Mediation of mitochondrial DNA copy number and oxidative stress in fluoride-related bone mineral density alteration in Chinese farmers.

Excessive fluoride can adversely affect bone mineral density (BMD). Oxidative stress and mitochondrial dysfunction are crucial mechanisms of health damage induced by fluoride. Here, a cross-sectional survey involving 907 Chinese farmers (aged 18-60) was carried out in Tongxu County in 2017, aiming to investigate the significance of mitochondrial DNA copy number (mtDNAcn) and oxidative stress in fluoride-related BMD change. Concentrations of urinary fluoride (UF), serum oxidative stress biomarkers, including total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA), as well as relative mtDNAcn in peripheral blood were determined. The multivariable linear model and mediation analysis were performed to assess associations between UF, oxidative stress, and relative mtDNAcn with BMD. Results showed that GSH-Px levels increased by 6.98 U/mL [95% confidence interval (CI) 3.41-10.56)] with each 1.0 mg/L increment of UF. After stratification, the T-AOC, relative mtDNAcn, and BMD decreased by 0.04 mmol/L (-0.08 ~ -0.01), 0.29-unit (-0.55 ~ -0.04), and 0.18-unit (-0.33 ~ -0.03) with every 1.0 mg/L elevation of UF in the excessive fluoride group (EFG, adults with UF > 1.6 mg/L), respectively. Furthermore, T-AOC and relative mtDNAcn were favorably related to the BMD in the EFG (ß = 0.82, 95%CI 0.16-1.48 for T-AOC; ß = 0.11, 95%CI 0.02-0.19 for relative mtDNAcn). Mediation analysis showed that relative mtDNAcn and T-AOC mediated 15.4% and 17.1% of the connection between excessive fluoride and reduced BMD, respectively. Findings suggested that excessive fluoride was related to lower BMD in adults, and the decrement of T-AOC and relative mtDNAcn partially mediate this relationship.

Environmentally related microcystin-LR-induced ovarian dysfunction via the CCL2-CCR10 axis in mice ameliorated by dietary mulberry.

Microcystin-LR (MC-LR) is a reproductive toxin produced by cyanobacteria in the aquatic environment and can be ingested by humans through drinking water and the food chain, posing a threat to human reproductive health. However, the toxic mechanisms and prospective interventions for MC-LR-induced ovarian dysfunction at environmental doses are unknown. The mulberry fruit is a traditional natural product of plant origin, with various pharmacological effects, such as antioxidant and anti-inflammatory effects. Here, mice were exposed to MC-LR (10, 100 µg/L) in drinking water for 90 days, during which mice were gavage 600 mg/kg/week of mulberry fruit extract (MFE). It was found that MC-LR can accumulate in mouse ovaries, causing sexual hormone disturbance, inflammatory infiltration, and ovarian pathological damage. Results from RNA-seq were shown that CCL2, a chemokine associated with inflammatory response, was significantly increased in mouse ovary after MC-LR exposure. Further investigation revealed that MC-LR exposure aggravates apoptosis of granulosa cells via the CCL2-CCR10 axis-mediated Jak/Stat pathway. Importantly, MFE can significantly ameliorate these ovarian dysfunction phenotypes by inhibiting the activation of the CCL2-CCR10 axis. This study broadened new insights into the ovarian toxicity of MC-LR and clarified the pharmacological effects of mulberry fruit on ovarian function protection.

Dissecting causal links between gut microbiota, inflammatory cytokines, and DLBCL: a Mendelian randomization study.

