytopathic effect, we applied DNA fluores-cent dyes with differential cell permeability to visualize them by live cell imaging. We could observe different stages of that cytopathic effect corresponding to an early wave of cells with chromatin-condensation followed by a wave of dead cells with membrane permeabilization within plaques generated by different animal viruses. This approach enables an automated plaque identification using image analysis to increase single plaque resolution compared to crystal violet counterstaining and allows its application to plaque tracking and plaque reduction assays to test compounds for both antiviral and cytotoxic activities. This fluorescent real-time plaque assay sums to those next-generation technologies by combining this robust classical method with modern fluorescence microscopy and image analysis approaches for future applica-tions in virology.

ccJE+Advax is an inactivated cell culture Japanese encephalitis (JE) vaccine formulated with Advax™, a novel polysaccharide adjuvant based on delta inulin. This vaccine has previously shown promise in murine and equine studies and the current study sought to better understand its mechanism of action and assess the feasibility of single dose vaccine protection. Mice immunised with ccJE-Advax had higher serum neutralisation titres than those immunised with ccJE alone or with alum adjuvant. ccJE+Advax induced extraordinarily broad cross-neutralising antibodies against multiple flaviviruses including West Nile virus (WNV), Murray Valley Encephalitis Virus (MVEV), St Louis Encephalitis virus (SLE) and Dengue-1 and -2 viruses. Notably, the DENV-2 cross-neutralising antibodies from ccJE+Advax immunised mice uniquely had no DENV-2 antibody dependent enhancement (ADE) activity, by contrast to high ADE activity seen with DENV-1 cross-reactive antibodies induced by mbJE or ccJE alone or with alum adjuvant. JEV-stimulated splenocytes from ccJE+Advax immunised mice showed increased IL-17 and IFN-γ production, consistent with a mixed Th1 and Th17 response, whereas ccJE-alum was associated with production of mainly Th2 cytokines. There is an ongoing lack of human vaccines against particular flaviviruses, including WNV, SLE and MVEV. Given its ability to provide single-dose JEV protection as well as to induce broadly neutralising antibodies free of ADE activity, ccJE+Advax vaccine could be highly useful in all situations where rapid protection is desirable but ADE needs to be avoided, e.g. during a local outbreak or for use in travellers or the military requiring rapid travel to JEV endemic regions.

In Cameroon, Aedes mosquitoes transmit various arboviruses, posing significant health risks. We aimed to characterize the Aedes virome in southwestern Cameroon and identify potential core viruses which might be associated with vector competence. A total of 398 Aedes mosquitoes were collected from four locations (Bafoussam, Buea, Edea and Yaounde). Aedes albopictus dominated all sites except for Bafoussam where Aedes africanus prevailed. Metagenomic analyses of mosquitoes grouped per species into 54 pools revealed notable differences in eukaryotic viromes between Ae. africanus and Ae. albopictus, with the former exhibiting greater richness and diversity. Thirty-seven eukaryotic virus species from 16 families were identified, including six novel viruses with near complete genome sequences. Seven viruses were further quantified in individual mosquitoes via qRT-PCR. Although none of them could be identified as core viruses, Guangzhou sobemo-like virus and Bafoussam mosquito solemovirus virus were highly prevalent regionally in Ae. albopictus and Ae. africanus, respectively. This study highlights the diverse eukaryotic virome of Aedes species in southwestern Cameroon. Despite their shared Genus, Aedes species exhibit limited viral sharing, with varying viral abundance and prevalence across locations. Ae. africanus, an understudied vector, harbors a rich and diverse virome, suggesting potential implications for arbovirus vector competence.

