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An unusual pattern among the scaling laws in nature is that the fastest animals are neither the largest, nor the smallest, but rather intermediately sized. Because of the enormous diversity in animal shape, the mechanisms underlying this have long been difficult to determine. To address this, we challenge predictive human musculoskeletal simulations, scaled in mass from the size of a mouse (0.1 kg) to the size of an elephant (2000 kg), to move as fast as possible. Our models replicate patterns observed across extant animals including: (i) an intermediate optimal body mass for speed; (ii) a reduction in the cost of transport with increasing size; and (iii) crouched postures at smaller body masses and upright postures at larger body masses. Finally, we use our models to determine the mechanical limitations of speed with size, showing larger animals may be limited by their ability to produce muscular force while smaller animals are likely limited by their ability to produce larger ground reaction forces. Despite their bipedal gait, our models replicate patterns observed across quadrupedal animals, suggesting these biological phenomena likely represent general rules and are not the result of phylogenetic or other ecological factors that typically hinder comparative studies. The fastest animals are neither the largest, nor the smallest, but rather intermediately sized, though the mechanism for this is unknown. This study built predictive musculoskeletal simulations, scaled in mass from the size of a mouse to an elephant to understand the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Tissue stem cells (TSCs), which reside in specialized tissues, constitute the major cell sources for tissue homeostasis and regeneration, and the contribution of transcriptional or epigenetic regulation of distinct biological processes in TSCs has been discussed in the past few decades. Meanwhile, ATP-dependent chromatin remodelers use the energy from ATP hydrolysis to remodel nucleosomes, thereby affecting chromatin dynamics and the regulation of gene expression programs in each cell type. However, the role of chromatin remodelers in tissue stem cell fate determination is less well understood. In this review, we systematically discuss recent advances in epigenetic control by chromatin remodelers of hematopoietic stem cells, intestinal epithelial stem cells, neural stem cells, and skin stem cells in their fate determination and highlight the importance of their essential role in tissue homeostasis, development, and regeneration. Moreover, the exploration of the molecular and cellular mechanisms of TSCs is crucial for advancing our understanding of tissue maintenance and for the discovery of novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Accurate population data is crucial for assessing exposure in disaster risk assessments. In recent years, there has been a significant increase in the development of spatially gridded population datasets. Despite these datasets often using similar input data to derive population figures, notable differences arise when comparing them with direct ground-level observations. This study evaluates the precision and accuracy of flood exposure assessments using both known and generated gridded population datasets in Sweden. Specifically focusing on WorldPop and GHSPop, we compare these datasets against official national statistics at a 100 m grid cell resolution to assess their reliability in flood exposure analyses. Our objectives include quantifying the reliability of these datasets and examining the impact of data aggregation on estimated flood exposure across different administrative levels. The analysis reveals significant discrepancies in flood exposure estimates, underscoring the challenges associated with relying on generated gridded population data for precise flood risk assessments. Our findings emphasize the importance of careful dataset selection and highlight the potential for overestimation in flood risk analysis. This emphasises the critical need for validations against ground population data to ensure accurate flood risk management strategies. [ABSTRACT FROM AUTHOR]

The GDS(L)-like lipase from the Basidiomycota Pleurotus sapidus (PSA_Lip) was heterologously expressed using Trichoderma reesei with an activity of 350 U L−1. The isoelectric point of 5.0 was determined by isoelectric focusing. The novel PSA_Lip showed only 23.8–25.1%, 25.5%, 26.6% and 28.4% identity to the previously characterized GDSL-like enzymes phospholipase, plant lipase, acetylcholinesterase and acetylxylan esterase, from the carbohydrate esterase family 16, respectively. Therefore, the enzyme was purified from the culture supernatant and the catalytic properties and the substrate specificity of the enzyme were investigated using different assays to reveal its potential function. While no phospholipase, acetylcholinesterase and acetylxylan esterase activities were detected, studies on the hydrolysis of ferulic acid methyl ester (~ 8.3%) and feruloylated carbohydrate 5-O-transferuloyl-arabino-furanose (~ 0.8%) showed low conversions of these substrates. By investigating the hydrolytic activity towards p-nitrophenyl-(pNP)-esters with various chain-lengths, the highest activity was determined for medium chain-length pNP-octanoate at 65 °C and a pH value of 8, while almost no activity was detected for pNP-hexanoate. The enzyme is highly stable when stored at pH 10 and 4 °C for at least 7 days. Moreover, using consensus sequence analysis and homology modeling, we could demonstrate that the PSA_Lip does not contain the usual SGNH residues in the actives site, which are usually present in GDS(L)-like enzymes. [ABSTRACT FROM AUTHOR]

Background: Pregnant and postpartum women are at high risk of depression due to hormonal and biological changes. Antenatal depression is understudied compared to postpartum depression and its predictors remain highly controversial. Aim: To estimate the prevalence of depressive symptoms during pregnancy and investigate factors associated with this condition including vitamin D, folate and Vitamin B12 among participants in the Kuwait Birth Study. Methods: Data collection occurred as part of the Kuwait Birth Cohort Study in which pregnant women were recruited in the second and third trimester during antenatal care visits. Data on antenatal depression were collected using the Edinburgh Postnatal Depression Scale (EPDS), considering a score of ≥ 13 as an indicator of depression. Logistic regression was used to investigate factors associated with depressive symptoms in pregnant women. Results: Of 1108 participants in the Kuwait Birth Cohort study, 1070(96.6%) completed the EPDS. The prevalence of depressive symptoms was 21.03%(95%CI:18.62–23.59%) and 17.85%(95%CI:15.60-20.28%) as indicated by an EPDS ≥ 13 and EPDS ≥ 14 respectively. In the multivariable analysis, passive smoking at home, experiencing stressful life events during pregnancy, and a lower level of vitamin B12 were identified as predisposing factors. Conversely, having desire for the pregnancy and consumption of fruits and vegetables were inversely associated with depressive symptoms. Conclusion: Approximately, one fifth of pregnant women had depressive symptoms indicating the need to implement screening program for depression in pregnant women, a measure not systematically implemented in Kuwait. Specifically, screening efforts should focus on pregnant women with unintended pregnancies, exposure to passive smoking at home, and recent stressful live events. [ABSTRACT FROM AUTHOR]

