Ajuga arabica is an essential medicinal plant found naturally in Saudi Arabia, recognized for its therapeutic characteristics. Nevertheless, research on the genetic diversity and population arrangement of this species in Saudi Arabia is deficient. In this study, we conducted a comparative examination of DNA and gene sequences to evaluate the genetic diversity and population configuration of Ajuga arabica in Saudi Arabia. Our findings demonstrate that there are high levels of genetic diversity within populations, but low levels of genetic differentiation among populations. Moreover, we discovered proof of gene flow among populations, suggesting that there are no significant genetic barriers to gene flow. Our results offer valuable insights into the genetic diversity and population structure of Ajuga arabica in Saudi Arabia, which can support conservation efforts and promote the sustainable use of this valuable medicinal plant.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

RNA extraction from human cumulus cells (CCs) is considered challenging due to low cell’s pop-ulation and small cell. The successful gene expression analysis from cumulus cells ultimately de-pends on an excellent concentration of Ribonucleic acid (RNA) yield by an appropriate technique. Our study aims to consolidate appropriate cumulus cell collection method, preparation and ex-traction techniques to ensure a good yield of RNA for better gene expression analysis. From the results obtained, the optimal strategy found involved mechanical denudation without an enzy-matic process, followed by the use of RNA stabilizer prior to RNA extraction. Subsequently, uti-lizing a smaller homogenizer, preferably manual pressure control with filter (Bio-Masher III®) is paramount for a pure and homogenize sample. Subsequently, during RNA extraction, the use of RNeasy micro kit and RNA carriers is recommended. These sample collection, preparation, and extraction techniques yielded an excellent-quality RNA concentration and successful gene expres-sion analysis. We also conducted a systematic review to consolidate our findings with current evidence of RNA extraction technique. Our results added a value as a current strategy for opti-mizing RNA extraction in CCs for experimental studies. Thus, our findings can contribute to for-mulating a better strategy for optimizing the RNA extraction in CCs for transcriptomic studies.

Preventing the rebound of black and odorous water bodies is critical for improving the ecological environment of water bodies. This study investigated the effect and mechanism of in-situ improvement of sediment microenvironment by nitrate in tailwater of wastewater treatment plants combined with aerobic denitrifying bacteria under low-DO regulation (TailN+CFM+LDO). On the 60th day of remediation, the dissolved oxygen and oxidation-reduction potential in the overlying water increased to 5.6 mg/L and 300 mV, respectively, the acid volatile sulfide in the sediment decreased by 70.4%, and the organic matter in the sediment was reduced by 62.7%, in which the HFOM was degraded from 105 g/kg to 56 g/kg, and the potential risk of water reverting to black and odorous conditions significantly decreased. Amplicon sequencing analysis revealed that the relative abundance of electroactive bacteria Thiobacillus and Pseudomonas with denitrification capacity was found to be significantly higher in the TailN+CFM+LDO group than in the other remediation groups. Functional prediction of 16S sequencing results indicated that both the quantity and activity of critical microbial enzymes involved in nitrification and denitrification processes could enhance in the TailN+CFM+LDO group. These results improved our understanding of the improvement of the sediment microenvironment and could thus facilitate its application.

The study titled "Molecular Choreography of DNA: Insights and Innovations" explores the intricate dance of DNA, shedding light on its structure, function, and regulation. This comprehensive review delves into the historical significance of DNA research, from Watson and Crick's double helix discovery to recent innovations in genomics and molecular biology. The review highlights DNA's roles in replication, repair, gene regulation, and chromatin dynamics, emphasizing the precision and complexity of its molecular choreography. Innovations like CRISPR-Cas9 gene editing and advanced sequencing technologies have revolutionized our understanding of DNA, opening new avenues for scientific exploration. This study aims to provide readers with a deeper appreciation of DNA's central role in life's choreographed processes.

The epigenetic mechanism of DNA methylation is essential for regulating gene expression and adaptation in plants, especially when exposed to various environmental stressors such as drought, heat, and nutrient availability. The impact of these stressors can lead to alterations in DNA methylation patterns and gene expression, which this study aims to investigate. Specifically, we are interested in understanding how DNA methylation plays a role in controlling the expression of stress-response genes, as well as genes involved in plant growth and development. To accomplish this, we are analyzing the changes in DNA methylation patterns and gene expression in response to different stressors like drought and heat. Our research findings suggest that DNA methylation is a vital regulator of plant adaptation to environmental stress, and we hope to gain further insight into these mechanisms by identifying genes that exhibit differential expression in response to stress and analyzing their DNA methylation status. This study offers valuable insights into the development of crops that can thrive under changing climate conditions.

The study addresses the urgent environmental issue of climate change, focusing specifically on the role of local food, which is produced and consumed locally, helps reduce carbon emissions by eliminating the need for long-distance transportation. Through quantitative analysis, this study elucidates the potential benefits in environmental impact achieved through the consumption of local food: the significant reduction in carbon emissions. Specifically, the consumption of local food is found to yield an annual decrease of 2,421,296 tCO2 emissions, representing 2.5% of South Korea’s total greenhouse gas emissions from the transportation sector. This reduction further translates into an estimated economic value of USD 54.23 million (KRW 70.5 billion). This study underscores the potential of local food consumption as a tangible strategy to overcome environmental problems. Moreover, its academic contribution lies in its comprehensive analysis of the economic and empirical impacts of local food consumption on environment. Moving forward, we propose policies such as supporting local food distribution networks, providing public education on local food, fostering the local food industry, and providing incentives to revitalize local food consumption.

The Upper Hunter Valley is a major coal mining area containing approximately 40% of the currently identified total coal reserves in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. This paper summarises the spatial and temporal variability modes of PM10 pollution in the region, based on long-term multi-site monitoring data and the application of the rotated principal component analysis (RPCA) and wavelet analysis techniques. RPCA identified two distinct air quality clusters/subregions in the valley, one in the west/northwest, the other in the southeast. Wavelet analysis revealed the annual cycle to be most persistent temporal mode of PM10 variability in both subregions, with intermittent signals observed at time scales of around 120, 30~90 and under 30 days. How these variation modes are related to the effects of local PM10 emissions and the influence of meteorology at different time scales deserves further attention in future work. The findings will be used in air quality reporting and forecasting in NSW. The methodology and results can also be useful for air quality research in similar regions elsewhere.

BackgroundThe use of antimicrobials to treat food animals may result in antimicrobial residues in foodstuffs of animal origin. The European Medicines Association (EMA) and World Health Organization (WHO) define safe antimicrobial concentrations in food based on acceptable daily intakes (ADIs). It is unknown if ADI doses of antimicrobials in food could influence the antimicrobial susceptibility of human-associated bacteria. ObjectivesThis aim of this study was to evaluate if the consumption of ADI doses of erythromycin could select for erythromycin resistance in a Galleria mellonella model of Streptococcus pneumoniae infection. Methods A chronic model of S. pneumoniae infection in G. mellonella larvae was used for the experiment. Inoculation of larvae with S. pneumoniae was followed by injections of EMA (0.0875 μg/ml) and WHO (0.012 μg/ml) ADI doses of erythromycin proceeded by isolation of S. pneumoniae colonies on selective agar plates. Minimum inhibitory concentrations (MICs) of resistant colonies were measured, and whole genome sequencing (WGS) was performed followed by variant calling to determine the genetic modifications.   Results Exposure to single doses of both EMA and WHO ADI doses of erythromycin resulted in the emergence of erythromycin resistance in S. pneumoniae. Emergent resistance to erythromycin was associated with a mutation in rplA. Conclusion In our in vivo model, even single dose of erythromycin that are classified as acceptable by the WHO and EMA induced significant increases in erythromycin MICs in S. pneumoniae. These results suggest the need to include the induction of antimicrobial resistance (AMR) as a significant criterion for determining ADIs.

The global craft beer market is witnessing substantial growth, with a particular spotlight on sour beers. These unique brews are created through lactic fermentation initiated by lactic acid bacteria (LAB). However, the presence of hops, renowned for their antimicrobial properties, can pose a limitation within the realm of sour beer production. This research aims to explore and assess the potential of sour beer as a probiotic beverage. It involves a comparative analysis of the viability of Lacticaseibacillus paracasei subsp. paracasei F19 (F19) and 431 (L431) in a sour beer with an International Bitterness Unit (IBU) value of 26.65, alongside examining the ex-pression of genes such as horA, horB, horC, hitA, bsrA, and recA, which are associated with hop resistance. The study encompasses the development of two formulations of sour beers characterized by both high hop content and a robust probiotic count (8.44 – 8.77 log CFU/mL). The findings suggest that both probiotic strains of F19 and L431, are well-suited to produce sour beers with elevated hop levels, demonstrating excellent stability. Notably, the expression of genes responsible for hops resistance exhibited distinct modulation patterns among the two strains. It appears that a higher concentration of bsrA, as observed in strain L431, may be more effective in mitigating the effects of hop-related stress, potentially surpassing the combined expression of horA and bsrA. Nonetheless, further research is essential to validate this observation in gene expression. F19 and L431 emerge as promising candidates for the development of sour beers with increased hop intensity.

Hox gene clusters are crucial in Embryogenesis. It was observed that some Hox genes are located in order along the telomeric to centromeric direction of the DNA sequence: Hox1, Hox2, Hox3…. These genes are expressed in the same order in the ontogenetic units of the Drosophila embryo along the Anterior-Posterior axis. The two entities (genome and embryo) differ significantly in linear size and in-between distance. This strange phenomenon was named Spatial Collinearity (SP). Later, it was observed that, particularly in the Vertebrates, a Temporal Collinearity (TC) coexists: first is Hox1 expressed, later Hox2 and even later Hox3,…,. According to a Biophysical Model (BM), pulling forces act at the anterior end of the cluster while a cluster fastening applies at the posterior end. Hox clusters are irreversibly elongated along the force direction. During Evolution, the elongated Hox clusters are broken at variable lengths thus split clusters may be created. An Empirical Rule was formulated distinguishing development due to a complete Hox cluster from development due to split Hox clusters. BM can ‘explain’ this Empirical Rule. In a spontaneous mutation where the cluster fastening is dismantled, a weak pulling force automatically shifts the cluster inside the Hox activation domain. This cluster translocation can probably explain the absence of Temporal Collinearity in Drosophila.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, wings, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects and all other arthropods. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. As a means of renaming this protein family, this review article discusses the latest findings (“CSP” is attached to the tail of bigger intracellular proteins) and attempts to compel all the data. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins) and use at least for abbreviations for distinctive animal proteins the common peptide 5-letter code, such as “Bommo-4CSPs”.

This review article offers an in-depth look at DNA, its discovery, structure, functions, and the significant role it plays in modern biomedical research. It begins by revisiting the landmark discovery of the DNA double helix by scientists Watson and Crick, a structure resembling a twisted ladder that forms the blueprint of life. The review explains the basic processes of DNA replication (copying DNA), transcription (converting DNA to RNA), and translation (turning RNA into proteins), which are fundamental to understanding how genetic information is passed on and used by living organisms. The article then explores gene regulation and epigenetics, which involve how genes are turned on or off and how environmental factors can affect gene expression without changing the DNA sequence itself. It examines how DNA interacts with various proteins and modifiers, which play crucial roles in these processes. A major focus is on the advancements in DNA sequencing technologies. From the initial Sanger sequencing method, which was labor-intensive and time-consuming, to the highly efficient next-generation sequencing (NGS) and the latest single-molecule sequencing techniques, the review covers how these technologies have revolutionized genomics and personalized medicine. It also highlights the importance of computational genomics and bioinformatics, fields that deal with analyzing and interpreting the vast amounts of data generated by DNA sequencing. The review discusses DNA's crucial role in understanding human diseases. It covers DNA-based research in cancer, rare genetic disorders, infectious diseases, and pharmacogenomics (how genes affect a person's response to drugs). It emphasizes studies that have led to new ways of diagnosing and treating diseases. The article looks at the future of DNA research. It talks about emerging technologies like CRISPR-Cas9, a revolutionary gene-editing tool that allows scientists to modify DNA with high precision. Synthetic biology, an interdisciplinary field that combines biology and engineering for designing and constructing new biological parts and systems, is also discussed. Furthermore, DNA nanotechnology, which involves designing DNA molecules for technological uses, is explored. Finally, the review addresses ethical issues in DNA research, such as privacy concerns and debates over genome editing.

