Existing patient-reported outcome measures (PROMs) for Chinese patients with chronic obstructive pulmonary disease (COPD) exacerbations have limited conceptual frameworks, uncertain post-COVID-19 validity, and poor clinical interpretability. We conducted a multicenter, two-stage study (pre-pandemic: n = 300; post-pandemic: n = 423) to develop and validate a comprehensive COPD-PROM. The conceptual framework was derived from literature review, expert consultation, and patient interviews. Reliability, validity, and sensitivity were examined, and the minimal clinically important difference (MCID) was established using anchor- and distribution-based methods. The final 52-item COPD-PROM included four domains-physiological, psychological, social, and therapeutic-with Cronbach's α > 0.7 across domains except social. Confirmatory factor analysis indicated acceptable model fit (pre-pandemic: CFI = 0.993, RMSEA = 0.014; post-pandemic: CFI = 0.934, RMSEA = 0.054). The COPD-PROM provides a reliable and interpretable measure of health-related quality of life in COPD, supporting patient-centred assessment and individualized management across healthcare settings.

This study aimed to determine the coverage of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the influenza vaccine, along with related factors, among elderly individuals aged 60 y and above in the capital urban of China. In 2023, 14 out of 43 streets or townships in Chaoyang District were selected using a random sampling method. Elderly participants completed a questionnaire. Logistic regression analysis was employed to identify influencing factors. Among 1,422 respondents, 235 (16.53%) had received the PPV23 vaccine; 747 (52.53%) expressed willingness but had not yet been vaccinated; and 440 (30.94%) indicated unwillingness. Influenza vaccine coverage was higher than that of PPV23: 437 respondents (30.73%) received annual influenza vaccination; 385 (27.07%) were willing but did not consistently receive the vaccine annually; 284 (19.97%) were willing but had not yet been vaccinated; and 316 (22.22%) explicitly refused influenza vaccination. The primary reason for refusal among unwilling participants for both vaccines was the perception that vaccination was unnecessary. For those willing but not ultimately vaccinated, the most frequent reason was lack of awareness regarding available vaccination services. Groups more likely to receive PPV23 and influenza vaccines included individuals who frequently experienced influenza and those recommended by medical staff. These groups also showed a greater inclination to continue influenza vaccination. It is imperative to strengthen community health education on these vaccines, encourage uptake among residents and healthcare professionals, and actively promote the benefits and convenience of PPV23 vaccination.

A new species of Gesneriaceae, Petrocosmea pengzhouensis K.Huang & Z.X.Fu, sp. nov., from the Feilaifeng Scenic Area of Longmen Mountain National Geological Park (Pengzhou, Chengdu City, Sichuan Province, China), is described and illustrated. Morphological and phylogenetic analyses provide robust evidence for its recognition as a new species. While morphologically most similar to P. duclouxii Craib, phylogenetic reconstructions reveal its closest affinities with P. duclouxii and P. intraglabra (W. T. Wang) Z. J. Qiu. The new species is morphologically distinguished from P. duclouxii by a suite of diagnostic characters: leaf shape (ovate to oblique-ovate vs. ovate to nearly orbicular), corolla throat (spotless vs. bearing two deep purple spots), and filament pubescence (translucent-puberulent vs. rust-brown puberulent). A distribution map and a comparative morphological table with P. duclouxii, P. intraglabra, and P. hexiensis S. Z. Zhang & Z. Y. Liu, and a preliminary conservation assessment following IUCN criteria are provided.

