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ObjectiveChronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.DesignA murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.ResultsGut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.ConclusionThe gut microbiota–lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.

Achieving the activation of drugs within cellular systems may provide targeted therapies. Here we construct a tumour-selective cascade activatable self-detained system (TCASS) and incorporate imaging probes and therapeutics. We show in different mouse models that the TCASS system accumulates in solid tumours. The molecules show enhanced accumulation in tumour regions via the effect of recognition induced self-assembly. Analysis of the molecular penetration in tumour tissue shows that in vivo self-assembly increases the penetration capability compared to typical soft or hard nanomaterials. Importantly, the in vivo self-assembled molecules exhibit a comparable clearance pathway to that of small molecules, which are excreted from organs of the reticuloendothelial system (liver and kidney), while are relatively slowly eliminated from tumour tissues. Finally, this system, combined with the NIR probe, shows high specificity and sensitivity for detecting bladder cancer in isolated intact patient bladders. The activation of drugs within cellular systems may provide targeted therapies for cancer. Here, the authors make a drug delivery system that is activated within the cell and exploits XIAP expression to cleave a linker region, resulting in the self-assembly of the system and drug release within cancer cells.

Existing compendia of non-coding RNA (ncRNA) are incomplete, in part because they are derived almost exclusively from small and polyadenylated RNAs. Here we present a more comprehensive atlas of the human transcriptome, which includes small and polyA RNA as well as total RNA from 300 human tissues and cell lines. We report thousands of previously uncharacterized RNAs, increasing the number of documented ncRNAs by approximately 8%. To infer functional regulation by known and newly characterized ncRNAs, we exploited pre-mRNA abundance estimates from total RNA sequencing, revealing 316 microRNAs and 3,310 long non-coding RNAs with multiple lines of evidence for roles in regulating protein-coding genes and pathways. Our study both refines and expands the current catalog of human ncRNAs and their regulatory interactions. All data, analyses and results are available for download and interrogation in the R2 web portal, serving as a basis for future exploration of RNA biology and function. The human transcriptome from 300 tissues and cell lines reveals novel non-coding RNAs.

Altitudinal changes in the diversity of plants and animals have been well documented; however, soil animals received little attention in this context and it is unclear whether their diversity follows general altitudinal distribution patterns. Changbai Mountain is one of few well‐conserved mountain regions comprising natural ecosystems on the Eurasian continent. Here, we present a comprehensive analysis of the diversity and community composition of Collembola along ten altitudinal sites representing five vegetation types from forest to alpine tundra. Among 7834 Collembola individuals, 84 morphospecies were identified. Species richness varied marginally significant with altitude and generally followed a unimodal relationship with altitude. By contrast, the density of Collembola did not change in a consistent way with altitude. Collembola communities changed gradually with altitude, with local habitat‐related factors (soil and litter carbon‐to‐nitrogen ratio, litter carbon content, and soil pH) and climatic variables (precipitation seasonality) identified as major drivers of changes in Collembola community composition. Notably, local habitat‐related factors explained more variation in Collembola assemblages than climatic variables. The results suggest that local habitat‐related factors including precipitation and temperature are the main drivers of changes in Collembola communities with altitude. Specifically, soil and litter carbon‐to‐nitrogen ratio correlated positively with Collembola communities at high altitudes, whereas soil pH correlated positively at low altitudes. This documents that altitudinal gradients provide unique opportunities for identifying factors driving the community composition of not only above‐ but also belowground invertebrates. The results suggest that local habitat‐related factors including precipitation and temperature are the main drivers of changes in Collembola communities with altitude. Specifically, soil and litter carbon‐to‐nitrogen ratio correlated positively with Collembola communities at high altitudes, whereas soil pH correlated positively at low altitudes. This documents that altitudinal gradients provide unique opportunities for identifying factors driving the community composition of not only above‐ but also belowground invertebrates.

