Abstract: Autism spectrum disorders (ASDs) are complex, lifelong, neurodevelopmental conditions of largely unknown cause. The global prevalence of autism has increased twentyfold to thirtyfold since the earliest epidemiologic studies were conducted in the late 1960s and early 1970s. Recent reports agree on the association of ASD with the alteration of the microbiome (dysbiosis), which raises the possible role of external factors. Our study aimed at identifying antibiotic classes that might be associated with the development of ASD-related dysbiosis either promoting or inhibiting the process. Statistical comparison was made between the average yearly consumption of different antibiotic classes (1997-2020) and the number of individuals living with ASD estimated for 2023/100000 population in 30 European countries and the results were statistically analyzed. Tetracycline (J01A) showed significant positive (promoting) association with the prevalence of ASD (Pearson r: 0.373, p: 0.043. OR: 1.312, CI95%: 0.995-1.791, p: 0.065) and narrow-spectrum, beta-lactamase resistant penicillin (J01CF) (Pearson r: 0.524, p: 0.003, OR: 3.240, CI95%: 1.710-8.853, p: 0.004, Kruskal-Wallis p: 0.032). Mild, negative (inhibitory) association was observed with broad-spectrum, beta-lactamase sensitive penicillin (J01CA) (Pearson r: -0.278, p: 0.157, OR: 0.808, CI95%: 0649-0957, p: 0.028) and narrow-spectrum, beta-lactamase-sensitive penicillin (J01CE) (Pearson p: -0.032, r: 0.865, OR: 0.725, CI95%: 0.543-0.885, p: 0,009). Our findings strongly support the animal experiments when penicillin-exposed newborn mice developed "autism-like" behavior.

An increasing amount of evidence indicates the critical role of the cutaneous nervous system in the initiation and maintenance of psoriatic skin lesions by neurogenic inflammation. However, molecular mechanisms affecting cutaneous neurons are largely uncharacterized. Therefore, we reanalyzed a psoriatic RNA sequencing dataset from published transcriptome experiments of nearly 300 individuals. Using the Ingenuity Pathway Analysis software, we associated several hundreds of differentially expressed transcripts (DETs) to nervous system development and functions. Since neuronal projections were previously reported to be affected in psoriasis, we performed an in-depth analysis of neurite formation-related processed. Our in silico analysis suggests that SEMA-PLXN and ROBO-DCC-UNC5 regulating axonal growth and repulsion are differentially affected in non-lesional and lesional skin samples. We identified opposing expressional alterations in secreted ligands for axonal guidance signaling (RTN4/NOGOA, NTNs, SEMAs, SLITs) and non-conventional axon guidance regulating ligands, including WNT5A and their receptors, modulating axon formation. These differences in neuritogenesis may explain the abnormal cutaneous nerve filament formation described in psoriatic skin. The processes also influence T cell activation and infiltration, thus highlighting an additional angle of the crosstalk between the cutaneous nervous system and the immune responses in psoriasis pathogenesis, in addition to the known neurogenic pro-inflammatory mediators.

Treating relapsed and refractory diffuse large B-cell lymphoma is still challenging for clinicians, but the available CAR-T and bispecific antibodies revolutionized therapy. Autologous stem cell transplantation was the most effective treatment modality previously. The authors report data from a single center over ten years. The retrospective study included 116 patients. There were 53 relapsed, 39 primary refractory cases, 19 had CNS involvement, and 5 received primary consolidation transplants. The median duration of follow-up was 46 months. The median event-free survival was 75 months, and the median overall survival was 105 months for all cases. Five-year overall survival was 59%, and event-free survival was 54%. Pretreatment prognostic factors at diagnosis had no effect on the outcome of transplantation. The authors found no difference between survival in relapsed or refractory cases, and the number of salvage lines or the germinal center / activated B-cell type also did not influence the results. Complete metabolic response before transplant confirmed by 18FDG PET/CT strongly affected survival. The pretransplant creatinine and CRP levels significantly influenced the long-term outcome. The number of stem cells infused did not affect survival, but engraftment within nine days did result in better survival. These data support the finding that the response to salvage therapy did select a better prognostic group who may still benefit from autologous transplantation.

Transmembrane transport of small organic and inorganic molecules is one of the cornerstones of cellular metabolism. Among transmembrane transporters, solute carrier (SLC) proteins form the largest, albeit very diverse, superfamily with over 400 members. It has been early on recognized that xenobiotics can directly interact with SLCs and that this interaction can fundamentally determine their efficacy, including bioavailability and intertissue distribution. Apart from the well-established prodrug strategy, the chemical ligation of transporter substrates to nanoparticles of various chemical composition has recently been used as a means to enhance their targeting or absorption. In this review, we summarize efforts in drug design exploiting interactions with specific SLC transporters to optimize their therapeutic effects. Furthermore, we describe current and future challenges as well as new directions for the advanced development of therapeutics that target SLC transporters.

Mitochondrial carriers facilitate the transfer of small molecules across the inner mitochondrial membrane (IMM) to support mitochondrial function and core cellular processes. In addition to the classical mitochondrial carrier family SLC25, the past decade led to the discovery of additional protein families that exhibit IMM localization and transporter-like properties. These include mitochondrial pyruvate carriers, sideroflexins and mitochondrial cation/H+ exchangers that have been linked to vital physiological functions and disease. Their structures and transport mechanisms are still largely unknown and understudied. Protein sequence analysis per se can often pinpoint hotspots that are of functional or structural importance. In this review, we summarize current knowledge about sequence features of mitochondrial transporters with a special focus on the newly included SLC54, SLC55 and SLC56 families of the SLC solute carrier superfamily. Taking a step further, we combined sequence conservation analysis with transmembrane segment and secondary structure prediction methods to extract residue positions and sequence motifs that likely play a role in substrate binding, binding site gating or structural stability. We hope that our review will help guide future experimental efforts by the scientific community to unravel the transport mechanism and structure of these novel mitochondrial carriers.

This study investigated the factors that influence consumer acceptance of fungus-resistant grape varieties (FRGV) in Germany. The qualitative research methodology involved conducting semi-structured interviews including sensory evaluation test with focus groups consisting of 48 consumers, and the data were evaluated using content analysis. The findings revealed that the attractiveness of a grape variety is determined by four distinct attributes. Furthermore, FRGV can be made more attractive to consumers by using denominations based on established grape varieties or by using and associating them with their sensory patterns. The sensory acceptance of FRGV varies significantly across consumer segments and vinification methods. Providing relevant information about the benefits of resistant grape varieties has a positive impact on consumer acceptance, and the level of interest and relevance varies by the target group. The study suggests that it is possible to enhance consumer acceptance by offering attractive grape varieties, targeting group-specific sensory profiles and engaging in storytelling campaigns that educate consumers about the advantages of resistant grapes.

Easy to use satellite-based water quality visualizations are needed for monitoring and understanding coastal and inland waters, but to date, no publicly accessible real-time global visualization system was in place. Here we introduce the Ulyssys Water Quality Viewer (UWQV), a Sentinel Hub EO Browser Custom script designed for qualitative views of aquatic chlorophyll and suspended sediment concentrations. The viewer avoids unmixing of the chlorophyll and suspended sediment spectral signal by visualizing these parameters together, with high concentrations of suspended sediment obscuring chlorophyll if present. Cloud masking uses the Hollstein and Braaten algorithms (existing EO Browser custom script code), additionally water surfaces are masked using the Normalized Differential Water Index. Chlorophyll is estimated using reflectance line height-based indicators such as fluorescence line height and maximum chlorophyll index. Suspended sediment is visualized based on single-band reflectances at 620 or 700 nm. Data sources are Sentinel-2 and Sentinel-3 images, allowing either 20 m spatial resolution or up to daily imaging. This visualization system is easy to operate and interpret, and combined with the data service capacity of the Sentinel Hub, it is expected that UWQV will contribute to monitoring of remote water bodies and to our overall understanding of physical limnology and aquatic ecology.

Down syndrome (DS) is a leading human genomic abnormality resulting from the trisomy of chromosome 21. The genomic base of the aneuploidy behind this disease is complex, and this complexity poses formidable challenges to understanding the underlying molecular basis. In the spectrum of the classic DS risk factor associations the role of nutrients, vitamins, and in general, the foodborne associated background as part of the events leading ultimately to chromosome nondisjunction has long been recognized as a well-established clinical association. The integrity of the microbiome is a basic condition in these events, and the dysbiosis may be associated with secondary health outcomes, the possible association of DS development with maternal gut microbiota should require more attention. We have hypothesized that different classes of antibiotics might promote or inhibit the proliferation of different microbial taxa and hence, we might find associations between the use of different classes of antibiotics and the prevalence of DS through the modification of the microbiome. As antibiotics are considered major disruptors of the microbiome, it could be hypothesized that the consumption/exposure of certain classes of antibiotics might be associated with the prevalence of DS in European countries (N=30). Utilizing three different statistical methods, comparisons have been made between the average yearly antibiotic consumption (1997-2020) and the prevalence of people living with DS estimated for 2019 as a percentage of the population in European countries. We have found strong statistical correlations between the consumption of tetracycline (J01A) and the narrow-spectrum, beta-lactamase-resistant penicillin (J01CF) and the prevalence of DS.

In this study, the field measurement-based validation of a novel sediment transport calculation method is presented. River sections with complex bed topography and inhomogeneous bed material composition highlight the need for an improved sediment transport calculation method. The complexity of the morphodynamic features can result in the simultaneous appearance of the gravel and finer sand dominated sediment transport (e.g. parallel bed armoring and siltation) at different regions within a shorter river reach. For the improvement purpose of sediment transport calculation in such complex river beds, a novel sediment transport method was elaborated. The base concept of it is the combined use of two already existing empirical sediment transport models. The method was already validated against laboratory measurements. The major goal of this study is the verification of the novel method with a real river case study. The combining of the two sediment transport models is based on the implementation of a recently presented classification method of the locally dominant sediment transport nature (gravel or sand transport dominates). The results are compared with measured bed change maps. The verification clearly refers to the meaningful improvement in the sediment transport calculation by the novel manner in case of spatially varying bed content.

