Diverse Mechanisms Research Articles

Heat alters diverse thermal tolerance mechanisms: An organismal framework for studying climate change effects in a wild bird

Abstract The ability to cope with heat is likely to influence species success amidst climate change. However, heat coping mechanisms are poorly understood in wild endotherms, which are increasingly pushed to their thermoregulatory limits. We take an organismal approach to this problem, unveiling how behavioural and physiological responses may allow success in the face of sublethal heat. We experimentally elevated nest temperatures for 4 h to mimic a future climate scenario (+4.5°C) during a critical period of post‐natal development in tree swallows (Tachycineta bicolor). Heat‐exposed nestlings exhibited marked changes in behaviour, including movement to cooler microclimates in the nest. They panted more and weighed less than controls at the end of the four‐hour heat challenge, suggesting panting‐induced water loss. Physiologically, heat induced high levels of heat shock protein (HSP) gene expression in the blood, alongside widespread transcriptional differences related to antioxidant defences, inflammation and apoptosis. Critically, all nestlings survived the heat challenge, and those exposed to milder heat were more likely to recruit into the breeding population. Early life but sub‐lethal heat may therefore act as a selective event, with the potential to shape population trajectories. Within the population, individuals varied in their physiological response to heat, namely in HSP gene expression, which exhibited higher mean and higher variance in heat‐exposed nestlings than in controls. Heat‐induced HSP levels were unrelated to individual body mass, or among‐nest differences in brood size, temperature, and behavioural thermoregulation. Nest identity explained a significant amount of HSP variation, yet siblings in the same nest differed by an average of ~4‐fold and individuals in the population differed by as much as ~100‐fold in their HSP response. This massive variation extends previous laboratory work in model organisms showing that heat shock proteins may harbour cryptic phenotypic variation. These results shed light on oft‐ignored elements of thermotolerance in wild birds at a critical stage of post‐natal development. By highlighting the scope of heat‐induced HSP gene expression and coupling it with a suite of organismal traits, we provide a framework for future testing of the mechanisms that shape species success in the face of change. Read the free Plain Language Summary for this article on the Journal blog.

Endotyping in Chronic Rhinosinusitis-An EAACI Task Force Report.

Chronic rhinosinusitis (CRS) is a clinical syndrome defined by typical sinonasal symptoms persisting for at least 12 weeks. CRS is divided into two distinct phenotypes, CRS with nasal polyps (CRSwNP) and without (CRSsNP). The aim of the review is to provide an update on the current knowledge in CRS endotypes. The prevailing hypothesis regarding the pathogenesis of CRS suggests that dysfunctional interactions between the host and environmental stressors at the mucosal surface drive the diverse inflammatory mechanisms. Genetic and epigenetic variations in the mucosal immune system are believed to play a significant role in the pathomechanisms of CRS. Various environmental agents (such as microbes and irritants) have been implicated in CRS. In a healthy state, the sinonasal mucosa acts as a barrier, modulating environmental stimulation and mounting appropriate immune responses against pathogens with minimal tissue damage. Different endotypes may exist based on the specific mechanistic pathways driving the chronic tissue inflammation of CRS. There is a need to understand endotypes in order to better predict, diagnose, and treat CRS. This literature review provides an update on the role of the endotypes in CRS and the limitations of endotyping CRS in clinical practice. Understanding of the pathogenesis and optimal management of CRS has progressed significantly in the last decades; however, there still are several unmet needs in endotype research.

Rifaximin-Alpha Increases Lactase Activity in Patients with Irritable Bowel Syndrome Without Constipation and Small Intestinal Bacterial Overgrowth.