At the plasma membrane, transmembrane receptors are at the interface between cells and their environment. They allow sensing and transduction of chemical and mechanical extracellular signals. The spatial distribution of receptors and the specific recruitment of receptor subunits to the cell membrane is crucial for the regulation of signaling and cell behavior. However, it is challenging to define what regulates such spatial patterns for receptor localization, as cell shapes are extremely diverse when cells are maintained in standard culture conditions. Bone morphogenic protein receptors (BMPRs) are serine-threonine kinases, which build heteromeric complexes of BMPRI and II. These are especially interesting targets for receptor distribution studies, since the signaling pathways triggered by BMPR-complexes depends on their dimerization mode. They might exist as pre-formed complexes, or assemble upon binding of BMP, triggering cell signaling which leads to differentiation or migration. In this work we analyzed BMPR receptor distributions in single cells grown on micropatterns, which allows not only to control cell shape, but also the distribution of intracellular organelles and protein assemblies. We developed a script called ComRed (Center Of Mass Receptor Distribution), which uses center of mass calculations to analyze the shift and spread of receptor distributions according to the different cell shapes. ComRed was tested by simulating changes in experimental data, showing that shift and spread of distributions can be reliably detected. Our ComRed-based analysis of BMPR-complexes indicates that receptor distribution depends on cell polarization. The absence of a coordinated internalization after addition of BMP suggests that a rapid and continual recycling of BMPRs occurs. Receptor complexes formation and localization in cells induced by BMP might yield insights into the local regulation of different signaling pathways.

ACE2, the putative receptor for the novel coronavirus (2019-nCoV), played an important role in cell entry of 2019-nCoV. However, it is not yet clear what cell types within the human body express ACE2. Here, a systematic analysis was undertaken using published single cell datasets. In total, our study analyzed 229652 cells, from five different organs, derived from 88 donors. The top ACE2 expressing cells include proximal tubule cells in the kidney and enterocytes in the intestine. Other major ACE2 expressing cells in the kidney include podocytes, intercalated cells and endothelial cells. Our results offer a comprehensive atlas of ACE2 expression at the single cell level and unravel the enormous potential targets of 2019-nCoVinfection beyond the lung.

The Akosombo Nile tilapia is the only approved local strain for aquaculture production in Ghana. In this study, an exotic red tilapia sample suspected to be cultured in a fish farm within the Lower Volta River Basin of the Lake Volta was collected for species identification. A molecular screening using DNA barcoding sequencing was performed on the samples targeting the cytochrome C oxidase subunit 1 mitochondrial gene (COX1). We confirmed the identity of the red tilapia fish to be a non-native Oreochromis sp. recently introduced into the country. The data obtained clearly demonstrates a breach of biosecurity that potentially threatens Ghana’s native tilapia genetic resources and aquaculture development.

Lymphocyte collection by apheresis for CAR-T production usually does not include mobilized blood using Granulocyte Colony Stimulating Factor (G-CSF) due to the widespread knowledge that it causes a decrease in the number and functionality of lymphocytes. However, it is used for stem cell transplant, which is a common treatment for hematological malignancies. The growing demand for CAR therapies (CAR-T and NK-CAR), both in research and clinic, makes necessary to evaluate whether mobilized PBSC products may be potential candidates for use in such therapies. This review collects recent work that experimentally verifies the role and functionality of T and NK lymphocytes, and the generation of CAR-T, from apheresis after G-CSF mobilization. As discussed, T cells do not vary significantly in their phenotype, the ratio of CD4+ and CD8+ remains constant and the different sub-populations remain stable. In addition, its expansion and proliferation rate are invariant regardless mobilization with G-CSF, as well as the secretion of proinflammatory cytokines and the cytotoxic ability. Therefore, cells mobilized before apheresis are postulated as a new alternative source of T cells for adoptive therapies that will serve to alleviate high demand, increase availability, and take advantage of the substantial number of existing cryopreserved products.

Chimeric antigen receptor (CAR) T-cell therapy has greatly improved outcomes for patients with relapsed or refractory hematological malignancies. However, challenges such as treatment resistance, relapse, and severe toxicity still hinder its widespread clinical application. Traditional transcriptome analysis has provided limited insights into the complex transcriptional landscape of both leukemia cells and engineered CAR-T cells, as well as their interactions within the tumor microenvironment. However, with the advent of single-cell sequencing techniques, a paradigm shift has occurred, providing robust tools to unravel the complexities of these factors. These techniques enable unbiased analysis of cellular heterogeneity and molecular patterns. These insights are invaluable for precise receptor design, guiding gene-based T cell modification, and optimizing manufacturing conditions. Consequently, this review utilizes modern single-cell sequencing techniques to clarify the transcriptional intricacies of leukemia cells and CAR-Ts. The aim of this manuscript is to discuss the potential mechanisms that contribute to the clinical failures of CAR-T immunotherapy. We will examine the biological characteristics of CAR-Ts, the mechanisms that govern clinical responses, and the intricacies of adverse events. By exploring these aspects, we hope to gain a deeper understanding of CAR-T therapy, which will ultimately lead to improved clinical outcomes and broader therapeutic applications.

Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: small duct type and large duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes–inflammation and proliferation–have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.

Estrogen receptor-positive (ER+) breast cancer is common among postmenopausal women and is frequently treated with Letrozole. Letrozole inhibits aromatase from synthesizing estrogen from androgens. Decreased estrogen slows the growth of tumors and can be an effective treatment. Letrozole resistance is increasingly being observed, which poses a unique problem for patients. We reanalyzed transcriptomic data comparing individuals who responded to Letrozole therapy (responders) to those who were resistant to treatment (non-responders). We identified SOX11 and S100A9 as two genes that significantly differed between these patients; with “PLK1 signaling events” being the most significant signaling pathway. We also identified PRDX4 and E2F8 as the top transcriptional biomarkers for ER+ treatment resistance. Many of the other significant gene products play a known role in ER+ breast cancer or other types of cancer, which partially validate our results. Several of the gene products we identified do not have a characterized role in ER+ breast cancer. Our analysis identified a set of genes that warrant further research to elucidate the molecular mechanism of Letrozole resistance in this patient population, as well as novel high-performing biomarkers. We anticipate that these findings could contribute to improved therapeutic outcomes in human patients.

To obtain an accurate and reproducible experimental results in microbial fuel cell (MFC), it is important to know ‘anode maturation biofilm’ to produce a stable and maximum performance. For this purpose, four single chamber MFCs were tested in this study. The linear sweep voltammetry (LSV) polarization tests illustrated that maximum power densities of three MFCs became stable after 9 weeks. Although there were variations afterwards, such variations were negligible. Average maximum power densities from the 9th to the 17th week were 2,990 mW/m2 (MFC-4), 2,983 mW/m2 (MFC-2), 2,368 mW/m2 (MFC-3) and 837 mW/m2 (MFC-1). Polarization resistance shows that MFC-1 had much larger anode resistance (36.6-85.4 Ω) than the other MFCs (1.7-11.6 Ω). Anodic cyclic voltammetry (CV) shows that current production increased over time and MFC-1 had much smaller current production (24.4 mA) than the other MFCs (31.0-34.9 mA) at 17th week. The increased current production indicates anode biofilm became more mature over time, but overall cell performance did not increased accordingly. Possibly due to the bad inoculation, MFC-1 showed the lowest performance. However, its performance was restored to the initial performance and anode resistance was reduced by 47% at 17th week. This study shows that the optimum anode maturation time is 9 weeks and that bioanode performance is a key factor for MFC performance. This study also shows than LSV polarization and CV tests are accurate and non-destructive measurement methods for diagnosing anode performance.

Photocatalytic ammonia decomposition to produce N2 and H2 was achieved using single-walled carbon nanotube (SWCNT) nanohybrids. Physical modification of ferrocene-dye-encapsulated CNTs by amphiphilic C60-dendron yielded nanohybrids with a dye/CNT/C60 coaxial heterojunction. Upon visible light irradiation, an aqueous solution of NH3 and dye@CNT/C60-dendron nanohybrids produced both N2 and H2 in a stoichiometric ratio of 1:3. Action spectra of this reaction clearly demonstrated that the encapsulated dye acted as the photosensitizer, with an apparent quantum yield (AQY) of 0.22% at 510 nm (the λmax of the dye). This study presents the first example of dye-sensitized ammonia decomposition and offers a new avenue for developing efficient and sustainable photocatalytic hydrogen production systems.