Pulmonary fibrosis (PF) is a common hallmark of several types of interstitial lung diseases (ILDs), for which effective therapeutic drugs are lacking. The small-molecule chemical compound cinobufotalin (CB) has demonstrated significant anti-cancer effects in lung cancer. In this study, we first found that CB attenuated bleomycin (BLM)-induced PF and inhibited transforming growth factor-beta 1 (TGF-β1)-induced myofibroblast activation and epithelial-mesenchymal transition (EMT). Subsequently, comparative RNA sequencing (RNA-Seq) was conducted to analyse the lung gene expression profiles in mice. Interestingly, peptidase inhibitor 15 (PI15) was identified as a significantly differentially expressed gene (DEG) and may be a potential target in PF progression. Mechanistic studies showed that CB exerts anti-PF effects by inhibiting PI15 and thereby regulating the TGF-β/Smad signalling pathway. Our data demonstrated that CB represents a promising anti-PF drug and may be a candidate therapeutic for PF patients.

BACKGROUND: The dysfunction of osteoblasts has been identified as a pivotal contributor to bone erosion in rheumatoid arthritis (RA). Emerging evidence shows long non-coding RNAs (lncRNAs) as important regulators in various pathological processes, including RA. However, the specific regulatory mechanisms of lncRNAs in osteoblast dysfunction of RA remain poorly understood and worth further investigation. METHODS: Collagen induced arthritis (CIA) rat model was established, tarsal tissue was isolated for sequencing of lncRNAs. The differentially expressed lncRNA was screened and verified in vivo and in vitro. The target microRNA of lncRNA and the target protein of microRNA were predicted by bioinformatics analysis and validated. The biology function of the lncRNA and microRNA was further investigated by knockdown or overexpression experiment in murine osteoblastic cell MC3T3-E1. RESULTS: LncRNA MIAT was highly expressed in tarsal tissue and serum of CIA rat as well as TNF-α-induced osteoblasts, and its high expression was negatively correlated with the expression of bone formation marker osteocalcin. Functionally, knockdown of lncRNA MIAT promoted the proliferation and mineralization of osteoblasts. Mechanistically, lncRNA MIAT directly bound to let-7i-5p and exerted a negative regulatory influence on its expression. CKIP-1 was a target of let-7i-5p. Overexpression of let-7i-5p promoted osteoblast proliferation and mineralization by targeting CKIP-1. CONCLUSIONS: Taken together, this study demonstrated that lncRNA MIAT was involved in the regulation of osteoblast proliferation and mineralization through the lncRNA MIAT/let-7i-5p/CKIP-1 axis in RA.

BACKGROUND: Sleep quality, fatigue, and depressive symptoms are highly prevalent and frequently co-occur as a symptom cluster in maintenance hemodialysis (MHD) patients. This cluster significantly impairs patients’ health-related quality of life and increases mortality risk. Although cross-sectional studies suggest interconnections, the temporal dynamics and interrelationships within this triad remain unclear, particularly regarding gender differences. Therefore, this study aimed to explore the temporal dynamics and longitudinal relationships among sleep quality, fatigue, and depressive symptoms in patients undergoing MHD. METHODS: A longitudinal survey of 242 MHD patients in Urumqi, Xinjiang, China, was conducted to examine the interrelationships between sleep quality, fatigue, and depressive symptoms using a cross-lagged panel model. The Pittsburgh Sleep Quality Index(PSQI), Functional Assessment of Chronic Illness Therapy-Fatigue(FACIT-F), and Self-Rating Depression Scale(SDS) were used for assessment at baseline (T1, December 2024 to February 2025) and at follow-up (T2, March 2025 to May 2025). RESULTS: Cross-lagged analyses revealed a bidirectional longitudinal relationship between lower fatigue severity (higher FACIT-F scores) and lower depressive symptoms (lower SDS scores) (β = -0.195, P < 0.05; β = -0.205, P < 0.05, respectively). Furthermore, lower baseline fatigue (higher FACIT-F scores) was longitudinally associated with better subsequent sleep quality (lower PSQI scores) (β = -0.227, P < 0.01). Conversely, more severe baseline depressive symptoms (higher SDS scores) predicted poorer subsequent sleep quality (higher PSQI scores) (β = 0.260, P < 0.01). Exploratory gender-stratified analyses revealed distinct patterns in these symptom dynamics. CONCLUSIONS: This study highlights the dynamic and reciprocal relationships among sleep quality, fatigue, and depressive symptoms in MHD patients. The reciprocal longitudinal associations between fatigue and depressive symptoms, and their links to subsequent sleep quality, underscore the importance of early identification and intervention. Interventions aimed at reducing fatigue and depressive symptoms, alongside sleep-focused strategies, may help improve sleep quality in MHD patients. CLINICAL TRIAL NUMBER: Not applicable.

