Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors， and it may progress to liver cirrhosis， portal hypertension， and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury， inflammatory cell infiltration with the release of inflammatory mediators， hepatic stellate cell activation， and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression， including the molecular pathways for hepatic fibrosis driven by metabolic disorders， energy deficiency， oxidative stress， mitochondrial dynamic imbalance， and autophagic dysfunction， all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis， in order to provide new therapeutic strategies for clinical management.

Background Climate change poses a significant threat to public health. In China, relevant health intervention research is still in its early stages, and evidence for evaluating the effectiveness of regional climate change health adaptation strategies and measures is scarce. Objective To investigate the level of climate change-related health literacy among residents in Shenzhen, implement targeted health interventions, and assess the intervention effects as well as their influencing factors. Methods From July 2023 to January 2024, 4 communities were randomly selected in Shenzhen, and a total of 896 community residents were enrolled and divided into an intervention group (444 participants) and a control group (452 participants). Baseline and follow-up surveys on climate change-related health literacy were conducted among residents for both groups. During the period between the two surveys, the intervention group received targeted health interventions. Health literacy—comprising 3 dimensions: basic health knowledge and concepts, basic health skills, and healthy lifestyles—was defined as achieving ≥80% of the total score. A differences-in-differences model was adopted to analyze the impact of the intervention, and multiple linear regression was used to explore the factors influencing the intervention effect. Results The baseline survey showed that 240 out of the 896 surveyed residents (26.79%) possessed climate change health literacy. For the 3 dimensions, the number of residents and the proportions with corresponding literacy in descending order were: basic health skills (521, 58.15%), healthy lifestyles (345, 38.50%), and basic health knowledge and concepts (44, 4.91%). After the intervention, the intervention group showed a 3.19% increase in the total health literacy score, a 3.55% increase in basic health knowledge and concepts, and a 4.24% increase in basic health skills (t=2.79, 2.77, and 2.47 respectively) (P<0.05). No significant change was observed in healthy lifestyle scores (t=0.70, P>0.05). Further analysis showed that awareness of the “dual carbon goals” and occupation were significantly associated with the intervention effect on overall health literacy (P<0.05). For basic health knowledge and concepts, occupation, history of chronic diseases, and awareness of the “dual carbon goals” had statistically significant effects on the intervention outcomes (P<0.05). Regarding basic health skills, awareness of the “dual carbon goals” significantly influenced the intervention effect (P<0.001). In terms of healthy lifestyles, gender, educational level, occupation, and awareness of climate change were significantly associated with the intervention effect (P<0.05). Conclusion The climate change-related health literacy among community residents in Shenzhen is in urgent need of improvement. Health interventions can effectively enhance residents' basic health knowledge and concepts, basic health skills, and overall literacy level. In the future, it is necessary to strengthen the popularization of climate change health knowledge based on different population characteristics and further optimize intervention strategies, to comprehensively improve residents' health adaptation capacity to climate change.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

The culture of suspended Vero cells is facing difficulties such as low cell viability and long doubling time. To investigate the main reasons for the slow growth and low viability of suspended Vero cells, this study conducted transcriptomic analysis of suspended Vero cells (Vero-XF) and adherent Vero cells (Vero-AD) to screen the differentially expressed genes (DEGs) affecting the growth of suspended cells. In addition, epidermal growth factor (EGF) was supplemented to the culture system to improve the growth of Vero-XF. The results showed that compared with the Vero-AD group, the Vero-XF group had 7 376 significant DEGs. Kyoto encyclopedia of genes and genomes enrichment analysis revealed that the DEGs were mainly enriched in the autophagy and mitophagy pathways. Eleven DEGs were selected and verified by quantitative real-time PCR, which showed up-regulated expression of ATG9B, WIPI2, LAMP2, OPTN, Rab7a, and DEPTOR and down-regulated expression of ATG4D, being consistent with the results of transcriptomic analysis. In addition, the Vero-XF group showed significantly up-regulated expression of ATG101, ATG2A, and STX17 and insignificant change in the expression of NBR1, compared with the Vero-AD group. The protein levels of LC3 and P62 in Vero-XF and Vero-AD were determined by Western blotting, which showed up-regulated expression of LC3Ⅱ/Ⅰ and down-regulated expression of P62 in Vero-XF, indicating a higher level of autophagy. Finally, the exogenous supplementation of EGF at 10, 20, and 30 μg/L in the culture system reduced the autophagy level of Vero-XF by 22.35%, 48.15%, and 71.29%, increased the specific growth rate by 15.48%, 33.33%, and 57.14%, and decreased the apoptosis rate by 2.84%, 15.46%, and 16.23%, respectively. The results of this study preliminarily reveal that the activation of autophagy is one of the reasons for the slow growth of Vero-XF, which provides reference for the subsequent culture of suspended Vero cells.
Animals ; Vero Cells ; Autophagy/genetics* ; Chlorocebus aethiops ; Epidermal Growth Factor/pharmacology* ; Gene Expression Profiling ; Transcriptome ; Cell Survival

As a medicinal and edible fungus, Inonotus obliquus has a long history of folk application in Russia, Japan, and Northeast China. It is rich in terpenoids, steroids, polysaccharides, phenols, alkaloids, etc, and exhibits pharmacological activities including anti-tumor, hypoglycemic, anti-inflammatory, antioxidant, and lipid-lowering effects. Among these, lanostane-type tetracyclic triterpenes represent its characteristic constituents. This review systematically summarizes the research progress on the chemical components isolated and identified from I. obliquus and their pharmacological activities in recent years. The structures of terpenoids, steroids, and phenolic compounds are compiled and illustrated, with a particular focus on the skeletal types and structural characteristics of lanostane-type tetracyclic triterpenes. This work aims to provide some reference for the further investigation and comprehensive development and utilization of I. obliquus.