This study employed two prevalent plastic products - straws and microfiber as microplastics (MPs) to elucidate their largely unexplored effects on soil's properties and the growth of the tomato plant (Solanum lycopersicum L.). For this experiment, a completely randomized design (CRD) was adopted where, straw - polypropylene (PP), microfiber - polyester (PES) + polyamide (PA), and their combinations (PP + PES + PA) were mixed with soil using different concentrations – 0% (control), 0.4%, 1%, and 2% (treatments) and kept for 45 days at room temperature. The findings demonstrated that incorporating 2% mixed MPs in soil significantly decreased bulk density and electrical conductivity 7.29% and 67.3%, respectively, while soil pH increased 17.84% in cultures containing 1% microfiber. Maximum water holding capacity (MWHC), soil organic carbon (SOC), and soil organic matter (SOM) showed varied responses based on MPs type and concentration. Specifically, MWHC increased 16.4% with 2% microfiber but declined 13.3% with 0.4% straw. The highest decreased (30.65%) in SOC and SOM were evident in cultures with 1% microfiber whereas increased 9.68% and 8.33% in cultures with 0.4% straw. In terms of the growth traits of S. lycopersicum, substantial reductions in plant height (56.37%), leaf number (54.37%), and girth diameter (56.43%) were observed in 2% straw containing cultures. Although no plant mortality was noted, the most pronounced reductions in leaf area (62.44%) and total plant biomass (68.16%) occurred in 2% microfiber cultures. Therefore, the ramifications of these findings may contribute to a deeper comprehension of the mechanisms and effects of MPs on soil properties and above-ground plant growth. [ABSTRACT FROM AUTHOR]

This review explores the hidden hazards associated with the reuse of treated wastewater and sewage sludge in agriculture while proposing mitigation strategies. It examines the origins and pathways of microplastics (MPs) in wastewater treatment plants and how these pollutants infiltrate agricultural ecosystems. The review assesses the effectiveness of MP removal from wastewater and its fate in soil after reuse, highlighting contamination dynamics and the need for proactive measures. Introducing soil remediation methods is crucial for addressing this issue. Alarming evidence of MPs in human blood, testis, semen, and placenta underscores the urgency for solutions, revealing significant threats to human health, particularly reproductive health. The review advocates for sustainable agricultural practices and effective soil remediation strategies to mitigate MP contamination, promoting environmental preservation, food safety, and human health protection. [ABSTRACT FROM AUTHOR]

Microplastics persist as a challenging pollutant in agroecosystems, posing potential risks to soil health and crop productivity. Root growth, elongation and expansion may significantly influence the vertical transport and infiltration of microplastics into the soil profile. Wheat plants (Triticum aestivum) grown in 70 cm deep rhizotrons were investigated for their influence on the vertical movement of two prevalent microplastic shapes, polyester fibres and polyvinyl chloride (PVC) fragments. Wheat was chosen for its dense and extensive fibrous and fine root system, which is a robust model for studying root-soil-microplastic interactions. Microplastics at a 0.24% w/w dry soil weight concentration were homogeneously distributed in the topsoil (0–20 cm). Infiltration of polyester fibres up to 50 cm into the soil profile was discerned as strong adherence to plant roots. PVC fragments exhibited greater mobility, reaching depths of 70 cm in the presence and absence of wheat plants. Plant growth response on exposure to microplastics appeared in the form of increased root branching and decreased shoot biomass, indicating a stress response in wheat plants. The results prove the vertical movement of microplastics, while the infiltration depth was influenced by microplastic shape. Movement was detected as either strong adherence of polyester fibres to plant roots or infiltration of PVC fragments. PVC fragments may have infiltrated through preferential flow paths in soil pores and the fissures created by root elongation and water movement. [ABSTRACT FROM AUTHOR]

Excessive tidal stretching may initiate damage or retard healing after lung injury. However, it is seldom considered whether intracycle power and ventilatory forces of lesser magnitude than those required to cross an injury threshold might stimulate or accelerate beneficial adaptive responses. Acute lung injury is a dynamic process that may exhibit phase-dependent reparative responses to mechanical stress broadly similar to physical training, body trauma or sepsis. We propose that lower stress may not always be better through all phases of ARDS; moderately high tidal airway pressures that stay below the threshold of global injury may have potential to speed healing of the injured lung. [ABSTRACT FROM AUTHOR]

Near-surface similarities and atmospheric turbulence characteristics have a large impact on numerical weather prediction models. However, the validity of these similarities is unclear during precipitation. This study investigates the modulations in atmospheric boundary layer turbulence and the variations of the near-surface scaling similarities caused by rainfall. Here we present our field observations on the effects of rainfall on the near-surface similarities and atmospheric turbulence in the stable boundary layer using a Parsivel2 disdrometer and a 3D ultrasonic anemometer at our outdoor rainfall laboratory in San Antonio, Texas, USA. During moderate to heavy rainfall conditions, higher turbulent energy was observed than those in non-rainy conditions when the turbulence intensity and the wind speeds were relatively low. On the contrary, when the turbulence intensity and the wind speeds were relatively high, the turbulence energy in the stable boundary layer were dampened due to the raindrops. Raindrops with high particle Reynolds numbers ( R e p = D m v t / ϑ ; D m —mean volume diameter, v t —terminal raindrop fall speed, and ϑ —kinematic viscosity of the surrounding air) can act as either a source or a sink of turbulent kinetic energy depending on the turbulence intensity of the atmosphere. Our field observations showed that near-surface similarities deviated from the scaled similarities under the influence of rainfall. The normalized standard deviations of the streamwise and vertical velocity components and the dissipation rate were higher during rainy than non-rainy times. Rainfall effects on turbulence modulations and near-surface scaling parameters of the stable boundary layer are discussed with considerations of the relevant mechanisms. [ABSTRACT FROM AUTHOR]

Polypropylene is commonly used as a binder for ceramic injection molding, and rapid cooling is often encountered during processing. However, the crystallization behavior of polypropylene shows a strong dependence on cooling rate due to its semi-crystalline characteristics. Therefore, the influence of cooling rate on the quality of final product cannot be ignored. In this study, the fast differential scanning calorimetry (FSC) test was performed to study the influence of cooling rate on the non-isothermal crystallization behavior and non-isothermal crystallization kinetics of a copolymer polypropylene (PP BC03B). The results show that the crystallization temperatures and crystallinity decrease as the cooling rate increases. In addition, two exothermic peaks occur when cooling rate ranges from 30 to 300 K·s-1, indicating the formation of another crystal phase. Avrami, Ozawa and Mo equations were used to explore the non-isothermal crystallization kinetics, and it can be concluded that the Mo method is suitable for this study. [ABSTRACT FROM AUTHOR]

