This article presents a novel computational approach to visualizing memristor dynamics within a simulated neural network. Memristors, known for their ability to emulate synaptic plasticity due to their variable resistance characteristics, are key components in neuromorphic computing and hold potential for advancing our understanding of neural processes. Our study introduces a sophisticated memristor model that incorporates non-linear resistance changes, simulating the complex behavior of synaptic connections in a neural network.The neural network, consisting of multiple interconnected neurons with memristor-based synapses, is subjected to a series of electrical stimuli. Each memristor's resistance is modulated in response to the applied voltage, mimicking the synaptic weight adjustments that occur during learning and memory formation in biological neural networks. To effectively illustrate these changes, we employ a high-contrast color mapping scheme, where the varying resistance of each memristor is represented by distinct colors, providing a clear and intuitive visualization of synaptic modifications over time.Our simulation runs through multiple iterations, demonstrating how synaptic weights evolve in response to different input patterns. The use of an extended voltage range and increased scaling factors ensures pronounced changes in memristance, enhancing the visibility of synaptic adaptations. The resulting visualizations offer a compelling representation of how memristors can mimic the dynamic nature of biological synapses, contributing to the field of neuromorphic engineering and deepening our comprehension of neural mechanisms underlying learning and memory.This work not only showcases the potential of memristors in simulating neural behavior but also provides a valuable educational tool for illustrating complex concepts in neuroscience and neuromorphic computing. The insights gained from this study pave the way for further exploration into the development of advanced neural network models and the design of memristor-based computing systems.

In virology, the term reverse genetics refers to a set of methodologies in which changes are introduced into the viral genome and their effects on the generation of infectious viral progeny and their phenotypic features are assessed. Reverse genetics emerged thanks to advances in recombinant DNA technology, which made the isolation, cloning, and modification of genes through mutagenesis possible. Most virus reverse genetics studies depend on our capacity to rescue an infectious wild-type virus progeny from cell cultures transfected with an “infectious clone”. This infectious clone generally consists of a circular DNA plasmid containing a functional copy of the full-length viral genome, under the control of an appropriate polymerase promoter. For most DNA viruses, reverse genetics systems are very straightforward, since DNA virus genomes are relatively easy to handle and modify and are also (with few notable exceptions) infectious per se. This is not true for RNA viruses, whose genomes need to be reverse transcribed into cDNA before any modification can be done. Establishing reverse genetics systems for members of the Caliciviridae has proven exceptionally challenging, due to the low number of members of this family that propagate in cell culture. Despite the early successful rescue of a calicivirus from a genome-length cDNA more than two decades ago, reverse genetics methods are not routine procedures that can be easily extrapolated to other members of the family. Reports of calicivirus reverse genetics systems have been few and far between. In this review, we discuss the main pitfalls, failures, and delays behind the generation of several successful calicivirus infectious clones.

Senna rugosa is a species found in the Cerrado and used in folk medicine as a vermifuge and in the treatment of poisonous snakebites accidents. In this work, we identified the main secondary metabolites present in ethanolic extracts of the leaves (ELSR) and roots (ERSR) of S. rugosa and evaluated the potential cytoprotective effect against cellular macromolecular damage, as well as the cytotoxic properties of the extracts on the K562 and Jurkat leukemic cell lines. The identification of metabolites was done by liquid chromatography coupled with mass spectrometry. The antioxidant activities were investigated by direct ABTS•+ and DPPH• radical scavenging methods, protection against oxidative damage in proteins and DNA. The cytotoxic properties were investigated against healthy cells, isolated from human peripheral blood (PBMC) and leukemic cell lines. The leaf extract contains catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, and dimeric and trimeric procyanidins, while the root extract profile shows obtusichromoneside derivatives, 2-methoxystypandrone, stilbene derivatives, naphthopyranones, and flavanone derivatives. The extracts showed antioxidant activity, with IC50 of 4.86 ± 0.51 µg/mL and 8.33 ± 0.90 µg/mL in the ABTS assay for ELSR and ERSR, respectively. And in the DPPH• assay, the IC50 was 19.98 ± 1.96 µg/mL for ELSR and 13.37 ± 1.05 µg/mL for ERSR. The extracts protected macromolecules against oxidative damage at concentrations of 5 µg/mL. The cytotoxicity test against leukemic strains was observed after 24 and 48 hours of treatment. After 48 h, results against the K562 cell line demonstrate IC50 of 242.54 ± 2.38 µg/mL and 223.00 ± 2.34 µg/mL for ELSR and ERSR , respectively. While against the Jurkat cell line, these extracts showed IC50 of 171.45 ± 2.25 µg/mL and 189.30 ± 2.27 µg/mL, respectively Results on PBMC viability, demonstrate that the extracts showed selectivity for the leukemic cell lines. Together, our results reveal that the leaves and roots of S. rugosa have completely distinct and complex chemical compositions. This study expands the repertoire of identified chemical compounds and underscores their significant pharmacological potential in conditions related to oxidative stress and leukemia.

Cell mechanics is a biophysical indicator of cell state, such as cancer metastasis, leukocyte activation, and cell cycle progression. Atomic force microscopy (AFM) is a widely used technique to measure cell mechanics, where the Young modulus of a cell is usually derived from the Hertz contact model. However, the Hertz model assumes that the cell is an elastic, isotropic, and homogeneous material and that the indentation is small compared to the cell size. These assumptions neglect the effects of the cytoskeleton, cell size and shape, and cell environment on cell deformation. In this study, we investigated the influence of cell size on the estimated Young’s modulus using liposomes as cell models. Liposomes were prepared with different sizes and filled with phosphate buffered saline (PBS) or hyaluronic acid (HA) to mimic the cytoplasm. AFM was used to obtain the force indentation curves and fit them to the Hertz model. We found that the larger the liposome, the lower the estimated Young’s modulus for both PBS-filled and HA-filled liposomes. This suggests that the Young modulus obtained from the Hertz model is not only a property of the cell material, but also depends on the cell dimensions. Therefore, when comparing or interpreting cell mechanics using the Hertz model, it is essential to account for cell size.

Plant viral diseases constitute a major contributor to agricultural production losses, significantly impacting the economies of exporting countries by more than $30 billion annually. Understanding and researching the biology and genomics of viruses is crucial for developing virus-resistant, genetically edited or genetically modified plants. Genetic modifications can be targeted to specific regions within genes of target plants which are important or essential for the virus to establish a systemic infection, thus fostering resistance or enabling plants to effectively respond to invading agents while preserving their yield. This review provides an overview of viral incidence and diversity in tropical fruit crops and aims to examine the current state of the knowledge on recent research efforts aimed at reducing or eliminating the damage caused by viral diseases, with emphasis on genetically edited products that have reached the market in recent years.

RNA-seq faces persistent challenges due to the ongoing expanding array of data processing workflows, none of which have yet achieved standardization to date. It is imperative to determine which method most effectively preserves biological facts. Shannon entropy serves as a tool for depicting the biological status of a system. Thus, we assessed the measurement of Shannon entropy by several RNA-seq workflow approaches, employing RPKM and median normalization on paired samples of 475 TCGA RNA-seq datasets spanning eight different cancer types with 5-year overall survival rates ranging from 30% to 98%. Our analysis revealed that the RPKM normalization coupled with a threshold of log2 fold change ≥1 for indentifying differentially expressed genes, yielded the best results with a correlation coefficient of 0.91. We propose that Shannon entropy can serve as an objective metric for refining the optimization of RNA-seq workflows.

The sweetpotato whitefly, Bemisia tabaci MEAM1, is a pest known to significantly impact tomato development and yields through direct damage and virus transmission. To manage this pest, the current study compared the effectiveness of various insecticide rotations. Field trials included rotations involving synthetic insecticides, biochemicals, and microbial agents, applied according to their labeled highest concentrations. Results indicated that while standard synthetic insecticides consistently reduced whitefly egg and nymph counts significantly, microbial biopesticide rotations also achieved reductions, although less consistently. This study demonstrated that while traditional chemical treatments remain highly effective, integrating microbial biopesticides containing Beauveria bassiana and Cordyceps javanica present a viable alternative that could mitigate resistance development and reduce environmental impact. The findings suggest the potential for optimizing integrated pest management (IPM) and Insecticide Resistance Management (IRM) strategies by incorporating a variety of modes of action to sustainably manage B. tabaci MEAM1 populations in agricultural settings.

Left ventricular (LV) longitudinal function is mechanically coupled to the elasticity of the ascending aorta (AA). The pathophysiologic link between stiff AA and reduced longitudinal strain and subsequent deterioration in longitudinal LV systolic function is likely relevant in heart failure with preserved ejection fraction (HFpEF). A proposed therapeutic effect of freeing the LV apex and allowing for LV inverse longitudinal shortening was studied in-silico utilizing Living Left Heart Human Model (Dassault Systémes Simulia Corporation). LV function was evaluated in a model with A) Elastic AA; B) Stiff AA; and C) Stiff AA with free LV apex. The cardiac model simulation demonstrated that freeing the apex caused inverse LV longitudinal shortening that can abolish the deleterious mechanical effect of a stiff AA on LV function. A stiff AA and impairment of LV longitudinal strain are common in patients HFpEF. The hypothesis-generating model strongly suggests that freeing the apex and inverse longitudinal shortening may improve LV function in HFpEF patients with a stiff AA.

Buttonweed (Cotula coronopifolia) is native to South Africa but invasive in wetlands in Europe, North America, and Australasia, where it excludes native plants. Despite being dry-fruited, field studies suggest migratory waterbirds can disperse its seeds via gut passage (endozoochory), aiding its expansion. To explore the potential for endozoochory in different regions and habitats, we collected seeds from six populations in Spain, Sweden, and the UK. Germination was tested under different salinity levels (0, 5, 10, 15 g/L) and simulated gut passage treatments: scarification, acidification, or both. No germination occurred at 15 g/L. Higher salinity reduced and delayed germination, but full gut passage treatment increased germinability and accelerated germination. Scarification or acid treatment alone resulted in intermediate germination patterns. There were significant salinity x population and gut passage x population interactions on germinability. The acceleration effect of gut passage on germination was stronger at 5-10 g/L than at 0 g/L. This study highlights how migratory birds can facilitate the spread of alien plants introduced by humans. Non-classical endozoochory by waterbirds is an understudied mechanism for the long-distance dispersal of dry-fruited alien plants. Further research on C. coronopifolia, including population genetics, is necessary to understand dispersal mechanisms and facilitate management strategies.

Sporotrichosis’ clinical manifestations, lesions in the cutaneous or subcutaneous tissues, it is caused by dimorphic fungi of the Sporothrix complex, is a cosmopolitan mycosis that affects humans and animals. This study aimed to identify prevalent species in Minas Gerais, Brazil, and characterize virulence profiles and antifungal susceptibility associated with Sporothrix isolates. Isolates were identified using macro and micro-morphological traits as well molecular biology techniques. Antifungal susceptibility was determined using the Minimal Inhibitory Concentration test, while, virulence factors such as growth at different temperatures, biofilm formation, melanin production, and urease activity were assessed. Our findings revealed S. brasiliensis as a predominant species isolated. Urease activity was a crucial factor associated with growth at 50°C in S. brasiliensis isolates, highlighting their high thermotolerance. Furthermore, strains isolated from humans produced a more robust biofilm compare to those from felines. Strains of S. brasiliensis isolated from Felis catus exhibited faster melanin production, decreased susceptible to antifungal agents tested, and superior growth capacity at 50°C to strains isolated from humans. Therefore, our study highlights the prevalence of S. brasiliensis causing sporotrichosis in both human and felines. However, it underscores the circulation of different strains, with varying levels of virulence and susceptibility to antifungal agents.

Oncomelania Hupensis is the exclusive intermediary host of Schistosoma japonicum in China. The alteration of its habitat and population distribution directly affects the safety of millions of individuals residing in the Yangtze River Economic Belt (YREB), and the ecological stability. Therefore, it is crucial to analyse the influence of climate change on the distribution of O. Hupensis in order to achieve accurate control over its population. This study utilised the MaxENT model to forecast possible snail habitats by utilising snail distribution data obtained from historical literature. The subsequent outcomes were achieved: The primary ecological factors influencing the distribution of O. Hupensis are elevation, minimum temperature of coldest month, and precipitation of wettest month; Furthermore, future climate scenarios indicate a decrease in the distribution area and a northward shift of the distribution centre for O. hupensis; Specifically, those in the upstream will move northeast, while those in the midstream and downstream will move northwest; These changes in suitable habitat area, the average migration distance of distribution centers across different climate scenarios, time periods, and sub-basins within the YREB, resulting in uncertainty. This study offers theoretical justification for the prevention and control of O. hupensis along the YREB.

Despite the high quality of soybean protein, raw soybeans and soybean meal cannot be directly included into animal feed mixtures due to the presence of Kunitz (KTi) and Bowman Birk protease inhibitors (BBi) which reduces animal performance. Heat treatment can substantially inactivate trypsin and chymotrypsin inhibitors (BBi) but such treatment is energy intensive, adds expense, and negatively impact the quality of seed proteins. As an alternative approach we have employed CRISPR/Cas9 gene editing to create mutations in BBi genes to drastically lower the protease inhibitor content in soybean seed. Agrobacterium-mediated transformation was used to generate several stable transgenic soybean events. These independent CRISPR/Cas9 events were examined in comparison to wild type plants using Sanger sequencing, proteomic analysis, trypsin/chymotrypsin inhibitor activity assays and q15RT-PCR. Collectively, our results demonstrate the creation of an allelic series of loss of function mutations affecting the major BBi gene in soybean. Mutations in two of the highly expressed seed specific BBi genes lead to substantial reductions in both trypsin and chymotrypsin inhibitor activities.