To evaluate the safety and deliverability of neoadjuvant chemotherapy (NAC) with three-drug-intensity chemotherapy [oxaliplatin, irinotecan, and fluorouracil (FOLFOXIRI)] in patients with high-risk factors for recurrence and metastasis of locally advanced colon cancer (hr-LACC).

The murine endogenous retrovirus MERVL is dynamically activated in a small population of in vitro cultured mouse embryonic stem cells (mESCs) exhibiting totipotent-like features. Yet, the relationship between MERVL activation and cell fate decisions of mESCs is incompletely understood. Through a genome-wide knockout screen, we discovered that MERVL activity is intrinsically linked to DNA damage response pathways. Loss of Ints7, a backbone subunit of the Integrator complex, increased DNA damage and triggered MERVL expression. Mechanistically, Ints7 depletion induced phosphorylation of Kap1, increased chromatin accessibility at MERVL loci, and activated the p53-Dux axis to drive MERVL transcription. Intriguingly, DNA damage-induced MERVL resurgence followed the cleavage of caspase-3, often accompanying a process known as anastasis-cell survival after transient apoptotic signaling. Collectively, our study uncovered that MERVL activation in mESCs is integrated into the cellular circuit for decision-making in response to DNA damage, suggesting that sublethal caspase activation can influence the developmental potential of stem cells.

To evaluate the diagnostic potential of fluid suppression (FS) techniques combined with amide proton transfer-weighted imaging (APTw) for assessment of isocitrate dehydrogenase (IDH) mutation status, glioma subtypes, and tumor proliferation.

Myocardial ischemia (MI) is a pathological state of abnormal energy metabolism caused by insufficient blood and oxygen supply to the coronary arteries. The "gut-heart axis" theory plays an important role in myocardial ischemia occurrence, mechanism, prevention, and cure. Traditional Mongolian medicine posits that "internal diseases originate from gastrointestinal dysfunction," linking the intestine, a key component of the digestive system, to physiological and pathological changes in the heart. Furthermore, the traditional Mongolian clinical treatment of cardiovascular diseases includes guidelines for digestive system function corresponding to the modern concept of the gut-heart axis. Accordingly, Zadi-5, a traditional Mongolian medicine, has been used for over 200 years to prevent and treat cardiovascular diseases. However, the mechanism by which the gut microbiota and metabolism are regulated to protect an ischemic heart is unclear.

Neuromyelitis Optica Spectrum Disorder (NMOSD), a rare antoimmune condition, is characterized by a high relapse rate, necessitating long-term maintenance therapy even during clinically stable periods. This prolonged treatment regimen imposes a significant financial burden on patients, which may be greater than that associated with many other chronic diseases. However, data on the impact of financial toxicity (FT) specifically in NMOSD populations remain limited. This study aims to identify factors influencing FT in NMOSD patients using the ABC-X model as a conceptual framework.

Cell fate decisions in the early embryo rely on reciprocal transcriptional networks that balance pluripotency with lineage commitment. NANOG is essential for directing the epiblast-primitive endoderm (PrE) fate choice, but the molecular mechanisms underlying its repressive activity remain incompletely understood. Here we show that NANOG partners with TBX3 and the PRC2 complex to maintain embryonic stem cell (ESC) identity by silencing PrE genes through newly identified distal enhancers. Loss of Nanog reduces PRC2-mediated repression of Gata6, initiating its expression independently of TBX3. Subsequent TBX3 upregulation enables its association with GATA6, driving a feed-forward programme that activates Gata6, Gata4 and Sox17 and promotes PrE differentiation. Thus, NANOG suppresses PrE fate not only by direct repression but also by preventing TBX3 from switching partners. These findings define a Nanog-Tbx3-Gata6 regulatory axis that integrates enhancer control, chromatin regulation and transcription factor redeployment to couple ESC maintenance with lineage commitment.

