Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

ObjectiveTo investigate the status of overlapping hepatitis B virus （HBV） infection in patients with chronic hepatitis C virus （HCV） infection and the serological characteristics of such patients. MethodsA total of 8 637 patients with HCV infection who were hospitalized from January 1， 2010 to December 31， 2020 and had complete data of HBV serological markers were enrolled， and the composition ratio of patients with overlapping HBV serological markers was analyzed among the patients with HCV infection. The patients were divided into groups based on age and year of birth， and serological characteristics were analyzed， and the distribution of HBV-related serological characteristics were analyzed across different HCV genotypes. ResultsThe patients with HCV/HBV overlapping infection accounted for 5.85%， and the patients with previous HBV infection accounted for 48.10%； the patients with protective immunity against HBV accounted for 14.67%， while the patients with a lack of protective immunity against HBV accounted for 31.39%. The patients were divided into groups based on age： in the 0 — 17 years group， the patients with protective immunity against HBV accounted for 61.41% （304 patients）； the 18 — 44 years group was mainly composed of patients with previous HBV infection （698 patients， 37.31%）， the 45 — 59 years group was predominantly composed of patients with previous HBV infection （1 945 patients， 50.38%）， and the ≥60 years group was also predominantly composed of patients with previous HBV infection （1 486 patients， 61.66%）. The patients were divided into groups based on the year of birth： in the pre-1992 group， the patients with previous HBV infection accounted for 51.63% （4 112 patients）； in the 1992 — 2005 group， the patients with protective immunity against HBV accounted for 54.72% （168 patients）； in the post-2005 group， the patients with protective immunity against HBV accounted for 64.38% （235 patients）. In this study， 6 301 patients underwent HCV genotype testing： the patients with genotype 1b accounted for the highest proportion of 51.71% （3 258 patients）， followed by those with genotype 2a （1 769 patients， 28.07%）， genotype 3b （63 patients， 1.00%）， genotype 3a （10 patients， 0.16%）， genotype 4 （21 patients， 0.33%）， and genotype 6a （5 patients， 0.08%）. ConclusionWith the implementation of hepatitis B planned vaccination program in China， there has been a significant reduction in the proportion of patients with previous HBV infection among the patients with HCV/HBV overlapping infection， but there is still a relatively high proportion of patients with a lack of protective immunity against HBV.

Objective: To evaluate the current situation of thermal environment in primary and secondary school classrooms during winter, and to analyze students thermal comfort needs, so as to provide a basis for improving classroom thermal environment. Methods: From December 16 to 26, 2024, a stratified cluster random sampling method was used to select 90 classrooms from 15 primary and secondary schools in centralized/air conditioned heating areas(Liaoning Province, Tianjin City, Shanghai City) and naturally ventilated areas(Anhui Province and Jiangxi Province)for on site environmental measurement. A questionnaire survey was conducted among 743 students. The differences between groups using the χ 2 test were compared. Based on actual measurement data, a predicted mean vote prepared percentage of dissatisfied (PMV-PPD) model for centralized/air conditioned classrooms and an adaptive model for naturally ventilated classrooms were established, and the thermal neutral temperature and comfort interval were calculated. Results: The average outdoor temperature during on site measurement was 4.00(0.20，7.00)℃. In classrooms with centralized or air conditioned heating systems, the measured average temperature was (19.33±2.59)℃, with a thermal comfort range of 20.35-25.35 ℃ and a thermal neutral temperature of 22.85 ℃. And 13.92% of students reported feeling cold, while 80.80% felt comfortable. In classrooms with natural ventilation, the measured average temperature was (12.26±1.83)℃, with a thermal neutral temperature of 19.67 ℃ and a thermal comfort range of 16.17-23.17 ℃. About 48.33% of students reported feeling cold, and 49.81 % felt comfortable.The results of univariate analysis showed that there were statistically significant differences in shoe thickness, temperature sensation, relative humidity sensation and wind speed sensation between centralized/air conditioned heating areas ( χ 2= 7.01 , 31.47, 13.57, 13.80,all P <0.05). There were also statistically significant differences in school stage for primary and secondary school students, body mass index, classroom location for seat, temperature sensation, relative humidity sensation and wind speed sensation between naturally ventilated areas ( χ 2=42.13, 11.13, 11.04, 60.39, 29.27, 38.46,all P <0.05). Conclusions There are differences in thermal environment and students subjective thermal comfort in primary and secondary schools under different ventilation modes in winter. The temperature standards for heated classrooms should be revised, and differentiated environmental regulation strategies should be adopted based on different ventilation methods to improve students health and comfort levels.

