Energy metabolism in the context of erythropoiesis and related diseases remains largely unexplored. Here, we developed a primary cell model by differentiating hematopoietic stem progenitor cells toward the erythroid lineage and suppressing the mitochondrial oxidative phosphorylation (OXPHOS) pathway. OXPHOS suppression led to differentiation failure of erythroid progenitors and defects in ribosome biogenesis. Ran GTPase-activating protein 1 (RanGAP1) was identified as a target of mitochondrial OXPHOS for ribosomal defects during erythropoiesis. Overexpression of RanGAP1 largely alleviated erythroid defects resulting from OXPHOS suppression. Coenzyme Q10, an activator of OXPHOS, largely rescued erythroid defects and increased RanGAP1 expression. Patients with Diamond-Blackfan anemia (DBA) exhibited OXPHOS suppression and a concomitant suppression of ribosome biogenesis. RNA-seq analysis implied that the substantial mutation (approximately 10%) in OXPHOS genes accounts for OXPHOS suppression in these patients. Conclusively, OXPHOS disruption and the associated disruptive mitochondrial energy metabolism are linked to the pathogenesis of DBA.

INTRODUCTION: During normal pregnancy, changes in the gut microbiota (GM) in response to physiological alterations in hormonal secretion, immune functions and homeostasis have received extensive attention. However, the dynamic changes in the GM during three consecutive trimesters of pregnancy and their relationship with glucose and lipid metabolism have not been reported. In this study, we aimed to investigate the dynamic changes in the diversity and species of the GM during three consecutive trimesters in women who naturally conceived, and their relationships with abnormal fasting blood glucose (FBG) and serum lipid levels.; METHODS: A total of 30 pregnant women without any known chronic or autoimmune inflammatory disease history before pregnancy were enrolled during the first trimester. Serum and stool samples were collected during the first trimester, the second trimester, and the third trimester. Serum samples were tested for FBG and blood lipid levels, and stool specimens were analyzed by 16S rDNA sequencing.; RESULTS: The abundance ratio of bacteroidetes/firmicutes showed an increasing tendency in most of the subjects (19/30, 63.3%) from the first to the third trimester. LEfSe analysis showed that the abundance of Bilophila was significantly increased from the first to the third trimester. In addition, at the genus level, the increased relative abundance of Mitsuokella, Clostridium sensu stricto and Weissella were potentially involved in the development of high FBG during pregnancy. The raised relative abundance of Corynebacterium, Rothia and Granulicatella potentially contributed to the occurrence of dyslipidemia during pregnancy.; CONCLUSIONS: There are dynamic changes in the GM during the three trimesters, and the alterations in some bacterium abundance may contribute to the development of high FBG and dyslipidemia during pregnancy. Monitoring enterotypes and correcting dysbiosis in the first trimester may become new strategies for predicting and preventing glucolipid metabolism disorders during pregnancy. © 2024. The Author(s).

Background and AimDiet is a major contributor to irritable bowel syndrome (IBS) and is also a powerful tool for treatment of IBS. This study compared two diets and explored the effectiveness of the diets when combined with a probiotic for treatment of IBS-D patients. MethodsPhase I, patients were randomized into groups; control, cold/spicy/fried restricted diet (CSF res diet), IgG positive restricted diet (IgG res diet), and a combination both diets (CSF + IgG res diet). Phase II, patients were randomized into IgG res diet + placebo and IgG res diet + probiotic. Both interventions were 12 weeks in duration. Symptom Severity Scale (IBS-D-SSS) and IgG titer were assessed at the beginning and the end of the study. ResultsTotals of 214 and 167 patients completed the two parts of the study, respectively. After intervention, IBS-D-SSS and TIgG grade were significantly improved compared to baseline, with results similar to the control group. In general, there were decreases in IBS-D-SSS and TIgG grade that were significantly different among the groups. There were exceptions; no differences were observed for IBS-D-SSS between the IgG res diet and CSF + IgG res diet, or TIgG grade between the CSF res diet, IgG res diet, and CSF + IgG res diet. However, the CSF res diet and IgG res diet had a synergistic effect that decreased IBS-D-SSS and TIgG titer, with a greater contribution by the IgG res diet. Therefore, we evaluated the IgG res diet with either placebo or probiotic and found that IBS-D-SSS and TIgG grade decreased from baseline. There was a significant decrease in IBS-D-SSS with the probiotic but TIgG grade was not significantly different between the IgG diet + placebo and IgG diet + probiotic diet. ConclusionsBoth the CSF res diet and IgG res diet improved IBS symptoms and demonstrated synergy, although the IgG res diet had a greater contribution. Further, when intolerant foods cannot be eliminated from a diet, avoiding uncooked, cold, spicy, fried, and alcoholic foods is a superior choice. The IgG res diet combined with Bifidobacteria was the best dietary choice and may function though a non-IgG pathway.

