Globally, the demand for plant-based alternative food is increasing rapidly as these products are getting quite popular in vegan and vegetarians. However, it is still in the early stage and faces various technological challenges, but the imitation of sensory profile is the most challenging part as the products are meant to be an alternative of meat. The development of similar product to meat requires an accurate selection of ingredients and processing. An understanding about the sensory profile can help to construct the product and technologies that are consumer centric and sustainable. In this review, we focus on the comparative differences in the sensory profile of animal meat and plant-based meat alternative specially in the color, texture and flavor, along with the method used to resemble them. The paper also explains about the sensory evaluation and how it affects the consumer preference and acceptability. Additionally, a direction to further research for developing better plant-based alternative products has also been suggested.

Excessive nitrogen application has become a hidden danger threatening the sustainable development of agriculture. Exploring the potential genes will help to improve the nitrogen availability of wheat through molecular breeding. We therefore conducted wheat transcriptomics and proteomics researches under complete culture medium without nitrogen (N0) and complete culture medium with nitrogen (N1). The results showed that, the nitrogen deficit decreased the fresh weight, N content and net photosynthetic rate of winter wheat. 3949 and 2675 differentially expressed genes (DEGs) were identified in the shoot and root, respectively, while 164 and 129 differentially expressed proteins (DEPs) were identified in the shoot and root respectively. 9 genes in shoot and 26 genes in root showed the same trends in RNA and protein levels. 5 genes in shoot and 4 genes in root showed the opposite trends in RNA and protein levels. Pathway enrichment of wheat transcriptome and proteome under nitrogen deficit proposed 3 candidate genes related to photosynthesis in shoot, 4 candidate genes related to carbon metabolism in shoot, and 12 candidate genes related to carbon metabolism in root. Meanwhile, the chromosomal and subcellular localization of these genes were listed, which will provide reference for improving nitrogen availability through molecular breeding.

This prospective observational cohort pilot study included 22 cats diagnosed with partial traumatic brachial plexus injury (PTBPI), aiming to explore the response of an early intensive neurorehabilitation protocol in a clinical setting. This protocol included functional electrical stimulation (FES), locomotor treadmill training and kinesiotherapy exercises, starting at the time with highest probability of nerve repair. The synergetic benefits of this multimodal ap-proach were based on the potential structural and protective role of proteins and release of neurotrophic factors. Furthermore, parametrization of FES was according to the presence or absence of deep pain. Results have shown that 72.6% (16/22) cats achieved ambulation, with 9 cats within 15 days, 2 cats until 30 days and 5 cats until 60 days. During the 4 years follow-up, there was evidence of improvement on both muscle mass and muscle weakness, in addition to the disappearance of neuropathic pain. Notably, after the 60 days of neurorehabilitation, 3 cats improved ambulation after arthrodesis of the carpus. Thus, early rehabilitation, with FES ap-plied at the first weeks after injury and accurate parametrization according to the deep pain perception, is suggestive to help in functional recovery and ambulation, reducing probability of amputation.

Climate change is unpredictable and can change rapidly or over time; anthropogenic stressors work synergistically to strengthen their impact on vulnerable ecosystems and the fisheries sector. This study documented the past occurrence of extreme climate change impacts, such as supertyphoon Pablo (ST: Bopha), which severely affected Baganga, Davao Oriental, about ten years ago. A mixed-methods data collection was used, combining semi-structured interviews with small-scale fishers (N=120) in four fishing villages and focus group discussions (N=4, participated by about 4 focus groups) on assessing the impacts and their adaptation after climatic events occurred. Our findings indicate that the four selected fishing villages were exposed to common factors of climate change events that destroyed many lives and their livelihood. Including a decrease in catch per trip and the fishing operations disruption (98%). However, due to the impact of the supertyphoon, small-scale fishers in Baganga developed psychological distress (emotional 44% and physical 24%) due to the extreme event or disaster and economic losses (32%). In order to survive, their adaptation strategies relied on government and non-government-provided provisions and projects, e.g., planting trees, constructing a sea wall with wave breakers, cash for work, and tourism as an alternative livelihood. Despite this, our study revealed that the community had limited knowledge on the impacts of climate change, lack clear management goals especially for fishers, and the widespread use of illegal fishing gears. The local government must strongly implement rules, policies, and adaptation measures that will contribute to better and more resilient communities. This can help them to withstand future shocks and provide sustainable fisheries resources that will benefit all the fishers. The study will be useful to policymakers, disaster management group and organization that will help assist affected communities highly affected by climatic events.

Accurate determination of protein localization, levels, or protein-protein interactions is pivotal for the study of their function, and in situ protein labeling via homologous recombination has emerged as a critical tool in many organisms. While this approach has been refined in various model fungi, the study of protein function in most plant pathogens has predominantly relied on ex-situ or overexpression manipulations. To dissect the molecular mechanisms of development and infection for Verticillium dahliae, a formidable plant pathogen responsible for vascular wilt diseases, we have established a robust, homologous recombination-based in situ protein labeling strategy in this organism. Utilizing Agrobacterium tumefaciens-mediated transformation (ATMT), this methodology facilitates the precise tagging of specific proteins at their C-termini with epitopes, such as GFP and Flag, within the native context of V. dahliae. We demonstrate the efficacy of our approach through the in situ labeling of VdCf2 and VdDMM2, followed by subsequent confirmation via subcellular localization and protein-level analyses. Our findings confirm the applicability of homologous recombination for in situ protein labeling in V. dahliae and suggest its potential utility across a broad spectrum of filamentous fungi. This labeling method stands to significantly advance the field of functional genomics in plant pathogenic fungi, offering a versatile and powerful tool for the elucidation of protein function.

Abstract: The septum pellucidum is a thin, translucent double-membrane structure located between the anterior horns of the lateral ventricles. This mini-review explores the gross and radiological anatomy, variations, and clinical significance of the septum pellucidum. The article elaborates on the different types of variations, including cavum septum pellucidum (CSP), cavum vergae (CV), and cavum veli interpositi (CVI). The CSP is a fluid-filled pocket located within the two leaflets of the SP. It forms during fetal development and gradually obliterates before birth. However, the fusion may be prolonged or persist into adulthood in some individuals. The CV is formed when the two commissural plates fail to fuse completely during foetal development. When associated with CSP, the CV is collectively known as the cavum septum pellucidum et vergae (CSPV). However, the isolated CV is rare. The CVI is a CSF-filled space between two tela choroidea layers and communicates with the quadrigeminal cistern, superior to the pineal gland. This article discusses the radiological features of these variations using imaging techniques such as ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT). Ultrasonography is particularly useful for evaluating the SP in fetuses and infants, while MRI and CT scans provide detailed visualisation of the SP and its variations. The SP has the potential to be associated with cerebral anomalies, hydrocephalus, mental disorders, and neurological symptoms. Knowing the related anatomy and detecting variations using imaging modalities are crucial for accurately diagnosing and managing these conditions.

Microcrystal delivery instruments are pivotal to perform serial femtosecond crystallography experiments at the XFEL facilities. We present a novel sample delivery technique based on a micro-tubing reeling system (MRS). Even though the tiny size of the micro-tubing, the MRS device has an advantage of operation without real-time position adjustment of the tube to match with the XFEL pulses. Moreover, the applicable repetition rate is more flexible than the previously reported chip-based one-dimensional fixed target system.

The amalgamation of mineral and targeted bacterial preparations represents a new generation of agricultural technology. Inoculation with combined preparations of microorganisms is more effective than inoculation with a single microorganism in stimulating plant growth by providing a more balanced diet for various crops. In this work, the effect of inoculation of 20 consortium variants on the yield indicators of three crops (wheat, buckwheat, corn) and the soil microbiome in the open field was investigated. The soil microbiome was defined by 16S rRNA sequences through NGS. Species richness of the soil microbial community (alpha diversity) was similar for all studied samples. Beta-diversity analysis revealed that the microbial diversity of three soil samples (C.bw, F.bw and Soil.bw) differed significantly from all others. At the phylum level, the number of Acidobacteriota and Firmicutes in these samples was increased. For the combination “Consortium C (Rothia endophytic GMG9 and Azotobacter chroococcum GMG39) - buckwheat”, a systemic positive improvement in all growth and yield indicators was observed. The soil of the site where buckwheat grew, inoculated by Consortium C, contained significantly more available phosphorus than all other soil samples. Such results can be explained both by the direct action of a consortium of phosphate-immobilizing and nitrogen-fixing bacteria and to acidification of the medium due to an increase in phylum Acidobacteriota bacteria in the soil.

Oxidoreductase (OXR) enzymes are in high demand for biocatalytic applications in food industry and cosmetics: glucose oxidase (GOx), cellobiose dehydrogenase (CBDH), bioremediation: horseradish peroxidase (HRP), laccase (LAC), and medicine for biosensors and miniature biofuel cells (GOx, CBDH, LAC, HRP). They can be used in a soluble form and/or within the yeast cell walls expressed as chimeras on the surface of yeast cells (YSD), such as P. pastoris and S. cerevisiae. However, most of the current studies suffer from either low yield for soluble enzyme expression or low enzyme activity when expressed as chimeric proteins using YSD. This is always the case in studies dealing with heterologous expression of oxidoreductase enzymes, since there is requirement not only for multiple OXR genes integrations into the yeast genome (super transformations), and codon optimization, but also very careful design of fermentation media composition, and fermentation conditions during expression due to need for adding transition metals (copper, iron), and metabolic precursors of FAD and heme. Therefore, scientists are still trying to find optimal formula using above mentioned approaches, and most recently also using protein engineering and directed evolution for additional increase in the yield of recombinant enzyme production. In this review article we will cover all the current state of the art technologies and most recent advances in the field that yielded high expression level for some of these enzymes in specially designed expression/fermentation systems. We will also tackle and discuss new possibilities for further increase in fermentation yield by the cutting-edge technologies such are directed evolution, protein and strain engineering, high-throughput screening methods based on in vitro compartmentalization, flow cytometry and microfluidics.

The impact of drought stress on plant growth in arid regions is a critical concern, necessitating the exploration of strategies to enhance plant drought resistance, particularly during the early stages of drought stress. This study focuses on the ectomycorrhizal fungus Cenococcum geophilum, renowned for its extensive genetic diversity and broad host compatibility, making it a crucial ally for host plants facing external stresses. We utilized approximately 5-month-old Pinus massoniana seedlings inoculated with different ecotypic strains of C. geophilum for 7 days of drought stress. The results showed that the inoculation of most strains of C. geophilum enhanced the drought resistance of P. massoniana seedlings under the early stages of drought stress, by influencing the water content, photosynthesis, accumulation of osmotic adjustment substances, and antioxidant enzyme activities in both shoots and roots of seedlings. These responses were further validated through transcriptome analysis. Notably, the level of drought resistance observed in mycorrhizal seedlings was irrespective of the level of drought tolerance of C. geophilum strains. This study contributes essential data for understanding the drought response mechanisms of mycorrhizal P. massoniana seedlings inoculated by distinct C. geophilum ecotypes, and guidance on selecting candidate species of ectomycorrhizal fungi for mycorrhizal afforestation in drought areas.

The retinal pigment epithelium (RPE) is an important monolayer of cells present in the outer retina forming a major part of the blood-retina-barrier (BRB). It performs many essential tasks for the maintenance of retinal integrity and function. With increasing knowledge of the retina, it is getting clearer that both common retinal disorders, like age related macular degeneration, and rare genetic disorders originate in the RPE. This calls for a better understanding of the functions of various proteins within the RPE. In this regard, mice enabling an RPE-specific gene deletion are a powerful tool to study the role of a particular protein within the RPE cells in their native environment, simultaneously negating any potential influences of systemic changes. Moreover, since the RPE cells interact closely with the adjacent photoreceptors, these mice also provide an excellent avenue to study the importance of a particular gene function within the RPE to the retina as a whole. In this review, we outline and compare the features of various Cre mice created for this purpose, allowing researchers a well-informed decision on the choice of Cre mouse to use in relation to their research needs.

The development of modern genomic tools has sped up the breeding program of food crops. More recently, genomic resources are being developed for tropical forages and will be key resources for developing climate resilient high yielding forage varieties. In this study, we present a genome-wide association study for biomass yield and feed quality traits in buffel grass (Cenchrus ciliaris L. aka Pennisetum ciliare L.,). Genome-wide markers generated using the DArTSeq platform and mapped onto the reference genome of Setaria italica were used for the genome-wide association study. The results revealed several markers associated with biomass yield and feed quality traits. A total of 78 marker trait associations were identified with R2 values ranging from 0.138 to 0.236. The marker trait associations were distributed across different chromosomes. Of these associations, the most marker trait associations (23) were observed on Chr9, followed by Chr5 with 12. The fewest number of marker trait associations were observed on Chr4 with 2. In terms of traits, 17 markers were associated with biomass yield, 24 with crude protein, 26 with TDN, 14 with ADF, 10 with NDF and six with DMI. Twenty of the identified markers were associated with at least two traits. The identified marker trait associations provide a useful genomic resource for future improvement and breeding of buffel grass.

Recently, Mulroney,et.al., demonstrated that Pfizer’s ModRNA Covid vaccine, but not AstraZeneca Covid vaccine, produce aberrant foreign proteins in vivo due to reading frame shift in ribosomes. This phenomenon could elucidate the notable surge in autoimmune diseases following the administration of ModRNA vaccines compared to Influenza vaccines between 2020 and 2023, as found in the VAERS database. These findings bear significant implications for the future application of mRNA technology, emphasizing the necessity of modifying the design of the mRNA sequence to mitigate these defects. Remarkably, Mulroney and collaborators achieved a reduction in frame shift proteins by introducing additional edits to the mRNA sequences. This adjustment is pivotal for rectifying the flawed design of the ModRNA employed by Pfizer. In light of these findings, many advocate for the immediate recall and further investigation of these products. The notion of a "future mRNA-based therapy" should be postponed indefinitely.

