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Frailty associated with aging increases the risk of falls, disability, and death. We investigated gender-associated factors for frailty. Data of 3,079 geriatric subjects were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 database. After excluding 1,126 subjects with missing data on frailty, medical history and survival, data of 1,953 patients were analyzed. Main endpoints were frailty prevalence, mortality rates and causes of death. Frailty prevalence was 5.4% in males, 8.8% in females. Significant risk factors for geriatric frailty in males were being widowed/divorced/separated, low daily total calorie intake, physical inactivity, sleeping >9 h, smoking and hospitalization history; and in females were obesity, physical inactivity, sleeping <6 h, family history of diabetes and heart attack, and hospitalization history. Frail subjects had higher mortality rates (22.5% male; 8.5% female) than pre-frail (8.7% male; 6.4% female) and non-frail (5.4% male; 2.5% female). Main causes of death were heart diseases (41%) and chronic lower respiratory diseases (23.0%) in males and nephritis/nephrosis (32.3%) and chronic lower respiratory diseases (17.6%) in females. Factors associated with frailty differ by gender, with higher frailty prevalence in females and higher mortality in males. Gender-associated factors for frailty identified in this study may be useful in evaluating frailty and guiding development of public health measures for prevention. Common predictive factors for frailty among older adults of both genders, including more frequent previous hospitalizations, physical inactivity, and certain gender-associated factors for frailty, are consistent with results of other NHANES studies in which self-reported higher levels of illness and sedentary behavior were directly associated with frailty.

The direct conversion, or transdifferentiation, of non-cardiac cells into cardiomyocytes by forced expression of transcription factors and microRNAs provides promising approaches for cardiac regeneration. However, genetic manipulations raise safety concerns and are thus not desirable in most clinical applications. The discovery of full chemically induced pluripotent stem cells suggest the possibility of replacing transcription factors with chemical cocktails. Here, we report the generation of automatically beating cardiomyocyte-like cells from mouse fibroblasts using only chemical cocktails. These chemical-induced cardiomyocyte-like cells （CiCMs） express cardiomyocyte-specific mark- ers, exhibit sarcomeric organization, and possess typical cardiac calcium flux and electrophysiological features. Genetic lineage tracing confirms the fibroblast origin of these CiCMs. Further studies show the generation of CiCMs passes through a cardiac progenitor stage instead of a pluripotent stage. Bypassing the use of viral-derived factors, this proof of concept study lays a foundation for in vivo cardiac transdifferentiation with pharmacological agents and possibly safer treatment of heart failure.

Embryonic stem cells (ESCs) can propagate in an undifferentiated state indefinitely in culture and retain the potential to differentiate into any somatic lineage as well as germ cells. The catabolic process autophagy has been reported to be involved in ESC identity regulation, but the underlying mechanism is still largely unknown. Here we show that EPG5, a eukaryotic-specific autophagy regulator which mediates autophagosome/lysosome fusion, is highly expressed in ESCs and contributes to ESC identity maintenance. We identify that the deubiquitinating enzyme USP8 binds to the Coiled-coil domain of EPG5. Mechanistically, USP8 directly removes non-classical K63-linked ubiquitin chains from EPG5 at Lysine 252, leading to enhanced interaction between EPG5 and LC3. We propose that deubiquitination of EPG5 by USP8 guards the autophagic flux in ESCs to maintain their stemness. This work uncovers a novel crosstalk pathway between ubiquitination and autophagy through USP8-EPG5 interaction to regulate the stemness of ESCs. Autophagy is implicated in self-renewal of stem cells, including embryonic stem cells (ES cells). Here the authors demonstrate EPG5 is highly expressed in ES cells, and its deubiquitylation by USP8 stimulates its interaction with LC3 to promote autophagy and maintenance of stemness.

Most aquatic environments are suffering from microplastic pollution, which poses a threat to the physiological and ecological characteristics of aquatic animals. The phospholipid hydroperoxide glutathione peroxidase gene (PHGPx) has an important function in the antioxidative defense of organisms. Here, we revealed for the first time that the full-length cDNA of PHGPx in Brachionus calyciflorus was 817 bp long and contained a 512 bp open reading frame. B. calyciflorus was exposed to 0 (control), 1 × 104, 1 × 105, 1 × 106, and 1 × 107 particles mL−1 polystyrene (particle size: 1 µm). Specific growth rate (SGR); reproductive rate (R); superoxide dismutase (SOD), catalase (CAT), and PHGPx activities; manganese superoxide dismutase (MnSOD), copper and zinc superoxide dismutase (CuZnSOD), CAT, and PHGPx expression; and reactive oxygen species (ROS) levels were investigated. Our results showed that polystyrene enhanced ROS production. SGR, R, PHGPx activity, and PHGPx expression decreased with the increase in polystyrene concentrations. SOD and CAT activities and MnSOD, CuZnSOD, and CAT expression levels increased upon exposure to 1 × 104–1 × 106 particles mL−1 polystyrene but decreased under exposure to 1 × 107 particles mL−1 polystyrene. These results revealed that PHGPx, MnSOD, CuZnSOD, and CAT expression regulates antioxidant enzyme activities, which are involved in the PHGPx-associated antioxidant defense of rotifers in response to polystyrene.