Irritable bowel syndrome symptoms are associated with diverse pathophysiological mechanisms including small intestinal bacterial overgrowth and food intolerance. Small intestinal bacterial overgrowth leads to the decreased activity of several digestive enzymes, including lactase. To assess the efficacy of rifaximin-alpha on the symptoms and lactase activity of patients with irritable bowel syndrome without constipation. This was a prospective, pilot study. The recruited patients had irritable bowel syndrome without constipation (Rome IV criteria), a positive lactulose-Hydrogen Breath Test for small intestinal bacterial overgrowth, low urinary D-Xylose levels measured using the Lactest® test, and self-reported lactose intolerance. In addition, lactose HBT was performed. All patients received 400mg rifaximin-alpha every 8h for 2weeks. Four weeks after the intervention, lactose and lactulose HBT were performed, and the symptoms and urinary D-Xylose levels were evaluated. After treatment with rifaximin-alpha, 60% of the patients reported improvement in abdominal pain, 44% in bloating, 36% in flatulence, 60% in borborygmi, and 72% in stool consistency. A negative lactulose-Hydrogen Breath Test result for SIBO was documented in 32% of patients, and lactose maldigestion by lactose-Hydrogen Breath Test was reduced from 88 to 52% of the studied subjects. The median D-Xylose levels before and after treatment were 7.6 (IQR 4.34-13.7)mg/dL vs. 10.4 (IQR 7.1-17.3)mg/dL, p = 0.002. Rifaximin-alpha caused symptomatic improvement, reduced lactose maldigestion, and reduced positive Hydrogen Breath Test results for small intestinal bacterial overgrowth in patients with irritable bowel syndrome without constipation.

Amidoximes and their Cyclized Analogue Oxadiazoles as New Frontiers in Chemical Biology: Mini Review

Abstract: This comprehensive review delves into the medicinal chemistry of amidoxime and 1,2,4- oxadiazole scaffolds. These scaffolds have been modified to address bacterial infections, malaria, inflammation, Alzheimer's disease, and cancer, yielding novel lead compounds with significant therapeutic potential. The review scrutinizes recently developed bioactive candidates, highlighting their antibacterial and anti-biofilm properties through the targeting of essential bacterial replication and virulence factors. In oncology, these derivatives exhibit promise by interacting with critical macromolecules, presenting diverse mechanisms of action. Notably, amidoxime hybrids have shown potential in inhibiting indoleamine 2,3-dioxygenase 1 (IDO1), whereas oxadiazole hybrids demonstrate anti-proliferative effects by targeting the epidermal growth factor receptor (EGFR). These hybrids also display dual inhibition of cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX), indicating significant anti-inflammatory potential. In the context of Alzheimer's disease, oxadiazoles are emerging as promising agents targeting human carbonic anhydrase (hCA) I and II enzymes. Additionally, they exhibit anti-malarial activity by targeting the Plasmodium parasite. The review further examines marketed drugs such as Ximelagatran, Upamostat, and Naldemedine, underscoring their versatile and targeted therapeutic approaches. The aim of this review is to guide medicinal chemists in synthesizing amidoximes and oxadiazoles with enhanced efficacy and reduced side effects. These scaffolds hold promising potential for future development and clinical trials.

Tumor Microenvironment: Nurturing Cancer Cells for Immunoevasion and Druggable Vulnerabilities for Cancer Immunotherapy.

The tumor microenvironment (TME) is an intricate ecosystem where cancer cells thrive, encompassing a wide array of cellular and non-cellular components. The TME co-evolves with tumor progression in a spatially and temporally dynamic manner, which endows cancer cells with the adaptive capability of evading immune surveillance. To this end, diverse cancer-intrinsic mechanisms were exploited to dampen host immune system, such as upregulating immune checkpoints, impairing antigens presentation and competing for nutrients. In this review, we discuss how cancer immunoevasion is tightly regulated by hypoxia, one of the hallmark biochemical features of the TME. Moreover, we comprehensively summarize how immune evasiveness of cancer cells is facilitated by the extracellular matrix, as well as soluble components of TME, including inflammatory factors, lactate, nutrients and extracellular vesicles. Given their important roles in dictating cancer immunoevasion, various strategies to target TME components are proposed, which holds promising translational potential in developing novel therapeutics to sensitize anti-cancer immunotherapy such as immune checkpoint blockade.