To analyse Xuanwei ham flavour quality at different post-ripening times, and to elucidate its microbial diversity, we studied free amino acids and volatile flavouring compounds (VOCs) and their relationships. We determined microbial community changes in Xuanwei ham at 1, 2, 3 and 4 years (W1-4) by high-throughput sequencing, and simultaneously, VOCs and free amino acid contents by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC), respectively. Then heatmap analysis was used to determine correlations between microbial communities, free amino acids and VOCs. A total of 25 free amino acids were detected, among which W3 contained the fewest and most were generally lower than in hams in the other three years. Fifty-nine VOCs were detected, among which were 17 esters, and the highest ester content was found in W4. Atotal of 87508391 reads were obtained from the samples, of which 812844 were clean reads, and the bacterial Chao1 index and Shannon index were significantly higher in W3 than in the other three ham years. In differetly-aged Xuanwei hams, Pseudomonadota was the dominant bacterial phylum, and the most abundant genera were Sarocladium, Klebsiella and Vibrio. Klebsiella was the most abundant genus in W1, and Vibrio in W3, and the second most abundant genera were Sarocladium and Gammaretrovirus. We elucidated differences in Xuanwei ham microflora structures in different years and the main flavor-related microorganisms, thus providing a theoretical basis for subsequent Xuanwei ham storage, quality and improvement.

The fish found in the Tibetan Plateau and the Himalayas are referred to as schizothoracids, and they have evolved unique biological adaptations to high elevations. These adaptations include changes in the shape of the mouth, size, and length of gill rakers according to the prey size, sucking attachment organs to cope with fast currents, and genetic differences due to hypoxia and UV light. Nevertheless, there are recent threats like destruction of natural habitats, pollution, overfishing, and global warming that have posed serious conservation issues for numerous species. Conservation measures have been initiated even though well-articulated management techniques or other protective measures are absent from several protected areas for freshwater fisheries located in India. To resolve these issues, Schizothoracid population rescue, rehabilitation and restocking in safe water bodies should be implemented. For achieving their sustainability, scientists, conservationists, and legislators need to coordinate with each other.

Currently, there is an increase in the aging of the population, which represents a risk factor for many diseases, including sarcopenia. Sarcopenia involves progressive loss of mass, strength, and function of the skeletal muscle. Some mechanisms include alterations in muscle structure, reduced regenerative capacity, oxidative stress, mitochondrial dysfunction, and inflammation. The zebrafish has emerged as a new model for studying skeletal muscle aging because of its numerous advantages, including histological and molecular similarity to human skeletal muscle. In this study, we used fish of 2, 10, 30, and 60 months of age. The older fish showed a higher frailty index because of reduced locomotor activity and alterations in biometric measurements. We observed changes in muscle structure with a decreased number of myocytes and an increase in collagen with aging, corresponding to alterations in the synthesis, degradation, and differentiation pathways. These changes were accompanied by mitochondrial alterations, such as a decrease in intermyofibrillar mitochondria, increased mitochondrial damage, and reduced mitochondrial dynamics. Overall, we demonstrated a similarity in the aging processes of muscle aging between zebrafish and mammals.

The valorization of aquaculture/fisheries processing by-products, as well as unavoidable/unwanted catches and discards in Greece is currently an underutilized activity despite the fact that there are several best practices in Northern Europe and overseas. One of the main challenges is to determine whether the available quantities for processing are sufficient to warrant valorization of discards and fish side streams. This is the first attempt to systematically record and analyze the available quantities of fish by-products and discards in Greece in a spatial and temporal way in an effort to create a national exploitation Master Plan for the valorization of this unavoidable and unwanted biomass. A thorough survey conducted within the VIOAXIOPIO project unveiled a substantial biomass of around 19,000 tonnes annually that could be harnessed for valorization. Furthermore, the production of various High Added Value Biomolecules (HAVB) was investigated, and experimental trials were conducted to assess the potential yields and the collected data were used to formulate four valorization scenarios.

Livestock in the northern highlands of Peru is fed on the association of ryegrass (Lolium multiflorum L.) ecotype cajamarquino - white clover (Trifolium repens L.) Ladino variety constantly varies in its agronomic characteristics and nutritional value due to management considerations and its association with the soil and the animal. The objective was to evaluate yield, plant height, growth rate, number of tillers, spikelets, basal diameter in ryegrass, elongation rate, internode length, and decrease points in clover over one year. Nutritional value was represented by crude protein (CP), neutral detergent fibre (NDF), in vitro digestibility of dry matter (IVDDM) and metabolisable energy (ME) at three cutting frequencies. Better yield (5588 kg DM ha) and plant height (47.1 cm) showed the 60-day cutting frequency; however, there was no difference (p>0.05) among the three cutting frequencies in annual yield. There was no difference between number of tillers and basal diameter. Clover height, elongation rate and internode length were higher at 60 days. The highest CP concentration and lowest NDF value (p<0.05) were achieved by clover at 30 and 45 days. The producers should consider the findings obtained to decide the time of use of this association in dairy cattle feeding.

Fibropapillomatosis in sea turtles is a potentially debilitating and fatal disease for which there is still a lack of knowledge, especially for specific regions of Brazil. The diagnosis is made through the observation of clinical manifestations, and despite its association with Chelonid Alphaherpesvirus 5 (ChHV5) as the etiological agent, the expression of the disease may also be related to immunological and environmental factors caused by anthropic degradation of the environment. Thus, this review aims to elucidate what is known about this disease globally and especially in various regions of Brazil, promoting a better understanding of its evolution, spatiotemporal prevalence and relationship with human activities. Furthermore, the review explores the molecular biology of ChHV5, including its genomic structure, replication cycle, and mechanisms of pathogenesis. The role of environmental factors, such as temperature and pollution, in modulating ChHV5 infection and FP development is also discussed. Additionally, the review summarizes current diagnostic methods for detecting ChHV5 infection in sea turtles, highlighting the importance of early detection and monitoring for effective disease management and conservation efforts. Finally, the review outlines future research directions aimed at improving our understanding of ChHV5 and developing strategies for FP control and prevention in sea turtle populations.

Human immunodeficiency virus (HIV) and malaria, caused by infection with Plasmodium spp., are endemic in similar geographical locations. As a result, there is high potential for HIV/Plasmodium co-infection, which increases the pathology of both diseases. However, the immunological mechanisms underlying the exacerbated disease pathology observed in co-infected individuals are poorly understood. Here, we used the rhesus macaque (RM) model to characterize the immunopathogenic impact of Plasmodium fragile co-infection during antiretroviral therapy (ART)-treated simian immunodeficiency virus (SIV)-infection. We observed that P. fragile co-infection resulted in parasitemia and anemia, as well as persistently detectable viral loads (VL) and decreased absolute CD4+ T-cell counts despite daily ART treatment. Notably, P. fragile co-infection was associated with increased levels of inflammatory cytokines linked with neutrophil function, including monocyte chemoattractant protein 1 (MCP-1). P. fragile co-infection was associated with increased levels of neutrophil elastase, a plasma marker of neutrophil extracellular trap (NET) formation, but significant decreases in markers of neutrophil degranulation, potentially indicating a shift in neutrophil functionality during co-infection. Finally, we characterized levels of plasma markers of gastrointestinal (GI) barrier permeability and microbial translocation and observed significant correlations between indicators of GI dysfunction, clinical markers of SIV and Plasmodium infection, and neutrophil frequency and function. Taken together, these data indicate that neutrophil-driven inflammation and GI dysfunction may underlie heightened SIV/P. fragile co-infection pathogenesis.

We produced a recombinant eel luteinizing hormone (rec-eel LH) analog with high potency in Chinese hamster ovary DG44 (CHO DG44) cells. The eel LH mutant (LH-M), which had a linker comprising the equine chorionic gonadotropin (eCG) β-subunit carboxyl-terminal peptide (CTP) region (amino acids 115 to149), was inserted between the β-subunit and α-subunit of wild-type tethered eel LH (LH-wt). Monoclonal cells transfected with the eel LH-wt and eel LH-M plasmids were isolated from five and nine clones of CHO DG44 cells, respectively. The secreted quantities abruptly increased on day 3, with peak levels of 5,000–7,500 ng/mL on day 9. The molecular weight of eel LH-wt was 32–36 kDa while that of eel LH-M increased to approximately 38–44 kDa, indicating the detection of two bands. Treatment with peptide N-glycanase F decreased the molecular weight by approximately 8 kDa. The oligosaccharides at the eCG β-subunit O-linked glycosylation sites were appropriately modified post-translation. The EC50 value and maximal responsiveness of eel LH-M increased by approximately 2.90- and 1.29-fold, respectively, indicating that the mutant exhibited more potent biological activity than eel LH-wt. Phosphorylated extracellular regulated kinase (pERK1/2) activation resulted in a sharp peak 5 min after agonist treatment, with a rapid decrease thereafter. These results indicate that the new rec-eel LH analog which contains the eCG β-subunit CTP linker comprising O-linked glycosylation sites, had more potent activity than the wild-type in vitro. Taken together, this new eel LH analog can be produced in large quantities using a stable CHO DG44 cell system.

Dinoflagellates belonging to Hematodinium are important parasites of marine crustaceans, primarily dec-apods. In this study, we document the first report of H. perezi Chatton & Poisson, 1930 on the African Atlantic coast. This is also the first parasite record in the invasive American blue crab Callinectes sapidus Rathbun, 1896 in Morocco. Specimens of C. sapidus were sampled in winter 2023 from two Ramsar sites on the Atlantic coast of Morocco, namely Merja Zerga and Oualidia Lagoons, and were screened to detect the presence of parasites in their hemolymph. Based on staining fresh hemolymph smears, we did not de-tect Hematodinium in any of the 36 investigated individuals (20 and 16 from Merja Zerga and Oualidia lagoons, respectively), probably due to methodological artifacts. The PCR-based method was revealed to be more accurate in diagnosing the Hematodinium parasite. It showed that 13 blue crabs were infected by the parasite at Merja Zerga Lagoon (prevalence 65%) and four individuals at Oualidia Lagoon (25%). Ge-netic analysis, based on the ITS1 rDNA gene from Hematodinium, confirmed the sequences as being those of Hematodinium perezi.

The leading cause of gastroenteritis in children under the age of five is rotavirus infection, accounting for 37% of diarrhoeal deaths in infants and young children globally. Oral rotavirus vaccines have been widely incorporated into national immunisation programs, but whilst these vaccines have excellent efficacy in high-income countries, they protect less than 50% of vaccinated individuals in low- and middle-income countries. In order to facilitate the development of improved vaccine strategies, a greater understanding of the immune response to existing vaccines is urgently needed. However, the use of mouse models to study immune responses to human rotavirus strains is currently limited as rotaviruses are highly species-specific and replication of human rotaviruses is minimal in mice. To enable characterisation of immune responses to human rotavirus in mice, we have generated chimeric viruses that combat the issue of rotavirus host range restriction. Using reverse genetics, the rotavirus outer capsid proteins (VP4 and VP7) from either human or murine rotavirus strains were encoded in a murine rotavirus backbone. Neonatal mice were infected with chimeric viruses and monitored daily for development of diarrhoea. Stool samples were collected to quantify viral shedding, and antibody responses were comprehensively evaluated. We demonstrated that chimeric rotaviruses were able to efficiently replicate in mice. Moreover, the chimeric rotavirus containing human rotavirus outer capsid proteins elicited a robust antibody response to human rotavirus antigens, whilst the control chimeric murine rotavirus did not. This chimeric human rotavirus therefore provides a new strategy for studying human rotavirus-specific immunity, and could be used to investigate factors causing variability in rotavirus vaccine efficacy. This small animal platform therefore has the potential to test the efficacy of new vaccines and antibody-based therapeutics.

One aspect of reproducibility in preclinical research that is frequently overlooked is the physical condition in which physiological, pharmacological, or behavioural recordings are conducted. In this study, the physical conditions of mice were altered through the attachments of wireless electrophysiological recording devices (Neural Activity Tracker-1, NAT-1). NAT-1 devices are miniaturised multichannel devices with on-board memory for direct high-resolution recording of brain activity for >48 hrs. Such devices may limit the mobility of animals and affect their behavioural performance due to the added weight (total weight of approximately 3.4 g). Mice were additionally treated with saline (control), N-methyl-D-aspartate (NMDA) receptor antagonist MK801 (0.85 mg/kg), or the muscarinic acetylcholine receptor blocker scopolamine (0.65 mg/kg) to allow exploration of the effect of NAT-1 attachments in pharmacologically treated mice. We found only minimal differences in behavioural outcomes with NAT-1 attachments in standard parameters of locomotor activity widely reported for the open field test between drug-treatments. Hypoactivity was globally observed as a consistent outcome in MK801-treated subjects and hyperactivity in scopolamine groups regardless of NAT-1 attachments. These data collectively confirm the reproducibility for combined behavioural, pharmacological and physiological endpoints even in the presence of lightweight wireless data loggers. The NAT-1 therefore constitutes a pertinent tool for investigating brain activity in e.g. drug discovery, models of neuropsychiatric and/or neurodegenerative diseases with minimal effects on pharmacological and behavioural outcomes.

Larus michahellis increased its population throughout the 20th century in its worldwide distribution area. The increase in the Salinas de San Pedro del Pinatar has produced changes in the habitats due to the contribution of guano, predation on birds, incidents with workers, and the production of salt. The objective is to analyze the impacts of L. michahellis on the landscape, habitats, waterfowl, salt production, and workers, as well as to evaluate the effectiveness of control activities. Censuses of wintering L. michahellis have been carried out between 1990-2021, of nesting aquatic birds between 1994-2021, and nests and eggs of L. michahellis have been eliminated between 2000-2021. The result has been a decrease in pairs of L. michahellis, recovery of waterfowl populations, colonization of others, absence of incidents with workers, and reduction of damage to salt production. However, to reach a definitive solution, measures should be adopted to prevent L. michahellis from accessing the main sources of human food: urban solid waste dumps, aquaculture farms, and fish discards.

