OBJECTIVE To study how resveratrol(Res)mitigates acute lung injury(ALI)in mice induced by sulfur mustard(SM)and potential mechanism.METHODS Male C57BL/6N mice were randomly divided into the control group(50 μL physiological saline via nebulization),SM group(SM 5 mg·kg-1 via nebulization),SM+Res 10 or 20 mg·kg-1 groups(1 h after administration of SM 5 mg·kg-1,Res 10 or 20 mg·kg-1 was administered via nebulization).Mice in each group were weighed 0,24,48 and 72 h after SM administration.Mice were sacrificed 72 h after SM administration,and lung tissues were collected,weighed for wet and dry weights,and the wet/dry ratio was calculated.HE staining was employed to detect the pathological changes of lung tissues while real-time quantitative PCR(RT-qPCR)was used to detect the mRNA expression levels of interleukin 6(IL-6)and IL-1β.Transcriptomic changes of the SM group and the SM+Res 20 mg·kg-1 group were detected with the next-generation sequencing technology.RT-qPCR was used to detect the mRNA expression changes of adenosine 5'-monophos-phate-activated protein kinase(AMPK)and silence information regulator 1(SIRT1)in lung tissues.RESULTS 72 h after SM administration,the body mass of mice in the SM group was significantly decreased compared with normal control group,while the wet/dry ratio of the lung was significantly increased,so were the mRNA expression levels of IL-6 and IL-1β in lung tissues were also significantly increased.Pathological changes of lung tissues included alveolar cavity atrophy,marked parenchymal tissues,and diffuse infiltration of local inflammatory cells.Compared with the SM group,the body mass of mice in the SM+Res 10 and 20 mg·kg-1 groups significantly increased,the wet/dry ratio of lung tissues was significantly reduced,and expressions of IL-6 and IL-1β mRNA were significantly decreased in SM+Res 10 and 20 mg·kg-1 groups.Compared with the normal control group,the mRNA expression levels of AMPK and SIRT1 in lung tissues of the SM group were significantly decreased.Compared with the SM group,the mRNA expression levels of AMPK in lung tissues of the SM+Res 10 and 20 mg·kg-1 groups were significantly increased while the mRNA expression level of SIRT1 was significantly decreased.CONCLUSION Res can mitigate ALI in mice induced by SM,and the mechanism may be related to the inhibition of cell apoptosis by regulating the AMPK/SIRT1 signaling pathway.

Objective To integrate multi-source heterogeneous literature data from China Na-tional Knowledge Infrastructure(CNKI),Wanfang,VIP,and Web of Science(WoS)databases u-sing bibliometric methods,and to comparatively analyze the differences in knowledge structure charac-teristics and evolutionary pathways of organoid research between China and foreign countries.Meth-ods CiteSpace software was employed to conduct a visual atlas analysis of the publication volume,countries,institutions,authors,and keywords of 1,118 Chinese literatures and 10,871 English lit-eratures.Results China ranked the second globally in terms of publication volume(accounting for 22.09％),but exhibited low centrality in international collaboration networks.The density of the do-mestic institutional collaboration network was 0.003,indicating a relatively loose structure,with Fudan University leading domestic output with 15 Chinese papers.Keyword emergence analysis revealed that"organ-on-a-chip"and"biomechanics"have emerged as new hotspots since 2024.Conclusion It is recommended to establish an interdisciplinary collaborative innovation alliance to focus on break-throughs in the translational directions of organ-on-a-chip and biomechanics,thereby addressing the imbalance between"scale and quality"in China's organoid research.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

