Lei Tang

Obesity is closely associated with excessive adipose accumulation, chronic low-grade inflammation, and gut microbiota dysbiosis. Although needle extracts from several Pinus species have been reported to attenuate body weight gain and modulate the gut microbiota, the pharmacological properties of Pinus squamata X.W. Li—an endangered coniferous species endemic to northeastern Yunnan, China—remain largely unexplored. This study evaluated the effects of Pinus squamata needle extract (PSNE) on high-fat diet (HFD)-induced obesity in mice. Our results demonstrated that PSNE significantly mitigated HFD-induced body weight gain, adipose accumulation, hepatic steatosis and injury, dyslipidaemia, oxidative stress, and systemic low-grade inflammation, while concomitantly improving glucose homeostasis. Furthermore, 16S rRNA amplicon sequencing of cecal contents revealed that PSNE increased amplicon sequence variant (ASV) richness and α-diversity, remodelled the cecal microbiota, and reversed HFD-associated dysbiosis. These beneficial alterations were characterised by significant enrichment of taxa with reported metabolic benefits, such as Bacteroides , Muribaculaceae and Ruminococcaceae, together with a concomitant reduction in obesity-associated lineages. Collectively, these findings establish PSNE as a promising preclinical candidate for alleviating obesity and related metabolic disorders, potentially through targeted remodelling of the cecal microbiota.

Carbon dots (CDs) have demonstrated broad-spectrum biological activity, with particle size considered a key determinant of their biological efficacy. However, the interrelationships among size, structure, and function remain unclear. To address this, we synthesized CDs under identical hydrothermal protocols and separated them into four size fractions (NPDCDs₁-NPDCDs₄), to directly investigate how particle size influences physicochemical and antibacterial properties. The four fractions exhibited distinct optical and structural properties: NPDCDs₁ (3.2 nm) emitted at 510 nm with the highest C-O content; NPDCDs₂ (2.2 nm) emitted at 510 nm with high C-C/C=C content; NPDCDs₃ (2.1 nm) showed red-shifted emission at 570 nm and the highest C=C ratio; NPDCDs₄ (1.9 nm) displayed the most red-shifted emission at 580 nm (λex = 380 nm) with the highest C=O content. Notably, NPDCDs₁ demonstrated excellent biocompatibility and potent antibacterial activity, primarily through efficient disruption of bacterial biofilms, possibly due to its high C-O content and appropriate particle size. Thus, particle size modulated biological function via corresponding changes in structural and surface chemical properties. These findings clarify that particle size critically influences both the physicochemical properties and antibacterial activity of CDs, providing an empirical foundation for the rational design of highly efficient and low-toxicity carbon-based antimicrobial materials.

To overcome the high computational expense of conventional quantum chemistry techniques and the limited incorporation of physical constraints in machine learning models, we present SphereDiff-TS: a diffusion-based method for predicting 3D transition state (TS) structures using a spherical coordinate system with flexible boundary and dynamic radius constraints. Evaluated against true transition states, the model achieves chemical accuracy in both geometry (median RMSD: 0.048 Å; median of 0.022 Å on selected cross-system cases) and energy (median absolute error: 0.55 kcal/mol; 0.328 kcal/mol on the same cases). Moreover, comparative analysis with the literature-reported structures confirms that the model accurately reproduces barrier heights, with deviations generally below 1.5 kcal/mol. These results highlight the potential of SphereDiff-TS as a robust computational tool for exploring reaction mechanisms and aiding in computer-driven reaction design.

Non-small-cell lung cancer (NSCLC) is one of the most prevalent cancer types and accounts for the majority of cancer-related deaths worldwide. Tanshinone and its derivatives exhibit diverse biological activities, and their prominent antitumor potential has been well documented. In this study, we rationally designed a series of tanshinone derivatives with a scaffold-hopping strategy. Thirty-five tanshinone derivatives were synthesized, and their cytotoxic activities against the NSCLC cell lines A549 and H838 were investigated. Concurrently, their safety profile was assessed in BEAS-2B cells. The results showed that compounds S2-1, S2-4, and S2-8 exhibited superior inhibitory activity against A549 cells compared with the positive control, β-lapachone. Meanwhile, compounds S2-1, S2-3, S2-4, S2-8, S2-13, and S2-14 exhibited similar or increased antiproliferation activity against H838 cells. Compounds S2-4 (0.58 ± 0.07 μM) and S2-8 (0.42 ± 0.04 μM) demonstrated the greatest potency towards H838 cells; compounds S2-13 (1.28 ± 0.13 μM) and S2-14 (1.80 ± 0.24 μM) exhibited potent and selective activity towards H838 cells. Molecular docking studies of S2-4/NLRP3 and S2-14/STAT3, combined with the structure–activity relationship (SAR) analysis, indicated that the benzofuran core containing an ortho-quinone, along with an amide linkage and a 1,2,3-triazole group introduced at the C-2 position of the furan ring, is an effective chemical scaffold for enhancing the anti-NSCLC activity of tanshinone derivatives.

