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Oxidative potential of fresh vs. O₃-aged PM2.5 across urban and rural sources in China.

Fine particulate matter (PM2.5) is a major health risk, yet its impacts are still largely assessed using mass concentration, which does not capture toxicity. Recently, oxidative potential (OP) has emerged as a more relevant metric, reflecting the ability of particles to generate reactive oxygen species. A current challenge, especially in China, is understanding how emission sources and ozone (O3) aging affect PM2.5 toxicity, given that O3 is an increasingly important pollutant there. A work by Ma and co-workers published in J. Environ. Sci. (doi.org/10.1016/j.jes.2024.04.023) addressed this by evaluating the OP of fresh and O3-aged PM2.5 from multiple sources in China using the dithiothreitol (DTT) assay. Biomass burning particles exhibited the highest OP, up to 35 times greater than suburban PM2.5, driven by water-soluble organics and transition metals. While O3 aging generally reduced OP, it also induced complex chemical transformations. These findings highlight that PM2.5 toxicity is dynamic and source-dependent, underscoring the need to move beyond mass-based air quality metrics.

Particulate Matter

From host response to genomic targets: electrochemical biosensing of tuberculosis biomarkers.

Tuberculosis (TB) remains one of the leading causes of death from a single infectious agent worldwide, with timely diagnosis continuing to be a major challenge, particularly in resource-limited settings. Conventional TB diagnostic methods are limited by low sensitivity, long turnaround times, and an inability to reliably differentiate latent from active disease. Biomarker-based diagnostic strategies have therefore gained increasing attention as they offer the potential to improve early detection, disease differentiation, and treatment monitoring. Herein, we examine electrochemical biosensing strategies for TB diagnostics using a biomarker-class-driven framework, covering host-response biomarkers (IFN-γ and TNF-α), pathogen-derived antigens (ESAT6, CFP10, CFP10-ESAT6, MPT64, Ag85, HspX and LpqH), cell-wall signatures and whole-cell markers (LAM and whole cell Mtb), and genomic markers (Mtb DNA and IS6110). Through structured comparison of recognition elements, biointerface designs, signal amplification strategies, electrochemical techniques, matrices, and validation levels, this review identifies the most promising technical approaches for different TB biomarker classes. It further highlights key translational bottlenecks, including limited clinical validation, buffer-based testing, complex multistep amplification, redox-probe dependence, matrix fouling, and insufficient evidence of manufacturability. This review therefore provides practical guidance for developing electrochemical TB biosensors that are analytically sensitive, clinically relevant, and suitable for decentralized diagnostic applications.

Biosensing Techniques

CAR-T Cell Therapy: Manufacturing Platforms and Clinical Consequences.

Chimeric antigen receptor (CAR) T-cell therapy has transformed hematological cancer care, yet variability in efficacy, durability, and safety cannot be explained solely by antigen selection or patient factors. We propose that manufacturing platforms are active biological determinants of outcome. Viral vectors, used in all licensed products, provide stable genomic integration and durable expression but are limited by cost, cargo capacity, and centralized production. Nonviral strategies, including transposons, CRISPR knock-ins, and messenger RNA delivery, enable faster, less-expensive manufacturing with larger payloads, while introducing distinct safety and persistence profiles. This review presents a three-layer mechanistic framework that reframes manufacturing as biology: integration biology determines genomic risk and transgene stability; clonal fitness shapes persistence, dominance, and exhaustion; and epigenomic imprinting, influenced by gene transfer method, cytokines, and culture stress, preconfigures functional trajectories. Clinical observations link platform choice to immune recovery, where prolonged B-cell aplasia and delayed T-cell reconstitution contribute to infection-related nonrelapse mortality, and hematopoietic reserve at apheresis emerges as a practical predictor. Finally, manufacturing is positioned as the key to democratizing cell therapy. Decentralized, nonviral production aligned with regulatory standards may enable equitable access and transition CAR-T therapy from innovation to sustainable global care.

Humans

Identification of aquaporin (AQP) genes in the noble scallop Chlamys nobilis and characterization of their expression under low-temperature stress.

