Climate change is intensifying summer stress conditions, with significant impacts on vine physiology and grape production. Kaolin is commonly used to mitigate heat stress, though its effectiveness may vary depending on vineyard conditions. This study aimed to compare the effects of kaolin application (K) with an untreated control (C) on Verdicchio grapevines across two distinct vineyard sites differing in environmental conditions over two consecutive growing seasons, focusing on leaf gas exchange, leaf temperature, grape composition and yield, and wine characteristics. Results showed that the effects of kaolin varied between sites. Under high thermal stress and low vine vigor, kaolin application improved gas exchange, sustained higher photosynthetic rates, and reduced leaf temperature. Conversely, in higher-vigor vineyards, the effects were less pronounced and mainly limited to reductions in leaf temperature. Under low-vigor conditions, K resulted in higher berry weight and lower total soluble solids. Wines from kaolin-treated grapes exhibited slightly reduced alcohol content and pH. These findings suggest that kaolin’s effectiveness is strongly influenced by climatic conditions and vine vigor. In Mediterranean regions, where heatwaves and drought are common, kaolin application may be a promising tool to alleviate heat stress, supporting improved grape yield and composition.

Cellular metabolites have emerged as noncanonical RNA caps. Despite its early discovery as an RNA cap, the dephospho-CoA (dpCoA) cap remains largely uncharacterized because of a lack of detection technologies. Here we use biochemical and structural analysis to identify Arabidopsis NUDT11 as a specific decapping enzyme toward dpCoA-RNA. Leveraging this specificity, we develop biochemical and transcriptomic methods to quantify and profile dpCoA-RNA across the genome, revealing that dpCoA-RNAs exist across species and exhibit tissue-specific and/or condition-specific variations. In Arabidopsis, dpCoA-RNAs possess distinct transcription start sites and respond more rapidly to high light intensity as compared to 7-methylguanosine (m7G)-capped RNAs. Moreover, Arabidopsis dpCoA-RNAs can reach up to 15% of m7G-capped RNAs in abundance and are associated with translating ribosomes. We further demonstrate that an in vitro transcribed dpCoA-RNA is translated in human cells. This study uncovers a dynamic dpCoA cap that may potentially influence gene expression and establishes a toolkit for future investigations.

Spiraea japonica is widely used for landscaping in China, particularly in urban gardens and parks. During the summer of 2024, leaf blight symptoms were observed on S. japonica in Tongbai County, Henan Province, China (32°22′21″ N, 113°24′10″ E). Field surveys across different areas recorded a disease incidence of 51% (n = 100 plants). Initial symptoms appeared as small, dark brown to nearly black, circular to irregular leaf spots that expanded with tan centers and darker margins; lesions frequently coalesced, producing large, blighted areas and occasional premature defoliation. Diseased leaves (n = 15) were collected and surface sterilized. From each leaf, two pieces were excised from the lesion margin and placed on potato dextrose agar (PDA). Twenty-seven Colletotrichum isolates were recovered (positive isolation rate 90%); three representative isolates from distinct sites (X-21, X-22, X-23) were selected for detailed analyses. On PDA after 5 days of incubation, colonies were fast-growing with aerial mycelium; colonies exhibited a salmon-pink surface with a vinaceous-red reverse. Conidia were hyaline, aseptate, smooth-walled, and cylindrical to fusiform, measuring 9.1–16.6 × 1.6–5.2 μm (n = 100). Appressoria were medium to dark brown, ovoid with entire margins. These features are consistent with members of the Colletotrichum acutatum species complex (Talhinhas et al. 2023). For molecular identification, five loci—the internal transcribed spacer (ITS), dehydrogenase (gapdh), chitin synthase (chs-1), actin (act), and calmodulin (cal)—were amplified for each isolate. All newly generated sequences have been deposited in GenBank under the following accession numbers: PV342493-PV342495 (ITS), PV798316-PV798318 (gapdh), PV575167- PV575169 (chs-1), PV417281, PV417282, PV468789 (act), PV755113, PV660595, PV755114 (cal). A maximum-likelihood phylogeny based on the concatenated dataset placed X-21, X-22, and X-23 within the Colletotrichum fioriniae clade, clearly separated from other congeners. BLAST results showed ≥99–100% identity to reference C. fioriniae strains for all loci. Together, morphology and multilocus phylogeny support the identification of these isolates as C. fioriniae (Zhang et al. 2023). Pathogenicity was assessed by applying 50 μL droplets of a conidial suspension (10⁶ conidia mL⁻¹) onto the adaxial surface of unwounded leaves on five potted S. japonica plants; leaves on five additional plants received 50 μL of sterile water as mock-inoculated controls. Plants were maintained at 28 °C and ~90% relative humidity, lesion consistent with symptoms observed in the field development was evaluated 3 days post-inoculation, whereas control plants remained symptomless. The pathogen was consistently re-isolated from symptomatic tissues and identified as Colletotrichum spp. based on morphology and ITS sequences, thereby fulfilling Koch’s postulates. C. fioriniae causes anthracnose in various hosts in China, including walnut, persimmon, Camellia oleifera, Rhus chinensis (Zhu et al. 2015; Fan et al. 2024; Liu et al. 2025; Xu et al. 2023). Because S. japonica is extensively cultivated for its decorative foliage and profuse flowering, the emergence of anthracnose poses a tangible threat to aesthetic function in public landscapes. Accurate identification of C. fioriniae is thus critical to guide fungicide selection, and support early intervention in landscape maintenance programs.