Food safety in dairy shops has gained increasing attention. Consequently, this study aims to evaluate dairy handlers' knowledge of food safety practices, assess compliance with food safety codes regarding facility maintenance and personal hygiene, and understand retail dairy shops' capacity to implement food safety standards. This research involved surveys and interviews with 110 dairy retail workers to gauge their grasp of food safety principles, their recognition of its importance, and the obstacles they encounter in implementing proper food safety measures. Among the participants, 93% were males under 35 years old, with experience ranging from 1 to 8 years. The study revealed that while over 83% of participants were familiar with standard procedures ensuring dairy product safety, only 37% understood “HACCP” in relation to food safety. Additionally, 42% believed that freezing food at -18°C eliminates food bacteria, and 56% thought food contamination could be identified by taste, indicating misconceptions among respondents. Results showed that 90% of survey participants had a strong awareness of food safety, with 98% emphasizing the importance of regular inspection of production areas for cleanliness to ensure a safe dairy production environment. However, less than 45% had received formal training on dairy-specific food safety practices, and only 53.6% had a documented system for correctly labeling and providing production dates for dairy products. These findings have significant implications for public health and food safety policies in Jordan. Furthermore, the study provides valuable insights to enhance food safety practices among dairy retail vendors.

Maize is the staple cereal in Malawi, with a daily per capita consumption of 383g (dry matter basis), primarily consumed as dehulled maize flour used to cook nsima, a thick porridge. However, the extent of mass and nutrient loss during dehulling remains unclear in this food-insecure country, where the household maize harvest typically lasts only 6–7 months. In the current study, a milling experiment to determine yield and micronutrient losses was conducted. Milling batches (30 kg) of four maize grain varieties were dehulled at three abrasive disk dehullers under controlled conditions. Mass losses ranged from 18.8% to 42.7%, with a mean of 28.2±5.7%. Maize variety and dehuller significantly affected mass loss (p<0.05). Initial protein, iron, and zinc concentrations were 8.8 ±1.0 g/100g, 20.5±2.0 µg/g, and 18.2 ±2.6 µg/g, respectively. Post-dehulling nutrient true retention varied for protein (49.7% to 75.6%, mean=64.7±7.0%), iron (18.7% to 71.6%, mean=37.6±12.0 %), and zinc (11.0% to 46.2%, mean=27.9±8.7 %). Maize variety significantly influenced mass and protein loss (p < 0.05), while dehuller influenced mass, iron, and zinc losses. However, no significant difference (p > 0.05) was found in the interaction between dehullers and variety on mass and nutrient losses, respectively. Given Malawi's precarious food insecurity situation, transitioning from dehulled maize flour nsima to whole maize flour or less refined nsima, is imperative. Our study findings can have food and nutritional savings for other southern Africa countries where the dehulling practice is rampant.

The pathogenicity of grapevine geminivirus A (GGVA), a recently identified DNA virus, to grapevine plants remains largely unclear. Here, we report a new GGVA isolate (named GGVAQN) obtained from grapevine ‘Queen Nina’ plants with severe disease symptoms; the infectious clone of GGVAQN (pXT-GGVAQN) was also constructed. Infection assays indicated that Nicotiana benthamiana plants inoculated with GGVAQN display upward leaf curling and chlorotic mottling symptoms. Direct injection of Agrobacterium tumefaciens cells carrying pXT-GGVAQN into roots of in vitro-grown ‘Red Globe’ grape plantlets by syringe led to systemic infection with GGVAQN, and the plants exhibited chlorotic mottling symptoms on their upper leaves, and downward curling, interveinal yellowing, and leaf-margin necrosis symptoms on their lower leaves. Our results provide insights into the pathogenicity of GGVA, and a simple and efficient inoculation method to deliver infectious viral clones to woody perennial plants.

Vaginitis is a widespread issue for women worldwide, yet current diagnostic tools are lacking. Bacterial vaginosis (BV) is the most prevalent type of vaginitis, found in 10-50% of reproductive aged women. Current diagnostic methods for BV rely on clinical criteria, microscopy, or detection of a few microbes by qPCR. However, many vaginal infections lack a single etiological agent and are characterized by changes in the vaginal microbiome community structure (e.g. BV is defined as a loss of protective lactobacilli resulting in an overgrowth of anaerobic bacteria). Shotgun metagenomic sequencing provides a comprehensive view of all the organisms present in the vaginal microbiome (VMB) allowing for a better understanding of all potential etiologies. Here, we describe a robust VMB metagenomics sequencing test with a sensitivity of 88.5%, specificity of 96.2%, and a positive predictive value of 95.8% certified by Clinical Laboratory Improvement Amendments (CLIA), the College of American Pathologist (CAP) and the Clinical Laboratory Evaluation Program (CLEP). We sequenced over 7,000 human vaginal samples with this pipeline and described general findings and comparison to US census data.

Salmonella sp. is a globally prevalent organism responsible for causing salmonellosis, a foodborne illness. Salmonella Typhimurium represents a type of Salmonella sp. not associated with typhoid fever but capable of causing stomach and intestinal inflammation or severe infection. In the present study, 150 uncharacterized proteins of S. Typhimurium were randomly selected from UniProtKB and analyzed using TMHMM, PROSITE, STRING, DEG, and BLASTp. Results indicated that 32 uncharacterized proteins (21%) were predicted to be transmembrane proteins involved in various biological pathways. Among them, 30 transmembrane proteins were predicted to be essential and non-host homologous. This study's findings suggest their potential as drug targets against salmonellosis.

Methylmercury (MeHg) intoxication is a global health concern. Although MeHg neurotoxicity is well-recognized, less is known about MeHg's effects on metabolism. In this study, we evaluated MeHg intoxication (20mg/L in drinking water for 20 days) effects on liver and epididymal white fat (EWF) in young ApoE knockout (ko) and wild-type mice. The former is well-known to show spontaneous dyslipidemia. Hg levels in hair, liver, and EWF were measured to assess the degree of MeHg exposure. We also evaluated body weight gain, plasma triglycerides, total cholesterol levels, and liver injury by assessing steatosis score, AST, ALT, SOD, and TBAR levels. To evaluate EWF, we analyzed mean wet weight and adipocyte diameter, plasma leptin levels and metabolomics. Hg levels were markedly higher among intoxicated mice. ApoE ko mice showed higher Hg in the hair but lower levels in the liver and EWF than wild-type controls. Among wild-type mice, MeHg compromised weight gain and increased liver TBAR levels compared to non-challenged controls. Among non-intoxicated mice, ApoE deficiency significantly increased triglyceride, total cholesterol, and liver transaminases with reduced EWF wet weight, hepatic SOD, and plasma leptin levels. MeHg accumulation together with ApoE deficiency elevated total cholesterol, triglycerides, hepatic transaminases, and TBARS. We found distinct EWF metabolite activity in different scenarios of ApoE deficiency and MeHg intoxication, highlighting increased cardiovascular risk especially when both challenges occur. Further studies are required to elucidate the underlying mechanisms involved in these effects and the target nutritional interventions in most need to ameliorate them.

Viral tropism is most commonly linked to receptor use, but host cell protease use can be a notable factor in susceptibility to infection. Here we review the use of host cell proteases by human viruses, focusing on those with primarily respiratory tropism, particularly SARS-CoV-2. We first describe the various classes of proteases present in the respiratory tract, as well as elsewhere in the body, and incorporate the targeting of these proteases as therapeutic drugs for use in humans. Host cell proteases are also linked to the systemic spread of viruses and play important roles outside of the respiratory tract; therefore, we address how proteases affect viruses across the spectrum of infections that can occur in humans, intending to understand the extrapulmonary spread of SARS-CoV-2.

Solar pasteurization, as a means of treating milk in remote rural areas without electrical power, is based on using solar energy to thermally inactivate pathogenic microorganisms at temperatures below the boiling point to maintain or improve milk quality. A solar milk pasteurizer of flat‐plate water‐heating glass acting as the solar collector, connected to a stainless-steel cylindrical milk vat, was constructed and evaluated in Navrongo, in the tropical savanna zone of Ghana, West Africa. The novel approach taken in this project is to integrate the solar collection and heat exchanger into a single unit using materials and fabrication techniques readily available in the developing world. The vat comprises a 1.5 mm thick stainless steel cylindrical tank, a 2.2 cm wide hot water jacket, and an outer layer of 5.0 mm thick aluminium foil insulation. Hot water produced by the collector was used for pasteurizing milk. The optimum quantity of milk that this device could pasteurize under the study conditions was 8 L. The device could pasteurize raw milk to a maximum temperature of 74 °C at 14:00 h GMT. The ambient temperature during the pasteurization ranged from 30 °C to 43 °C. The microbial analysis before and after the pasteurization was done, and the result shows that the total bacteria count before pasteurization was 6.6x10⁶ log CFU/mL per unit volume, and the total bacteria count after pasteurization was 1.0x10² log CFU/mL. By acceptable standards, the total bacteria count after pasteurization is within a safe range for consumption, and coliform counts were negative. The solar milk pasteurization system is cost-effective. Hence, it is appropriate for milk producers in arid pastoral areas without electricity to adopt the solar pasteurizer as an alternative to firewood as a fuel source for milk pasteurization. This approach can potentially create a cottage industry that may also play a crucial role as a water treatment technology that will improve the health of rural populations.

Pyrolyzed organic matter – commonly referred to as biochar – generally has positive effects on plant growth and can enhance early seedling development. Biochar-based seed coatings may thus be beneficial, specifically under adverse soil conditions such as high soil salinity. We evaluated germination and early plant development in radish (Raphinus sativa) seeds coated with conifer-feedstock slow-pyrolysis biochar; following the precedent of prior studies, polyvinyl acetate (PVAc) was used as the binding agent. Biochar-based seed coatings reduced germination rates and radicle extension in Petri dish trials; however, leaching of coated seeds largely eliminated this effect. PVAc applied in solution inhibited seed germination to a similar extent, suggesting that toxicity of PVAc or chemical products derived from it is the main mechanism for germination inhibition; a meta-analysis of published literature also indicates negative effects of biochar-based seed coatings using PVAc. In greenhouse trials the same biochar seed coatings improved aspects of plant growth and physiological status relative to controls, specifically enhancing root development. We conclude that biochar-based seed coatings have promise in promoting early seedling growth, and in combating salinity stress in agronomic and restoration applications. However, our findings contraindicate PVAc use as a binding agent. Further research is needed to test non-phytotoxic, readily biodegradable binding agents and to optimize biochars and seed coating processes for specific applications in agronomy and ecological restoration.

In order to study the effects of soybean isoflavones on the growth performance and lipid metabolism of juvenile Chinese mitten crab, six experimental diets were formulated by gradient supplementation 0%, 0.004% and 0.008% soybean isoflavones at different dietary lipid levels (10% and 15%), which were named to NF-0 group (10% fat and 0% SIF), NF-0.004 group (10% fat and 0.004% SIF), NF-0.008 group (10% fat and 0.008% SIF), HF-0 group (15% fat and 0% SIF), HF-0.004 group (15% fat and 0.004% SIF) and HF-0.008 group (15% fat and 0.008% SIF). All crabs with an initial weight of 0.4 ± 0.03 g were fed for 8 weeks. The results showed that diets supplementation with 0.004% or 0.008% SIF significantly increased the weight gain and specific growth rate of crabs. Diets supplementation with 0.004% or 0.008% SIF significantly reduced the content of non-esterified free fatty acids and triglycerides in the hepatopancreas of crabs at 10% dietary lipid level. Dietary SIF significantly decreased the relative mRNA expressions of elongase of very long-chain fatty acids 6 (elovl6), triglyceride lipase (tgl), sterol regulatory element binding protein 1 (srebp-1), carnitine palmitoyltransferase-1a (cpt-1a), fatty acid transporter protein 4 (fatp4), carnitine palmitoyltransferase-2 (cpt-2), Δ9 fatty acyl desaturase (Δ9 fad), carnitine palmitoyltransferase-1b (cpt-1b), fatty acid binding protein 10 (fabp10) and microsomal triglyceride transfer protein (mttp) in the hepatopancreas of crabs. At 15% dietary lipid level, 0.008% SIF significantly increased the relative mRNA expressions of fatty acid binding protein 3 (fabp3), carnitine acetyltransferase (caat), fatp4, fabp10, tgl, cpt-1a, cpt-1b and cpt-2 and significantly down regulated the relative mRNA expressions of Δ9 fad and srebp-1. In conclusion, SIF can improve the growth and utilization of high-fat diet by inhibiting genes related to lipid synthesis and promoting lipid decomposition in juvenile Chinese mitten crab.

Agroforestry is often seen as a sustainable land-use system for agricultural production providing ecosystem services. Intercropping with food crops leads to equal or higher productivity than monoculture and results in food production for industry and subsistence. Low rubber price and low labor productivity in smallholdings have led to a dramatic conversion of rubber plantations to more profitable crops. The literature analysis performed in this paper aimed at better understanding the ins and outs that could make rubber-based agroforestry more attractive for farmers. A library was set-up consisting of 415 scientific references. Of the 232 journal articles, 141 studies were carried out on rubber agroforestry. Since 2011, the number of studies per year has increased. Studies on rubber-based agroforestry systems are performed in most rubber producing countries, in particular in Indonesia, Thailand, China and Brazil. These studies focus more or less equally on perennials (forest species and fruit trees), annual intercrops and mixed plantations. Of the 47 annual crops associated with rubber in the literature, 20 studies dealt with rice, maize, banana and cassava. Agronomy is the main discipline in the literature followed by socio-economy and then ecology. Only 4 papers are devoted to plant physiology and breeding. The discussion section has attempted to analyze the evolution of rubber agroforestry research, progress in the selection of food crop varieties adapted to agroforestry systems, and to draw some recommendations for rubber-based agroforestry systems associated with food crops.