Aquaporins (AQPs) are transmembrane channel proteins essential for water homeostasis and cellular stress responses. In marine bivalves, their roles in cold tolerance remain poorly understood despite frequent winter mortality events in aquaculture. Here, we identified nine AQP genes in the genome of the economically important noble scallop Chlamys nobilis. Phylogenetic analysis revealed strong conservation with other bivalve AQPs, and structural features, including conserved NPA motifs and ar/R selectivity filters, support their canonical water/glycerol transport functions. Tissue-specific expression profiling showed predominant enrichment in osmoregulatory tissues (gills, intestine) and gonads. Under both chronic and acute low-temperature stress from 23 °C to 9 °C, most CnAQP genes exhibited transient upregulation followed by suppression. Notably, CnAQP4 displayed sustained upregulation, implicating it as a key mediator of long-term cold adaptation. Promoter analysis further revealed abundant cis-elements linked to growth and development as well as immune regulation. Our findings provide the first comprehensive characterization of the AQP family in C. nobilis, highlighting its critical role in maintaining cellular integrity during cold stress and offering molecular targets for selective breeding of cold-tolerant scallop strains.

Animals

Association between seminal and serum iron parameters and male infertility: a systematic review and meta-analysis.

BACKGROUND: Iron is an essential trace element for normal spermatogenesis, yet excessive iron accumulation may impair male fertility. Preliminary studies imply a link between elevated iron levels and male infertility, but evidence remains limited without systematic quantitative synthesis. This metaanalysis assessed the association between iron concentrations and male infertility. METHODS: We systematically searched PubMed, CBM, CNKI and Cochrane Library. RevMan, Stata and R were used for data analysis. Randomeffects models pooled effect sizes, with forest and funnel plots generated to evaluate seminal and serum iron levels in male infertility. RESULTS: After screening studies published up to April 2025, a total of ten eligible articles involving 985 participants were finally included in this meta-analysis. Pooled results revealed that seminal and serum iron concentrations were notably higher in infertile males compared with fertile controls. Specifically, infertile men presented higher seminal iron levels (SMD&#x2009;=&#x2009;0.44, 95% CI: 0.12-0.76, P&#x2009;<&#x2009;0.05), as well as elevated serum iron levels (SMD&#x2009;=&#x2009;3.77, 95% CI: 1.68-5.87, P&#x2009;<&#x2009;0.05). The present results suggest that increased seminal and serum iron concentrations may be potentially correlated with male infertility risk.

Humans

Dynamics of antibiotic resistance genes co-occurrence with pathogenic and non-pathogenic bacteria throughout wastewater treatment processes.

Wastewater treatment plants (WWTPs) are recognized hotspots for antibiotic resistance genes (ARGs) and pathogenic bacteria. Despite advancements in treatment technologies, the persistence of ARGs and pathogenic bacteria remains a concern. In this study, we analyzed the dynamic changes in ARGs and bacterial communities throughout the treatment processes within an anaerobic-anoxic-oxic (AAO) WWTP over one week by using HT-qPCR coupled with 16S rRNA gene amplicon sequencing. The connectedness index, based on network analysis, showed that the dynamics of ARGs and mobile genetic elements (MGEs) were more strongly associated with potentially pathogenic bacteria than with non-pathogenic bacteria, suggesting that ARG immigration and dissemination in the WWTP were likely driven by potentially pathogenic taxa. The AAO treatment significantly reduced ARGs in final effluent (EF) (&#x223c;64 %) and residual sludge (RS) (&#x223c;81 %); however, potential hosts of ARGs such as Comamonas testosteroni and Clostridioides difficile persisted with minimal changes in relative abundance and remained detectable in EF and RS. Notably, the abundance of ARGs was lower in RS than in EF, and source tracking analysis identified influent as the primary source of ARGs and potentially pathogenic taxa in EF, underscoring the greater health risks associated with effluent discharge.

Wastewater

Parent-of-origin effects on allelic expression bias in interspecific poplar hybrids.