Canonical activation of G protein-coupled receptors (GPCRs) by hormone binding occurs at the plasma membrane, resulting in the diffusion of second messengers to intracellular effector sites throughout the cell. In contrast, recent evidence suggests that functional GPCRs can induce signaling from distinct intracellular domains, contributing to specificity in signaling. Functional adrenergic receptors have been identified at intracellular sites in the cardiac myocyte such as endosomes, the sarcoplasmic reticulum, the Golgi, and the inner nuclear membrane. These receptors are key regulators of cardiac physiology, mediating the response of the heart to sympathetic stimulation. Under conditions of prolonged cardiac stress leading to chronic adrenergic receptor stimulation, these receptors stimulate pathways that lead to cardiac pathophysiology such as myocyte hypertrophy, apoptosis, and fibrosis, ultimately leading to heart failure. Hence, significant work has resulted in the pharmacological modulation of β-adrenergic receptors for therapeutic benefit. Here, we discuss how the localization of β1- and β2-adrenergic receptors to different sites within the cardiac myocyte dictates control over specific physiological and pathological events. We discuss how therapeutically targeting receptors at these distinct sites may be used for the treatment of cardiac disease.

Transformation behaviors of polybrominated diphenyl ethers (PBDEs) in electronic waste during thermal dismantling processes: Effect mechanisms of coexisting metals.

Biochar-induced microregional pH elevation enhances synergistic immobilization of tetracycline and copper during transport in saline soil water-bearing media: Quantum and molecular insights.

The crystallization of a trimetallic cobalt-molybdenum-sodium metal-organic <!?tlsb=-0.05pt>framework, poly[μ-benzene-1,3,5-tricarboxylato-tetra-μ-oxido-cobaltmolybdenumtrisodium], UOW-10 or [Na3Co(MoO4)(BTC)]n, is achieved by solvothermal synthesis using benzene-1,3,5-tricarboxylic acid (H3BTC, C9H6O6) as a ligand precursor, Na2MoO4·2H2O and Co(NO3)2·2H2O as metal sources, and N,N-dimethylformamide (DMF) as the solvent. 3D electron diffraction (3D ED) reveals that the structure crystallizes in the monoclinic space group P21/c, with lattice parameters of a= 9.718 (2), b= 18.250 (3), c= 6.892 (9) Å, α= γ= 90, β= 96.156 (15)°, V= 1214.7 (4) Å3 and Z= 4. The phase purity of the bulk sample was confirmed using synchrotron powder X-ray diffraction. The organic ligands form a 2D layer, where cobalt and molybdenum are found, with sodium cations located between the layers. There are four crystallographically distinct sodium sites: three exhibit a distorted octahedral coordination geometry, while the remaining site is seven-coordinate. The cobalt has trigonal bipyramidal coordination geometry and molybdenum exhibits a tetrahedral coordination geometry. Half the sodium cations in the structure forms 1D column-like motifs via shared oxygen edges along the crystallographic c axis, which are cross-linked in b by the cobalt and molybdenum sites via bridging O atoms, while the other half of the sodium cations form 2D ribbons in the ac plane, propagating along c, linked by sharing oxygen edges and faces. The optical properties of UOW-10 were investigated through the use of UV-Vis spectroscopy, showing a bandgap of 1.8 eV. Deconvolution of the features in the visible-light region reveals that four peaks are present, which can all be ascribed to the d-d transitions from the trigonal bipyramidal cobalt. By means of thermogravimetric analysis (TGA) and variable-temperature powder X-ray diffraction (VT-PXRD), it is demonstrated that the material has thermal stability to 410 °C, after which structure collapse occurs, leading to a mixture of Na2MoO4, CoO and Co3Mo above 900 °C.