The phytoplankton community in 66 reservoirs ubicated at the hydrographic basin of the Ebro River (Spain) was analyzed. Samples were collected in the summer season during the period 2010-2015, with the main purpose of evaluate the Trophic State and Ecological Potential according to the Water Framework Directive of the European Union. In this work we presented a representative overview of several consecutive years of the state of the reservoirs and their associated trophic status; methodology was to obtain statistically significant relationships between the phytoplankton community and main physicochemical water quality variables (water transparency, pH, chlorophyll a, total and soluble phosphorus, anoxic zone depth, nitrite, nitrate and ammonium concentrations). We provide data for retrospective comparative of the state of the reservoirs with previous and current studies in order to improve the management of these reservoirs, and to serve as data reference for future works in a context of global change (climate and pollution).

Currently the bimatoprost implant (DURYSTA) is approved for a single administration secondary to concern for progressive corneal endothelial cell (CEC) loss with intracameral administration. In order to better understand the cause of CEC loss and other adverse events (AEs) with intracameral administration, multimodal imaging of the implant utilizing optical coherence topography (OCT), robotic ultrasound and bio microscopy video recording was utilized. Inherently the anterior chamber is a non-confined space. In certain examples the implant assumed a round and spotted structure as it picked up iris pigment as it migrated around the anterior chamber. Accordingly, we explored delivery of the implant in the middle segment behind the iris and in front of the pseudophakic lens. We then evaluated the suitability of various imaging modalities to assess the implant in this location. For middle segment administration, the ArcScan Insight 100 robotic ultrasound provided resolution and repeatability sufficient to monitor the implant behind the iris. This preliminary study hypothesizes that DURYSTA migration in the anterior chamber is the main source of AEs. Through use of a confined location, the middle segment, the implant is unlikely to migrate and cause CEC loss while also delivering drug closer to its site of action, the ciliary body. Further efforts are underway to understand the suitability of the middle segment for serial DURYSTA administration to maximize intraocular pressure lowering while minimizing AEs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic, represents a serious threat to public health. The spike (S) glycoprotein of SARS-CoV-2 mediates viral entry into host cells and is heavily glycosylated. In this study, we systemically analyzed the roles of 22 putative N-linked glycans in SARS-CoV-2 S protein expression, membrane fusion, viral entry, and stability. Using α-glycosidase inhibitors, castanospermine and NB-DNJ, we confirmed that disrupting the N-linked glycosylation process blocked the maturation of the S protein, leading to impairment of S protein-mediated membrane fusion. Single substitution of each of the 22 N-linked glycosylation sites with glutamine revealed that 9 out of the 22 N-linked glycosylation sites were critical for S protein folding and maturation, resulting in reduced S protein-mediated cell-cell fusion and viral entry. Of note, N1074Q mutation markedly affected S protein stability and induced significant receptor-independent syncytium (RIS) formation in HEK293T/hACE2-KO cells, and removal of the furin-cleavage site partially compensated instability of N1074Q mutation. Although the corresponding mutation in the SARS-CoV S protein (N1056Q) did not induce RIS in HEK293T cells, the mutants N669Q and N1080Q exhibited increased fusogenic activity and induced syncytia formation in HEK293T cells. Therefore, N-glycans on the SARS-CoV and SARS-CoV-2 S2 subunits are of great importance in maintaining the prefusion state of the S protein. The study revealed the critical roles of N-glycans in S protein maturation and stability, which have implications for the design of vaccines and anti-viral strategies.

We investigated the prevalence and genetic diversity of Wolbachia pipientis strains in Aedes albopictus populations in Greece. Using a combination of PCR and Sanger sequencing techniques, we genotyped Wolbachia strains in 105 mosquitoes collected across eight different prefectures in 2021. We found a high prevalence of Wolbachia in both male (90%) and female (97%) mosquitoes. Among the infected samples, 84% had double infections with both wAlbA and wAlbB strains, while 16% had infections with only wAlbB. Our comparison of the Multi-Locus Sequence Typing (MLST) profile, employing gatB-coxA-hcpA-ftsZ-fbpA genotyping, revealed a single MLST profile for each wAlbA and wAlbB strain in Greek populations. The same MLST profiles were also reported in populations from China, Russia, and Argentina, suggesting low levels of global diversity in wAlbA and wAlbB strains. Furthermore, our results indicated a significant association between temperature and the prevalence of single infections (P = 6.498E-07), with higher temperatures correlating with an increased likelihood of single infections. Although male-bias showed a tendency towards single infections, the effect was marginally non-significant (P = 0.053). These results were confirmed using a bootstrap-with-replacement analysis approach. Overall, our findings offer novel insights into the distribution and species diversity of Wolbachia strains in Greek Ae. albopictus populations, emphasizing the importance of understanding the short-term plastic and adaptive responses of these organisms to environmental stressors and rapid climate change.

Trees, often referred to as the "lungs of the Earth," hold immense significance for both the natural world and human society. Their contributions span a multitude of ecological, environmental, economic, and social domains, making them essential components of a healthy and thriving planet. Phytoplasma association not only compromise tree aesthetics but also reduce photosynthetic capacity and overall vigour. Phytoplasma diseases also lead to increased tree mortality, altering ecosystem dynamics.This review article provides an in-depth exploration of phytoplasma diseases affecting trees worldwide, encompassing their epidemiology, symptomatology, impact and management strategies.

The utilization of wild genera in sugarcane has been recognized as an important strategy to enhance the genetic base to impart biotic and abiotic stress tolerance in hybrid cultivars. A set of 15 Erianthus procerus derived hybrids along with five popular check varieties were evaluated for two years (2018–19 and 2019–20) for agro-morphological, quality, physiological traits and three years (2018–19, 2019–2020, and 2020–21 for winter sprouting potential. The E. procerus hybrid GU 12-19 recorded the highest winter sprouting potential with a winter sprouting index (WSI) of 10.6 and a percent superiority of 279 over best check (Co 0238) followed by GU 12-22 with WSI: 8.5 and % superiority over best check was 204. The other top-performing hybrids, GU 12-21 and GU 12-29, recorded the excellent winter sprouting potential with WSI of 7.2 and 6.9 respectively. The four E. procerus hybrids identified with higher WSI were also resistant to the prevalent races of red rot in both tropical and subtropical conditions. The association analysis revealed significant correlations between various traits, particularly fibre content with a maximum number of associations, which indicates its multifaceted impact on sugarcane characteristics. Principal component analysis (PCA) summarized the data, explaining 57.6% of the total variation for measured traits and genotypes, providing valuable insights into the performance and characteristics of the E. procerus-derived hybrids under subtropical climate. The anthocyanin content of E. procerus hybrids was better than the check varieties with a mean of 0.147 (2018–19) and 0.144 (2019–20) and range of 0.123–0.179 (2018–19) and 0.111–0.172 (2019–20), anthocyanin plays a vital role in mitigating the cold injury, acting as an antioxidant in cool weather conditions, particularly in sugarcane. Further, seven hybrids recorded more than 22% fibre threshold, indicating their industrial potential. These hybrids would be potential donors for cold tolerance and high ratooning ability along with red rot resistance under subtropical climate.

The pandemic SARS-CoV-2 continues to evolve to give rise to variants of concern that can escape vaccine-induced immunity. As such, more effective vaccines are urgently needed. In this study, we evaluated virus-like particle (VLP) as a vaccine platform for SAS-CoV-2. The spike, envelope, and membrane proteins of the SARS-CoV-2 Wuhan strain were expressed by a single recombinant baculovirus BacMam and assembled into VLPs in cell culture. The morphology and size of the SARS-CoV-2 VLP as shown by transmission electron microscopy was found to be similar to the authentic SARS-CoV-2 virus particle. In a mouse trial, two intramuscular immunizations of the VLP BacMam with no adjuvant elicited spike-specific binding antibodies in both sera and bronchoalveolar lavage fluids. Importantly, BacMam VLP -vaccinated mouse sera showed neutralization activity against SARS-CoV-2 spike pseudotyped lentivirus. Our results indicated that the SARS-CoV-2 VLP BacMam stimulated spike-specific immune responses with neutralization activity.

1. Background Septic shock is a rare and serious infectious disease. Patients surviving the early phase are at high risk of multiple amputations of limbs. They are potential sources of serious disability. 2. Methods The objective was to describe the functional prognosis and quality of life of the four-limb amputee patients following septic shock. This is a descriptive, retrospective and mono-centric study. The patients included between 2010 and 2019 had septic shock after 18 years, responsible for amputation of the four limbs. We studied the mean age of septic shock, the causative organisms, the infectious door enter, the different levels of amputation, the fitting process, the resumption of walking, the Functional Independence Measure (FIM) and the SF-12 Quality of Life Questionnaire. 3. Results We suceed to include 15 patients.. 53.3% women and 46.7% men with an average age of 46.1 years. 80% presented bilateral trans-tibial amputations, all were able to return walking even over short distances, within an average of 8.4 months. 40% did not require a technical walking aid, 33.3% had no walking perimeter limitation. 47% had a higher mental and social quality of life score than the general population. The younger the patients, the better their physical quality of life. After two years of follow-up, the younger the patients, the better their functional autonomy. Patients with better functional autonomy had a better physical quality of life. 4. Conclusion The number of amputations due to spetic shock is likely to increase in the years to come throughout the world. Our study prove that quadri-amputee patient can regain a fully acceptable functional and quality of life being monitored in a specialized health center with multidisciplinary health professional to help him.

The presence of the mite, Varroa destructor, requires the use of acaricide treatments in most honeybee colonies. Amitraz is one of the most common acaricide substances used by beekeepers. Some Varroa mite populations have developed resistance to amitraz leading to a loss of efficacy of amitraz-based treatments. Two products, Apivar and Supatraz were applied in the same apiary. Both treatments are amitraz-based but have a different galenics. Thanks to field data, a dynamic model was used to simulate the action of Apivar and Supatraz on the mite population. We consider two parameters to compare the products: daily mortality rate and treatment duration. In the field, the percentage of efficacy between the two products was not significantly different but Supatraz kills mite faster and decreases 90% of the mite infestation in 28.4 days compared to 50.9 days for Apivar. Thanks to modelling, we showed the daily impact of the two different products on mite population. Supatraz has a higher daily mortality rate during the first two weeks than Apivar. Supatraz requires a lower efficacy to stabilize the varroa mite population due to its faster release of active ingredient than Apivar, needing a shorter period to achieve the same result. Depending on the model, Supatraz conserve a good efficacy for low resistant mites but not for high resistant mites. These results show that the comparison of the efficacy of two products with different characteristics (duration of treatment and daily mortality rate) should be analyzed with caution.

Aerobic glycolysis in cancer cells, originally observed by Warburg 100 years ago, which involves production of lactate as the end product of glucose breakdown even in the presence of adequate oxygen, is the foundation for the current interest in cancer cell-specific reprograming of metabolic pathways. The renewed interest in cancer cell metabolism has now gone well beyond the original Warburg effect related to glycolysis to other metabolic pathways to include amino acid metabolism, one-carbon metabolism, pentose phosphate pathway, nucleotide synthesis, antioxidant machinery, etc. Since glucose and amino acids constitute the primary nutrients that fuel the altered metabolic pathways in cancer cells, the transporters that mediate the transfer of these nutrients and their metabolites not only across the plasma membrane but also across the mitochondrial and lysosomal membranes have become an integral component of expansion of the Warburg effect. In this review, we focus on the interplay between these transporters and metabolic pathways that facilitates the metabolic reprogramming which has become the hallmark of cancer cells. The beneficial outcome of this recent understanding of the unique metabolic signature surrounding the Warburg effect is the identification of novel drug targets for development of a new generation of therapeutics to treat cancer.

The lengthy maturation period is the key cause of the reduced hot pepper market value. An experiment was performed to assess the effects of R/B/W light qualities on reducing the maturation period. The maturation period was shortened by 16 days under 4R:1B:5W compared to the control. The appearance of the first flower is a limiting factor affecting the maturation period. It exhibited a dark purple color and an abnormal petal under 4R:1B:5W compared to the control, which was associated with increased contents of flavonoids, total organic acids, and phenolics and decreased total amino acid and carbohydrate contents. Plant hormone, flavonoid, ABC transporters, key metabolites (such as amino acid, carbohydrate, organic acid) was associated with first flower development. Ethylene response factors (ERFs) mediated by light, especially ERF021, were identified as potential hub regulators during the development of the first flower due to their involvement in all the associated metabolic pathways.

Wild-caught shrimp and prawns are the single most numerous group of animals directly killed for human food consumption on the planet. Recent scientific developments have led to greater understanding of the probability that at least some species of shrimp are sentient beings and, should that be the case, policies that could improve shrimp welfare. We begin with an overview of global shrimp fisheries and their characteristics. The world's shrimp fisheries can be understood as a spectrum between large, industrial trawlers in developed and developing countries (e.g. Western Europe, the Americas, Russia) and small-scale fisheries for subsistence in developing countries (e.g. South-East Asia, East Africa). Each has different implications for animal welfare, particularly in light of human wellbeing challenges associated with shrimp fisheries. Secondly, we turn to the emerging science of shrimp welfare and examine recent developments in government and industry policy. In large-scale trawl fisheries, animal welfare can be improved by installing electrical stunning equipment; continuing existing work on bycatch reduction; and optimising on-board processes to reduce the stress endured by shrimp during capture and slaughter. In small-scale fisheries, improving government capacity and supply chain practices may bring benefits for communities in the short-term while opening up opportunities for more specific shrimp welfare policies in the long-term. Thirdly, we provide a new dataset of the estimated numbers of individual shrimp caught by country and species. Drawing on this data, we provide a description of the shrimp fishing industry in the world's top 25 countries by estimated catch of individual shrimp. By our estimates, the wild-catch shrimp industry catches 37.4 trillion individual shrimp (36.3 trillion sergestids, 781 billion carideans, and 287 billion penaeids). Finally, we explore the ethical implications of the probability that shrimp and prawns are capable of feeling pain and the welfare policies that could be adopted.