A qualitative analysis by high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-QTOF-MS/MS) was performed for the identification of main constituents in Gentiana veitchiorum. High-performance liquid chromatography (HPLC) was developed for the quantification of seven major components, including loganic acid (1), swertiamarin (2), gentiopicroside (3), sweroside (4), isoorientin (5), isoscoparin (6), and gentiournoside A (7). A total of 42 compounds, including 31 flavonoids, and 11 Iridoids, were identified based on their retention behaviors, and MS fragment information. Furthermore, regression equations for these seven chemical components were established, with good linear relationships (r2 > 0.9999), and the sample recovery rate was 97.02%-103.08%. This method was successfully applied for simultaneous determination of seven components in 7 batches of G. veitchiorum samples by HPLC-UV method. The method established in this study is simple and reliable, capable of qualitatively and quantitatively analyzing the main chemical components of G. veitchiorum, and is applicable to its quality evaluation.

The patients with skeletal Class Ⅱ high-angle malocclusion are frequently complicated by idiopathic condylar resorption(ICR),which may lead to temporomandibular joint(TMJ)dysfunction and dentofacial deformities.This article reports the diagnosis and treatment process of a 24-year-old female patient with skeletal Class Ⅱ high-angle malocclusion accompanied by ICR.The patient's chief complaints were anterior open bite and TMJ pain,and was diagnosed with ICR through clinical examination and imaging.After stabilizing condylar resorption with occlusal splint therapy,combined orthodontic-orthognathic treatment was performed.The 42-month follow-up revealed:well-aligned dentition with complete closure of diastemas,significant improvement of protrusive facial profile(ANB angle reduced by 4.2°),complete resolution of TMJ pain and clicking,and establishment of stable Class Ⅰ occlusion.Three-dimensional CT demonstrated satisfactory condylar bone remodeling and normalized joint space.Through multidisciplinary treatment,both occlusal function and facial aesthetics were significantly improved.This case demonstrates that orthodontic-orthognathic treatment should be performed after condylar stabilization in ICR patients,and occlusal splint therapy serves as an effective preoperative intervention.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Objective: To reveal the therapeutic effects of moxibustion in collagen-induced arthritis (CIA) rat models using the combined analysis of plasma and synovial membrane lipidomic profiling and to enhance the understanding of how moxibustion affects lipid metabolism in rheumatoid arthritis (RA). Methods: A total of 32 male Sprague-Dawley (SD) rats were randomly assigned to four groups: control, moxibustion control (MC), model, and moxibustion model (MM) groups, with 8 rats in each group. CIA was induced in SD rats by two immunizations. The paw volume was measured before the induction of CIA. Following induction, after assessing paw volume and arthritis index (AI) scores, the MC and MM groups received treatment at bilateral Shenshu (BL23) and Zusanli (ST36) acupoints for 10 min per acupoint. The intervention included three treatment courses, each spanning 6 d and followed by a 1-d interval. Paw volume and AI scores were assessed after each treatment course. After the completion of the three treatment courses, serum, plasma, synovial tissue, and ankle joint samples were collected. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in serum. Hematoxylin and eosin (HE) staining was performed for histopathological examination of the ankle joint tissues. Meanwhile, ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) was utilized to analyze the plasma and synovial tissue samples. In addition, multivariate statistical analysis was performed to identify differential lipid metabolites, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was applied to explore metabolic pathways modulated by moxibustion therapy. Results: No significant difference in hind paw volume and AI scores was observed among the groups (P > 0.05). After CIA induction, model group showed increased hind paw volume and AI scores compared with control group (P < 0.05), which were significantly reduced after moxibustion treatment in MM group compared with model group (P < 0.05). The levels of IL-6 and TNF-α were significantly higher in model and MM groups compared with control group (P < 0.05), but were lower in MM group than those in model group (P < 0.05). Histopathological analysis showed improved cartilage and reduced inflammation in MM group. A total of 33 differential lipid metabolites in the plasma and 24 in the synovial membranes of CIA rat models were identified when compared with control group. Among these lipid metabolites, 31 in the plasma and all 24 in the synovial membranes were regulated by moxibustion treatment. Pathological analysis revealed upregulation of diacylglycerol (DG) and fatty acid (FA) levels, alongside downregulation of lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Under physiological conditions, the treatment specifically reduced LPC and PC levels. Pathway enrichment analysis revealed that moxibustion predominantly affected α-linolenic acid, glycerophospholipid, and sphingolipid metabolism under pathological conditions. Under physiological conditions, the regulation was centered around α-linolenic acid and glycerophospholipid metabolism. Conclusion The RA rat models exhibited significant lipid metabolic disturbances. Moxibustion alleviated paw swelling, reduced AI scores, modulated inflammatory cytokine levels, and partially corrected the altered levels of multiple lipid metabolites. The potential metabolic pathways implicated in the regulation of lipid metabolism under both physiological and pathological conditions include α-linolenic acid, glycerophospholipid, and sphingolipid metabolism.