Structural extension of the human exocyst is enabled by a minimal interface.

Effects of protein-glutaminase on structural and functional properties and the interaction mechanism in casein micelle suspensions: convergence of multiscale experiments and molecular dynamics simulations.

The binding of human growth hormone (hGH) to the human growth hormone receptor (hGHR) is a key endocrinological process that controls critical aspects of cell growth, proliferation and differentiation. Mechanistically, this sequential, asymmetric binding event involves the interaction between a single hGH molecule and distinct sites (site 1 and site 2) on the extracellular domain of a preformed hGHR homodimer. Our group recently identified S1H, a rationally-designed peptide sequence mimetic of the hGH site 1-binding helix (residues 36-51) that disrupts the hGH-hGHR interaction and inhibits hGH-mediated phosphorylation of signal transducer and activator of transcription 5 (STAT5) in hGHR-positive cell lines. Structure-activity relationship studies revealed a positive correlation between helical propensity and inhibitory potency of the S1H peptide, prompting the design of structurally "stabilized" S1H variants (SS1H) with improved biological activity. In this study, we employed a chemical strategy, termed hydrocarbon stapling, to generate a series of SS1H peptides that proved to be more helical, proteolytically stable and biologically active compared to linear (unstructured) S1H. Notably, one SS1H derivative (SS1HB) inhibited hGH-induced STAT5 phosphorylation in hGHR-positive human bladder cancer cells more effectively than pegvisomant, the only hGHR antagonist currently approved by the FDA. Collectively, our results demonstrate that hydrocarbon stapling improves the antagonistic effects of S1H peptides and elevates their potential as chemical probes to study the molecular mechanisms of hGH signaling. It is also anticipated that SS1H peptides will serve as potent lead compounds for developing next-generation therapeutics designed to treat endocrine disorders that manifest along the hGH-hGHR signaling axis.

This study investigates the prevalence and sources of microplastics (MPs, 300–5,000 µm) in the marine environment of Abu Dhabi Emirate, UAE—an underexplored region with significant anthropogenic influence. Samples were collected from ten ecologically distinct site categories, including areas near oilfields, near desalination plants, port and marinas, aquaculture activities, public beaches, confined areas, newly developed areas, point sources, near offshore islands and natural habitats. “Natural habitats” showed the lowest MP levels (3.33 particles/100 g sediment; 4.5 P/L water), while sites near oilfields, ports, and offshore islands had the highest (8.2–9.3 P/L water; 5.0–6.6 P/100 g sediment). A total of 1,493 MPs were characterized by size, shape, and color. Polymer analysis of 240 MPs identified acrylonitrile–butadiene–styrene (31%), cellulose acetate (27%), nylon-66 (20%), and PET (10%) as dominant types. Smaller MPs (100–300 µm) were also quantified at selected categories. Pollution Load Index (PLI) analysis, using natural habitats as a baseline, indicated the greatest anthropogenic impact near offshore oilfields and islands, highlighting spatial variations in MP contamination.