While previous studies link larger ischemic penumbra volumes to worse AIS outcomes, clinical results are inconsistent. This study seeks to explore how baseline mismatch volume (a proxy for ischemic penumbra) relates to 90-day AIS prognosis and the mediating role of inflammatory markers herein.

BACKGROUND: Congenital cataract is a leading cause of childhood blindness worldwide, often caused by genetic mutations that disrupt lens transparency. This study aimed to investigate the molecular mechanisms by which crystallin beta B1 (CRYBB1) mutation contributes to cataract formation. METHODS: We identified a novel heterozygous deletion mutation (c.688_733del) in CRYBB1 in a Chinese Han family with autosomal dominant congenital nuclear cataract. Functional assays were conducted in human lens epithelial cells to assess effects on cell proliferation, migration, cell cycle progression, apoptosis, and oxidative stress. Mechanistic studies evaluated activation of mitochondrial apoptosis pathways. RESULTS: The c.688_733del mutation disrupts conserved domains essential for βB1-crystallin protein folding and stability. Mutant protein impaired cell proliferation and migration, induced G1 cell cycle arrest, and significantly increased apoptosis. Elevated intracellular reactive oxygen species were observed, triggering mitochondrial apoptosis via Bax/Bcl-2 imbalance and caspase-3 activation. CONCLUSION: Oxidative stress-mediated apoptosis is a key pathogenic mechanism in CRYBB1-related cataractogenesis. These findings expand the CRYBB1 mutational spectrum and provide a molecular basis for future diagnostic and therapeutic strategies.

Kynurenine (Kyn) 3‑monooxygenase (KMO) is a key enzyme of the tryptophan (Try)‑Kyn pathway and is located on the outer membrane of mitochondria. Notably, it has not yet been elucidated as to whether KMO is involved in hepatocellular carcinoma (HCC) progression by affecting mitochondria. In the present study, KMO was revealed to be downregulated in HCC patients and this downregulation was associated with a poor prognosis. Notably, the downregulation of KMO promoted the proliferation and migration of HCC cells and increased mitochondrial mass. The levels of the Try metabolite 3‑hydroxyanthranilic acid (3‑HAA) were elevated in HCC cells overexpressing KMO. The results indicated that 3‑HAA may inhibit HCC cell growth promoted by KMO downregulation and reverse the KMO downregulation‑induced increase in mitochondrial mass. Furthermore, KMO and 3‑HAA were shown to regulate the expression of the transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) and reduce NR4A1 mitochondrial translocation, thus inhibiting the growth of HCC cells. In summary, the current study elucidated that low KMO expression in HCC affects mitochondrial mass and function by reducing the level of the Try metabolite 3‑HAA, downregulating the expression of NR4A1 and promoting its mitochondrial translocation, which in turn may promote the progression of HCC. These findings provide new insights into the treatment of HCC, potentially targeting the mitochondria and the Try‑Kyn pathway.

Archipelagos and oceanic islands have remarkably high levels of endemism, which is associated with rapid speciation. The Malayan pangolin (Manis javanica), one of critically endangered Asia pangolin species, occurs in southern Yunnan, China, and on oceanic islands via the Malay peninsula. The question of whether the distribution of Malayan pangolins between the mainland and nearby marine islands has led to deep population differentiation is not well addressed. In-depth investigation of population structure and genetic consequences is of vital importance for protection and conservation of Malayan pangolins. Here we carried out a large-scale population genomic analysis for Malayan pangolins, which revealed three highly distinct genetic populations. The largest population was found to be distributed over a wide area extending from mainland China to almost the whole of South East Asia. The other two smaller populations reported in this study were inferred from Borneo. In addition, based on multiple lines of genomic and skull morphological evidences, we confirmed the existence of a fifth Asian pangolin species (M. mysteria). Genetic diversity and genome-wide inbreeding were at moderate levels, indicating that anthropogenic factors did not significantly weaken the basis of genetic sustainability for Malayan pangolins. However, Malayan pangolins from northeastern Borneo exhibited low genetic diversity, high levels of inbreeding and mutational load, thereby necessitating attention to their protection.