Objective: To understand the serum vitamin D and vitamin K 1 levels of children in the Qingdao area, so as to provide scientific grounds for appropriate vitamin supplementation. Methods: A total of 4 469 children aged 0-14 years old, who attended the children s healthcare outpatient clinics of a tertiary hospital in Qingdao, were enrolled in the current study between January 2023 and July 2024. The levels of vitamin D and vitamin K 1 were measured by liquid chromatography tandem mass spectrometry. The inter group differences were analyzed using Chi square test, Wilcoxon rank sum test, and Kruskal-Wallis H test. The correlation analysis of vitamin D and vitamin K 1 levels with age was performed using the Spearman correlation. Results: The serum vitamin D level among children was 28.72(22.67, 36.26)ng/mL. The vitamin D deficiency and insufficiency rates were 2.10% and 14.59 %, respectively. The serum 25-(OH)D 2 level was 0.29(0.14, 0.53)ng/mL, the serum 25-(OH)D 3 level was 27.99( 21.78 , 35.57)ng/mL and the serum vitamin K 1 level was 0.54(0.29, 1.04)ng/mL. The vitamin K 1 deficiency rate was 13.76%. Among different age stages, the serum vitamin D level was highest in infancy [37.45(30.39, 43.87)ng/mL] and lowest in school age children [22.39(18.00, 26.97)ng/mL]; the level of vitamin K 1 was highest in preschool children [0.79(0.41, 1.51) ng/mL] and lowest in school age children[0.45 (0.26, 0.76) ng/mL]; the serum vitamin D deficiency and insufficiency rates were highest in school age children (5.03% and 30.81%); the vitamin K 1 deficiency rate was highest in infancy (21.53%) ( H/χ 2=1 698.31, 253.70 , 137.85 , 583.79, 89.30, all P <0.05). Among different seasons, the serum vitamin D and vitamin K 1 levels were lowest in the winter [26.74(18.37, 35.86) and 0.50 (0.27, 0.94)ng/mL; H =50.71, 7.86]; the vitamin D deficiency and insufficiency rates were highest in the winter (5.41% and 24.80%; χ 2=59.93, 83.35) (all P <0.05). The serum vitamin D level had a moderate negative correlation with age ( r =-0.62), and there was a low positive correlation between the serum vitamin D and vitamin K 1 levels in infancy and early childhood ( r =0.21, 0.26) (all P <0.05). Conclusions The serum vitamin D and vitamin K 1 levels are lowest in school age children and in the winter, and the serum vitamin K 1 deficiency rate is highest in infancy. There is a need to focus on critical periods of infancy and school age, and strengthen interventions during the high risk winter season. The nutritional status of vitamin D and vitamin K 1 in children should be enhanced.

Objective To systematically analyze the disease burden, long-term trends, and age-sex distribution of major valvular heart disease (VHD) subtypes—rheumatic heart disease (RHD), non-rheumatic valvular disease (NRVD), and non-rheumatic calcific aortic valve disease (CAVD)—in global, Chinese, and US populations from 1990 to 2021, providing evidence for public health strategies and clinical resource allocation. Methods Based on publicly available data from the Global Burden of Disease (GBD) Study 2021, we extracted incidence, mortality, and disability-adjusted life years (DALYs) for VHD from 1990 to 2021. Age-standardized rates (ASRs) were calculated using the GBD 2021 global standard population, and the estimated annual percentage change (EAPC) with its 95% uncertainty interval (UI) was computed for the period. Data from the Agency for Healthcare Research and Quality (AHRQ), the European Society of Cardiology (ESC)/Eurostat surveys, and Chinese national registries were used for trend triangulation and contextual background. Results From 1990 to 2021, the ASR and disease burden of RHD significantly decreased globally and in China (EAPC for DALYs in China: −4.8%, 95%UI: −5.0% to −4.6%). In contrast, the burden of NRVD and CAVD steadily increased in aging populations like those in China and the US, with a higher burden observed in older adults and males. In 2021, the incidence of NRVD and CAVD peaked in individuals aged ≥65 years, with rates being significantly higher in men than in women. RHD burden was concentrated in low socio-demographic index (SDI) regions, whereas NRVD/CAVD burden was strongly associated with high-SDI regions. Conclusion The global VHD epidemiological landscape is transitioning from an RHD-dominant to an NRVD/CAVD-dominant pattern. China faces a dual challenge of a residual RHD burden and a rapidly growing burden of degenerative valvular diseases. Developing tailored screening, prevention, and treatment strategies for different disease subtypes and populations is crucial.