The aim of this study is to introduce a novel method which can separate sand or gravel dominated bed load transport in rivers with mixed-size bed material. In engineering practice, the Shields-Parker diagram could be used for such purposes, however, the method has certain applicability limits, due to the fact that it is based on uniform bed material and provides information rather on river-scale, instead of reach or local scale. When dealing with large rivers with complex hydrodynamics and morphodynamics the bed load transport modes can also indicate strong variation even locally, which requires a more suitable approach to estimate the locally unique behavior of the sediment transport. Here, we suggest that the decision criteria utilizes the shear Reynolds number (Re*). The method was verified against field and laboratory measurement data, both performed at non-uniform bed material compositions. The comparative assessment of the results show that the shear Reynolds number based method operates more reliably than the Shields-Parker diagram and it is expected to predict the sand or gravel transport domination with a < 5% uncertainty. The introduced results can greatly contribute to the improvement of numerical sediment transport modeling as well as to the field implementation of bed load transport measurements.

Background and objectives: Alzheimer's disease (AD) is a progressive neurodegenerative illness, responsible for 60-70% of all dementias, affecting over 50 million people worldwide, and nearly 11 million in European countries. Several putative factors are identified in the literature as causative agents or risk factors for the development of AD. The amyloid cascade hypothesis has been the main hypothesis about the pathophysiology of AD for decades. Recent studies raised the possible role of dysbiosis in the development of AD which prevents memory loss. The amyloid-β (Aβ) deposition might be considered as an inflammatory reaction to certain molecular products arising from the altered microbiome. Based on the above observations, it has been suspected, that antibiotic consumption patterns of different antibiotic classes might be associated with the prevalence of AD in European countries. Methods: Antibiotic consumption (ECDC) for 1997-2007, 2008-2018, and as the whole 1997-2018 period, have been compared to the AD prevalence for 2018 expressed in percentage of the population and statistically analyzed by Pearson calculation. Results: A significant positive correlation has been found between the AD prevalence (2018) and the average quinolone consumption for the year 1997-2007 (p: 0.044). A similar association was not observed for the entire 22 years (1997-2018) of the average quinolone consumption, and the years 2008-18, indicating 10-20 years of time-lapse between the antibiotic exposure and the development of AD. The ratio of broad-spectrum and narrow-spectrum antibiotics (B/N) estimated in the ECDC database for the years of 2008-2018 showed a strong positive association with AD prevalence (2018) (p: 0.026) and a positive correlation tendency for the entire 22 years 1997-2018 (p: 0.063), but none for the years 1997-2007 (p: 0.241). Broad-spectrum, beta-lactamase sensitive penicillin (J01CA) consumption showed a positive (non-significant) correlation with the prevalence of AD for the years 2008-2018 (p:0.080).Discussion: Our study indicated the possible sequential role of certain classes of antibiotics in the development of dysbiosis leading to amyloid deposits of AD, which strengthen the possible role of different mediator molecules (short-chain fatty acids, lipopolysaccharides, etc.) produced by the altered microbiome in the development of AD.

Abstract: Several publications have raised the issue that the development of diabetes is preceded by alteration of the microbiome (dysbiosis) and hence, the role of environmental factors, triggering dysbiosis, should be considered. Antibiotics are powerful agents inducing dysbiosis and the authors wanted to explore the possible relationship between the consumption of different major classes of antibiotics and the prevalence of diabetes (type-1, /T1D/, type-2 /T2D/) in thirty European countries. According to our hypothesis, if such association exists, the dominant use of certain major antibiotic classes might be reflected in the prevalence of T1D and T2D in different countries. Comparisons were performed between the prevalence of diabetes (T1D and T2D) estimated for 2019 and featured in the Diabetes Atlas with the average yearly consumption of major antibiotic classes of the previous 10 years (2010-19) extracted from the ECDC yearly reports on antibiotic consumption in Europe. Pearson correlation and variance analysis were used to estimate the possible relationship. Strong, positive (enhancer) associations were found between the prevalence of T1D and the consumption of tetracycline (J01A /p: 0.001/) and the narrow spectrum penicillin (J01CE /p: 0,006/, CF /p: 0.018/). Strong negative (inhibitor) association was observed with broad-spectrum, beta-lactamase resistant penicillin (J01CR /p: 0.003/), macrolide (J01F /p: 0.008/) and quinolone (J01M /p: 0.001/). T2D showed significant positive associations with cephalosporin (J01D /p: 0.048/) and quinolone (J01M /p: 0.025/), and a non-significant negative association was detected with broad-spectrum, beta-lactamase-sensitive penicillin (J01CA /p: 0.67/). Countries with the highest prevalence of diabetes (first 10 positions) showed concordance with the higher consumption of “enhancer” and the lower consumption of “inhibitor” antibiotics (first 10 positions) as indicated by variance analysis. Countries with high prevalence of T1D showed high consumption of tetracycline (p: 0.015), and narrow spectrum, beta-lactamase sensitive penicillin (p: 0.008), and low consumption of “inhibitor” antibiotics (broad-spectrum, beta-lactamase resistant, combination penicillin (p: 0.005), cephalosporin (p: 0.036), and quinolone (p: 0.003). Countries with a high prevalence of T2D consumed more cephalosporin (p: 0.084), quinolone (p: 0.54), and less broad-spectrum, beta-lactamase sensitive penicillin (p: 0.012) than other countries. Conclusion/Interpretation: The development of diabetes-related dysbiosis might be attached to higher consumption of specific classes of antibiotics, showing positive (enhancer) associations with the prevalence of diabetes, and the low consumption of other classes of antibiotics shoving negative (inhibitory) associations. Those groups of antibiotics are different in T1D and T2D

Vision is our primary sense as the human eye is the gateway for more than 65% of information reaching the human brain. Today’s increased exposure to different wavelengths and intensities of light from Light Emitting Diodes (LEDs) sources could induce retinal degeneration and accompanying neuronal cell death. Damage induced by chronic phototoxic reactions occurring in the retina accumulates over years and it has been suggested to be responsible for the etiology of many debilitating ocular conditions. In this work, we examined how LED stimulation affects vision by monitoring changes in the expression of death and survival factors as well as microglial activation in LED-induced damage (LID) of the retinal tissue. We found an LED exposure-induced increase in the mRNA levels of major apoptosis-related markers -BAX, Bcl-2, and Caspase-3 and an accompanying wide-spread microglial and Caspase-3 activation. Everyday LED light exposure was accounted for all the described changes in the retinal tissue of mice in this study, indicating that overuse of non-filtered direct LED light can have detrimental effects on the human retina as well.

Purpose: There is limited research on the reasons behind startup failure, and none of the available studies use a competency approach. In this study we applied Spencer’s competency model to identify the competencies in startups which, according to their CEOs, contributed to failure. Methodology: Three coders analyzed the stories of 50 startup failures published online using modified Critical Incident Technique. Findings: Two salient competencies were identified playing a fundamental role in startup failures if missing: Information seeking and Customer service orientation. A network pattern of 9 more prevalent competency deficits was created: Technical/professional/managerial expertise, Analytical thinking, Flexibility, Self-control, Concern for order, quality and accuracy, Interpersonal understanding, Self-confidence, Team leadership and Teamwork and cooperation. Besides startup-specific behavior descriptions were added to Spencer’s competencies. Research implications: Competency approach and Critical Incident Technique method proved to be feasible to identify competency deficits in failed startups. Practical implications: The identified competency deficits offer relevant focus areas for the assessment and development of startup teams. Originality: The study provided research evidence to describe the competency deficits of startup teams that are connected to their failure.

Magnetic resonance elastography (MRE) has revealed sexual dimorphism in brain stiffness in healthy individuals and multiple sclerosis (MS) patients. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), we showed previously that inflammation-induced brain softening was associated with alterations of the extracellular matrix (ECM). However, it remained unclear whether the brain ECM presents sex-specific properties that can be visualized by MRE. Therefore, we aimed here at quantifying sexual dimorphism in brain viscoelasticity in association with ECM changes in healthy and inflamed brains. Multifrequency MRE was applied to the midbrain of healthy and EAE mice of both sexes to quantitatively map regional stiffness. To define differences in brain ECM composition, gene expression of the key basement membrane components laminin (Lama4, Lama5), collagen (Col4a1, Col1a1) and fibronectin (Fn1) was investigated by RT-qPCR. We showed that the healthy male cortex expressed less Lama4, Lama5, Col4a1 but more Fn1 (all p < 0.05) than the healthy female cortex, which was associated with 9% softer properties (p = 0.044) in that region. At peak EAE, cortical softening was similar in both sexes compared to healthy tissue, with an 8% difference remaining between males and females during EAE (p < 0.001). Cortical Lama4, Lama5 and Col4a1 expression increased 2 to 3-fold in EAE in both sexes while Fn1 decreased only in males (all p < 0.05). No significant sex differences in stiffness were detected in other brain regions. In conclusion, sexual dimorphism in the ECM composition of cortical tissue in the mouse brain is reflected by in vivo stiffness measured with MRE and should be considered in future studies by sex-specific reference values.

Canine mammary tumors represent one of the leading malignant pathology in female dogs, displaying the importance of efficient therapeutic findings, beside the golden standard surgery, able to limit the development of the disease. Studies in human cancers demonstrated that Doxorubicin presents a good effect in different biological processes like apoptosis, autophagy, cell cycle, cell invasion and epithelial to mesenchymal transition. Our study following the effects of Doxorubicin on two canine mammary cancer cell lines P114 and CMT-U27, showing an inhibitory effect in cell proliferation and an expression alteration of the EMT related genes.

The short-term intake (ESTI) of Hungarian consumers to pesticide residues was assessed based on 2331 test results obtained during 2017-2021 monitoring program in the frequently analyzed apples, sour cherries, table grapes, peaches, nectarines, peppers and strawberries (23.5% of all samples taken from 119 crops). The age-specific consumption data were obtained from two representative national food consumption surveys (2009 and 2018-2020). The exposure was characterized with Hazard Quotient and Hazard Index considering the acute reference doses of pesticide residues detected in the samples. When ESTI was calculated with all detected “single“ residues and variability factor of 3.6, recommended for evaluation of monitoring results, the HI only exceeded 1 for children &lt;3 years old eating grape (1.50-1.81). HI was &lt;1 when any of the 6 foods were eaten together within one day. Between forty and fifty percent of samples contained 2-23 residues. Though, the individual residue concentrations were below the corresponding MRLs, multiple residues being present in one sample resulted in maximum HI values in apples (1.14); grapes (6.57); peaches and nectarines (2.57); strawberries (2.74); peppers (10.44). Residues with low ARfD values contributed most. Applying HI is simple, but provides only point estimates; therefore, it should only be used in first-tier risk assessment.