ABSTRACT: Causal relationships between gut microbiota, inflammatory cytokines, and diffuse large B-cell lymphoma (DLBCL) remain elusive. In addressing this gap, our Mendelian randomization (MR) study used data from the MiBioGen consortium encompassing 211 microbiota taxa (n = 18 340), genome-wide association study meta-analyses of 47 inflammatory cytokines, and DLBCL cases and controls from the FinnGen consortium (cases, n = 1010; controls, n = 287 137). Through bidirectional MR analyses, we examined the causal links between gut microbiota and DLBCL and used mediation analyses, including 2-step MR and multivariable MR (MVMR), to identify potential mediating inflammatory cytokines. Our findings revealed that 4 microbiota taxa were causally associated with DLBCL, and conversely, DLBCL influenced the abundance of 20 taxa. Specifically, in the 2-step MR analysis, both the genus Ruminococcaceae UCG-002 (odds ratio [OR], 1.427; 95% confidence interval [CI], 1.011-2.015; P = .043) and the inflammatory cytokine monokine induced by gamma (MIG) (OR, 1.244; 95% CI, 1.034-1.487; P = .020) were found to be causally associated with an increased risk of DLBCL. Additionally, a positive association was observed between genus Ruminococcaceae UCG-002 and MIG (OR, 1.275; 95% CI, 1.069-1.520; P = .007). Furthermore, MVMR analysis indicated that the association between genus Ruminococcaceae UCG-002 and DLBCL was mediated by MIG, contributing to 14.9% of the effect (P = .005). In conclusion, our MR study provides evidence that supports the causal relationship between genus Ruminococcaceae UCG-002 and DLBCL, with a potential mediating role played by the inflammatory cytokine MIG.

Change characteristics, bacteria host, and spread risks of bioaerosol ARGs/MGEs from different stages in sewage and sludge treatment process.

The spread of antibiotic resistance genes (ARGs) in the atmospheric environment has seriously threatened human health. Wastewater treatment plants (WWTPs) are an important source of aerosol ARGs. A large WWTP, including sewage treatment process (SWP) and sludge treatment process (SDP), was selected in North China for sampling in this study. The content of ARGs, mobile genetic elements (MGEs), and bacterial genera in sewage/sludge and aerosols from different process stages was detected. The possible correlation between ARGs/ MGEs and bacteria was analyzed. The risk of antibiotic-resistant bacteria was evaluated and the diffusion of ARGs/MGEs was simulated. The results showed that the concentration of ARGs/MGEs varied as the process progressed, and which in the aeration tank was relatively high. The ARGs/MGEs content in SWP aerosol (8.35-163.27 copies/m3) was higher than that in SDP (5.52-16.36 copies/m3). The main ARGs/MGEs detected in SWP aerosol were tnpA-05, tnpA-04, and ermF, while the main ARGs/MGEs detected in SDP aerosol were sul1, ermF, and blaPAO. ARGs were positively correlated with most bacteria and Escherichia coli with ARGs carries higher cytotoxicity. ARGs/MGEs mainly diffused towards the southeast, which may cause harm to urban residents with the diffusion of aerosols. This study provides clues and theoretical basis for preventing the hazards of ARGs from WWTP sources.

Correlations between bone metabolism biomarkers and fluoride exposure in adults and children.

Increased exposure to fluoride, which notably affects bone metabolism, is a global concern. However, the correlations and sensitivity of bone metabolism to fluoride remain controversial. In this cross-sectional study, 549 children (aged 7-12 years) and 504 adults (≥ 18 years old) were recruited in the high-fluoride areas of the Henan Province. Urinary fluoride (UF) level was determined using a fluoride electrode. Fasting venous blood serum was collected to measure bone metabolism biomarkers. The selected bone metabolism biomarkers for children included bone alkaline phosphatase (BALP), serum alkaline phosphatase (ALP), osteocalcin (OCN), calcitonin (CT), parathyroid hormone (PTH), phosphorus (P5+), and calcium (Ca2+). For adults, the biomarkers included ALP, CT, PTH, ß-CrossLaps (ß-CTX), P5+, and Ca2+. The correlations between UF and bone metabolism biomarkers were analyzed using binary logistic regression, a trend test, a generalized additive model, and threshold effect analysis. Regression analysis indicated a significant correlation between serum OCN, PTH, and UF levels in children aged 7-9 years. Serum OCN, PTH, and BALP contents were significantly correlated with UF in boys (P < 0.05). Furthermore, the interaction between age and UF affected serum P5+ and PTH (P < 0.05). The generalized additive model revealed nonlinear dose-response relationships between P5+, BALP, and UF contents in children (P < 0.05). Serum OCN level was linearly correlated with the UF concentration (P < 0.05). Similarly, a significant correlation was observed between ß-CTX and UF levels in adults. In addition, significant correlations were observed between UF-age and serum Ca2+, ß-CTX, and PTH contents. There was a non-linear correlation between serum Ca2+, P5+, and ß- CTX and UF levels (P < 0.05). Overall, serum OCN, BALP, and P5+ levels can serve as sensitive bone metabolism biomarkers in children, while ß-CTX, P5+, and Ca2+ can be considered fluoride-sensitive bone metabolism biomarkers in adults.