Bacterial Diversity Profiles of Desert Sand and Salt Crusts from the Gran Desierto de Altar, Sonora, Mexico

The Gran Desierto de Altar, located in Sonora, Mexico, represents an arid region that offers an opportunity to study microbial life under extreme conditions. This study analyzed the bacterial diversity present in two distinct types of desert sediments: sand dunes (SDs) and salt crusts (SCs) by culture-dependent and culture-independent methods. Environmental DNA was obtained for 16S rRNA gene amplicon sequencing to obtain taxonomic information using QIIME2. In SD, the bacterial communities comprised 24 phyla, with Actinobacteriota (30–40%), Proteobacteria (22–27%), Bacteroidota (9–11%), Firmicutes (7–10%), and Chloroflexi (3–6%) emerging as the most abundant. Notably, in SC, the archaeal phylum Halobacterota was predominant (37–58%). SC hosted 12 bacterial phyla, the most abundant being Firmicutes (14–30%), Bacteroidota (3–24%), and Proteobacteria (1–12%). Bacteria belonging to the phylum Firmicutes, including Metabacillus niabensis, Bacillus subtilis, Bacillus licheniformis, and Alkalibacillus haloalkaliphilus, were isolated using nutrient and saline media. Overall, our findings indicate that the taxonomic composition of the samples analyzed from the Gran Desierto de Altar is consistent with that found in arid environments worldwide. This study provides a basis for future studies focusing on microbial diversity, genetic potentials, and resistance mechanisms of microorganisms from arid environments.

Comparative analysis of community composition and network structure between phyllosphere endophytic and epiphytic fungal communities of Mussaenda pubescens.

The phyllosphere constitutes a critical habitat for microorganisms, exerting profound influences on host vitality, developmental dynamics, reproductive functions, and stress resilience. However, the diversity and network structure of endophytic and epiphytic fungal communities within this microecosystem have not been thoroughly explored. In this investigation, high-throughput sequencing technologies were employed to assess the diversity, community composition, and network structure of endophytic and epiphytic fungal communities associated with Mussaenda pubescens across six geographically distinct locations in Southeast China. The results revealed significant differences in community composition and diversity between endophytic and epiphytic fungi, with pronounced geographical variation observed within these phyllosphere fungal communities. Network analysis indicated that epiphytic fungal networks possess enhanced complexity compared with their endophytic counterparts, although the latter exhibit greater network stability. Moreover, stochastic processes were identified as pivotal in shaping the composition of these fungal communities. This research substantially enriches our comprehension of the diversity and organizational mechanisms of phyllosphere fungal communities, providing novel insights into the modalities of species coexistence and the stability of community equilibrium within ecosystems.IMPORTANCEThis study employs high-throughput sequencing technologies to explore the fungal communities within the phyllosphere of Mussaenda pubescens across Southeast China, offering significant insights into plant mycobiome. It demonstrates geographical variations in these fungal communities, with epiphytic fungi exhibiting more complex interaction networks compared with the endophytic fungi. Crucially, the research indicates that stochastic processes play a substantial role in the composition of fungal communities. These findings enhance our comprehension of plant-associated microecosystems and underscore the intricate interplay of randomness in maintaining ecosystem stability and diversity.

Ursolic acid in colorectal cancer: mechanisms, current status, challenges, and future research directions.

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally, contributing to approximately 10% of all cancer cases and representing the second leading cause of cancer-related mortality worldwide. Ursolic acid (UA), a widely studied pentacyclic triterpenoid, has attracted substantial attention from researchers and clinicians due to its potential therapeutic effects against malignant tumors. Multiple studies have confirmed that UA inhibits tumor cell proliferation, induces differentiation and apoptosis, suppresses invasion, and impedes tumor angiogenesis via diverse mechanisms. However, research specifically addressing UA's anti-CRC effects remains limited, and systematic reviews of its underlying mechanisms in CRC are scarce. This study seeks to provide a comprehensive review of UA's mechanisms of action against CRC, offering valuable insights and references for researchers and clinicians.