This article examines air sampling as an environmental surveillance strategy for early pathogen detection and offers a preliminary comparison of air and wastewater surveillance. Air sampling involves collecting bioaerosols to analyze the microbial composition of the air, utilizing techniques like PCR and metagenomic sequencing. Air sampling appears especially promising for detecting respiratory pathogens and highly transmissible pandemic agents, as these spread primarily via aerosols and droplets. The article details various air sampling techniques, their efficiency, and practical considerations, categorizing them into filtration, impaction, impingement, electrostatic precipitation, and condensation methods. It also explores the composition of airborne microbes, emphasizing the low concentration of viral nucleic acids and the challenges this poses for metagenomic sequencing. The selection of sampling locations, including indoor environments and airplanes, is discussed as critical for effective pathogen detection. Finally, the article contrasts air and wastewater sampling, concluding that while both methods should ideally be explored as layered defenses, air sampling does not collectively appear more promising than wastewater sampling.

Watermelon fruits of different ploidy exhibit significant variations in texture. In order to investigate the primary factors influencing texture differences, this study was conducted to investigate the differences in fruit texture development using homozygous autogamous diploid (2X)lines and their autotriploid (3X) and autotetraploid (4X) lines 'Yixuan'. The research encompassed fruit development, flesh texture profile analysis (TPA), flesh cell wall polysaccharide content, and flesh cell microstructure analysis, specifically in 2X, 3X, and 4X watermelon fruits.The results showed that as watermelon fruits matured, several characteristics exhibited an ascending trend, including fruit weight, TSS (total soluble solids) content, rind hardness, flesh cell size, and cell wall polysaccharide contents such as crude fiber, cellulose, hemicellulose, lignin, and protopectin. Conversely, the flesh texture parameters and soluble pectin content of the flesh cell wall gradually declined. Notably, significant differences in fruit flesh texture and flesh cell structure were observed among fruits of different ploidy at the 32d. Specifically, 2X fruits displayed considerably lower rind hardness, reduced flesh texture (Hardness, Fracturability, Chewiness, Gumminess), and cell density compared to 3X and 4X fruits. Additionally, 2X fruits exhibited larger cell sizes than 3X and 4X fruits. However, no significant differences were observed in the content of flesh cell wall polysaccharide contents across various ploidy levels.These findings suggested that the variation in texture among watermelon fruits of different ploidy can be attributed to the size and arrangement of flesh cells. Importantly, this research provided a foundation for further exploration of the intrinsic regulatory factors and molecular mechanisms contributing to texture variation in polyploid watermelon fruits.

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). These two components of CI have historically been viewed as separate processes, but emerging research indicates that they share both distinctive and common pathways. Moreover, they exhibit intriguing intersections with mechanotransduction, a process that involves cells sensing and responding to mechanical forces. This review article describes the intricate interplay between mechanical forces and CI, shedding light on how these forces regulate CIL and CIP. Emphasis is placed on filamin A (FLNA)-mediated mechanotransduction, elucidating how FLNA senses mechanical forces and translates them into crucial biochemical signals that regulate cell locomotion and proliferation. In addition to FLNA, trans-acting factors (TAFs) emerge as sensitive players in both CI and the mechanotransduction process. This article presents methods for identifying these TAFs and profiling the associated changes in chromatin structure, offering valuable insights into CI and mechanotransduction regulation. Finally, it addresses unanswered research questions in these fields and delineates their possible future directions.

Silkworm ovary-derived BmN4 cells rely on chromatin-induced spindle assembly to form microtubule-based square mitotic spindles that ensure accurate segregation of holocentric chromosomes during cell division. The chromosome passenger protein Aurora B regulates chromosomal condensation and segregation, spindle assembly checkpoint, and cytokinesis; however, its role in holocentric organisms needs further clarification. This study examined the architecture and dynamics of spindle microtubules during prophase and metaphase in BmN4 cells and those with siRNA-mediated BmAurora B knockdown using immunofluorescence labelling. Anti-α-tubulin and anti-γ-tubulin antibodies revealed faint γ-tubulin signals co-localized with α-tubulin in early prophase during nuclear membrane rupture, which intensified as prophase progressed. At this stage, bright regions of α-tubulin around and on the nuclear membrane surrounding the chromatin suggested the start of microtubule assembling in the microtubule organizing centers (MTOCs). In metaphase, the number and size of γ-tubulin foci increased and were detected on both sides of the chromosomes. This resulted in a distinctive multipolar square spindle with holocentric chromosomes aligned at the metaphase plate. siRNA-mediated BmAurora B knockdown significantly reduced the γ-tubulin foci during prophase, impacting microtubule nucleation and spindle structure in metaphase. Spatiotemporal BmAurora B expression analysis provided new insights into the regulation of this mitotic kinase in silkworm larval gonads during gametogenesis. Our results suggest that BmAurora B is crucial for the formation of multipolar square spindles in holocentric insects, possibly through the activation of γ-tubulin ring complexes in multiple centrosome-like MTOCs.

Universal Stress Protein (USP) plays an important regulatory role in the response to abiotic stress. Most of the research related to USP so far has been conducted on plant models such as Arabidopsis, rice, and cotton. The potato is one of the four major food crops in the world. Therefore, it is of great significance to study the expression pattern of the potato StUSP gene family under abiotic stress conditions. In this study, a total of 108 USP genes were identified from the genome of the Atlantic potato, divided into four subgroups. And based on the genetic structure, the physical and chemical properties of proteins and other aspects of their biological characteristics are comprehensively analyzed. Collinear analysis showed that the homologous genes of StUSPs and four other representative species (Arabidopsis, rice, coyote tobacco, and tomato) were highly conserved. The cis-regulatory elements of the StUSPs promoter are involved in plant hormones, environmental stress, mechanical damage, and light response. RNA-seq analysis showed that under different abiotic stresses, there are differences in the expression patterns of members of each subgroup. WGCNA co-expression analysis of the central gene showed that the differential co-expression gene is mainly involved in the plant-pathogen response process, plant hormone signal transduction, and the biosynthesis process of secondary metabolites. Through qRT-PCR analysis, it was confirmed that StUSP13, StUSP14, StUSP15, and StUSP41 may be important candidate genes involved in the response to adversity stress in potatoes. The results of this study provide the basis for further research on the functional analysis of StUSPs in the potato response to adversity stress.

Epitranscriptomic RNA modifications play a crucial role in the posttranscriptional regulation of gene expression. N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic RNA and plays a pivotal role in RNA fate. RNA m6A modification is regulated by a group of cellular proteins, methyltransferases (writers) and demethylases (erasers), which add and remove the methyl group from adenosine, respectively. m6A modification is recognized by a group of cellular RNA-binding proteins (readers) that specifically bind to m6A-modified RNA, mediating effects on RNA stability, splicing, transport, and translation. The functional significance of m6A modification of viral and cellular RNA is an active area of virology research. In this review, we summarize and analyze current literature on m6A modification of HIV-1 RNA, the multifaceted functions of m6A in regulating HIV-1 replication, and the role of viral RNA m6A modification in evading the innate immune responses to infection. Furthermore, we briefly discuss future directions and therapeutic implications of mechanistic studies of HIV-1 epitranscriptomic modifications.

Genetic diversity is the foundation of evolutionary resilience, adaptive potential, and the flourishing vitality of living organisms, serving as the cornerstone for robust ecosystems and the continuous evolution of life on Earth. The landscape of directed evolution, a powerful biotechnological tool inspired by natural evolutionary processes, has undergone a transformative shift propelled by innovative strategies for generating genetic diversity. This shift is fuelled by several factors, encompassing the utilization of advanced toolkits like CRISPR-Cas and base editors, enhanced comprehension of biological mechanisms, cost-effective custom oligo pool synthesis, and the seamless integration of artificial intelligence and automation. This comprehensive review looks into the myriad methodologies employed for constructing gene libraries, both in vitro and in vivo, categorized into three major classes: random mutagenesis, focused mutagenesis, and DNA recombination. The objectives of this review are threefold: firstly, to present a panoramic overview of recent advances in genetic diversity creation, secondly, to inspire novel ideas for further innovation in the genetic diversity generation, and thirdly, to provide a valuable resource for individuals entering the field of directed evolution.

Heterosis plays a significant role in enhancing variety, boosting yield, and raising economic value, but the molecular mechanism is still unclear. We analyzed the transcriptomes and 3D genomes of hybrid (F1) and its parents (w30 and 082). Analysis of the expression revealed a total of 485 specially expressed genes (SEGs), 173 differentially expressed genes (DEGs) above parental expression level, more actively expressed genes and up-regulated DEGs in F1. Further study revealed that the DEGs detected in F1 and its parents were mainly involved in response to auxin, plant hormone signal transduction, DNA metabolic process, Purine metabolism, starch and sucrose metabolism, which suggested that these biological processes may play a crucial role in the heterosis of B. rapa. The analysis of 3D genome data revealed that hybrid F1 tend to contain more transcriptionally active A compartments after hybridization. Additionally, F1 had a smaller TAD (topologically associated domain) genome length, but the number was the highest, and the expression change of activated TAD was higher than repressed TAD. More specific TAD boundaries were detected between parents and F1. Subsequently, 140 DEGs with genomic structural variants were selected as potential candidate genes. Among them, we found two DEGs with consistent expression changes in A/B compartments and TADs. Our findings suggest that genomic structural variants, such as TADs and A/B compartments, may affect gene expression and contribute to heterosis in B. rapa. This study provides further insight into the molecular mechanism of heterosis in B. rapa.

Neurodegeneration is becoming one of the leading causes of death worldwide as the population expands and grows older. There is a growing desire to understand the mechanisms behind prion proteins as well as the prion-like proteins that make up neurodegenerative diseases (NDs) including Alzheimer’s Disease (AD). Both amyloid β (Aβ) and hyperphosphorylated tau (p-tau) proteins behave in ways similar to that of the infectious form of the prion protein, PrPSc, such as aggregating, seeding, and replicating under not yet fully understood mechanisms, thus the designation of prion-like. This review aims to highlight the shared mechanisms between prion-like proteins and prion proteins in the structural variations associated with aggregation and disease development. These mechanisms are largely focusing on the dysregulation of protein homeostasis, self-replication, and protein aggregation, and how this knowledge could contribute to diagnoses and treatments for the given NDs.

This review centers on the pivotal role of the oncoprotein FOSL1, within the dimeric AP-1 transcription factor consisting of FOS-related elements. FOSL1 emerges as a key regulator governing invasion and metastatic dissemination, therefore making it a promising target for therapeutic intervention in cancer patients. The review provides a comprehensive survey of the regulatory mechanisms that exert influence over FOSL1. These encompass a spectrum of transcriptional and post-translational modifications. Notably, we unveiled the intricate involvement of diverse non-coding RNAs, specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in the modulation of FOSL1 expression through targeted interactions with its mRNA transcripts. Furthermore, an exploration into the functional dimensions of FOSL1 unfolds, encompassing apoptosis, proliferation, and migration. This investigation is accompanied by a thorough examination of the elaborate signaling pathways that underpin these multifaced roles. Additionally, emphasis is placed on the role of FOSL1 in orchestrating the stimulation of various cytokines, including TGF-beta, and the initiation of IL-6 and VEGF production in tumor-associated macrophages (TAMs) that transverse into the tumor microenvironment. A distinct focus is dedicated to appraising the prognostic implications associated with FOSL1. Finally, insights emerge into the evolving roles of FOSL1 in the context of mechanisms governing resistance and dependency on targeted therapeutic modalities.

Open-source devices are nowadays used in a vast number of research fields like medicine, education, agriculture, and sports among others. In this work, an open-source, portable, low cost pH logger, appropriate for in situ meas-urements was designed and developed to assist in experiments on agricultural produce manufacturing. Τhe device was calibrated manually using pH buffers for values of 4.01 and 7.01. Then it was tested by manually measuring pH from the juice of citrus fruits. A waterproof temperature sensor was added to the device for temperature compen-sation when measuring pH. A formal method comparison process between the open-source device and a Hanna HI9024 Waterproof pH Meter was designed to assess their agreement. We derived indices of agreement and graph-ical assessment tools using mixed-effects models. Advantages and disadvantages for interpreting agreement through the proposed procedure are discussed. In our illustration, indices reported mediocre agreement and the subsequent similarity analysis revealed a fixed bias of 0.22 pH units. After recalibration, agreement between the devices im-proved to excellent levels. The process can be followed in general to avoid misleading or over-simplistic results of studies reporting solely correlation coefficients for formal comparison purposes.

Honey has been employed for the treatment of wounds and diseases for ancient time, thanks to its antimicrobial and curative properties. This study aims to present the biochemical characteristics, including the amount of sugar, total phenols, phenolic chemicals, antioxidant properties, and antibacterial activities of a specific type of French honey (Sologne summer forest) in comparison with a manuka honey. According to our findings, the Manuka honey tested has 23% fewer polyphenols total than Sologne summer forest honey. The results showed that the Sologne summer honey had a different polyphenols profile than Manuka honey with specific polyphenol like p- Hydroxybenzoic acid. Additionally, the antioxidant activity of the two honeys is comparable (9 μmole Trolox.g-1 honey). Furthermore, the antibacterial activity of the two honeys is comparable against Pseudomonas aeruginosa and Staphylococcus aureus. Our research indicates for the first time that there are significant nutritional and biological potentials for a French honey from the Sologne summer forest.

Viruses rely on host cells to replicate their genomes and assemble new viral particles. Thus, they have evolved intricate mechanisms to exploit host factors. Host cells, in turn, have developed strategies to inhibit viruses, resulting in a nuanced interplay of co-evolution between virus and host. This dynamic often involves competition for resources crucial for both host cell survival and virus replication. Iron and iron-containing cofactors, including iron-sulfur clusters, are known to be a heavily battled resource during bacterial infections where control over iron can tug the war in favor of the pathogen or the host. It is logical to assume that viruses also engage in this competition. Surprisingly, our knowledge about how viruses utilize iron (Fe) and iron-sulfur (FeS) clusters remains limited. The handful of reviews on this topic primarily emphasize the significance of iron in supporting the host immune response against viral infections. The aim of this review, however, is to organize our current understanding of how viral proteins utilize FeS clusters, to give perspectives on what questions to ask next and to propose important avenues for future investigations.