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

Retrospective information about the climate system and plant ecophysiology are key inputs in climate and Earth system modelling. Dendrochronology provides such information with large spatiotemporal coverage, and stable carbon isotope (¹³C/¹²C) analysis across tree-ring series is among the most advanced dendrochronological tools. For the past seventy years, this analysis was performed on whole molecules, and, to this day, ¹³C/¹²C variation is attributed to ¹³C discrimination during CO₂ diffusion into leaves and assimilation by rubisco. By contrast, ¹³C discrimination by post-rubisco processes is presumed constant. Here, recently reported results on the first dataset of intramolecular ¹³C discrimination in tree rings were synthesised by variance component analysis. The emerging picture is not consistent with the classical (DR-discrimination-centred) concepts and practices of carbon-isotope dendrochronology. Specifically, leaf and stem post-rubisco discrimination each account for more variation in the data than diffusion-rubisco discrimination, i.e., post-rubisco discrimination is not constant. Furthermore, diffusion-rubisco discrimination is used widely as proxy of leaf intrinsic water-use efficiency (iWUE), a key determinant in the responses of global biogeochemical cycles to climate change. However, since diffusion-rubisco discrimination is a small component of the total data variance, whole-molecule analysis yields confounded iWUE estimates, yet intramolecular analysis will likely offer solutions. Lastly, all currently observed ¹³C/¹²C-climate relationships are attributed to diffusion-rubisco discrimination. However, here, relationships with temperature and radiation derive from leaf-level post-rubisco discrimination while relationships with precipitation derive from stem-level post-rubisco discrimination. That said, advances in mass spectrometry may soon make intramolecular ¹³C/¹²C analysis broadly available taking carbon-isotope dendrochronology to the next level.

In the context of sustainable development, integrating the work aspect into health promotion systems is essential, ensuring that employees maintain a healthy balance between their professional and personal lives, which respects and amplifies the potential of every individual. Lately, there has been a noticeable shift of medical professionals from the public to the private sector. This trend paints a bleak picture, highlighting the vulnerabilities of a system teetering on the brink of failure, with significant impacts on patient care. Among the myriad reasons behind this shift, burnout stands out prominently. Medical professionals face increasing pressures due to understaffing, limited organizational support, and insufficient resources, leading to feelings of cynicism, exhaustion, and detachment from their roles. Utilizing the Maslach et al. questionnaire, we assessed the risk of burnout among physicians in public hospitals to identify and underscore preventive measures and improvements, correlating our findings with key aspects of organizational empowerment. Our research indicates that enhancing interpersonal relationships and resources—both within teams and between the organization and its physicians—is crucial for the revival of the healthcare system. This approach aims at improving the delivery of healthcare services and offering appropriate recognition to healthcare professionals, aligning with the principles of sustainable employment.

Simple Summary: The distribution of typical bacterial redox enzymes such as pyruvate-ferredoxin oxidoreductase (PFOR) in protozoa remains interestingly puzzling. Previous studies have demonstrated diverse cellular localizations of PFOR in some amitochondriate anaerobic protozoa. PFOR is of particular pharmacological importance because it catalyzes the reductive bio-activation of nitro-based prodrugs to cytotoxic radical metabolites. Metronidazole was developed primarily as an antiprotozoal agent against infections caused by Trichomonas vaginalis. However, its antimicrobial spectrum was subsequently expanded to cover anaerobic bacterial infections. It has been shown that mutations in the genes encoding PFOR result in inherent resistance of PFOR-possessing anaerobic protozoa and bacteria to nitro-based prodrugs. Deciphering the evolutionary history of PFOR is crucial in deepening our understanding of the evolution of anaerobic pathogens and unfold new approaches for drug discovery and targeting in pathogen chemotherapy. Abstract: The present frontrunners in the chemotherapy of infections caused by protozoa are nitro-based prodrugs that are selectively activated by PFOR-mediated redox reactions. This study seeks to analyze the distribution of PFOR in selected protozoa and bacteria by applying comparative bioinformatics approaches to test the hypothesis that PFOR was most likely acquired through horizontal gene transfer (HGT) from bacteria. Furthermore, to identify other genes that were putatively acquired using proteome-wide and gene expression analyses. A plausible explanation for the patchy occurrence of PFOR in protozoa is based on the hypothesis that bacteria are potential sources of genes that enhance optimal adaptation of protozoa in hostile environments. The exclusively expressed proteins obtained from Entamoeba histolytica and the putative gene donor, Desulfovibrio vulgaris, showed an over-expression of eleven genes involved in intermediary metabolism. If these results can be reproduced in other PFOR-possessing protozoa, it would provide a more validated evidence to support the horizontal transfer of pfor from bacteria.

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

Allergic reactions are the most frequent adverse effects of blood transfusion, and anaphylactic shock, although less frequent, is systemic and serious. The causes of allergic reactions to blood transfusions are largely unknown, but deficiencies in serum proteins such as haptoglobin (Hp) can lead to anaphylactic shock. A complete deletion of the haptoglobin gene (HPdel) was first identified in families with anomalous inheritance and then verified as a genetic variant that can cause anaphylactic shock because homozygotes of HPdel have an Hp deficiency. Thereby, they may produce antibodies against Hp from blood transfusions. HPdel is found in East and Southeast Asian populations, but not in other populations, with a frequency of approximately 0.9% to 4%. Diagnosis of Hp deficiency due to HPdel prior to transfusion is desirable because severe adverse reactions can be prevented by washing the red blood cells and/or platelets with saline or by administrating plasma products obtained from an Hp deficient donor pool. This review outlines the background of the identification of HPdel and several genetic and immunological methods developed for diagnosing Hp deficiency caused by HPdel.

Recurrent pregnancy loss (RPL) affects around 2 % of women of reproductive age. Primary RPL is defined by ≥2 pregnancy losses and no normal birth delivery. In secondary RPL, the losses are after a normal pregnancy and delivery. Most cases have no clear aetiology, although primary cases are the most complex. Several gene polymorphisms have been associated with RPL. Some polymorphisms are increased in women of Asian or Caucasian race. In admixed RPL populations, the information on possible genetic links is scarce and contradictory. The study aimed to assess the frequency of two SNP in different enzymes involved in medical conditions observed during pregnancy. Microsomal epoxy hydrolase (mEPH) is involved in detoxifying xenobiotics. It is present in ovaries, and it is hormonally regulated. The endothelial nitric oxide synthase forms nitric oxide from arginine and is involved in vascular tone. Two SNPs, rs1051740 and rs1799983, were assessed. The study included 26 controls and 63 primary RPL patients. Significant differences were observed in the frequencies of both SNP (p<0.05). The frequency of mutated alleles was higher in patients. Double mutated homozygotes were encountered only in RLP patients (p<0.05). Genetic polymorphisms rs1051740 and rs1799983 may be involved in primary RPL in the Venezuelan admix population. Genetic studies could provide crucial information on the aetiology of primary RPL.

Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. Neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. This systematic review provides an overview on the value of NfL in early detection of neuropathy, central nervous system involvement, monitoring of neuropathy progression, and treatment effect in systemic amyloidosis. A literature search in PubMed, Embase and Web of Science was performed on 14-02-2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene variant (TTRv) carriers. Only studies containing original data were included. Included were twelve full-text articles and six abstracts describing 1604 participants: 298 controls and 1306 TTRv carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has potential to be used for early detection of neuropathy, monitoring treatment effect, and monitoring disease progression in patients with systemic amyloidosis.

Space exploration is an arduous journey, with future explorations extending in duration, increasing the risk for common space-related health issues such as bone density loss due to microgravity, impaired gut microbiota, cardiovascular ailments, and exposure to cosmic radiation. These ailments can be addressed using medicinal plants. Enhancing their efficacy entails employing gene editing to target specific secondary metabolite pathways associated with therapeutic properties. Moreover, gene editing can combine multiple medicinal properties from various plants, culminating in a singular 'superplant' with enhanced therapeutic benefits. This review discusses the current usage of medicinal plants in promoting human health during space travel, the application of gene editing technology in modifying medicinal plants and presents a vision for the utilization of gene-edited medicinal plants in space to mitigate the risk of various space-related health issues.

Environment pollution is the major problem for all the sectors. In environment pollution there are different types of pollution is included such as air pollution, water pollution, soil pollution etc. In these types of pollution most of it is air pollution. There are many reasons for pollution of air. Human advance in science but one of the major draw backs of science is the pollution of air rapidly. Air pollution is injurious to health. Every year a large number of people died for the effects of air pollution. It can be improved in many ways among these ways technology upgradation plays a major role here. There are various method that prevent air pollution. Many researchers tried and is trying to prevent the air pollution in many ways. In this review paper I summarise the existing research on different ways for preventing air pollution in addition I will discuss the gaps and future aspect on this topic.

Proton-pump inhibitors (PPIs) are the most administered first-line treatment for eosinophilic esophagitis (EoE). However, only around half of EoE patients respond histologically to PPI at double dosage. In addition, 70% of responders maintain EoE in remission after tapering the PPI dose. In order to avoid endoscopy with biopsies − the only accurate method of assessing PPI response − efforts have been made to identify PPI responder patients. Clinical or endoscopic features and biomarkers evaluated so far however, have not proved good enough in predicting PPI response. Although new approaches based on omics technologies have uncovered promising biomarkers, the specialized and complex procedures required are difficult to implement in clinical settings. Alternatively, PPI pharmacogenetics based on identifying variations in CYP2C19 and STAT6 genes have shown promising results in EoE, and could easily be performed in most laboratories. Other genetic variations have also been associated with PPI response and may explain those cases not related to CYP2C19 or STAT6. Here, we give an overview of PPI treatment in EoE and evidence of how genetic variations in CYP2C19 and other genes could affect PPI effectiveness, and also discuss studies evaluating the role of pharmacogenetics in predicting PPI response in patients with EoE.

Although charcoal production is a source of income, it is often associated with deforestation due to the felling of trees in rural areas. The study quantifies the yield of carbonization in the rural area of Lubumba-shi, DRC, and identifies its determinants. By analyzing 20 kilns from professional producers in different villages, the study reveals that these charcoal producers build large kilns, containing an average of 46.9±21.5 m3 of wood from 19 species of miombo trees. The average carbonization yield is 10.2%, varying from village to village due to parameters such as kiln size, quantity of wood used, kiln coverage time, wind exposure, substrate type and tree species. It was noted that the moisture content and size of the wood did not correlate significantly with the quantity of charcoal harvested per kiln. Yield improvement should therefore take these parameters into account to enable charcoal producers to increase their income while adopting sustainable production practices.

Hereditary hemochromatosis (HH) is the main genetic cause of iron overload and is regarded as metal-related human toxicosis. HH may result from HFE and non-HFE gene mutations causing hepcidin deficiency or hepcidin resistance. The disorder has a high biochemical penetrance, but a low clinical prevalence. Unfortunately, the majority of patients with HH remain undiagnosed at their disease-curable stage. The main aim of HH therapy is to prevent iron overload in the early-phase disease and elimination of excess iron from the body by phlebotomy in its late stage. Raising global awareness of HH among health professionals, their training to pay attention to early HH signs and symptoms, and strict patient monitoring are critical management strategies for preventing treatment delays, upgrading its efficacy, and improving patient prognosis.

.(1) Background: Groundwater resources management in dry lands, characterized by climate var-iability and population growth, is difficult. Exploration and exploitation of groundwater, due to inadequate surface water is very costly. The present study employed Analytic Hierarchy Process (AHP) and GIS to identify Ground-Water Potential (GWP) areas in a semi-arid region of Nigeria; (2) Methods: Land-use-land-cover, drainage density, slope, rainfall, static water level, soil media, vadose media and aquifer media were selected for GWP analysis. Parameters weights were de-termined using AHP and ranked based on their contribution to GWP by experts. The parameters were then integrated using weighted overlay tool in ArcGIS 10.5 to produce GWP map of the study area. Boreholes yield data from 245 wells were collected to determine the model accuracy and model validation; (3) Results: Results classified the study area into very high GWP (1.9%), high GWP (8.8%), moderate GWP (62%), low GWP (20.70%) and very low GWP (6.6%). Validation of the AHP model with boreholes yield data shows a correlation coefficient of 71.3% giving a good prediction; (4) Conclusions: AHP and GIS can be used to successfully map GWP areas which could serve as an exploration guide for sustainable management of groundwater resources in semi-arid areas.

The hyper-arid environment is characterized by high inter-annual climatic fluctuations. The yearly average rainfall can change substantially for several years, forming wet or dry sub-periods. Observing rainfall trends over a sub-period can lead to a false perception of a change in the trend but may in fact represent a periodic cycle when examined on a larger time scale. We aimed to better characterize the rainfall regime prevailing in the hyper-arid Arava Valley (Israel/Jordan), and to examine the response of vegetation to annual rainfall. We hypothesized that annual and perennial vegetation would respond differently to wet and dry sub-periods, and that grazing activities will impact vegetation growth. We used a time series of monthly rainfall, from which we calculated Standard Precipitation Index (SPI), and calculated proxies of perennial and annual vegetation over the last four decades using Landsat-derived Normalized Difference Vegetation Index (NDVI). We found no clear trend in rainfall amounts during this period, however we did identify wet and dry sub-periods which were statistically distinct in rain and in vegetation patterns from each other. The highest levels of correlation between rainfall and the NDVI derived proxies were found when examining average rainfall over a period of two- three years for the annual vegetation and over four years for perennial vegetation. Using the Mann-Kendall test, we identified a time lag of two to four years, with the proxies of annual vegetation responding faster than the proxies of perennial vegetation, to shifts between wet and dry sub-period. In addition, we found a consistent difference between natural vegetation cover in Jordan (grazed) and Israel (non-grazed), favoring the development of natural vegetation on the Israeli side. We conclude that integrating between long-term remote sensing satellite imagery and climatic records revealed the greater resilience of perennial vegetation in the hyper-arid region to climatic fluctuation, and enabled us to identify the vegetation’s sensitivity to anthropogenic impact.