The central nervous system (CNS) is the final frontier in drug delivery because of the blood-brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 μmol/4 μL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 μmol/4 μL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

The renin-angiotensin system (RAS) plays a role in cardiovascular homeostasis and hydro-electrolyte balance influencing organ function throughout the body. The classical view of RAS focused on a single biologically active metabolite, the octapeptide angiotensin (Ang)ll, created by the Angiotensin-converting enzyme (ACE). The past two decades have revealed new functions for intermediate products of the RAS beyond their role as substrates. Angiotensin 1-7 (Ang-(1—7), a RAS peptide product with actions at the Mas receptor, reportedly prevents cardiovascular disease-induced cognitive decline and cancer-induced bone pain (CIBP). However, Ang-(1—7) has a short half-life in vivo; here, we hypothesized that activating the MasR1 with a lactoside Ang-(1—7) analogue- PNA6-would attenuate inflammatory, cancer pain confined to the long bones, and chemotherapy-induced peripheral neuropathy (CIPN) for a longer-lasting efficacious therapeutic effect. PNA6, Asp-Arg-Val-Tyr-Ile-His-Ser-(O-β-Lact)-amide, was successfully synthesized on solid phase peptide synthesis (SPPS). PNA6 significantly reversed inflammatory pain induced by 2% carrageenan in mice. In a second study modeling a complex pain state, E0771 breast adenocarcinoma cells were implanted into the femur of female C57BLK/6J wild-type mice to induce cancer-induced bone pain (CIBP). Both acute and chronic dosing of PNA6 significantly reduced the spontaneous pain behaviors associated with CIBP. A third murine model of platinum drug-induced painful peripheral neuropathy was established using oxaliplatin. Mice in the oxaliplatin-vehicle treatment groups demonstrated significant mechanical allodynia compared to oxaliplatin- PNA6 treatment group mice. These data suggest that PNA6 is a viable lead candidate for treating chronic inflammatory and complex neuropathic pain.

Engine oil degradation and tribological properties are strongly interrelated. Hence, understanding the chemical processes resulting in additive depletion and degradation products is necessary. In this study, in-service engine oils from petrol and diesel vehicles were analyzed with conventional and advanced methods (mass spectrometry). Additionally, the effect of the utilization profile (short- vs. long-range) was studied. Petrol engine oils generally showed accelerated antioxidant and antiwear degradation and higher oxidation, especially in case of a short-range utilization profile, which can be attributed to the higher air-to-fuel ratio (more rich combustion) compared to diesel engines. A detailed overview of oxidation and nitration products, as well as degradation products resulting from zinc dialkyl dithiophosphate and boron ester antiwear additives, diphenylamine antioxidants and salicylate detergents is given. A side-reaction between oxidation products (aromatic carboxylic acids) and the boron ester antiwear is highlighted. This reaction was only detected in the petrol engine oils, where the oxidation products were measured in a high abundance. However, no side reaction was found in the samples from the diesel vehicle, since there the aromatic carboxylic acids were largely absent due to lower oxidation.

Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than parent the cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable material for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal and epithelial type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as non-toxic. Based on these results, fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cells protection against oxidative stress.

In this study, we examined the effect of salinity and alkalinity on the metabolic potential and taxonomic composition of microbiota inhabiting the sodic soils at different plant communities. The soil samples were collected in the Pannonian steppe (Hungary, Central Europe) under extreme dry and wet weather conditions. The metabolic profiles of microorganisms were analysed by MicroResp method, the bacterial diversity was assessed by cultivation and next generation amplicon sequencing based on the 16S rRNA gene. Catabolic profiles of microbial communities varied primarily according to the alkali vegetation types. Most members of the strain collection were identified as plant associated and halophilic/alkaliphilic species of Micrococcus, Nesterenkonia, Nocardiopsis, Streptomyces (Actinobacteria) and Bacillus, Paenibacillus (Firmicutes) genera. Based on the pyrosequencing data, the relative abundance of phyla Proteobacteria, Actinobacteria, Acidobacteria, Gemmatimonadetes and Bacteroidetes changed also mainly with the sample types, indicating distinctions within the compositions of bacterial communities according to the sodic soil alkalinity-salinity gradient. The effect of weather extremes was the most pronounced in the relative abundance of phyla Actinobacteria and Acidobacteria. The type of alkali vegetation caused greater shifts in both the diversity and activity of sodic soil microbial communities than the extreme aridity and moisture.

The nervous system demands an adequate oxygen and metabolite exchange, making pericytes (PCs), the only vasoactive cells on the capillaries, essential to neural function. Loss of PCs is a hallmark of multiple diseases, including diabetes, Alzheimer’s, amyotrophic lateral sclerosis (ALS) and Parkinson’s. Platelet-Derived Growth Factor Receptors (PDGFRs) have been shown to be critical to the PC function and survival. However, how PDGFR-mediated PC activity affects vascular homeostasis is not fully understood. Here, we tested the hypothesis that imatinib, a chemotherapeutic agent and a potent PDGFR inhibitor, alters the PC distribution and thus induces vascular atrophy. We performed a morphometric analysis of the vascular elements in sham control and imatinib-treated NG2-DsRed mice. Vascular morphology and the integrity of the blood-retina barrier (BRB) were evaluated using blood albumin labeling. We found that imatinib decreased the number of PCs and blood vessel (BV) coverage in all retinal vascular layers, this was accompanied by a shrinkage of BV diameters. Surprisingly, the total length of capillaries was not altered, suggesting a preferential effect of imatinib on PCs. Furthermore, the blood-retina barrier disruption was not evident. In conclusion, our data suggest that imatinib could help in treating neurovascular diseases and serve as a model for PC loss, without BRB disruption.

(1) Background: Mouse-mammary tumor virus (MMTV) might play a role in the etiology of some breast cancers in humans. The purpose of our study was to identify MMTV DNA sequences in breast tissue samples from breast cancer patients operated in our regional center from Romania. (2) Methods: We have selected 75 patients with non-metastatic breast cancer treated with curative intent and searched with PCR the MMTV-like DNA sequence in the breast cancer tissue and normal breast tissue obtained from the same patients. (3) Results: None of the examined samples was positive for MMTV-like target sequences on PCR. (4) Conclusions: We could not prove that MMTV plays a role in the etiology of breast cancer in our patient group. This finding is similar to findings of other geographically related research groups and might be due to the fact that only the Mus musculus domesticus mouse species was proven to carry infectious MMTV, but not the Mus musculus musculus species, which is specific to South-Eastern Europe and some parts of Asia.

Breast cancer, although the most frequently diagnosed malignant tumour in humans, has a less clear aetiology compared to other frequent cancer types. Mouse-mammary tumour virus (MMTV) is involved in breast cancer in mice and dogs and might play a role in the aetiology of some breast cancers in humans, since it has been identified in 20-40% of breast cancer samples in Western Europe, USA, Australia and some other parts of the world population. The purpose of our study was to identify MMTV DNA sequences in breast tissue samples from breast cancer patients operated in our regional centre from Romania. We have selected 75 patients with non-metastatic breast cancer treated with curative intent and searched with PCR the MMTV-like DNA sequence in the breast cancer tissue and normal breast tissue obtained from the same patients. Since none of the examined samples was positive for MMTV-like target sequences on PCR we could not prove that MMTV plays a role in the aetiology of breast cancer in our patient group. This finding is similar to publications of other geographically related research groups and might be due to the fact that only the Mus musculus domesticus mouse species was proven to carry infectious MMTV, but not the Mus musculus musculus species, which is specific to South-Eastern Europe (including Romania) and some parts of Asia.

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3’-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair which holds considerable advantages over urinalysis for anti-doping tests.

Copper(II), nickel(II) and zinc(II) complexes of various peptide fragments of tau protein were studied by potentiometric and spectroscopic techniques. All peptides contained one histidyl residue and represented the sequences of tau(91-97) (Ac-AQPHTEI-NH2), tau(385-390) (Ac-KTDHGA-NH2) and tau(404-409) (Ac-SPRHLS-NH2). Imidazole-N donors of histidine were the primary metal binding sites for all peptides and all metal ions but in case of copper(II) and nickel(II) the deprotonated amide groups were also involved in metal binding by increasing pH. The most stable complexes were formed with copper(II) ion but the presence of prolyl residues resulted in significant changes in the thermodynamic stability and speciation of the systems. It was also demonstrated that nickel(II) and especially zinc(II) complexes have relative low thermodynamic stability with these peptides. Copper(II) catalyzed oxidation of the peptides was also studied. In the presence of H2O2 the fragmentation of peptides can be detected in all cases. In the simultaneous presence of of H2O2 and ascorbic acid the extent of the fragmentation of the peptide is less preferred, and the formation of 2-oxo-histidine also occurs.

The most prevalent Ca2+-buffer proteins (CaBPs: parvalbumin—PV; calbindin—CaB; calretinin—CaR) are widely expressed by various neurons throughout the brain, including the retinal ganglion cells (RGCs). Even though their retinal expression has been extensively studied, a coherent assessment of topographical variations is missing. To examine this, we performed immunohistochemistry (IHC) in the mouse retina. We found variability in the expression levels and cell numbers for CaR, with stronger and more numerous labels in the dorso-central area. CaBP+ cells contributed to RGCs with all soma sizes, indicating heterogeneity. We separated 4-9 RGC clusters in each area based on expression levels and soma sizes. Besides the overall high variety in cluster number and size, the peripheral half of the temporal retina showed the greatest cluster number, indicating a better separation of RGC subtypes there. Multiple labels showed that 39% of the RGCs showed positivity for a single CaBP, 30% expressed two CaBPs, 25% showed no CaBP expression and 6% expressed all three proteins. Finally, we observed an inverse relation between CaB and CaR expression levels in CaB/CaR dually- and CaB/CaR/PV triple labeled RGCs, suggesting a mutual complementary function.