ObjectiveTo investigate the therapeutic effect and mechanism of Huatan Qushi Huoxue prescription on rats with metabolic dysfunction-associated steatohepatitis （MASH）. MethodsA total of 60 specific pathogen-free Sprague-Dawley rats were randomly divided into blank control group， model A group， model B group， Western medicine group （polyene phosphatidylcholine， 143.64 mg/kg）， high-dose Chinese medicine group （Huatan Qushi Huoxue prescription， 20.16 g/kg）， and middle-dose Chinese medicine group （Huatan Qushi Huoxue prescription， 10.08 g/kg）. All rats except those in the blank control group were given high-fat diet. Samples were collected from the model A group at week 8， and since week 12， the other groups were given the corresponding drug once a day for 8 consecutive weeks， with samples collected at week 20. Body weight， liver wet weight， and liver index were measured for all rats； the microplate method was used to measure the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and free fatty acids （FFA）； ELISA was used to measure the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and soluble triggering receptor expressed on myeloid cells 2 （sTREM2）； HE staining and oil red O staining were performed to observe liver histopathological changes； immunofluorescence assay was used to measure CD68⁺TREM2⁺ cells in liver tissue and calculate the phagocytosis rate of macrophages； quantitative real-time PCR was used to measure the mRNA expression levels of sphingosine 1-phosphate （S1P）， sphingosine 1-phosphate receptor 1 （S1PR1）， a disintegrin and metalloproteinase 17 （ADAM17）， and triggering receptor expressed on myeloid cells 2 （TREM2） in liver tissue， and immunohistochemistry was used to measure the protein expression levels of S1P， S1PR1， ADAM17， and TREM2 in liver tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data with homogeneity of variance between groups， and the least significant difference t-test was used for further comparison between two groups； the Welch’s test was used for comparison of normally distributed continuous data with heterogeneity of variance between groups， and the Tamhane’s test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups， and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the blank control group， the model A group and the model B group had significant increases in body weight and liver wet weight， and the model B group had a significant increase in liver index （all P<0.05）. HE staining showed diffuse macrovesicular steatosis of liver tissue in the model A group and a large number of hepatocytes with ballooning degeneration in liver tissue in the model group B， with the presence of mixed inflammatory cell infiltration and mild perisinusoidal fibrosis in the lobules and the portal area. Compared with the blank control group， the model A group and the model B group had significant increases in NAS score and oil red O-positive area （all P<0.05）， and the model B group had significant increases in these two indicators than the model A group （both P<0.05）. Compared with the blank control group， the model A group and the model B group had significant increases in the serum levels of TC， TG， LDL-C， FFA， IL-1β， IL-6， and sTREM2 and a significant reduction in the serum level of HDL-C， and the model B group had significant increases in the serum levels of ALT， AST， and TNF-α （all P<0.05）； compared with the model A group， the model B group had significant increases in the serum levels of ALT， AST， TC， TG， FFA， TNF-α， IL-1β， IL-6， and sTREM2 and a significant reduction in the serum level of HDL-C （all P<0.05）. Immunofluorescence assay showed that compared with the blank control group， the model A group had a significant increase in the phagocytosis rate of macrophages （P<0.05）， while the model B group had a significantly lower phagocytosis rate of macrophages than the model A group （P<0.05）. Quantitative real-time PCR showed that compared with the blank control group， the model A group and the model B group had a significant increase in the mRNA expression level of TREM2， and the model B group had significant increases in the mRNA expression levels of S1P and S1PR1 （both P<0.05）； moreover， compared with the model A group， the model B group had significant increases in the mRNA expression levels of S1PR1 and TREM2 （both P<0.05）. Immunohistochemistry showed that compared with the blank control group， the model A group and the model B group had significant increases in the protein expression levels of S1P， S1PR1， and ADAM17， and the model A group had a significant increase in the protein expression level of TREM2 （all P<0.05）； compared with the model A group， the model B group had significant increases in the protein expression levels of S1P， S1PR1， and ADAM17 and a significant reduction in the protein expression level of TREM2 （all P<0.05）. Compared with the model B group， each medication group had significant reductions in body weight， liver wet weight， and liver index （all P<0.05）； each medication group had significant improvements in hepatic steatosis and inflammatory damage， with significant reductions in NAS score and oil red O-positive area （all P<0.05）； each medication group had significant reductions in the serum levels of ALT， AST， TC， TG， FFA， IL-1β， and IL-6 （all P<0.05） and a significant increase in the serum level of HDL-C （P<0.05）， and the high-dose Chinese medicine group had a significant reduction in the serum level of TNF-α （P<0.05）； each medication group had a significant increase in the phagocytosis rate of macrophages （all P<0.05）； the high- and middle-dose Chinese medicine groups had a significant reduction in the protein expression level of ADAM17， and the high-dose Chinese medicine group had a significant increase in the protein expression level of TREM2 （all P<0.05）. ConclusionHuatan Qushi Huoxue prescription improves lipid metabolism and inflammation in the liver of MASH rats by regulating hepatic macrophage phagocytosis.