ObjectivesTo determine the incremental diagnostic value of radiomics signature of pericoronary adipose tissue (PCAT) in addition to the coronary artery stenosis and plaque characters for detecting hemodynamic significant coronary artery disease (CAD) based on coronary computed tomography angiography (CCTA).MethodsIn a multicenter trial of 262 patients, CCTA and invasive coronary angiography were performed, with fractional flow reserve (FFR) in 306 vessels. A total of 13 conventional quantitative characteristics including plaque characteristics (N = 10) and epicardial adipose tissue characteristics (N = 3) were obtained. A total of 106 radiomics features depicting the phenotype of the PCAT surrounding the lesion were calculated. All data were randomly split into a training dataset (75%) and a testing dataset (25%). Then three models (including the conventional model, the PCAT radiomics model, and the combined model) were established in the training dataset using multivariate logistic regression algorithm based on the conventional quantitative features and the PCAT radiomics features after dimension reduction.ResultsA total of 124/306 vessels showed functional ischemia (FFR <= 0.80). The radiomics model performed better in discriminating ischemia from non-ischemia than the conventional model in both training (area under the receiver operating characteristic (ROC) curve (AUC): 0.770 vs 0.732, p < 0.05) and testing datasets (AUC: 0.740 vs 0.696, p < 0.05). The combined model showed significantly better discrimination than the conventional model in both training (AUC: 0.810 vs 0.732, p < 0.05) and testing datasets (AUC: 0.809 vs 0.696, p < 0.05).ConclusionsThe PCAT radiomics model showed good performance in predicting myocardial ischemia. Addition of PCAT radiomics to lesion quantitative characteristics improves the predictive power of functionally relevant CAD.

Plant-based diets are recommended for cancer survivors; however, their effects on lung cancer mortality are limited. We conducted this study to evaluate the association between plant-based dietary patterns and lung cancer mortality. A total of 408 newly diagnosed lung cancer patients aged 18 to 79 years were enrolled in the study. Dietary intake was assessed using a validated 111-item food frequency questionnaire (FFQ). The survival status was confirmed by medical records and an active follow-up until March 31, 2023. We calculated three dietary indices: the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI). Cox proportional hazards regression models were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of plant-based indices with lung cancer mortality. During the follow-up period (median: 40.97 months; interquartile: 29.77-45.63 months), 240 patients died from lung cancer. An inverse association was observed between hPDI scores and lung cancer mortality (Q4 vs. Q1, HR, 0.66, 95% CI, 0.45-0.97, the P value for trend, 0.042), while each 10-unit increment was associated with a decreased risk of lung cancer mortality (HR, 0.75; 95% CI, 0.57-0.99). Regarding PDI and uPDI, no significant association was found with lung cancer mortality. Our study suggests that adherence to a diet with a high hPDI score may reduce lung cancer mortality. © 2023 The Royal Society of Chemistry.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF), affected collectively by genetic and environmental factors, is the common subtype of chronic heart failure. Although the available risk assessment methods for HFpEF have achieved some progress, they were based on clinical or genetic features alone. Here, we have developed a deep learning framework, HFmeRisk, using both 5 clinical features and 25 DNA methylation loci to predict the early risk of HFpEF in the Framingham Heart Study Cohort.; RESULTS: The framework incorporates Least Absolute Shrinkage and Selection Operator and Extreme Gradient Boosting-based feature selection, as well as a Factorization-Machine based neural network-based recommender system. Model discrimination and calibration were assessed using the AUC and Hosmer-Lemeshow test. HFmeRisk, including 25 CpGs and 5 clinical features, have achieved the AUC of 0.90 (95% confidence interval 0.88-0.92) and Hosmer-Lemeshow statistic was 6.17 (P=0.632), which outperformed models with clinical characteristics or DNA methylation levels alone, published chronic heart failure risk prediction models and other benchmark machine learning models. Out of them, the DNA methylation levels of two CpGs were significantly correlated with the paired transcriptome levels (R<-0.3, P<0.05). Besides, DNA methylation locus in HFmeRisk were associated with intercellular signaling and interaction, amino acid metabolism, transport and activation and the clinical variables were all related with the mechanism of occurrence of HFpEF. Together, these findings give new evidence into the HFmeRisk model.; CONCLUSION: Our study proposes an early risk assessment framework for HFpEF integrating both clinical and epigenetic features, providing a promising path for clinical decision making. © 2022. The Author(s).