OBJECTIVE To study how resveratrol(Res)mitigates acute lung injury(ALI)in mice induced by sulfur mustard(SM)and potential mechanism.METHODS Male C57BL/6N mice were randomly divided into the control group(50 μL physiological saline via nebulization),SM group(SM 5 mg·kg-1 via nebulization),SM+Res 10 or 20 mg·kg-1 groups(1 h after administration of SM 5 mg·kg-1,Res 10 or 20 mg·kg-1 was administered via nebulization).Mice in each group were weighed 0,24,48 and 72 h after SM administration.Mice were sacrificed 72 h after SM administration,and lung tissues were collected,weighed for wet and dry weights,and the wet/dry ratio was calculated.HE staining was employed to detect the pathological changes of lung tissues while real-time quantitative PCR(RT-qPCR)was used to detect the mRNA expression levels of interleukin 6(IL-6)and IL-1β.Transcriptomic changes of the SM group and the SM+Res 20 mg·kg-1 group were detected with the next-generation sequencing technology.RT-qPCR was used to detect the mRNA expression changes of adenosine 5'-monophos-phate-activated protein kinase(AMPK)and silence information regulator 1(SIRT1)in lung tissues.RESULTS 72 h after SM administration,the body mass of mice in the SM group was significantly decreased compared with normal control group,while the wet/dry ratio of the lung was significantly increased,so were the mRNA expression levels of IL-6 and IL-1β in lung tissues were also significantly increased.Pathological changes of lung tissues included alveolar cavity atrophy,marked parenchymal tissues,and diffuse infiltration of local inflammatory cells.Compared with the SM group,the body mass of mice in the SM+Res 10 and 20 mg·kg-1 groups significantly increased,the wet/dry ratio of lung tissues was significantly reduced,and expressions of IL-6 and IL-1β mRNA were significantly decreased in SM+Res 10 and 20 mg·kg-1 groups.Compared with the normal control group,the mRNA expression levels of AMPK and SIRT1 in lung tissues of the SM group were significantly decreased.Compared with the SM group,the mRNA expression levels of AMPK in lung tissues of the SM+Res 10 and 20 mg·kg-1 groups were significantly increased while the mRNA expression level of SIRT1 was significantly decreased.CONCLUSION Res can mitigate ALI in mice induced by SM,and the mechanism may be related to the inhibition of cell apoptosis by regulating the AMPK/SIRT1 signaling pathway.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

To evaluate the therapeutic effect and mechanism of rapamycin (RAPA) on pulmonary fibrosis induced by chlormethine in C57BL/6N mice. Based on body weight, the 18-20 g C57BL/6N mice were randomly divided into five groups: control group, chlormethine group, chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group, with ten mice in each group. Mice were put to death on the 21st day after the first administration of chlormethine. HE staining and Masson staining were used to observe the pathological changes and degree of fibrosis in the lung tissue of mice, and RT-PCR was used to detect collagen Ⅰ, E-cadherin, vimentin, and α-SMA mRNA expression. After 21 days of administration of chlormethine to mice, significant pulmonary fibrosis characteristics were observed in the lung tissue of the mice. Compared with the chlormethine group, the weight of mice in the chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group, significantly increased ( P<0.05). Compared with the chlormethine group, the expression of pulmonary fibrosis-related indicators (collagen Ⅰ, E-cadherin, vimentin, and α-SMA) significantly improved ( P<0.05) in the chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group. Compared with the chlormethine group, the pathological changes and collagen deposition in the lung tissue of mice in the chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group, were significantly improved. Transcriptome analysis of the lung tissue of mice revealed that RAPA treatment of chlormethine-induced pulmonary fibrosis might be related to NF-kappa B signaling pathway. Compared with the chlormethine group, the mRNA expression of p65 in the lung tissue of mice in the chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group, significantly decreased ( P<0.01). RAPA has a protective effect on pulmonary fibrosis induced by chlormethine in mice. Its efficacy is comparable to that of dexamethasone, which is currently being used in clinical practice. It is a new alternative therapy, and its mechanism may be related to inhibiting the activation of the NF-kappa B signaling pathway.

To evaluate the therapeutic effect and mechanism of rapamycin (RAPA) on pulmonary fibrosis induced by chlormethine in C57BL/6N mice. Based on body weight, the 18-20 g C57BL/6N mice were randomly divided into five groups: control group, chlormethine group, chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group, with ten mice in each group. Mice were put to death on the 21st day after the first administration of chlormethine. HE staining and Masson staining were used to observe the pathological changes and degree of fibrosis in the lung tissue of mice, and RT-PCR was used to detect collagen Ⅰ, E-cadherin, vimentin, and α-SMA mRNA expression. After 21 days of administration of chlormethine to mice, significant pulmonary fibrosis characteristics were observed in the lung tissue of the mice. Compared with the chlormethine group, the weight of mice in the chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group, significantly increased ( P<0.05). Compared with the chlormethine group, the expression of pulmonary fibrosis-related indicators (collagen Ⅰ, E-cadherin, vimentin, and α-SMA) significantly improved ( P<0.05) in the chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group. Compared with the chlormethine group, the pathological changes and collagen deposition in the lung tissue of mice in the chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group, were significantly improved. Transcriptome analysis of the lung tissue of mice revealed that RAPA treatment of chlormethine-induced pulmonary fibrosis might be related to NF-kappa B signaling pathway. Compared with the chlormethine group, the mRNA expression of p65 in the lung tissue of mice in the chlormethine+dexamethasone (1 mg/kg) group, chlormethine+RAPA (1 mg/kg) group and chlormethine+RAPA (2 mg/kg) group, significantly decreased ( P<0.01). RAPA has a protective effect on pulmonary fibrosis induced by chlormethine in mice. Its efficacy is comparable to that of dexamethasone, which is currently being used in clinical practice. It is a new alternative therapy, and its mechanism may be related to inhibiting the activation of the NF-kappa B signaling pathway.