The impact of long-term soil and crop management practices on soil biological and chemical properties in oilseed brassica-based production systems were deliberated for holistic soil health improvement in the present study. Different tillage, crop residue re-cycling and cropping systems were studied for 5-years in 0-15 and 15-30 cm soil profiles. No-till permanent beds with crop residue (PB+R) noticeably improved soil organic carbon (SOC), microbial biomass carbon (MBC), enzymes [dehydrogenase (DHA) and alkaline phosphatase (AlP)], nitrogen fractions (available, nitrate and total), and available phosphorus and potassium content in both the soil layers compared to conventional tillage without crop residues. Though, the plow soil layer (0-15 cm) showed higher concentration of soil carbon, enzymes, N fractions and available P than in the sub soil (15-30 cm). The dynamic soil biological and chemical properties were also varied with the crop stage, and recorded higher MBC at 30 days, SOC and enzymatic activities at 60 days, and N fractions and available P and K at harvest of mustard crop. Green gram-mustard rotation showed higher values of biological and chemical parameters. Thus, the legume-based mustard crop rotation following no-till permanent beds and residue re-cycling found holistic in improving soil health, and nutrient cycling.

Dystonias, characterized by excessive muscle contractions resulting in involuntary postures and movements, impact 3 million people globally, making them the third most common movement disorder. Often accompanied by tremors, dystonias have epidemiological links and non-motor features shared with isolated tremor, such as essential tremor. Both dystonia and tremor present with balance dysfunction and abnormal involuntary movements, potentially linked to abnormal cerebellar function. This study explores the perception of one’s own linear movement, heading, particularly discrimination of heading direction, in isolated cervical dystonia, isolated tremor, and their combination. The focus is on the perception of heading direction during isolated visual star-cloud movement (visual heading perception) and en bloc body movement (vestibular heading perception). Nineteen participants underwent a two-alternative forced-choice task in the vestibular and visual domains. Results reveal elevated vestibular heading perception thresholds in cervical dystonia with or without tremor, and isolated tremor compared to healthy controls. Vestibular heading perception threshold was comparable in cervical dystonia with tremor and isolated tremor, but it was even worse in isolated cervical dystonia. Visual heading perception, however, remained less affected all three conditions – isolated cervical dystonia, isolated tremor, and their combination. These findings indicate shared deficits and distinctions in the perception of linear translational heading across movement disorders, such as isolated cervical dystonia, tremor, or their combination, offering insights into their pathophysiology, particularly the involvement of cerebellum regions responsible for vestibular processing.

As an essential component of our innate immune system, the complement system is responsible for our defense against pathogens. The complement cascade has complex roles in the central nervous system (CNS), most of what we know about it stems from its role in brain development. However, in recent years, numerous reports have implicated the classical complement cascade in both brain development and decline. More specifically, complement dysfunction has been implicated in neurodegenerative disorders, such as Alzheimer’s disease (AD), which is the most common form of dementia. Synapse loss is one of the main pathological hallmarks of AD and correlates with memory impairment. Throughout the course of AD progression, synapses are tagged with complement proteins and are consequently removed by microglia which express complement receptors. Notably, astrocytes are also capable of secreting signals that induce the expression of complement proteins in the CNS. Both astrocytes and microglia are implicated in neuroinflammation, another hallmark of AD pathogenesis. In this review, we provide an overview of previously known and newly established roles for the complement cascade in the CNS and we explore how complement interactions with microglia, astrocytes, and other risk factors such as TREM2 and ApoE4, modulate the processes of neurodegeneration in both amyloid and tau models of AD.

Peanut leaf spot is a worldwide disease whose prevalence poses a major threat to peanut yield and quality, and accurate prediction models are urgently needed for timely disease management. In this study, we proposed a novel peanut leaf spot prediction method based on an improved long short-term memory (LSTM) model and multi-year meteorological data combined with disease survey records. Our method employed a combination of convolutional neural network (CNN) and LSTM to capture spatial-temporal patterns from the data and improve the model ability to recognize dynamic features of the disease. In addition, we introduced an attention mechanism module to enhance model performance by focusing on key features. Through several hyper-parameter optimization adjustments, we identified a peanut leaf spot disease condition index prediction model with a learning rate of 0.001, a number of cycles (Epochs) of 800, and an optimizer of Adma. The results showed that the integrated model demonstrated excellent prediction ability, obtaining an RMSE of 0.063 and an R2 of 0.951, which reduced the RMSE by 0.253 and 0.204, and raised the R2 by 0.155 and 0.122, respectively, compared to the single CNN and LSTM. Predicting the incidence and severity of peanut leaf spot disease based on the meteorological conditions and neural networks is feasible and valuable to help growers made accurate management decisions and reduced disease impacts through optimal fungicide application timing.

MicroRNAs (miRNAs) play a pivotal role in important biological processes by regulating posttranscriptional gene expression and exhibit differential expression patterns during development, immune responses, and stress challenges. The diamondback moth causes significant economic damage to crops worldwide. Despite substantial advancements in understanding the molecular biology of this pest, our knowledge regarding the role of miRNAs in regulating key immunity-related genes remains limited. In this study, we leveraged whole transcriptome resequencing data from P. xylostella infected with Metarhizium anisopliae to identify specific miRNAs targeting the prophenoloxidase-activating protease1 (PAP1) gene through bioinformatic analysis. Seven miRNAs (pxy-miR-375-5p, pxy-miR-4448-3p, pxy-miR-279a-3p, pxy-miR-3286-3p, pxy-miR-965-5p, pxy-miR-8799-3p and pxy-miR-14b-5p) were identified and validated. Luciferase reporter assays confirmed that pxy-miR-279a-3p binds to the open reading frame (ORF) and pxy-miR-965-5p to the 3’ untranslated region (3’ UTR) of PAP1. Our experiments demonstrated that injecting a pxy-miR-965-5p mimic significantly reduced PAP1 expression in P. xylostella larvae, suppressing PO activity and increasing larval mortality rate. Conversely, the injection of inhibitors obtained opposite results. Furthermore, we identified four LncRNAs (MSTRG.32910.1, MSTRG.7100.1, MSTRG.6802.1, and MSTRG.22113.1) that potentially interact with pxy-miR-965-5p. Interference assays using antisense oligonucleotides (ASO) revealed that silencing MSTRG.7100.1 and MSTRG.22113.1 increased the expression of pxy-miR-965-5p. These findings shed light on the potential role of pxy-miR-965-5p in the immune response of P. xylostella to M. anisopliae infection and provide a theoretical basis for biological control strategies targeting the immune system of this pest.

Thoracic aortic aneurysm (TAA) has a prevalence of 0.16%-0.34% and an incidence of 7.6 per 100,000 person-years, accounting for 1%-2% of all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development and prevent TAA rupture. Large TAAs are treated with open surgical repair and less invasive thoracic endovascular aortic repair, both of which have high perioperative mortality risk. Therefore, there is an urgent medical need to identify the cellular and molecular mechanisms underlying TAA development and rupture to develop new therapies. In this review, we summarize animal TAA models including recent developments in porcine and zebrafish models: porcine models can assess new therapeutic devices or intervention strategies in a large mammal and zebrafish models can employ large-scale small-molecule suppressor screening in microwells. The second part of the review covers current views of TAA pathogenesis, with a focus on the roles of the transforming growth factor-beta (TGFβ) pathway and the vascular smooth muscle cell (VSMC)-elastin-contractile unit. The last part discusses TAA treatment options as they emerge from recent preclinical studies.

O26 enteropathogenic Escherichia coli (EPEC), possesses a unique pseudocapsule composed of polysaccharides identical to the O antigen in their lipopolysaccharide (LPS) membrane. Therefore, the impact of O26 polysaccharides on the immune evasion mechanisms of capsulated O26 EPEC was investigated. Our findings reveal that the concentration of GlcNAc, an immunodominant unit of O26 polysaccharides capable of activating the MBL (Mannose Biding Lecting) pathway of the complement system, was found to be lower in capsulated EPEC O26 compared to naked shiga toxin-producing E. coli (STEC) O26 strain. It was noted that, unlike the naked STEC strain, the capsulated EPEC O26 strain was protected against lysis by the alternative pathway of the com-plement system by inhibiting C3b adhesion to its bacterial surface. Capsulated EPEC O26 strains were also able to avoid phagocytosis by macrophages. However, the immune evasion provided by the capsule was overcome in the presence of anti-O26 polysaccharide antibodies. Additionally, these antibodies were able to recognize O26 EPEC in the presence of biofilm and inhibit their adhesion to human epithelial cells. Overall, the results indicate that the O26 polysaccharides can generate an effective humoral immune response, making them promising antigens for the de-velopment of a vaccine against capsulated O26 E. coli

This study conducted an extensive analysis of campylobacteriosis surveillance in Portugal from 2009 to 2021, aiming to investigate demographic shifts, seasonal variations, and antimicrobial resistance (AMR) within Campylobacter isolates. Surveillance network and sentinel laboratory-based system data revealed a substantial under-notification of campylobacteriosis cases, suggesting an underestimated disease burden. A paradigm shift was observed in notification rates, with a notable prevalence among the pediatric population, particularly in children aged 1-4 years, diverging from European reports. However, the study also highlighted an emerging trend of Campylobacter infections in younger adults (15-44 years). The study unveiled a unique seasonal distribution of cases, defying typical summer peaks seen elsewhere. AMR analysis revealed extremely to very high-level resistance to ciprofloxacin and tetracycline, both in C. jejuni (93.7% and 79.2%, respectively) and in C. coli (96.5% and 93.2%, respectively), stable throughout the studied period (2013-2021). C. coli also exhibited significantly higher resistance to erythromycin, gentamicin, ampicillin, amoxicillin-clavulanic acid (decreased resistance), and ertapenem compared to C. jejuni (P<0.001). In conclusion, the study highlights the need for enhanced surveillance efforts and emphasizes worrying AMR levels. The implementation of WGS-based surveillance is recommended to attain a more profound comprehension of disease patterns and the evolving landscape of AMR.

The differentiation of ESCs into cardiomyocytes in vitro is an excellent and reliable model system for studying normal cardiomyocyte development in mammals, modeling cardiac diseases, and for use in drug screening. Mouse ESC differentiation still provides relevant biological information about cardiac development. However, the current methods for efficiently differentiating ESCs into cardiomyocytes are limiting. Here, we describe a “WNT Switch” method to efficiently commit mouse ESCs into cardiomyocytes using the small molecule WNT signaling modulators CHIR99021 and XAV939 in vitro. This method significantly improves the yield of beating cardiomyocytes, reduces number of treatments, and is less laborious.

Sleep disorders are a frequent problem in pediatrics. The prevalence is variable (from 15 to 50%) although the majority of papers coincide in that 1 every 3 kids can experiment some kind of sleep disorder. Underlying medical problems usually manifest by difficulty to fall asleep or stay asleep. The diagnosis and resolution of the medical problems with the specific treatment should be the prime concern, before starting with the treatment of the sleep behavioral problem

Abstract This study focuses on the toxicity assessment of various flavonoids, with particular emphasis on Hesperidin. Among the investigated compounds, Hesperidin exhibits notable potential and low toxicity in both short and long-term evaluations. The toxicity parameters for Hesperidin include a low Max. Tolerated Dose (Human) (0.525 log mg/kg/day), indicative of its minimal potential harm to humans. Additionally, its Oral Rat Acute Toxicity (LD50) (2.506 mol/kg) suggests a relatively low acute toxicity level. The Oral Rat Chronic Toxicity (LOAEL) (3.167 log mg/kg_bw/day) signifies a higher dose threshold for observing adverse effects over the long term. Furthermore, Hesperidin demonstrates low Minnow Toxicity (7.131 log mM), suggesting minimal impact on aquatic organisms. Overall, this comprehensive assessment positions Hesperidin as a promising flavonoid with favorable properties and minimal toxicity.

Ras homolog enriched in brain (Rheb1 and Rheb2), a small GTPase, regulates neuronal activity and has drawn attention for its implications in cancer development, especially breast cancer. This study explores the multifaceted role of Rheb1 in cancer, elucidating its involvement in crucial cel-lular processes such as proliferation, apoptosis resistance, migration, invasion, metastasis, and inflammatory responses. Despite these acknowledged connections, a comprehensive understanding of the intricate interplay between Rheb1 and cancer remains elusive. This review consolidates cur-rent knowledge on the impact of Rheb1 on cancer hallmarks and examines the potential of Rheb1 as a therapeutic target in cancer treatment. The review underscores the need for a more profound comprehension of the molecular mechanisms underlying Rheb1-mediated oncogenic processes. Furthermore, the review emphasizes the exploration of Rheb1 inhibitors as a promising avenue for cancer therapy. This study, by bringing to light the complex associations between Rheb1/Rheb2 and cancer, delivers valuable insights to the scientific community. These insights are instrumental in guiding the identification of novel targets and advancing the development of effective therapeu-tic strategies for treating cancer.

Annelids are well-known for their ability to regenerate. The morphological development in terms of regeneration physiology, involves several cellular factors which play crucial roles in the developmental phenomena. The physiological process of regeneration involves critical biomechanical processes which is effectively regulated by the cellular factors. In today’s biological research, the fundamental analysis of regeneration is necessary for the scientific assessment of cellular-biomechanical advancements, which eventually helps to develop adequate insight in the biomedical research in regenerative sciences. In this review we have elucidated the recent research on explaining the developmental physiology of regeneration in annelids.