The requirement for a high number of training episodes has been a major limiting factor for the application of Reinforcement Learning (RL) in robotics. Learning skills directly on real robots requires time, causes wear and tear and can lead to damage to the robot and environment due to unsafe exploratory actions. The success of learning skills in simulation and transferring them to real robots has also been limited by the gap between reality and simulation. This is particularly problematic for tasks involving contact with the environment as contact dynamics are hard to model and simulate. In this paper we propose a framework which leverages a shared control framework for modeling known constraints defined by object interactions and task geometry to reduce the state and action spaces and hence the overall dimensionality of the reinforcement learning problem. The unknown task knowledge and actions are learned by a reinforcement learning agent by conducting exploration in the constrained environment. Using a pouring task and grid-clamp placement task (similar to peg-in-hole) as use cases and a 7-DoF arm, we show that our approach can be used to learn directly on the real robot. The pouring task is learned in only 65 episodes (16 min) and the grid-clamp placement task is learned in 75 episodes (17 min) with strong safety guarantees and simple reward functions, greatly alleviating the need for simulation. [ABSTRACT FROM AUTHOR]

Nasally colonized staphylococci carry antibiotic resistance genes and may lead to serious opportunistic infections. We are investigating nasal carriage of Staphylococcus aureus and Staphylococci other than S. aureus (SOSA) among young volunteers in Egypt to determine their risk potential. Nasal swabs collected over 1 week in June 2019 from 196 volunteers were cultured for staphylococcus isolation. The participants were interviewed to assess sex, age, general health, hospitalization and personal hygiene habits. Identification was carried out using biochemical tests and VITEK 2 automated system. Disc diffusion and minimum inhibitory concentration tests were performed to determine antibiotic susceptibility. Screening for macrolide resistance genes (ermA, ermB, ermC, ermT and msrA) was performed using polymerase chain reaction. Thirty four S. aureus and 69 SOSA were obtained. Multi-drug resistance (MDR) was detected among most staphylococcal species, ranging from 30.77% among S. hominis to 50% among S. epidermidis. Phenotypic resistance to all tested antibiotics, except for linezolid, was observed. Susceptibility to rifampicin, vancomycin and teicoplanin was highest. ermB showed the highest prevalence among all species (79.41% and 94.2% among S. aureus and SOSA, respectively), and constitutive macrolide-lincosamide-streptogramin B (MLSB) resistance was equally observed in S. aureus and SOSA (11.11% and 16.22%, respectively), whereas inducible MLSB resistance was more often found in S. aureus (77.78% and 43.24%, respectively). The species or resistance level of the carried isolates were not significantly associated with previous hospitalization or underlying diseases. Although over all colonization and carriage of resistance genes are within normal ranges, the increased carriage of MDR S. aureus is alarming. Also, the fact that many macrolide resitance genes were detected should be a warning sign, particularly in case of MLSB inducible phenotype. More in depth analysis using whole genome sequencing would give a better insight into the MDR staphylococci in the community in Egypt. [ABSTRACT FROM AUTHOR]

Although licensed vaccines against influenza virus have been successful in reducing pathogen-mediated disease, they have been less effective at preventing viral infection of the airways and current seasonal updates to influenza vaccines do not always successfully accommodate viral drift. Most licensed influenza and recently licensed RSV vaccines are administered via the intramuscular route. Alternative immunisation strategies, such as intranasal vaccinations, and "prime-pull" regimens, may deliver a more sterilising form of protection against respiratory viruses. A bivalent ChAdOx1-based vaccine (ChAdOx1-NP + M1-RSVF) encoding conserved nucleoprotein and matrix 1 proteins from influenza A virus and a modified pre-fusion stabilised RSV A F protein, was designed, developed and tested in preclinical animal models. The aim was to induce broad, cross-protective tissue-resident T cells against heterotypic influenza viruses and neutralising antibodies against RSV in the respiratory mucosa and systemically. When administered via an intramuscular prime-intranasal boost (IM-IN) regimen in mice, superior protection was generated against challenge with either RSV A, Influenza A H3N2 or H1N1. These results support further clinical development of a pan influenza & RSV vaccine administered in a prime-pull regimen. [ABSTRACT FROM AUTHOR]

Single-cell RNA sequencing (scRNA-seq) has been widely used to characterize cell types based on their average gene expression profiles. However, most studies do not consider cell type-specific variation across donors. Modelling this cell type-specific inter-individual variation could help elucidate cell type-specific biology and inform genes and cell types underlying complex traits. We therefore develop a new model to detect and quantify cell type-specific variation across individuals called CTMM (Cell Type-specific linear Mixed Model). We use extensive simulations to show that CTMM is powerful and unbiased in realistic settings. We also derive calibrated tests for cell type-specific interindividual variation, which is challenging given the modest sample sizes in scRNA-seq. We apply CTMM to scRNA-seq data from human induced pluripotent stem cells to characterize the transcriptomic variation across donors as cells differentiate into endoderm. We find that almost 100% of transcriptome-wide variability between donors is differentiation stage-specific. CTMM also identifies individual genes with statistically significant stage-specific variability across samples, including 85 genes that do not have significant stage-specific mean expression. Finally, we extend CTMM to partition interindividual covariance between stages, which recapitulates the overall differentiation trajectory. Overall, CTMM is a powerful tool to illuminate cell type-specific biology in scRNA-seq. Single-cell RNA sequencing (scRNA-seq) is widely used to characterize cell types based on their average gene expression profiles, however most studies do not consider cell type-specific variation across individuals. Here the authors introduce a model to study cell type-specificity of inter-individual variation in scRNA-seq data and show that it can identify biologically meaningful signals missed by conventional differential expression tests. [ABSTRACT FROM AUTHOR]

Microbial communities often exhibit more than one possible stable composition for the same set of external conditions. In the human microbiome, these persistent changes in species composition and abundance are associated with health and disease states, but the drivers of these alternative stable states remain unclear. Here we experimentally demonstrate that a cross-kingdom community, composed of six species relevant to the respiratory tract, displays four alternative stable states each dominated by a different species. In pairwise coculture, we observe widespread bistability among species pairs, providing a natural origin for the multistability of the full community. In contrast with the common association between bistability and antagonism, experiments reveal many positive interactions within and between community members. We find that multiple species display cooperative growth, and modeling predicts that this could drive the observed multistability within the community as well as non-canonical pairwise outcomes. A biochemical screening reveals that glutamate either reduces or eliminates cooperativity in the growth of several species, and we confirm that such supplementation reduces the extent of bistability across pairs and reduces multistability in the full community. Our findings provide a mechanistic explanation of how cooperative growth rather than competitive interactions can underlie multistability in microbial communities. This study explores alternative stable states in microbial communities. Focusing on a respiratory tract community of 6 species, the authors identified four distinct stable states that are predicted to be driven by cooperative growth. The findings contrast with the common association between competitive interactions and multistability in microbial communities. [ABSTRACT FROM AUTHOR]