Role of Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitors in Weight Loss: Understanding the Clinical Evidence

Obesity is ubiquitous, affecting millions of people all over the world. Its prevalence is increasing day by day in all age groups, ranging from children to adolescents to adults. It has a significant impact on the overall quality of life. Obesity has a strong relationship with various chronic conditions, including type 2 diabetes mellitus. The risk of developing diabetic mellitus considerably increases in obese individuals. Similarly, obesity in diabetic patients increases their probability of developing serious complications. Moreover, the optimal approach to managing diabetes mellitus (type 2) and obesity should be carried out by means of sustained weight loss and glycemic control. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to be a revolutionary class of medications with noteworthy weight-loss benefits in addition to their ability to lower blood sugar levels. These remarkable benefits are mentioned in detail in several different clinical trials. Additionally, diverse mechanisms have also been demonstrated comprehensively via which SGLT-2 inhibitors put forth their function of weight loss. FDA-approved SGLT2 inhibitors show a unique mechanism of action by inhibiting the reabsorption of glucose in the renal proximal tubule. By excreting glucose in the urine and by visceral fat lipolysis, these drugs provide a new avenue for weight reduction. SGLT2 inhibitors are now fundamental parts of weight-loss regimens in patients with type 2 diabetes, going beyond their original role as anti-diabetic medications. This article attempts to review the up-to-date literature on the effectiveness of this particular contemporary function of SGLT2 inhibitors.

Tweaking the redox properties of PpcA from Geobacter metallireducens with protein engineering

Geobacter’s unique ability to perform extracellular electron transfer (EET) to electrodes in Microbial Fuel Cells (MFCs) has sparked the implementation of sustainable production of electrical energy. However, the electrochemical performance of Geobacter’s biofilms in MFCs remains challenging to implement industrially. Multiple approaches are being investigated to enhance MFC technologies. Protein engineering of multihaem cytochromes, key components of Geobacter’s EET pathways, can, conceivably, be pursued to improve the EET chain. The periplasmic cytochrome PpcA bridges ET from the inner to the outer membrane and its deletion impairs this crucial step. The functional characterisation of PpcA homologs from G. sulfurreducens (Gs) and G. metallireducens (Gm) revealed a significantly different redox behaviour even though they only differ by thirteen amino acids. In a previous study, we found that the single replacement of a tryptophan residue by methionine (W45M) in PpcAGm shifted the reduction potential value 33% towards that of PpcAGs. In this work, we expanded our investigation to include other non-conserved residues by conducting five mutation rounds. We identified the most relevant residues controlling the redox properties of PpcAGm. With just four mutations (K19, G25, N26, W45) the reduction potential value of PpcAGm was shifted 71% toward that of PpcAGs. Additionally, in the quadruple mutant, it was possible to replicate the haem oxidation order and the functional mechanisms of PpcAGs, which differ from those in PpcAGm. Overall, the mutants exhibit diverse redox and functional mechanisms that could be explored as a library for the future design of minimal, synthetic, ET chains in Geobacter.

Neddylation steers the fate of cellular receptors

AbstractCellular receptors regulate physiological responses by interacting with ligands, thus playing a crucial role in intercellular communication. Receptors are categorized on the basis of their location and engage in diverse biochemical mechanisms, which include posttranslational modifications (PTMs). Considering the broad impact and diversity of PTMs on cellular functions, we focus narrowly on neddylation, a modification closely resembling ubiquitination. We systematically organize its canonical and noncanonical roles in modulating proteins associated with cellular receptors with the goal of providing a more detailed perspective on the intricacies of both intracellular and cell-surface receptors.

Recent Crop-To-Weed Adaptive Introgression Has Reshaped the Genomic Composition and Geographical Structure of US Weedy Rice (Oryza spp.).