This retrospective begins with Galvani's experiments on frogs at the end of the 18th century and his discovery of ‘animal electricity’. It goes on to illustrate the numerous contributions in the fields of physical chemistry in the second half of the 19th century (Nernst’s equilibrium potential, based on the work of Wilhelm Ostwald, Max Planck's ion electrodiffusion, Einstein's studies of Brownian motion), which led Bernstein to propose his membrane theory in the early 1900s as an explanation of Galvani’s findings and cell excitability. These processes were fully elucidated by Hodgkin and Huxley in 1952, by detailing the ionic basis of resting and action potentials, but without addressing the question of where these ions passed. The emerging question of the existence of ion channels, widely debated over the next two decades, was finally accepted and, a decade later, many of them began to be cloned. This led to the possibility of modelling the activity of individual neurons in the brain and then of simple circuits. Taking advantage of the remarkable advances in computer science in the new millennium, together with a much deeper understanding of brain architecture, more ambitious scientific goals were dreamed of to understand the brain and how it works. The retrospective concludes by reviewing the main efforts in this direction, namely the construction of a digital brain, an in silico copy of the brain that would run on supercomputers and behave just like a real brain.

Background: Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delay leading to worse outcomes and decreased quality of life. Therefore, there is an urgent need for an approach to predict normal mucosa response in patients prior to treatment. Methods: We here describe an assay to detect irradiation response in patient healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated, and cultured for three days. Seven samples were irradiated with X-ray and three additional samples were irradiated with both X-ray and protons. Results: Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample, using standardized automated image analysis. Furthermore, increased levels of inflammation inducing factors - major drivers in mucositis development - could be detected after irradiation. Conclusion: This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

Escherichia coli is an indicator microorganism in One Health antibiotic resistance surveillance programmes. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole genome sequencing (WGS). Porcine E. coli isolates were proportionally more resistant phenotypically and harboured a richer diversity of antibiotic resistance genes, as compared to human E. coli isolates. Different pathovars, namely ExPEC (12.43%, 21/169), ETEC (4.14%; 7/169), EPEC (2.96%, 5/169), EAEC (2.96%, 5/169) and STEC (1.18%, 2/169) were detected at low frequencies. Sequence type complex (STc) 10 were the most prevalent (85.51%, 59/169) among human and porcine isolates. Six STcs (STc10, STc86, STc168, STc206, STc278 and STc469) were shared at the human-livestock interface according to multilocus sequence typing (MLST). Core genome MLST and hierarchical clustering (HC) showed that human and porcine isolates were overall genetically diverse, but some clustering at HC2 to HC200 were observed. In conclusion, even though the isolates shared a spatio-temporal relationship, there were still differences in the virulence potential, antibiotic resistance profiles, and cgMLST and HC according to the source of isolation.

Skeletal muscle contraction evokes numerous genetic and biochemical alterations that underpin the beneficial effects of exercise. The present study aimed to elucidate the mechanism and significance for contraction-evoked antioxidant adaptation in C2C12 myotubes using electrical pulse stimulation (EPS). As NQO1 and GSTA2 are the top antioxidants upregulated by Nrf2, dose-response and time-course experiments of EPS were performed to optimize the parameter at 10 volts for 4 days by evaluating their protein expression. Western blot analysis demonstrated that EPS-cells expressed significantly higher Nrf2 and a broad array of downstream antioxidant enzymes involved in multiple antioxidant systems. These effects were completely abolished by pretreatment with a ROS scavenger, N-acetylcysteine. MitoSOX-Red, CM-H2DCFDA, and EPR spectroscopy revealed a significantly higher ROS level in mitochondria and cytosol in EPS-cells compared to non-stimulated cells. Seahorse and Oroboros revealed that EPS significantly increased maximal mitochondrial oxygen consumption rate, along with upregulated protein expression of mitochondrial complexes I/V, mitofusin-1, and mitochondrial fission factor. A post-stimulation time-course experiment demonstrated that upregulated NQO1 and GSTA2 last at least 24 hours following the cessation of EPS, whereas elevated ROS declines immediately. These finding suggest an antioxidant preconditioning effect in the EPS-cells. A cell viability study using the CCK-8 assay suggested that EPS-cells displayed 11- and 36-fold higher survival rate compared to control-cells in response to 2 and 4 mM H₂O₂ treatment, respectively. In summary, we found that EPS upregulated a large group of antioxidant enzymes in C2C12 myotubes via a contraction-mitochondrial-ROS-Nrf2 pathway. This antioxidant adaptation protects cells against oxidative stress-associated cytotoxicity.

Amitriptyline is a tricyclic antidepressant commonly used for depressive disorders and pre-scribed off-label for several neurological conditions like neuropathic pain, migraine and anxiety. Amitriptyline potentiates the monoaminergic transmission by blocking the reuptake of norepi-nephrine and serotonin. However, antidepressants also act on additional targets that contribute to either therapeutic or adverse effects and may suggest new indications for their repurposing. Furthermore, since depression is often a co-morbidity in patients with chronic conditions (i.e. cancer, neurodegenerative diseases) the use of antidepressants interfering with pathways in-volved in cell homeostasis may affect the progression and outcome of these pathologies. Here we investigate the effects of amitriptyline on proliferation and autophagy in human SH-SY5Y neuroblastoma cells. Dose and time-dependent upregulation of the autophagy markers LC3II and autophagy receptor p62, with accumulation of LAMP1 positive compartments, were observed in SH-SY5Y cells exposed to amitriptyline. Alteration of autophagy was accompanied by reduced cell viability and decreased clonogenic capacity, without a significant induction of apoptosis. Decrease viability and clonogenic activity were still observed in autophagy deficient Atg5 -/- MEF and following pre-treatment of SH-SY5Y culture with the autophagy inhibitor chloroquine suggesting that the amitriptyline’s effects on cell proliferation were not caused by the modulation of autophagy. Our findings demonstrate that amitriptyline acts on pathways that are crucial for cell and tissue homeostasis and pose the basis for further studies on the potential application of these effects and the consequences during long-term antidepressant treatment.

Papain-like protease PLpro, a domain within a large polyfunctional protein nsp3, plays key roles in the life cycle of SARS-CoV-2, being responsible for the first events of cleavage of a polyprotein into individual proteins (nsp1-4) as well as for the suppression of cellular immunity. Here, we developed a new genetically encoded fluorescent sensor, named PLpro-ERNuc, for detection of PLpro activity in living cells using translocation-based readout. The sensor was designed as follows. A fragment of nsp3 protein was used to direct the sensor on the cytoplasmic surface of endoplasmic reticulum (ER) membrane, thus closely mimicking the natural target of PLpro. The fluorescent part included two bright fluorescent proteins - red mScarlet I and green mNeonGreen, separated by a linker with the PLpro cleavage site. Nuclear localization signal (NLS) was attached to ensure accumulation of mNeonGreen into the nucleus upon cleavage. We tested PLpro-ERNuc in the model of recombinant PLpro expressed in HeLa cells. The sensor demonstrated expected cytoplasmic reticular network in the red and green channels in the absence of protease, and efficient translocation of the green signal into nuclei in the PLpro-expressing cells (14-fold increase of the nucleus/cytoplasm ratio). Then, we used PLpro-ERNuc in the model of Huh7.5 cells infected with SARS-CoV-2 virus, where it showed robust ER-to-nucleus translocation of the green signal in the infected cells 24 h post infection. We believe that PLpro-ERNuc represents a useful tool for screening PLpro inhibitors as well as for monitoring virus spread in a culture.

Equine herpesvirus-1 (EHV-1) causes respiratory diseases, abortion, and encephalomyelitis in horses. EHV-1 immediate-early (IE) protein, essential for viral replication, is transactivated by the binding of a multiprotein complex including the open reading frame 12 (ORF12) and some host factors to the IE promoter region. Promoter-associated non-coding RNAs (pancRNAs), which are transcribed from bidirectional promoters, regulate the transcription of neighboring genes in mammals and pathogens. In this study, we identified a novel pancRNA transcribed from across the areas of the 5’-untranslated region and promoter of EHV-1 IE and named it IE pancRNA. IE pancRNA and mRNA were simultaneously expressed in EHV-1-infected RN33B-A68B2M cells. This pancRNA was also transcribed in RK13 and E. Derm cells, which are highly susceptible to EHV-1 infection. Furthermore, IE pancRNA upregulated IE gene expression in the presence of ORF12, and stable expression of IE pancRNA increased the number of EHV-1-infected RN33B-A68B2M cells. These results suggest that IE pancRNAs facilitate EHV-1 proliferation by promoting IE gene expression.

The rapid and accurate detection of viruses and the discovery of single nucleotide polymorphisms (SNPs) are crucial for disease management and understanding viral evolution. In this study, a pipeline for virus detection, validation, and SNP discovery from next-generation sequencing (NGS) data is presented. By integrating state-of-the-art bioinformatics tools with artificial intelligence, the pipeline processes raw sequencing data to identify viral sequences with high accuracy and sensitivity. Before aligning the reads to the reference genomes, quality control measures and adapter trimming are performed to ensure the integrity of the data. Unmapped reads are subjected to de novo assembly to reveal novel viral sequences and genetic elements. The effectiveness of the pipeline is demonstrated by the identification of virus sequences, illustrating its potential for the detection of known and emerging pathogens. SNP discovery is performed using a custom Python script that compares the entire population of sequenced viral reads to a reference genome. This approach provides a comprehensive overview of viral genetic diversity and identifies dominant variants and a spectrum of genetic variations. The robustness of the pipeline is confirmed by the recovery of complete viral sequences, which improves our understanding of viral genomics. This study highlights the synergy between traditional bioinformatics techniques and modern approaches, providing a robust tool for analyzing viral genomes and contributing to the broader field of viral genomics.

This study examines the synergistic interaction between the immunomodulatory functions of lactic acid bacteria postbiotics and the anti-inflammatory properties of Smilax China L. extract through a combined fermentation process. Using atopic dermatitis (AD) as a model, characterized by an immune imbalance that leads to skin inflammation, we developed a fermented product, MB-2006, and compared its effects to those of heat-killed probiotics, Lactobacillus acidophilus (LAC) and Lac-tobacillus rhamnosus (LRH). Our experiments focused on elucidating the mechanism of action of MB-2006 in AD-like HaCaT keratinocyte cells, particularly its impact on the NF-kB pathway, a pivotal regulator of inflammation. MB-2006 proved more effective in reducing inflammation markers such as IL-4 and thymic stromal lymphopoietin (TSLP), and in inhibiting NF-kB activation, compared to LAC and LRH. Significantly, MB-2006 also reduced the expression of thymus- and activation-regulated chemokine (TARC), highlighting a synergistic effect that enhances its thera-peutic potential. These results suggest that the combined fermentation of Smilax china L. extract with lactic acid bacteria enhanced both the anti-inflammatory and immunomodulatory effects, pre-senting a promising integrative approach to treating conditions like AD. Further studies are needed to validate these results in clinical settings and fully explore the potential of this synergistic fer-mentation process.

Viral contamination in the aquaculture industry is a significant challenge that requires further research. Emerging evidence suggests that long noncoding RNAs (lncRNAs) play a role in regulating various biological processes, including immunity. However, most studies have focused on model organisms, and little is known about non-coding RNAs in the immune response to viral hemorrhagic septicemia (VHS) in rainbow trout. In this study, we investigated the listing of non-coding RNAs (ncRNAs) in rainbow trout challenged with VHS virus. We explored their potential role in defense-like responses based on transcriptomic analysis of the virus-treated and control groups. As a result of this research, 4207 lncRNAs were identified, of which 182 lncRNAs were differentially expressed between treated and untreated samples. Among 7753 lncRNA transcripts, 1920 were novel intergenic (class code “u”), and 3748 transcripts were potentially novel isoform of lncRNAs. Gene ontology analysis revealed biological pathways associated with the stress response and immune signaling. Pairs of genes such as TP63-MSTRG.62, IL10-MSTRG.9783, IL10-MSTRG.9784, TK1-MSTRG.22826, and MSTRG.17881-GLI1 showed cis interactions, while DOCK10-MSTRG.30015, MSTRG.36357-LOC101268921, and MSTRG.34190-ENPP2 showed trans interactions. In this study, the role of lncRNAs in regulating the expression of the target genes was clearly identified. This finding is consistent with the regulatory processes of immune system responses mediated by cytokines, as well as the regulation of oxygen levels in response to viral infection. The information presented here highlights the various regulatory mechanisms of lncRNAs in the expression of immune system genes in fish treated with VHS virus.

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

Introduction: Type 1 diabetes mellitus is a chronic disease of autoimmune etiology that is highly prevalent in childhood. In the last decade, the possibility of using the Bacillus Calmette-Guérin vaccine for the treatment of this disease has been studied thanks to its immunomodulatory action . Objectives: The objective of this work is to carry out a systematic review of the available scientific evidence on the relationship between the tuberculosis vaccine and the treatment of diabetes in childhood. Secondarily, the aim is to study the incidence of Type 1 Diabetes Mellitus in a cohort of children from the Basque Country according to whether or not they have received the vaccine. Methods: An exhaustive bibliographic search has been carried out on the evidence available to date. For the epidemiological study in Euskadi, a comparison of accumulated incidences between vaccinated and unvaccinated population groups was made. Results: According to the literature analyzed, There is more and more evidence about the possible use of the tuberculosis vaccine in Type 1 Diabetes Mellitus. The results of our study were not conclusive, but we believe that it is necessary to continue with long-term studies to eliminate biases. Conclusions: The Bacillus Calmette-Guérin vaccine could be used for the treatment of autoimmune, allergic, infectious or oncological processes, although more studies are still necessary in this regard.