Histone post-translational modifications (PTMs) often serve as distinct recognition sites for the recruitment of chromatin-associated proteins (CAPs) for epigenome regulation. While CAP:PTM interactions are extensively studied using histone peptides, this cannot represent the regulatory potential of multisite binding on intact nucleosomes. To overcome this limitation, we applied Nucleosome Mass Spectrometry (Nuc-MS), a native Top-Down MS approach that enables the controlled disassembly and proteoform analysis of CAP:nucleosome (CAP:nuc) complexes. As proof of principle, we show the BPTF plant homeodomain (PHD)-bromodomain (BD) native tandem reader binds synergistically to both PTM classes in fully defined ([H3K4me3K9acK14acK18ac]2) nucleosomes. We then extend to explore the engagement of BRD4 (native BD1-BD2), DNMT3A-MPP8 (chimeric PWWP-CD), and Populus trichocarpa Short Half Life (PtSHL) (native bromodomain-adjacent homology (BAH-PHD) tandem readers with endogenous HeLa nucleosomes. In the resulting enrichment profiles, BRD4 favors di- and triacetylated histone H4 proteoforms, whereas DNMT3A-MPP8 and PtSHL recover distinct hypermethylated H3 proteoforms. Of note, PtSHL enriches a potential {H3K4me3K27me3} cis combinatorial that expands the biology of this bivalent signature previously only described in trans. By directly characterizing CAP:nuc complex composition, Nuc-MS informs on the nucleoforms driving binding and thus identifies primary candidates for direct biochemical, structural, and genomic studies.

Beta-arrestins (βarrs) are key regulators and transducers of G-protein coupled receptor signaling; however, little is known of how βarrs communicate with their downstream effectors. Here, we delineate structural mechanisms underlying βarr-mediated signal transduction. Using cryo-electron microscopy, we elucidate how βarr1 recruits and activates the non-receptor tyrosine kinase Src, a well-established signaling partner of βarrs. βarr1 engages Src SH3 through two distinct sites, each employing a different recognition mechanism: a polyproline motif in the N-domain and a non-proline-based interaction in the central crest region. At both sites βarr1 interacts with the aromatic surface of SH3, disrupting the autoinhibited conformation of Src and directly triggering its allosteric activation. This structural evidence establishes βarr1 as an active regulatory protein rather than a passive scaffold and suggests a potentially general mechanism for βarr-mediated signaling across diverse effectors.

Estuaries and their associated forests together comprise the mangrove ecosystem, one of the most productive environments on the planet and characterized by distinctive euryhaline biodiversity. Although Brazil possesses the world’s second largest expanse of mangroves, comprehensive knowledge regarding the organisms inhabiting these systems, including cyanobacteria, remains limited, a pattern also observed globally. This gap is particularly pronounced in Brazil’s northeastern region, where studies on cyanobacterial diversity in mangroves are scarce, especially those incorporating morphometric and taxonomic analyses. Herein, we aimed to identify and characterize phytoplanktonic and periphytic cyanobacteria from four mangrove systems along the northeastern Brazilian coast: the Barra de Jangadas Estuarine Complex, Santa Cruz Estuarine Complex, Formoso River Estuary, and Una River Estuary. Phytoplankton samples were collected using a 20 μm mesh plankton net at three distinct sites within each estuary, representing different sections along the salinity gradient (upstream, middle, and mouth). Sampling was conducted during both tidal periods. Periphyton samples were mostly obtained from Rhizophora mangle pneumatophores located near the phytoplankton sampling sites during low tide. A total of 66 cyanobacterial taxa were recorded, comprising 51 species, 10 generic-level taxa, three taxa identified as “cf.,” and two as “aff.,” distributed among 30 genera and 19 families. Oscillatoriaceae was the most representative family, with 27 infrageneric taxa identified. Notably, 15 of the taxa identified are new records for Brazil, and 22 are newly reported for the Brazilian Northeast. The significant diversity documented in this study, including numerous new occurrences, highlights the prominence of cyanobacterial biodiversity in these mangrove environments and highlights the substantial knowledge gap regarding their taxonomy in tropical estuaries and mangrove forests. The discovery of unclassified taxa further suggests the presence of species potentially new to science, emphasizing the importance of these ecosystems as reservoirs of novel cyanobacterial diversity.