Myocardial hypertrophy is the most common condition that accompanies heart changings in children. Transcriptional pathways regulating gene expression playing a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy and congenital heart diseases. This paper describes the state of cardiac gene expression and potential pharmacological modulators at different transcriptional levels. An experimental model of perinatal cardiac hypoxia showed downregulated expression of genes responsible for cardiac muscle integrity and overexpressed genes associated with energy metabolism and apoptosis, which may provide a basis for a therapeutic approach. Current evidence suggests that RNA drugs, theaflavin, neuraminidase, proton pump and histone deacetylase inhibitors are promising pharmacological agents in progressive cardiac hypertrophy. The different points of application of the above drugs makes combined use possible, potentiating the effects of inhibition in specific signaling pathways. The special role of N-acetyl cysteine in both the inhibition of several signaling pathways and the reduction of oxidative stress was emphasized.

Abstract: Brassinosteroids (BR) are essential plant hormones that play a crucial role in regulating plant growth and development, as well as their resistance to abiotic and biotic stresses, including pathogen infections. In the context of plant im-munity, BR influence various processes such as the expression of genes related to pathogen defense, the production of antimicrobial compounds, and the re-inforcement of the plant cell structure. The aim of work is understand the role of BR in plant defense against abiotic and biotic stresses. BR are involved in the regulation of metabolic processes, water economy, and photosynthesis, contributing to increased plant resistance to abiotic stresses. The study discusses various mechanisms of BR action on plant immunity, including the regulation of gene expression related to defense, activation of the plant defense system, in-teraction with other plant hormones, regulation of water and salt balance, and influence on photosynthetic processes. In the context of plant immunity, BR influence various processes, including the expression of genes related to pathogen defense, the production of antimicrobial compounds, and the reinforcement of the plant cell structure. Additionally, BR are involved in the regulation of metabolic processes, water economy, and photosynthesis, con-tributing to increased plant resistance to abiotic and biotic stresses. The paper emphasizes the importance of further research on the role and mechanisms of action of BR in plant immunity, which may contribute to the development of more effective strategies for the use of BR in agriculture, horticulture, and plant protection.

PURPOSE: Breast cancer tumors frequently have intratumor heterogeneity. Tumors with high intratumor heterogeneity have caused therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to poor prognosis for HER2-targeted adjuvant therapies resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with HER2 gene copy number within a tumor sample. Those heterogeneity classified each tumor into the biphasic grade graph (high heterogeneity [HH]) group and the monophasic grade graph (low heterogeneity [LH]) group. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: P < 0.001 (HH:63% vs LH:91% at 10 years), and OS: P = 0.012 (HH:78% vs LH:95% at 10 years). CONCLUSION: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach of heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

In the area of dental healthcare services, where patients and professionals deal with multiple auditory stimuli, this cross-sectional study reports on the intricate dynamics of sound preferences, noise obstacles, and the profound impact of music on anxiety reduction within dental office set-tings. The sample comprises of 134 dental patients, primarily females (56.7%), with varying age groups, education levels, and therapy durations in the university clinics of the department of Dentistry, National and Kapodistrian University of Athens and four private dental offices at the metropolitan area of Athens, Greece. Notably, 92.5% of the participants report no hearing loss, and 56.7% exhibit some level of noise sensitivity. The study reveals a moderate to good perceived health status (M=3.84, SD=0.95) among participants, with low perceived noise disturbance in university dental clinics. Preferences for instrumental music, foreign pop, and classical music are prominent during waiting times. Potential irritations include impersonal treatment (44%) and staff behavior (41.8%). Music player usage within the settings of the dental clinic involves radios (49.3%) and headphones (41.0%). Correlations and predictors indicate associations between health status, music preferences, and noise disturbances. More specifically, visiting the university dental clinics (β = .300, p = .005) as well as younger age (β = .300, p = .034) were significant predictors of better perceived health status. Clearer perception of external sounds while using the music player (β = .190, p = .039) was a significant predictor of better perceived health status, while poorer health was predicted by the preference of Greek folk songs (β = -.200, p = .030). Also, the use of smartphones for playing music was related to poorer health (β = -.370, p < .001). Following, younger age (β = -.270, p = .015), lower education (β = -.210, p = .035), higher noise sensitivity (β = .190, p = .027), as well as feelings of anxiety and nervousness due to ambient noise from people and machines (β = .510, p = .027) were significant predictors of noise disturbance from machines. Also, visiting private clinics (β = .240, p = .018), preferences of specific playlist (β = .310, p = .012), no music (β = .280, p = .016) and use of smartphones to play music (β = .230, p = .029) were significant predictors of noise disturbance from patients or staff. Finally, the preference of listening to a specific playlist was related to better health status (r = .190, p < .05). Findings aim to optimize eco-soundscapes in dental offices, con-tributing to enhanced patient well-being. The research underscores the potential of music inter-ventions to alleviate dental anxiety and improve the overall dental experience and quality care.

During public health events, Active Mobility (walking and cycling) plays an important role in securing residents' travel. To enhance the resilience of urban transportation, this article integrates the travel environment elements for walking and cycling and constructs a travel environment for Active Mobility evaluation index system. This article uses survey data from the main urban area of Harbin in the context of the COVID-19 pandemic in May 2022, and combines the Gradient Boosting Decision Tree (GBDT) and Impact-Asymmetry Analysis (IAA) methods to analyze the satisfaction of the travel environment for Active Mobility. It proposes strategies for optimizing the travel environment for Active Mobility, ensuring residents' travel during public health events, guiding them to adopt Active Mobility, and improving urban transportation resilience. This research shows that Active Mobility can enhance urban transportation resilience. In addition, there are differences in resident demand for walking and cycling environments in the travel environment for Active Mobility. Residents are more concerned about the comfort of the walking environment, while they prioritize the convenience of the cycling environment.

Toxoplasmosis is a zoonosis of warm-blooded animals, affecting also humans, caused by Toxo-plasma gondii, an obligate intracellular parasite with a complex biological cycle. Toxoplasmosis is considered a re-emerging zoonosis and an important public health threat, also for the absence, up to now, of efficient vaccines and preventive measures. Sources of transmission to humans are environmental or food-borne, mainly through the consumption of raw and undercooked meat, predominantly of Sus scrofa, considered highly susceptible to T. gondii. Mainly in the last dec-ades, an effective strategy to counter animal infectious diseases was based on the discovery of resistance immuno-genetic markers, possibly to be used for association studies between geno-typic and phenotypic traits and consequently in Marker Assisted Selection. Until now, this gen-otyping approach has never been adopted for T. gondii infection, so this study aimed, for the first time, to fill this gap. In particular, pigs, reared in different farms of Central Italy, were serologically characterized by an ELISA assay performed on diaphragm meat juice. Out of 179 tested animals, 98 resulted seropositive (54.74%), 57 seronegative (31.84%) and 24 doubtful (10.6%), underlining a possible re-emerging diffusion of this protozoan in the investigated areas. Atten-tion was firstly focused on IL-18 gene, encoding for a pro-inflammatory cytokine that plays a key role starting from the upstream steps of the immunity pathway towards T. gondii. A RT-PCR assay followed by Sanger sequencing of IL-18 cDNA was de novo developed. For this interleukin, at this stage, genetic analysis has not highlighted significant polymorphic variations compared to the reference sequence, except for a seropositive animal. However, the outcomes of this pre-liminary innovative study will be investigated in depth analyzing other relevant genetic re-gions and other target genes.

This review provides an overview of advancements in plant genomics, emphasizing key stages in genomics projects and addressing associated challenges. Long read sequencing enables the cost-effective sequencing of plant DNA and assembly of highly continuous genome sequences - often even separating haplophases. Incorporating external hints, such as cDNA sequences from RNA-seq or full length cDNA sequencing, enhances the identification of gene models. While these steps enable high-throughput exploration of numerous plant genomes, a significant bottleneck lies in elucidating gene functions. The classical approach based on wet lab methods is impractical when dealing with thousands of genes in a new genome sequence. To overcome this challenge, computational tools harnessing existing information for cross species knowledge transfer are essential for expediting the functional annotation process. In support of researchers entering the field of plant genomics, a collection of recommended tools has been curated and is accessible at https://github.com/bpucker/ToolOverview.

Many protein expression systems are primary utilised to produce a single, specific recombinant protein. In contrast, most biological processes such as virus assembly rely upon a complex of several interacting proteins rather than the activity of a sole protein. The high complexity of the baculovirus genome, coupled with a multiphase replication cycle incorporating distinct transcriptional steps, made it the ideal system to manipulate for high-level expression of a single or co-expression of multiple foreign proteins within a single cell. We have developed and utilised a series of recombinant baculovirus systems to unravel the sequential assembly process of a complex non-enveloped model virus, Bluetongue virus (BTV). The high protein yields expressed by the baculovirus system not only facilitated structure-function analysis of each viral proteins but were also advantageous to crystallography studies and supported the first atomic level resolution of a recombinant viral protein, the major BTV capsid protein. Further, the formation of recombinant double-shelled virus-like particles (VLPs) provided insights into the structure-function relationships among the four major structural proteins of the BTV whilst also representing a potential candidate for a viral vaccine. The baculovirus multi-gene expression system facilitated the study of structurally complex viruses (both non-enveloped and enveloped viruses) and heralded in a new generation of viral vaccines.

The current study was formulated with the aim of assessing the impact of the Extent of Drug addiction on the Family environment and interventions for drug-addicted youth in rural areas of Dir Lower Khyber Pakhtunkhwa, Pakistan. The study comprised a dependent variable (Extent of Drug addiction) and an independent variable (Family Environment). A sample size of 266 was randomly selected for primary data collection through structured interviews. The collected information was evaluated through descriptive analysis (frequency and percentage distribution) and inferential analysis, specifically utilizing the Chi-square Statistical Test. The study concluded that drug addiction among youth has an adverse impact on the family environment, leading to instability and violent behavior. Further, families of drug-addicted youth experience a high level of dissatisfaction in relationships, often culminating in divorce. Similarly, the families of drug-addicted are characterized by low cohesion, role conflict, and tolerance. Thus, the government should formulate polices and strategies for the prevention of drug addiction, with speedy implementation across all institutional dynamics, including family. Moreover, It is also crucial to rehabilitate the lifeblood of a nation (youth) in terms of socio-economic, emotional and psychological growth. These recommendations were put forward in the light of the current study.

Thymomas (TH) are a unique group of heterogeneous tumors of the thymic epithelium. In particular, the subtypes B2 and B3 tend to be aggressive and metastatic. Radical tumor resection remains the only curative option for localized tumors, while more advanced TH require multimodal treatment. Deep sequencing analyses have failed to identify known oncogenic driver mutations in TH, with the notable exception of the GTF2I mutation, which occurs predominantly in type A and AB TH. However, there are multiple alternative non-mutational mechanisms (e.g., perturbed thymic developmental programs, metabolism, non-coding RNA networks) that control cellular behavior and tumorigenesis through deregulation of critical molecular pathways. Here, we attempted to show how the results of studies investigating such alternative mechanisms could be integrated into a current model of TH biology. This model could be used to focus ongoing research and therapeutic strategies.

The AREB/ABF (ABA response element binding) proteins in plants are vital for plant stress responses, but the understanding of AREB/ABFs in orchid species, an important traditional medicinal and ornamental plants, is limited. Here, twelve AREB/ABF genes were identified within three orchids’ complete genome and classified into three groups (groups I, II, and III) via a phylogenetic analysis, which was further supported by the analysis of their conserved motifs and gene structures. The cis-elements analysis showed that hormone response elements followed by light and stress responses were widely rich in AREB/ABFs. A prediction analysis of orchid ABRE/ABF-mediated regulatory network was further constructed through cis-regulatory elements (CREs) analysis of their promoter regions and revealed that several transcriptional factor (TF) gene family were abundant as the potential regulators for orchid AREB/ABFs. Expression profile analysis based on public transcriptomic data showed that most AREB/ABF genes have distinct tissue-specific expression patterns in orchid plants. Additionally, DcaABI5 as the homolog of ABA INSENSITIVE 5 (ABI5) from Arabidopsis was selected for further analysis. The results showed that Arabidopsis transgenic overexpressing DcaABI5 could rescue the ABA insensitive phenotype in the mutant abi5. Collectively, these findings will provide valuable information on AREB/ABF genes in orchids.