This manuscript offers a concise overview of paper microfluidics, emphasizing its sustainable sensing applications in healthcare, environmental monitoring, and food safety. Researchers have developed innovative sensing platforms for detecting pathogens, pollutants, and contaminants by leveraging the paper’s unique properties, such as biodegradability and affordability. These portable, low-cost sensors facilitate rapid diagnostics and on-site analysis, making them invaluable tools for resource-limited settings. The review discusses fabrication techniques, principles, and applications of paper microfluidics, showcasing its potential to address pressing challenges and enhance human health and environmental sustainability.

Alternative splicing is an essential regulatory mechanism for gene expression in mammalian cells contributing to protein, cellular, and species diversity. Isoform switching, the process where cells alter the expression of various splice forms (isoforms) of a gene, plays a critical role in cellular function and adaptation. Our study provides a comprehensive analysis of splice forms prevailing across ten of the most studied human cell lines using public RNAseq data. We analyzed the occurrence of splice forms and found substantial justification for revising the canonical sequences for 56 genes, suggesting that these alternative splice forms should be recognized as canonical. Additionally, distinct profiles of splice form prevalence across these cell lines offer new insights into their specific biological roles. Our findings reinforce and expand upon previous insights into the link between isoform expression and oncological processes. Notably, we identified three genes exhibiting statistically significant changes between cancerous and normal tissues. Moreover, a comparative analysis of prevailing isoforms across diverse cell lines with prior research unveiled 140 common splice variants associated with cancer, highlighting their importance for prognostication and understanding oncogenesis. We revealed unique patterns and variations in isoform switching of these lines that provide new insights into the importance of selecting specific ones for research.

The study of ecosystems, both natural and artificial, has historically been mediated by population dynamics theories. In this framework, quantifying population numbers and related variables (associated with metabolism or biological-environmental interactions) plays a central role in measuring and predicting system-level properties. As we move towards advanced technological engineering of cells and organisms, the possibility of bioengineering ecosystems (from the gut microbiome to wildlands) opens several questions that will require quantitative models to find answers. Here, we present a comprehensive survey of quantitative modelling approaches for managing three kinds of synthetic ecosystems, sharing the presence of engineered strains. These include test tube examples of ecosystems hosting a relatively low number of interacting species, mesoscale closed ecosystems (or ecospheres), and macro-scale, engineered ecosystems. The potential outcomes of synthetic ecosystem designs and their limits will be relevant to different disciplines, including biomedical engineering, astrobiology, space exploration and fighting climate change impacts on endangered ecosystems. We propose a space of possible ecosystems that captures this broad range of scenarios and a tentative road map for open problems and further exploration.

Age-related diseases place an intense and growing stress on healthcare systems. Numerous theories of ageing exist. Yet prediction, prevention and treatment limitations of age-related disease persist because we lack a complete aetiological understanding of their origins. Here we propose a new theory that aims to provide a blueprint-type understanding of ageing and disease aetiology, working across multiple scientific disciplines. Supported by specific examples, we demonstrate that the primary driver of much of age-related diseases is the futile triggering of specific molecular pathways in a pathological manner, which we term patho-pathways. Patho-pathways induce pathological cell, tissue and system changes in the form of hyperactivity (undesirable increased and new biological activities that are typical of age related disease). As part of patho-pathways, all wild-type (normal) genes have the potential to contribute to age-related diseases (though specific risk varies and can be formularised). In a domino-style effect, one patho-pathway typically triggers others, resulting in complex, but traceable, cascades. Utility, in terms of changing clinical and scientific practice, is derived from mapping these cascades to create Blueprint Maps that allow identification of biomarkers and therapeutic targets far upstream in the causal chain of events. Finally, our theory provides testable hypotheses concerning predictions of links between otherwise seemingly disparate diseases as well as new interventions into ageing.

(1) Background: Since microplastics in the aquatic environment are difficult to prevent and can cause adverse physiological and biochemical reactions to various organisms, we aimed to analyze the effectiveness of an eco-friendly removal method using aquatic plants with high ornamental value and excellent water purification ability. (2) Methods: Iris pseudacorus and Lythrum anceps were planted in tap water contaminated with microplastics to analyze the removal rate and root adsorption of microplastics. (3) Results: The amount of microplastics in the planting boxes of Iris pseudacorus and Lythrum anceps was significantly reduced, and the adsorption of microplastics on the roots was confirmed. (4) Conclusions: It was found that the removal of microplastics in water by aquatic plants is effective and that microplastic pollution does not significantly affect plant growth. However, the removal of microplastics by adsorption on plant roots may be affected by various environmental factors, so it is necessary to consider various limitations.

Carotenoids are common and diverse organic compounds with various functional roles in ani-mals. Except for certain aphids, mites, and gall midges, all animals acquire necessary carotenoids only through their diet. The House fly (Musca domestica) is a cosmopolitan pest insect that populates diverse habitats. Its larvae feed on organic substrates that may vary in carotenoid composition according to their specific content. We hypothesized that the carotenoid composition in the adult House fly’s body would reflect its composition in the larval feed. We reared house fly larvae on substrates that differed in carotenoid composition and characterized the carotenoid composition of the emerging adults. Our results indicate that the carotenoid composition of adult House flies is related to the carotenoid composition in its natal substrate, but does not directly reflect it. We suggest that these findings may be developed to identify sources of House fly in-festations. We also recommend that care should be taken when considering the rearing substrates of House fly larvae used for animal feed.

Chronic exposure to the nephrotoxic metal pollutant, cadmium (Cd), has been associated with hypertension, but the mechanism by which it raises blood pressure is not understood. We hypothesize that exposure to Cd reduces the glomerular filtration rate (GFR), which in turn, causes a rise in blood pressure. Data were collected from 447 Thai subjects with a mean age of 51.1 years, of which 48.8% had hypertension, 15.4% had diabetes and 6.9% had an estimated GFR (eGFR) below 60 mL/min/1.73 m2 (low eGFR). The mean blood and urinary Cd concentrations were 2.75 and 4.23 µg/L, respectively. The prevalence odds ratio (POR) for hypertension rose twofold in those with blood Cd levels of 0.61-1.69 µg/L or urinary Cd excretion levels ≥ 0.98 µg/g creatinine. In the hypertensive group, the eGFR was inversely associated with age (β =−0.517), the Cd excretion rate (β = −0.177), and diabetes (β = −0.175). Mean eGFR in the normotensive group was 7.5 mL/min/1.73 m2 higher than the hypertensive with a similar Cd body burden. Mean systolic blood pressure (SBP) in those with low or medium eGFR plus heavy Cd body burden was 9.5 mmHg higher than those with the same Cd body burden and a normal eGFR. By mediation analysis, a 22.7% increase in SBP and a 5% increase in diastolic blood pressure (DBP) were attributable to the effect of Cd on GFR. Thus, a rise of blood pressure appears to be a consequence of GFR loss due to Cd-induced kidney damage. This finding is consistent with a well-known role of the kidney in long-term blood pressure regulation.

Reviewed are recent efforts leading to chemo-enzymatic syntheses of strongly fluorescent ribosides of nucleobase analogs, potentially applicable in analytical biochemistry and cell biology. Described are syntheses and properties of fluorescent purine, 8-azapurine and etheno-purine ribosides, obtained using various types of the purine nucleoside phosphorylase (PNP) as catalysts of ribosylation, and -ribose-1-phosphate (r1P) as a second substrate. In several instances, the ribosylation sites were different than the canonical purine N9. Some of the obtained ribosides show fluorescence yields close to 100%. Their main applications are assays of PNP, nucleoside hydrolases, and other enzyme activities both in vitro and, possibly, within the living cells, using fluorescence microscopy.

Energy metabolism regulates the proliferation of stem cells by regulating energy production and the production of substrates through biosynthetic pathways. It is an important target for cell regulation and stem cell applications, and is crucial for determining the pluripotency and cell fate of stem cells. In this context, this article focuses on reviewing the latest research progress on the association between glucose metabolism, amino acid metabolism, fatty acid metabolism, and mitophagy with stem cell function, elucidating how key energy metabolism pathways affect stem cell function by regulating signal transduction and epigenetic modifications. In this review, we discuss the key factors affecting energy metabolism and their association with stem cell function. The integration of energy metabolism and stem cell fate regulation will open up a new path for future regenerative medicine practices.

Nutrition therapy is the best solution to human chronic diseases, especially beer and barley which play an important role in human health and civilization. We demonstrated the actional mechanism of functional ingredients in beer and barley to combat chronic diseases, based on PubMed, google, CNKI, and ISI Web of Science databases from 1997 to 2024. Beer is rich in functional ingredients that is a complex of barley malt and hops; the health effect of beer against 26 chronic diseases is highly similar to that of barley, due to molecular mechanism of polyphenols (phenolic acids, flavonoids), melatonin, minerals, bitter acids, vitamins, and peptides. The ancient German Beer Purity Law provides much scientific basis today, especially indirectly supporting the human one cell disease theory. Low purine beer can be produced by enzymatic and biological degradation and adsorption of purines as well as dandelion addition. Functional beer with low purine and high active ingredients made from Beer Purity and barley malt as well as functional foods addition will be the key and important development direction, such as ginger beer and ginseng beer, especially coix-lily beer at the ancestors ca. 9000 years ago. This review paper not only reveals the actional mechanism of beer overcoming human chronic diseases, but also provides scientific basis for the development of functional beer for the prevention and treatment of human chronic diseases.

The yak (Poephagus grunniens) has evolved unique adaptations to survive the harsh environment of the Tibetan Plateau, while their gut microorganisms play a crucial role in maintaining the health of the animal. Gut microbes spread through the animal population not only by horizontal transmission but also vertically, which enhances microbial stability and inheritance between generations of the population. Homogenization of gut microbes in different animal species occurs in the same habitat enhancing interspecies coexistence. Using the yak as a model animal, this paper reviews the adaptive strategies under extreme environments and how the gut microbes of the yak circulate throughout the Tibetan Plateau system, which not only affects other plateau animals such as plateau pikas, but can also have a profound impact on the health of people. By examining the relationships between yaks and their gut microbes, this review provides new perspectives in understanding the adaptations of plateau animals and the stability of the ecosystem.

Passion fruit is a valued tropical fruit crop that faces environment-related growth strains. TCP genes are important for both growth modulation and stress prevention in plants. Herein, we systematically analyzed the TCP gene family in passion fruit, recognizing 30 members. Genes exhibiting closer phylogenetic relationships exhibited similar protein and gene structures. Gene members of the TCP family showed developmental stage or tissue-specific expression profiles during the passion fruit life cycle. Transcriptome data also demonstrated that many PeTCPs showed induced expression in response to hormonal treatments and cold, heat, and salt stress. Based on transcriptomics data, eight candidate genes were chosen for preferential gene expression confirmation under cold stress conditions. Additionally, four TCP genes exhibited in silico binding with cold stress-related miRNA319s. This study will aid in the establishment of novel germplasm, as well as the further investigation of the roles of PeTCPs and their cold stress resistance characteristics.

Phylogenomics has enriched our understanding that the Tree of Life can have network-like or reticulate structures among some taxa and genes. Non-vertical modes of evolution—such as hybridization/introgression and horizontal gene transfer—deviate from a strictly bifurcating tree model, causing non-treelike patterns. Here, we present a brief overview of a phylogenomic workflow for inferring organismal histories and compare methods for detecting reticulate evolution. We discuss how the timing of coalescent events can help disentangle introgression from incomplete lineage sorting and how horizontal gene transfer events can help determine the relative timing of speciation events. In doing so, we identify pitfalls of certain methods and discuss how to extend their utility across the Tree of Life. Workflows, methods, and future directions discussed herein underscore the need to embrace reticulate evolutionary patterns for understanding the timing and rates of evolutionary events, providing a clearer understanding of life’s history.

Anxiety is a multifactorial pathology associated with oxidative stress and changes in different neurotransmitters in the central nervous system (CNS). Sarcomphalus joazeiro (Rhamnaceae) has a predicted effect on the CNS, being considered an alternative for pre-clinical investigations of anxiolytic drugs. The objective of this study is to evaluate the chemical composition, analyze the antioxidant capacity and the anxiolytic effect of the ethanolic extract of S. joazeiro leaves (EEFSJ) in zebrafish. The chemical profile was analyzed by liquid chromatography coupled to mass spectrometry (UPLC-PDA-ESI-QDA). Antioxidant action by DPPH• elimination and ABTS•⁺ capture assays. The 96 h acute toxicity and open field and light and dark tests, for sedative and anxiolytic evaluation, respectively, were applied in vivo, using zebrafish. It was possible to identify 11 compounds from the flavonoid and saponin class. EEFSJ exhibited a mean inhibitory concentration (IC50) of 185.2 ± 2.2 µg/mL and 74.17 ± 1.5 µg/mL against the DPPH• and ABTS•⁺ radicals, respectively. In vivo, EEFSJ demonstrated reduced locomotor activity and an anxiolytic effect similar to diazepam via GABAergic systems, without presenting toxicity within 96 h. These results suggest the safety of using EEFSJ for the development of clinical trials for the production of new anxiolytic drugs.