Landfill leachate contains antibiotic resistance genes (ARGs) and microplastics (MPs), making it an important reservoir. However, little research has been conducted on how ARGs are enriched on MPs and how the presence of MPs affects pathogens and ARGs in leachates and soil. MPs possess the capacity to establish unique bacterial populations and assimilate contaminants from their immediate surroundings, generating a potential environment conducive to the growth of disease-causing microorganisms and antibiotic resistance genes (ARGs), thereby exerting selection pressure. Through a comprehensive analysis of scientific literature, we have carried out a practical assessment of this topic. The gathering of pollutants and the formation of dense bacterial communities on microplastics create advantageous circumstances for an increased frequency of ARG transfer and evolution. Additional investigations are necessary to acquire a more profound comprehension of how pathogens and ARGs are enriched, transported, and transferred on microplastics. This research is essential for evaluating the health risks associated with human exposure to these pollutants. [ABSTRACT FROM AUTHOR]

The article delves into the crucial role of effective human-robot interactions in collaborative tasks, exploring diverse communication channels like hearing, speech, sight, touch, and learning. Topics include human-robot collaboration mirroring human-human collaboration, brain-computer interfaces, and emotional intelligence perception in robotics.

Soil, as a primary repository of plastic debris, faces an escalating influx of microplastics. Microplastics have the potential to decrease soil bulk density and pH, as well as alter soil pore structure and aggregation. These changes in soil physicochemical properties subsequently lead to habitat degradation for microbes and environmental shifts that impact plant growth. Masquerading as soil carbon storage, microplastics can distort assessments of the soil carbon pool by introducing plastic-carbon and associated leachates, influencing soil organic matter (SOM) turnover through priming effects (e.g., dilution, substrate switching, and co-metabolisms). Additionally, microplastics can influence the distribution of soil carbon in particulate and mineral-associated organic matter, consequently affecting the accumulation and stability of soil carbon. Furthermore, microplastics can also influence the chemodiversity of dissolved organic matter (DOM) in soils by increasing DOM aromaticity and molecular weight while deepening its humification degree. The changes observed in soil DOM may be attributed to inputs from microplastic-derived DOM along with organo-organic and organo-mineral interactions coupled with microbial degradation processes. Acting as an inert source of carbon, microplastics create a distinct ecological niche for microbial growth and contribute to necromass formation pathways. Conventional microplastics can reduce microbial necromass carbon contribution to the stable pool of soil carbon, whereas bio-microplastics tend to increase it. Furthermore, microplastics exert a wide range of effects on plant performance through both internal and external factors, influencing seed germination, vegetative and reproductive growth, as well as inducing ecotoxicity and genotoxicity. These impacts may arise from alterations in the growth environment or the uptake of microplastics by plants. Future research should aim to elucidate the impact of microplastics on microbial necromass accumulation and carbon storage within mineral-associated fractions, while also paying closer attention to rhizosphere dynamics such as the microbial stabilization and mineral protection for rhizodeposits within soils. Highlights: • Microplastics (MPs) have either positive or negative effects on SOM mineralization. • MPs affect soil carbon distribution in particulate and mineral-associated fraction. • MPs increase the aromaticity, molecular weight and humification degree of soil DOM. • Conventional MPs can reduce microbial necromass, whereas bio-MPs cannot. • MPs influence plant performance through both internal and external factors. [ABSTRACT FROM AUTHOR]

Surface layers (S-layers) are proteinaceous, two-dimensional paracrystalline arrays that constitute a major component of the cell envelope in many prokaryotic species. In this study, we investigated S-layer biogenesis in the bacterial model organism Caulobacter crescentus. Fluorescence microscopy revealed localised incorporation of new S-layer at the poles and mid-cell, consistent with regions of cell growth in the cell cycle. Light microscopy and electron cryotomography investigations of drug-treated bacteria revealed that localised S-layer insertion is retained when cell division is inhibited, but is disrupted upon dysregulation of MreB or lipopolysaccharide. We further uncovered that S-layer biogenesis follows new peptidoglycan synthesis and localises to regions of high cell wall turnover. Finally, correlated cryo-light microscopy and electron cryotomographic analysis of regions of S-layer insertion showed the presence of discontinuities in the hexagonal S-layer lattice, contrasting with other S-layers completed by defined symmetric defects. Our findings present insights into how C. crescentus cells form an ordered S-layer on their surface in coordination with the biogenesis of other cell envelope components. Surface layers (S-layers) are proteinaceous, two-dimensional paracrystalline arrays that constitute a major component of the cell envelope in many prokaryotic species. Here, Herdman et al. investigate S-layer biogenesis in the bacterium Caulobacter crescentus, providing insights into its coordination with the synthesis of other cell envelope components. [ABSTRACT FROM AUTHOR]

Allelopathy has been considered as a natural method of weed control. Despite the nature of allelochemical compounds has been studied, little is known about the genetic basis underlying allelopathy. However, it is known that rice exhibits diverse allelopathic potentials across varieties, and breeding for rice plants exhibiting allelopathic potential conferring an advantage against weeds in paddy fields would be highly desirable. Knowledge of the gene factors and the identification of the genomic regions responsible for allelopathy would facilitate breeding programs. Taking advantage of the existing genetic diversity in rice, particularly in temperate japonica rice, we conducted a comprehensive investigation into the genetic determinants that contribute to rice allelopathy. Employing Genome-Wide Association Study, we identified four Quantitative Trait Loci, with the most promising loci situated on chromosome 2 and 5. Subsequent inspection of the genes located within these QTLs revealed genes associated with the biosynthesis of secondary metabolites such as Phenylalanine Ammonia Lyase (PAL), a key enzyme in the synthesis of phenolic compounds, and two genes coding for R2R3-type MYB transcription factors. The identification of these two QTLs associated to allelopathy in rice provides a useful tool for further exploration and targeted breeding strategies. [ABSTRACT FROM AUTHOR]

Psychological stress and intestinal leakage are key factors in atopic dermatitis (AD) recurrence and exacerbation. Here, we demonstrate the mechanism underlying bacterial translocation across intestinal epithelial barrier damaged due to stress and further aggravation of trimellitic anhydride (TMA)–induced itch, which remain unclear, in AD mice. Immobilization (IMO) stress exacerbated scratching bouts and colon histological damage, and increased serum corticosterone and lipopolysaccharide (LPS). Orally administered fluorescein isothiocyanate (FITC)-dextran and surgically injected (into the colon) Cy5.5-conjugated LPS were detected in the serum and skin after IMO stress, respectively. The relative abundance of aerobic or facultative anaerobic bacteria was increased in the colon mucus layer, and Lactobacillus murinus, E. coli, Staphylococcus nepalensis, and several strains of Bacillus sp. were isolated from the spleens and mesenteric lymph nodes. Oral antibiotics or intestinal permeability blockers, such as lubiprostone (Lu), 2,4,6-triaminopyrimidine (TAP) and ML-7, inhibited IMO stress-associated itch; however, it was reinduced through intradermal or i.p. injection of LPS without IMO stress. I.p. injection of TAK-242 (resatorvid), a TLR4 inhibitor, abrogated IMO stress-associated itch, which was also confirmed in TLR4-KO mice. IMO stress alone did not cause itch in naïve mice. IMO stress-induced itch aggravation in TMA-treated AD mice might be attributed to the translocation of gut-derived bacterial cells and LPS, which activates peripheral TLR4 signaling. [ABSTRACT FROM AUTHOR]

