Untargeted metabolomics reveals that declined PE and PC in obesity may be associated with prostate hyperplasia

by Guorui Fan, Xiaohai Guan, Bo Guan, Hongfei Zhu, Yongchao Pei, Chonghao Jiang, Yonggui Xiao, Zhiguo Li, Fenghong Cao

Background

Recent studies have shown that obesity may contribute to the pathogenesis of benign prostatic hyperplasia (BPH). However, the mechanism of this pathogenesis is not fully understood.

Methods

A prospective case–control study was conducted with 30 obese and 30 nonobese patients with BPH. Prostate tissues were collected and analyzed using ultra performance liquid chromatography ion mobility coupled with quadrupole time-of-flight mass spectrometry (UPLC-IMS-Q-TOF).

Results

A total of 17 differential metabolites (3 upregulated and 14 downregulated) were identified between the obese and nonobese patients with BPH. Topological pathway analysis indicated that glycerophospholipid (GP) metabolism was the most important metabolic pathway involved in BPH pathogenesis. Seven metabolites were enriched in the GP metabolic pathway. lysoPC (P16:0/0:0), PE (20:0/20:0), PE (24:1(15Z)/18:0), PC (24:1(15Z)/14:0), PC (15:0/24:0), PE (24:0/18:0), and PC (16:0/18:3(9Z,12Z,15Z)) were all significantly downregulated in the obesity group, and the area under the curve (AUC) of LysoPC (P-16:0/0/0:0) was 0.9922. The inclusion of the seven differential metabolites in a joint prediction model had an AUC of 0.9956. Thus, both LysoPC (P-16:0/0/0:0) alone and the joint prediction model demonstrated good predictive ability for obesity-induced BPH mechanisms.

Conclusions

In conclusion, obese patients with BPH had a unique metabolic profile, and alterations in PE and PC in these patients be associated with the development and progression of BPH.

Metabolomic signature between diabetic and non-diabetic obese patients: A protocol for systematic review

by Yuxing Tai, Xiaoqian Yang, Xiaochao Gang, Zhengri Cong, Sixian Wang, Peizhe Li, Mingjun Liu

Background

Type 2 diabetes mellitus (T2DM) is a chronic and progressive condition defined by hyperglycemia caused by abnormalities in insulin production, insulin receptor sensitivity, or both. Several studies have revealed that higher body mass index (BMI) is associated with increasing risk of developing diabetes. In this study, we perform a protocol for systematic review to explore metabolite biomarkers that could be used to identify T2DM in obese subjects.

Methods

The protocol of this review was registered in PROSPERO (CRD42023405518). Three databases, EMBASE, PubMed, and Web of Science were selected to collect potential literature from their inceptions to July December 2023. Data for collection will include title, authors, study subjects, publication date, sample size, detection and analytical platforms, participant characteristics, biological samples, confounding factors, methods of statistical analysis, the frequency and directions of changes in potential metabolic biomarkers, and major findings. Pathway analysis of differential metabolites will be performed with MetaboAnalyst 5.0 based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Human Metabolome Database.

Results

The results of this systematic review will be published in a peer-reviewed journal.

Conclusion

This systematic review will summarize the potential biomarkers and metabolic pathways to provide a new reference for the prevention and treatment of T2DM in obese subjects.

Effect of probiotics or prebiotics on thyroid function: A meta-analysis of eight randomized controlled trials

by Qinxi Shu, Chao Kang, Jiaxin Li, Zhenzhu Hou, Minfen Xiong, Xingang Wang, Hongyan Peng

Background

Microbiome-directed therapies are increasingly utilized to optimize thyroid function in both healthy individuals and those with thyroid disorders. However, recent doubts have been raised regarding the efficacy of probiotics, prebiotics, and synbiotics in improving thyroid function. This systematic review aimed to investigate the potential relationship between probiotics/prebiotics and thyroid function by analyzing the impact on thyroid hormone levels.

Methods

We conducted a comprehensive systematic review and meta-analysis of randomized controlled trials that investigated the effects of probiotics, prebiotics, and synbiotics on free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroid stimulating hormone receptor antibody (TRAb) levels. We searched for articles from PubMed, Scopus, Web of Science, and Embase up until April 1st, 2023, without any language restriction. Quantitative data analysis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval as summary statistics. The methods and results were reported according to the PRISMA2020 statement.