Food waste is a common issue arising from grinding of food by experimental animals, leading to excessive food scraps falling into cages. In the wild, animals grind food by gnawing vegetation and seeds, potentially damaging the ecological environment. However, limited ecology studies have focused on food grinding behavior since the last century, with even fewer on rodent food grinding, particularly recently. Although food grinding function is partially understood, biological purposes remain under-investigated and driving factors unclear. This review aims to explain potential causes of animal food grinding, identify influencing factors, and discuss contexts and limitations. Specifically, we emphasize recent progress on gut microbiota significance for food grinding. Moreover, we show abnormal food grinding is determined by degree of excess normal behavior, emphasizing food grinding is not meaningless. Findings from this review promote comprehensive research on the myriad factors, multifaceted roles, and intricate evolution underlying food grinding behavior, benefiting laboratory animal husbandry and ecological environment protection, and identifying potential physiological benefits yet undiscovered.

Fine dust causes various disorders, including cardiovascular, neurological, renal, reproductive, motor, systemic, respiratory, and cancerous diseases. Therefore, it is necessary to study functional materials to prevent these problems. In this study we used various methods, including quantitative PCR, flow cytometry, ELISA, and Alizarin O staining, to study the beneficial effects of erucic acid against fine dust. Erucic acid and erucic acid-induced exosomes (EIE) strongly suppress the attenuation of osteocytic differentiation and inflammation induced by fine dust. Erucic acid effectively suppresses inflammation in fibroblasts exposed to fine dust. Notably, despite exposure to fine dust, EIE promoted osteocytic differentiation in adipose-derived stem cells (ASC) and osteogenesis in macrophages, in addition to phagocytosis. Dramatic upregulation of RunX2 and BMP7 by EIE indicates that it is a strong activator of osteocytic differentiation in ASC and protects them from the effects of fine dust. Moreover, EIE induces immune activity and acts as an osteogenic trigger for macrophages. Therefore, this study suggests the potential use of erucic acid and erucic acid-induced exosomes (EIE) as biomaterials to prevent environment-borne diseases.

Blood cancers, including leukemia, lymphoma, and myeloma, pose significant diagnostic challenges due to their diverse and complex nature. Detecting these cancers early and accurately is crucial for timely intervention and improved patient outcomes. This review explores current and emerging detection methods for human blood cancers, focusing on their principles, advantages, limitations, and potential clinical applications.

Extracellular vesicles (EVs) carry diverse cargo of DNA, RNA, proteins, and lipids. They are crucial mediators for regulating various functions through interactions with the host. Recent investigations suggest that EVs or their constituent proteins derived from probiotics could improve the effectiveness of probiotic strains in disease management compared to probiotic strains themselves. This enhanced effec-tiveness arises from their innate antimicrobial properties, which can specifically target pathogenic mol-ecules or cells, in addition to their significant ability to regulate immune responses. Significantly, previous studies have highlighted the inhibitory potential of Lactobacillus crispatus PMC201 against Mycobacterium tuberculosis. In this study, we focused on optimizing isolation conditions for studying extracellular vesicles and proteins from anti-TB potent strains. We provide analysis results based on food-grade media (FGM) optimization and isolation methods. Nanoparticle tracking analysis (NTA) was used to determine se-cretion patterns. Proteomic analysis was performed by liquid chromatography and tandem mass spec-trometry (LC-MS/MS). A total of 64 proteins were identified in the L. crispatus PMC201 strain, particularly enriched in s-layer and splX. Questions remain about their relevance to anti-TB. This anti-tuber strain has potential as a therapeutic agent, given its significant role in intercellular killing. Further studies are needed to investigate its mechanisms of action.

Recent studies releaved that the high production of reactive oxidative species due to exposure of fine or ultrafine particles are implicated in many chronical respiratory disorders. However, the poor standard of clinical data in sub-Saharan countries makes very difficult the assessment of knowledge of air pollution health impact in urban cities. Objective: the aim of this study was to evaluate distribution of respiratory disorders associated to exposure of air fine and ultrafine particles through changes of some oxidative stress biomarkers among motorbike drivers from two cities of Cameroon Methods: A cross-sectional survey using a standardized questionnaire was conducted in 2019 on 191 motorcycle drivers (MD) working in Douala and Dschang. Then, the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were measured by colorimetric methods. The data of participants after clustered in Excel Microsoft were analysed and statistically compared using Spss 2.0 software. Results: The motorbike drivers recruited to both cities were aged from 21 to 40, with mean age of 29.93 (± 0.82). The distribution of respiratory disorders as running nose, cold, dry cough, chest discomfort, and breathlessness, was significantly increased among MD in Douala. According to results of biological assays, SOD and MDA, were significantly more increased among MD recruited in Douala, compared to those of Dschang. The change of these oxidative stress markers was significantly correlated with mobilization of neutrophils and Monocytes showing initiation and evolution of subjacent inflammatory reactions, and seemed to be significantly influenced by place of habitation of MD. Conclusion: Through this study it is confirmed the evidence of initiation and evolution of oxidative stress with long-term exposure to air fine or ultrafine particles among active people in Urban cities. Further studies should be conducted with more analysis to provide evidence cellular damage and dysfunction related to chronically exposure to fine air PM among active people in metropolitan of sub-Saharan Africa context.

The in vitro cultivation of M. leprae has not been possible since it was described as causing leprosy, and the limitation of animal models for clinical aspects makes studies on leprosy and bacteria-human host interaction a challenge. Our aim was to standardize the ex vivo skin model (hOSEC) to maintenance and study of M. leprae as an alternative animal model. Bacillary suspensions were inoculated into human skin explants and sustained in DMEM medium until 60 days. Explants were evaluated by RT-PCR-16SrRNA, and cytokines gene expression. Viability and infectivity of bacilli recovered from explant (D28 and D60) were evaluated using the Shepard’s model. All explants were RT-PCR-16srRNA positive. Viability and infectivity of recovered bacilli from explants, analyzed after 5 months of inoculation in mice showed an average positivity of 31%, being the highest positivity in the D28 groups (80%). Furthermore, our work showed different pattern in cytokines gene expression (TGF-β, IL-10, IL-8 and TNF-α) in the presence of alive or dead bacilli. Although changes can be made for improve future experiments, our results have demonstrated that it is possible to use the hOSEC to maintain M. leprae for 60 days, interacting with the host system, an important step in the development of experimental models for studies on the biology of the bacillus, its interactions, and drug susceptibility.

Under different pathophysiological conditions endothelial cells lose endothelial phenotype and gain mesenchymal cell-like phenotype via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, endothelial cells lose the expression of endothelial cell-specific markers such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, and vascular-endothelial cadherin and gain the expression of mesenchymal cell markers such as α-smooth muscle actin, N-cadherin, vimentin, fibroblast specific protein-1 and collagens. EndMT is induced by numerous different pathways triggered and modulated by multiple different and often redundant mechanisms in a context-dependent manner depending on the pathophysiological status of the cell. EndMT plays an essential role in embryonic development, particularly in atrioventricular valve development, however, EndMT is also implicated in pathogenesis of several genetically determined and acquired diseases including malignant, cardiovascular, inflammatory, and fibrotic disorders. Among cardiovascular diseases aberrant EndMT is reported in atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis and cardiac fibrosis. Accordingly, understanding the mechanisms behind cause and/or effect of EndMT to eventually target EndMT appears to be a promising strategy to treat aberrant EndMT-associated diseases. However, this approach is limited by a lack of precise functional and molecular pathways, causes and/or effects, and lack of robust animal model and human data about EndMT in different diseases. Here, we review different mechanisms in EndMT and the role of EndMT in various cardiovascular diseases.

The mortality rate of women during the gestation period or after delivery is very high worldwide. ToRCH pathogens [Toxoplasma gondii (T.gondii), Rubella Virus (RV), Cytomegalovirus (CMV), and Herpes Simplex Virus (HSV)] are transmitted vertically and are associated with mortality and complications both in the mother and the fetus or children. Therefore, this study is designed to investigate the ToRCH pathogen-induced histopathological changes in placental tissues and associated post-obstetric complications in Pakistani women. Women (N = 68) included in this study were divided into Group A (women with current abortion and bad obstetric history-BOH) and Group B (women with normal delivery and BOH). The venous blood collected was analyzed for ToRCH antibodies through ELISA. A small piece of placenta tissue taken after delivery or abortion was subjected to nucleic acid (NA) detection through PCR using ToRCH pathogen-specific primers. The placental tissue was analyzed for histopathological changes under a microscope. The data obtained were analyzed using percentages and the Chi square test. Overall ToRCH antibody positivity was 64.70% (44/68). Of these, IgM (Immunoglobulin M) was found in 17.65% (12/68), IgG (Immunoglobulin G) in 45.59% (31/68), and one case (1.47%) was seropositive for both IgM and IgG. The NA was detected in 66.18% (45/68) of the placental tissues of the study population. The higher prevalence of antibodies for T.gondii and RV (23.53% each) and NA for RV, CMV, and HSV (17.99% each) was observed in the study population. The ToRCH infection (antibodies and NA) with BOH complications was statistically found to be non-significant (p> 0.05). Overall discrepancies in ToRCH antibodies and NA positivity were found in 86.76% (59/68) of cases, especially for RV (26.47%). Chorionic villitis (CV) in placental tissues was observed in 20.59% (14/68), i.e., 13.23% of Group A and 7.35% of Group B. Of the total, four women with T.gondii, six with RV, and three each with CMV and HSV infection were found with CV. The most common BOH complications observed were recurrent spontaneous abortions (RSAs) (47.05%, 32/68), stillbirth (22.05%, 15/68), congenital abnormalities (14.70%, 10/68), etc. It was observed that RSAs were associated with CV (10.29%) in the study population. The BOH complication and CV were found to be statistically non-significant (p> 0.05). It is concluded that ToRCH pathogens are prevalent in the study population, and CV was the only histopathological change found and associated with BOH complications.

Adeno-associated viruses (AAVs) have been used for liver gene therapy. Hemgenix and Roctavian are AAV-based treatments for hemophilia B and A, respectively. They cost $3 million and $2.8 million per dose, respectively. While AAV vectors may eventually be cheaper to mass produce, a bacteria-based DNA delivery system might be much cheaper for patients. Also, “bactofection” would allow for the delivery of much larger DNA packages. Such a bacterial system may now be possible, and a prototype for the liver could possibly be developed immediately.

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.

Maternal obesity and/or Western diet (WD) is associated with increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring, driven, in part, by dysregulation of the early life microbiome. Here, using a mouse model of WD-induced maternal obesity, we demonstrate that exposure to a disordered microbiome from WD-fed dams suppressed circulating levels of endogenous ligands of the aryl hydrocarbon receptor (AHR; indole, indole-3-acetate) and TMAO (a product of AHR-mediated transcription), as well as hepatic expression of Il10 (an AHR target), in offspring at 3 weeks of age. This signature was recapitulated by fecal microbial transfer from WD-fed pregnant dams to chow-fed germ-free (GF) lactating dams following parturition, and was associated with reduced abundance of Lactobacillus in GF offspring. Further, expression of Il10 was downregulated in liver myeloid cells and in LPS-stimulated bone marrow-derived macrophages (BMDM) in adult offspring, suggestive of a hypo-responsive, or tolerant, innate immune response. BMDMs from adult mice lacking AHR in macrophages exhibited a similar tolerogenic response, including diminished expression of Il10. Overall, our study shows that exposure to maternal WD alters microbial metabolites in the offspring that affect AHR signaling, potentially contributing to innate immune hypo-responsiveness and progression of MASLD, and highlights the impact of early life gut dysbiosis on offspring metabolism. Further investigations are warranted to elucidate the complex interplay between maternal diet, gut microbial function, and development of neonatal innate immune tolerance and potential therapeutic interventions targeting these pathways.

Receptor-interacting protein kinase 1 (RIPK1) plays a crucial role in controlling inflammation and cell death. Its function is tightly controlled through post-translational modifications, enabling its dynamic switch between promoting cell survival and triggering cell death. Phosphorylation of RIPK1 at various sites serves as a critical mechanism for regulating its activity, exerting either activating or inhibitory effects. Perturbations in RIPK1 phosphorylation status have profound implications for the development of severe inflammatory diseases in humans. This review explores the intricate regulation of RIPK1 phosphorylation and dephosphorylation and highlights the potential of targeting RIPK1 phosphorylation as a promising therapeutic strategy for mitigating human diseases.

Understanding the molecular mechanism whereby an environmental chemical causes a disease is important for downstream purposes. In this study, an analytical workflow was designed to combine several publicly available datasets in order to identify CpG sites and genes that mediate the impact of exposure to environmental chemicals on cardiometabolic traits. Organophosphate and prenatal lead exposure were previously reported to change methylation level at the cg23627948 site. I found as cg23627948 site becomes methylated, the expression of GNA12 gene decreases and this leads to higher body fat percentage. Prenatal perfluorooctane sulfonate expo-sure was reported to increase the methylation level at cg21153102 site. The outcome of analyses revealed higher methylation at this site contributes to higher diastolic blood by changing the expression of CHP1 and GCHFR genes. Furthermore, HKR1 mediates the impact of B12 supple-mentation-cg05280698 hypermethylation on higher kidney function; while, CTDNEP1 mediates the impact of air pollution-cg03186999 hypomethylation on higher systolic blood pressure. This study reports CpG sites and genes that mediate the impact of environmental chemicals on cardiometabolic traits and describes a framework to investigate the underlying molecular paths using publicly available data.