ObjectiveTo construct a rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）， and evaluate the macroscopic manifestations and microscopic indicators of the model. MethodsTwenty-two SD rats were divided into normal group （n=3）， common psoriasis group （n=5）， spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）， and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）. The spleen deficiency and dampness obstruction syndrome （external dampness type） rat model was established through 32-week exposure to an artificially simulated high-humidity environment， while the common psoriasis model was developed via 7-day topical application of imiquimod cream， and these two approaches were combined to construct a composite model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）. Rats in the normal group were housed under normal humidity conditions. The general state， tongue manifestation of rats were observed to evaluate the macroscopic syndrome manifestations； the microscopic syndrome manifestations of rats were evaluated through adipose tissue and liver tissue changes； the severity of psoriasis in rats was evaluated through skin pathological changes， psoriasis area and severity index （PASI）， proliferating cell nuclear antigen （PCNA） expression and spleen tissue changes； changes in rat CD4⁺ interferon-γ⁺ cells （CD4⁺IFN-γ⁺ cells）， CD4⁺ tumour necrosis factor-α+ cells （CD4⁺ TNF-α⁺ cells）， and forkhead framing protein P3⁺ regulatory T cells （CD3⁺CD4⁺FoxP3⁺ Treg cells） were detected by flow cytometry. ResultsMacroscopically， both the spleen deficiency and dampness obstruction syndrome （external dampness type） group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited manifestations of spleen deficiency and dampness obstruction， including lethargy， huddling behavior， dull and disheveled fur， as well as soft or loose stools and perianal soiling in some individuals； both these two groups displayed enlarged tongue， swollen， and moist tongue texture， accompanied by slippery tongue surface. Microscopically， compared to the common psoriasis group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group showed increased epididymal fat index （P＜0.05）； compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group demonstrated significantly elevated spleen mass （P＜0.05）， while hepatic gross morphology and HE staining revealed no significant histopathological changes across all groups. Dorsal skin lesions were markedly exacerbated in the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group when compared to those in common psoriasis group. Both the common psoriasis group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited significantly higher erythema scores， scaling scores， infiltration scores， PASI total scores， and proportions of CD3⁺CD4⁺FoxP3⁺Treg cells compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）， with pronounced PCNA-positive expression observed in the epidermal basal layer and dermis； the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group displayed significantly increased proportions of CD4⁺TNF-α⁺cells compared to the spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）； whereas no significant differences were detected in CD4⁺IFN-γ⁺cell proportions among groups （P＞0.05）. ConclusionThe rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） can be successfully constructed by artificially simulating a high-humidity environment combined with imiquimod induction.