Results

A total of eight articles were included in this review. The meta-analysis showed no significant alterations in TSH (SMD: -0.01, 95% CI: −0.21, 0.20, P = 0.93; I²: 0.00%), fT4 (SMD: 0.04, 95% CI: −0.29, 0.21, P = 0.73; I²: 0.00%) or fT3 (SMD: 0.45, 95% CI: −0.14, 1.03, P = 0.43; I²: 78.00%), while a significant reduction in TRAb levels was observed (SMD: -0.85, 95% CI: -1.54, -0.15, P = 0.02; I²: 18.00%) following probiotics/prebiotics supplementation. No indication of publication bias was found.

Conclusions

Probiotics/prebiotics supplementation does not influence thyroid hormone levels, but may modestly reduce TRAb levels in patients with Graves’ disease.

Dynamic asymmetric spillovers and connectedness between Chinese sectoral commodities and industry stock markets

by Yu Lou, Chao Xiao, Yi Lian

This study investigates the dynamic and asymmetric propagation of return spillovers between sectoral commodities and industry stock markets in China. Using a daily dataset from February 2007 to July 2022, we employ a time-varying vector autoregressive (TVP-VAR) model to examine the asymmetric return spillovers and dynamic connectedness across sectors. The results reveal significant time-varying spillovers among these sectors, with the industry stocks acting as the primary transmitter of information to the commodity market. Materials, energy, and industrials stock sectors contribute significantly to these spillovers due to their close ties to commodity production and processing. The study also identifies significant asymmetric spillovers with bad returns dominating, influenced by major economic and political events such as the 2008 global financial crisis, the 2015 Chinese stock market crisis, the COVID-19 pandemic, and the Russia-Ukraine war. Furthermore, our study highlights the unique dynamics within the Chinese market, where net information spillovers from the stock market to commodities drive the financialization process, which differs from the bidirectional commodity financialization observed in other markets. Finally, portfolio analysis reveals that the minimum connectedness portfolio outperforms other approaches and effectively reflects asymmetries. Understanding these dynamics and sectoral heterogeneities has important implications for risk management, policy development, and trading practices.

Relationship between methods of monitoring training load and physiological indicators changes during 4 weeks cross-country skiing altitude training

by Yichao Yu, Dongye Li, Yifan Lu, Jing Mi

This study aimed to: (i) analyze the load characteristics of 4 weeks cross-country skiing altitude training; (ii) analyze the relationships between methods of monitoring training load and physiological indicators changes of elite male Chinese cross-country skiers during this period. Practitioners collected load data during 4 weeks of altitude training camp. Participants performed maximal oxygen uptake, lactate threshold, body composition, and skierg power test before and after the training camp to investigate the changes in physiological performance. Edwards TRIMP, Lucia TRIMP, and session rating of perceived exertion were collected as internal load. Training distance, time recorded by the Catapult module were collected as external load. The result revealed a " pyramid " pattern in the load characteristics during the altitude training camp. The correlation between luTRIMP and percent change in physiological indicators was highest. Percentage changes in lactate threshold velocity (r = .78 [95% CI -.01 to .98]), percentage changes in lactate threshold HR (r = .71 [95% CI .14- .99]), percentage changes in maximum HR (r = .83 [95% CI .19–1.00]), percentage changes in skierg power-to-weight ratio (r = .75 [95% CI -.28 to .98]) had very large relationships with luTRIMP. In cross-country skiing altitude training, training loads should be reasonably controlled to ensure that athletes do not become overly fatigued. Methods of training load monitoring that combine with athletes’ physiological characteristics and program characteristics have the highest dose-response relationships, it is an important aspect of cross-country ski training load monitoring. The luTRIMP could be a good monitoring tool in cross-country skiing altitude training.

Landscape changes and livelihood outcomes in rural tea farming communities: A case study in Fuding City, Fujian Province, Southeast China

