Mitofusin 2 (MFN2) residing on the outer mitochondrial membrane is a pivotal factor participating in mitochondrial fusion and maintaining mitochondrial morphology. Due to its multifaceted cellular functions, MFN2 is implicated in the pathogenesis of diverse maladies, notably type 2 Charcot-Marie-Tooth disease, which has catalyzed a surge in pharmaceutical endeavors directed towards MFN2. This article reviews the function of MFN2 and its role in a variety of diseases, outlines the current status of drug discovery against MFN2, and summarizes potential drug molecules currently in preclinical research, aiming to provide some reference for the research and development of drugs and therapies targeting MFN2.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Stresses induced by the deficiency or excess of trace mineral elements, such as manganese (Mn), represent a common limiting factor for the production of crops like Brassica napus. To identify key genes involved in Mn allocation in B. napus and elucidate the underlying mechanisms, a member of the metal tolerance protein (MTP) family obtained in the previous screening of cDNA library of B. napus under Mn stress was selected as the research subject. Based on the sequence information and phylogenetic analysis, it was named as BnMTP10. It belongs to the Mn-cation diffusion facilitator (CDF) subfamily. Expression of BnMTP10 in yeast significantly improved the tolerance of transformants to excessive Mn and iron (Fe) and reduced the accumulation of Mn and Fe. However, the yeast transformants exhibited no significant changes in tolerance to excess cadmium, boron, aluminum, zinc, or copper. The qRT-PCR results demonstrated that the flowers of B. napus had the highest expression of BnMTP10, followed by roots and leaves. Subcellular localization studies revealed that BnMTP10 was localized in the endoplasmic reticulum (ER). Compared with wild-type plants, transgenic Arabidopsis overexpressing BnMTP10 exhibited enhanced tolerance to excessive Mn stress but showed no significant difference under Fe stress. Correspondingly, under excessive Mn stress, the Mn content in the roots of transgenic Arabidopsis increased significantly. However, under excessive Fe stress, the Fe content in transgenic Arabidopsis did not alter significantly. According to the results, we hypothesize that BnMTP10 may alleviate excessive Mn stress in plants by mediating Mn transport to the ER. This study facilitated our understanding of efficient mineral nutrients, and provided theoretical foundations and gene resources for breeding B. napus.
Brassica napus/genetics* ; Manganese/metabolism* ; Plants, Genetically Modified/genetics* ; Plant Proteins/physiology* ; Arabidopsis/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Cation Transport Proteins/metabolism* ; Stress, Physiological

Objective To explore the feasibility and clinical value of endoscopic resection of duodenal papilla tumors with a maximum diameter greater than 3 cm. Methods A retrospective analysis was conducted on the clinical data of all 12 patients who underwent endoscopic resection of duodenal papilla tumors at the Endoscopy Center of Zhongshan Hospital (Xuhui Hospital), Fudan University and Rongcheng Hospital of Traditional Chinese Medicine from September 2017 to May 2023. The size of the tumors all exceeded 3 cm. Results All 12 patients successfully completed the operation, with a complete resection rate of 91.7% (11/12) and an en-bloc resection rate of 91.7% (11/12). One patient experienced delayed bleeding due to unclosed wound during operation and received endoscopic hemostasis; 11 cases underwent partial wound closure operation with pancreatic and biliary stent placement, without perforation or postoperative stenosis. Among them, 2 cases (18.2%) experienced delayed bleeding and received endoscopic hemostasis treatment. After operation, 1 case (8.3%) experienced nausea, vomiting, upper abdominal discomfort, and elevated blood amylase levels, who was later treated conservatively. During the mean follow-up period of 30.5 (1.0-69.0) months, 1 patient experienced recurrence and underwent surgical resection. Conclusions Endoscopic resection of duodenal papilla tumors can treat large diameter duodenal papilla tumors exceeding 3 cm, but postoperative complications may occur and require special attention. Postoperative placement of pancreatic and biliary stents and wound closure may reduce the incidence of complications.

Objective:To evaluate the nutritional status of patients with decompensated liver cirrhosis and explore the correlation with malnutrition and the risk factors of depressed mood.Methods:190 cirrhotic patients admitted to the Department of Gastroenterology of the First Hospital of Shanxi Medical University from June to September 2023 were selected according to the inclusion and exclusion criteria. Eligible patients were divided into subgroups based on the presence or absence of malnutrition as determined by subjective global assessment (SGA). The Center for Epidemiological Studies Depression (CES-D) scale was used to assess patients' propensity for depressed mood. Relevant clinical data were also collected and analyzed.Results:A total of 185 patients were included, of which 126 were in the non-malnutrition group and 59 malnutrition group. There were significant between-group differences in terms of CES-D results, age, body mass index, platelets, D-dimer, serum sodium, third lumbar skeletal muscle index, grip strength, triceps skinfold thickness, and upper arm muscle circumference (all P<0.05). Correlation analysis showed that grip strength, triceps skinfold thickness, upper arm muscle circumference, serum sodium, and depressed mood tendency status were correlated with the development of cirrhotic malnutrition ( P<0.05). The diagnostic model for malnutrition in cirrhosis using these five indicators showed the area under the curve of 81.9%. Conclusions:Depression is closely related to the development of malnutrition in patients with liver cirrhosis. Independent risk factors for malnutrition in cirrhosis include serum sodium≤135 mmol/L, grip strength, triceps skinfold thickness, lower-than-normal upper arm circumference , and the tendency of depression , which demonstrate the combined contribution to the diagnosis of malnutrition in cirrhosis.