Objective To investigate disparities in health levels among populations across different regions of China and analyze the relationship between these disparities and regional, social, and economic factors, and to provide recommendations to promote health equity. Methods Based on the data from the Seventh National Population Census, this study employed spatial autocorrelation analysis and the spatial Durbin model to conduct spatial and temporal analyses of the health status of the national population from 2012 to 2021, focusing on the regional distribution of health levels and related influencing factors. Results 1. Regional disparities: The mortality rate in Gansu Province rose from 6.05‰ in 2012 to 8.26‰ in 2021, whereas the mortality rate in eastern provinces such as Hainan Province was relatively low in 2021 (5.39‰). 2. Spatial clustering: The spatial correlation of mortality rates was weak (Moran's I: 0.134-0.245), and the high mortality clusters showed a shift from southwest to northeast region. 3. Influencing factors: Economic conditions, education quality, urbanization levels, and healthcare resources significantly impacted population mortality rates. Conclusion The present study identifies pronounced regional disparities in population health, providing a scientific basis for formulating targeted healthcare policies. Additionally, this study highlights the critical importance of spatial analysis in understanding and addressing public health issues to advance health equity.

ObjectiveJunctophilin-2 (JPH2) is an essential structural protein that maintains junctional membrane complexes (JMCs) in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum, thereby facilitating excitation-contraction (E-C) coupling. Mutations in JPH2 have been associated with hypertrophic cardiomyopathy (HCM), but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus (MORN) repeat motifs remain incompletely understood. This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis. MethodsA recombinant N-terminal fragment of mouse JPH2 (residues1-440), encompassing the MORN repeats and an adjacent helical region, was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain. Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features. Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells. In addition, site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations, including R347C, was used to evaluate their effects on membrane interaction and subcellular localization. ResultsThe crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6 Å, revealing a compact, elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration, forming a continuous hydrophobic core stabilized by alternating aromatic residues. A C-terminal α-helix further reinforced structural integrity. Conservation analysis identified the inner groove of the MORN array as a highly conserved surface, suggesting its role as a protein-binding interface. A flexible linker segment enriched in positively charged residues, located adjacent to the MORN motifs, was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes. Functional assays demonstrated that mutation of these basic residues impaired membrane association, while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays, despite preserving the overall MORN-Helix fold in structural modeling. ConclusionThis study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2, highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions. The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis. These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.

OBJECTIVE To develop a long-acting light-protective nanogel with both physical barrier and chemical clearance functions， and evaluate its performance. METHODS The photoprotective nanogel composed of mussel mucin and sodium hyaluronate was constructed based on a fullerenol-cerium oxide composite nano system， namely fullerenol-cerium oxide nanogel （FCN）， and was characterized. The antioxidant capacity of FCN was evaluated using in vitro free radical scavenging experiments； its UV shielding ability was assessed by using an SPF value detector； its biosafety was assessed according to the requirements of the Guidelines for Drug Safety Evaluation； skin adhesion was assessed using small animal 3D live imaging technology； its sun protection ability was assessed through skin sunscreen detection and histopathological observation. RESULTS The average particle sizes of cerium oxide and fullerenol nanoparticles in FCN were about 20 and 10 nm， respectively， and FCN exhibited good UV absorption and free radical scavenging abilities. SPF value of FCN was 58.95±0.82， and the ultraviolet A protection level value was 6.21±0.15. No pathogenic colonies such as Staphylococcus aureus， were detected in the nanogel， and the contents of lead， arsenic， mercury and cadmium all met the standards for pharmaceutical excipients； FCN group did not show any irritating reactions such as erythema， edema， or desquamation； blood biochemical indicators of the FCN group were within the normal reference range. The material clearance rate of mice in the artificial sweat flushing group was less than 30%， while the material clearance rate of mice in the dry cleaning group reached about 92%. The mice in the protective group did not show obvious erythema or ulcer formation throughout the experiment. Histopathology showed that the fibers were arranged in an orderly manner， and the number of collagen fibers was close to that of the control group. CONCLUSIONS The FCN formulation constructed in this study meets the relevant requirements of the Chinese Pharmacopoeia， has good safety and skin compatibility， and achieves dual synergistic protection of UV shielding and free radical scavenging.