Network analysis of smoking-related sleep characteristics in Chinese adults.

The associations between multiple sleep characteristics and smoking behavior are inconsistent, and it is unclear which sleep characteristics are most crucial for tobacco prevention. This study aimed to explore the associations between smoking status/intensity and multiple sleep characteristics and to identify the potential core domain of smoking-related sleep using network analysis. Data were obtained from a survey of cancer-related risk factors among Chinese adults. Logistic regression models were used to quantify the associations between sleep characteristics and smoking status/intensity. Network analyses were employed to identify the core sleep characteristics. A total of 5,228 participants with a median age of 44 years old were included in the study. Current smoking was significantly positively associated with long nap time, difficulty falling asleep, late bedtime, getting up after 7 am, and waking up earlier than expected. There was significant positive association between current smoking and short sleep duration in young adults under 45 years old. Late bedtime and getting up after 7 am were only associated with current heavy smoking, but not current light smoking. Network analyses showed that multiple smoking-related sleep characteristics were interconnected, with difficulty falling asleep and late bedtime as central characteristics in the network. The study found that the associations between sleep characteristics and smoking varied by age and smoking intensity and highlights the potential benefits of sleep health promotion in smoking cessation, with a particular focus on difficulty falling asleep and late bedtime.

Nanosensors Monitor Intracellular GSH Depletion: GSH Triggers Cu(II) for Tumor Imaging and Inhibition.

Glutathione (GSH) is the primary antioxidant in cells, and GSH consumption will break the redox balance in cells. Based on this, a method that uses high concentrations of GSH in the tumor microenvironment to trigger the redox reaction of Cu(II) to generate copper nanoprobes with fluorescence and tumor growth inhibition properties is proposed. The nanoprobe mainly exists in the form of Cu(I) and catalyzes the decomposition of hydrogen peroxide into hydroxyl radicals. At the same time, a simple and controllable carbon micro-nano electrode is used to construct a single-cell sensing platform, which enable the detection of glutathione content in single living cells after Cu(II) treatment, providing an excellent example for detecting single-cell biomolecules.

Passive exercise is an effective alternative to HRT for restoring OVX induced mitochondrial dysfunction in skeletal muscle.

Background: Postmenopausal women are more prone to develop muscle weakness, which is strongly associated with impairment of mitochondrial function in skeletal muscle. This study aimed to examine the impact of a passive exercise modality, whole-body vibration training (WBVT), on muscle mitochondrial function in ovariectomized (OVX) mice, in comparison with 17ß-estradiol (E2) replacement. Methods: Female C57BL/6J mice were assigned to four groups: sham operation control group (Sham), ovariectomized group (OVX), OVX with E2 supplement group (OVX+E), and OVX with WBVT group (OVX+W). The estrous cycle, body weight, body composition, and muscle strength of the mice were monitored after the operation. Serum E2 level was assessed by enzyme-linked immunosorbent assay (ELISA). The ATP levels were determined using a luciferase-catalyzed bioluminescence assay. The activity of mitochondrial respiration chain complexes was evaluated using high-resolution respirometry (O2K). Expression levels of oxidative phosphorylation (OXPHOS), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), and mitochondrial transcription factor A (TFAM) were detected using western blotting. Results: We observed decreased muscle strength and impaired mitochondrial function in the skeletal muscle of OVX mice. The vibration training alleviated these impairments as much as the E2 supplement. In addition, the vibration training was superior to the ovariectomy and the estradiol replacement regarding the protein expression of PGC-1α and TFAM. Conclusion: WBVT improves the OVX-induced decline in muscle strength and impairment of mitochondrial function in the skeletal muscle. This passive exercise strategy may be useful as an alternative to E2 replacement for preventing menopausal muscular weakness. Further studies are needed to understand the effects of WBVT on various physiological systems, and precautions should be taken when implementing it in patient treatment.