Weedy rice is a close relative of cultivated rice (Oryza sativa) that infests rice fields worldwide and drastically reduces yields. To combat this agricultural pest, rice farmers in the southern US began to grow herbicide-resistant (HR) rice cultivars in the early 2000s, which permitted the application of herbicides that selectively targeted weedy rice without harming the crop. The widespread adoption of HR rice coincided with increased reliance on hybrid rice cultivars in place of traditional inbred varieties. Although both cultivated and weedy rice are predominantly self-fertilising, the combined introductions of HR and hybrid rice dramatically altered the opportunities and selective pressure for crop-weed hybridization and adaptive introgression. In this study, we generated genotyping-by-sequencing data for 178 weedy rice samples collected from across the rice growing region of the southern US; these were analysed together with previously published rice and weedy rice genome sequences to determine the recent genomic and population genetic consequences of adaptive introgression and selection for herbicide resistance in US weedy rice populations. We find a reshaped geographical structure of southern US weedy rice as well as purging of crop-derived alleles in some weed strains of crop-weed hybrid origin. Furthermore, we uncover evidence that related weedy rice strains have made use of different genetic mechanisms to respond to selection. Lastly, we identify widespread presence of HR alleles in both hybrid-derived and nonadmixed samples, which further supports an overall picture of weedy rice evolution and adaptation through diverse genetic mechanisms.

Established and Emerging Roles of DEAD/H‐Box Helicases in Regulating Infection and Immunity

ABSTRACTThe sensing of nucleic acids by DEAD/H‐box helicases, specifically retinoic acid‐inducible gene I (RIG‐I) and melanoma differentiation‐associated protein 5 (MDA5), plays a critical role in inducing antiviral immunity following infection. However, this DEAD/H‐box helicase family includes many additional proteins whose immune functions have not been investigated. While numerous DEAD/H‐box helicases contribute to antiviral immunity, they employ diverse mechanisms beyond the direct sensing of nucleic acids. Some members have also been identified to play proviral (promoting virus replication/propagation) roles during infections, regulate other non‐viral infections, and contribute to the regulation of autoimmunity and cancer. This review synthesizes the known and emerging functions of the broader DEAD/H‐box helicase family in immune regulation and highlights ongoing efforts to target these proteins therapeutically.

The Petri dish under the ice: permafrost pathogens and their impact on global healthcare and antibiotic resistance.

A shallow active layer of soil above the permafrost thaws during the summer months which promotes microbial growth and releases previously confined pathogens which result in bacterial epidemics in circumpolar regions. Furthermore, these permafrost sources harbor several antibiotic resistance genes (ARGs) which may disseminate and pose a challenge for pharmacologists worldwide. The authors examined the potential association between climate change-induced permafrost thawing, and the resulting release of antibiotic-resistant pathogens, as well as the potential impact this can have on global healthcare systems in the long run. A cursory abstract screening was done to rule out any articles that did not have to do with viral pathogens caused by melting permafrost. Articles that were not available in English or that our institutions library did not have full-text access were weeded out by a secondary screen. A comprehensive analysis of 13 relevant studies successfully revealed a wide variety of bacterial genera, including Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., and Achromobacter spp., along with a total of 1043 antibiotic resistance genes (ARGs), with most pertaining to aminoglycosides and beta-lactams, offering resistance via diverse mechanisms such as efflux pumps and enzymatic modifications, within the permafrost isolates. Additionally, mobile genetic elements (MGEs) housing antibiotic resistance genes (ARGs) and virulence factor genes (VFGs), including plasmids and transposons, were also discovered. Permafrost thawing is an underrated healthcare challenge warranting the need for further articles to highlight it alongside concerted efforts for effective mitigation.