Oral squamous cell carcinoma is a prominent cancer worldwide, particularly in Taiwan. By integrating omics analyses in 50 matched samples, we uncover in Taiwanese patients a predominant mutation signature associated with cytidine deaminase APOBEC, which correlates with the upregulation of APOBEC3A expression in the APOBEC3 gene cluster at 22q13. APOBEC3A expression is significantly higher in tumors carrying APOBEC3B- deletion allele(s). High-level APOBEC3A expression is associated with better overall survival, especially among patients carrying APOBEC3B -deletion alleles, as examined in a second cohort ( n  = 188; p  = 0.004). The frequency of APOBEC3B -deletion alleles is ~50% in 143 genotyped oral squamous cell carcinoma -Taiwan samples (27 A3B −/− :89 A3B +/− :27 A3B +/+ ), compared to the 5.8% found in 314 OSCC-TCGA samples. We thus report a frequent APOBEC mutational profile, which relates to a APOBEC3B -deletion germline polymorphism in Taiwanese oral squamous cell carcinoma that impacts expression of APOBEC3A , and is shown to be of clinical prognostic relevance. Our finding might be recapitulated by genomic studies in other cancer types. Oral squamous cell carcinoma is a prevalent malignancy in Taiwan. Here, the authors show that OSCC in Taiwanese show a frequent deletion polymorphism in the cytidine deaminases gene cluster APOBEC3 resulting in increased expression of A3A, which is shown to be of clinical prognostic relevance.

The relative importance of deterministic versus stochastic processes in community assembly is widely discussed in ecology. Stochastic models explain community assembly by ignoring the niches of species, whereas deterministic models assume the niche concept to be key for understanding the assembly of species. Whether stochastic or deterministic processes dominate in shaping the community composition of soil animals is gaining increased attention. Here, we investigated the spatial heterogeneity of soil microarthropod communities (Collembola, Oribatida, Mesostigmata) along a salt marsh transect from the upper salt marsh (USM) to the lower salt marsh (LSM) to the pioneer zone (PZ) on three islands, that is, Norderney, Spiekeroog, and Wangerooge, in the Wadden Sea of Germany. We hypothesized that microarthropod communities are predominantly structured by niche‐based processes and change in a deterministic way from the USM to the LSM to the PZ, whereas microarthropod communities differ little between the three islands of similar history and position in the Wadden Sea. Supporting our hypothesis, Oribatida and Mesostigmata communities differed more strongly between the three zones than between the islands indicating that environmental factors changing along the saltmarsh gradient select for specific mite communities in a deterministic way. Collembola communities also differed between the three zones but also between the islands indicating that they are structured by both environmental filtering as well as stochasticity. However, even the differences in mite and Collembola communities between the islands may—at least in part—be explained by environmental filtering, for example, by differences in nutrient input from the Ems river estuarine. Overall, the results indicate that stochasticity plays only a limited role in structuring microarthropod communities in the dynamic marine—terrestrial boundary of salt marshes pointing to the importance of niche differentiation and environmental filtering. We combined α‐ and β‐diversity to investigate the community assembly of soil microarthropods (Collembola, Oribatida, Mesostigmata) along a salt marsh transect from the upper salt marsh to the lower salt marsh to the pioneer zone on three islands in the Wadden Sea of Germany. The results suggest that soil microarthropod communities in the dynamic marine–terrestrial boundary of salt marshes are predominantly structured by deterministic factors.

Understanding the role of microbiota in supporting animal survival and activity under extreme environmental conditions provides valuable insights into adaptation and resilience mechanisms in ecosystems. While vertebrate microbiota have received considerable attention, those associated with arthropods, particularly species capable of surviving sub‐zero temperatures, remain poorly understood. Springtails (Collembola), key contributors to litter decomposition and soil ecosystem functioning, require specialized adaptations to endure harsh winter conditions. Using the α‐ and β‐niche trait concept and phylogenetic comparative approaches, we investigated the microbiota of 10 coexisting springtail species with different overwintering strategies. Our results revealed that certain bacterial genera, including Marmoricola, Mycobacterium, Rhodococcus, and Vibrionimonas, exhibited phylogenetic signal, suggesting evolutionary constraints on their potential roles in hosts. Winter‐active springtail species harbored higher bacterial diversity and distinct microbial community compositions compared to inactive species, with enrichment in bacteria such as Wolbachia, Morganellaceae, and Micrococcaceae. Additionally, winter‐active species exhibited higher energy metabolism and lower lipid metabolism, alongside more frequent positive interactions within bacterial networks. These findings suggest that microbiota may play a functional role in supporting the metabolic demands of winter‐active springtails, potentially contributing to their adaptation to cold environments. Overall, our study highlights the role of microbiota in shaping ecological success and adaptation of arthropods to extreme conditions, providing new perspectives for soil animal research by integrating microbial functional traits with the evolutionary context of microbe‐host interactions. Microbiota in 10 springtail species were analyzed using phylogenetic comparative methods. Winter‐active species showed higher bacterial diversity, enriched with Wolbachia, Morganellaceae, and Micrococcaceae, while some bacteria exhibited a phylogenetic signal, suggesting evolutionary constraints. These microbiota may support host metabolism and adaptation to cold environments.