This paper proposes a solution for the development of microclimate monitoring for Low Voltage / High Voltage switchgear using the PRTG Internet of Things (IoT) platform. This IoT-based real time monitoring system can enable predictive maintenance to reduce the risk of electrical station malfunctions due to unfavorable environmental conditions. The combination of humidity and dust can lead to unplanned electrical discharges along the isolators inside a low or medium voltage electric table. If no predictive measures are taken, the situation may deteriorate and lead to significant damage inside and outside the switchgear cell. Thus, the mentioned situation can lead to unprogrammed maintenance interventions that can conduct to the change of the entire affected switchgear cell. Using a low-cost and efficient system, the climate conditions inside and outside the switchgear is monitored and transmitted remotely to a monitoring center. From the results obtained using a 365-day time interval, we can conclude that the proposed system is integrated successfully in the switchgear maintaining process, having as result the reducing of maintenance costs.

Infection by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) results in the novel coronavirus disease COVID-19, which has posed a serious threat globally. Infection of SARS-CoV-2 during pregnancy is associated with complications like preterm labor and premature rupture of membranes; a proportion of neonates born to the infected mothers are also positive for the virus. During pregnancy, the placental barrier protects the fetus from pathogens and ensures healthy development. However, whether or not SARS-CoV-2 can infect the placenta is unknown. Herein, utilizing single-cell RNA-seq data, we report that the SARS-CoV-2 binding receptor ACE2 and the S protein priming protease TMPRSS2 are co-expressed by a subset of syncytiotrophoblasts (STB) in the first trimester and extra villous trophoblasts (EVT) in the second trimester human placenta. The ACE2- and TMPRSS2-positive (ACE2+TMPRSS2+) placental subsets express mRNA for proteins involved in viral budding and replication. These cells also express mRNA for proteins that interact with SARS-CoV-2 structural and non-structural proteins in the host cells. We also discovered unique signatures of genes in ACE2+TMPRSS2+ STBs and EVTs. The ACE2+TMPRSS2+ STBs are highly differentiated cells and express genes involved mitochondrial metabolism and glucose transport. The second trimester ACE2+TMPRSS2+ EVTs are enriched for markers of endovascular trophoblasts. Further, both these subtypes abundantly expressed genes in Toll like receptor pathway, the second trimester EVTs (but not first trimester STBs) are also enriched for component of the JAK-STAT pathway that drive inflammation. To conclude, herein we uncovered the cellular targets for SARS-CoV-2 entry and show that these cells can potentially drive viremia in the developing human placenta. Our results provide a basic framework towards understanding the paraphernalia involved in SARS-CoV-2 infections in pregnancy.

The continues evolution of coronaviruses has gained considerable attention prior to the outbreak of COVID 19. Although, COVID-19 is currently not recognized as a global pandemic, the virus's ability to evolve and cause disease outbreaks in both humans and animals necessitates ongoing research into its genetic and structural characteristics. Therefore, understanding the molecular origin, rapid evolution, as were as the immunogenicity of coronaviruses is a critical step towards preparing for and preventing future outbreaks. This study aimed to uncover the genetic diversity and evolutionary relationships among the main viral proteins of SARS-CoV-2 and other related coronaviruses. Amino acid sequences of structural viral proteins spike glycoprotein, nucleocapsid protein, membrane protein, and envelope protein were retrieved from the NCBI database for SARS-CoV-2 and 13 other coronaviruses. Here, we identified that SARS-CoV-2 is closely related to BatCoV RaTG13 and Pangolin-CoV, suggesting their potential role in the emergence of the virus. Additionally, we predicted novel epitopes, glycosylation sites, and cleavage sites, identifying three novel glycosylation sites (NATR, NXSN, and NGTK) and six new CTL epitopes (XSNQVAVLY, NSFTRGVYY, NATRFASVY, STQDLFLPF, NSASFSTFK, and ASFSTFKCY). Our comparative analysis revealed that BatCoV RaTG13 has the closest cleavage site to SARS-CoV-2, with significant similarities also observed with Pangolin-CoV. The study highlighted the unique features of SARS-CoV-2, including its furin cleavage site, which may account for its high infectivity during the pandemic. These findings contribute to the understanding of SARS-CoV-2 evolution and its relationship with other coronaviruses, providing critical insights for the development of broad-spectrum vaccines and antiviral therapies.