Mapping elevational patterns of functional diversity of canopy species in an alpine forest using drone multispectral and LiDAR data

Understanding the patterns and drivers of plant functional diversity is crucial for assessing the functioning and resilience of terrestrial ecosystems to global climate change. Despite the well-documented variability in plant species richness with elevation, the elevational patterns and underlying mechanisms of functional diversity remain poorly understood. This study employed drone equipped with multispectral and light detection and ranging (LiDAR) sensors to investigate the elevational gradients (3208 m to 3984 m) of physiological and morphological functional diversity of canopy tree species in six 1-hectare plots in Baima Snow Mountain, Yunnan, China. Results demonstrated that drone-based multispectral and LiDAR data enabled high-resolution mapping of physiological and morphological functional diversity in forest canopies over large areas. Importantly, functional diversity declined with increasing elevation, with a more pronounced pattern observed for physiological traits compared to morphological traits. Variance partitioning analysis revealed that functional richness was primarily driven by climatic and edaphic factors, particularly temperature, while plant factors played a subordinate role, interacting with climate and soil. Our findings highlight the potential of drone for rapid, large-scale monitoring and mapping of canopy species functional diversity in forests. Moreover, the influence of climate and soil factors on functional diversity suggests that future global warming may enhance functional diversity in alpine forest ecosystems, with implications for ecosystem functioning and services.

New permeability model considering multiscale migration mechanism of deep coalbed methane and its application

Deep coalbed methane (CBM) flow exhibits various transportation mechanisms within the multiscale pore structures of reservoirs, including continuous flow, Knudsen diffusion, and surface diffusion. Current research predominantly emphasizes the effects of individual or partial flow mechanisms and single-factor influences on the multiscale migration of CBM. We proposed a new apparent permeability model that integrates multiple flow mechanisms to enhance our understanding of the factors governing CBM flow in complex fractured networks. This model accounted for stress sensitivity, adsorbed gas desorption, and matrix shrinkage. By assigning appropriate weights to different flow mechanisms, the model yielded a more accurate representation of the deep CBM apparent permeability, avoiding the overestimation resulting from the linear superposition of diverse migration mechanisms. Our findings indicated that the apparent permeability was positively correlated with compressibility and negatively correlated with the tortuosity and Poisson's ratio. In the presence of the adsorbed gas, the apparent permeability of organic matter showed heightened sensitivity to formation pressure, rock compressibility, and tortuosity. However, the impacts of these factors became less pronounced when the pressure differential was small. The proposed model was applied to the flow simulations for a multi-fractured horizontal well within a deep coal reservoir characterized by a complex fracture network. The simulation results agreed well with the production data. We found that continuous flow was the dominant contributor to the apparent permeability of organic and inorganic matter within the coal rock, followed by Knudsen diffusion and surface diffusion. This study provided insights into the evolution of apparent permeability of CBM during development and offered valuable guidance for the analysis of CBM production dynamics, productivity forecasting, and production system design.

Ubiquitin proteasome system in cardiac fibrosis.

Cardiac fibrosis, including reactive fibrosis and replacement fibrosis, is a common pathological process in most cardiovascular diseases. The ubiquitin proteasome system (UPS) plays an important role in the development of fibrosis by mediating the degradation and synthesis of proteins involved in transforming growth factor-β (TGF-β)-dependent and TGF-β-independent fibrous pathways. This review aims to provide an overview of ubiquitinated and deubiquitinated molecules that participating in cardiac fibrosis, with the ultimate purpose to identify promising targets for therapeutic strategies. The UPS primarily impacts cardiac fibrosis through modulation of the TGF-β signaling pathway targeting key molecules involved, including the TGF-β receptors, Smad2/3/4 complexes, and inhibitory Smad7, thereby influencing fibrotic processes. In addition to its effect on TGF-β signaling, UPS also regulates pro-fibrotic pathways independent of TGF-β, including p53, AKT1-p38, and JNK1/2. Understanding these pathways is critical due to their involvement in diverse fibrotic mechanisms. The interplay between ubiquitination and deubiquitination of crucial pathways and molecules is pivotal in cardiac fibrosis and represents a promising area for identifying novel therapeutic targets. Different types of cardiac fibrosis involve distinct fibrotic pathways, leading to differential effects of E3 ligases and DUBs across various cardiac fibrotic diseases. Insights into UPS-mediated regulation of cardiac fibrosis provides potential anti-fibrotic therapeutic strategies, emphasizing the importance of targeting UPS components specific to the heart for effective therapy against cardiac fibrosis.