BACKGROUND Chronic obstructive pulmonary disease (COPD) and mental health conditions represent intersecting public health challenges, especially in resource-limited rural China. Existing care models often neglect the psychosocial needs of populations at high risk for COPD, resulting in limited effectiveness of prevention and management strategies. This study evaluates an integrated intervention designed to improve both mental and physical health outcomes among high-COPD-risk individuals with mental health symptoms, using a population medicine framework. OBJECTIVE This study aims to evaluate the effect of an integrated, population medicine–based multimorbidity intervention package among high-COPD-risk individuals with mental health symptoms in Xishui County, Guizhou Province, China. METHODS We are conducting a 12-month, 2-arm cluster randomized controlled trial across 26 townships in Xishui County, Guizhou, China. A total of 44,000 residents aged ≥35 years were screened using the Chronic Obstructive Pulmonary Disease Screening Questionnaire, identifying 10,000 individuals at high risk of COPD. Among them, 3807 individuals with Warwick-Edinburgh Mental Well-Being Scale scores below 45 were enrolled as participants. Intervention components include digital cognitive behavioral therapy–based mental health support, community screening, chronic disease management, patient education, digital follow-up, and team-based care. The primary outcomes are depressive symptoms (9-item Patient Health Questionnaire), anxiety symptoms (7-item General Anxiety Disorder), and mental well-being (Warwick-Edinburgh Mental Well-Being Scale). Secondary outcomes are control of chronic diseases, physiological and functional indicators such as lung function, health-related quality of life, mental and behavioral health, health care utilization, knowledge of COPD and asthma, productivity loss, and care cascade indicators for chronic conditions. RESULTS Data collection for the POPMIX-MH trial began in June 2024. Baseline, 3-month, and 6-month assessments have been completed, and the 12-month follow-up assessments are planned to be completed in March 2026. CONCLUSIONS This study is the first to integrate psychological support, chronic disease management, and community-based screening into a single scalable intervention package targeting multimorbidity in China. It tests the feasibility of applying population medicine principles, emphasizing integrated, preventive, and population-level care, within primary care systems in low-resource settings. By targeting both mental and physical health, it redefines chronic care beyond traditional organ-specific approaches. CLINICALTRIAL ClinicalTrials.gov NCT06458218; https://clinicaltrials.gov/ct2/show/NCT06458218 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/85853

BACKGROUND Tobacco-related noncommunicable diseases (NCDs) present a major public health challenge in China, requiring population-level management. Chronic obstructive pulmonary disease (COPD) is the most common and prevalent chronic respiratory disease associated with tobacco use. In addition, COPD shares risk factors with other NCDs that frequently co-occur, leading to multimorbidity. This study focuses on the early detection and integrated management of COPD and related multimorbidity among high-risk populations. Population medicine, an emerging and evolving concept aimed at maximizing population health and well-being, provides a promising framework for shifting interventions against COPD from an individual patient focus to a population-level approach. OBJECTIVE This study aims to evaluate the effectiveness of a population medicine–based multimorbidity intervention package among individuals at high risk for COPD. METHODS We are conducting a 2-arm, population-based, stratified cluster randomized controlled trial (cRCT). The intervention integrates community screening, chronic disease management, patient education, digital follow-up, and team-based care. The trial is being implemented in Xishui County, Guizhou Province, a low-resource county in Southwestern China. Each of the 26 townships in Xishui County was considered a cluster and stratified into large and small townships based on population size. An equal number of residents from each township stratum (large and small) were randomized to undergo the COPD Screening Questionnaire. Individuals identified as being at high risk for COPD were considered study participants and were subsequently enrolled in either the intervention or control arm. The target sample size was approximately 2850 individuals. RESULTS Data collection for the POPMIX-COPD trial began in June 2024. Baseline, 3-month, and 6-month assessments have been completed, and 12-month follow-up assessments are planned to be completed in March 2026. All participants in the intervention arm are being followed for 1 year, with 1 telephone follow-up at month 3 and in-person follow-ups at months 6 and 12. Primary outcomes for each participant include the number of chronic conditions controlled, receipt of lung function testing, and forced expiratory volume in 1 second. In addition, secondary outcomes were health-related quality of life, mental and behavioral health status, health care utilization, knowledge of COPD and asthma, and care cascade indicators for chronic conditions. CONCLUSIONS This cRCT is the first multimorbidity intervention study designed within the population medicine framework to target populations at high risk for COPD. It was featured as a case study in the report of the Lancet Commission on Investing in Health. The results of the trial are expected to inform the next generation of multimorbidity management and population medicine practices among global health authorities and practitioners. CLINICALTRIAL ClinicalTrials.gov NCT06456996; https://clinicaltrials.gov/ct2/show/NCT06456996 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/85597