Mitochondria are highly dynamic organelles capable of altering their sizes and shapes to maintain metabolic balance through coordinated fission and fusion processes. In various cancer types, mitochondrial hyperfragmentation has been frequently observed, contributing to the progression of cancer toward metastasis. Inverted formin 2 (INF2), which resides in the endoplasmic reticulum (ER), has been found to accelerate actin polymerization and drive mitochondrial fission. In this study, we demonstrate that INF2 expression is significantly upregulated in endometrial cancer (EC) and is associated with a poor prognosis in EC patients. INF2 promotes anchorage-dependent and independent EC cell growth in part by facilitating mitochondrial fission. Furthermore, in conditions of energy stress, AMP-activated protein kinase (AMPK) phosphorylates INF2 at Ser1077, leading to increased localization of INF2 to the ER and enhanced recruitment of the dynamin-related protein 1 (DRP1) to mitochondria. This AMPK-mediated phosphorylation of INF2 at Ser1077 facilitates mitochondrial division and promotes EC cell growth. Pathological examination using immunohistochemical analyses revealed a positive correlation between AMPK activity and phosphorylated INF2 (Ser1077) in EC specimens. Collectively, our findings uncover novel molecular mechanisms involving the AMPK-INF2 axis, which regulates mitochondrial dynamics and malignant cell growth in EC.

Objectives: Intrauterine malnutrition has a long-term effect on respiratory and lung function. However, few studies have explored the association between early-life exposure to famine with asthma and chronic obstructive pulmonary disease (COPD) in adulthood. Therefore, we aimed to investigate the association of early-life exposure to the Chinese famine of 1959–1962 with asthma and COPD later in life. Methods: This national population-based study included 6,771 participants from the baseline survey of the China Health and Retirement Longitudinal Study (CHARLS) who were born around the time of the Chinese famine. The famine exposure groups were determined according to the participants' birth year as non-exposed (1964–1967), fetal-exposed (1959–1962), preschool-exposed (1954–1957), and school-age exposed (1950–1953). Information about the demographic characteristics, self-reported doctor-diagnosed asthma and COPD, behavior and lifestyles, and indoor pollution were collected using validated questionnaires. In addition, peak expiratory flow (PEF) was measured to assess pulmonary function. Multivariable logistic regression and generalized linear mixed models were performed to explore the risk of adult asthma and COPD, PEF changes during various famine exposure periods compared with the non-exposed group. Stratified and sensitivity analyses were conducted to examine the modification and robustness of the association. Results: The prevalence of doctor-diagnosed asthma and COPD was 2.8 and 8.1%, respectively. Compared with the non-exposed group, the risk was significantly higher in the fetal-exposed group for asthma [adjusted odds ratio, (aOR) = 1.87, 95% confidence interval (CI):1.14–3.07] and the school-age exposed group [1.30 (1.00–1.69)] for COPD after controlling for confounders. Furthermore, we observed that fetal exposure to famine was significantly associated with a decrement of PEF in adulthood [β = −11.38 (−22.75 to −0.02)] compared with the non-exposed group. Stratified analyses showed that the association of asthma was stronger in men, who resided in severely famine-affected areas, smoked, and used solid fuels for cooking. No clearly consistent association was observed for subsequent COPD. Conclusions: Our results suggest that fetal exposure to the Chinese famine is significantly associated with the increased risk of asthma in adulthood. Future prospective studies are warranted to examine the association and mechanisms.

Background: Environmental factors, including air pollution, can strongly impact on spatio-temporal patterns of infectious diseases outbreak. In this study, we aimed to investigate the association and correlation between ambient air pollutants and case fatality rate (CFR) of the novel coronavirus disease (COVID-19) in China. Methods: Publicly accessible data on COVID-19 average CFR were utilized in the data analysis. The ambient daily air pollutants including fine particulate matter (PM _2.5 ), inhalable particles (PM ₁₀ ) and nitrogen dioxide (NO ₂ ) during the period from December 25, 2019 to March 5, 2020 were obtained from National Air Quality Real-time Publishing System of China. Ecological analysis was performed to explore the association and correlation between the cumulative average exposure of ambient air pollutants at different lag days (14 and 28 days) and average CFR in China outside Hubei and cities in Hubei province via model fitting. Results: The average case fatality rate was highest in Wuhan city (4.53%) and the cumulative average exposure of ambient PM _2.5 , PM ₁₀ and NO ₂ at lag 28 days was 55.8±12.1μg/m ³ , 66.8±9.2μg/m ³ , 20.7±4.4μg/m ³ , respectively in Hubei province during the study period. Ecological analysis showed that ambient PM _2.5 , PM ₁₀ and NO ₂ exposure at both lag 14 and 28 days was positively correlated with average CFR in China outside Hubei (province-level). For city-level analysis in Hubei, significant associations were only found between cumulative ambient NO ₂ exposure and average CFR(r=0.693 for Lag0-14, r=0.697 for Lag0-28, respectively) during the same period. Conclusion: Our findings suggested ambient PM _2.5 , PM ₁₀ and NO ₂ exposure, especially at 28 lag days, positively associated with the case fatality rate of COVID-19 in China. These results could help provide guidance for identifying potential exposure window and preventing and controlling the epidemic.

Objective To investigate differential associations of traditional and novel adiposity indices with visual impairment (VI) in the middle-aged and older Chinese population. Methods and analysis Based on the China Health and Retirement Longitudinal Study, 7750 Chinese older adults aged over 45 were included at baseline 2011, and 4133 participants who accomplished all three interviews from 2011 to 2015 were adapted for longitudinal analyses. We enrolled six adiposity indices, including the body mass index (BMI), waist-to-height ratio (WHtR), weight-adjusted-waist index (WWI), a body shape index (ABSI), body roundness index (BRI) and conicity index (ConI). Visual status and other covariates included sociodemographic characteristics, medical supports and lifestyle-related factors. Cross-sectional correlations were assessed using univariate and multivariate logistic regression analyses. For longitudinal analysis, generalised linear models with generalised estimating equations were used to determine the association between time-varying adiposity and visual status. Results Higher levels of WHtR/WWI/ABSI/BRI/ConI were significantly associated with an increased prevalence of VI, whereas a higher BMI was associated with a decreased prevalence of VI. Only WWI was significantly related to the prevalence of VI after adjustment for multiple confounders in both cross-sectional and longitudinal analyses (all p values <0.05). The multivariable-adjusted OR (95% CI) of VI associated with the highest (vs lowest) quintile of WWI was 1.900 (1.407 to 2.565). Conclusion WWI is a reliable alternative adiposity index that exhibits a dose–response association with the prevalence of VI in the Chinese population. The WWI-VI correlation may eliminate the obesity paradox in the ophthalmic epidemiological area and indicate the detrimental impact of changes in body composition on VI.