We hypothesized that epigenetics is a link between smoking/allergen exposures and the development of Asthma and chronic obstructive pulmonary disease (ACO). A total of 75 of 228 COPD patients were identified as ACO, which was independently associated with increased exacerbations. Microarray analysis identified 404 differentially methylated loci (DML) in ACO patients, and 6575 DML in those with rapid lung function decline in a discovery cohort. In the validation cohort, ACO patients had hypermethylated PDE9A (+ 30,088)/ ZNF323 (− 296), and hypomethylated SEPT8 (− 47) genes as compared with either pure COPD patients or healthy non-smokers. Hypermethylated TIGIT (− 173) gene and hypomethylated CYSLTR1 (+ 348)/ CCDC88C (+ 125,722)/ ADORA2B (+ 1339) were associated with severe airflow limitation, while hypomethylated IFRD1 (− 515) gene with frequent exacerbation in all the COPD patients. Hypermethylated ZNF323 (− 296) / MPV17L (+ 194) and hypomethylated PTPRN2 (+ 10,000) genes were associated with rapid lung function decline. In vitro cigarette smoke extract and ovalbumin concurrent exposure resulted in specific DNA methylation changes of the MPV17L / ZNF323 genes, while 5-aza-2′-deoxycytidine treatment reversed promoter hypermethylation-mediated MPV17L under-expression accompanied with reduced apoptosis and decreased generation of reactive oxygen species. Aberrant DNA methylations may constitute a determinant for ACO, and provide a biomarker of airflow limitation, exacerbation, and lung function decline.

Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and social deficits. Probiotics have been demonstrated to play a promising role in managing the severity of ASD. However, there are no effective probiotics for clinical use. Identifying new probiotic strains for ameliorating ASD is therefore essential. Using the maternal immune activation (MIA)-based offspring ASD-like mouse model, a probiotic-based intervention strategy was examined in female mice. The gut commensal microbe Parabacteroides goldsteinii MTS01, which was previously demonstrated to exert multiple beneficial effects on chronic inflammation-related-diseases, was evaluated. Prenatal lipopolysaccharide (LPS) exposure induced leaky gut-related inflammatory phenotypes in the colon, increased LPS activity in sera, and induced autistic-like behaviors in offspring mice. By contrast, P. goldsteinii MTS01 treatment significantly reduced intestinal and systemic inflammation and ameliorated disease development. Transcriptomic analyses of MIA offspring indicated that in the intestine, P. goldsteinii MTS01 enhanced neuropeptide-related signaling and suppressed aberrant cell proliferation and inflammatory responses. In the hippocampus, P. goldsteinii MTS01 increased ribosomal/mitochondrial and antioxidant activities and decreased glutamate receptor signaling. Together, significant ameliorative effects of P. goldsteinii MTS01 on ASD relevant behaviors in MIA offspring were identified. Therefore, P. goldsteinii MTS01 could be developed as a next-generation probiotic for ameliorating ASD.

Background Pan-cancer studies have disclosed many commonalities and differences in mutations, copy number variations, and gene expression alterations among cancers. Some of these features are significantly associated with clinical outcomes, and many prognosis-predictive biomarkers or biosignatures have been proposed for specific cancer types. Here, we systematically explored the biological functions and the distribution of survival-related genes (SRGs) across cancers. Results We carried out two different statistical survival models on the mRNA expression profiles in 33 cancer types from TCGA. We identified SRGs in each cancer type based on the Cox proportional hazards model and the log-rank test. We found a large difference in the number of SRGs among different cancer types, and most of the identified SRGs were specific to a particular cancer type. While these SRGs were unique to each cancer type, they were found mostly enriched in cancer hallmark pathways, e.g., cell proliferation, cell differentiation, DNA metabolism, and RNA metabolism. We also analyzed the association between cancer driver genes and SRGs and did not find significant over-representation amongst most cancers. Conclusions In summary, our work identified all the SRGs for 33 cancer types from TCGA. In addition, the pan-cancer analysis revealed the similarities and the differences in the biological functions of SRGs across cancers. Given the potential of SRGs in clinical utility, our results can serve as a resource for basic research and biotech applications.