Research with deuterium-depleted water (DDW) in the last two decades proved that deuterium/hydrogen ratio has a key role in cell cycle regulation and cellular metabolism. The present study aimed to investigate the possible effect of deuterium-depleted organic compounds (DDOC) alone and in combination with DDW on cancer growth in two in vivo mouse models. To produce DDOC, drinking water of laying hens was replaced with DDW (25 ppm) for 6 weeks, resulting in 60 ppm D level in dried egg yolk that was used as deuterium-depleted food additive. In one model, 4T1, a cell line with high metastatic capacity to the lung, was inoculated in the mice’s mammary pad. After three weeks of treatment with DDW and/or DDOC, the tumor volume in the lungs was smaller in all treated groups vs. controls with natural D level. Tumor growth and survival in mice transplanted with MCF-7 breast cancer cell line showed that the anticancer effect of DDW was enhanced by food containing the deuterium-depleted yolk. The study confirmed the importance of D/H ratio not only in consumed water but also in metabolic water produced by the mitochondria while oxidizing nutrient molecules. This is in line with the concept that initiation of cell growth requires the cells to generate a higher D/H ratio, but DDW, DDOC, or the naturally low-D lipids in a ketogenic diet, have significant effect on tumor growth by preventing the cells from raising D/H ratio to the threshold.

Background: After the increasingly common anterior cruciate ligament reconstruction (ACLR) procedure in competitive athletes, rehabilitation is crucial for facilitating a timely return to sports (RTS) and preventing re-injury. This pilot study investigates the biomechanical and psychological outcomes of postoperative rehabilitation in competitive athletes, comparing supervised rehabilita-tion (SVR) and home-based rehabilitation (HBR). Methods: After ACLR, 60 (out of 74 screened) athletes were recruited and equally divided into 2 groups using non-probability convenience sam-pling: 30 HBR and 30 SVR (each group comprising 15 males and 15 females). Rehabilitation out-comes in respective groups were evaluated at 8 months using measures (Tegner-Activity-Scale [TAS], International Knee Documentation Committee subjective knee form [IKDC-SKF], ACL Return to Sport after Injury [ACL-RSI]) and objective parameters (isometric muscle strength, hamstring/quadriceps asymmetry). RTS was evaluated at 9 months; with ACL re-injury rates rec-orded approximately 6 months post-RTS. Results: Both groups exhibited decreased TAS scores (HBR: 8 to 6, SVR: 8 to 7), with the SVR group demonstrating superior post-operative IKDC-SKF scores (81.82 vs. 68.43) and lower ACL-RSI scores (49.46 vs. 55.25). Isometric and isokinetic mus-cle strength, along with asymmetry values, favored the SVR group 8 months post-ACLR (p

The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- and endobiotics, contributes to cancer drug resistance and the development of gout. In this work we have analyzed the effects of selected variants, residing in a structurally unresolved cytoplasmic region (a.a. 354-367) of ABCG2, on the function and trafficking of this protein. A cluster of four lysines (K357-360) and the phosphorylation of a threonine (T362) residue in this region have been previously suggested to significantly affect the cellular fate of ABCG2. Here we report that the naturally occurring K360del variant in human cells increased ABCG2 plasma membrane expression and accelerated cellular trafficking. The variable alanine replacements of the neighboring lysines had no significant effect on transport function, and the apical localization of ABCG2 in polarized cells has not been altered by any of these mutations. Moreover, in contrast to previous reports, we found that the phosphorylation incompetent T362A, or the phosphorylation mimicking T362E variants in this loop, had no measurable effects on the function or expression of ABCG2. Molecular dynamics simulations indicated an increased mobility of the mutant variants with no major effects on the core structure of the protein. These results may help to decipher the potential role of this unstructured region within this transporter.

Roma is the largest ethnic minority of Europe with poor health status, which is poorly explored due to legal constrains of ethnicity assessment. We aimed to elaborate health-indicators for adults living in segregated Roma settlements (SRS) representing the most vulnerable Roma subpopulation. SRSs were mapped in a study area populated by 54682 adults. Records of all adults living in the study area were processed in the National Institute of Health Insurance Fund Management. Aggregated, age-sex standardized SRS-specific and non-SRS-specific indicators on healthcare utilization and premature death along with the ratio of them (RR) were computed with 95% confidence intervals. The rate of GP appointments was significantly higher among SRS inhabitants (RR=1.152, 95%CI: 1.136–1.167). The proportion of subjects hospitalized (RR=1.286, 1.177–1.405), and the reimbursement for inpatient care (RR=1.060, 1.057–1.064) were elevated for SRS. Premature mortality was significantly higher in SRSs (RR=1.711, 1.085-2.696). Our study demonstrated that it is possible to compute the SRS-specific version of the routine healthcare indicators without violating the protection of personal data by converting a sensitive ethical issue to a non-sensitive small area geographical analysis; there is an SRS-specific healthcare utilization pattern, which is associated with elevated costs and increased risk of premature death.

A Traumatic brain injury (TBI) is among the main causes of sudden death after head trauma. These injuries can result in severe degeneration and neuronal cell death in the CNS, including the retina which is a crucial part of the brain responsible for perceiving and transmitting visual information. The long-term effects of mild-repetitive TBI (rmTBI) are far less studied thus far, even though damages induced by repetitive injuries occurring in the brain are more common, especially amongst athletes. rmTBI can also have a detrimental effect on the retina and the pathophysiology of these injuries are likely to differ from the severe TBI (sTBI) retinal injury.Here we showed how rmTBI and sTBI can dissimilarly affect the retina. Our results indicate an increase in the number of activated microglial cells and Caspase3-positive cells in the retina in both traumatic models, suggesting a rise in the level of inflammation and cell death after TBI. The pattern of microglial activation appears evenly distributed and widespread but differs amongst the various retinal layers. sTBI induced microgial activation in both the superficial and deep retinal layers. In contrast to sTBI, no significant change occurred following the repetitive mild injury in the superficial layer, only the deep layer (spanning from the inner nuclear layer to the outer plexiform layer) shows microglial activation. This difference suggests that alternate response mechanisms play a role in the case of the different TBI incidents. The Caspase3 activation pattern showed a uniform increase in both the superficial and deep layers of the retina. This suggests a different action in the course of the disease in sTBI and rmTBI models and points to the need for new diagnostic procedures.Our present results suggest that the retina might serve as such a model of head injuries since the retinal tissue reacts to both forms of TBI and is the most accessible part of the human brain.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.

Vascular impairment, muscle atrophy, and cognitive decline are important age-related conditions that have a significant impact on health. Vascular impairment directly disrupts the flow of blood, leading to the decline of muscle mass associated with aging (sarcopenia) and the decline of neuronal functions (neurodegeneration). Our inadequate understanding of the complex relationships between these conditions impedes precise diagnosis and effective treatment. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can enhance therapeutic strategies and lead to better outcomes for patients. Here, we highlight the intricate relationship among vascular dysfunction, degenerative muscle, and cognitive decline, underscoring the need for multidisciplinary approaches to treatment. Progress in this field can result in improved diagnosis, more potent therapeutic options, and enhanced preventative measures, all of which can contribute to an improved quality of life for the aging population.

Landraces are considered a crucial component of biodiversity conservation, serving as a reservoir of genetic diversity. Consequently, the collection, cultivation and detailed characterization of such landraces constitute an inherent aspect of the world’s natural resource heritage. This effort holds promise for the development of elite varieties capable of thriving amidst continuous global climate fluctuations. In this context, we conducted a comprehensive assessment of the main agronomic attributes, physico-chemical properties, and functional quality traits of the major hot pepper landraces adapted to diverse climatic conditions in Tunisia. These landraces include ‘Dhirat’, ‘Semmane’, ‘Beldi’, ‘Nabeul’, ‘Jerid’, ‘Mahdia’, ‘Cayenne’, ‘Kairouan’ and ‘Baklouti’. Most of the pepper landraces exhibited satisfactory yields, ranging from 1163.25 to 1841.67 g plant-1 in ‘Jerid’ and ‘Kairouan’, respectively, indicating robust productivity, especially under prevailing climatic changes and high temperatures. Landraces such as ‘Baklouti’, ‘Beldi’, ‘Nabeul’, ‘Semmane’, ‘Kairouan’ and ‘Mahdia’ appear suitable for both fresh consumption and processing, owing to their favorable average fruit weight and soluble solids content. Functional quality and the levels of antioxidants, as well as radical scavenging activity, emerged as key discriminating factors among pepper landraces. Irrespective of genotype, capsaicin and dihydrocapsaicin constituted the major capsaicinoids, accounting for at least 87% of the total. Total capsaicinoids ranged from 1.81 µg g−1 to 193.71 µg g−1, with ‘Baklouti’ and ‘Jerid’ identified as the most pungent landraces. Total carotenoids ranged from 45.94 µg g−1 to 174.52 µg g−1 with ‘Semmane and ‘Jerid’ exhibiting the highest levels. Considerable variation was observed in β-carotene content, spanning from 3% to 24% of the total carotenoids. α-Tocopherol content ranged from 19.03 µg g-1 fw in ‘Kair-ouan’ to 30.93 µg g-1 fw in ‘Beldi’, exerting a notable influence on the overall tocopherol content. Conversely, the other isomers were detected at very low concentrations. The total vitamin C content ranged from 132 mg 100g-1 fw in ‘Mahdia’ to 200 mg 100 g-1 fw in ‘Nabeul’, indicating relatively low genetic variability. However, large variability was detected in total phenolics content, ranging from 168.58 mg GAE kg-1 fw in ‘Beldi ‘to 302.98 mg GAE kg-1 fw in ‘Cayenne’. Among the pepper landraces tested, ‘Cayenne’ achieved the highest value of radical scavenging activity in both hydrophilic and lipophilic fractions (RSAHF and RSALF), with variations rang-ing from 59% to 120% for RSAHF and from 4% to 64% for RSALF. This study aims to: 1) preserve and enhance the value of local genetic resources, 2) identify desiderable traits for incorporation into breeding programs, and 3) develop high-quality, high-yielding cultivars capable of with-standing climate variations.

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords GB in AD and dementia yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show Ginkgo biloba has promising potential in these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

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

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

In recent years, electroencephalogram (EEG) emotion recognition has emerged as a research hotspot in the field of artificial intelligence (AI). Despite advancements in EEG-based emotion recognition, room for enhancing performance persists due to EEG signal redundancy and limitations in feature extraction, leading to inefficient models and emotional information loss. To fully utilize EEG's emotional information and improve recognition accuracy while reducing computational costs, this paper proposes a Convolutional-Recurrent Hybrid Network with a dual-stream adaptive approach and an attention mechanism (CSA-SA-CRTNN). Firstly, the model utilizes a CSAM module to assign corresponding weights to EEG channels. Then, an adaptive dual-stream convolutional-recurrent network (SA-CRNN and MHSA-CRNN) is applied to extract local spatial-temporal features. After that, the extracted local features are concatenated and fed into a temporal convolutional network with a multi-head self-attention mechanism (MHSA-TCN) to capture global information. Finally, the extracted EEG information is used for emotion classification. We conducted binary and ternary classification experiments on the DEAP dataset, achieving 99.26% and 99.15% accuracy for arousal and valence in binary classification, and 97.69% and 98.05% in ternary classification, surpassing relevant algorithms. Additionally, the model's efficiency is significantly higher than other models, achieving better accuracy with lower resource consumption.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4,202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 27 for fiber length (FL), 16 for fiber strength (FS), 24 for micronaire (MC), 17 for fiber uniformity (FU), and 24 for fiber elongation rate (FE). Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosome D1 and D11. Each QTL contributed 1.98%–21.45% to the phenotypic variation (PV), including 13 major effect QTLs that contributed more than 10% toward PV. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18%–21.45% of PV, qFS-A11-1 in F2:3, F2:4 and F2:5 with 6.05%–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.