In hybrid plants, phenotypic outcomes are governed by interactions between the two parental genomes. However, the mechanisms underlying the interplay of divergent regulatory networks from these genomes remain poorly understood. In this study, we compared gene-level and allele-specific expression patterns, as well as differentially enriched pathways between F&#x2081; and complex backcross (CBC) lines derived from a natural interspecific hybrid population of Populus fremontii (Pf) and P. angustifolia (Pa). Metabolic differences between Pf and Pa which exhibit low and high levels respectively of phenylpropanoid-derived condensed tannins were leveraged. Using individualized transcriptome references, differential expression and clustering analyses revealed CBC-biased and F&#x2081;-biased expression for genes involved in phenylpropanoid metabolism and photosynthesis, respectively. Biased expression of these genes at the allele level was also observed in F1. At the whole-transcriptome level, Pa-biased genes predominated in F&#x2081; hybrids, and Pa alleles displayed more conserved expression patterns than Pf alleles across examined samples. Further analyses indicated that allelic expression bias was significantly associated with parental origin, which could be driven by sequence variations in cis-regulatory elements and differences in CpG island length. Our findings demonstrate strong parent-of-origin effects on divergent regulatory networks governing gene expression in poplar hybrids and provide clues for strategic parental selection tailored to specific metabolic pathways of interest.

cis-regulation

Morphology-Encoded Colorimetric Hydrogen Sensing Using Embedded Reactive Pd Absorbers in Fabry-Perot Cavities.

Chemical reactions offer a powerful strategy for generating visible optical responses through localized changes in absorption, dielectric environment, and interfacial wetting. A palladium (Pd)-embedded Fabry-Perot cavity is introduced as a reaction-active optical platform in which structural color is governed by intracavity absorption coupled with reaction-induced dielectric perturbation. Positioning Pd within the dielectric spacer creates a spatially controllable reactive absorber whose vertical location relative to the standing-wave field dictates wavelength-selective absorption within the cavity. The morphology of the embedded Pd layer provides an additional design parameter by modulating both optical loss and interfacial wetting. Under hydrogen exposure in the presence of oxygen, catalytic water formation at the Pd/polymer interface generates localized dielectric heterogeneity and interfacial water droplets, thereby perturbing the optical path length and amplifying the visible response. As a result, the cavity exhibits pronounced, morphology-dependent color transitions that are inaccessible through dielectric-layer engineering or Pd/PdH refractive-index changes alone, enabling direct visual hydrogen sensing under ambient light, as well as flexible optical devices capable of large-area patterning. These findings establish a design framework for reaction-active optical cavities that translate localized chemistry into a colorimetric hydrogen sensing mechanism.

Fabry&#x2013;Perot resonator

Molecular Determinants and Therapeutic Targeting of Stop Codon Readthrough in Eukaryotic Translation.

Accurate translation termination is essential for proteome integrity and in eukaryotes is primarily governed by the release factors eRF1 and eRF3, which ensure precise recognition of stop codons and efficient release of nascent polypeptides. However, proteome integrity is challenged by mutations that generate premature termination codons (PTCs), leading to truncated, nonfunctional proteins and degradation of the aberrant transcript via nonsense-mediated mRNA decay (NMD). Collectively, these events account for &#x223c;1800 human genetic diseases. Translational readthrough, the process by which near-cognate tRNAs decode stop codons and allow ribosomes to continue elongation beyond the stop codon, represents a possibility to suppress PTCs and restore full-length protein synthesis. Initially discovered in viruses as a mechanism to expand coding capacity, readthrough is now recognized as a regulated feature of eukaryotic gene expression influenced by both cis-acting sequence elements and trans-acting factors. Recent evidence highlights the remarkable context dependence of readthrough, revealing variation across transcripts, tissues, and developmental stages. In this review, we examine the molecular determinants that define stop codon recognition and readthrough efficiency, with particular emphasis on nucleotide context. We further discuss the mechanisms and binding sites of small molecules that promote PTC readthrough, and summarize the clinical development landscape of readthrough-inducing compounds for the treatment of diseases caused by nonsense mutations.

Humans

Context matters: coordinated transcriptional regulation and root plasticity under multinutrient conditions.