by Chengchao Wang, Xianqiang Song, Dongshen Luo, Xu Dan, Tingting Lin

Landscape changes driven by cash crop plantations have been prevalent in tropical and subtropical regions worldwide in recent decades. Investigating the landscape changes and concluding livelihood outcomes are fundamental to figure out the solutions for rural sustainability. This paper examined the landscape changes which was caused by land use changes in tea plantations as well as investigated the resultant livelihood impacts, based on a case study in Fuding City, Southeast China. A questionnaire survey of 114 rural households in four sampled villages was conducted. Results demonstrated that expansion and intensification of tea plantations were two major proximate causes of landscape changes in recent decade. Our survey indicated that some existing intensively-managed tea plantations had derived from intensification and expansion of tea plantations, respectively. We identified four underlying driving forces of landscape changes, including economic benefit, governmental policies, wildlife destruction on grain crops, and rural return migration. Our study confirmed that landscape changes have significant positive effects on farmers’ livelihoods, including increasing employment and incomes, raising living standards, enhancing livelihood assets and livelihood sustainability. Especially, the aged rural populations could have a relatively decent living standard. Meanwhile, the excessive expansion of tea plantations may impair livelihood resilience. Lastly, three policy suggestions based on different time scales have been put forward to promote rural households’ livelihood sustainability and resilience.

Exploring the motivations for rural tourism in China during the COVID-19: The existence of a single motivation

by Songting Zhang, Yichao Wu, Wen Bao

The COVID-19 epidemic had an appropriate impact on tourists’ trip psychology and their subsequent behavior in participating in rural tourism activities. The purpose of this paper is to explore the types of motivations Chinese tourists have for participating in rural tourism in the context of COVID-19, and to comparatively analyze the similarities and differences in motivations for rural tourism during the epidemic and in normal times. An interpretive paradigm qualitative data collection method was used: semi-structured interviews and focus group discussions. Respondents were 21 tourists, who were selected through purposive and snowball sampling. Through content analysis, we found that rural tourism motivations during the epidemic included both diversified and singular motivations. The pull effect of rural destinations is related to distance and ease of realization. For rural areas in close proximity, a single motivation is sufficient to drive tourists. In addition, we found that there was no "altruistic motivation" for rural tourism during the COVID-19 period, but "altruistic feelings" for the preservation of ancient villages were generated during rural tourism. Finally, we discuss the theoretical and practical significance of this study and make suggestions for future research. The study explains tourists’ companionship preferences, activity choices, and affective changes, and provides a basis for the operation and advertising strategies of rural destinations to attract tourists and promote their sustainable development.

Traumatic brain injury and risk of heart failure and coronary heart disease: A nationwide population-based cohort study

by Ching-Hui Huang, Chao-Tung Yang, Chia-Chu Chang

Background

This study examined the long-term risks of heart failure (HF) and coronary heart disease (CHD) following traumatic brain injury (TBI), focusing on gender differences.

Methods

Data from Taiwan’s National Health Insurance Research Database included 29,570 TBI patients and 118,280 matched controls based on propensity scores.

Results

The TBI cohort had higher incidences of CHD and HF (9.76 vs. 9.07 per 1000 person-years; 4.40 vs. 3.88 per 1000 person-years). Adjusted analyses showed a significantly higher risk of HF in the TBI group (adjusted hazard ratio = 1.08, 95% CI = 1.01–1.17, P = 0.031). The increased CHD risk in the TBI cohort became insignificant after adjustment. Subgroup analysis by gender revealed higher HF risk in men (aHR = 1.14, 95% CI = 1.03–1.25, P = 0.010) and higher CHD risk in women under 50 (aHR = 1.32, 95% CI = 1.15–1.52, P Conclusion

Our results suggest that TBI increases the risk of HF and CHD in this nationwide cohort of Taiwanese citizens. Gender influences the risks differently, with men at higher HF risk and younger women at higher CHD risk. Beta-blockers have a neutral effect on HF and CHD risk.

Prime editing-mediated correction of the <i>CFTR</i> W1282X mutation in iPSCs and derived airway epithelial cells

by Chao Li, Zhong Liu, Justin Anderson, Zhongyu Liu, Liping Tang, Yao Li, Ning Peng, Jianguo Chen, Xueming Liu, Lianwu Fu, Tim M. Townes, Steven M. Rowe, David M. Bedwell, Jennifer Guimbellot, Rui Zhao

A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of nonsense CFTR mutations via genomic editing represents a promising therapeutic approach. In this study, we tested whether prime editing, a novel CRISPR-based genomic editing method, can be a potential therapeutic modality to correct nonsense CFTR mutations. We generated iPSCs from a CF patient homozygous for the CFTR W1282X mutation. We demonstrated that prime editing corrected one mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. We further demonstrated that prime editing may directly repair mutations in iPSC-derived airway epithelial cells when the prime editing machinery is efficiently delivered by helper-dependent adenovirus (HDAd). Together, our data demonstrated that prime editing may potentially be applied to correct CFTR mutations such as W1282X.