A precise diagnosis in medicine allows appropriate disease-specific management. Kidney failure of unknown aetiology remains a frequent diagnostic label within the haemodialysis unit and kidney transplant clinic, accounting for 15–20% of these patients. Approximately 10% of such cases may have an underlying monogenic cause of kidney failure. Modern genetic approaches can provide a precise diagnosis for patients and their families. A search for extra-renal disease manifestations is also important as this may point to a specific genetic diagnosis. Here, we present two patients where molecular genetic testing was performed because of kidney failure of unknown aetiology and associated retinal phenotypes. The first patient reached kidney failure at 16 years of age but only presented with a retinal phenotype at 59 years of age and was found to have evidence of rod-cone dystrophy. The second patient presented with childhood kidney failure at the age of 15 years and developed visual difficulties and photophobia at the age of 32 years and was diagnosed with cone dystrophy. In both cases, genetic tests were performed which revealed a homozygous whole-gene deletion of NPHP1-encoding nephrocystin-1, providing the unifying diagnosis of Senior-Løken syndrome type 1. We conclude that reviewing kidney and extra-renal phenotypes together with targeted genetic testing was informative in these cases of kidney failure of unknown aetiology and associated retinal phenotypes. The involvement of an interdisciplinary team is advisable when managing such patients and allows referral to other relevant specialities. The long time lag and lack of diagnostic clarity and clinical evaluation in our cases should encourage genetic investigations for every young patient with unexplained kidney failure. For these and similar patients, a more timely genetic diagnosis would allow for improved management, a risk assessment of kidney disease in relatives, and the earlier identification of extra-renal disease manifestations. [ABSTRACT FROM AUTHOR]

Research on amateur mountaineers is scarce, and this study aims to delve into the emotional experiences of ten amateur mountaineers during their ascent using the "Befindlichkeitsskala" (BFS) and Lake Louise Acute Mountain Sickness scoring system (LLS). These subjects were exposed to altitudes of 3140 m, 4300 m, and 5276 m, respectively. We found that LLS scores were negatively correlated with positive emotions (β = −27.54, p < 0.05) and positively correlated with negative emotions (β = 21.97, p < 0.05). At an altitude of 4300 m, individuals with AMS exhibited significant differences in depression, anger, excitement, and inactivity compared to climbers without AMS. Upon returning to 3140 m after completing the climb, significant differences were observed in emotions such as happiness, calmness, anger, excitement, and depression. Throughout the three-day climb, noteworthy differences emerged in activity, happiness, calmness, inactivity, positive emotions (p < 0.01), negative emotions, and overall emotional scores (p < 0.05). Our study suggests a decline in the emotional well-being of amateur climbers with increasing altitude, highlighting AMS as a pivotal predictive factor for emotional experiences while climbing. [ABSTRACT FROM AUTHOR]

Matching the language or content of a message to the psychological profile of its recipient (known as "personalized persuasion") is widely considered to be one of the most effective messaging strategies. We demonstrate that the rapid advances in large language models (LLMs), like ChatGPT, could accelerate this influence by making personalized persuasion scalable. Across four studies (consisting of seven sub-studies; total N = 1788), we show that personalized messages crafted by ChatGPT exhibit significantly more influence than non-personalized messages. This was true across different domains of persuasion (e.g., marketing of consumer products, political appeals for climate action), psychological profiles (e.g., personality traits, political ideology, moral foundations), and when only providing the LLM with a single, short prompt naming or describing the targeted psychological dimension. Thus, our findings are among the first to demonstrate the potential for LLMs to automate, and thereby scale, the use of personalized persuasion in ways that enhance its effectiveness and efficiency. We discuss the implications for researchers, practitioners, and the general public. [ABSTRACT FROM AUTHOR]

Objective: Medication overuse headache (MOH) was recently shown to be associated with leaky gut in rodents. We aimed to investigate whether chronic migraine (CM) patients with MOH have elevated lipopolysaccharide levels and inflammatory molecules in blood circulation. Materials and methods: The study included women participants (40 CM patients with NSAID overuse headache, 35 episodic migraine (EM) patients, and 20 healthy non-headache sufferers). Migraine duration, monthly migraine headache days, MigSCog, HADS-D, HADS-A, and HIT-6 scores were recorded. Serum samples were collected to measure circulating LPS, LPS binding protein (LBP), tight junction protein occludin, adherens junction protein vascular endothelial cadherin (VE-cadherin), CGRP, HMGB1, HIF-1α, IL-6, and IL-17 levels. Results: Serum LPS, VE-Cadherin, CGRP, HIF-1α, and IL-6 levels were significantly higher in the CM + MOH group compared to the EM group and healthy controls while serum LBP and HMGB1 were higher in the CM + MOH group compared to healthy controls. IL-17 and occludin levels were comparable between the three groups. Serum HMGB1 levels in EM patients were higher compared to the control group. Mig-SCog and HIT-6 scores were higher in the CM + MOH group compared to EM patients. HADS-A and HADS-D scores were significantly higher in the CM + MOH group compared to EM patients and healthy controls, and they were also higher in EM patients compared to healthy subjects. LPS levels were correlated with VE-cadherin and occludin levels. The number of monthly migraine headache days was positively correlated with serum LPS, HIF-1α, VE-cadherin, and IL-6 levels, HADS-A, HADS-D, HIT-6, and MigSCog scores. Conclusion: We have evidence for the first time that CM + MOH is associated with elevated serum LPS and LBP levels suggestive of LPS leak into the systemic circulation. Higher levels of nociceptive and/or pro-inflammatory molecules such as HMGB1, HIF-1α, IL-6, and CGRP may play a role in trigeminal sensitization and neurobiology of MOH. Intestinal hyperpermeability and consequent inflammatory response should be considered as a potential contributory factor in patients with MOH. [ABSTRACT FROM AUTHOR]