Benign prostatic hyperplasia (BPH) is an age-related disease, affecting a majority of elderly men worldwide. Medical management of BPH is an alternative to surgical treatment of this disease. Currently, α1-adrenergic receptor (α1-AR) antagonists are among the first line drugs to treat BPH by reducing the tension of urinary track and thus the obstructive symptoms in voiding. In drug development, old male dogs with spontaneous BPH are considered the golden standard of the animal models. However, old dogs (>6 years) are expensive and not all old dogs develop BPH. So it is necessary to develop more accessible animal models for drug efficacy evaluation. Here we describe the development of testosterone-induced BPH models in both rats and young adult dogs and their applications in the in vivo evaluation of α1-AR antagonist. The BPH rats and dogs induced by chronic testosterone treatment have significantly increased micturition frequency and reduced mean voided volume, very similar to the clinical symptoms of BPH patients. Silodosin, an α1-AR antagonist, significantly reduces the urinary frequency and increases the voided volume in BPH model animals in a dose-dependent manner. The results demonstrate that testosterone-induced BPH rat and dog models might provide a more efficient way to evaluate micturition behavior in anti-BPH drug studies.

Functional traits of plants and animals play a pivotal role in shaping mutualistic or predatory interactions within plant–animal systems, directly regulating the structure and function of forest ecosystems. Yet, the outcomes of multispecies interactions—particularly in seed–rodent systems—remain inadequately resolved, largely because traditional methods fail to track individual‐level interactions and seed fates with sufficient precision. To address this gap, we applied a novel double‐duplex passive integrated transponder (PIT) tagging technique to investigate the fates of seeds from four sympatric tree species (with distinct seed traits) when exploited by two sympatric rodent species (with contrasting body sizes) in a subtropical forest of Southwest China from 2018 to 2019. Our results revealed that rodent body size and seed size are key determinants of seed fates. The larger rat Niviventer confucianus scatter‐hoarded and consumed seeds of all four trees, with a significant preference for large‐sized seeds of Quercus variabilis and Lithocarpus harlandii . In contrast, the smaller mouse Apodemus draco did not hoard the large‐sized seeds of L. harlandii and showed a significant preference for small‐sized seeds of Camellia oleifera . Additionally, N. confucianus exhibited a higher interspecific pilfering rate on seeds of C. oleifera and L. harlandii than A. draco . Our study highlights the significant role of size traits in shaping the mutualistic or predatory interactions in seed–rodent systems and demonstrates the utility of individual‐based tracking in disentangling complex species interactions.

To investigate the impact of treatment modality on survival of International Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer. Patients with FIGO stage IIB cervical cancer registered in the Surveillance, Epidemiology, and End Results database between 1988 and 2015 were identified and grouped according to their treatment modalities. Propensity score matching (PSM) was performed to adjust the baseline characteristics. A total of 4718 stage IIB patients with eligible data were identified. Of them, 902 underwent surgery and 3816 received chemoradiotherapy alone. After PSM, 1208 patients were paired without baseline difference. Patients undergoing surgery ( n  = 604) had significantly improved overall survival (OS, 5-year rate: 68.0%, P  = 0.007) and cancer-specific survival (CSS, 5-year rate: 70.4%, P  = 0.007) compared with those receiving chemoradiotherapy alone (5-year rates: 59.9% for OS, 62.9% for CSS, n  = 604). On multivariate analysis, treatment modality was an independent factor for both OS (hazard ratio [HR] = 1.334, P  = 0.002) and CSS (HR = 1.369, P  = 0.002). In subgroup analyses, surgery provided significantly better survival than chemoradiotherapy in subgroups with ≤ 4 cm squamous-cell carcinoma ( P  = 0.046 for OS, P  = 0.020 for CSS, n  = 143) and > 4 cm non-squamous-cell carcinoma ( P  = 0.010 for OS, P  = 0.004 for CSS, n  = 240). However, these differences were not observed in subgroups with > 4 cm squamous-cell carcinoma ( P  = 0.665 for OS, P  = 0.816 for CSS, n  = 523) or ≤ 4 cm non-squamous-cell carcinoma ( P  = 0.173 for OS, P  = 0.293 for CSS, n  = 30). In this population-based analysis, a surgery-based strategy was associated with improved survival compared to chemoradiation in patients with FIGO stage IIB cervical cancer. Exploratory subgroup analyses suggested that this benefit may vary by histology and tumor size.