Heavy metals are dangerous contaminants constituting a threat to human health because they persist in soils and are easily transferred into the food chain, causing damages to human health. Among heavy metals, nickel appears to be one of the most dangerous responsible for different disorders. Public health protection requires nickel detection in environment and food chains; a simple, rapid and sensitive method to detect nickel contamination is represented by biosensors. In this paper we report the setup of a whole-cell based system, in which protoplasts, obtained from Nicotiana tabacum leaves, were used as transducers to detect the presence of heavy metal ions and, in particular, nickel ions. Protoplasts were genetically modified with a plasmid containing the GFP reporter gene under the promoter region of a sunflower small HSP gene control. By this device the presence of heavy metal ions was detected. Thus, the possibility to use this whole-cell system as a novel tool to detect the presence of nickel ions in food matrices was assessed.

The endocannabinoid system (ECS) is a complex neuromodulatory network in the human body that have enormous impact in developing the central nervous system, as well as modulates various physiological processes. The ECS is made up of anandamide, 2-arachidonoylglycerol (2-AG), which are responsible for the synthesis and degradation of endocannabinoids, and enzymes such as FAAH and MAGL ensures the precise control over endocannabinoid levels. The ECS relies on CB1 receptors found in the central nervous system (CNS), and CB2 receptors found in the peripheral nervous system and immune cells. Dysregulation of the ECS has been associated with several health conditions, prompting investigations into its association with phytocannabinoids to harness their therapeutic potential. The ECS is intricately linked with the nervous system, and it is known to modulate neuronal activities in the CNS, influencing pain and mood modulation. The ECS is also associated with neuropathies-peripheral nerve damage leading to symptoms such as weakness, numbness and pain as evidenced in diabetic neuropathy, Guillain-Barré Syndrome, carpal tunnel syndrome, peripheral neuropathy, and postherpetic neuralgia. The focus of this review is on the interplay between 2-arachidonoylglycerol and anandamide amidohydrolase in neuropathy, elucidating their roles in pain regulation, inflammation, and specific neuropathies. The knowledge generated is expected to have broad implications, providing comprehensive insights into neuropathic conditions and how to improve on them. Ultimately, this understanding may lead to more effective treatments and improved quality of life for individuals affected by these conditions.

Chemotherapy treatment against pancreatic ductal adenocarcinoma (PDAC) is thwarted by tumoral activation of multiple therapy-resistance pathways. The growth hormone (GH) – GH receptor (GHR) pair is a covert driver of multimodal therapy resistance in cancer, and is overexpressed in PDAC tumors, yet the therapeutic potential of targeting the same has not been explored. Here, we report that GHR expression is a negative prognostic factor in patients with PDAC. Combinations of gemcitabine with different GHR antagonists (GHRAs) markedly improve therapeutic outcomes in nude mice xenografts. Employing cultured cells, mouse xenografts, and analyses of the human PDAC transcriptome, we identified that attenuation of the multidrug transporter and epithelial-to-mesenchymal transition programs in the tumors underlie the observed augmentation of chemotherapy efficacy by GHRAs. Moreover, in human PDAC patients, GHR expression strongly correlates with a gene signature of tumor-promotion and immune-evasion, which corroborate with that in syngeneic tumors in wild-type vs. GH transgenic mice. Overall, we found that GH action in PDAC promoted a therapy-refractory gene signature in vivo, which can be effectively attenuated by GHR antagonism. Our results collectively present a proof of concept towards considering GHR antagonist to improve chemotherapeutic outcome in the highly chemoresistant PDAC.

Cerebral cavernous malformation (CCM) is a collection of irregular small blood vessels that may be present in the brain or spinal cord. These vessels contain slow – moving blood that commonly clot. These malformations are frequently caused by mutations in one of the CCM genes. The CCM1 (also known as KRIT1) gene is essential for vascular morphogenesis however, its interactions with transcriptional regulators are unknown. Inhibitor of DNA-Binding/Differentiation-3 (ID3) has been recognized to be involved in different vascular/blood vessel diseases such as peripheral arterial disease, stroke, arteriovenous malformations, and atherosclerosis. We show interactions between ID3 and additional key differential expressed genes (DEGs) in microarray data of overexpressed CCM1 in endothelial cells through bioinformatic and data analytic tools. Improved understanding of how ID3, CCM1, and DEGs interact will play an important role in adding to the increasing knowledge for creating therapeutic targets for cerebral cavernous malformations.

As critical biocontrol agents, Trichoderma and Metarhizium have demonstrated vast potential in disease prevention and pest control respectively. Current applications, however, are predominantly confined to singular use or simplistic combinations of the two fungi. This study innovatively utilizes Metarhizium and Trichoderma as experimental subjects, employing non-targeted metabolomics to compare the differences in metabolites between co-culture and separate fermentation. The metabolite distinctions in co-culture are meticulously analyzed using sample correlation, least squares discriminant analysis, cluster analysis, and KEGG enrichment analysis. Metabolome sequencing analysis is then applied to compare the co-culture fermentation filtrate with Trichoderma atroviride and Metarhizium anisopliae. Differential metabolite analysis found that co-culture had significantly up-regulated or down-regulated metabolites compared to singular cultures.However,significant metabolite discrepancies are discovered in singular cultures, notably the up-regulated metabolites such as osthole and spirocyclic amine, which have documented antibacterial functions that may prove effective against Fusarium graminearum. Ultimately, the findings from this research contribute to the exploration of synergistic applications of biocontrol fungi and serve as a valuable reference for future development of bio-pesticides for disease and pest control.

The timely and accurate detection of HIV infection is pivotal in stemming the tide of this global pandemic and facilitating early treatment initiation. This review offers a comprehensive examination of the diverse array of methods employed for HIV detection, spanning traditional serological assays to cutting-edge technologies such as nucleic acid amplification, biosensor innovations, and artificial intelligence-driven diagnostics. Each method is scrutinized in terms of its principles, applications, strengths, and limitations. By integrating these complementary approaches and fostering collaboration across disciplines, researchers and clinicians gain a multifaceted understanding of HIV infection, enabling them to navigate the complexities of the virus with precision and insight. Through a multidisciplinary lens, encompassing immunology, molecular biology, engineering, and public health, this review aims to inform future directions in HIV detection, ultimately guiding efforts towards personalized, precise, and accessible diagnostics for all individuals affected by the HIV/AIDS epidemic.

This study presents a computational simulation to explore the distinctive patterns of neural connectivity in Autism Spectrum Disorder (ASD), focusing on the concepts of spatial and topological proximities. ASD is characterized by unique cognitive and behavioral profiles, often attributed to atypical neural development and connectivity. Our simulation employs a two-pronged approach: first, by modeling spatial proximity through the generation of clustered 3D node positions, we mimic the observed over-connectivity in localized brain regions in ASD. Second, we construct a topological network to represent the complex interplay of under-connectivity and over-connectivity in functional brain networks, a hallmark of ASD's neural landscape. The spatial model demonstrates pronounced clustering, reflecting the structural brain differences and atypical growth patterns reported in neuroimaging studies of individuals with ASD. In contrast, the topological model reveals a network with a mix of sparse and dense connections, simulating the diverse and often contradictory findings of functional connectivity in ASD, such as reduced long-range connections and increased local connections. Our simulation provides a visual and conceptual framework for understanding the altered neural connectivity in ASD. It underscores the importance of considering both physical (spatial) and functional (topological) aspects of brain connectivity to grasp the full extent of neurodevelopmental deviations in ASD. This approach not only aids in elucidating the neural underpinnings of ASD's core symptoms but also offers a foundation for developing targeted interventions. Future research, integrating more complex and individual-specific data, could further refine this model, enhancing our understanding of ASD's neural dynamics and contributing to personalized therapeutic strategies.

To analyze the combined response of ocular cyclotorsion and head tilt during body tilt and to interpret the physiologic role of those movements, each of the three subjects completed six different experiments of body tilt not fixating their head movements using a flight simulator, which consisted of combinations of three tilt angles (30, 45, and 60) and two visual conditions. Head tilt and ocular cyclotorsion of the right eye before, during, and after the tilt maneuver were recorded and analyzed by time sequence. In the active tilting phase, the right eye showed a stepladder pattern of multiple repeats of fast and slow cyclotorsion along with head tilt to obtain maximum visual information. During the stationary tilting phase, there occurred a small amount (mean, 2.3) of ocular cyclotorsion which was reciprocal to that of head tilt. The visual cue of body tilt through the central visual field induced a larger amount of head tilt but affected little ocular cyclotorsion. The maximum degree of ocular cyclotorsion during each experiment was 10.2 on average. In conclusion, the combined response of ocular cyclotorsion and head tilt develops during body tilt and it compromises the conflicting needs between binocular vision and gravitational orientation.

Tumor cells display abnormal growth and division, avoiding the natural process of cell death. These cells can be benign (non-cancerous growth) or malignant (cancerous growth). Over the past few decades, numerous in vitro or in vivo tumor models have been employed to understand the molecular mechanisms associated with tumorigenesis in diverse aspects. However, our comprehension of how non-tumor cells transform into tumor cells at molecular and cellular levels remains incomplete. The nematode C. elegans has emerged as an excellent model organism for exploring various phenomena, including tumorigenesis. Although C. elegans does not naturally develop cancer, it serves as a valuable platform for identifying oncogenes and the underlying mechanisms within a live organism. In this review, we describe three distinct germline tumor models in C. elegans, highlighting their associated mechanisms and related regulators. Given the conservation of many of the regulators implicated in C. elegans tumorigenesis, it is proposed that these unique models hold significant potential for enhancing our comprehension of the broader control mechanisms governing tumorigenesis.

With its unique properties and potential applications, nanoparticle-based delivery platforms for vac-cines have gained significant attention in recent years. Nanoparticles have the advantages of enhancing immunogenicity, targeting delivery and improving stability, providing a new solution for drug and vaccine delivery. And in some clinical studies, a variety of nanoparticle delivery platforms have been gradually applied to a wide range of vaccine applications. Current research priorities are exploring various types of nanoparticles as vaccine delivery system to enhance vaccine stability and immunogen-icity. Lipid nanoparticles have shown promising potential in preclinical and clinical studies to efficiently deliver antigens to immune cells. Moreover, lipid nanoparticles (LNPs) and other nanoparticles as nu-cleic acids especially mRNA delivery system, have shown vast potential for vaccine development. In this review, we present various vaccine platforms with an emphasis on nanoparticles for mRNA nano-vaccine delivery vehicles. We introduce several novel nanoparticles delivery platforms for mRNA vac-cine such as lipid, polymer, protein-based nanoparticle and so on. In addition, we overview the an-ti-tumor immunity of nanovaccine against different tumors in cancer immunotherapy. Finally, we give an outlook future perspectives and remaining challenges for this promising technolo-gy-nanoparticle-based delivery platforms for vaccines.

Cancer patients, susceptible to severe COVID-19 outcomes, exhibit varied vaccine responses, particularly those who are receiving chemotherapy. This prospective cohort study enrolled 115 cancer patients, and data from 91 patients who received two doses of COVID-19 vaccines were analyzed. Blood was drawn at baseline, day 28, and 6 months post-second dose for neutralizing antibody analysis. The primary outcome was seroconversion rate against wild type and Omicron at day 28. Secondary outcomes included seroconversion at 6 months, factors associated with seroconversion, and safety. Of the 157 cancer patients screened, 91 were enrolled, with 45% receiving chemotherapy. Seroconversion rates at day 28 were 77% for the wild type and 62% for Omicron. Chemotherapy did not affect seroconversion (p=0.789 for wild type, p=0.597 for Omicron). Vaccine type positively correlated with seroconversion, with an adjusted ORR of 25.86 (p=0.029) for the wild type and 17.38 (p<0.001) for Omicron with the primary heterologous vaccine. Adverse events were grade 1 in 34.0% and grade 2 in 19.7% of participants. Despite lower seroconversion against Omicron, no difference was noted between chemotherapy and non-chemotherapy groups. COVID-19 vaccinations demonstrated good tolerability. This data underscores vaccine efficacy considerations in cancer patients, informing tailored strategies for this vulnerable population.

In tropical developing regions, typhoid fever and malaria often co-occur, posing serious health risks. The two illnesses have similar symptoms, which makes diagnosis and treatment more difficult. Through a thorough analysis of existing literature on typhoid fever, malaria, and co-infection, including research articles, case studies, and review papers, this review seeks to understand the dynamic interactions between typhoid fever and malaria co-infection. The review highlights important problems with co-infection between typhoid and malaria, such as higher morbidity and death, diagnostics-related challenges, and antibiotic resistance. Overlapping symptoms and limitations in current diagnostic tests impede accuracy. Treatment plans are made more difficult by the advent of typhoid strains that are resistant to drugs. The analysis concludes by highlighting the necessity of developing more sensitive and specific diagnostic methods in order to accurately diagnose co-infections. Going forward, the review emphasizes the need for more investigation into the immunological connections between malaria and typhoid illnesses. Essentially, this paper offers a thorough summary of the difficulties and possibilities related to co-infection between typhoid and malaria. It provides a framework for upcoming studies and initiatives that seek to improve public health and patient outcomes in the face of these intricately linked health problems.