The feeling of beauty is one of the positive human feelings. In architecture and design, it is associated with forms appropriate to their purpose. The usefulness of products to meet needs is also important. They are well received by users. The task of designers is to achieve perfection in their work. The rational design and use of artificial living environments are expressions of concern for natural resources (sustainable environment). These issues are addressed, i.e., by an interdisciplinary initiative of the New European Bauhaus. The aim of the paper is to expand knowledge about beauty and utility. They are important when choosing mass-produced goods. The article uses research methods: interpretive research, analyses, comparisons, logical argumentation, etc. Experimental qualitative research using a checklist was used. The results expand the knowledge on the selected topic and research scope of the research of the paper. The survey can be used to rationally evaluate architecture, interiors, and design facilities. It can be helpful for various aesthetic and functional strategies dedicated to different users. The paper demonstrates the role of beauty and functionality in the built environment. They are analyzed in the context of social and technical conditions, as well as contemporary sustainable design

A novel educational platform called Shared Modeling and Simulation Environment (SMSE) was initiated in the ERASMUS+ “CybPhys” project. It integrates the Jupyter platform, including Ju-pyter Notebooks, for e-learning in the STEM field. A novel platform enhances e-learning by combining Moodle with Jupyter's capabilities to create virtual labs. A survey was conducted in the spring of 2023 among bachelor and master students of Chernihiv National Polytechnic Uni-versity aimed to gather feedback from students using SMSE in their e-learning process. Two student groups were involved: one of them consisted of students using SMSE in both the autumn and spring semesters and another represented the students starting with SMSE in the spring se-mester. The survey based on the adjusted Technology Acceptance Model (TAM) was conducted to understand the acceptance of this e-learning approach. A comprehensive analysis of students’ answers based on the TAM approach revealed the inside of the process of transformation of stu-dents’ perceptions during the acquisition of the SMSE platform. Our research demonstrates that SMSE effectively merges Moodle's online learning capabilities with Jupyter notebooks, provid-ing a flexible and interactive learning experience for both in-class and remote students. It pro-vides a web-based, multifunctional e-learning environment that combines a variety of tools and technologies, giving students the possibility to be involved in all sorts of teaching activities, such as lectures, exercises, simulations, etc., through the use of one single online environment.

Because it can make exact double-strand breaks in DNA, CRISPR-Cas9 can help almost every species and type of cell. It is a powerful way to change the DNA code. CRISPR-Cas9 can be used for a lot more than just changing genes. We are close to being able to do high-throughput gene screening, epigenome editing, in-vivo cell tagging, and RNA change. With the help of CRISPR-Cas9, the function of genes can be studied better, and more realistic disease models can be made. The revolutionary new discipline of gene editing has the potential to profoundly impact healthcare and the life sciences. By simplifying the process of creating double-strand breaks in the DNA of almost any species or kind of cell, CRISPR-Cas9 has revolutionized gene editing. Numerous applications have been found for the CRISPR-Cas9 system. High-throughput gene screening, RNA modification, live-cell chromosome marking, and epigenome editing are all examples. CRISPR-Cas9 facilitates gene research, leading to the development of CRISPR-based disease models. CRISPR-Cas9-based methods of altering the genome will aid researchers in learning more about sickness and discovering better ways to cure it, despite the fact that there are still many questions and large difficulties to answer.

Intratumoral immune cytolytic activity (CYT), measured as the geometric mean of the expression of Granzyme-A (GZMA) and Perforin-1 (PRF1), has emerged as a critical factor in cancer immunotherapy, with significant implications for patient prognosis and treatment outcomes. Here, we review how different immune checkpoint pathways, the composition of Tumor Microenvironment (TME), antigen presentation and metabolic pathways, all regulate CYT. We also discuss the various methods through which CYT can be assessed. The detection and analysis of tumor-infiltrating lymphocytes using flow cytometry or immunohistochemistry provide important information on the immune cell populations within the TME. Gene expression profiling and spatial analysis techniques, such as multiplex immunofluorescence and imaging mass cytometry, allow researchers to study CYT in the context of the TME. We further report the significant clinical implications that CYT has, as its increased levels are associated with positive clinical outcomes and a favorable prognosis. Moreover, CYT can be used as a prognostic biomarker and aid in patient stratification. Measuring CYT through different methods offers promising paths for improving treatment responses. Overall, we highlight that the understanding and modulation of CYT levels is critical for improving cancer immunotherapy. Research into CYT and the factors that influence it has the potential to transform cancer treatment and improve patient outcomes.

The variety of risks due to climate change with a potential impact on Cultural Heritage CH requires a multidisciplinary approach and a preliminary overview of the existing methods for risk analysis and assessment in different fields. Thus, the starting point of the research conducted by the Sapienza PNRR working group consists in a systematic literature review of risk assessment approaches, methods and indicators. As a first outcome, the research has designed a multidisciplinary comprehensive framework consisting of the definition of risk categorization, the framework represented by a measurable index and the main target, according to the classification of Cultural Heritage based on the harmonization of European vocabularies definitions and protocols. The risk assessment framework sets the methodological core of a future multi criteria matrix and digital platform for decision focused on the historic built environment and it is functional to the definition of specific operational guidelines connected to each risk for elaborating descriptive/predictive Architectural Heritage’s transformation scenarios to support the development of mitigation and adaptation strategies.

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterized by persistent open skull sutures whit bulging calvaria, hypoplasia or aplasia of clavicles permitting abnormal opposition of the shoulders, wide public symphysis, short middle phalanx of the fifth fingers and vertebral, craniofacial and dental anomalies. It is a rare disease, with a prevalence of 1-9/1,000,000, high penetrance, and variable expression. The responsible gene of CCD is the runt-related transcription factor 2 gene (RUNX2). We characterize the clinical, genetic and bioinformatic results of four CCD cases. Two Mexican familial with 6 affected members, 9 asymptomatic individuals, and two sporadic cases with CCD, as well as 100 healthy controls. Genomic DNA analyses of the RUNX2 gene was performed for Sanger sequencing. Bioinformatics tools, used to predict the function, stability, and structural changes of the mutated RUNX2 proteins. Three novel heterozygous mutations (c.651_652del; c.538_539delinsCA; c.662T>A) and a previously reported mutation (c.674G>A) were detected. In silico analysis showed that all mutations had functional, stability, and structural alterations in RUNX2 protein. Our results show novel mutations that enrich the pool of RUNX2 gene mutations with CCD. In addition, one patient presented clinical data not previously reported that could represent an expanded phenotype of sever expression.

The architecture, organization and functioning of biocatalytic reaction networks, which are coded in the cell specific genome and which work together in the small space of biological cells, are a fascinating feature of life evolved over more than 3 billion years. The knowledge about the diversity of biocatalytic functions and metabolic pathways sustaining life on our planet is highly important, especially as the currently occurring loss of biodiversity is considered a planetary boundary which is at high risk, and knowledge about the life of current biological organisms should be gained before they become extinct. In addition to the well-known enzymatic reactions involved in biochemical pathways, the enzyme universe offers numerous opportunities for discovering novel functions and pathways. Maintaining thousands of molecules and reactions functioning properly within biological cells, which may be exposed to various kinds of external hazards, environmental stress, enzymatic side reactions or non-enzymatic chemical reactions, is key for keeping cellular life healthy. This review aims at outlining advances in assigning enzyme functions to protein sequences and the discovery of novel biocatalytic functions and pathways.

Glioblastoma multiforme (GBM), the most prevalent primary malignant brain tumor in adults, exhibits a dismal 6.9% five-year survival rate post-diagnosis. Thymoquinone (TQ), the most abundant bioactive compound in Nigella Sativa, has been extensively researched for its anti-cancer properties across various human cancers. Yet, its specific anticancer mechanisms and pathways in glioblastoma remain to be elucidated. In this study, we assessed the impact of different TQ concentrations on the viability of A172 cells using WST-8 and Toluidine blue assays, followed by RNA sequencing (RNA-seq) to identify differentially expressed genes (DEGs). We confirmed their expression levels through quantitative RT-PCR and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for these DEGs. RNA-seq revealed no significant gene expression changes at 2.5 µM and 5 µM TQ concentrations. However, at 25 µM and 50 µM, TQ significantly reduced cell viability in a dose-dependent manner. We identified 1548 DEGs at 25 µM TQ (684 upregulated, 864 downregulated) and 2797 DEGs at 50 µM TQ (1528 upregulated, 1269 downregulated), with 1202 DEGs common to both concentrations. TQ inhibited key pathways such as PI3K-Akt signaling, calcium signaling, focal adhesion, and ECM-receptor interaction in A172 cells. It downregulated several potential oncogenes (e.g., AEBP1, MIAT) and genes linked to GBM proliferation and migration (e.g., SOCS2, HCP5), while modulating Wnt signaling and upregulating tumor suppressor genes (e.g., SPRY4, BEX2). TQ also affected p53 downstream targets, maintaining p53 levels. This study elucidates the anticancer mechanisms of TQ in A172 GBM cells, underscoring its effects on multiple signaling pathways and positioning TQ as a promising candidate for innovative glioblastoma treatment strategies.

Ribosomal proteins (r-proteins) are abundant, highly conserved, and multifaceted cellular proteins in all domains of life. Most r-proteins have RNA-binding properties and are able to form protein-protein contacts. Bacterial r-proteins govern the co-transcriptional rRNA folding during ribosome assembly and participate in formation of the ribosome functional sites such as the mRNA binding site, tRNA binding sites, the peptidyl- transferase center, and the protein exit tunnel. In addition to their primary role in a cell as integral components of the protein synthesis machinery, many of r-proteins can function beyond the ribosome (the phenomenon known as moonlighting), acting either as individual regulatory proteins or in complexes with various cellular components. Extraribosomal activities of r-proteins have been intensively studied over decades (reviewed in [1]). The past decade brought significant advancement in our knowledge of r-protein functions due to expanding studies on ribosomes and gene expression mechanisms not only in model bacteria like Escherichia coli or Bacillus subtilis, but also in previously little-explored bacterial species from various phyla. This review is aimed to update the information on multiple functions of r-proteins in bacteria.

The advent of CRISPR/Cas9 technology has revolutionized genome editing, enabling the attainment of once-unimaginable goals. CRISPR/Cas's groundbreaking attributes lie in its simplicity, versatility, universality, and its independence from customized DNA-protein systems, erasing the need for specialized expertise and broadening its scope of applications. Beyond its editing prowess, the discovery of novel Cas-based systems has spawned an array of additional biotechnological tools, empowering both fundamental and applied research. Researchers have harnessed CRISPR/Cas for gene regulation, deepening insights into gene expression and epigenetic changes. Precisely targeting DNA or RNA sequences, CRISPR/Cas effectively identifies and counters pathogens. Furthermore, it aids in genome imaging and sequencing, revealing genome spatial organization and chromatin dynamics. The non-editing applications of CRISPR/Cas exhibit tremendous potential across diverse domains, including diagnostics, biotechnology, and fundamental research. This article reviews and critically evaluates the primary CRISPR/Cas-based tools developed for plants and animals, underlining their transformative impact.

Traditional gene set enrichment analysis falters when applied to large genomic domains, where neighboring genes often share functions. This spatial dependency creates misleading enrichments, mistaking mere physical proximity for genuine biological connections. Here we present Spatial Adjusted Gene Ontology (SAGO), a novel cyclic permutation-based approach, to tackle this challenge. SAGO separates enrichments due to spatial proximity from genuine biological links by incorporating the genes' spatial arrangement into the analysis. We applied SAGO to various datasets in which the identified genomic intervals are large, including replication timing domains, H3K9me3 and H3K27me3 large domains, HiC compartments and lamina associated domains (LADs). Intriguingly, applying SAGO to prostate cancer samples with large copy number alteration (CNAs) domains eliminated most of the enriched GO terms, thus helping to accurately identify biologically relevant gene sets linked to oncogenic processes, free from spatial bias.

Subclinical inflammation in protocol biopsies relates to tacrolimus exposure and human leukocyte antigen (HLA) matching. We aimed to characterize transcripts associated with rejection and tacrolimus exposure and its association with transplant outcome. We tested whether gene expression is associated with rejection using strictly normal protocol biopsies (n = 17) and biopsies with TCMR or ABMR according to Banff criteria (n = 12). Subsequently, we analyzed these transcripts in a set of 4-month protocol biopsies (n = 137) to assess their association with donor and recipient characteristics, the intensity of immunosuppression, and graft outcome. Differential expression (FDR&gt;3) between normal and rejection biopsies yielded a set of 111 genes. Nineteen out of these 111 genes were correlated with tacrolimus trough levels (TAC-C0) at the time of biopsy in the protocol biopsy cohort (n=137) and allowed us to define 2 clusters of biopsies. The 2 clusters differed in donor age and tacrolimus levels. Subclinical rejection, including borderline lesions, tended to occur in the same cluster. Logistic regression analysis indicated that TAC-C0 at the time of biopsy (OR: 0.83, 95%CI:0.72-0.06, p=0.0117) was associated with cluster 2. In a follow-up averaging 70±30 months, this patient group displayed a significant decline in renal function (p=0.0135). The expression of rejection-associated transcripts in early protocol biopsies is associated with tacrolimus exposure and a faster decline in renal function.