The sustainability of global agricultural systems, a cornerstone for both economic security and food supply chains, is increasingly compromised by phytopathogen invasions. Herein, we characterize RP151—a novel biopesticide engineered through rational concatenation of plant immunity-stimulating peptides. This recombinant protein demonstrates exceptional bioavailability in Solanaceous crops like tobacco and tomato, inducing multifaceted defense responses within 24 h post-application, as evidenced by ROS burst, MAPK cascade activation, and localized callose deposition. Mechanistic studies reveal that RP151-mediated resistance against TMV and its co-infection with CMV primarily operates through SA-dependent signaling. ‌In comparative trials, RP151 significantly prolonged SAR duration and effectively suppressed lesion expansion in TMV-challenged plants relative to conventional antiviral agents. Notably, the broad-spectrum efficacy of RP151 was further validated against necrotrophic fungi (Botrytis cinerea) in tomato. RP151’s deployment could lead to a substantial reduction in the use of harmful pesticides, offering a sustainable, safe solution for enhancing plant defense against a variety of pathogens.

Acne is a common skin condition that seriously affects the physical and mental health of patients. In addition to the standard acne treatment, anti-acne skin care products are gradually becoming essential in preventing and treating acne. Herbal Balance Solution contains multiple botanical ingredients with potential anti-inflammatory and barrier-supportive properties. This pilot study aimed to explore the safety and preliminary clinical effects of Herbal Balance Solution in patients with mild-to-moderate acne vulgaris.

Neuraxial block failure in obese parturients is a significant clinical challenge, leading to inadequate pain relief and increased maternal risk. Novel techniques such as the Combined Spinal-Epidural (CSE) and Dural Puncture Epidural (DPE) have emerged as promising alternatives to standard epidural, but their comparative efficacy and safety have not been systematically evaluated in a comprehensive network. This systematic review and network meta-analysis aimed to determine the optimal neuraxial technique for preventing analgesia and anesthesia failure in obese parturients, with specific attention to morbidly obese subgroups and procedural efficiency.

Newcastle disease virus (NDV) has been well established as a versatile vector platform for heterologous antigen delivery in poultry vaccine development. However, the prospects for combined application of two recombinant NDV (rNDV) vaccines remain poorly understood. In previous studies, we generated two rNDVs based on the thermostable TS09-C strain, expressing glycoprotein B (gB) of infectious laryngotracheitis virus (ILTV) and hemagglutinin (HA) of the H9N2 subtype avian influenza virus (H9N2 AIV). In the present study, we evaluated the potential interference between the two rNDVs and using both in vitro and in vivo models. When two rNDVs co-infected BHK-21 and CEK cells, their viral replication kinetics and expression levels of heterologous antigens (gB and HA) were comparable to those in the respective single-virus infection groups. This finding indicates that the two rNDVs do not exhibit significant interference in vitro. SPF chickens co-immunized with the two rNDVs via intranasal and intraocular routes elicited effective H9N2-, ILTV-, and NDV-specific antibody responses comparable to those in the single-virus immunization group. Compared with control chickens, co-immunized chickens displayed milder clinical signs and reduced viral shedding following challenge with H9N2 AIV, ILTV, and NDV. Based on these findings, spray co-immunization was further tested in commercial chickens and proven to confer effective protection against challenges with NDV, H9N2 AIV, and ILTV. In conclusion, this study confirms the feasibility of co-immunization using the two rNDVs, thereby providing a highly viable strategy for the simultaneous control of multiple avian pathogens.