Lodging poses a significant challenge to rice yield, prompting the need to identify elite alleles for lodging resistance traits to improve cultivated rice varieties. In this study, a natural population of 518 rice accessions was examined to identify elite alleles associated with plant height (PH), stem diameter (SD), stem anti-thrust (AT/S), and various internode lengths: (first (FirINL), second (SecINL), third (ThirINL), fourth (ForINL), and fifth (FifINL) internode lengths). 262 SSR markers linked to these traits were uncovered through association mapping in two environmental conditions. Phenotypic evaluations revealed striking differences among cultivars, and genetic diversity assessments showed polymorphisms across the accessions. Favorable alleles were identified for PH, SD, AT/S, and 1 to 5 internode lengths, with specific alleles displaying considerable effects. Noteworthy alleles include RM6811-160 bp on chromosome 6 (which reduces PH) and RM161-145 bp on chromosome 5 (which increases SD). The study identified a total of 42 novel QTLs. Specifically, seven QTLs were identified for PH, four for SD, five for AT/S, five for FirINL, six for SecINL, five for ThirINL, six for ForINL, and four for FifINL. QTLs qAT/S-2, qPH2.1, qForINL2.1, and qFifINL exhibited the most significant phenotypic variance (PVE) of 3.99% for the stem lodging trait. AT/S, PH, ForINL and FifINL had additive effects of 5.31 kPa, 5.42 cm, 4.27cm and 4.27cm, respectively, offering insights into eight distinct cross-combinations for enhancing each trait. This research suggests the potential for cross-breeding superior parents based on stacked alleles, promising improved rice cultivars with enhanced lodging resistance to meet market demands.

Extracellular vesicles (EVs) are lipid bilayer envelopes that encapsulate cell-specific cargo, rendering them promising biomarkers for diverse diseases. Chagas disease, caused by the parasite Trypanosoma cruzi, poses a significant global health burden, transcending its initial epicenter in Latin America to affect individuals in Europe, Asia, and North America. In this study, we aimed to characterize circulating EVs derived from patients with chronic Chagas disease (CCD) experiencing reactivation of acute symptoms. Blood samples collected in EDTA were processed to isolate plasma and subsequently subjected to ultracentrifugation for particle isolation and purification. The EVs were characterized using nanoparticle tracking analysis and enzyme-linked immunosorbent assay (ELISA). Our findings revealed distinctive differences in size, concentration, and composition of EVs between immunosuppressed patients and those with CCD. Importantly, these EVs play a critical role in the pathophysiology of Chagas disease and demonstrate significant potential as biomarkers in the chronic phase of the disease. Overall, our findings support the potential utility of the CL-ELISA assay as a specific sensitive tool for detecting circulating EVs in chronic chagasic patients, particularly those with recurrent infection following immunosuppressive treatment or with concurrent HIV and Chagas disease. Further investigations are warranted to identify and validate the specific antigens or biomarkers responsible for the observed reactivity in these patient groups, which may have implications for diagnosis, monitoring of treatment and prognosis.

The study of paraneoplastic syndromes in humans has a long history, whereas for domestic animals – only since the beginning of the 21^th century. There are various forms of paraneoplastic syndromes; many classifications based on pathogenetic, organ-system principles are described. In accordance with the modern classification, paraneoplastic syndromes are divided into endocrinopathies, hematological paraneoplastic syndromes, gastrointestinal, renal, dermatological, neurological, ophthalmological. The purpose of this study was to develop a scientifically based algorithm for diagnosing ophthalmopathies against the background of paraneoplastic syndrome in dogs, including a multifactorial system of “hormonal-drug treatment” of paraneoplastic ophthalmopathies. The work used a comprehensive methodological approach, including the collection of anamnestic data, clinical examination of the animal, examination of the area of the pathological process, hematological studies, cytomorphological studies, visual diagnostic methods with complete oncological and ophthalmological examinations using the necessary equipment. Treatment for cancer included surgical removal of the tumor, chemotherapy and radiotherapy. The choice of treatment protocol depended on the location of the disease, tumor phenotype (if present) and stage of the malignancy. The only chemotherapy was applied using complex protocols in the treatment of dog lymphomas. Treatment of melanoma in dogs was carried out using an integrated approach which combined methods of surgery, chemotherapy, and radiotherapy. The obtained results can be recommended for use in the diagnosis and treatment of paraneoplastic ophthalmopathies in dogs.

The Qinghai-Tibetan Plateau area (QTPA) features a unique environment that has witnessed the selective breeding of diverse breeds of domestic livestock, exhibiting remarkable adaptability. Nevertheless, Anaplasma spp., Rickettsia spp., Coxiella spp., and Borrelia spp. represent tick-borne bacterial pathogens that pose a global threat and have substantial impacts on both human and animal health, as well as on the economy of animal husbandry within the Qinghai-Tibetan plateau area. In this study, a total of 428 samples were systematically collected from 20 distinct areas within the Qinghai plateau. The samples included 62 ticks and 366 blood samples obtained from diverse animal species, to detect the presence of Anaplasma spp., Rickettsia spp., Coxiella spp., and Borrelia spp. The prevalence of infection in this study was determined as follows: Anaplasma bovis accounted for 16.4% (70/428), A. capra for 4.7% (20/428), A. ovis for 5.8% (25/428), Borrelia burgdorferi sensu lato for 6.3% (27/428), Coxiella burnetii for 0.7% (3/428), and Rickettsia spp. for 0.5% (2/428). Notably, no cases of A. marginale and A. phagocytophilum infections were observed in this study. The findings revealed an elevated presence of these pathogens in Tibetan sheep and goats, with no infections detected in yaks, Bactrian camels, donkeys, and horses. To the best of our knowledge, this study represents the first investigation of tick-borne bacterial pathogens infecting goats, cattle, horses, and donkeys within the Qinghai plateau of the Qinghai-Tibetan Plateau Area. Consequently, our findings contribute valuable insights into the distribution and genetic diversity of Anaplasma spp., Rickettsia spp., Coxiella spp., and Borrelia spp. within China.

Fresh-cut apple is commonly known as minimally processed agriculture products because of their convenience and ease of consumption. However, during storage, the quality of the apple rapidly changes after the cutting process due to enzymatic and non-enzymatic processes. This study aimed to monitor the quality changes of fresh-cut apples at various temperatures and different types of products in the application of a cold chain system during distribution and storage. The results showed that the total viable count in fresh-cut apples initially differed between apple only and mixed products (apple, orange, and tomato) during storage (p < 0.05). Moreover, there are no significant differences (p > 0.05) in physicochemicals except firmness, titratable acidity, and pH, which are highly correlated to microbial growth (total viable count and total coliform number). Furthermore, the optimal temperature for extending the shelf-life of fresh-cut apples was at 4°C.

The consumption of foods with fiber and phenolic compounds can be part of treating obesity through interaction with the gastrointestinal tract. Treatment with common bean leaves (BL) for obesity was evaluated in mice on a high-fat, high-fructose diet (HFFD). The proximal and phytochemical characterization of BL was determined. Obesity was induced with a HFFD for 14 weeks. Immediately after, the animals were supplemented with BL (10%) or standard diet (SD) as a strategy to seem a healthy diet (12 additional weeks). Changes in body composi-tion, lipid profile, and intestinal integrity were analyzed. BL contained 27.2% dietary fiber, total phenolics (475.04 mg/100 g), and saponins (2.2 mg/100 g). The VAT consumption of the BL group decreased by 52% compared to the HFFD group. Additionally, triglyceride concentrations were 23% lower in the BL consumption group compared to the HFFD group. The improvement in lipid profile was attributed to the (1.77-fold) higher fecal lipid excretion in the BL consumption group compared to the HFFD group. Likewise, pancreatic lipase decreased by 29%. Furthermore, BL supplementation reduced the level of IL-6 (4.4-fold) and FITC-dextran in serum by 50% compared with that in the HFFD group. Metabolic endotoxemia was inhibited after BL supplementation (-33%) compared to the HFFD group. BL consumption as a treatment in obese mice reduces adipose tissue accumulation and improves the lipid profile. Furthermore, we report for the first time that BL consumption improves intestinal integrity.

In recent years, the emergence of cancer drug resistance is one of the crucial tumor hallmarks which is supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters and stemness are among the several key contributing molecular and cellular response mechanisms. Topo-active drugs, e.g., doxorubicin and topotecan, are clinically active and are utilized extensively against a wide variety of human tumors and often results in the development of resistance and failure to therapy. Thus, there is an urgent need for an incremental and comprehensive understanding of mechanisms of cancer drug resistance specifically in the context of topo-active drugs. This review delves into the intricate mechanistic aspects of these intracellular and extracellular topo-active drug resistance mechanisms and explores use of potential combinatorial approaches by utilizing various topo-active drugs and inhibitors of pathways involved in drug resistance. We believe that this review will help guide basic scientists, pre-clinicians, clinicians, and policymakers toward holistic and interdisciplinary strategies that transcend resistance, renewing optimism in the ongoing battle against cancer.

Glioblastoma (GB), even though not frequent, is an extremely aggressive brain tumor, with a strong impact on patient outcomes, in terms of both length and quality of life. The protocol estab-lished by Stupp and coworkers in 2005, based on radiotherapy and temozolomide chemotherapy, after maximum safe surgical resection, remains the gold standard for GB treatment. However, it is evident nowadays that the extreme GB intratumoral and intertumoral heterogeneity, invasive-ness and recurrence are not compatible with a routinary and unfortunately uneffective treatment. In this review article, we summarize the principal challenging issues in finding new valuable therapies for GB and focus on the impact that extracellular vesicle (EV) research and exploitation can have in the field. EVs are natural particles delimited by a lipidic bilayer and full of functional cellular content, released and uptaken by cells as key means of cell communications. Moreover, being stable in body fluids, well-immunotolerated, able to cross physiological, inter-species, and inter-kingdom barriers, and to target specific cells, releasing inherent or externally loaded functionally active molecules, EVs can be potentially ideal allies in fighting GB and assuring to GB patients a better prognosis. Here we report the main results obtained until now, focusing on both EV sources and molecular cargo used in the different functional studies, mainly in vivo. Finally, we perform a SWOT analysis reporting both the main advantages and the pitfalls of developing EV-based GB therapeutic strategies to highlight the main directions to explore for realizing the promise of EV exploitation for GB treatment.

Peptide/Histidine Transporter PHT1 (SLC15A4) is expressed in lysosomal membranes of immune cells where it plays an important role in metabolic and inflammatory signaling. PHT1 is an H+-coupled/histidine symporter that can transport a broad range of oligopeptides, including a variety of bacterial-derived peptides. Moreover, it enables the scaffolding of various metabolic signaling molecules and interacts with key regulatory elements of the immune response. Therefore, it is not surprising that PHT1 is associated with the development of autoimmune diseases, such as systemic lupus erythematosus (SLE). Unfortunately, the pharmacological development of PHT1 has been hampered by the lack of appropriate transport assays. With the aim to address this shortcoming, a novel transport assay based on solid supported membrane-based electrophysiology (SSME) is presented. Key findings of the present SSME studies include the first recordings of electrophysiological properties, a pH dependence analysis, an assessment of PHT1 substrate selectivity, as well as the transport kinetics of the identified substrates. In contrast to previous works, PHT1 is studied its native lysosomal environment. Moreover, observed substrate selectivity is validated by molecular docking. Overall, this new SSME-based assay is expected to contribute to unlock the pharmacological potential of PHT1 and to deepen the understanding of its functional properties.

Background: Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine-controlled and uncontrolled hemorrhagic shock (HS) model. Methods: Anesthetized female swine underwent controlled hemorrhage (22 ml/kg) and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven® resuscitation. Blood chemistry, physiologic variables, systemic and tissue levels of complement proteins and cytokines, coagulation parameters, organ function, and damage were recorded and assessed. Results: HS resulted in systemic and local complement activation, cytokine release, metabolic acidosis, hyperkalemia, MOF, and no animal survival. Resuscitation with LR and Voluven® after HS improved hemodynamic parameters (MAP and SI), metabolic acidosis, hyperkalemia, and survival but resulted in increased complement activation and worse coagulopathy. Compared with the LR group, the HS animal treated with Voluven® had worse dilutional anemia, coagulopathy, renal and hepatic dysfunction, increased myocardial complement activation and renal damage, and decreased survival rate. Conclusions: Hemorrhagic shock triggers early immunopathy and coagulopathy that appear associated with MOF and death. This study indicates that immunopathy and coagulopathy are therapeutic targets that may be addressed with a high-impact adjunctive treatment to conventional resuscitation.

This review explores the potential of microalgae as a sustainable and nutritionally rich alternative for mineral supplementation in poultry diets, addressing both the opportunities and challenges in this emerging field. Poultry nutrition, pivotal to the health and productivity of birds, traditionally relies on inorganic and organic mineral sources, which, while effective, raise environmental and economic concerns. Microalgae offer a promising solution with their high content of essential minerals, proteins, vitamins, and bioactive compounds. The review delves into the nutritional profile of various microalgae, highlighting their rich mineral content, crucial for physiological processes in poultry. It examines the bioavailability of these minerals and their impact on poultry health and productivity. Furthermore, it evaluates the environmental sustainability of microalgae cultivation and acknowledges the challenges in using microalgae in poultry diets, particularly in terms of the economic viability of large-scale production and the consistency of nutrient composition. It discusses the importance of rigorous safety assessments and regulatory compliance, given the potential risks of toxins and heavy metals. Overall, this analysis aims to provide a clear understanding of the role microalgae could play in poultry nutrition and address sustainability challenges in animal agriculture, while also considering future perspectives and advancements needed in this field.