This work aimed to identify chemical compounds of Cinnamomum burmannii leaf essential oil (CBLEO) and to unravel antibacterial mechanism of CBLEO at molecular level for developing antimicrobial. CBLEO had 37 volatile profiling with abundant borneol (28.40 %), and showed good potential to control foodborne pathogens, of which Staphylococcus aureus had the greatest inhibition zone diameter (28.72 nm) with the lowest values of minimum inhibitory concentration (1.0 μg/mL) and bactericidal concentration (2.0 μg/mL). To unravel antibacterial action of CBLEO on S. aureus, a dynamic exploration of antibacterial growth, material leakage, ROS formation, protein oxidation, cell morphology and interaction with genome DNA were conducted on S. aureus exposed to CBLEO at different doses (1/2-2×MIC) and times (0-24 h), indicating that CBLEO acts as inducer for ROS production and oxidative stress of S. aureus. To highlight antibacterial action of CBLEO on S. aureus at molecular level, a comparative association of ROS accumulation with some key virulence-related gene (sigB/agrA/sarA/icaA/cidA/rsbU) transcription, protease production and biofilm formation in S. aureus subjected to CBLEO at different levels and times, revealing that CBLEO-induced oxidative stress caused transcript suppression of virulence regulators (RsbU and SigB) and its targeted genes, causing protease level increase destined for biofilm formation and growth inhibition of S. aureus, which may be as key bactericidal action. Our findings provide valuable information for studying the antibacterial mechanism of essential oil against pathogens.

Streptomyces sp. HNS054, which was previously isolated from a marine sponge, demonstrates vigorous growth and facile genetic modification. This study explores its potential as a marine ac-tinomycete chassis through complete genome sequencing and genetic engineering. With a 7.5 Mb genome containing 6678 predicted genes, 21 secondary metabolic biosynthetic gene clusters (BGCs), and 8 common site-specific recombination (SSR) system attB loci, HNS054 shows a close phylogenetic relation to S. griseoincarnatus strain RB7AG. Utilizing multiplexed site-specific ge-nome engineering (MSGE) and the CRISPR/Cas9 method, engineered strains derived from HNS054 (with three copies of the target BGCs) produce higher amounts of aborycin and ac-tinorhodin than S. coelicolor M1346 (containing three copies of the same BGCs). HNS054 stands out for its remarkable characteristics, including salt tolerance, rapid growth, and compatibility with synthetic biology tools, and positions it as a promising candidate for developing marine ac-tinomycete hosts to enhance secondary metabolite production.

Age-related macular degeneration (AMD) is an eye disease and the most common cause of vision loss in the Western World. In its advanced stage, AMD occurs in two clinically distinguished forms: dry and wet, but only wet AMD is treatable. However, the treatment based on repeated injections with vascular endothelial growth factor A (VEGFA) antagonists may at best stop the disease progression and prevent or delay vision loss but without an improvement of visual dysfunction. Moreover, it is a serious mental and financial burden for patients and may be linked with some complications. The recent first success of intravitreal gene therapy with ADVM-022, which transformed retinal cells to continuous production of aflibercept, a VEGF antagonist, after a single injection, has opened a revolutionary perspective in wet AMD treatment. Promising results obtained so far in other ongoing clinical trials support this perspective. In this narrative/hypothesis review, we present basic information on wet AMD pathogenesis and treatment, the idea of gene therapy in retinal diseases, update evidence on completed and ongoing clinical trials with gene therapy for wet AMD, and perspectives on the road to the clinic of “one and done” therapy for wet AMD to replace a lifetime of injections. Gene editing targeting the VEGFA gene is also presented as another gene therapy strategy to improve wet AMD management.

The corneal epithelium (CE) is spread between two domains, the outer vascularized limbus and the avascular cornea proper. Epithelial cells undergo constant migration from the limbus to the vision-critical central cornea. Coordinated with this migration the cells undergo differentiation changes where a pool of unique stem/precursor cells at the limbus yields the mature cells that reach the corneal center. Differentiation is heralded by the expression of the corneal-specific Krt12. Processing data acquired by scRNA-Seq we found that the increase of Krt12 expression occurs in four distinct steps within the limbus plus a single continuous increase in the cornea. Differential gene analysis demonstrated that these domains reflect discreet stages of CE differentiation and yielded extensive information of the genes undergoing down or up regulation in the sequential transition from less to more differentiate conditions. The approach allowed the identification of multiple gene cohorts, including a) the genes that have maximal expression in the most primitive, Krt12-negative cell cohort, which is likely to include the stem/precursor cells; b) the sets of genes that undergo continuous increase or decrease along the whole differentiation path, and c) and the genes showing maximal positive or negative correlation with the changes in Krt12.

The field of water management is continually changing. Water has been subject to external shocks in the form of climate change and globalization. Analysis of water management is subject to disciplinary developments and inter-disciplinary interactions. Are these developments well documented in the literature? Initial observations on interdisciplinary literature suggest that results are fragmented, implying that a state-of-the-art review is needed. The objective of this paper is to close this gap by reviewing recent developments in water economics that address the increasing perceptions of water scarcity by looking first at changes in supply and quality of water, and then at impacts of climate change on water extremes. Among responses to such challenges, the paper identifies changes to water use patterns by including and co-managing water from different sources—surface and groundwater, wastewater, and desalinated water. Technological advancements also are among the resources that address water challenges. Water challenges reflect also on management of internationally shared water. A recent surge in scientific work identified international treaties as playing a significant role in water management. The paper reviews recently employed economic tools, such as experimental economics, game theory, institutional economics, and valuation methods. And finally, it explores modeling approaches, including hydro-economic and computable general equilibrium models that are being used to deal with water challenges.

The air transport industry has experienced important transformations over the last decades, despite its continuous global trend of growth. After air transport liberalization process, the present market situation depicts a reduced number of large hub & spoke airlines and an important number of so-called low-cost carriers (LCC). One may wonder why airlines that were once thriving and profitable before liberalization have disappeared, some even recently amid an expansion in demand. To answer that question and others related to it, this paper proposes a management model focused on the airline business, putting in relation the main variables defining the business behavior of an airline. The lessons learned from the past, and the solutions gathered from the model related with, will provide a sound basis to address the new challenges for the next years to come, as it is the case of the new environmental regulations focused on the air transport decarbonization.

The MQTT IoT connection technology is widely used, becoming the primary means for IoT devices to communicate with servers amid the vigorous development of IoT technology. On the OneNET cloud platform, MQTT protocol connection and data communication, message sending, and subscription are established, one-to-many message transmission is solved, and the reverse control from server to device is realized in big data environment. This technology can provide fast and secure messaging services for remote devices with a small code capacity and limited bandwidth. Experiments indicated that the communication mode has low cost, small bandwidth, and slight delay, which meets the requirements of device data acquisition and control in a large area and has broad application prospects and reference significance in the field of mobile applications.

Breeding for low hydrogen cyanide (HCN) varieties is a major objective of programmes targeting boiled cassava food product. To enhance breeding for low HCN, knowledge on genetic variation and trait heritability is essential. In this study, 64 cassava clones established across four locations and evaluated for HCN using three HCN assessment methods; 1 to 9 scale, 0 ppm to 800 ppm scale and a quantitative assay based on spectrophotometer readings (HCN_Spec). Data were also collected on the weather variables precipitation, relative humidity, and temperature. Significant differences were observed among clones (P &lt; 0.001) and locations (p &lt; 0.001). There were also significant (p &lt; 0. 001) clone by environment interactions. Locations Arua and Serere posted higher HCN scores among clones and were associated with significantly higher (p &lt; 0.001) mean daily temperature (K) and lower relative humidity (%) across 12-hour and 18-hour intervals. Within locations HCN broad sense heritability estimates ranged 0.22 – 0.64 while combined location heritability estimates ranged 0.14 to 0.32. Relationships between the methods were positive and strong (R2 = 0.75 – 0.92). It is expected that the information herein will accelerate efforts towards breeding for low HCN cassava varieties.

(1) Background: Intracortical microelectrodes (IMEs) are an important part of interfacing with the central nervous system (CNS) and recording neural signals. However, recording electrodes have shown a characteristic steady decline in recording performance owing to chronic neuroinflammation. The topography of implanted devices has been explored to mimic the nanoscale three-dimensional architecture of the extracellular matrix. Our previous work used histology to study the implant sites of non-recording probes and showed that a nanoscale topography at the probe surface mitigated the neuroinflammatory response compared to probes with smooth surfaces. Here, we hypothesized that the improvement in the neuroinflammatory response for probes with nanoscale surface topography would extend to improved recording performance. (2) Methods: A novel design modification was implemented on planar silicon-based neural probes by etching nanopatterned grooves (with a 500 nm pitch) into the probe shank. To assess the hypothesis, two groups of rats were implanted with either nanopatterned (n=6) or smooth control (n=6) probes, and their recording performance was assessed over 4 weeks. Postmortem gene expression analysis was performed to compare the neuroinflammatory response from the two groups. (3) Results: Nanopatterned probes demonstrated increased impedance and noise floor compared to controls. However, the recording performance of the nanopatterned and smooth probes was similar, with active electrode yield for control probes and nanopatterned probes being approximately 50% and 45%, respectively by 4 weeks post-implantation. Gene expression analysis showed 1 gene, Sirt1, differentially expressed out of 152 in the panel. (4) Conclusions: This study provides a foundation for investigating novel nanoscale topographies on neural probes.

Carotid intima-media thickness (CIMT) is a surrogate indicator for atherosclerosis and has been shown to predict cardiovascular risk in multiple large studies. Identifying and characterizing molecular markers for carotid atheroma plaque formation can be critical for early intervention and prevention of atherosclerosis. This study performed transcription factor (TF) network analysis of transcriptomic data focusing on two TF genes, ZNF385D, HAND2, whose polymorphisms reportedly associate with carotid atherosclerosis. Gene expression data were measured from pieces of carotid endarterectomy of hypertensive patients each paired with one sample of distant macroscopically intact tissue. TF networks were reconstructed for ZNF385D and HAND2 and their association with carotid atheroma progression examined using gene-set enrichment analysis with high statistical significance (p<6.95e-7) suggesting involvement of expression quantitative loci (eQTL). Examination of the regulation and correlation patterns suggests high clinical and interventional impacts of the two TF genes on impairing carotid atheroma plaque formation and preventing carotid atherosclerosis.

Human Epidermal Growth Factor Receptor 2(HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. It is generally considered as a poor prognostic marker. Targeted therapies, such as small molecule tyrosine kinase inhibitors (TKIs), showed limited efficacy in HER2-mutant advanced Non-Small Cell Lung Cancer (NSCLC). In the 2023 NCCN guidelines for NSCLC, Antibody-Drug Conjugate(ADC) Trastuzumab emtansine (T-DM1) is recommended for the treatment of HER2-mutant Lung Cancer (LC). However, this medication is currently not approved in certain regions.So it is necessary to explore alternative treatment options for HER2-mutant NSCLC patients.In our study of a patient with HER2 exon 20ins Lung Adenocarcinoma who had previously failed multiple TKI treatments, we discovered that Sunvozertinib could stabilize the patient's condition, achieving a progression-free survival (PFS) of 87 days. This is a novel finding that may provide new treatment options for HER2 exon 20ins patients who have failed TKI therapy.

Abstract: There are a large number of cross-linked chemical bonds such as tight disulfide bonds, hydrogen bonds,and salt bonds in keratin, which makes it difficult to break the structural stability of the protein using conventional methods. The degradation of feather waste using keratinases produced by microorganisms has the advantage of being efficient and environmentally friendly. In this study, 23 strains capable of producing transparent circles were obtained via preliminary screening with skim milk as the sole carbon and nitrogen source, and 9 strains capable of degrading feathers were obtained via rescreening with feathers as the sole carbon and nitrogen source. Finally, through the determination of enzyme activity, the strain CY-A with a high ability to degrade feathers was obtained. The strain was identified as Bacillus tequilensis via morphological observation, physiological and biochemical identification, and 16 S rRNA molecular biology. The keratinase gene (bta) of Bacillus tequila was cloned, and its full-length gene sequence was 1110 bp, containing an open reading frame of 1089, encoding 369 amino acids (GeneBank accession number OR733336). The physicochemical properties, secondary structure, and tertiary structure of the recombinant protein were analyzed using bioinformatics tools such as ProtParm, SOPMA, MEGA, and SWISS-MODELS. It was found that the relative molecular mass was 37.953 kD and that the isoelectric point was 8.48. The protein was a hydrophilic protein. The keratinase bta gene was ligated to the expression vector pET28a(+) using T4 ligase, and the recombination expression plasmid pET28-bta was constructed and transformed into E. coli BL21(DE3) to obtain recombinant engineered bacteria. The expressed keratinase was purified using a Ni2+ affinity chromatography column to obtain recombinant bta keratinase bta with a molecular weight of 37.953 kD. The identification and characterization of this keratinase gene provides some theoretical basis for the further enhancement of keratinase activity by means of genetic engineering.