Currently there are fewer depth models applied to pepper picking detection, while the existing generalized neural networks have problems such as large model parameters, long training time, and low model accuracy.In order to solve the above problems, this paper proposes a Yolo-chili target detection algorithm for chili pepper detection. First, the classical target detection algorithm yolov5 is used as a benchmark model, and an adaptive spatial feature pyramid structure combining the attention mechanism and the idea of multi-scale prediction is introduced to improve the model's detection effect on occluded peppers and small target peppers. Secondly, a three-channel attention mechanism module is introduced to improve the algorithm's long-distance recognition ability and reduce the interference of redundant testers. Finally, the quantized pruning method is used to reduce the model parameters and realize the lightweight processing of the model. Applying the method to the homemade chili pepper dataset, the AP value of chili pepper reaches 93.11%; the accuracy rate is 93.51% and the recall rate is 92.55%.The experimental results show that yolo-chili is able to achieve accurate and real-time pepper detection under complex orchards.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

The aim of this retrospective study was to compare the clinical outcomes of treating isolated surgical neck fractures of the humerus using either the intramedullary nail or the MIROS (Minimally Invasive Reduction and Osteosynthesis System®) system. The study included 42 patients who underwent surgical treatment at the Polyclinic from January 2014 to June 2020. The results indicated that both treatments were effective; however, the MIROS system exhibited a higher complication rate. Intramedullary nailing was more reliable, thus recommended as the primary treatment method. This study underscores the importance of selecting the appropriate fixation technique to minimize complications and enhance patient outcomes.

Aiming at the problems of inaccurate segmentation of long object and information loss of small object in real-time semantic segmentation algorithm, this paper proposes a lightweight multi-branch real-time semantic segmentation network based on BiseNetV2. The new auxiliary branch makes full use of spatial details and context information to cover the long object in the field of view. Meanwhile, in order to ensure the inference speed of the model, the asymmetric convolution is used in each stage of the auxiliary branch to design a structure with low computational complexity. In the multi-branch fusion stage, the alignment and fusion module is designed to provide guidance information for deep and shallow feature mapping, so as to make up for the problem of feature misalignment in the fusion of information at different scales, and thus reduce the loss of small target information. In order to further improve the model’s awareness of key information, a global context module is designed to capture the most important features in the input data. The proposed network uses NVIDIA GeForce RTX 3080 Laptop GPU experiment, on the road street view data set Cityscapes and CamVid average occurring simultaneously ratio reached 77.1% and 78.4% respectively, with running speed of 127 frames/s respectively and 112 frames/s. The experimental results show that the proposed algorithm can achieve real-time segmentation and improve the accuracy significantly, showing good semantic segmentation performance

Excess nitrogen in agricultural drainage poses a serious threat to the water quality safety of the Yellow River basin. Utilizing aquatic plants to modify the rhizosphere microbial community structure and facilitate nitrogen transformation is a crucial strategy for mitigating regional water eutrophication. Our results revealed that the denitrification rate (DR), dissimilatory nitrate reduction to ammonium rate (DNRAR) and nitrogen fixation rate (NFR) of rhizosphere sediments exhibited a significant increase in artificially cultivated ditch. Compared with those in natural ditches, the richness of the bacterial community and the relative abundances of Bacteroidota, Verrucomicrobiota, Firmicutes, Anaeromyxobacter and Geobacter, which are involved mainly in the nitrogen cycle, in the rhizosphere sediments of artificially cultivated ditch were significantly greater due to improvements in environmental conditions. In artificially cultivated ditch, the dominant functional genes affecting DRNARs in the rhizosphere sediments of P. australis were nrfC and nrfA, while DRs were driven mainly by norB and napA, which were influenced by the nitrogen and carbon levels; and the dominant functional genes affecting NFRs in the rhizosphere sediments of T. orientalis were nifD, nifK and nifH. Our results provide a scientific basis for the use of aquatic plants for mitigating excess nitrogen levels in agricultural drainage.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

In this paper we study a class of impulsive delayed neural networks with parameter uncertainties and reaction-diffusion terms. Using the properties of M-matrices and some inequality techniques, some sufficient conditions are derived to guarantee the global exponential stability of the given system. The results obtained are presented by simple algebraic inequalities, which are certainly more concise than previous methods. Finally, the validity and usefulness of our results are illustrated by arithmetic examples.

Pyrops candelaria is one of the common pests of fruit trees, but the research on the pathogenic microorganisms it may carry is very limited. Therefore, it is essential to reveal the pathogenic microbes it carries and their potential hazards. This study found a new virus from the transcriptome of P. candelaria, which was first reported in P. candelaria and named as PyCaV (Pyrops candelaria associated virus). RACE and bioinformatics assay revealed that the full-length of PyCaV is 10855 bp with the polyA tail, containing a single open reading frame (ORF) encoding a polyprotein consisting of 3171 amino acid (aa). The virus has a typical Iflavirus structure, including two rhv domains, a RNA helicase domain (HEL), a 3C cysteine protease domain (Pro), and a RNA-dependent RNA polymerase domain (RdRp). Further phylogenetic analysis revealed that this virus belongs to family Iflaviridae and sequence alignements analysis suggedted PyCaV is new member in unassigned genus of family Iflaviridae. Further in-depth analysis of virus-infection-part showed that PyCaV is distributing in the whole longan lanternfly, including its head, chest, and abdomen, but more PyCaV was identified in the chest. The distribution of PyCaV in different parts of P. candelaria was further explored, which showed that more PyCaV were detected in its piercing-sucking mouthparts and chest viscera. Statistical analysis showed that the PyCaV infection was affected by time and locations.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

Our previous studies demonstrated a tight connection between simvastatin (SIM) inhibition of B16.F10 murine melanoma cell proliferation in vivo and in vitro and strong suppression of the subunit α of hypoxia inducible factor 1 (HIF-1) (HIF-1 α) production in these cancer cells. Since the translation of HIF-1α is modulated by signaling pathways coordinated by Akt, SIM effects on the link between these two regulatory factors and cancer cell metabolism under normoxia was investigated, which to our knowledge have never been described before. To achieve the proposed aim, SIM effects on cell metabolism were analysed at mRNA (via RNA-seq and RT-qPCR) as well as protein level (via western blot and catalytic activity of the key enzymes) Our data suggested that SIM might orientate glucose transport and metabolism to ensure replenishment of tricarboxylic acid (TCA) cycle activity. Moreover, it seems that SIM enhanced biosynthetic role of TCA over its energy role to further support synthesis of lipid-derived signaling molecules. Thus, under normoxia SIM treatment orientated lipid metabolism to stimulate isoprenoid and prostaglandin synthesis which might favor melanoma cell survival and aggressiveness.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

In this paper, we extend the KdVSKR equations in (1+1)-dimension and (2+1)-dimension to fractional KdVSKR equations with modified Riemann-Liouville derivative. The (2+1)-dimensional KdVSKR equation, which is a recent extension of (1+1)-dimensional KdVSKR equation, can model the resonances of solitons in shallow water. By means of the Hirota bilinear method, finite symmetry group method and consistent Riccati expansion method, many new interaction solutions have been derived. Soliton-cnoidal interaction solution of the (1+1)-dimensional fractional KdVSKR equation has been derived for the first time. For the (2+1)-dimensional frac-tional KdVSKR equation, two-wave interaction solutions and three-wave interaction solutions, including dark-soliton-sine interaction solution, bright-soliton-elliptic interaction solution, and lump-hyperbolic-sine interaction solution, have been derived. Impact of the fractional order on the shapes of these solutions has been illustrated by figures. Three-wave interaction solutions of fractional systems have not been reported in the existing references. The research idea in this paper can be applied to other fractional differential equations.

With the burgeoning growth of online retail, the issue of counterfeit products has become a significant threat to both consumer trust and brand integrity, posing challenges to sustainable market practices. Online retail platforms are promoted to redesign their channel structures and enhance brand traceability to tackle counterfeits using blockchain technology. To investigate the interactions between blockchain technology and the channel structures of online retail platforms, we design a game theory model incorporating a manufacturer with(out) blockchain participation selling products via an online retail platform that operates an agency channel and/or a reselling channel. We show that the critical trade-off of blockchain participation comprises the brand assurance effect of the blockchain, the channel competition intensification effect, and the blockchain adoption cost. The platform is capable of strategically designing the channel structure to encourage (while discouraging) blockchain participation by the manufacturer. Our analysis highlights the complementarity between blockchain participation and the channel structure. Furthermore, the effect of the consumer’s belief in the reselling channel, the commission fee in the agency channel, and the substitutability between channels are investigated in depth. The research provides valuable insights for online retail platforms and policymakers seeking to foster a sustainable and trustworthy e-commerce ecosystem.