Plants often encounter simultaneous imbalances in multiple nutrients, but the regulatory logic coordinating their responses remains poorly understood. We aimed to uncover shared transcriptional programs and regulatory nodes underpinning multinutrient adaptation in Arabidopsis thaliana roots. We analyzed publicly available RNA-seq datasets spanning 15 nutrient and beneficial element conditions using differential expression, co-expression network (WGCNA), and gene regulatory network analysis. Selected transcription factors (TFs) were validated via root phenotyping, suberin staining, and ionomic profiling under two-nutrient stress conditions. We identified a core set of 2050 genes responsive to multiple nutrient treatments, enriched for suberin biosynthesis, and structured into modular co-expression clusters. Eight prioritized candidate TFs (ARR10, GBF3, HHO5, NAC32, NF-YA3, NF-YB2, SARD1, and WRKY33) were&#xa0;shown to modulate root system architecture under specific nutrient combinations. WRKY33 and NF-YB2, in particular, regulated nutrient-responsive suberin deposition and ionomic plasticity. These findings reveal suberin remodeling as a shared downstream process in multinutrient responses and suggest that plasticity is not a fixed trait but a modular, polygenic, and context-dependent outcome. Repurposed TFs with pleiotropic functions coordinate structural and physiological traits, providing regulatory entry points for improving nutrient resilience.

Plant Roots

Maize ZmMYB59 inhibits post-germinative shoot and root elongation through ZmGA2ox3/10-mediated gibberellin catabolism.

Gibberellin (GA) promotes seed germination, but sustained or excessive GA signaling after germination can lead to aberrant root and shoot elongation. How GA homeostasis is transcriptionally restrained during post-germinative seedling development remains unclear. Using overexpression and gene-edited maize materials, we demonstrate that ZmMYB59 inhibits root and shoot elongation during post-germinative growth. Integrated RNA-Seq and CUT&Tag analyses identified the GA catabolism genes ZmGA2ox3 and ZmGA2ox10 as candidate direct targets of ZmMYB59. Hormone profiling analysis showed elevated bioactive GA1 and GA4 levels in the scutellum and aleurone layer cells of zmmyb59 mutants. Dual-luciferase assays, electrophoretic mobility shift assays, and ChIP-qPCR further confirmed that ZmMYB59 directly binds AC8 cis-elements in the ZmGA2ox3/10 promoters and activates their transcription. The zmga2ox3/10 double mutant, but neither single mutant, exhibited enhanced root and shoot elongation, accompanied by GA4 accumulation. This phenotype was suppressed by exogenous application of the GA biosynthesis inhibitor uniconazole. Transcriptomic and biochemical analyses further revealed enhanced starch degradation, reduced starch content, and increased soluble sugar accumulation in the double mutant. Taken together, these findings reveal that the ZmMYB59-ZmGA2ox3/10 module restrains GA accumulation and starch mobilization after germination, thereby coordinating reserve utilization with post-germinative root and shoot growth in maize.

Gibberellins

Viral community in Aspergillus spp. isolated from commercially available fermented dried bonito.

Katsuobushi is a traditional processed seafood product used in Japanese-style cooking, and when it is produced through fermentation by fungi, it is called karebushi. The fungi involved in katsuobushi fermentation are collectively referred to as katsuobushi molds. We previously discovered seven novel viruses from katsuobushi molds and determined their genome sequences. However, our previous explorations used only nine fungal strains available from culture collections, leaving the diversity of viruses infecting fungi involved in katsuobushi fermentation unclear. Therefore, in this study, we aimed to isolate fungi from commercially available karebushi and clarify the prevalence of viruses in the isolates. Karebushi produced by three manufacturers was obtained, and 30 fungal strains (including Aspergillus spp.) were isolated from each. Double-stranded RNA (dsRNA) fractions were prepared from the mycelia of the isolated strains. Electrophoresis suggested that a relatively high proportion of the isolates harbored dsRNA elements consistent with RNA virus infection (30-70% per manufacturer; 59% overall). Furthermore, dsRNA sequencing identified four novel viruses in isolates of Aspergillus chevalieri and Aspergillus montevidensis: a beny-like virus, a gammapartitivirus, a narnavirus, and a victorivirus, in addition to two previously reported viruses. Notably, this represents the first report of a beny-like virus in Aspergillus spp. This study provides insights into the diversity of viruses infecting fungi involved in katsuobushi fermentation.