The ability of S. aureus to infect humans and cause a wide range of infections so efficiently is a consequence of the many variant virulence factors that it can produce. Superantigens (SAgs) make up a group of them and include staphylococcal enterotoxins (SE). The main objective of this study was to detect enterotoxin gene cluster (EGC) in S. aureus isolates that caused infections in Paraguayan children in the year 2017, through an observational and cross-sectional study. The detection of the EGC including the seg, sei, sem, sen, seo, and seu genes, was carried out by end-point PCR. 181 S. aureus isolates were collected, most of them caused skin and soft tissue infections (SSTI, n=140, 77%) and came from children under 6 years 50% (n=90). At least one SE gene was detected in 96% (174/181) of isolates and 24% (44/181) carried the entire EGC. An association between methicillin resistance and seg, sei, seo, and seu gene carriage (p ≤0.05) was observed. A high prevalence of EGC was detected in S. aureus isolates collected from infected children attending the main health care centers in Paraguay, its importance is due to the potential of these toxins to aggravate staphylococcal infections.

Background A diet rich in red meat, and poor in fruits and vegetables, can hinder the body's ability to detoxify, therefore, an alternative vegetarian diet maintained over a certain period, determines the elimination of excess toxins and accumulated residues, helping the body to regenerate and recharge energy. Following this simple rule, there are a multitude of benefits for our health. Significance of the autophagy process An even better regeneration of the body takes place during the black fast, in which senescent cells, (dead cells that no longer exercise any function, but instead produce inflammation in the body), are eliminated by autophagy, and in their place, the cells are stimulated stem. Aging can be associated with various pathological conditions if autophagy is not promoted by a healthy lifestyle. In elderly people, cells can show DNA mutations and accumulations of protein aggregates that impair the body's physiological processes. Several studies have shown that the activation of autophagy slows down the ageing process. Conclusions Aging, and its associated conditions of illness, are due to genomic instability caused by DNA damage, telomere shortening and epigenome changes that modulate gene expression.

Phytoene desaturase (PDS) is a plant enzyme involved in carotenoid biosynthesis. The PDS gene has been used as a selective marker for genome editing in several plant species, including banana (Musa spp.). Its knockout promotes dwarfism and albinism, characteristics that are easily recognizable and highly favorable. In Musa spp., the A genome increases fruit production and quality, whereas the B genome is associated with tolerance to biotic and abiotic stresses. The objective of this study was to identify a molecular marker in the PDS gene to easily discriminate the A and B genomes of banana. A 2166 bp fragment for the ‘PDSMa’ marker was identified as polymorphic for the A genome (identification accuracy of 99.33%), whereas ~332 and ~225 bp fragments were detected for the ‘PDSMb’ primer with 100% accuracy using MedCalc software. To the best of our knowledge, this is the first study to use the PDS gene to determine doses of the A genome and identify the B genome in Musa spp., which will aid in evaluating the genomic constitution of banana hybrids and accessions at the seedling stage, and accelerating their classification in crop genetic improvement programs.

Expansins (EXPs) which are the essential components of plant cell wall function as relaxation factors to directly promote turgor-driven expansion of cell wall and control plant growth and development and diverse environmental stress responses. A lot of EXPs genes have been widely identified and characterized in numerous plant species, but not in sweetpotato. In the present study, a total of 59 EXPs genes that unevenly distributed onto 14 of 15 chromosomes were identified from sweetpotato genome, and segmental and tandem duplications were exhibited to act as dominant functions in IbEXPs diversity. Phylogenetic analysis exhibited that IbEXPs members were clustered into four subfamilies according to EXPs in Arabidopsis and rice and the regularity of motif, domain and gene structures was in accordance with the subfamily classification. The collinearity analysis between IbEXPs and related homologous sequences in 9 plants provided the phylogenetic insights of EXPs gene family. Cis-element analysis futhrer revealed the potential roles of IbEXPs in sweetpotato development and stress responses. Evidence from RNA-seq and qRT-PCR analysis of eight selected IbEXPs genes displayed their various tissue specificity in different tissues, and their transcripts were varyingly induced or suppressed under multiple hormone treatments (ABA, SA, JA and ACC) and abiotic stresses (low and high temperature). These results supply worthy foundations to further comprehensively investigate the exact functions of IbEXPs genes, and multiple members may function as promising regulators to control plant development and enhance the stress resistance of transgenic plants.

Floating wind is becoming an essential part in terms of renewable energy. Therefore, highlighting the perspectives in developing the floating wind platforms is very important. In this paper, we focus on floating wind concepts and projects around the world. This will give a taste to the reader about what is going on in terms of the projects around the world. The main aim of this work is to further explain the collected data regarding the floating wind concepts and projects, and further classify them in terms of cost, power capacity, wind speed, water depth, and distance to shore.

Resistance to therapy and disease progression are the main causes of mortality in most cancers. In particular, the development of resistance is an important limitation affecting the efficacy of therapeutic alternatives for cancer, including chemotherapy, radiotherapy, and immunotherapy. Signaling pathways are largely responsible for the mechanisms of resistance to cancer treatment and progression, and multiple myeloma is no exception. p38 mitogen-activated protein kinase (p38) is downstream of several signaling pathways specific to treatment resistance and progression. Therefore, in recent years, developing therapeutic alternatives directed at p38 MAPK has been of great interest, in order to reverse chemotherapy resistance and prevent progression. In this review, we discuss recent findings on the role of p38, including recent advances in our understanding of its expression and activity as well as its isoforms, and its possible clinical role based on the mechanisms of resistance and progression in multiple myeloma.

Gut luminal dysbiosis and pathobiosis result in compositional and biodiversify alterations in the microbial and host co-metabolites. The main mechanism of bacterial evolution is horizontal gene transfer (HGT) and acquisition of new traits can be achieved through mobile genetic element (MGEs) exchange. Introducing genetically engineered microbes (GEMs) might break the harmonized balance in the intestinal compartment. The present objectives are: 1. To reveal the role played by GEMs' horizontal gene transfers in changing the landscape of the enteric microbiome eubiosis 2. To expand on the potential detrimental effects of those changes on human genome and health. A search of articles published in PubMed/MEDLINE, EMBASE, and Scielo from 2000 to august 2023, using appropriate MeSH entry terms were performed. GEMs' horizontal gene exchanges might induce multiple human diseases. The new GEMs can change the long-term natural evolution of the enteric pro- or eukaryotic cells inhabitants. The worldwide regulatory authority's safety control of GEMs is not enough to protect public health. Viability and biocontainment and many other aspects are only partially controlled and harmful consequences for public health should be avoided. Always remember that prevention is the most cost- effective strategy and "primum non nocere" is the name of the game.

New insights into the causes and mechanisms of congenital heart disease (CHD) have been gained through the use of next-generation sequencing. Examination of the whole exome sequence detects detrimental gene variations modifying single or contiguous nucleotides, that are characterised as pathogenicity based on statistical assessments of families. and correlates with congenital heart disease, elevated expression during heart development, and reduction of harmful protein-coding mutations in the general population. Patients with CHD and extracardiac abnormalities enriched for gene classes meeting these criteria. CHDs and extracardiac defects, supporting a common set of pathways in the organogenesis of CHDs. Single-cell transcriptomics data reveal the expression of genes associated with CHD in specific cell lineages, and emerging evidence suggests that genetic variants disrupt multicellular genes essential for cardiogenesis. Metrics and units are being tracked in whole genome sequence studies.

The agricultural sector faces challenges due to climate change and the growing global population. Alkaline stress could adversely impact plant growth and crop production. This stressor diminishes water quality essential for crop cultivation, consequently impairing plant growth and overall productivity. Gamma-aminobutyric acid (GABA), a non-protein amino acid, may exhibit multifaceted roles in plant responses to adverse environmental conditions. Optimization of crop production in controlled environmental agriculture under artificial light attracted much attention. In the present study, we investigated the effects of different light spectra and GABA concentrations on Lollo Rosso lettuce plants under alkaline stress. Seedlings were placed under different light spectra [red (R), blue (B), white (W), 3R:1B, and 2R:1B:1far-red (FR)] and treated by GABA (0 and 50 µmol). Alkaline conditions were instituted by applying NaHCO3 at a concentration of 40 mM. The experiment incorporated a control treatment without NaHCO3. In general, R light exposure caused the highest growth performance of lettuce plants. GABA augmented biomass production in control and alkaline-treated plants across all light spectra. Additionally, it increased the concentrations of photosynthetic and protective pigments under alkaline conditions. GABA also improved the photosynthetic performance under all light spectra. Non-photochemical quenching and pigmentation were enhanced by exposure to B light, especially in plants treated with GABA. Alkaline stress induced an increase in soluble carbohydrate content in the lettuce leaves. These findings highlight the support of GABA application in facilitating coping plants to alkaline stress.

Targeted therapies are effective cancer treatments when accompanied by accurate diagnostic tests that can help identify patients that will respond to those therapies. The YAP/TAZ-TEAD axis is activated and plays a causal role in several cancer types, and TEAD inhibitors are currently in early phase clinical trials in cancer patients. However, mutations that predict YAP/TAZ-TEAD activation are not commonly found in most cancer types, making it hard to determine which tumors are de-pendent upon YAP/TAZ-TEAD. Here, we used a combination of RNA-seq and bioinformatics analysis of metastatic melanoma cells to develop a YAP/TAZ gene signature. We found that the genes in this signature are TEAD-dependent, and that their expression strongly correlates with YAP/TAZ activation in human melanomas. Using DepMap dependency data, we found that this YAP/TAZ signature was predictive of melanoma cell dependence upon YAP/TAZ or TEADs. Importantly, this was not limited to melanoma because this signature was also predictive when tested on a panel of over 1000 cancer cell lines representing numerous distinct cancer types. Our results suggest that YAP/TAZ gene signatures like ours may be an effective tool to predict tumor cell sensitivity to YAP/TAZ-TEAD inhibition, and thus provide a means to identify patients likely to benefit from TEAD inhibitors.

Phase change refers to the process of maturation and transition from the juvenile to the adult stage. In response to this shift, certain species like chestnut lose the ability to form adventitious roots, thereby hindering the successful micropropagation of adult plants. While auxin is the main hormone involved in adventitious root formation, other hormones, such as ethylene, are also thought to play a role in its induction and development. In this study, experiments were carried out to determine the effects of ethylene on the induction and growth of adventitious roots. The analysis was performed in two types of chestnut microshoots derived from the same tree, a juvenile-like line with high rooting ability derived from basal shoots (P2BS) and a line derived from crown branches (P2CR) with low rooting responses. By means of the application of compounds to modify ethylene content or inhibit its signalling, the potential involvement of this hormone in the in-duction of adventitious roots was analyzed. Our results show that ethylene can modify the rooting competence of mature shoots, while the response in juvenile material was barely affected. To further characterize the molecular reasons underlying this maturation-derived shift in behaviour, specific gene expression analyses were developed. Findings suggest that several mechanisms, including ethylene signalling, auxin transport and epigenetic modifications, relate to the modu-lation of the rooting ability of mature chestnut microshoots and their recalcitrant behaviour.

Cardiovascular comorbidity is a common companion of psoriasis and psoriatic arthritis (PsA). Recently, a significant link has been found between the HLA-Cw6 allele and a better cardiometabolic profile in these patients. We aimed to check this finding in our setting. Cross-sectional observational study (n: 572 psoriasis patients, 30% with PsA). Different study variables were collected in detail, as well as classic cardiometabolic risk factors. The distribution of the HLA-Cw6 allele and the IFIH1/MDA5 gene variants previously linked to disease risk was determined in the study cohort and stratified according to the cardiometabolic comorbidity. Linear and logistic regression models were constructed to analyze these associations. The study cohort included 309 men and 263 women, mean age 46.7 years (SD 14.5), mean disease duration 19.4 years (SD 14.8). We confirmed the known association between HLA-Cw6 and type I psoriasis (familial, severe, early onset). Psoriasis severity (OR: 2.14), female sex (OR: 1.63), and the IFIH1/MDA5 rs1990760 TT genotype (OR: 1.62) were significantly related to PsA, while HLA-Cw6 resulted protective (OR: 0.65). HLA-Cw6 carriers showed lower waist perimeter, lower BMI, and lower risk of both hypertension (OR: 0.52, p<0.001) and diabetes (OR: 0.36, p<0.001), but these findings were no longer apparent upon adjusted regression models. No IFIH1/MDA5 gene variant was associated with any cardiometabolic risk factor. The influence of HLA-Cw6 on the cardiometabolic risk profile of psoriatic patients seems to be explained by other factors (age, sex, duration of the disease or arthritis) and not by this biomarker itself.