Understanding the dynamics of phytoplankton assemblages in various and variable aquatic ecosystems is of paramount importance, given the strategic supporting services offered by these organisms. Such knowledge is implicitly based on the analysis of the realized niche of the different populations, i.e. of the sets of conditions within which populations show a positive growth. The range of phytoplankton morphological traits variability is evolutionarily selected to maximize the ecological performance of species while they are entrained in the spectrum of turbulent flows. In addition, most phytoplankton species exhibit high morphological plasticity that can further optimize their performance under reduced environmental variability. Although this plasticity is well known, it is seldom considered in phytoplankton studies. Morphological analysis could therefore be used as a tool to estimate the environmental variability within which a species can persist and, ultimately, the niche width of phytoplankton populations. This opinion paper tries to answer the questions: to what extent can the morphological variability of phytoplankton offer a synthesis of the environmental variability of aquatic ecosystems?. Do the morphological traits contain sufficient information to describe the width of the realized niche of phytoplankton species? What can we do to fill eventual gaps in our knowledge? [ABSTRACT FROM AUTHOR]

Tanshinones, are a group of diterpenoid red pigments present in Danshen – an important herbal drug of Traditional Chinese Medicine which is a dried root of Salvia miltiorrhiza Bunge. Some of the tanshinones are sought after as pharmacologically active natural products. To date, the biosynthetic pathway of tanshinones has been only partially elucidated. These compounds are also present in some of the other Salvia species, i.a. from subgenus Perovskia, such as S. abrotanoides (Kar.) Sytsma and S. yangii B.T. Drew. Despite of the close genetic relationship between these species, significant qualitative differences in their diterpenoid profile have been discovered. In this work, we have used the Liquid Chromatography–Mass Spectrometry analysis to follow the content of diterpenoids during the vegetation season, which confirmed our previous observations of a diverse diterpenoid profile. As metabolic differences are reflected in different transcript profile of a species or tissues, we used metabolomics-guided transcriptomic approach to select candidate genes, which expression possibly led to observed chemical differences. Using an RNA-sequencing technology we have sequenced and de novo assembled transcriptomes of leaves and roots of S. abrotanoides and S. yangii. As a result, 134,443 transcripts were annotated by UniProt and 56,693 of them were assigned as Viridiplantae. In order to seek for differences, the differential expression analysis was performed, which revealed that 463, 362, 922 and 835 genes indicated changes in expression in four comparisons. GO enrichment analysis and KEGG functional analysis of selected DEGs were performed. The homology and expression of two gene families, associated with downstream steps of tanshinone and carnosic acid biosynthesis were studied, namely: cytochromes P-450 and 2-oxoglutarate-dependend dioxygenases. Additionally, BLAST analysis revealed existence of 39 different transcripts related to abietane diterpenoid biosynthesis in transcriptomes of S. abrotanoides and S. yangii. We have used quantitative real-time RT-PCR analysis of selected candidate genes, to follow their expression levels over the vegetative season. A hypothesis of an existence of a multifunctional CYP76AH89 in transcriptomes of S. abrotanoides and S. yangii is discussed and potential roles of other CYP450 homologs are speculated. By using the comparative transcriptomic approach, we have generated a dataset of candidate genes which provides a valuable resource for further elucidation of tanshinone biosynthesis. In a long run, our investigation may lead to optimization of diterpenoid profile in S. abrotanoides and S. yangii, which may become an alternative source of tanshinones for further research on their bioactivity and pharmacological therapy. [ABSTRACT FROM AUTHOR]

Background: The Patient-Reported Outcomes Measurement and Information System (PROMIS®) global health items (global-10) yield physical and mental health scale scores and the PROMIS-Preference (PROPr) scoring system estimated from PROMIS domain scores (e.g., PROMIS-29 + 2) produces a single score anchored by 0 (dead or as bad as being dead) to 1 (full health). A link between the PROMIS global-10 and the PROPr is needed. Methods: The PROMIS-29 + 2 and the PROMIS global-10 were administered to 4102 adults in the Ipsos KnowledgePanel in 2022. The median age was 52 (range 18–94), 50% were female, 70% were non-Hispanic White, and 64% were married or living with a partner. The highest level of education completed for 26% of the sample was a high school degree or general education diploma and 44% worked full-time. We estimated correlations of the PROPr with the PROMIS global health items and the global physical and mental health scales. We examined the adjusted R2 and estimated correlations between predicted and observed PROPr scores. Results: Product-moment correlations between the PROMIS global health items and the PROPr ranged from 0.50 to 0.63. The PROMIS global physical health and mental health scale scores correlated 0.74 and 0.60, respectively, with the PROPr. The adjusted R2 in the regression of the PROPr on the PROMIS global health items was 64%. The equated PROPr preference scores correlated (product-moment) 0.80 (n = 4043; p < 0.0001) with the observed PROPr preference scores, and the intra-class correlation (two-way random effects model) was 0.80. The normalized mean absolute error (NMAE) was 0.45 (SD = 0.43). The adjusted R2 in the OLS regression of the PROPr on the PROMIS global health scales was 59%. The equated PROPr preference scores correlated (product-moment) was 0.77 (n = 4046; p < 0.0001) with the observed PROPr preference scores, and the intra-class correlation was 0.77. The NMAE was 0.49 (SD = 0.45). Conclusions: Regression equations provide a reasonably accurate estimate of the PROPr preference-based score from the PROMIS global health items or scales for group-level comparisons. These estimates facilitate cost-effectiveness research and meta-analyses. The estimated PROPr scores are not accurate enough for individual-level applications. Future evaluations of the prediction equations are needed. [ABSTRACT FROM AUTHOR]

Obesity, which can arise from genetic or environmental factors, has been shown to cause serious damages to the reproductive system. The ovary, as one of the primary regulators of female fertility, is a complex organ comprised of heterogeneous cell types that work together to maintain a normal ovarian microenvironment (OME). Despite its importance, the effect of obesity on the entire ovary remains poorly documented. In this study, we performed ovary single-cell and nanoscale spatial RNA sequencing to investigate how the OME changed under different kinds of obesity, including high-fat diet (HFD) induced obesity and Leptin ablation induced obesity (OB). Our results demonstrate that OB, but not HFD, dramatically altered the proportion of ovarian granulosa cells, theca-interstitial cells, luteal cells, and endothelial cells. Furthermore, based on the spatial dynamics of follicular development, we defined four subpopulations of granulosa cell and found that obesity drastically disrupted the differentiation of mural granulosa cells from small to large antral follicles. Functionally, HFD enhanced follicle-stimulating hormone (FSH) sensitivity and hormone conversion, while OB caused decreased sensitivity, inadequate steroid hormone conversion, and impaired follicular development. These differences can be explained by the differential expression pattern of the transcription factor Foxo1. Overall, our study provides a powerful and high-resolution resource for profiling obesity-induced OME and offers insights into the diverse effects of obesity on female reproductive disorders. [ABSTRACT FROM AUTHOR]