Objective:To evaluate the value of the ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) in evaluating right ventricular function of patients with hypertrophic cardiomyopathy (HCM) and heart failure with preserved ejection fraction (HFpEF).Methods:A total of 74 patients with HCM and HFpEF and 22 healthy individuals who visited the First Affiliated Hospital of Zhengzhou University from January 2021 to January 2023 were included in this study. The HCM patients with HFpEF were divided into three groups based on the tertiles of the TAPSE/PASP (low group: <0.280 0 mm/mmHg; middle group: 0.280 0-0.476 2 mm/mmHg; high group: >0.476 2 mm/mmHg). Conventional echocardiographic parameters were collected, and two-dimensional speckle tracking technology was used to obtain right ventricular strain parameters. The differences in parameters among the groups were compared, and the correlations between TAPSE/PASP and clinical parameters and right ventricular function parameters were analyzed.Results:The results of difference analysis showed that there were significant differences in 6-minute walking test, New York Heart Association grade (NYHA grade), incidence of atrial fibrillation, left atrial area (LAA), left ventricular global longitudinal strain (LVGLS), TAPSE, PASP, right ventricular fractional area change (RVFAC), right ventricular global longitudinal strain (RVGLS), right ventricular free wall strain (RVFWST) and cardiac magnetic resonance right ventricular ejection fraction (CMR-RVEF) among the three groups. The results of correlation analysis and multiple linear regression analysis showed that the TAPSE/PASP was positively correlated with 6-minute walking distance, RVFAC, tricuspid annulus peak systolic velocity (RV s′), and CMR-RVEF ( r=0.449, 0.284, 0.358, 0.577; all P<0.05). It was negatively correlated with N-terminal pro-brain natriuretic peptide (NT-proBNP), NYHA grade, LAA, mitral early diastolic peak velocity / mitral annulus early diastolic peak velocity (LV E/e′), LVGLS, RVGLS, RVFWST and tricuspid early diastolic peak velocity / tricuspid annulus early diastolic peak velocity (RV E/e′) (r/ rs=-0.336, -0.349, -0.468, -0.452, -0.444, -0.339, -0.405, -0.320; all P<0.05). The LAA and CMR-RVEF correlated independently with TAPSE/PASP(all P<0.05). Conclusions:The TAPSE/PASP can provide an early, simple, rapid, and convenient evaluation of right ventricular function in patients with HCM and HFpEF, so as to guide clinical treatment and monitoring disease progression.

Objective:To understand the characteristics of sexual behaviors in the elderly aged ≥60 years and provide evidence for AIDS prevention and control in the elderly.Methods:Local residents who were aged ≥60 years and had lived in Yongchuan District of Chongqing for more than half a year were recruited by multi-stage sampling with a sample size of 2 721 from September to December 2022 for a face to face questionnaire survey to collect the information about their demographic characteristics, awareness of AIDS related knowledge and sexual behaviors, and the incidence of non-marital sexual behaviors. Multivariate logistic regression model was used to analyze related factors non-marital sexual behaviors in the elderly aged ≥60 years. SPSS 23.0 software was used for statistical analysis.Results:A total of 2 974 valid questionnaires were collected from 3 000 old persons aged ≥60 years, the male to female ratio of the elderly who returned the questionnaires was about 1∶1 (1 488∶1 486). The average age of them was (69.3± 7.0) years, and the awareness rate of AIDS related knowledge was 78.5% (2 336/2 974), 26.9% of them (801/2 974) had sexual behavior in the past year, 20.9% (493/2 350) of them had sexual behaviors with their spouses in the past year, and 10.8% (322/2 974) of them had non-marital sexual behaviors. The proportions of the elderly with commercial sexual behaviors and non-marital/non-commercial sexual behaviors were 10.2% (304/2 974) and 1.2% (36/2 974). The results of multivariate logistic regression analysis showed that being man (a OR=89.08, 95% CI: 36.30-218.60), age 70-79 years (a OR=1.93, 95% CI:1.44-2.59) and ≥80 years (a OR=2.41, 95% CI: 1.56-3.74), and unawareness of AIDS related knowledge (a OR=2.72, 95% CI: 2.04-3.64) were associated with the incidence of non-marital sex. Conclusions:The proportions of non-marital sexual behaviors were higher among the elderly aged ≥60 years in Yongchuan District of Chongqing. It is necessary to pay attention to the sexual needs and sexual health of the population, improve the awareness rate of AIDS prevention and treatment knowledge, advocate safe sex, and improve the sexual health and quality of life in the elderly.

Pulmonary fibrosis(PF)is a chronic progressive end-stage lung disease.However,the mechanisms un-derlying the progression of this disease remain elusive.Presently,clinically employed drugs are scarce for the treatment of PF.Hence,there is an urgent need for developing novel drugs to address such diseases.Our study found for the first time that a natural source of Prismatomeris connata Y.Z.Ruan(Huang Gen,HG)ethyl acetate extract(HG-2)had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic(TGF-β1/Smad)pathway.Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation,cellular response to reactive oxygen species,and extracellular matrix(ECM)disassembly.Moreover,mass spec-trometry imaging(MSI)was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2,which was related to arginine biosyn-thesis and alanine,asparate and glutamate metabolism,the downregulation of arachidonic acid meta-bolism,and the upregulation of glycerophospholipid metabolism.In conclusion,we elaborated on the relationship between metabolite distribution and the progression of PF,constructed the regulatory metabolic network of HG-2,and discovered the multi-target therapeutic effect of HG-2,which might be conducive to the development of new drugs for PF.