Keywords: Demographics, Diversity, Gender, Race, Age, Professionals, Built Environment, Construction Industry, South Africa

With the constant growth of Software Defined Radio (SDR) technologies in wireless communications related fields the need for efficient ways to test and evaluate the Physical Layer (PHY) protocols developed for these technologies in real life traffic scenarios become more critical. This paper proposes a software testbed that enhances the creation of network environments that allow feeding GNU Radio applications with test traffic in a simple way and through an interoperable interface. This makes possible the use of any traffic generator, existent one or custom built to evaluate the GNU Radio application. In addition, the paper proposes an efficient way to collect PHY layer specific monitoring data that improves the performance of the critical components of the message delivery path by employing the Protocol Buffers library. The paper considers the entire testing and evaluation ecosystem and demonstrates how PHY layer specific monitoring information is collected, handled, stored, and processed as time series allowing complex visualization and real time monitoring.

Plastid-encoded RNA polymerase (PEP) forms a multisubunit complex in operating chloroplasts, where PEP subunits and a sigma factor are tightly associated with 12 additional nuclear-encoded proteins. Mutants with disrupted genes encoding PEP-associated proteins (PAPs) provide unique tools for deciphering mutual relationships among phytohormones. A block of chloroplast biogenesis in Arabidopsis pap mutants specifying highly altered metabolism in white tissues induced dramatic fluctuations in the content of major phytohormones and their metabolic genes, whereas hormone signaling circuits mostly remained functional. Reprogramming of the expression of biosynthetic and metabolic genes contributed to a greatly increased content of salicylic acid (SA) and a concomitant decrease in 1-aminocyclopropane-1-carboxylic acid (ACC) and oxophytodienoic acid (OPDA), precursors of ethylene and jasmonic acid, respectively, in parallel to reduced levels of abscisic acid (ABA). The lack of differences in the free levels of indole-3-acetic acid (IAA) between the pap mutants and wild-type plants was accompanied by fluctuations in the contents of IAA precursors and conjugated forms as well as multilayered changes in the expression of IAA metabolic genes. Along with cytokinin (CK) overproduction, all of these compensatory changes aim to balance plant growth and defense systems to ensure viability under highly modulated conditions.

Non-coding RNAs, specifically microRNAs (miRNAs), exhibit altered expression and contribute significantly to the pathological processes observed in numerous diseases, encompassing various types of human cancers. Recent discoveries regarding miRNAs underscore their crucial roles in tumor pathogenesis and their responses to diverse therapeutic interventions. miRNAs are a subset of non-coding RNAs that regulate the expression of a multitude of genes post-transcriptionally and thus are potential diagnostic, prognostic, and predictive biomarkers and have also emerged as potential therapeutics. Because miRNAs are involved in the post-transcriptional regulation of their target mRNAs via repressing gene expression, defects in the miRNA biogenesis pathway and miRNA expression perturb the expression of a multitude of oncogenic or tumor-suppressive target genes that are involved in the pathogenesis of various cancers. As such, numerous miRNAs have been identified to be downregulated or upregulated in many types of cancers functioning as either oncomiRs or oncosuppressor miRs. Moreover, dysregulation of miRNA biogenesis pathways can also change miRNA expression and function in cancer. Profiling deregulated miRNAs in many cancer types has been shown to correlate with disease diagnosis, indicate optimal treatment options, and predict response to a specific therapy. Specific miRNA signatures can track all stages of disease including many cancer types and hold potential as biomarkers and therapeutic targets as well as therapeutics as miRNA mimics and inhibitors (antagomirs). As such, identifying specific miRNAs and mRNAs they regulate in many types of cancer along with downstream pathways can be used as potential therapeutic targets. Because a single miRNA can regulate a pool of targets involved in similar cellular processes and pathways, thereby amplifying the cellular response, this potentially makes miRNAs powerful therapeutics to restore cell functions that are altered as part of a disease phenotype. However, because a single miRNA regulates multiple gene expressions their cellular effects are numerous leading to potential off-target effects. Besides their intended targeting issues, there is a need to reduce the immunogenic reactions and determine the minimal dosing to achieve the desired effect while minimizing side effects. As such, a careful risk evaluation of miRNA therapeutics is needed to minimize off-target effects and to avoid overdosing of miRNA drugs. Furthermore, a limited understanding and validation of the specific roles of miRNAs limits their clinical application. In addition, there are many challenges concerning the delivery, sensitivity, specificity, toxicity, and applicability of the potential utility of miRNAs as therapeutic targets or therapeutics. Thus, future work will warrant if miRNAs can be used as cancer biomarkers as well as therapeutics for clinical application.

The visual perception of leisure spaces between residences in cold regions is important for public health. To compensate for the existing researches` lack of ignoring the cold snow season`s influence, this study selected two types of outdoor leisure space environments in non-snow and snow seasons as research objects. An eye tracker combined with a Semantic Difference (SD) questionnaire was used to verify the feasibility of the application of virtual reality technology, screen out leisure gaze characteristics, and reveal the environmental factors related to leisure visual perception. In snow season, spatial aspect ratio (SAR), building elevation saturation (BS), and grass proportion in the field of view (GP) showed strong correlation to the leisure visual perception scores (W). In non-snow season, apart from the above three factors, roof height difference (RHD), tall tree height (TTH) and color contrast (HC) also influenced W obviously. The effects of factors on W were revealed in immersive virtual en-vironment (IVE) orthogonal experiments and genetic algorithm (GA) and k-nearest neighbor algorithm (KNN) were combined to optimized the environmental factors. The optimized threshold ranges in the non-snow season environment were SAR: 1.82‒2.15, RHD: 10.81 m‒20.09 m, BS: 48.53‒61.01, TTH: 14.18 m‒18.29 m, GP: 0.12‒0.15, and HC: 18.64‒26.83. In the snow season environment, the optimized threshold ranges were SAR: 2.22‒2.54, BS: 68.47‒82.34, and GP: 0.1‒0.14.

Coilia nasus is a typical anadromous migratory fish in the lower reaches of the Yangtze River. Every year, C. nasus cluster offshore and swim upstream along the Yangtze River into the tributaries and lakes in the middle and lower reaches of the Yangtze River to breed. In this study, female C. nasus collected as the subjects from Chongming section in Shanghai, Taizhou section in Jiangsu and Anqing section in Anhui. The ovaries were used for examining in tissue sections and researching of gene expression including follicle stimulating hormone receptor (fshr), luteinizing hormone receptors (lr), kisspeptin-1 (kiss1) and forkhead box l2 (foxl2) related to the reproductive development, and the estrogen (estradiol, E2) and progesterone (17α,20β-dihydroxy-4-pregenen-3-one, 17α,20β-DHP) were also analyzed in serum levels. The results showed that, first, the growth period of oocytes was small in stage II of ovarian development, in which both E2, 17α,20β-DHP levels and gene expression were low. Then, in stage Ⅲ, the growth period of oocytes were become large, as well as the yolk granules and oil droplets began to appear. Simultaneously, E2 and expression of kiss1 and foxl2 were significantly elevated. Finally, stage Ⅳ was the period of large accumulation of nutrients in oocytes, and 17α,20β-DHP level and expression of fshr and lhr were significantly elevated. The results have enriched the theoretical study of ovarian development in the natural population of C. nasus, supplemented the biological basis of C. nasus reproduction, and scientifically supported the study of C. nasus population ecology and resource conservation.

The enhancement of human living conditions has resulted in an increase in average life expectancy, giving rise to a novel social and medical challenge: aging, which diminishes the overall quality of human life. The aging process of the body begins through the activation of effector signaling pathways of aging in cells, loss of their normal functions and deleterious effects on the microenvironment, which leads to chronic inflammation and similar transformation of neighboring cells. The cumulative retention of these senescent cells over a prolonged period results in the deterioration of tissues and organs, ultimately leading to a reduced quality of life and an elevated mortality risk. Among the most encouraging methods for addressing aging and age-related illnesses are pharmacological, genetic, and cellular therapies. Elevating the activity of aging-suppressing genes, employing specific groups of native and genetically modified cells, and utilizing senolytic medications may offer the potential to delay aging and age-related ailments over the long term. The review explores the strategies and advancements in the field of anti-aging therapies that are currently under investigation, with a particular emphasis on gene therapy involving adeno-associated vectors and cell-based therapeutic approaches.

Interdisciplinary STEM and STEAM education give us an opportunity for creativity and educational innovation in a world scenario that needs training in which students can achieve all educational objectives and are prepared to achieve sustainable development. The rural environment with its land is a scenario that provides us with a range of educational resources for the development of STEM and STEAM projects in which students who are better trained and prepared for the needs of today's world are developed, as well as students who are more linked and sensitized to the environment, with the rural environment and its land, so important in our time.  In this article, we will collect examples from Latin America; STEM projects are being developed in which young people establish links with their environment, territory, and the local environment surrounding them. We must look carefully at projects and works in which students' ties with their land and environment are valued through the STEM and STEAM education necessary today. In this scenario, a comparison has been made between Latin American countries and Spain.

Abstract: Considering the significance of postural balance in shooting ability, and consequently soldiers’ occupational performance and survivability, it is of importance to promote the use of balance training programs to improve shooters' efficiency. This study explored how a balance training program affects shooting performance. Twenty participants were divided into two equal groups. They all performed 60 shots in a shooting simulator while standing. The participants went through this process twice, before and after a 4-week balance training program. The shoot-ing was done under four different conditions: without load on a stable surface, with load on a stable surface, without load on an unstable surface, and with load on an unstable surface. The training program had a significant impact on the experimental group, improving their balance by 76 ± 9% (p < 0.01). Additionally, in the experimental group, shooting score increased by 47% and the % center of gravity by 20% (p < 0.01). The stability of the shots, measured by holding time in the target, doubled from 2.2 to 4.5 seconds (p < 0.01). These improvements were more pronounced when participants had a load and/or were on an unstable surface. In conclusion, a balance training program can be beneficial for improving shooting performance.

Several specialized terpenoids that are used as phytoalexins are produced in the plant of tobacco. They play a key role in plant defense against pests and pathogens. Here, we performed genome-wide identification, classification, and expression profiling of the terpene synthase (TPS) genes in the tobacco genome. A total of 186 TPS genes were identified, which is significantly higher than that in wild Nicotiana, Capsicum and Solanum species. Phylogenetic analysis of these TPS genes in tobacco and Solanaceous relatives as well as Arabidopsis showed that a few tobacco-exclusive TPS clades occurred recently through gene duplication events. These clades are likely to be responsible for a range of compounds that separate N. tabacum cultivars from its wild relatives. Transcriptome sequencing of two cultivars of N. tabacum at several developmental stages revealed that some TPS genes from the TPS-a and TPS-b lineages are constitutively expressed and a few duplicated TPS genes are only expressed post anthesis at the time of harvest. Additionally, some TPS genes underwent alternative splicing, further diversifying the gene products of the TPS genes. Our findings provide an important candidate genes for further understanding of the diversity and evolution as well as functionality of TPS genes in the plant of tobacco.

Biodiversity conservation is a key factor in meeting sustainable development goals. This is even more important in cities, where green spaces are becoming increasingly scarce. This study analyzes the Kinshasa's proliferating ornamental plant nurseries, known as informal horticultural sites (IHS). The analysis focused on characterizing the profile of horticulturists, their production conditions and the ornamental species produced. Fifteen IHSs were sampled using the "snowball" technique, and 178 horticulturists were surveyed. Based on the socio-professional profile of the horticulturists, five groups of IHS are distinguished after a hierarchical classification on principal components. We found that IHSs exclusively employed men, most of whom were new to the trade, from all levels of education, and most of whom ranged from 19 to 45 years old. Production conditions are relatively similar from one site to another. However, all IHS are characterized by permanent land insecurity, the use of phytosanitary products, plant conditioning methods that are not very diversified and calibrated to growers' investment capacities, and diversified seed acquisition methods. A total of 139 ornamental species, most of them exotic, were identified. Of these, 37% are phanerophytes and 24% are considered potentially invasive. We suggest ways of professionalizing the activity and protecting the urban environment.