Antimicrobial peptides represent a promising alternative to traditional drugs in relation to cost, toxicity and, primarily, the growing problem of drug resistance. Here we report on the activity against HSV-1 and HSV-2 of a previously described wide-spectrum synthetic decapeptide, Killer Peptide (KP). As determined by plaque reduction assays, treatment with KP at 100 μg/mL resulted in a reduction in the viral yield titer of 3.5 Logs for HSV-1 and 4.1 Logs for HSV-2. Further evaluation of KP antiviral activity focused on the early stages of virus replicative cycle, including the determination of the residual infectivity of viral suspensions treated with KP. A direct effect of the peptide on viral particles, impairing virus absorption and penetration, was shown. The toxicity profile proved to be extremely good with a selectivity index of 29.6 for HSV-1 and 156 for HSV-2. KP was also active against an acyclovir (ACV)-resistant HSV-1 strain, while HSV-1 subcultures in the presence of sub-inhibitory doses of KP did not lead to the emergence of resistant strains. Finally, the antiviral action of KP proved to be synergistic with that of ACV. Overall, these results demonstrate that KP could represent an interesting addition/alternative to acyclovir for antiviral treatment.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

As the world population grows, fulfilling the need for biomaterials in the healthcare system becomes increasingly important. Biomaterials, which include metals, polymers, ceramics, and composites, play an important role in the creation of medical devices that improve people's lives. The European Society for Biomaterials described biomaterials as non-biological materials used in medical devices to interact with biological systems. This definition has developed to encompass materials that treat, assess, or replace tissues or bodily functions. Biocompatibility, as defined by the FDA, is a key feature of biomaterials, as is the requirement to fulfil design requirements such as mechanical performance, geometry, and electrical control. Over the last decade, advances in regenerative medicine and tissue engineering have boosted biomaterials' usage in medical applications dramatically. Despite its promise, scientists, engineers, and physicians continue to face significant challenges due to the complexity of biomaterials. Biomaterials have various benefits, including biodegradability, non-toxicity, and biocompatibility, making them extremely useful for replacing, sustaining, or improving biological activities in damaged tissues. They are used in a wide range of applications, including tissue engineering implants, human tissue healing and regeneration, medication delivery systems, and biosensors. This study gives insights into the fundamental characteristics, case studies, and ethical issues associated with the usage and use of biomaterials, further examining their potential and significance in healthcare and medicine.

The paper describes the new method for image compression based on coordinated group signal transformation. The algorithm is a type of difference coding. Coordinated processing significantly simplifies the difference signal conversion scheme using a single group codec for all signals. The described method considers color channels as correlated signals of a multi-channel communication system. The specifics of the processed data required modification of the coordinated group processing algorithm. First, we changed how to calculate the difference signals to prevent data loss. Secondly, the group codec was supplemented with a neural network to improve the quality of reconstructed images. We considered the following types of neural networks: fully connected, recurrent, convolution, and convolution in the Fourier space. Based on the simulation results, it is best to use fully connected neural networks if the goal is to minimize processing delay time. These networks have a response time of 13 ms. On the other hand, if the priority is to improve quality in cases where delays are not critical, then convolution neural networks in the Fourier space should be used. These networks have a response time of 140 ms and are of significant interest.

In electromagnetic ultrasonic testing, it is difficult to recognize small-size bottom cracks by time of flight (ToF), and the lift-off fluctuation of the probe affects the accuracy and consistency of the inspection results. In order to overcome the difficulty, a novel EMAT (electromagnetic acoustic transducer)-PEC (pulse eddy current) composite sensor is designed. We use amplitude of bottom echo recorded by EMAT to identify the tiny bottom crack as well as the amplitude of PEC signals picked up by the integrated symmetric coils to measure the average lift-off of the probe in real time. Firstly, the effects of lift-off and bottom cracks on amplitude of bottom echo are distinguished combining the theoretical analysis and finite element method (FEM). And then an amplitude correction method based on the fusion of EMAT and PEC signals is proposed to reduce the impact of lift-off on the defect signal. The experimental results demonstrate that the designed composite sensor can effectively detect the bottom crack as small as 0.1mm* 0.3mm. The signal fusion method can accurately correct the amplitude of defect signal and the relative error is less than ±8%.

The studied solar pot is a recent invention, which gained a utility model protection in 2021 from the Hungarian Intellectual Property Office under patent number 5489. The device is made for environmentally friendly cooking or heating (by utilizing solar energy) of foods and liquids. Its structure is similar to a double pipe heat exchanger, it has an outer mantle and an inner cooking tank. The goals of the paper are proposing a new physically-based mathematical model describing the solar pot and carrying out computer experiments with it, assembling an experimental system of the pot connected with a solar collector and performing measurements on it. Based on the results, the solar pot can successfully be used for cooking or sterilizing foods or liquids during the studied time period, in Hungary.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Abstract: Transcription factors are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of transcription factors with extensive roles in plant growth and development. Our previous research indicated a decrease in iron content in chlorotic bamboo leaves. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism-related (IMR) genes in bamboo and determined the transcription factors that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF transcription factors in D. latiflorus.

Surgical site infections (SSIs) are a major concern in public healthcare, leading to increased morbidity, pro-longed hospital stays length, and significant economic costs. Understanding the epidemiology and risk fac-tors of SSIs is crucial for developing effective prevention and management strategies. In the last century, CDC ‘s HICPAC improved a bundle for prevention of HAIs based on the use of aseptic procedures, disin-fection of the skin and correct use of antibiotics for SSIs. In our country, Gelli-Bianco law introduced the national health guidelines system that include the prophylaxis antibiotic therapy pre- and post-surgery. The aim of our study is to evaluate adherence and appropriateness of the use of antibiotic-preoperative prophylaxis in a province of southern Italy and to identify risk factors that may influence the development of an SSI. The study found many statistically significant associations among the factors examined, i.e. the timing of administration adherent to guidelines, with 47% of the analyzed files administering antibiotics within 60 min before the intervention and 62.7% using intravenous administration.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by &gt;6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

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

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

The main purpose of this study is the determination of the optimal data acquisition and processing parameters of electric and seismic tomographic techniques, for the investigation of complex geological environments. Two different study areas, in central-east Peloponnese and SW Attica were selected, where a detailed geological mapping and surface geophysical survey were carried out. The applied geophysical survey included the application of electrical resistivity tomography (ERT) and seismic refraction tomography (SRT). The geoelectrical measurements were acquired with different arrays and electrode configurations. Moreover, various types of seismic sources were used at seventeen shot locations along the seismic arrays. For the processing of geoelectrical data, clustered datasets were created increasing the depth of investigation and the discriminatory capability. The seismic data processing included: (a) creation of synthetic models and seismic records to determine the effectiveness and capabilities of the technique, (b) spectral analysis of the seismic records to determine the optimal seismic source type and (c) inversion of the field data to create representative subsurface velocity models. The results of the two techniques successfully delineated the complex subsurface structure that characterizes these two geological environments. The application of the ERT combined with the SRT, are the two dominant, high-resolution techniques for the elucidation of complex subsurface structures.

Cocoa (Theobroma Cacao, L.) represents an important market that gained relevance and became an esteemed commodity thanks to cocoa powder, chocolate, and other related products. This work has analyzed 59 cocoa powder samples from the European market. Three distinct subgroups were identified: organic or conventional, alkalized or not alkalized, and raw or roasted processing. The impact of the technological process was evaluated on the pH, color, and compositional traits, as content of biogenic amines and salsolinol. The phenolic fraction was also investigated trough both common and emerging methods. Results depict that the influence of the agronomical practices (organic/conventional) did not affect significatively (p&lt;0.05) the composition of cocoa powders; similarly, the roasting process was not discriminative for the compounds traced. On the other hand, the alkalinization process greatly impacted on color, and pH, no matter of cocoa provenience, obtention, or other processes, also resulting reducing the phenolic fraction of treated samples. Principal components analysis confirmed that the alkali process acts on pH, color, and phenolic composition, but not on other bioactives molecules (BAs and salsolinol). All samples resulted safe while alkalized powders have a great reduction in beneficial biocompounds. A novel strategy could be to emphasize non-alkalized powders in the label, to meet the demand for more beneficial products.

This study explores the implementation of the ANSI/373: Sustainable Production of Natural Dimension Stone standard within the North American dimension stone industry to identify driving forces behind the initiative and consider potential outcomes as it advances. The method involves a thorough review of ANSI/373, comparing it with voluntary sustainability initiatives (VSIs) in the forest industry to assess its effectiveness and challenges, and semi-structured interviews with contacts in the dimension stone field. Key drivers such as corporate social responsibility and market pressures influence the adoption of sustainability standards. The results highlight the embedded environmental considerations within the emerging dimension stone standards and their implications for sustainable practices in the industry. While the ANSI/373 standard promotes sustainable awareness and practices, it faces challenges in certification credibility and industry acceptance, particularly due to inconsistency among firms in their response, rigorous certification demands, and skepticism about certification credibility. The research advocates for enhanced collaborative frameworks to increase the standard’s adoption and impact, suggesting that industry stakeholders prioritize showcasing dimension stone as a practical, environmentally considerate material.

The continuous casting process of helical fiber reinforced metal matrix composites was proposed, and the experimental equipment was designed and manufactured. The relationship model be-tween the process parameters and the helical shape of the fibers in the metal matrix is analyzed by differential geometry. Helical carbon fiber reinforced lead matrix composites were prepared under different conditions. When the melting temperature and cooling intensity were increased, the helical radius of helical carbon fiber in lead matrix was increased. When the fiber rotation speed was increased, the helical radius was decreased, and the helical pitch was de-creased proportionally. The experimental results are consistent with the process model. Carbon fiber rein-forced aluminum composites were prepared. Scanning electron microscopy showed that the infiltration between the aluminum matrix and the carbon fiber was not complete. As the volume fraction of carbon fiber which was added in composites is too small, the mechanical properties of the composites have not been significantly improved.

This article presents an innovative approach to the design of a safe adaptive backstepping control system. Tailored specifically for underactuated marine robots, the system utilizes simple sensors for enhanced practicality and efficiency. Given their operation in diverse oceanic environments fraught with various sources of uncertainties, ensuring the system's safe and robust behavior holds paramount importance in the control literature. To address this concern, this paper introduces a control strategy designed to ensure robustness at both the kinematic and dynamic levels. By emphasizing the compensation for the system uncertainties, the design integrates a straightforward fuzzy system structure. To further ensure the system's safety, a funnel surface is defined, followed by the design of a suitable nonlinear sliding surface as a function of the funnel and tracking error. Specifically leveraging the Lyapunov function, the study formally establishes the Semi-globally Practically Finite-time Stability of the closed-loop system, validated through simulations conducted on underactuated marine robots.