Microhabitats influence the distribution and abundance of benthic harmful dinoflagellate (BHAB) species. Currently, much of the information on the relationships between BHABs and microhabitat preferences is based on non-quantitative anecdotal observations, many of which are contradictory. The goal of this study was to better quantify BHAB and microhabitat relationships using a statistically rigorous approach. Between April 2016 to May 2017, a total of 243 artificial substrate samplers were deployed at five locations in the Perhentian Islands, Malaysia while simultaneous photo-quadrat surveys were performed to characterize the benthic substrates present at each sampling site. The screen samplers were retrieved 24 h later and the abundances of five BHAB genera, Gambierdiscus , Ostreopsis , Coolia , Amphidinium , and Prorocentrum were determined. Substrate data were then analyzed using a Bray–Curtis dissimilarity matrix to statistically identify distinct microhabitat types. Although BHABs were associated with a variety of biotic and abiotic substrates, the results of this study demonstrated differing degrees of microhabitat preference. Analysis of the survey results using canonical correspondence analysis explained 70.5% (horizontal first axis) and 21.6% (vertical second axis) of the constrained variation in the distribution of various genera among microhabitat types. Prorocentrum and Coolia appear to have the greatest range being broadly distributed among a wide variety of microhabitats. Amphidinium was always found in low abundances and was widely distributed among microhabitats dominated by hard coral, turf algae, sand and silt, and fleshy algae and reached the highest abundances there. Gambierdiscus and Ostreopsis had more restricted distributions. Gambierdiscus were found preferentially associated with turf algae, hard coral and, to a lesser extent, fleshy macroalgae microhabitats. Ostreopsis , almost always more abundant than Gambierdiscus , preferred the same microhabitats as Gambierdiscus and were found in microbial mats as well. With similar habitat preferences Ostreopsis may serve as an indicator organism for the presence of Gambierdiscus . This study provides insight into how BHAB-specific microhabitat preferences can affect toxicity risks.

Nudix Hydrolase 21 (NUDT21), an alternative polyadenylation (APA)-regulatory protein, exhibits tumor-suppressive effects. However, its role in cervical cancer (CxCa) remains unknown. In the present study, we found that NUDT21 expression was reduced in CxCa tissues and cells, and NUDT21 levels were highly associated with the clinical prognosis of patients with CxCa. Knockdown of NUDT21 promoted CxCa cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and lung metastasis in vivo. Overexpression of NUDT21 produces the opposite effects. Moreover, we performed polyadenylation site sequencing (PAS-Seq) and identified 457 transcripts with lengthened 3′ untranslated regions (3′ UTRs) upon NUDT21 overexpression. In particular, NUDT21 modulated the expression of several genes involved in fatty acid metabolism and the Wnt and NF-κB signaling pathways in CxCa development. Taken together, our study demonstrated that the APA regulatory effect of NUDT21 is an important mechanism for CxCa suppression.

In endangered species conservation, fecal samples are a vital non-invasive tool for gut microbiota analysis. Yet, the influence of external exposure time on microbial composition and function remains unclear, constraining data accuracy and reliability. To address this, we investigated the time-gradient effect in the globally endangered forest musk deer ( Moschus berezovskii ). Using non-invasive sampling under standardized captive conditions, fecal samples were collected at six storage times: (0, 1, 2, 4, 6, 8 days). Gut microbiota composition, diversity, enterotypes, and functional differences were assessed through 16S rRNA gene sequencing on the Illumina MiSeq platform. In total, 147,013 valid ASVs (amplicon sequence variants) were obtained showing significant shifts in microbial composition with storage time. Dominant phyla included Firmicutes , Bacteroidetes , Proteobacteria , and Actinobacteria . Increasing storage time led to declining α-diversity, reduced community stability, and more unique genera. PCoA (principal coordinates analysis) and NMDS (non-metric multidimensional scaling) indicated progressive separation of experimental groups from control groups, with Anosim and Adonis confirming progressive separation with storage time. Structurally, Firmicutes decreased while Proteobacteria , specifically the Acinetobacter genus, increased with storage time. Community assembly shifted from deterministic to stochastic processes, reflecting stronger environmental disturbance effects. These results demonstrate that the gut microbiota composition, diversity, and ecological functions in forest musk deer feces are highly sensitive to storage time. Thus, preservation duration must be strictly controlled as a critical variable in microbiome studies. This work establishes methodological standards for non-invasive fecal metagenomics in endangered species, providing theoretical insights and practical guidance for improving scientific rigor in conservation-related microbiome research. Key points Fecal microbiota diversity and stability decline significantly with longer storage. Firmicutes decrease while Proteobacteria, especially Acinetobacter, increase over time. Storage duration strongly impacts microbiome data, requiring strict sampling control. Graphical abstract