Long non-coding RNA SNHG17 may function as a competitive endogenous RNA in diffuse large B-cell lymphoma progression by sponging miR-34a-5p

by Shengjuan Lu, Lin Zeng, Guojun Mo, Danqing Lei, Yuanhong Li, Guodi Ou, Hailian Wu, Jie Sun, Chao Rong, Sha He, Dani Zhong, Qing Ke, Qingmei Zhang, Xiaohong Tan, Hong Cen, Xiaoxun Xie, Chengcheng Liao

We investigated the functional mechanism of long non-coding small nucleolar host gene 17 (SNHG17) in diffuse large B-cell lymphoma (DLBCL). lncRNAs related to the prognosis of patients with DLBCL were screened to analyze long non-coding small nucleolar host gene 17 (SNHG17) expression in DLBCL and normal tissues, and a nomogram established for predicting DLBCL prognosis. SNHG17 expression in B-cell lymphoma cells was detected using qPCR. The effects of SNHG17 with/without doxorubicin on the proliferation and apoptosis of DoHH2 and Daudi were detected. The effects of combined SNHG17 and doxorubicin were analyzed. The regulatory function of SNHG17 in DLBCL was investigated using a mouse tumor xenotransplantation model. RNA sequencing was used to analyze the signaling pathways involved in SNHG17 knockdown in B-cell lymphoma cell lines. The target relationships among SNHG17, microRNA, and downstream mRNA biomolecules were detected. A higher SNHG17 level predicted a lower survival rate. SNHG17 was highly expressed in DLBCL patient tissues and cell lines. We established a prognostic model containing SNHG17 expression, which could effectively predict the overall survival rate of DLBCL patients. SNHG17 knockdown inhibited the proliferation and induced the apoptosis of B-cell lymphoma cells, and the combination of SNHG17 and doxorubicin had a synergistic effect. SNHG17, miR-34a-5p, and ZESTE gene enhancer homolog 2 (EZH2) had common hypothetical binding sites, and the luciferase reporter assay verified that miR-34a-5p was the direct target of SNHG17, and EZH2 was the direct target of miR-34a-5p. The carcinogenic function of SNHG17 in the proliferation and apoptosis of DLBCL cells was partially reversed by a miR-34a-5p inhibitor. SNHG17 increases EZH2 levels by inhibiting miR-34a-5p. Our findings indicate SNHG17 as critical for promoting DLBCL progression by regulating the EZH2 signaling pathway and sponging miR-34a-5p. These findings provide a new prognostic marker and therapeutic target for the prognosis and treatment of DLBCL.

Identification and validation of aging-related genes in atrial fibrillation

by Yong Zhou, Chao Sun, Yingxu Ma, Yunyin Huang, Keke Wu, Shengyuan Huang, Qiuzhen Lin, Jiayi Zhu, Zuodong Ning, Ningyuan Liu, Tao Tu, Qiming Liu

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the clinic. Aging plays an essential role in the occurrence and development of AF. Herein, we aimed to identify the aging-related genes associated with AF using bioinformatics analysis. Transcriptome profiles of AF were obtained from the GEO database. Differential expression analysis was performed to identify AF-specific aging-related genes. GO and KEGG enrichment analyses were performed. Subsequently, the LASSO, SVM-RFE, and MCC algorithms were applied to screen aging-related genes. The mRNA expression of the screened genes was validated in the left atrial samples of aged rapid atrial pacing-induced AF canine models and their counterparts. The ROC curves of them were drawn to evaluate their diagnostic potential. Moreover, CIBERSORT was used to estimate immune infiltration. A correlation analysis between screened aging-related genes and infiltrating immune cells was performed. A total of 24 aging-related genes were identified, which were found to be mainly involved in the FoxO signaling pathway, PI3K-Akt signaling pathway, longevity regulating pathway, and peroxisome according to functional enrichment analysis. LASSO, SVM-RFE, and MCC algorithms identified three genes (HSPA9, SOD2, TXN). Furthermore, the expression levels of HSPA9 and SOD2 were validated in aged rapid atrial pacing-induced AF canine models. HSPA9 and SOD2 could be potential diagnostic biomarkers for AF, as evidenced by the ROC curves. Immune infiltration and correlation analysis revealed that HSPA9 and SOD2 were related to immune cell infiltrates. Collectively, these findings provide novel insights into the potential aging-related genes associated with AF. HSPA9 and SOD2 may play a significant role in the occurrence and development of AF.