Several types of guided bone regeneration materials are available with various properties and clinical indications. Among them, dentin-derived matrix from extracted teeth is an excellent alternative to traditional graft materials, such as allografts and xenografts. Different clinical preparation protocols exist: block form versus powder form, demineralized versus non-demineralized form. Out of these methods, demineralization protocols for dentin-derived matrix from extracted teeth have been noted for a wide range of successful clinical outcomes. The purpose of this animal study was to find out the most effective method of demineralizing dentin-derived matrix to result in the highest regenerative ability in the bone graft material in rabbit calvaria. The study conducted a comparative histomorphometric analysis of four groups in distinguished matrix conditions: a control group without graft placement, a non-demineralized dentin-derived matrix graft placement group, a 15-minute demineralized dentin-derived matrix graft placement group, and a 30-minute demineralized dentin-derived matrix graft placement group. Regenerative processes were evaluated three times at 2, 4, and 8 weeks post-graft placement. These groups of rabbits were evaluated randomly in a blinded setting to prevent bias. Among the four groups compared, the group with a 15-minute demineralized dentin-derived matrix graft showed the most efficient bone regeneration in the histomorphometric analysis. Based on this animal study, it was apparent that a 15-minute demineralization of dentin-derived matrix is the preferred preparation protocol to maximize the regenerative potential in the matrix.

Promoting green development has become an important way to optimize the ecological and economic structure and promote sustainable development. The Yangtze River Economic Belt is an important economic corridor in China, and it remains to be examined whether the implementation of environmental regulations has enhanced the green total factor productivity (GTFP) of cities. This paper calculates the green total factor productivity of 107 cities within the Yangtze River Economic Belt by using the super-efficient SBM model and the GML index with Chinese city panel data from 2007-2019 and measures the intensity of environmental regulations through textual analysis. The bidirectional fixed-effects model constructed in this paper suggests an inverted U-shaped relationship between environmental regulation and GTFP, which is confirmed by a series of robustness tests. Green technology innovation and advanced industrial structure play a mechanism role in this. In regions with lower levels of green technology and industrial structure, the inverted U-shaped relationship between environmental regulation and green total factor productivity is more significant. In addition, the phenomenon of GTFP rising and then falling because of environmental regulation is more obvious in cities in the middle and upper reaches of the Yangtze River and outside the urban agglomerations. Therefore, when formulating environmental regulation policies, it is necessary to balance the relationship between economic development and environmental protection and harmonize the environment and economic development of the entire Yangtze River Basin.

Hydrogen sulfide is present in active or extinct volcanic areas (mofettas). The habitable premises in these areas are affected by the presence of hydrogen sulfide, which, even in low concentrations, gives off a bad to unbearable smell. If the living spaces considered are closed enclosures, then a system can be designed to reduce the concentration of hydrogen sulfide. This paper presents a membrane way to reduce the hydrogen sulfide concentration to acceptable limits using a cellulosic derivative-propylene hollow fiber based composite membrane module. The cellulosic derivatives considered were carboxymethyl–cellulose (NaCMC), cellulose acetate (CA), methyl 2–hydroxyethyl–cellulose (MHEC), and 2–hydroxyethyl–cellulose (HEC). In the permeation module, hydrogen sulfide is captured with a solution of cadmium that forms cadmium sulfide, usable as a luminescent substance. The composite membranes were characterized by SEM, EDAX, FTIR, FTIR 2D maps, thermal analysis (TG and DSC) and from the perspective of hydrogen sulfide air removal performance. To determine the process performances, the variables were: the nature of the cellulosic derivative–polypropylene hollow fiber composite membrane, the concentration of hydrogen sulfide in the polluted air, the flow rate of polluted air, and the pH of the cadmium nitrate solution. Pertraction efficiency was maximum for the sodium carboxymethyl–cellulose (NaCMC)-polypropylene hollow fiber membrane, a hydrogen sulfide concentration in the polluted air of 20 ppm, polluted air flow rate of 50 L/min, and a pH of 2 and 4.

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

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates that reach 60%, mainly due to an excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules reported to be dysregulated in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting the reverse interplay between miRNA-levels and their target-genes’ expression. Incorporating gene expression data from our group’s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia and early-invasion OSCC, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is underexpressed in dysplasia and early-invasion. Malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p and miR-34a-5p. The identification of stage-specific miRNA molecules may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Estimating the ocean’s subsurface thermohaline information from satellite measurements is essential for understanding ocean dynamics and El Niño phenomenon. This paper proposes an improved double-output Residual Neural Network (DO-ResNet) model to concurrently estimate the ocean subsurface temperature (OST) and ocean subsurface salinity (OSS) in the tropical Western Pacific using multi-source remote sensing data, including sea surface temperature (SST), sea surface salinity (SSS), sea surface height anomaly(SSHA), sea surface wind (SSW), and geographical information (including longitude (LON) and latitude (LAT)). In the model experiment, Argo data were used to train and validate the model, and the root mean square error (RMSE), normalized root mean square error (NRMSE) and coefficient of determination (R²) were employed to evaluate the model's performance. The results showed that the sea surface parameters selected in this study have a positive effect on the estimation process, and the average RMSE and R² values for estimating OST (OSS) by the proposed model are 0.34 °C (0.05 psu) and 0.91 (0.95), respectively. Under the data conditions considered in this study, DO-ResNet demonstrates superior performance relative to the extreme gradient boosting model, random forest model, and artificial neural network model. Additionally, this study evaluates the model’s accuracy by comparing its estimations of OST and OSS across different depths with Argo-derived data, demonstrating the model's ability to effectively capture the most spatial features, and by comparing NRMSE across different depths and seasons, the model displays strong seasonal adaptability. In conclusion, this research introduces a novel artificial intelligence technique for estimating OST and OSS in the tropical Western Pacific Ocean.

Phased injection of natural gas into internal combustion marine engines is a promising solution for optimizing performance and reducing harmful emissions, particularly unburned methane, a potent greenhouse gas. This innovative practice distinguishes itself from continuous injection because it allows for more precise control of the combustion process with only a slight increase in system complexity. By synchronizing the injection of natural gas with the intake and exhaust valve opening and closing times while also considering the gas path in the manifolds, methane release into the atmosphere is significantly reduced, making a substantial contribution to efforts to address climate change. Moreover, phased injection improves the efficiency of marine engines, resulting in reduced overall fuel consumption, lower fuel costs, and increased ship autonomy. This technology has been tested on a single-cylinder, large-bore, four-stroke research engine designed for marine applications, operating in dual-fuel mode with diesel and natural gas. Performance was compared with that of the conventional continuous feeding method. Evaluation of the effect on equivalent CO2 emissions indicates a potential reduction of up to approximately 20%. This reduction effectively brings greenhouse gas emissions below those of the diesel baseline case, especially when injection control is combined with supercharging control to optimize the air-fuel ratio.

In numerical simulations, achieving high accuracy without significantly increasing computational costs is often challenging. To address this, this paper presents an improved finite volume weighted essentially non-oscillatory (WENO) scheme tailored for applicability in computational fluid dynamics (CFD) and implemented in the flow solver NUAA-Turbo for simulating turbomachinery flows using both RANS and RANS/LES coupling. Firstly, the new WENO scheme is validated against classic numerical test cases to assess its stability and reliability in handling discontinuities, the Double problem, and Raleigh-Taylor (RT) instability issues. Compared to the original format, this enhanced finite volume WENO scheme demonstrates superior stability near discontinuities and resolves flow features with the same grid resolution more effectively. Next, for engineering applications related to turbomachinery, such as compressor and turbine characteristics, computations are performed using RANS, and the results obtained using WENO-ZQ3 and WENO-JS3 are compared. Finally, the new fifth-order WENO scheme is applied to RANS/LES coupled simulations of turbine wakes and film cooling. The results show that the enhanced finite volume WENO scheme offers improved stability and accuracy in engineering applications, allowing for high-precision calculations with fewer grid points to capture more detailed flow physics, thereby reducing computational costs in aerodynamic applications.

To conduct high-precision and high-resolution numerical simulation of complex flow structures in turbomachinery, a high-order finite volume weighted essentially non-oscillatory (WENO) scheme for the large eddy simulation (LES) is improved and embedded into the three-dimensional viscous unsteady CFD solver NUAA-Turbo. Firstly, the spectral characteristics and unsteady convergence of the improved WENO scheme are studied. Compared with the classical WENO scheme, the improved WENO scheme has better dissipation and dispersion characteristics and faster convergence speed. Then, the coefficient CW of the Wall-Adapting Local Eddy-viscosity (WALE) model is calibrated by decaying homogeneous isotropic turbulence (DHIT) test case. Finally, the scheme is applied to conduct high-precision LES calculations of turbulent boundary layer flow, supersonic compression corner flow, and low-pressure turbine cascade separation flow. The numerical simulation results show that this WENO scheme has excellent shock wave capture ability and turbulence resolution and can capture more flow field details with less mesh size, greatly reducing the computational cost and laying a foundation for large-scale engineering application of LES.

To secure logic circuits against the illegal copying the insertion of the so-called key bit inputs using XOR/XNOR gates has been proposed in . The inserted gates modify (lock) the behavior of the original circuit and only the correct choice of the secret key bits guarantees the equivalent behaviour of the locked circuit to the original circuit. To break this kind of security, i.e. to find the secret key bits, there was a SAT solver based attack proposed in . The aim of this work is to experimentally verify this attack on several locked circuits with various number of primary inputs and outputs and with various number of gates. Except for the random placement of the key gates we evaluate also the positioning with chaining elimination. The obtained and presented results show that we were able to unlock 10 of 11 circuits within few minutes on a common PC.

Intermetallic compounds are increasingly being expected to utilize in tribological environments, but to date the works are hindered by insufficient ductility at low and medium temperature. This paper presents a novel multiphase intermetallic alloy with the chemical composition of Mo-40Ni-13Si (at.%). Microstructure characterization reveals that a certain amount of ductile Mo phases formed during the solidification process of ternary Mo-Ni-Si alloy melt, which is undoubtedly beneficial to the ductility improvement of intermetallic alloy. Tribological properties of the designed alloy, including wear resistance, friction coefficient and metallic tribological compatibility, were evaluated under dry sliding wear test conditions at room temperature. Results suggested that the multiphase alloy possesses an excellent property for room-temperature wear applications, which is attributed to the unique microstructural features and thereby good combination in hardness and ductility. The corresponding wear mechanism is also reported by observing the worn surface, subsurface and wear debris of alloy, which to be found is soft abrasive wear.