目的：探讨蒙古族聚居区内儿童青少年膳食模式与近视发生的关系，为近视预防在饮食方面提供针对性建议。方法：采用整群抽样的方法抽取内蒙古锡林郭勒盟阿巴嘎旗与正镶白旗10所中小学校的全体4 684名学生作为调查对象，进行问卷调查和身体健康检查。通过膳食频率法获得调查对象近1年内摄入各种食物的频率以及摄入量。采用因子分析法提取膳食模式，并通过Logistic回归分析探讨近视发生风险与膳食模式的相关性。结果：锡林郭勒盟近视患病率为51.53%,中学高于小学，女生高于男生，汉族高于蒙古族和其他民族（P均＜0.05）。该蒙古族聚居地中小学生存在4种膳食模式，分别为蔬菜豆制品膳食模式、主食禽肉膳食模式、饮料甜食膳食模式、蒙古族传统膳食模式。矫正混杂因素后Logistic回归分析结果显示，蒙古族传统膳食模式与近视患病风险呈负相关（OR=0.746,P＜0.05）。结论：锡林郭勒盟中小学生总体近视患病率接近全国水平，提示要继续开展学校近视预防保健工作。蒙古族传统膳食模式与近视存在一定关系，可以考虑从饮食方面进行干预以降低青少年近视发生风险。

BackgroundThe intake of ultra-processed foods (UPFs) has increased rapidly in recent years. Evidence has suggested that UPFs has adverse effects on several health outcomes. This study aimed to first evaluate the association between the intake of UPFs and asthenozoospermia odds. MethodsA hospital-based case-control study including 549 cases and 581 controls was performed in the infertility clinics of Shengjing Hospital of China Medical University from June 2020 to December 2020. Dietary intake was assessed using a validated food frequency questionnaire. Food items were categorized by the NOVA classification system based on the degree of processing. Semen parameters were analyzed according to the World Health Organization guidelines. ResultsThe highest tertile of UPFs intake (% of total energy intake) was positively associated with the odds of asthenozoospermia (odds ratio [OR] = 1.53; 95% confidence interval [CI]: 1.12, 2.10; P for trend < 0.05), compared with the lowest tertile. Similar patterns were also found in subgroup analyses among participants with age >= 32 years (OR = 1.58; 95% CI: 1.04, 2.40), BMI >= 24 kg/m(2) (OR = 1.52; 95% CI: 1.04, 2.22), ever cigarette smoking (OR = 1.78; 95% CI: 1.14, 2.79), and ever alcohol drinking (OR = 1.65; 95% CI: 1.01, 2.72), and in sensitivity analyses by using absolute amount (g/day) to calculate the intake of UPFs. ConclusionHigher consumption of UPFs was positively associated with the odds of asthenozoospermia. More studies are needed to confirm our findings.

Sleep has been related to a variety of health outcomes. However, no association between sleep and asthenozoospermia has been reported. The aim of this study is to first investigate the relationship between sleep status and asthenozoospermia risk. A case-control study, including 540 asthenozoospermia cases and 579 controls, was performed from June 2020 to December 2020 in the infertility clinic from Shengjing Hospital of China Medical University. Data on sleep status were collected by Pittsburgh sleep quality index questionnaires and asthenozoospermia was diagnosed based on the World Health Organization guidelines. Odds ratio (OR) with 95% confidence interval (95% CI) was calculated by logistic regression analysis to assess the aforementioned association. Results of this study demonstrated that compared with total sleep duration of 8-9 h/day, < 8 h/day was related to asthenozoospermia risk (OR: 1.44, 95% CI: 1.05-1.99); compared to good sleep quality, poor sleep quality was associated with asthenozoospermia risk (OR: 1.35; 95% CI: 1.04-1.77). There were multiplicative model interaction effects between sleep quality and tea drinking (p = 0.04), rotating night shift work (p < 0.01) on asthenozoospermia risk. However, we failed to detect any associations between night sleep duration, daytime napping duration, night bedtime, wake-up time, sleep pattern and asthenozoospermia risk. In conclusion, short total sleep duration and poor sleep quality might be related to asthenozoospermia risk. Further well-designed prospective studies are warranted to confirm our findings.

Epidemiological studies have suggested that dietary acid load (DAL) might be related to the risk and prognosis of cancer, whereas the evidence is contentious. Several high-quality observational studies have been published following a prior systematic review with only one study included. Consequently, we conducted an updated systematic review and meta-analysis to comprehensively investigate the relationship between DAL and cancer risk and prognosis. A systematic literature search was conducted in the PubMed, Embase, and Web of Science databases from inception to 26 October 2021. Summary relative risks (RRs) with 95% CIs were calculated using a random-effects model. Publication bias, subgroup, meta-regression, and sensitivity analyses were also conducted. Ten observational studies (six cohorts and four case-control studies) with 227,253 participants were included in this systematic review and meta-analysis. The summary RRs revealed a statistically significant associations between DAL and cancer risk (RR = 1.58, 95% CI = 1.23-2.05, I-2 = 71.9%, n = 7) and prognosis (RR = 1.53, 95% CI = 1.10-2.13, I-2 = 77.1%, n = 3). No evidence of publication bias was observed in the current analysis. Positive associations were observed in most subgroup analyses stratified by predefined factors, including region, study design, study quality, study population, participants' gender, age of participants, cancer type, DAL assessment indicator, and adjustment of potential confounding parameters. No evidence of heterogeneity between subgroups was indicated by meta-regression analyses. The high DAL might be associated with an increased risk of cancer, as well as a poor prognosis of cancer. More high-quality prospective studies are warranted to further determine the associations between DAL and risk and prognosis for specific cancers.