Aspergillus

Mining Stored-Specimen Studies for Information about Cancer Natural History.

The advent of new multicancer early detection tests and publication of early diagnostic results have generated expectations of clinical benefit from multicancer screening. The clinical benefit of a cancer screening test depends critically on disease natural history, which is typically learned from prospective screening studies. Retrospective studies of stored blood specimens are important in learning about a test's preclinical diagnostic performance but have rarely been used to infer natural history. The extent to which these studies might be harnessed to also learn natural history is discussed in the context of an article in this issue that infers the combined natural history of a range of cancers targeted by a multicancer early detection test using a case-control subsample of specimens from a large cohort study. The critical question concerns the identifiability of key transition rates in multistate models of natural history alongside state-specific sensitivities. The article suggests that these parameters are estimable within a Bayesian framework that leverages prior information about test sensitivity from diagnostic studies. We offer a heuristic discussion of identifiability in this setting and encourage formal study to determine the extent to which models with varying degrees of complexity may be learned from stored-specimen studies. See related article by Dai et al., p. 1535.

Humans

An impact assessment of the European medical device regulations implementation - the current status quo.

BACKGROUND: This research aims to assess the current impact of the medical and in-vitro diagnostic devices regulations (MDR/IVDR) on the device industry in the EU, under the lens of postimplementation and the amending regulation, and in advance of the final transition to the IVDR/MDR in the future. RESEARCH DESIGN AND METHODS: A quantitative survey was administered to a diverse cohort of medical device enterprises, ranging from micro to large organizations. RESULTS: The survey indicates that the MDR/IVDR has harmed innovation, leading many manufacturers to seek initial device approval and launch elsewhere before in Europe. There is evidence that some manufacturers have rationalized their existing product portfolios and removed devices from the market as they stated they would in previous industry surveys. The MDR/IVDR has been shown to negatively impact manufacturers, with increased costs related to notified body (NB) fees, maintaining and updating documentation, recertification fees, and hiring additional staff. CONCLUSION: This study provides a current status of the effects of MDR/IVDR on manufacturers and finds that despite amending regulations and other interventions taken by the EU to mitigate regulatory burden, ensure product availability, and address stakeholder concerns, the EU is no longer the market of choice for new products.

Equipment and Supplies

A Multi-omics Regulated Cell Death Framework Defines Immune Phenotypes and Guides Precision Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is molecularly and immunologically heterogeneous, contributing to variable treatment response. Because regulated cell death (RCD) intersects with tumor metabolism, immune regulation, and therapeutic susceptibility, we built an RCD-centered framework for CRC stratification. Multi-cohort transcriptomic data were used to infer RCD subtypes with non-negative matrix factorization (NMF) and non-negative least squares (NNLS). Genomic, bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic datasets were integrated to characterize subtype-associated biology. Machine-learning models were developed for immunotherapy response and survival-risk estimation. Candidate compounds were screened by GDSC2-based drug-sensitivity modeling and molecular docking, and FSTL3 was functionally assessed in vitro. The framework separated CRC samples into two RCD-related phenotypes resembling immune-hot and immune-cold states. RCD1 showed immune activation and higher mutational burden, whereas RCD2 showed immune-suppressed features, intratumoral heterogeneity, and aggressive biology. RCD-associated signatures showed potential for predicting immunotherapy response and survival risk. Dasatinib was prioritized for immune-cold, high-risk tumors, with preliminary evidence supporting its activity in CRC cells, while functional assays suggested a role for FSTL3 in growth, invasion, epithelial-mesenchymal transition, and apoptosis regulation. These findings suggest that RCD-based multi-omics analysis may refine CRC stratification and help generate therapeutic hypotheses.

Colorectal cancer

Recent advances in Strongyloides screening, diagnostics, therapeutics, and management.