BACKGROUND:In recent years,increasing studies have focused on the abnormal proliferation and differentiation of acinous cells in the meibomian gland,suggesting that this process is closely related to the occurrence and development of dry eye.Structural and functional abnormalities such as blockage of the lumen of the meibomian gland and atrophy of the glands can cause or exacerbate dry eye.Therefore,the study of changes in the meibomian glands in dry eyes is important for understanding the pathogenesis of dry eyes in depth and finding new targets for the treatment and prevention of dry eyes. OBJECTIVE:To investigate the changes of the meibomian gland in a mouse model of aqueous deficient dry eyes. METHODS:Thirty-two female C57/B6 mice at 6-8 weeks were selected and randomly divided into experimental and control groups with 16 mice in each group.The mice in the experimental group were constructed by removing both the extra-orbital and intra-orbital lacrimal glands,while those in the control group were not treated.After 2 weeks of normal feeding,the corneal changes of both groups were observed under a slit lamp,and the tear secretion of both groups was measured.The meibomian glands of the two groups of mice were removed after decapitation.The changes in the gross morphology of the meibomian glands were observed and the meibomian glands were made into frozen sections.Hematoxylin-eosin staining was used to observe the structure of the meibomian glands,oil red staining was used to evaluate the function of the meibomian glands,and immunofluorescence staining and RT-qPCR were used to observe the expression of cytokeratin 14,Ki67 and abnormally differentiated small proline-rich protein 1B in the meibomian glands of mice. RESULTS AND CONCLUSION:Two weeks after modeling,lamellar defects were seen in the corneas of the experimental mice,and neovascularization of the limbal corneal was generated and invaded the central cornea.(2)Tear secretion volume was significantly reduced in the experimental group compared with the control group(P<0.05).Microscopic findings showed that the ducts of the meibomian glands in the experimental group were interrupted and atrophied,and their arrangement was disorganized.Hematoxylin-eosin staining results showed a significant increase in lipid vacuoles in the meibomian glands of the experimental mice compared with the control group.Lipid deposition was seen in oil red staining in the experimental group.Immunofluorescence and RT-qPCR results showed a significant increase in the expression of cytokeratin 14,Ki67 and small proline-rich protein 1B in the meibomian glands of mice in the experimental group compared with the control group(P<0.05).To conclude,aqueous deficient dry eye can lead to compensatory hypertrophy,increased proliferation,and abnormal lipid metabolism in the meibomian gland,as well as abnormal differentiation of the meibomian gland.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

Objective To explore the correlation between lumbar spine bone mineral density and the occurrence of large rotator cuff tears. Methods A total of 109 patients with arthroscopic shoulder surgery in the Department of Arthroplasty Surgery in Kunshan Hospital of Traditional Chinese Medicine from January 2018 to October 2023 were selected and divided into large rotator cuff tear group (n=27) and small rotator cuff tear group (n=82) according to the severity of the rotator cuff tears. General materials of patients were collected, and multivariate Logistic regression analysis was used to investigate the correlation between lumbar spine bone mineral density and the occurrence of large rotator cuff tears. Results The large rotator cuff tear group had significant higher age and higher proportion of patients with a history of trauma compared to the small rotator cuff tear group (P < 0.05); additionally, the levels of total cholesterol, albumin, serum magnesium, total hip bone mineral density, and lumbar spine bone mineral density were significantly lower in the large rotator cuff tear group (P < 0.05). The results of multivariate Logistic regression analysis indicated that lumbar spine bone mineral density was associated with the occurrence of large rotator cuff tears. The prevalence of large rotator cuff tears across the four quartile intervals of lumbar spine bone mineral density named as Q1 (< 0.870 g/cm²), Q2 (0.870~ < 0.991 g/cm²), Q3 (0.991~1.137 g/cm²), and Q4 (>1.137 g/cm²) were 48.15%, 29.63%, 18.52% and 3.70% respectively, showing a gradual decreasing trend with significant differences (P < 0.05). Conclusion There is a correlation between lumbar spine bone mineral density and large rotator cuff tears. The lower the bone density of the lumbar spine is, the higher the risk of large rotator cuff tears will be.