In vitro methods provide a key opportunity to model human-relevant exposure scenarios for hazard identification of inhaled toxicants. Compared to in vivo tests, in vitro methods have the advantage of assessing effects of inhaled toxicants caused by differences in dosimetry, e.g., variations in concentration (exposure intensity), exposure duration, and exposure frequency, in an easier way. Variations in dosimetry can be used to obtain information on adverse effects in human-relevant exposure scenarios that can be used for risk assessment. Based on the published literature of exposure approaches using air-liquid interface models of the respiratory tract, supplemented with additional experimental data from the EU H2020 project "PATROLS" and research funded by the Dutch Ministry of Agriculture, Nature and Food Quality, the advantages and disadvantages of different exposure methods and considerations to design an experimental setup are summarized and discussed. As the cell models used are models for the respiratory epithelium, our focus is on the local effects in the airways. In conclusion, in order to generate data from in vitro methods for risk assessment of inhaled toxicants it is recommended that (1) it is considered what information really is needed for hazard or risk assessment; (2) the exposure system that is most suitable for the chemical to be assessed is chosen; (3) a deposited dose that mimics deposition in the human respiratory tract is used, and (4) the post-exposure sampling methodology should be carefully considered and relevant to the testing strategy used. Plain language summary The impact of airborne pollutants on human health is determined by what pollutant it is, how much we breathe in, for how long and how often. Testing in animals is cumbersome and results may not reflect human health impacts. Advanced cell models of the human lung allow prediction of the health impact of many different exposure scenarios. Here, we compare different models and exposure methods and provide criteria that may assist in designing experiments, interpreting the results, and thus assessing the risks posed by airborne pollutants. We recommend (1) determining what information is needed to plan the experiment, (2) choosing an exposure method that is suitable for the pollutant of interest, (3) determining the amount of pollutant that interacts with the human lung, to relate this to realistic deposition in the lung, and (4) considering the time between the exposure and measurement of the effect. [ABSTRACT FROM AUTHOR]

Learning dynamical systems in a sample-efficient way is important for model-based control. Active learning which sequentially selects the most informative data to sample is capable of greatly reducing sample complexity. The active learning problem for dynamical systems is hard as we can not arbitrarily draw samples from the system's state space under constraints of system dynamics. The existing approaches model the dynamical systems using Bayesian linear regression or Gaussian processes which can not be applied to complex dynamical systems with high-dimensional state spaces. In this article, we propose a new method to actively learn dynamical systems using Bayesian neural networks which allow for modeling high-dimensional systems with complex dynamics. By maximizing the accumulated differential entropies along the trajectory, the proposed method iteratively searches for the most informative action sequence which will yield informative samples when applied to the real system. With random exploration and model-based reinforcement learning as baselines, we verify the superiority of the proposed method via accuracy of one-step and multi-step predictions, the control performance, the exploration efficiency of the state space on numerical benchmarks. [ABSTRACT FROM AUTHOR]

Postoperative pulmonary complications (PPCs) arise from a complex interplay of patient, surgical, and anesthesia-related factors. Despite their significant impact, there are currently no standardized guidelines recommending a comprehensive preoperative approach to assessing patients with PPC risk factors. Preoperative pulmonary evaluation (PPE) plays a pivotal role in identifying underlying patient conditions, undiagnosed diseases and optimal treatments. PPE involves systematic identification of patient, surgical, and anesthesia-related risk factors. Severe PPCs include atelectasis, pneumonia, respiratory failure, pulmonary embolism, and worsening chronic lung disease. Surgical urgency, type, duration, approach of the surgical procedure, and comorbidities influence PPC rates, with cardiac, thoracic, abdominal, and vascular surgeries being particularly vulnerable. Patient-related risk factors encompass non-pulmonary and pulmonary factors. Aging populations increase surgical demand, with advanced age and frailty predicting higher morbidity and mortality risks. Conditions like congestive heart failure, obesity, obstructive sleep apnea, and smoking heighten PPC risks. Asthma, chronic obstructive pulmonary disease, interstitial lung diseases, pulmonary hypertension, previous pulmonary thromboembolism, acute respiratory infections, and COVID-19 impact pulmonary risk profiles. Surgery and anesthesia-related risk factors include the site of surgery, operation time, and emergency surgery. Surgery near the diaphragm elevates PPC risk, while longer operation times correlate with increased PPC incidence. Emergency surgeries pose challenges in risk assessment. Anesthetic techniques influence outcomes, with regional anesthesia often preferable. Neuromuscular blocking agents impact PPCs, and protective ventilation strategies can mitigate complications. As current literature lacks a comprehensive approach to PPE, in this review, we present a comprehensive approach to preoperative pulmonary approach to surgical patients to help in risk stratification, further optimization, as well as shared decision making between the surgeon and the patients and their family prior to consenting for a major surgical procedure. [ABSTRACT FROM AUTHOR]

This study re-examines the linguistic phylogeny of the South Caucasian linguistic family (aka the Kartvelian linguistic family) and attempts to identify its Urheimat. We apply Bayesian phylogenetics to infer a dated phylogeny of the South Caucasian languages. We infer the Urheimat and the reasons for the split of the Kartvelian languages by taking into consideration (1) the past distribution ranges of wildlife elements whose names can be traced back to proto-Kartvelian roots, (2) the distribution ranges of past cultures and (3) the genetic variations of past and extant human populations. Our best-fit Bayesian phylogenetic model is in agreement with the widely accepted topology suggested by previous studies. However, in contrast to these studies, our model suggests earlier mean split dates, according to which the divergence between Svan and Karto-Zan occurred in the early Copper Age, while Georgian and Zan diverged in the early Iron Age. The split of Zan into Megrelian and Laz is widely attributed to the spread of Georgian and/or Georgian speakers in the seventh-eighth centuries CE. Our analyses place the Kartvelian Urheimat in an area that largely intersects the Colchis glacial refugium in the South Caucasus. The divergence of Kartvelian languages is strongly associated with differences in the rate of technological expansions in relation to landscape heterogeneity, as well as the emergence of state-run communities. Neolithic societies could not colonize dense forests, whereas Copper Age societies made limited progress in this regard, but not to the same degree of success achieved by Bronze and Iron Age societies. The paper also discusses the importance of glacial refugia in laying the foundation for linguistic families and where Indo-European languages might have originated. [ABSTRACT FROM AUTHOR]

The Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) was a yearlong expedition supported by the icebreaker R/V Polarstern, following the Transpolar Drift from October 2019 to October 2020. The campaign documented an annual cycle of physical, biological, and chemical processes impacting the atmosphere-ice-ocean system. Of central importance were measurements of the thermodynamic and dynamic evolution of the sea ice. A multi-agency international team led by the University of Colorado/CIRES and NOAA-PSL observed meteorology and surface-atmosphere energy exchanges, including radiation; turbulent momentum flux; turbulent latent and sensible heat flux; and snow conductive flux. There were four stations on the ice, a 10 m micrometeorological tower paired with a 23/30 m mast and radiation station and three autonomous Atmospheric Surface Flux Stations. Collectively, the four stations acquired ~928 days of data. This manuscript documents the acquisition and post-processing of those measurements and provides a guide for researchers to access and use the data products. [ABSTRACT FROM AUTHOR]

Random Survival Forests (RSF) has recently showed better performance than statistical survival methods as Cox proportional hazard (CPH) in predicting conversion risk from mild cognitive impairment (MCI) to Alzheimer's disease (AD). However, RSF application in real-world clinical setting is still limited due to its black-box nature. For this reason, we aimed at providing a comprehensive study of RSF explainability with SHapley Additive exPlanations (SHAP) on biomarkers of stable and progressive patients (sMCI and pMCI) from Alzheimer's Disease Neuroimaging Initiative. We evaluated three global explanations—RSF feature importance, permutation importance and SHAP importance—and we quantitatively compared them with Rank-Biased Overlap (RBO). Moreover, we assessed whether multicollinearity among variables may perturb SHAP outcome. Lastly, we stratified pMCI test patients in high, medium and low risk grade, to investigate individual SHAP explanation of one pMCI patient per risk group. We confirmed that RSF had higher accuracy (0.890) than CPH (0.819), and its stability and robustness was demonstrated by high overlap (RBO > 90%) between feature rankings within first eight features. SHAP local explanations with and without correlated variables had no substantial difference, showing that multicollinearity did not alter the model. FDG, ABETA42 and HCI were the first important features in global explanations, with the highest contribution also in local explanation. FAQ, mPACCdigit, mPACCtrailsB and RAVLT immediate had the highest influence among all clinical and neuropsychological assessments in increasing progression risk, as particularly evident in pMCI patients' individual explanation. In conclusion, our findings suggest that RSF represents a useful tool to support clinicians in estimating conversion-to-AD risk and that SHAP explainer boosts its clinical utility with intelligible and interpretable individual outcomes that highlights key features associated with AD prognosis. [ABSTRACT FROM AUTHOR]

Fat intake is among the most significant triggers for symptom development in patients with irritable bowel syndrome (IBS). Nevertheless, long-term restriction in fatty foods ingestion may lead to nutritional inadequacies. This study aimed to identify the crucial genes involved in lipid-induced gastrointestinal symptoms, contributing to helping IBS patients regulate fat. The clinical characteristics of the subjects were collected by questionnaire investigation and analyzed using multivariate logistic regression. Differentially expressed genes (DEG) and signaling pathways were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. ImmuInfiltration and CIBERSORT packages evaluated small intestine immune cell infiltration. Random forest and SVM-RFE algorithms were used to select hub genes. A receiver operating characteristic curve was used to access the diagnostic significance of each hub gene. Gene Set Enrichment Analysis (GSEA) was performed to identify hub genes' molecular processes in IBS development after lipid infusion. IBS patients' risk, severity, and quality of life increased with fat intake. In total, 116 robust DEGs were identified in IBS patients after lipid infusion using the GSE166869 dataset and were mainly clustered in the immune and inflammatory pathways. IBS patients had greater Neutrophils, CD4+ T cells, and M1 Macrophages than healthy controls. Furthermore, infiltration levels of Neutrophils and resting memory CD4+ T cells were inversely related to the expression of hub genes (IGKV1D-43, IGKV1-12, APOD, FCGR2A and IGKV2-29). After lipid infusion, GSEA results of each hub gene indicated the relevance of proinflammatory pathways in IBS pathogenesis. After verification, only APOD and FCGR2A were stably downregulated in small intestinal mucosa and plasma of IBS patients. The area under the curve of APOD combined with FCGR2A expression was 0.9. APOD and FCGR2A may be promising biomarkers for IBS diagnosis and lipid-sensitive IBS patients. Their potential roles in the immune microenvironment of the small intestinal mucosa may provide a vital clue to IBS precision therapy. [ABSTRACT FROM AUTHOR]

The large superfamily of labdane-related diterpenoids is defined by the cyclization of linear geranylgeranyl pyrophosphate (GGPP), catalyzed by copalyl diphosphate synthases (CPSs) to form the basic decalin core, the copalyl diphosphates (CPPs). Three stereochemically distinct CPPs have been found in plants, namely (+)-CPP, ent-CPP and syn-CPP. Here, we used X-ray crystallography and cryo-EM methods to describe different oligomeric structures of a syn-copalyl diphosphate synthase from Oryza sativa (OsCyc1), and provided a cryo-EM structure of OsCyc1D367A mutant in complex with the substrate GGPP. Further analysis showed that tetramers are the dominant form of OsCyc1 in solution and are not necessary for enzyme activity in vitro. Through rational design, we identified an OsCyc1 mutant that can generate ent-CPP in addition to syn-CPP. Our work provides a structural and mechanistic basis for comparing different CPSs and paves the way for further enzyme design to obtain diterpene derivatives with specific chirality. Copalyl diphosphate synthases (CPSs) catalyze the crucial cyclization step in labdane diterpene biosynthesis to generate stereochemically distinct copalyl diphosphates (CPPs), however, the stereoselectivity within CPSs remains underexplored. Here, the authors report the 3D structure and oligomeric properties of syn-CPS from Oryza sativa, which originally produces syn-CPP but also ent-CPP after mutagenesis. [ABSTRACT FROM AUTHOR]

Rift Valley fever (RVF) is a zoonotic viral disease transmitted by mosquitoes and causes abortion storms, fetal malformations, and newborn animal deaths in livestock ruminants. In humans, RVF can manifest as hemorrhagic fever, encephalitis, or retinitis. Outbreaks of RVF have been occurring in Africa since the early 20th century and continue to pose a threat to both humans and animals in various regions such as Africa, Madagascar, the Comoros, Saudi Arabia, and Yemen. The development of RVF vaccines is crucial in preventing mortality and morbidity and reducing the spread of the virus. While several veterinary vaccines have been licensed in endemic countries, there are currently no licensed RVF vaccines for human use. This review provides an overview of the existing RVF vaccines, as well as potential candidates for future studies on RVF vaccine development, including next-generation vaccines that show promise in combating the disease in both humans and animals. [ABSTRACT FROM AUTHOR]