We investigated and quantified bacterial accumulation in facemasks used by the general population, using 16S rRNA (Sanger Sequencing), culture and biochemical analysis along with Rose Bengal staining. Additionally, a systematic overview of the literature on face mask contamination was undertaken. We found an average bacterial load of 4.24 × 10⁴ CFU recovered/mask, with a maximum load of 2.85 × 10⁵ CFU. This maximum is 310 times higher than the limit value for contamination of ventilation system outlet surfaces specified by the German standard VDI 6022. Biochemical and molecular identification predominantly found Staphylococcus species (80%), including Staphylococcus aureus, along with endospore-forming Bacillus spp. Literature reports also indicate contamination of masks by bacterial and fungal opportunists of the genera Acinetobacter, Aspergillus, Alternaria, Bacillus, Cadosporium, Candida, Escherichia, Enterobacter, Enterococcus, Klebsiella (including K. pneumoniae), Micrococcus, Microsporum, Mucor, Pseudomonas, Staphylococcus and Streptococcus. Bacterial counts increase linearly with wearing duration, and prolonged use may affect the skin and respiratory microbiomes, promoting consequential eye, skin, oral and airway conditions. These aspects underscore the urgent need for further research and a risk-benefit analysis in respect of mask use, particularly given their unproven efficacy in disrupting the transmission of respiratory viruses and their adverse social consequences.

This paper focuses on leveraging a cutting-edge 3D state-space model for a holistic eco-friendly assessment in petrochemical operations. - By applying the ecological carrying capacity theory and the three-dimensional state-space model, this research aims to unleash the next frontier of sustainability in the petrochemical industry. - The proposed methodology will enable advanced and comprehensive eco efficiency evaluation in petrochemical operations. - Through the integration of the ecological carrying capacity theory and advanced modeling techniques, this research seeks to revolutionize sustainability assessments in the petrochemical sector. - The utilization of the cutting-edge 3D state-space model will provide a more advanced and accurate understanding of eco-friendly practices in petrochemical operations. This research presents a unique approach distinct from existing literature, which primarily examines business eco efficiency from behavioral motivation and strategic perspectives. In contrast, this paper introduces a novel three-dimensional state-space model to evaluate the ecological efficiency of petrochemical operations. By combining the ecological carrying index and state space, this model represents the ecological impact of petrochemical operations in a three-dimensional geometric space. It considers petrochemical operations as a significant factor exerting pressure on natural resources and the natural environment. In this three-dimensional state-space model, the three axes represent different dimensions of petrochemical operations. The first axis represents the economic status, which quantitatively describes the financial aspects of the operation. The second axis represents the utilization of resources, capturing the extent to which resources are consumed in the operation. The third axis focuses on the impact of the operation on the environment, allowing for a quantitative assessment of its ecological footprint. By incorporating these dimensions, the model aims to provide a comprehensive and quantitative description of the economic activities of petrochemical operations and their interactions with resources and the environment.The primary focus of this research is to apply the three-dimensional state-space model to calculate the ecological carrying capacity of petrochemical operations. By doing so, it aims to verify the feasibility and applicability of the model in determining the ecological efficiency of these operations. The research also aims to provide theoretical tools that can assist operations in making more informed ecological efficiency judgments. By utilizing this model, petrochemical operations will have a quantitative framework to assess and improve their environmental impact, thus fostering more sustainable practices. The findings of this research demonstrate that the implementation of this method can effectively identify issues related to resources, economy, and environment throughout the development of petrochemical operations. By identifying these problems, it provides managers with a solid foundation for making strategic decisions that promote sustainable development. With this valuable information at their disposal, managers can proactively address challenges, optimize resource utilization, and minimize environmental impacts, thus steering the petrochemical operations towards a more sustainable and responsible path.

Malnutrition is prevalent in patients with chronic kidney disease (CKD), especially those on hemodialysis. Recently, our group described that a new oral nutritional supplement (ONS) for malnourished (or at-risk) hemodialysis patients with a "similar to the Mediterranean diet" model, improved caloric and protein intake, nutritional status and inflammation and oxidation biomarkers. Our aim in this study was to evaluate whether the new ONS, including probiotics, may produce changes in miRNAs expression and its target genes in malnourished hemodialysis patients, compared to individualized diet recommendations. We conducted a randomized, multicenter, parallel-group study in malnourished hemodialysis patients divided in 3 groups (1: Control -C- individualized diet 2: Oral nutritional supplement -ONS- + placebo -ONS-PL- and 3: ONS + probiotics -ONS-PR). Study registration: NCT03924089. The trial was open to the ONS diet or individual dietary advice, but double-blind for the intake of probiotics supplements. MiRNAs and gene expression levels were analyzed by RT-qPCR at baseline and after 3 and 6 months. We observed that the expression of miR-29a and miR-29b increased significantly in patients with ONS-PR at 3 months in comparison with baseline, stabilizing at the sixth month. Moreover, we observed differences between studied groups, where miR-29b expression levels were elevated in patients receiving ONS-PR compared to the control group in the third month. Regarding the gene expression levels, we observed a decrease in the ONS-PR group compared to the control group in the third month for RUNX2 and TNFα. TGFB1 expression was decreased in the ONS-PR group compared to baseline in the third month. PTEN gene expression was significantly elevated in the ONS-PR group at 3-months in comparison with baseline. LEPTIN expression was significantly increased in ONS-PL group at 3-month intervention compared to baseline. The new Oral Nutritional Supplement associated with probiotics; increases the expression levels of miR-29a and miR-29b after 3 months of intervention, modifying the expression of target genes with anti-inflammatory and anti-fibrotic actions. This study highlights the potential benefit of this Oral Nutritional Supplement, especially associated with probiotics, in malnourished patients with chronic renal disease on hemodialysis.

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.

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.

Radiation therapy is employed in treating various cancer types. However, depending on the type and stage of cancer, its benefits can be limited, and it may cause serious side effects that detrimentally affect the quality of life (QOL) for the patient. Preventing the side effects of radiation therapy can enhance the response to cancer treatment and improve the patient’s QOL. Independently, vitamin C and hydrogen have demonstrated potential in reducing the side effects of anticancer drugs and radiation therapy. Furthermore, both have been postulated to possess direct anticancer properties. However, the effects of their combined therapy remain underexplored. This study investigates the hypothesis that combining vitamin C and hydrogen efficiently prevents radiation-induced injuries. Survival rates were investigated in cancer cell lines (MDA-MB231 and GL261) and normal cells (HUVEC) treated with hydrogen, vitamin C and irradiation. Apoptosis was assessed using the FLICA test, and EMT gene expression was elucidated via the qPCR technique. In the normal cell line, the introduction of vitamin C and hydrogen to the culture medium boosted survival rates, exhibiting a radioprotective effect upon irradiation. In contrast, cancer cells showed a decreased survival rate with the introduction of vitamin C and hydrogen, which was further diminished with irradiation. Treated cancer cells showed signs of apoptosis. Caspase activity in viable cells was reduced by the combination treatment with vitamin C and hydrogen. Additionally, glioblastoma cells treated with this combination showed reduced EMT gene expression. This study reveals that a combined therapy of hydrogen and vitamin C offers radioprotective effects on normal cells and exerts direct anticancer effects on cancer cells, while also amplifying the anticancer effects of radiation. Importantly, this combined therapy attenuated the radiation-induced EMT signature in the GL261 murine glioma cell line, suggesting potential in diminishing treatment resistance and tumor invasion.

A systematic investigation of the dynamic clustering behavior of active particles under confinement, including the effects of both particle density and active driving force is presented based on a hybrid coarse-grained molecular dynamics simulation. First, a series of scaling laws were derived with power relationships for the dynamic clustering time as a function of both particle density and active driving force. Notably, the average number of clusters N ̅ assembled from active particles in the simulation system exhibits a scaling relationship with clustering time t described by N ̅∝t^(-m). Simultaneously, the scaling behavior of the average cluster size S ̅ is characterized by S ̅∝t^m. Our findings reveals the presence of up to four distinct dynamic regions concerning clustering over time, with transitions contingent upon the particle density within the system. Furthermore, as the active driving force increases, the aggregation behavior also accelerates, while an increase in density of active particles induce alterations in the dynamic procession of the system.

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.

Hypercholesterolemia plays a fundamental role in the development and progression of atherosclerosis. Current guidelines for treating dyslipidemia target low-density lipoprotein-cholesterol (LDL-C). Despite advances in the pharmacotherapy of atherosclerosis, the most successful agents used to treat this disease – statins – remain insufficient in the primary or secondary prevention of acute myocardial infarction. Advancing therapy for hypercholesterolemia with emerging new drugs, either as monotherapy or in combination, is expected to improve cardiovascular outcomes.

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.

Glaucoma is a group of ocular diseases that causes irreversible blindness worldwide and is characterized by a multifactorial degeneration of optic nerve and retinal ganglion cells (RGCs), leading to vision loss. One of the significant risk factors in glaucoma pathogenesis is glia-driven neuroinflammation. Impairment of mitochondrial dynamics and bioenergetics is associated with glaucomatous neurodegeneration and is linked to neuroinflammation. Apolipoprotein A-I binding protein (AIBP) binds to toll-like receptor 4 (TLR4) and facilitates the removal of excess cholesterol from the plasma membrane in activated cells, suggesting the regulation of cholesterol-driven inflammation by inhibiting the TLR4-associated lipid rafts. AIBP is localized in mitochondria and regulates mitophagy by ubiquitination of mitofusin 1 and 2. We observed elevated intraocular pressure-induced AIBP deficiency in glaucomatous neurodegeneration. We also observed that AIBP deficiency activated TLR4 in Müller glia, triggered mitochondrial dysfunction in both RGCs and Müller glia and impaired visual function. In mouse models of glaucoma, AIBP treatment protects RGCs by reducing inflammatory responses. Here, our review focuses on investigating the role of AIBP in the retina and examining the underlying mechanism by which AIBP contributes to the pathogenesis of glaucoma, aiming to provide new insight into the therapeutic potential for the treatment of glaucoma.

Abiotic stress is an adverse environmental factor that severely affects plant growth and development, and plants have developed complex regulatory mechanisms to adapt to these unfavourable conditions through long-term evolution. In recent years, many transcription factor families of genes have been identified to regulate the ability of plants to respond to abiotic stresses. Among them, AP2/ERF (APETALA2/ethylene responsive factor) family is a large class of plant-specific that regulate plant response to abiotic stresses and can also play a role in regulating plant growth and development. This paper reviews the structural features and classification of AP2/ERF transcription factors, that transcriptional regulation, reciprocal proteins, downstream genes and hormone-dependent signalling and hormone-independent signalling pathways are involved in the response to abiotic stress. The study of AP2/ERF transcription factors and interacting proteins, as well as the identification of their downstream target genes, can provide us with a more comprehensive understanding of the mechanism of plant action in response to abiotic stress, which can improve the tolerance ability of plants in abiotic stress, and provide more theoretical basis for rice to obtain more yields under abiotic stress.

Microplastics have been detected as widespread in an aquatic environment at the microscale, also known as plastic debris. They have continuously increased due to the increase in population, production of synthetic plastics and poor waste management. They are ubiquitous and slowly degrade in soil and water. They are emerging contaminants that have received attention from research communities and public audiences over the last few years. They have high stability and can absorb several other pollutants like heavy metals, pesticides, etc. After entering the environment, they can accumulate and persist for a long time. They can create a serious threat to freshwater ecosystems and human health. These particles can cause physical damage to freshwater organisms. Raman spectroscopy, Fourier-transform infrared spectroscopy, visual identification, density separation, microscopic method, chemical method, thermos-analytical method and hyperspectral imaging method are the commonly known approaches for identification and quantification of microplastics. The noticed concentration of microplastics depends on the analysis method, sampling location and technique. The authors reviewed the sources, health impact, transport and treatment of microplastics in freshwater environments in detail. This study will provide the baseline data for the researchers to do more research on microplastic pollution in the future.

Mechanical damage of plant tissues leads to the activation of methanol production and its release in the atmosphere. The gaseous methanol or vapors emitted by the damaged plant induce resistance in neighboring intact plants to bacterial pathogens but create favorable conditions for the viral infection spread. Among Nicotiana benthamiana methanol-inducible genes (MIGs) most are associated with plant defense and intercellular transport. Here we characterize NbMIG21 that encodes a 209-aa protein (NbMIG21p) which does not share any homology with annotated proteins. NbMIG21p was demonstrated to contain nucleolus localization signals (NoLS). Co-localization studies with fibrillarin and coilin, nucleolus and Cajal bodies marker proteins, revealed that NbMIG21p is distributed between these subnuclear structures. Our results show that recombinant NbMIG21 possess DNA-binding properties . Similar to gaseous methanol effect an increased NbMIG21 expression leads to the downregulation of the nuclear import of NLS-containing proteins as was demonstrated on the model GFP-NLS protein. Moreover, upregulated NbMIG21 facilitates tobacco mosaic virus (TMV) intercellular transport. We identified NbMIG21 promoter (PrMIG21) and showed that it is methanol-sensitive thus induction of NbMIG21 expression occurs at the level of transcription. Our findings suggest that methanol-activated NbMIG21 might participate in creating favorable conditions for the viral reproduction and spread.