The cellular nucleotide pool is a major focal point of the host immune response to viral infection. Immune effector proteins that disrupt the nucleotide pool enable animal and bacterial cells to broadly restrict diverse viruses, but reduced nucleotide availability induces cellular toxicity and can limit host fitness1-5. Here we identify Clover, a bacterial anti-phage defence system that overcomes this trade-off by encoding a deoxynucleoside triphosphohydrolase enzyme (CloA) that dynamically responds to both an activating phage cue and an inhibitory nucleotide immune signal produced by a partnering regulatory enzyme (CloB). Analysis of phage restriction by Clover in cells and reconstitution of enzymatic function in vitro demonstrate that CloA is a dGTPase that responds to viral enzymes that increase cellular levels of dTTP. To restrain CloA activation in the absence of infection, we show that CloB synthesizes a dTTP-related inhibitory nucleotide signal, p3diT (5'-triphosphothymidyl-3'5'-thymidine), that binds to CloA and suppresses activation. Cryo-electron microscopy structures of CloA in activated and suppressed states reveal how dTTP and p3diT control distinct allosteric sites and regulate effector function. Our results define how nucleotide signals coordinate both activation and inhibition of antiviral immunity and explain how cells balance defence and immune-mediated toxicity.

Abstract Background Screening guidelines for breast cancer typically begin at age 40, leaving younger women at risk for delayed detection. The survival outcomes and tumor site patterns by subtype in this younger population remain underexplored. Our analysis leverages comprehensive national data to fill this critical knowledge gap, offering one of the most detailed evaluations to date of molecular subtype distribution, prognostic disparities, and anatomical presentation in women under 40. Methods Using the SEER 18 registry, we identified 5,026 female patients diagnosed under age 40 with invasive breast cancer in 2018. This year was selected for the most recent data available on SEER with its complete molecular subtype, staging, and anatomical site information. Breast cancer subtypes were categorized as Luminal A (HR+/HER2−), Luminal B (HR+/HER2+), HER2-Enriched (HR−/HER2+), and Triple-Negative (HR−/HER2−). We stratified patients into four age groups (15-29, 30-39, 40-44, 45-49) and used Chi-square tests to assess distributional differences. Kaplan-Meier curves estimated 5-year cancer-specific survival by subtype, with log-rank tests for comparison. Multivariable Cox models, random survival forests, and Mahalanobis distance matching estimated prognostic outcome and treatment effects. ICD-O-3 topography codes (C50.0-C50.9) were used to analyze tumor primary site distributions across subtypes. Results Among women under 40 with breast cancer, Luminal A was the most common subtype (52.6%), followed by Triple-Negative (18.5%), Luminal B (17.0%), HER2-Enriched (6.1%), and unclassified (5.9%). Younger women presented more often with metastatic disease and had lower rates of localized tumors than women over 40 (5.0% and 60.2%, respectively). Luminal B demonstrated the highest 5-year survival probability in the case of young women, followed by Luminal A, HER2-Enriched, URNA, and Triple-Negative, which had the poorest prognosis (log-rank p &amp;lt; 0.0001), whereas Luminal A showed better survival in patients above 40. Black women under 40 had the highest rate of Triple-Negative cancers (22.6%) compared to 20.6% for Hispanic, 18% for Non-Hispanic White, and 12% for other. White/non-Hispanic and other (including Asian) women have a higher percentage of cases diagnosed as Luminal A (53.3% and 58.4%) to 49.3% for Black and 50.2% for Hispanic. Additionally, lower-income women under 40 had more aggressive subtypes and poorer survival than higher-income groups. Those living in rural areas also face significantly worse outcomes than those living in urban metros. The most common tumor site was the upper-outer quadrant (33.0%), especially in Luminal subtypes, followed by overlapping lesions (C50.8, 22.6%) and breast, NOS (C50.9, 14.8%). While Triple-Negative and HER2-Enriched tumors were more often in overlapping or non-specific locations (p &amp;lt; 0.0001). Conclusions Breast cancer in women under 40 presents distinct biological behavior, survival patterns, and tumor site distributions by subtype. The favorable prognosis of Luminal B tumors highlights the impact of targeted therapies and supports aggressive, subtype-specific treatment in young patients. In contrast, poorer outcomes among young women with Luminal A tumors suggest even traditionally low-risk subtypes require close monitoring. Triple-Negative disease remains the most lethal, emphasizing the urgent need for novel therapies and clinical trial inclusion. Subtype-related differences in tumor localization may inform imaging and surgical strategies. Our findings highlight the need for earlier detection strategies, personalized management approaches that consider tumor subtype biology, genetic risk, and fertility concerns in this high-risk population. Citation Format: M. Noorani, S. Goyal, S. Viduarri, A. Calderon, C. Pham, S. Singh, A. Dhasmana, S. Dhasmana, M. Yallapu, S. C. Chauhan, D. Nguyen, S. Fofana, S. Khan. Survival Outcomes and Tumor Site Distribution by Molecular Subtype in Breast Cancer Patients Under 40 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-12-08.