We present the first evidence of lethal interspecific aggressive behavior against Burmeister’s porpoise Phocoena spinipinnis, in a non-predatory context, and the first indications of such behavior in a cetacean from Chilean waters. Two cases, both adult males, are described. Analysis of the fresh tooth rakes, specifically the inter-rake distance, points to common bottlenose dolphin Tursiops truncatus as aggressor. Interdental distances measured on skulls allowed us to exclude Orcinus orca, Globicephala melas, Lagenorhynchus obscurus and Pseudorca crassidens. Evidence of severe blunt trauma, including extensive subdermal hematomas, rupture of pleura and extrusion of lung parenchyma, underscores the level of violent aggression. The reason is unknown but Tursiops truncatus is well-documented to occasionally harass and kill harbour porpoises Phocoena phocoena in the Northern Hemisphere. Considering the scarce information available on the biology and behavioral ecology of Burmeister’s porpoises in Chile and elsewhere, we recommend more systematic field research. Also, as to help formulate effective management measures that can mitigate the main threat for this species in Chile (as in Peru), i.e. fisheries interactions. In Chile, P. spinipinnis is classified as Data Deficient (D.S. N°06-2017), so its real conservation status is unknown.

Background: Although cerebral aneurysm (CA) is a defining complication of COL4A1/2-related vasculopathy, the specific factors influencing its onset remain uncertain. This study aimed to identify and analyze these factors. Methods: We described a family presenting with a novel variant in the COL4A1 gene complicated with CA. Concurrently, an exhaustive review of previously documented patients with COL4A1/2-related vasculopathy was conducted by sourcing data from PubMed, Web of Science, Google Scholar, and Ichushi databases. We compared the variant types and locations between patients with CA (positive group) and those without CA (negative group). Results: This investigation encompassed 53 COL4A1/2 variants in 76 patients. Except for one start codon variant, all the identified variants in CA were missense variants. Otherwise, CA was not associated with other clinical manifestations, such as small-vessel disease or other large-vessel abnormalities. A higher frequency of missense variants (95.5% vs 58.1%, p = 0.0035) was identified in the CA positive group. Conclusions: CA development appears to necessitate qualitative alterations in COL4A1/2, and the underlying mechanism seems independent of small vessel disease or other large vessel anomalies. Our findings suggest that a meticulous evaluation of CA is necessary when missense variants in COL4A1/2 are identified.

One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood–brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ42 containing isomerized Asp7 residue (iso-Aβ42) and Aβ42 containing phosphorylated Ser8 residue crossed the BBB better than unmodified Aβ42, which correlated with different contribution of endocytosis mechanisms to the transport of these isoforms. Using microscale thermophoresis, we observed that RAGE binds to iso-Aβ42 an order of magnitude weaker than to Aβ42. Thus, post-translational modifications of Aβ increase the rate of its transport across the BBB and modify the mechanisms of the transport, which may be important for AD pathology and treatment.

The mechanism of brain information processing unfolds within spatial and temporal domains inherently linked to the concept of symmetry. Biological evolution, beginning with the prevalent molecular chirality, results in the handedness of cognitive and psychological functions (the phenomena known as biochirality). The key element in the chain of chirality transfer from the downstream to upstream processes is the pyramidal neuron (PyrN) morphology-function paradigm (archetype). The most apparent landmark of PyrN is the geometry of the cell soma. However, “why/how PyrN soma gains the shape of quasi-tetrahedral symmetry” has never been explicitly articulated. Resolving the above inquiry is only possible based on the broad-view assumption that encoding 3D-space requires specific 3D-geometry of the neuronal detector and corresponding network. Accordingly, our hypothesis states that if the primary function of PyrNs, at the organism level, is sensory space perception, then the pyramidal shape of soma is the best evolutionary-selected geometry to support sensory-motor coupling.

Knowing that biomolecules, such as β-amyrin and α-amyrin, have some pharmacological effects, the aim of this study was directed towards exploring the protective effect of a Tomato Peel and Seed Extract (TPSE) for its soothing function but also for its capacity to modulate the adrenal axis, involved in stress response. Ex vivo tests were carried out on skin explants to evaluate the effectiveness of TPSE formulated at 0.5% on Calcitonin Gene-Related Peptide (CGRP) and IL-10 release, Kappa Opioid Receptor (KOR) and Caspase 14 expression. An in vivo study combined a clinical evaluation of skin homogeneity, psychological parameter as well as analysis of salivary cortisol and dehydroepiandrosterone concentrations. All measurements were carried out at the beginning and after 28 days of applying a TPSE face cream. TPSE regulated not only the release of CGRP and Il-10, reflecting an anti-neurogenic and anti-inflammatory properties, but also modulated KORs. Twenty height days of TPSE application induced a significant decrease in intensity and extent erythrosis, a lower output of salivary cortisol and a significant increase in pleasant emotions when compared to placebo. These results provide encouragement to continue exploring the impact of cosmetic ingredient on psychophysiological parameters to improve skin health and well-being.

Spodoptera frugiperda is a significant economic pest of maize in Uganda. Many Ugandan maize farmers employ synthetic insecticides as their main form of control despite the negative impacts of these chemicals. The study aimed to determine the effect of synthetic, semi-synthetic and bio-pesticides on maize leaf damage, and abundance of S, frugiperda and its parasitoids in Wakiso and Lira districts. The experiments were laid out in an RCBD with six treatments in 2020 and nine treatments in 2021, replicated four times. The treatments with the biggest decrease in leaf damage and infestation were Amdocs and Roket®, followed by Nimbecidine. The biopesticides were not always more effective than the untreated control, though; their efficacy was often lower than that of synthetics, semi-synthetics, and botanical. We recovered one egg parasitoid, Telenomus remus, and seven egg and egg-larval parasitoids (Coccygidium luteum, Coccygidium sp., Cotesia icipe, Chelonus sp., Micranisa sp., Charops cf. diversipes, and Tachinidae sp. Among these, C. cf diversipes, Chelonus sp., C. luteum, C. icipe and Tachinidae were the most abundant. Parasitism was low, averaging 10% for eggs and 5.3% for larvae. Synthetic, the semi-synthetic and Nimbecidine often increased higher yield when compared with the untreated control. There were genrally low population of parasitoids, althoguh there were some indications of reduced population of parasitoids in plots treated with Amdocs and Roket®, while percent parasitism was not affected. In some instances, higher yields were even realized in untreated control. While considering the tactics to integrate, assessing the practices more compatible with biological practices will be necessary.

A defining feature of a productive infection is the co-opting of host cell resources for viral replication. Despite their repertoire of molecular functions, viruses subvert host defenses to take control of cellular factors such as RNA binding proteins (RBPs). RBPs are involved in virtually all steps of mRNA life forming ribonucleoprotein complexes (mRNPs) in a highly ordered and regulated process to control RNA fate and stability in the cell. Thus, the hallmark of this viral takeover is to reshape RNA fate in the cell to modulate host gene expression and evade immune responses. Here we provide an extensive review of work in this area, particularly how the host-viral interplay influences RBP functions to modulate the host cell. Overall, in this review, we highlight the myriad of ways RBPs can regulate RNA stability in either a pro-viral or antiviral manner by gathering novel insights gained from research studies in this field.

Abstract: Objectives: To establish the expression profile of N6-methyladenosine(m6A) modifications in the hippocampus of mice with diabetic cognitive impairment (DCI) and elucidate the potential regulatory mechanism. Methods: A DCI model was established by feeding a high-fat diet to C57BL/6J mice. m6A and RNA sequencing was conducted to profile the m6A-tagged transcripts in the hippocampus. Results: Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing analyses yielded differentially m6A-modified and expressed genes in the hippocampus of DCI mice, which were enriched in pathways involving synaptic transmission and axonal guidance. Mechanistic analyses revealed a remarkable change in m6A modification levels through alteration of the mRNA expression of m6A methyltransferases (METTL3 and METTL14) and demethylase (FTO) in the hippocampus of DCI mice. Conclusions: We identified a co-mediated specific RNA regulatory strategy that broadens the epigenetic regulatory mechanism of RNA-induced neurodegenerative disorders associated with metabolic and endocrine diseases.

In this study, an analysis was conducted on 16 durum wheat genotypes cultivated under seven different crop management systems. The purpose was to investigate the influence of Genotype (G), Environment (E), and Genotype by Environment interactions (GxE) on the content of total free phenolic compounds (TPC) and the antioxidant capacity (AC) of durum wheat in Mediterranean environments and identify their adaptability in climatic change. Additionally, possible correlations between TPC and AC with protein content (PC), and vitreous-kernel percentage (VKP) of the samples were examined. The results indicated significant impacts from E, G, and GxE on both TPC and AC. Among the E, the mean values for TPC, ABTS, DPPH, and FRAP values were recorded at 48.8 mg TE/100 g dw, 121.3 mg TE/100 g dw, 23.0 mg TE/100 g dw, and 88.4 mg TE/100 g dw, respectively. Environments subjected to splitting topdressing N fertilization consistently showed low values, while the late sowing ones possessed high values. The Organic environment maintained a stable position in the middle across all measurements. The predominant influence was attributed to GxE, as indicated by the order GxE >E>G for ABTS, DPPH, and FRAP while for TPC was E>GxE>G. A comprehensive exploration of GxE interaction holds the potential to improve the total free phenolics content and antioxidant capacity of durum wheat within wheat farming systems. Achieving this enhancement involves the meticulous selection of cultivars that not only display high values but also exhibit stability across diverse conditions. Noteworthy genotypes for TPC include G5, G7 and G10, for ABTS include G3, G5 and G7, and for protein include G1, G9, and G16. G7 and G5 had high presence of frequency with G7 being the closest genotype to the ideal for both TPC and ABTS. These results suggest that the cultivation period as well as the nitrogen fertilization and its application method have a significant impact on the various antioxidant properties of durum wheat. This study holds significant importance as it represents the first comprehensive exploration of the impact of various E on the TPC and AC in durum wheat, with a special emphasis on the crop management. Notably, the significance of several statistical tools is also highlighted, such as the GGE biplot, Pi, and KR, in identifying superior genotypes, with the GGE biplot being highly valuable since it offers a visual representation of the study's outcomes.

Non-alcoholic beer (NAB) or low alcoholic beer (LAB) are taking over the market with a growing sale. Sus-tainable recycling and valorization of exhausted brewer’s spent grains (BSG) coming from craft beer is a relevant issue in brewing process. In this work, recycled BSG and BSG+GJ (supplemented with 10% grape juice) were used as wort-substrate to inoculate already selected non-conventional yeasts to produce NABLAB craft beer. Results showed that wort composed by only recycled BSG produced appreciate NAB beers (ethanol from 0.12% to 0.54 % v/v) while the addition of 10% of grape juice made LAB beers (ethanol from 0.82 to 1.66 % v/v). As expected, volatile compounds production was highest with the addition of grape juice. Lachancea thermotolerans confirmed the lactic acid production and, as Saccharomyces cerevisiae, is characterized by (in both worts) ethyl butyrate and isoamyl acetate, while Torulaspora delbrueckii produced relevant amounts of exanol, phenylethyl acetate and β-phenyl ethanol (wort added with grape juice). Wickeramhomyces anomalus and Pichia kluyvery showed consistent volatile production but only in wort with grape juice addition where a fermentation activity was exhibited. The overall results indicated that reused BSGs, non-conventional yeasts and grape juice is a suitable strategy for specialty NABLAB beer.

The field of biobanking human biospecimens has evolved significantly, transitioning from the basic, often poorly documented collection of clinical leftovers kept privately to well-organized and extensively documented collections overseen by both commercial and non-profit platforms. The increasing demand for high-quality and clinically annotated biospecimens is propelled by unprecedented levels of health research activities. Meeting this growing demand presents both new opportunities and challenges, particularly in developing strategies to establish international biospecimen sourcing (IBS) platforms. These platforms aim to facilitate collaboration among biobanks to address future biospecimen needs. In this manuscript, we delve into the advantages and challenges of establishing IBS platforms to provide high-quality and cost-effective biospecimens to drive drug discovery research, ultimately leading to improved health and quality of life for everyone.

Avian metapneumovirus subgroup C (aMPV/C) causes respiratory diseases and egg dropping in chickens and turkeys, resulting in severe economic losses to the poultry industry worldwide. Integrin β1 (ITGB1), a transmembrane cell adhesion molecule, is present in various cells and mediates numerous viral infections. Herein, we demonstrate that ITGB1 is essential for aMPV/C infection in cultured DF-1 cells, as evidenced by the inhibition of viral binding by EDTA blockade, Arg-Ser-Asp (RSD) peptide, monoclonal antibody against ITGB1, and ITGB1 short interfering (si) RNA knockdown in cultured DF-1 cells. Simulation of the binding process between the aMPV/C fusion (F) protein and avian-derived ITGB1 using molecular dynamics showed that ITGB1 may be a host-factor for benefiting aMPV/C attachment or internalization. Transient expression of avian ITGB1 rendered porcine and feline non-permissive cells (DQ cells and CRFK cells, respectively) susceptible to aMPV/C infection. Replication kinetic of aMPV/C in siRNA-knockdown cells revealed that ITGB1 plays an important role in aMPV/C infection at the early stage (attachment and internalization). aMPV/C was also able to infect efficiently human non-small cell lung cancer (A549) cells. This may be due to a consequence of the similar structures of both metapneumovirus F protein-specific motifs (RSD for aMPV/C and RGD for human metapneumovirus) recognized by ITGB1. Overexpression of avian-derived ITGB1 and human-derived ITGB1 in A549 cells enhanced aMPV/C infectivity. Taken together, this study demonstrated that ITGB1 acts as an essential receptor for aMPV/C attachment and internalization into host cells in which facilitates aMPV/C infection.

Uncoupling protein 3 (UCP3) belongs to the mitochondrial carrier protein superfamily SLC25 and is abundant in brown adipose tissue (BAT), heart and muscles. Unlike UCP1, which is localized in BAT and involved in non-shievering thermogenesis, its biological function is under dispute. The expression of UCP3 in tissues mainly dependent on fatty acid oxidation suggests its involvement in cellular metabolism and has drawn attention to its possible transport function beyond the transport of protons in the presence of fatty acids. Based on the high homology between UCP2 and UCP3, we hypothesized that UCP3 transports C4 metabolites similar to UCP2. To test this, we measured the transport of substrates against phosphate (32Pi) in proteoliposomes reconstituted with recombinant murine UCP3. We found that UCP3 mainly transports aspartate and sulfate but also malate, malonate, oxaloacetate and succinate. The transport rates calculated from the exchange of 32Pi against extraliposomal aspartate and sulfate were 23.9 ± 5.8 and 17.5 ± 5.1 µmol/min/mg, respectively. Using site-directed mutagenesis we revealed that mutation of R84 resulted in impaired aspartate/phosphate exchange, demonstrating its critical role in substrate transport. Difference in substrate preference between UCP2 and UCP3 may be explained by their different tissue expression pattern and biological function in these tissues.