Diversity, composition, and assembly processes of bacterial communities within per- and polyfluoroalkyl substances (PFAS)-contained urban lake sediments

Per- and polyfluoroalkyl substances (PFAS) are widespread, highly persistent, and bio-accumulative compounds that are increasingly found in the sediments of aquatic systems. Given this accumulation and concerns regarding the environmental impacts of PFAS, their influence on sedimentary bacterial communities remains inadequately studied. Here, we investigated the concentrations of 17 PFAS in sediments from six urban lakes in Nanjing, China, and assessed their effects on the diversity, composition, potential interactions, and assembly mechanisms of sedimentary bacterial communities. Sediment concentrations of PFAS ranged from 4.70 to 5.28 ng·g−1 dry weight. The high concentrations of the short-chain perfluorobutanesulfonic acid (PFBS) suggested its substitution for the long-chain perfluorooctanesulfonic acid (PFOS). As alternatives to long-chain PFAS, short-chain PFAS had similar effects on bacterial communities. The short-chain perfluoropentanoic acid (PFPeA) and the long-chain perfluorotridecanoic acid (PFTrDA) were the most important PFAS related to the ecological patterns of the co-occurrence network and may alter the composition of the sedimentary bacterial communities in the urban lakes. The Anaerolineaceae family represented as keystone bacteria within the PFAS-affected bacterial co-occurrence network. Deterministic processes (65.9 %), particularly homogeneous selection (63.2 %), were the dominant process driving bacterial community assembly. PFAS promoted the phylogenetic clustering and influenced the community dispersal capabilities to shape bacterial community assembly. This study provides a comprehensive analysis of PFAS distribution in sediments across six urban lakes in Nanjing and provides novel insights into the effects of PFAS on sedimentary bacterial communities. Further research is required to elucidate the mechanisms underlying the impacts of PFAS on microbial communities and to evaluate their broader ecological consequences.

Resveratrol: Protective Agent Against Alzheimer's Disease.

Resveratrol is a biologically active natural phenolic plant product. It has several properties which make them useful to treat the disease. In this review, we have highlighted the neuroprotective effects of resveratrol. Several available animal models have been proven to help understand the disease pathway and mechanism of action by resveratrol. In this review, we have highlighted the neuroprotective activity of resveratrol in AD, which effectively counter the neurodegenerative disease by decreasing the formation of plaques. Resveratrol is a natural plant product that is easily available, cost-effective, and possesses neuroprotective activity, which is useful for treating neurodegenerative diseases. Resveratrol presents a promising avenue for AD treatment due to its diverse neuroprotective mechanisms. Given the ongoing global challenge in treating AD, researchers have increasingly focused on exploring the therapeutic potential of resveratrol.

Aging in Place in a Depopulated, Mountainous Area: The Role of Hometown-Visiting Family Members in Shimogo, Japan

In this study, we examined the factors that contribute to successful aging in place in the town of Shimogo, a depopulated mountainous area in Japan, focusing on the interplay between household support types, the performance of daily activities, and the involvement of geographically dispersed family members. A mixed-methods approach was used, combining survey data with multiple correspondence analysis and cluster analysis. The resident household findings reveal significant differences in community engagement and reliance on community support across three household support types: self-help, mutual aid, and combined support. The self-help households demonstrated high self-sufficiency and community participation, while the mutual-aid and combined-support households exhibited greater reliance on family and community resources. An analysis of the activities of out-migrated relatives uncovered diverse engagement profiles, motivated by both providing practical support and strengthening family bonds. The visit frequencies and activity types of the relatives were significantly influenced by both their own characteristics and the levels of self-reliance and community support needs of the resident households. Four distinct relative engagement clusters emerged, reflecting varying levels of support, community involvement, and visit frequency. Our findings underscore the crucial role of both informal (family) and formal (community) support networks in facilitating successful aging in place in rural depopulated areas. Policy implications include strategies supporting both self-reliance and the diverse mechanisms of family- and community-based support to ensure the sustainability of life in these challenging environments.