Both soybean variety and processing affect product characteristics. This study’s objective was to characterize the effect of four extraction methods (variations of soaking and grinding) combined with cooking on the content and composition of phenolic substances, antioxidant and anti-DU145 prostate cancer cell proliferative properties of soymilk prepared from a yellow soybean of the ProSoy variety, which is a high protein variety. Results showed soymilk processing yield was the greatest by Method 4, but Method 2 gave the highest solids and protein yields by about 14 and 12%, respectively. Method 4, a two-step grinding also increased yields (8 and 7%, for solids and protein, respectively), and in all but one instance produced higher total phenolic content (TPC), total flavonoid content (TFC), condensed tannin content (CTC) and total isoflavone content in both raw and cooked soymilk as compared to Method 1. Cooking soymilk reduced 14-17% of total phenolic substances. Cooking reduced anticancer capacity of Method-4-prepared soymilk phenolic extract by increasing IC50 value from about 4.9 mg/mL to 6.8 mg/mL. The increases in phenolic compounds and antioxidants produced in Prosoy soymilk by Methods 2 and 4 with simultaneous increases in product solids yield are significant to benefit the soymilk industry and consumer health. Keywords: ProSoy yellow soybean, soymilk processing, phenolics, isoflavones, antioxidant capacity, anti-DU145 prostate cancer proliferation

Microglial cells are brain macrophages that support and protect the central nervous system enviroment. Aging induces alterations in microglial polarization, resulting in a shift towards a neurotoxic phenotype characterized by increased expression of pro-inflammatory markers. Dysregulation of microglial cells regulatory pathways and interactions with neurons contribute to chronic activation and neurodegeneration. A better understanding the involvement of microglia in neurodegenerative diseases like Alzheimer's and Parkinson's, is a critical topic to studying the role of inflammatory responses in disease progression. Furthermore, the metabolic changes in aged microglia, including downregulation of oxidative phosphorylation are discussed in this review. Understanding these mechanisms is crucial for developing better preventive and therapeutic strategies.

Cotton fiber, a crucial and sustainable resource for global textile production, undergoes a complex five-stage developmental process, encompassing initiation, elongation, transition, secondary cell wall biosynthesis, and maturation. These elongated single-cell fibers originate from the outer ovule epidermis. The development of cotton fibers involves intricate changes in gene expression and physiological processes, resulting in a nearly pure cellulose product vital for the global cotton industry. Decoding genes associated with fiber development enhances our understanding of cotton fiber mechanisms and facilitates the cultivation of varieties with enhanced quality. In recent decades, advanced omics approaches, including genomics, transcriptomics, and proteomics, have played a pivotal role in identifying genes and gene products linked to cotton fiber development, including the MYB transcription factor family which coordinates cotton fiber development. Molecular studies have revealed transcription factors like MYB, WRKY, Homeodomain Leucine Zipper (HD-ZIP) and basic Helix-Loop-Helix (bHLH) influencing fiber initiation and elongation. The intricate interplay of phytohormones like auxin, gibberellic acid (GA), brassinosteroid (BR), jasmonic acid (JA), ethylene, abscisic acid (ABA), and cytokinin is explored, providing a comprehensive perspective on shaping cotton fibers. Numerous candidate genes and cellular processes affecting various aspects of fiber development hold promise for genetic engineering or marker-assisted breeding to improve fiber quality. This review presents a comprehensive overview of key achievements in cotton molecular biology, with a specific emphasis on recent advancements in understanding transcription factors and phytohormones involved in cotton fiber initiation and elongation.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, showing reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

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

We analyze the humoral and B-cell mediated immunogenic response induced by GP5 lineal epitopes from porcine reproductive and respiratory syndrome virus (PRRSV) to explore the role of this protein in the protective response. For inoculation, pigs aged twenty-one days were allocated into six groups (seven pigs per group): control (PBS), vehicle (carrier), vaccinated (Ingelvac-PRRSV, MLV®), non-vaccinated and naturally infected, GP5-B and GP5-B3. Subsequently blood samples were collected and analyzed. Cytokine were measured by ProcartaPlex kit. Peptide-specific IgGs and cross-reactivity against peptides were analyzed by ELISA and B-cell subpopulations were analyzed by flow cytometry. At 2 days post-immunization (dpi), the GP5-B3 peptide increased the serum concentrations of cytokines associated to activate adaptive cellular immunity (IL-1β and IL-12). The concentration of IgGs anti-GP5-B increased in both cases at 21 and 42 dpi, while IgGs anti-GP5-B3 increased at 21 dpi and remained at the same level until 42 dpi. Also, antibody-forming/Plasma B cells (CD2+/CD21-) and primed B cells (CD2-/CD21+) from immunized pigs showed an increase at 42 dpi. Conversely the naïve B cells from immunized pigs decreased compared with the controls. Importantly, Both GP5-B and GP5-B3 peptides exhibited immunoreactivity against serum antibodies from vaccinated group, as well as non-vaccinated and naturally infected group. In conclusion, GP5-B and GP5-B3 peptides elicited immunogenicity mediated by antigen specific IgG´s and B-cell activation.

Tumor microenvironment (TME) is composed of various cellular components such as tumor cells, stromal cells including fibroblasts, adipocytes, mast cell, lymphatic vascular cells and infiltrating immune cells, macrophages, dendritic cells and lymphocytes. The intricate interplay between these cells influences tumor growth, metastasis and therapy failure. Significant advancements in breast cancer therapy have resulted in a substantial decrease in mortality. However, existing cancer treatments frequently result in toxicity and nonspecific side effects. Therefore, improving targeted drug delivery and increasing the efficacy of drugs are crucial for enhancing the treatment outcome and reducing the burden of toxicity. In this review, we provided an overview of how tumor and stroma-derived osteopontin (OPN) plays a key role in regulating the oncogenic potential of various cancers including breast. Next, we have dissected the signalling network by which OPN regulates tumor progression through interaction with selective integrins and CD44 receptors. This review addresses the latest advancement in role of various splice variants of OPN in cancer progression and OPN-mediated tumor-stromal interaction, EMT, CSCs enhancement, immunomodulation, metastasis, chemoresistance, metabolic reprogramming and further suggest that OPN might be a potential therapeutic target and prognostic biomarker for the evolving landscape of cancer management.

Paracetamol, also known as acetaminophen, is one of the most widely used over-the-counter analgesics and antipyretics globally. While generally considered safe when used as directed, excessive or prolonged use of paracetamol can lead to adverse effects on various organ systems within the human body. This comprehensive review explores the physiological mechanisms underlying paracetamol toxicity, its effects on different organs, risk factors for overdose, diagnostic methods, and potential management strategies.

Kombucha is a two-stage fermented sweetened-tea beverage that uses yeast and lactic acid bacteria (LAB) to convert sugars into ethanol and lactate, and acetic acid bacteria (AAB) to oxidize ethanol to acetate. Its popularity as a beverage grew from claims of health-benefits derived from this vibrant microbial bioconversion. While recent studies have shed light on the diversity of cultures during a Kombucha fermentation, there is limited information on the diversity, and especially viability, of cultures in retail beverages that advertise the presence of Kombucha and probiotic cultures. In this study, 12 Kombucha beverages produced by different manufacturers throughout the US were purchased and microbially characterized. Eight of the beverages contained viable Kombucha cultures, while 3 of the remaining 4 had viable Bacillus cultures as added probiotics. Amplicon profiling revealed all contained Kombucha yeast and bacteria cells. The dominant yeast detected were Lachancea cidri (10/12), Brettanomyces (9/12), Malassezia (6/12) and Saccharomyces (5/12). Dominant LAB included Liquorilactobacillus and Oenococcus oeni, and AAB were Komagataeibacter, Gluconobacter and Acetobacter. One beverage had a significant amount of Zymomonas mobilis, an ethanol producing bacterium from Agave cactus. While Kombucha beverages differ in the types and viability of cultures, all except one beverage contained detectable viable cells.

Biotic stressors pose serious threats to crop yield, jeopardizing food security and resulting in over US$220 billion per year losses to the agriculture industry. Plants activate innate defense mechanisms upon pathogen perception and invasion. The plant immune response comprises numerous concerted steps, including the recognition of invading pathogens, signal transduction, and activation of defensive pathways. However, pathogens have evolved various structures to evade plant immunity. Given these facts, genetic improvements of plants are required for sustainable disease management to ensure global food security. Advanced genetic technologies have provided new opportunities to revolutionize and boost plant disease resistance against devastating pathogens. Furthermore, targeting susceptibility (S) genes, such as OsERF922 and BnWRKY70, through CRISPR methodologies offers novel frontiers to disrupt the molecular compatibility of pathogens and introduce durable resistance against them in plants. Here, we provide a critical overview of advances in understanding disease resistance mechanisms. The review also critically examines management strategies under challenging environmental conditions and R gene-based plant genome engineering systems intending to enhance plant responses against emerging pathogens. This work underscores the transformative potential of modern genetic engineering practices in revolutionizing plant health and crop disease management while emphasizing the importance of responsible application to ensure sustainable and resilient agricultural systems.

The motor protein Prestin found in the outer hair cells (OHCs) of the inner ear is responsible for producing high sensitivity and sharp frequency selectivity for mammalian hearing. Some studies have suggested that Prestin could serve as a serological biomarker for cochlear damage since OHCs are highly vulnerable to damage from various sources of insults. However, the reported data are inconsistent and lack appropriate negative controls. To investigate this further, we measured Prestin quantities in the bloodstream using ELISA kits from different companies. Wildtype (WT) mice were exposed to different ototoxic treatments, including noise exposure and ototoxic reagents that kill OHCs rapidly. Prestin-knockout (KO) mice were used as a negative control. Our data show that some ELISA kits were not able to detect Prestin specifically. The ELISA kit that could detect Prestin protein from cochlear homogenates failed to detect Prestin in the bloodstream despite significant damage to OHCs in cochleae. Furthermore, the optical densities of samples, which correlate to Prestin quantities, were significantly influenced by hemolysis in the samples. In conclusion, Prestin from OHCs is not a sensitive and reliable serological biomarker for detecting cochlear damage in mice.

This study, conducted with meticulous attention to detail, comprehensively examines the state of plants and their adaptation to Kazakhstan's extra-arid climatic zone of the Mangistau. It uses the collections of woody plants from the Mangyshlak Experimental Botanical Garden in Aktau as a case study and extrapolates the results to the entire region. The study area is arid and unsuitable for many plants, so examining physiological adaptation mechanisms and strategies for preserving plants in unfavourable conditions is crucial. The study employed a range of methods, including the measurement of the intensity of transpiration, leaf hydration, and the content of chlorophyll A, B, and carotenoids. These methods were chosen for their proven effectiveness in similar studies and their ability to provide accurate and reliable data. The samples were also assessed using a point system for resistance to drought, phytophagy, gas tolerance, salt tolerance, winter hardiness, and soil fertility. The results obtained and entered into the IEBG platform “DinTseR” to assess the value of the introduction using a diagnostic scale revealed a high variability (up to 51.7-52.2%) of physiological indicators of growth and development. The highest values of transpiration intensity were observed in deciduous trees and shrubs, rose varieties (205-243 mg/g fresh leaf mass per hour), leaf water content - in climbing plants (68.9%), chlorophyll A and B content - in deciduous plants, and plants - old trees, fruit trees and varietal roses (3.46-3.93 and 1.34-1.84%). Their concentration in coniferous species is almost two times lower (0.63%). A correlation was also made between various significant factors. Twenty regression equations and forecasts have been identified that can be used to diagnose and assess resistance, thereby reducing the cost of determining the introduction value in the conditions of Mangistau. These findings are essential in understanding and preserving the unique flora of the Mangistau region.

Magnetogenetics emerges as a transformative approach for modulating cellular signaling pathways through the strategic application of magnetic fields and nanoparticles. This technique leverages the unique properties of magnetic nanoparticles (MNPs) to induce mechanical or thermal stimuli within cells, facilitating the activation of mechano- and thermosensitive proteins without the need for traditional ligand-receptor interactions. Unlike traditional modalities that often require invasive interventions and lack precision in targeting specific cellular functions, magnetogenetics offers a non-invasive alternative with the capacity for deep tissue penetration and the potential for targeting a broad spectrum of cellular processes. This review underscores magnetogenetics' broad applicability, from steering stem cell differentiation to manipulating neuronal activity and immune responses, highlighting its potential in regenerative medicine, neuroscience, and cancer therapy. Furthermore, the review explores the challenges and future directions of magnetogenetics, including the development of genetically programmed magnetic nanoparticles and the integration of magnetic field-sensitive cells for in vivo applications. Magnetogenetics stands at the forefront of cellular manipulation technologies, offering novel insights into cellular signaling and opening new avenues for therapeutic interventions.

The structure and expression of exogenous genes in transgenic crops are critical for the target traits. R7569 was a mutant event identified in this study with deletion at the 3' end of cry1Ac gene compared to the transgenic insect-resistant cotton MON531 event with commercial application. R7569 has the same exogenous insertion structure as MON531, but with a deletion in the 3' end of the cry1Ac gene and the terminator region. R7569 has a truncated cry1Ac gene with the length of 2,554 bp, encoding 881 amino acids. The transcription termination site was mainly concentrated downstream of the truncated position and extended 160-270 bp from the truncated position using rapid-amplification of cDNA ends (RACE). The transcript levels of cry1Ac genes of R7569 and MON531 decreased gradually at seedling, bud and bell stages, and the transcript levels of cry1Ac genes of R7569 were significantly higher than those of MON531 in seedling and bud stages, but there was no significant difference in the boll stage. The content of Cry1Ac protein in R7569 gradually decreased with the seedling, bud and boll stage, and the content of Cry1Ac protein in all three periods was higher than that of MON531. The insect resistance assay showed that the resistance levels of R7569 and MON531 were both at the high level, and the corrected mortality rate against bollworms was 99.5% and 95.2%, respectively, and there was no significant difference between them. The LC50 value of R7569 was 0.732ng/g dw, with a slope of 1.654 indicating a high level of resistance to bollworm. In this study, for the first time, we found a partial deletion of the target gene in commercially applied transgenic crops, and the partial deletion of the 3' end of the cry1Ac gene retained a better transcription, expression level and insecticidal activity, which can provide a specific case for the safety evaluation of transgenic crops.