With the integrated development of the Internet, wireless sensor technology, cloud computing, and mobile Internet, there has been a lot of attention given to research about and applications of the Internet of Things. A Wireless Sensor Network (WSN) is one of the important information technologies in the Internet of Things; it integrates multi-technology to detect and gather information in a network environment by mutual cooperation, using a variety of methods to process and analyze data, implement awareness, and perform tests. This paper mainly researches the localization algorithm of sensor nodes in a wireless sensor network. Firstly, a multi-granularity region partition is proposed to divide the location region. In the range-based method, the RSSI (Received Signal Strength indicator, RSSI) is used to estimate distance. The optimal RSSI value is computed by the Gaussian fitting method. Furthermore, a Voronoi diagram is characterized by the use of dividing region. Rach anchor node is regarded as the center of each region; the whole position region is divided into several regions and the sub-region of neighboring nodes is combined into triangles while the unknown node is locked in the ultimate area. Secondly, the multi-granularity regional division and Lagrange multiplier method are used to calculate the final coordinates. Because nodes are influenced by many factors in the practical application, two kinds of positioning methods are designed: the unknown node is in the positioning unit or not. When the unknown node is on the side of the positioning unit, we use the method of vector similarity. Moreover, we use the centroid algorithm to calculate the ultimate coordinates of unknown node. When the unknown node is not on the side of the positioning unit, we establish a Lagrange equation containing the constraint condition to calculate the first coordinates. Furthermore, we use the Taylor expansion formula to correct the coordinates of the unknown node. In addition, this localization method has been validated by establishing the real environment.

The electroencephalogram (EEG) is a record of brain activity. Brain Computer Interface (BCI) technology formed by the EEG signal has become one of the hotspots at present. How to extract the feature signal of EEG is the most basic research of BCI technology. In this paper, A new method of recognizing fatigue, conscious, concentrated state of human brain is proposed by the combination of discrete wavelet transform and the neural network based on EEG signal. First of all, the law signal is preprocessed by the wavelet denoising method because the law EEG signal contains a large number of high frequency noise, which is decomposed into multi-layer high frequency signal and low frequency signal. thus, δ wave, θ wave, α wave, β wave are obtained by the wavelet transform. And then, frequency band energy of the different wave is regards as the feature signal of EEG. In the experiment, the feature signal is classified by radial basic function (RBF) and annealed chaotic competitive learning network (ACCLN). RBF and ACCLN networks are trained with 500 sets of sample data and are tested by 100 sets of samples in different mental states. The experimental results show that the average accuracy of RBF network under three conditions are 88.75%, 88.25%, 88.5%, respectively, and the correct rate of ACCLN network is 97%, 98%, 98%, respectively.

Baijiu is popular with its long history and balanced flavor, and flavor type was the most widely used classification mode for Baijiu. However, the evolution relationship of Baijiu flavor types and the differential markers between flavor types are still unclear, which has greatly affected the development of Baijiu industry. In this study, a total of 319 trace components were identified by gas chromatography-olfactometry-mass spectrometry and gas chromatography-mass spectrometry. Among them, 91 trace components with high odor active values or taste active values were recognized as flavor components. Then random forests were conducted to screen differential markers between derived and basic flavor types, and principal component analysis was carried out to evaluate their effectiveness in distinguishing the flavor types of Baijiu. Finally, 19 differential markers were screened and proved to effectively reveal the evolution Baijiu flavor types, and were further verified as key differential markers by addition test and correlation analysis.

This study aimed to identify whether gyrate atrophy of the choroid and retina (GACR) heterozygous individuals have possible clinical manifestations and to explore the potential pathogenic mechanism. In this retrospective study, we surveyed a two-generation pedigree of an individual diagnosed with GACR. Two family members underwent ophthalmological, hematologic, and genetic tests. An arginine-restricted diet with vitamin B6 supplementation was implemented; clinical assessments were repeated every 3 months during follow-up. Relative OAT mRNA expression was determined using real-time quantitative polymerase chain reaction. The 19-year-old compound heterozygous daughter (OAT: c.1186C&gt;T; c.748C&gt;T), had bilateral high myopia, posterior staphyloma, chorioretinal atrophy, macular abnormalities, and elevated hematologic ornithine. The 54-year-old heterozygous mother (OAT: c.1186C&gt;T), presented with bilateral severe myopia, asymmetric posterior staphyloma, retina and choroidal capillary layer atrophy, retinal pigment epithelium abnormalities, and mildly elevated hematologic ornithine. Compared to normal individuals, the daughter and mother had 29% and 46% relative OAT mRNA expression, respectively (P&lt;0.001). We believe that this is the first report of a carrier of one OAT variant allele with mild phenotypes, suggesting that family members should be aware of the possible involvement of autosomal recessive conditions. Additional data suggests nonsense mediated decay-initiated mRNA degradation may cause GACR.

Early discharge after childbirth has led to a rise in neonatal readmission, becoming a major concern in recent decades. Our research aimed to identify the risk factors and incidence of neonatal readmission, as well as explore preventive measures. Our study at the Clinical Hospital of Pediatrics in Ploiești, Romania included 108 neonates admitted during the neonatal period. This accounted for 2.06% of all admissions (5226). The most prevalent cases were malnutrition (25%), fever (20.3%) and bronchiolitis (17.5%). Diarrhea and infectious gastroenteritis were also observed (14.8%), along with acute rhinoconjunctivitis (9.2%) and late onset sepsis (3.7%). No deaths were recorded. The most significant characteristics identified were number of children (p&lt;0.001) and age at maternity discharge (p&lt;0.001). By following the prevention rules, malnutrition, feeding errors, and infections can be avoided. This includes practicing proper hand hygiene for both mothers and medical staff, as well as educating and demonstrating to mothers the benefits of breastfeeding. In addition, all newborns discharged from the maternity ward should benefit from follow-up at 7-10 days of life. Our results confirm the effectiveness of a multidisciplinary team and endorse promoting breastfeeding. Implementing quality control measures and regularly evaluating the surveillance program will help improve its effectiveness.

A binary biomass-based solid electrolyte film (LSE) was successfully synthesized through the incorporation of lignin nanoparticles (LNP) with sodium alginate (SA). The impact of the mass ratio of SA to LNP on the microstructure, porosity, electrolyte absorption capacity, ionic conductivity, and electrochemical properties of the LSE was thoroughly investigated. The results indicated that as the proportion of SA increased from 5% to 15% LNP, the pore structure of the LSE became increasingly uniform and abundant. Consequently, enhancements were observed in porosity, liquid absorption capacity, ionic conductivity, and overall electrochemical performance. Notably, at a SA amount of 15% LNP, the ionic conductivity of resultant LSE-15 was recorded at 14.10 mS cm1, with porosity and liquid absorption rates reaching 308% and 58.4%, respectively. LSE-15 was employed as a solid electrolyte, while LNP-based carbon aerogel (LCA) served as the two electrodes in the construction of a symmetric all-solid-state supercapacitor (SSC). The SSC device demonstrated exceptional electrochemical storage capacity, achieving a specific capacitance of 197 F g1 at 0.5 A g1, along with maximum energy and power density of 27.33 W h kg1 and 4998 W kg1, respectively. Furthermore, the SSC device exhibited highly stable electrochemical performance under extreme conditions, including compression, bending, and both series and parallel connections. Therefore, the development and application of the binary biomass-based solid electrolyte film in supercapacitors represent a promising strategy for harnessing high-value biomass resources in the field of energy storage.

Wearable technology has been proposed as a potential tool to change the way of human life, such as the smart bracelet and the Google Glass. In the wearable technology, the inertial sensor has great significance in tracking the object movements. The paper focused on detecting the movements of user’s finger based on the inertial sensor to give the control signals. Firstly, the attitude matrix, which represented the transformation relation of carrier coordinate system and the navigation coordinate system, was obtained. Secondly, the attitude matrix was expressed based on the quaternions. Thirdly, the finger gesture was processed by the attitude matrix to get the attitude angle. Finally, the robot was controlled by attitude angle to make the moving action. The experimental results showed the detection of the finger movement is effective.

In terahertz communication systems, lens antennas used in transceivers are basically plano-convex dielectric lenses. As the aperture increases and the focal length decreases, the thickness and mass of the plano-convex lens increase rapidly. Through theory and simulation, we designed a Fresnel lens suitable for the terahertz band to meet the requirements of large aperture and short focal length, and simulated the performance, advantages and disadvantages of the terahertz Fresnel lens. A 300GHz terahertz wireless communication system was built to verify the gain effect of the Fresnel lens antenna. The experimental results show that the Fresnel lens can amplify the signal in the terahertz band. The theoretical gain of a 30 cm Fresnel lens is 48.83dB, while the actual measured gain is approximately 45dB.

Diabetes is a major health concern that the next-generation of on-demand insulin releasing implants may overcome for personalized therapy. Therein, 3D-printed phenylboronic acid-containing subcutaneous implants with on-demand glucose-triggered drug release abilities are produced using high resolution stereolithography technology. To that end, the methacrylation of phenylboronic acid is targeted following a two-step reaction. The resulting photocurable phenylboronic acid derivative is accordingly incorporated within bioinert polyhydroxyethyl methacrylate-based hydrogels at varying loadings. The end result are sub-centimeter scaled 3D-printed bionert implants that can be remotely activated with 1,2-diols and 1,3-diols such as glucose for on-demand drug administration such as insulin. As a proof of concept, varying glucose concentration from hypoglycemia to hyperglycemia levels readily allow the release of pinacol, i.e. a model molecule with similar release properties than insulin, at respectively low and high rates. In addition, the results demonstrated that adjusting the geometry and size of the 3D-printed part is a simple and suitable method for tailoring the release behavior and dosage.

The prevalence of sexual harassment and abuse in school sport, specifically from coaches to their athletes remains a concerning and pervasive issue. In an attempt to better understand and prevent specific coach-behaviours associated with such sexual misconduct, researchers have developed the Sexual Violence Questionaire in Sport. While the reliability of this measurement tool has been tested in anglo-saxon cultural contexts, it is not known whether the questionnaire is applicable to other cultural contexts. A sample of 146 (52 female, 94 male) Bachelor students from a university in the Basque Country participated in this cross cross-sectional study. The questionnaire was administered twice over a two-week period to assess test-retest reliability. The internal consistency of the Sexual Violence Questionaire in Sport was high, with Cronbach's alpha values of 0.891 for perceptions and 0.813 for experiences across all participants. Gender-specific analysis showed similar reliability, with females having slightly lower alpha values for perceptions. Significant differences between test and retest were found (10 from perceptions 2 from experiences). However, Cohen’s Kappa analysis showed significant agreement across all items. In conclusion, the study highlights the questionnaire’s overall reliability and suggests its effectiveness as a tool for measuring sexual violence in sports within the Spanish context. Nonetheless, the findings of this study underscore the need for further research to enhance the instrument's stability and to better understand gender differences in perceptions and experiences of sexual violence in sports contexts.