Early and rapid diagnosis of drug resistance in tuberculosis (TB) plays a key role in reducing the spread of resistance and enabling effective treatment. The aim of this study was to investigate mutations in drug resistance-associated gene regions of Mycobacterium tuberculosis complex (MTBC) isolates resistant to at least two first-line anti-tuberculosis drugs through sequence analysis, in order to characterize the core molecular features of these strains in the region and to identify previously unreported, geographically distinct novel mutation sites. The drug susceptibility of 23 clinical isolates was assessed using the BACTEC MGIT 960 system, and resistance-associated point mutations were identified through DNA sequence analysis and comparison with GenBank reference sequences. AAG → AGG mutation was detected in the rpsL gene region at codon 43 (n = 7) and codon 88 (n = 1). Additionally, GAG → GCG point mutation was identified at codon 70 (n = 2), representing a new region not previously reported in the literature. The most frequent mutation was AGC → ACC at katG codon 315 (n = 10), followed by a C → T substitution at position -15 of the inhA promoter region (n = 4). Additionally, TCG → TTG at rpoB codon 531 (n = 4) and ATG → GTG at embB codon 306 (n = 1) were detected. The detection of resistance-associated mutations is essential for controlling drug-resistant tuberculosis. In this study, a novel rpsL mutation (GAG → GCG) at codon 70 and a previously unreported codon 88 mutation in our country were identified, contributing to the understanding of molecular resistance mechanisms and epidemiology.

This study investigates the synthesis of the MAX phase Ti 3 SiC 2 using pressureless sintering of Ti-Si-C powder mixtures. The influence of sintering temperature on phase formation and microstructure was systematically analysed through differential thermal analysis (DTA), X-ray diffraction (XRD), scanning electron microscopy (SEM), and nuclear magnetic resonance (NMR) spectroscopy. DTA shows the complex phase transformations in the range 1300–1400 °C. XRD analysis showed that the MAX phase content increased with temperature, reaching 94 wt.% at 1395 °C, with minimal content of secondary phases. SEM confirmed that a clearly defined layered microstructure characteristic of the MAX phase is formed. NMR spectroscopy provided insights into the local atomic environment of titanium, revealing two distinct titanium sites with quadrupole coupling constants of 9.3 MHz and 1.7 MHz for ‘outer’ and ‘inner’ titanium atoms, respectively. These findings demonstrate that sintering temperature critically affects the phase yield but not the intrinsic structural characteristics of Ti 3 SiC 2 .