The life cycle of a microgrid covers all the stages from idea to implementation, exploitation until its end of life, but with a lifespan of around 25 years. Covering them usually requires several software tools, which can make integration of results from different stages very difficult and may imply costs hard to estimate from the beginning of a project. This paper proposes a single platform of four modules developed in Matlab to assist all the processes a microgrid passes during its lifetime. The authors detail the architecture, functions and the development of the platform, either by using existing tools available in Matlab, or by developing new ones and designing new user interfaces linked with scripts based on its complex mathematical libraries. A proof-of-concept for this platform was presented by applying the life-cycle assessment process on a real-case study, a microgrid consisting in a photovoltaic plant, an office building as consumer and energy storage units.

In recent decades, as eutrophication in inland and coastal waters (ICWs) has increased due to anthropogenic activities and global warming, so has the need for timely monitoring. Compared with traditional sampling and laboratory analysis methods, satellite remote sensing technology can provide macro-scale, low-cost, and near real-time water quality monitoring services. The Geostationary Ocean Color Imager (GOCI), integrated onboard the Communication Ocean and Meteorological Satellite (COMS) from the Republic of Korea, was the first geostationary ocean color observation satellite and was operational from April 1, 2011 to March 31, 2021. Over ten years, GOCI has observed oceans, coastal waters, and inland waters within its 2,500 km×2,500 km target area centered on the Korean Peninsula. The most attractive feature of GOCI, compared with other commonly used watercolor sensors, was its high temporal resolution (1h, eight times daily from 0 UTC to 7 UTC), providing the opportunity to monitor the quality of ICWs, where optical properties can change rapidly throughout the day. This systematic review aims to comprehensively review GOCI features and applications in ICWs, analyzing progress in atmospheric correction algorithms and water quality monitoring. Analyzing 123 articles from the Web of Science and China National Knowledge Infrastructure (CNKI) through a bibliometric quantitative approach, we examined GOCI’s strength and performance with different processing methods. These articles reveal that GOCI played an essential role in monitoring the ecological health of ICWs in its observation area in East Asia. GOCI has led the way to a new era of geostationary ocean satellites, providing new technical means for monitoring water quality in oceans, coastal zones, and inland lakes. We also discuss the challenges encountered by geostationary satellites in monitoring water quality and provide suggestions for improvements.

Rapeseed meal (RM) is an important agroindustrial by-product produced in large quantities by oil extraction from seeds. However, the efficient utilization of RM as animal feed is limited by its low metabolizable energy, poor palatability, and high levels of fiber and anti-nutritional components. Here, we investigate the potential of enriching RM with single-cell protein by fermentation with conventional and unconventional yeasts, to make a nutritionally improved feed component. The process of simultaneous saccharification and fermentation improved the parameters of the waste biomass, especially the protein content, the amount of crude fiber, and the degree of biotransformation of isoflavone compounds present in the waste material. Fermentation yielded the highest protein gain for the Saccharomyces cerevisiae Ethanol Red strain (ΔN=2.38%) at a biomass load of 12.5 g and for Scheffersomyces stipitis (ΔN=2.34%) at an enzyme dose of 0.125ml/10g DM. Crude fiber content (CF) was reduced by 2.55–7.18%. The SSF process resulted in the conversion of isoflavones to forms with fewer adverse effects and lower estrogenic activity.

To reveal rare phenotypes in bacterial populations conventional microbiology tools should be advanced to generate rapid, quantitative, accurate and high-throughput data. The main drawbacks of widely used traditional methods for antibiotic studies include low sampling rate and averaging data for population measurements. To overcome these limitations microfluidic-microscopy systems have great promise to produce quantitative single-cell data with high sampling rates. Using Mycobacterium smegmatis cells we applied both conventional assays and a microfluidic-microscopy method to reveal antibiotic-tolerance mechanisms of wild type and the msm2570::Tnmutant cells. Our results revealed that the enhanced antibiotic tolerance mechanism of the msm2570::Tn mutant was due to the low number of lysed cells during the antibiotic exposure compared with wild-type cells. This is the first study that characterized the antibiotic-tolerance phenotype of the msm2570::Tn mutant that has a transposon insertion in the msm2570 gene encoding a putative xanthine/uracil permease, which enrolls in uptake of nitrogen compound during nitrogen limitation. The experimental results indicate that the msm2570::Tn mutant can be further interrogated to reveal antibiotic killing mechanisms, in particularly, antibiotics those targets cell wall integrity.