PURPOSE OF REVIEW: Strongyloidiasis affects an estimated 30-100 million people globally and can have life-threatening consequences in immunocompromised hosts, yet it remains underdiagnosed due to limited access and performance of available diagnostics. Novel assays and anthelmintics may reshape screening, diagnosis, treatment, and prevention for at-risk populations. RECENT FINDINGS: Advances in molecular diagnostics coupled with robust stool extraction methods have supplanted traditional parasitologic methods in settings where nucleic acid amplification is feasible. Transition from standard immunoglobulin G (IgG)-based immunoassays to the new IgG- and IgG4-based rapid diagnostic tests using recombinant Strongyloides stercoralis nematode immunodominant E antigen (NIE) and/or S. stercoralis immunoreactive antigen (SsIR) has facilitated serologic screening at the point of care. The World Health Organization now conditionally recommends community-wide ivermectin mass drug administration in highly endemic settings. Regarding new treatment options, moxidectin is noninferior to ivermectin with 93-94% cure rates and a longer half-life, while emodepside shows 80-90% predicted cure rates in early trials and offers a mechanistically distinct option. Understanding of immunosuppressed populations at risk for hyperinfection has expanded, prompting updated screening recommendations. SUMMARY: Serologic and molecular tools are improving screening and diagnosis, and moxidectin and emodepside may broaden treatment options, but data in severe disease and special populations remain limited. Priorities include harmonized screening algorithms and prospective studies in high-risk groups.

Humans

3D epigenomic remodelling mediated by Foxa1 drives gemcitabine resistance in pancreatic cancer.

Gemcitabine remains a cornerstone treatment for pancreatic ductal adenocarcinoma (PDAC), yet the emergence of resistance constitutes a major clinical challenge with poorly understood epigenomic mechanisms. Here, we identified the pioneer transcription factor Foxa1 as a master regulator of gemcitabine resistance through multi-omics analysis. Mechanistically, Foxa1 drives widespread super-enhancer (SE) reprogramming and 3D genome remodelling in resistant cells, which coordinately activates the expression of key resistance genes, notably Rrm1 and Cdadc1. This is accompanied by increased chromatin accessibility, elevated H3K27ac enrichment at SEs, and enhanced Foxa1 binding at regulatory elements. Moreover, post-translational stabilization of Foxa1 via USP7-mediated deubiquitination sustains this epigenomic program. Genetic ablation of Foxa1 or specific SE regions near Rrm1 resensitizes resistant cells to gemcitabine. Building upon this mechanism, we demonstrate that bromodomain and extraterminal (BET) inhibitors, which disrupt SE function, potently reverse resistance. Notably, the clinical-stage BET inhibitor AZD5153, in combination with gemcitabine, achieves robust tumor suppression and overcomes resistance in cell-derived xenograft (CDX) models by dismantling the Foxa1-mediated resistant transcriptome and reinvigorating drug sensitivity. Our findings establish Foxa1-orchestrated enhancer reprogramming as a fundamental mechanism of gemcitabine resistance and unveil a promising epigenetic therapy to restore treatment efficacy in PDAC.

Hepatocyte Nuclear Factor 3-alpha

Systematic identification pepper CaE2F transcription factor reveals the role of CaDPb in drought stress response.

The EARLY 2 FACTOR (E2F) transcription factor (TF) family plays a pivotal role in regulating plant development and adaptations to environmental stresses. However, the physiological function of E2Fs in pepper (Capsicum annuum L.) are not well elucidated. In this work, we conduct a comprehensive genome-wide annotation of the E2F family within the Zunla-1 pepper genome and further explore the biological roles of CaDPb in response to drought stress. Through systematic bioinformatics analysis, we identify a total of nine CaE2F genes within the Zunla-1 genome, categorizing them into three distinct subgroups. Additionally, we discover multiple cis-regulatory elements in the CaE2F promoter regions associated with responses to plant hormones and drought stress. Public RNA-seq datasets reveal distinct expression profiles of CaE2F genes across various pepper tissues and their responses to environmental stimuli and plant hormones. Subsequently, the CaDPb gene is further functionally verified in drought response. Our findings indicate that TRV2:CaDPb silenced pepper plants are more sensitivity to drought. Furthermore, we show that CaDPb participates in the regulation of reactive oxygen species (ROS) production, the expression of drought-responsive genes, and the modulation of stomatal aperture. Taken together, our findings provide a comprehensive characterization of E2F genes in pepper and offer insights into the biological function of CaDPb in pepper drought stress response.

Capsicum