Phage therapeutics offer a potentially powerful approach to combat multidrug-resistant bacterial infections. However, to be effective, phage therapy must overcome existing and developing phage resistance. While phage cocktails can reduce this risk by targeting multiple receptors in a single therapeutic, bacteria have mechanisms of resistance beyond receptor modification. A rapidly growing body of knowledge describes a broad and varied arsenal of antiphage systems encoded by bacteria to counter phage infection. We sought to understand the types and frequencies of antiphage systems present in a highly diverse panel of Pseudomonas aeruginosa clinical isolates utilized to characterize novel antibacterials. Using web-server tool PADLOC (Prokaryotic Antiviral Defense Locator), putative antiphage systems were identified in these P. aeruginosa clinical isolates based on sequence homology to a validated and curated catalog of known defense systems. Coupling this host bacterium sequence analysis with host range data for 70 phages, we observed a correlation between existing phage resistance and the presence of higher numbers of antiphage systems in bacterial genomes. We were also able to identify antiphage systems that were more prevalent in highly phage-resistant P. aeruginosa strains, suggesting their importance in conferring the resistance.

Pseudoxanthoma Elasticum (PXE) is an inherited disease characterized by elastic fibers calcification in the eyes, the skin and the cardiovascular system. PXE results from mutations ABCC6 that encodes an ABC transporter primarily expressed in liver and kidneys. It took nearly 15 years after identifying the gene to better understand the etiology of PXE. the ABCC6 functions facilitates the efflux of ATP (and other nucleotides) which is sequentially hydrolyzed by the ectonucleotidases ENPP1 and CD73 into pyrophosphate (PPi) and adenosine, both inhibitors of calcification. PXE, together with General Arterial Calcification of Infancy (GACI caused by ENPP1 mutations) as well as Calcification of Joints and Arteries (CALJA caused by NT5E/CD73 mutations) form a disease continuum with overlapping phenotypes and sharing steps of the same molecular pathway. The explanation of these phenotypes places ABCC6 as an upstream regulator of a purinergic pathway (ABCC6 → ENPP1 → CD73) that notably inhibits mineralization by maintaining a physiological Pi/PPi ratio in connective tissues. Based on a review of the literature and our recent experimental data, we suggest that PXE (and GACI/CALJA) be considered as an authentic “purinergic disease”. In this article, we recapitulate the pathobiology of PXE, review molecular and physiological data showing that, beyond PPi deficiency and ectopic calcification, PXE is associated with wide and complex alterations of purinergic systems. Finally, we speculate on future prospects regarding purinergic signaling and other aspects of this disease.

APC mutation is the main driver mechanism of CRC development and leads to constitutively activated WNT signaling, overpopulation of ALDH+ stem cells (SCs), and incomplete differentiation. We previously reported that retinoic acid (RA) receptors are selectively expressed in ALDH+ SCs, which provides a way to target cancer SCs with retinoids to induce differentiation. Hypotheses: A functional link exists between WNT and RA pathways, and APC mutation generates a WNT:RA imbalance that decreases retinoid-induced differentiation and increases ALDH+ SCs. Accordingly, to restore parity in WNT:RA signaling, we induced wt-APC expression in APC-mutant CRC cells and assessed the ability of all-trans-retinoic acid (ATRA) to induce differentiation. Notably, ATRA substantially increased expression of the WNT-target gene, CYP26A1, and inducing wt-APC reduced this expression by 50%. Thus, RA and WNT pathways crosstalk to modulate CYP26A1 metabolism of retinoids. We found that inducing wt-APC augments ATRA-induced cell differentiation by: i) decreasing cell proliferation; ii) suppressing ALDH1A1 expression; iii) decreasing ALDH+ SCs; iv) increasing neuroendocrine cell differentiation. Furthermore, NanoString profiling/bioinformatics identified a novel CYP26A1-based network that links WNT and RA signaling. Moreover, CYP26A1 inhibitors sensitized CRC cells to the anti-proliferative effect of drugs that downregulate WNT signaling. Notably. in wt-APC-CRCs, decreased CYP26A1 improves patient survival. These findings have strong potential for clinical translation.

Background: Cognitive for patients with neurocognitive disorders are mostly measured by Montreal Cognitive Assessment (MoCA) and Visual Cognitive Assessment Test (VCAT) as screening tools. These cognitive scores are usually left skewed and the results of association analysis might not be robust. This study aims to study the distribution of the cognitive outcomes and to discuss potential solutions. Materials and Methods: The inverse transformed cognitive outcomes are modelled using different statistical distributions. Robustness of the proposed models are checked under different scenarios: with intercept only, models with covariate, with and without bootstrapping. Results: Main results were based on VCAT score, and validated via MoCA score. Findings suggested that the inverse transformation method improves modelling the cognitive scores compared to the conventional methods using the original cognitive scores. Association of baseline characteristics (age, gender and years of education) and the cognitive outcomes were reported as estimates and 95% confidence intervals. Bootstrap methods improved the estimate precision and the bootstrapped standard errors of the estimates are more robust. Cognitive outcomes are widely analyzed using linear regression models with default normal distribution as a conventional method. We compared the results of our suggested models with the normal distribution under various scenarios. Goodness-of-fit measurements were compared between proposed models and conventional methods. Conclusions: The findings support the use of the inverse transformation method to model the cognitive outcomes instead of the original cognitive scores for early stage neurocognitive disorders where the cognitive outcomes are left skewed.

Nitric oxide (NO) is synthesized and is involved in various physiological and developmental process regulation in all kingdoms of life. Fungi have been less explored in terms of endogenous NO biology than mammals, plants, and bacteria. In this review, we summarize and discuss the studies to date on intracellular NO biosynthesis and function in fungi. Two mechanisms for NO biosynthesis, NO synthase (NOS)-mediated arginine oxidation, and nitrate and nitrite reductase-mediated nitrite reduction, are most frequently reported. Furthermore, we summarize the multifaceted functions of NO in fungi, as well as its role as a signaling molecule in fungal growth regulation, development, abiotic stress, virulence regulation, and metabolism. Finally, we present potential directions for future research on fungal NO biology.

African swine fever virus (ASFV) is the causative agent of African swine fever, an economically important disease of pigs, often with a high case fatality rate. ASFV has demonstrated low genetic diversity among isolates collected within Eurasia. To explore the influence of viral variants on clinical outcomes and infection-dynamics in pigs experimentally infected with ASFV, we have designed a deep sequencing strategy. Variant analysis revealed 3 distinct SNPs present in the virus inoculum (at 2.4%, 0.7%, and 13% frequency, respectively) that were maintained within all infected pigs (1-6 % frequency, and the latter at 16-21%). Several pigs displayed other unique SNPs at <10% frequency. In addition, a deletion of 10487 bp (resulting in the complete loss of 21 genes) was present at nearly 100% frequency in the ASFV DNA from one pig at position 6362-16849. This deletion was also found to be present at low levels in the virus inoculum and in two other infected pigs. The current methodology can be used for the currently circulating Eurasian ASFVs and also adapted to other ASFV strains and genotypes. Comprehensive deep sequencing is critical for following ASFV molecular evolution, especially for identification of modifications that affect virus virulence.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the gastric mucosa and is associated with various gastrointestinal disorders. H. pylori is a pervasive pathogen, infecting nearly 50% of the world's population, and presents a substantial concern due to its link with gastric cancer, ranking as the third most common cause of global cancer-related mortality. This review article provides an updated and comprehensive overview of the current understanding of H. pylori infection, focusing on its pathogenesis, diagnosis, and treatment strategies. The intricate mechanisms underlying its pathogenesis, including virulence factors and host interactions, are discussed in detail. Diagnostic methods, ranging from traditional techniques to advanced molecular approaches, are explored, highlighting their strengths and limitations. The evolving landscape of treatment strategies, including antibiotic regimens and emerging therapeutic approaches, is thoroughly examined. Through a critical synthesis of recent research findings, this article offers valuable insights into the contemporary knowledge of Helicobacter pylori infection, guiding both clinicians and researchers toward effective management and future directions in combating this global health challenge.

Acanthamoeba keratitis (AK) is a severe, rare protozoal infection of the cornea. Acanthamoeba can survive in diverse habitats and at extreme temperatures. AK is mostly seen in contact lens wearers, whose lenses have become contaminated, or a history of water exposure, and in those without contact lens wear, who have experienced recent eye trauma involving contaminated soil or water. Infection usually results in severe eye pain, photophobia, inflammation, and corneal epithelial defects. The pathophysiology of this infection is multifactorial, including the production of cytotoxic proteases by Acanthamoeba that degrades the corneal epithelial basement membrane and induce the death of ocular surface cells, resulting in degradation of the collagen-rich corneal stroma. AK can be prevented by avoiding the risk factors, which include avoiding water contact such as swimming or showering in contact lenses, and wearing protective goggles when working on the land. AK is mostly treated with an antimicrobial therapy of biguanides alone or in combination with diaminidines, although the commercial availability of these medicines is variable. Other than anti-amoeba therapies, targeting host immune pathways in Acanthamoeba disease may lead to the development of vaccines or antibody therapeutics which could transform the management of AK.

Epidemiological evidence points to an inverse association between Parkinson's disease (PD) and almost all cancers except melanoma, for which this association is positive. The results of many studies have found that patients with PD are at reduced risk of the majority of neoplasm occurrence and death. Several potential biological explanations exist for the inverse relationship between cancer and PD. Recent results identified several PD-associated proteins and factors mediating cancer development and cancer-associated factors affecting PD. Accumulating data points to the role of genetic traits, members of the synuclein family, neurotrophic factors, ubiquitin-proteasome system, circulating melatonin, and transcription factors as such mediators. We present recent data about shared pathogenetic factors and mediators that might be involved in the association between these two diseases. We also discuss how these factors, individually or in combination, may be involved in pathology, serve as links between PD and cancer, and affect the prevalence of these disorders. Identification of these factors and investigations of their mechanisms will lead to the discovery of new targets for the treatment of both diseases

The use of antibiotics as growth promotors or for the prevention of some poultry diseases has face global concern and serious criticism. Their addition to poultry feed show hazardous effects including development of antimicrobial resistance and the potential harmful effect on humans’ health. To eliminate these threats, there is increasing interest to search for natural alternatives. Plant derivatives such as garlic (Allium sativum L.) and its derivatives are nowadays extensively used in poultry production system. Dietary supplementation of broilers and layers with garlic induced improvement of production parameters, carcass quality, and intestinal integrity. Modulation of the immune response against important viral diseases and increasing the immune organs body weight ratio resulting from supplementation of poultry with garlic. Moreover, garlic showed modulation of gut health through the antibacterial and antiparasitic activities. Treatment with garlic also can mitigate the oxidative stress and reduce the free radicals production. Reduction of cholesterol level, but improvement of some liver and blood parameters were also reported following dietary inoculation of garlic. This review was designed to search on the impact of garlic as feed additives on performance, immunity, gut health, antioxidant status, and blood parameters of poultry.

This study investigated the prevalence of embryonic and connective tissue elements in the filum terminale (FT) of patients with tethered cord syndrome (TCS), examining both typical and pathological histology. FT specimens from 288 patients who underwent spinal cord detethering from 2013-2021 were analyzed. Histopathological examination involved routine hematoxylin and eosin staining and specific immunohistochemistry when needed. Patient details were extracted from electronic medical records. The study found that 97.6% of FT specimens had peripheral nerves, and 70.8% had regular ependymal cell linings. Other findings included ependymal cysts and canals, ganglion cells, neuropil, and prominent vascular features. Notably, 41% showed fatty infiltration, and 7.6% had dystrophic calcification. Inflammatory infiltrates, an underreported finding, were observed in 3.8% of the specimens. The research highlights peripheral nerves and ganglion cells as natural components of the FT, with ependymal cell overgrowth and other tissues potentially linked to TCS. Enlarged vessels may suggest venous congestion due to altered FT mechanics. The presence of lymphocytic infiltrations and calcifications provides new insights into structural changes and mechanical stress in the FT, contributing to our understanding of TCS pathology.

We report the case of a four-year-old male patient with a complex medical history born prematurely as the result of intrauterine growth restriction due to placental insufficiency. His clinical manifestations include severe neurodevelopmental deficits, global developmental delay, Pierre-Robin sequence, and intractable epilepsy with both generalized and focal features. The proband’s low levels of citrulline and lactic acidosis provoked by administration of depakoke are evocative of a mitochondrial etiology. However, the genotype-phenotype correlation remains undefined in the absence of nuclear and mitochondrial pathogenic variants detected by deep sequencing of both genomes. However, live-cell mitochondrial metabolic investigations provide evidence of a deficient oxidative phosphorylation pathway responsible for ATP synthesis, leading to chronic energy crisis in the proband. In addition, our metabolic analysis reveals metabolic plasticity in favor of glycolysis for ATP synthesis. Our mitochondrial morphometric analysis by transmission electron microscopy confirms the suspected mitochondrial etiology, as the proband’s mitochondria exhibit an immature morphology with poorly developed and rare cristae. Thus, our results support the concept that sub-optimal levels of intrauterine oxygen and nutrients alter fetal mitochondrial metabolic reprogramming toward OXPHOS leading to a deficient postnatal mitochondrial energy metabolism. In conclusion, our collective studies shed light on the long-term postnatal mitochondrial pathophysiology caused by intrauterine growth restriction due to idiopathic placental insufficiency and its negative impact on the energy-demanding development of fetal and postnatal brain.