Abstract Background Urban rivers are critical recipients of untreated wastes, contributing to the environmental spread of antimicrobial resistance (AMR) and pathogenic microbes, as is exemplified in the Kathajodi River gradient. Methods Shotgun metagenomic sequencing using Illumina HiSeq was employed to profile community diversity, antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), metal resistance genes (MRGs), and virulence factors (VFs) across spatially distinct sites; upstream (US), catchment (CM), and downstream (DS) of the Kathajodi River. Functional pathways were annotated using the KEGG and COG databases, and Canonical Correspondence Analysis (CCA) connected functional shifts to environmental gradients. Results Relatively pristine upstream area hosts stable microbiomes predominately; Proteobacteria (80.32%) and Cyanobacteria (6.70%), has low species richness (138), and a modest resistome (33 ARGs), adapted to natural biogeochemical cycles. In contrast, the catchment, impacted by urban wastewater, shows elevated Bacteroidetes (31.11%), Firmicutes (3.63%), high species richness (663), and diverse ARGs (98) and MGEs (141), driven by heavy metals (Cu, Zn, Cd) and pollutants (TDS, BOD). It emerges as a hotspot for ARGs, MGEs, and virulence factors, reflecting intense selective pressure from faecal and industrial inputs. Downstream with intermediate diversity (704 species, 53 ARGs, 88 VFs), with persistent Bacteroidetes (25.33%) exhibits partial ecological recovery, yet persistent high-risk ARGs and elevated virulence genes signal ongoing contamination and microbial adaptation to fluctuating stressors. Prediction of energy production and primary metabolism in upstream exhibited core functions. Whereas, membrane transport, defence mechanisms, and mobile element activity in catchment and downstream, as well as pronounced signal transduction, xenobiotic degradation, and bacterial chemotaxis in Catchment indicates stress response. CCA highlights the role of environmental gradients: high dissolved oxygen upstream versus elevated pollutants at the catchment in shaping these microbial shifts. Network analysis further revealed strong co-occurrence between ARGs, MGEs, and MRGs, identifying MGEs as key connectors driving horizontal gene transfer and co-selection processes. The study underscores the co-selection of ARGs and virulence traits under pollution stress, facilitated by MGE-mediated horizontal gene transfer, amplifying public health risks. Conclusion First river metagenomic study from eastern India emphasizes that human activities reshape microbial landscapes. The research advocates for interdisciplinary strategies to mitigate urban pollution, safeguard environmental health, and curb the global spread of antimicrobial resistance, calling for proactive environmental management and policy interventions.

HNF1A-MODY is one of the most prevalent subtypes of maturity-onset diabetes of the young (MODY). Individuals with HNF1A-MODY display considerable clinical heterogeneity, potentially attributable to specific mutation sites. However, in the Chinese population, the relationship between distinct mutation sites and clinical manifestations remains to be investigated. In the initial analysis, 23 HNF1A-MODY patients diagnosed at the Department of Endocrinology, Qilu Hospital were included. These patients were followed up regularly to monitor glycemic control status and the progression of complications. In the subsequent analysis, baseline information of 113 Chinese HNF1A-MODY retrieved from public databases were further enrolled. Analysis of covariance was conducted to investigate the genotype-phenotype associations. This study included a total of 136 patients. Among the 23 from Qilu Hospital, 22 distinct HNF1A gene variants were identified, including 8 novel ones. After excluding cases classified as "variant of uncertain significance", the analysis showed that the median age of onset was earliest in patients with DNA-binding domain mutations (15.70 years), compared to the dimerization or transactivation domain mutations (p = 0.044). Fasting C-peptide levels were markedly lower in the dimerization domain and DNA-binding domain group (p = 0.005). Patients with DNA-binding domain mutations demonstrated lower low-density lipoprotein cholesterol (p = 0.049) and total cholesterol (p = 0.016) levels, but higher high-density lipoprotein cholesterol (p = 0.036) levels. Analysis of covariance indicated that mutations in the dimerization domain (mean difference = -0.757, p = 0.001) and DNA-binding domain (mean difference = -0.331, p = 0.041) were independently associated with lower fasting C-peptide, and DNA-binding domain mutations were also associated with low-density lipoprotein cholesterol (mean difference = -0.554, p = 0.015) and higher high-density lipoprotein cholesterol (mean difference = 0.224, p = 0.015) levels, whereas the other domain mutations showed no statistically significant associations. This study revealed the correlation between HNF1A mutation regions and pancreatic islet function as well as blood lipids in Chinese HNF1A-MODY patients, thereby underscoring the importance of early genetic identification in formulating individualized therapeutic strategies to improve prognosis.