Cholesterol siRNA conjugates attract attention because they allow the delivery of siRNA into cells without the use of transfection agents. In this study, we compared the efficacy and duration of silencing induced by cholesterol conjugates of selectively and totally modified siRNAs and their heteroduplexes of the same sequence and explored the impact of linker length between the 3' end of the sense strand of siRNA and cholesterol on the silencing activity of “light” and “heavy” modified siRNAs. All 3'-cholesterol conjugates were equally active under transfection, but the conjugate with a C3 linker was less active than those with longer linkers (C8 and C15) in a carrier-free mode. At the same time, they are significantly inferior in activity to the 5'-cholesterol conjugate. Shortening the sense strand carrying cholesterol by 2 nucleotides from the 3'-end did not have a significant effect on the activity of the conjugate. Replacing the antisense strand or both strands with fully modified ones has a significant effect on silencing as well as improving the duration in transfection-mediated and carrier-free modes. A significant 78% suppression of MDR1 gene expression in KB-8-5 xenograft tumors developed in mice promises an advantage from the use of fully modified siRNA cholesterol conjugates in combination chemotherapy.

Abstract: The recently described perivascular unit (PVU) resides immediately adjacent to the true capillary neurovascular unit (NVU) in the postcapillary venule and contains the normal-benign perivascular spaces (PVS) and pathological enlarged perivascular spaces (EPVS). The PVS are important, in that, they also have recently been identified to be the construct and the conduit responsible for the delivery of metabolic waste from the interstitial fluid to the ventricular cerebrospinal fluid for disposal into the systemic circulation and has been termed the glymphatic system. Importantly, the outermost boundary of the PVS is lined by protoplasmic perivascular astrocyte endfeet (pvACef) that communicate with regional neurons. As compared to the well-recognized and described neurovascular unit (NVU) and NVU coupling, the PVU is less well understood and remains an emerging concept. The primary focus of this narrative review is to compare the similarities and differences between these two units and discuss each of their structural and functional relationships and how they relate not only to brain homeostasis but also how they may relate to the development of multiple clinical neurological disease states and specifically how they may relate to obesity, metabolic syndrome, and type 2 diabetes mellitus. Additionally, the concept and importance of a perisynaptic astrocyte coupling to the neuronal synapses with pre- and postsynaptic neurons will also be considered as a perisynaptic unit to provide for the creation of the information transfer in the brain via synaptic transmission and brain homeostasis. Multiple electron microscopic images and illustrations will be utilized in order to help explain these complex units.

With the continuous update of gene editing technology, great progress has been made in livestock breeding, researchers have produced gene edited pigs, cattle, sheep and other improved livestock. Gene editing technology is a genetic means to knock in, knock out, delete, inhibit, activate or replace specific bases of DNA or RNA sequences at the genome level to achieve accurate modification, and can edit genes at a fixed point without the need for DNA templates. In recent years, although regular clusters of interspaced short palindromic repeats (CRISPR)/Cas9 system mediated gene editing technology has been widely used in animal genetic breeding research, but so far, the system's precise insertion efficiency of foreign genes is not high enough, and there are certain off-target effects, and it is not enough to be used in genome editing of large livestock such as cashmere goats. In this paper, the development status, challenges, application prospects and look into the distance of CRISPR/ Cas9-mediated precisiongene editing technology in livestock breeding were reviewed, in order to provide theoretical reference for livestock gene function analysis, genetic improvement and livestock breeding with local economic characteristics.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown origin, with a median survival time of ~3 years after diagnosis without anti-fibrotic therapy. It is characterized by progressive fibrosis indicated by increased collagen deposition and high numbers of fibroblasts in the lung. It was demonstrated that CCL18 induces collagen and αSMA synthesis in fibroblasts. We aimed to identify the CCL18 receptor responsible for its pro-fibrotic activities. Methods: We used a random phage display library to screen for potential CCL18-binding peptides, demonstrated its expression in human lungs and fibroblast lines by PCR and immunostaining and verified its function in cell lines. Results: We identified CCR6 (CD196) as a CCL18 receptor and found its expression in fibrotic lung tissue and on lung fibroblast lines derived from fibrotic lungs but it is almost absent in control lines and tissue. CCL18 induces receptor-internalization in a CCR6-overexpressing cell line. CCR6 blockade in primary human lung fibroblasts reduces CCL18-induced FGF2 release as well as collagen-1 and αSMA expression. Knock-down of CCR6 in a mouse fibroblast cell line abolishes the induction of collagen and -smooth muscle actin expression. Conclusion: Our data indicate that CCL18 triggers pro-fibrotic processes via CCR6, highlighting its role in fibrogenesis.

We discuss slip bonds, catch bonds and the tug-of-war mechanism using mathematical arguments. We propose simple 2-dimensional surface models to demonstrate how the potential energy surface of a molecule under an external force behaves. Examples are selectines. Catch bonds in particular are explained in more detail. We demonstrate that Newton trajectories are a powerful tool to describe these phenomena. Newton trajectories form the theoretical background of Mechanochemistry.

Both brain-derived neurotrophic factor (BDNF) and glucocorticoids (GCs) have multiple roles in the various aspects of neurons, including cell survival and synaptic function. BDNF and its receptor TrkB express in the central nervous system (CNS) neurons extensively, and contribution of BDNF/TrkB system in neuronal function is evident, thus, its downregulation has been considered to be involved in the pathogenesis of Alzheimer’s disease (AD). GCs, a stress-related molecule, and glucocorticoid receptor (GR) are also considered to be associated with AD, in addition to mental disorders such as depression. Importantly, a growing body of evidence suggest a close relationship between BDNF/TrkB-mediated signaling and GCs/GR system in the CNS. Here, we introduce current studies on the interaction among neurotrophic system and stress in CNS neurons, and discuss their involvement in the pathophysiology of AD.

A hallmark of Alzheimer’s disease (AD) are the proteinaceous aggregates formed by the amyloid-beta peptide (Aβ) that is deposited inside the brain as amyloid plaques. The accumulation of aggregated Aβ may initiate or enhance pathologic processes in AD. According to the amyloid hypothesis any agent that has the capability to inhibit Aβ aggregation and/or destroy amyloid plaques represents a potential disease modifying drug. In 2023, a humanized IgG1 monoclonal antibody (lecanemab) against the Aβ soluble protofibrils was approved by US FDA for AD therapy thus providing compelling support to the amyloid hypothesis. To acquire a deeper insight on the in vivo Aβ aggregation, various animal models, including aged herbivores and carnivores, non-human primates, transgenic rodents, fish and worms are widely exploited. This review is based on the recent data obtained using transgenic animal AD models and presents experimental verification of the critical role in Aβ aggregation seeding of the interactions between zinc ions, Aβ with the isomerized Asp7 (isoD7- Aβ) and the α4β2 nicotinic acetylcholine receptor.

The main function of dUTPases is to regulate the cellular levels of dUTP and dTTP, thereby playing a crucial role in the DNA repair mechanisms. Despite the fact that mutant organisms with the obliterated dUTPase enzymatic activity remain viable, it is not possible to knockout the dut gene completely due to the lethal consequences of such mutation for the organism. As a result, it is considered that this class of enzymes perform an additional function that is essential for the organism's survival. In this study, we provide the evidence that the dUTPase of bacteriophage T5 possesses supplemental function in addition to its canonical role. We determined the crystal structure of bacteriophage T5 dUTPase with a resolution of 2.0 Å, and discovered a distinct short loop, consisting of 6 amino acid residues which represents unique structural feature specific to the T5-like phages dUTPases. The removal of this element did not affect the overall structure of the homotrimer, but had significant effects on the development of the phage. Furthermore, it has been shown that the enzymatic function and the novel function of bacteriophage T5 dUTPase are unrelated and independent from each other.

Skeletal myogenesis is an intricate process involving the differentiation of progenitor cells into myofibers, which is regulated by actin cytoskeletal dynamics and myogenic transcription factors. Although recent studies have demonstrated the pivotal roles of actin-binding proteins (ABPs) as mechanosensors and signal transducers, the biological significance of WAVE2 (Wiskott-Aldrich syndrome protein family member 2), an ABP essential for actin polymerization, in myogenic differentiation of progenitor cells has not been investigated. Our study provides important insights into the regulatory roles played by WAVE2 in the myocardin-related transcription factor A (MRTFA)-serum response factor (SRF) signaling axis and differentiation of myoblasts. We demonstrate that WAVE2 expression is induced during myogenic differentiation and plays a pivotal role in actin cytoskeletal remodeling in C2C12 myoblasts. Knockdown of WAVE2 in C2C12 cells reduced filamentous actin levels, increased globular actin accumulation, and impaired the nuclear translocation of MRTFA. Furthermore, WAVE2 depletion in myoblasts inhibited the expression and transcriptional activity of SRF and suppressed cell proliferation in myoblasts. Consequently, WAVE2 knockdown suppressed myogenic regulatory factors (i.e., MyoD, MyoG, and SMYD1) expressions, thereby hindering the differentiation of myoblasts. Thus, this study suggests that WAVE2 is essential for myogenic differentiation of progenitor cells by modulating the mechanosensitive MRTFA-SRF axis.

Proteins in the crowded environment of human cells have often been studied regarding nonspecific interactions, misfolding, and aggregation, which may cause cellular malfunction and disease. Specifically, proteins with high abundance are more susceptible to these issues due to the law of mass action. Therefore, the surfaces of highly abundant cytoplasmic (HAC) proteins directly exposed to the environment can exhibit specific physicochemical, structural, and geometrical characteristics that reduce nonspecific interactions and adapt to the environment. However, the quantitative relationships between the overall surface descriptors still need clarification. Here, we used machine learning to identify HAC proteins using hydrophobicity, charge, roughness, secondary structures, and B-factor from the protein surfaces and quantify the contribution of each descriptor. First, several supervised learning algorithms were compared to solve binary classification problems for the surfaces of HAC and extracellular proteins. Then, logistic regression was adopted for the feature importance analysis of descriptors considering model performance (80.2% accuracy and 87.6% AUC) and interpretability. The HAC proteins showed positive correlations with negatively and positively charged areas but negative correlations with hydrophobicity, B-factor, beta structure proportion, roughness, and disordered regions proportion. Finally, the details of each descriptor could be explained concerning adaptative surface strategies of HAC proteins to regulate nonspecific interactions, protein folding, flexibility, stability, and adsorption. This study presented a novel approach using various surface descriptors to identify HAC proteins and provided quantitative design rules for the surfaces well-suited to human cellular crowded environments.

Precision agriculture including camera-guided row detection and hydraulic steering are often used as an alternative because crop damage can be decreased and driving speed can be increased comparable to herbicide applications.The effects of different approaches as uncontrolled (UC), mechanical weed control (MWC), herbicide weed control (HWC) and mechanical + herbicide control (MWC+HWC) on weed density and yield of sugar beet were tested and evaluated in two trials (2021 and 2022) in South Transylvania at the tested intervals BBCH 19 and 31. Weed control efficacy (WCE) depends on the emergence of the weeds and a good timing of weed controls in all the trials and methods, though the highest yield of sugar beet roots was recorded in the treatment MWC+HWC, with an increase up to 12-15% (56.48 t ha-1) yield from HWC (50.22 t ha-1) and a yield increase of more than 35- 40% than MWC (42.34 t ha-1). Our trials show that is possible to increase yield and have less chemical applications with the introduction of the new precision technologies in agriculture included here the sensor-guided mechanical controls.

The European Fish Index EFI+ is the only fish-based multimetric index for the assessment of the ecological status of running waters validated and thus applicable across the European Union. Metrics of the index rely on several attributes of the species present in the fish assemblage, irrespective of their native/alien status. The abundance of alien fish, together with other anthropogenic impacts, is one of the most important threats to the conservation of native fish and ecosystem health and is also an indicator of degraded stream conditions. Therefore, to improve the performance and utility of the EFI+ in regions with high incidence of alien species, the EFI+ was adapted to include the alien fish pressure by averaging the two original metrics with a new metric that reflects the number of alien species as well as the proportional abundance of alien individuals. The application of the adapted index (A-EFI+) is illustrated with data from several Iberian Mediterranean basins and showed similar or stronger correlations than the original EFI+ with anthropogenic pressure (land-use variables) and with other regional fish indices. EFI+ has been invaluable to intercalibrate fish indices across Europe and A-EFI+ is similar but explicitly includes the alien pressure, thus helping to provide a more comprehensive assessment of ecosystem health and to communicate it to society.

Adult mesenchymal stem cells (MSCs) are a promising cell source for tissue regeneration. However, ex vivo expansion results in cell senescence; cells lose their proliferation and differentiation capacity. Fetal MSCs can be an alternative due to their robust proliferation and differentiation capacities as well as immune privilege properties. Given the rejuvenation effect of decellularized extracellular matrix (dECM) on adult MSCs, it remains unknown whether dECM influences the regenerative potential of fetal stem cells. In this study, passage five fetal nucleus pulposus cells (fNPCs) and fetal synovium-derived stem cells (fSDSCs) were expanded on dECMs deposited by fNPCs (NECM) and fSDSCs (SECM) for one passage with expansion on tissue culture plastic (Plastic) as a control. We found that dECM expanded fNPCs and fSDSCs exhibited both similarities and differences in expression of stemness genes and surface markers. Expanded fNPCs yielded more differentiated pellets after chondrogenic induction but no adipogenic differentiation following adipogenic induction in both Plastic and dECM groups than the corresponding fSDSC group. Despite a significant increase in fNPCs, dECM expanded fSDSCs exhibited no increase in chondrogenic potential; however, compared to the Plastic group, dECM expanded fSDSCs exhibited a small increase in osteogenic potential and a great increase in adipogenic potential. These results suggest that fNPCs are more sensitive to NECM rejuvenation for cartilage tissue engineering and regeneration; in contrast, dECMs exhibited limited effects on fSDSC rejuvenation in chondrogenic capacity except for enhanced adipogenic capacity following expansion on SECM.