Potentiating Immunogenic Cell Death in Cold Tumor with Functional Living Materials of FeAu-Methylene Blue Composites.

Low immunogenicity, absence of tumor-infiltrating lymphocytes and immunosuppressive microenvironment of immune cold tumors are the main bottlenecks leading to unfavorable prognosis. Here, an integrated tumor bioimaging and multimodal therapeutic strategy is developed, which converts immune cold into hot by modulating oxidative stress levels, enhancing photo-killing efficacy, inducing immunogenic cell death and inhibiting the immune checkpoint. On that occasion, the unique tumor microenvironment can be harnessed to biosynthesize in situ self-assembly iron complexes and fluorescent gold nanoclusters from metal ions Fe(II) and Au(III) for active targeting and real-time visualization of the tumors, simultaneously regulating reactive oxygen species levels within tumors via peroxidase-like activity. Furthermore, methylene blue (MB)-mediated photodynamic therapy promotes the release of damage-associated molecular patterns (DAMPs), which acts as in situ tumor vaccine and further induces dendritic cells maturation, augments the infiltration of antitumor T cells and significantly impedes the primary tumor growth and proliferation. More strikingly, by synergizing with the programmed cell death receptor-1 (PD-1) checkpoint inhibitor, the immunosuppressive microenvironment is remodeled and the survival time of model mice is prolonged. In summary, this paradigm utilizes the tumor-specific microenvironment to boost robust and durable systemic antitumor immunity, providing a novel opportunity for precision cancer theranostics.

In situ monitoring of cytoplasmic dopamine levels by noble metals decorated carbon fiber tips.

Dopamine (DA), a catecholamine neurotransmitter, is crucial in brain signal transmission. Monitoring cytoplasmic DA levels can reflect changes in metabolic factors and provide valuable information for researching the mechanisms involved in neurodegenerative diseases. However, the in-situ detection of intracellular DA is constrained by its low contents in small-sized single cells. In this work, we report that noble metal (Au, Pt)-modified carbon fiber micro-nanoelectrodes are capable of real-time detection of DA in single cells with excellent sensitivity, selectivity, and anti-contamination capabilities. Notably, noble metals can be modified on the electrode surface through electrochemical deposition to enhance the conductivity of the electrode and the oxidation current of DA by 50 %. The nanosensors can work stably and continuously in rat adrenal pheochromocytoma cells (PC12) to monitor changes in DA levels upon K+ stimulation. The functionalized carbon fibers based nanosensors will provide excellent prospects for DA analysis in the brains of living animals.

Quantitative association between lead exposure and amyotrophic lateral sclerosis: a Bayesian network-based predictive study.

BACKGROUND: Environmental lead (Pb) exposure have been suggested as a causative factor for amyotrophic lateral sclerosis (ALS). However, the role of Pb content of human body in ALS outcomes has not been quantified clearly. The purpose of this study was to apply Bayesian networks to forecast the risk of Pb exposure on the disease occurrence. METHODS: We retrospectively collected medical records of ALS inpatients who underwent blood Pb testing, while matched controlled inpatients on age, gender, hospital ward and admission time according to the radio of 1:9. Tree Augmented Naïve Bayes (TAN), a semi-naïve Bayes classifier, was established to predict probability of ALS or controls with risk factors. RESULTS: A total of 140 inpatients were included in this study. The whole blood Pb levels of ALS patients (57.00 µg/L) were more than twice as high as the controls (27.71 µg/L). Using the blood Pb concentrations to calculate probability of ALS, TAN produced the total coincidence rate of 90.00%. The specificity, sensitivity of Pb for ALS prediction was 0.79, or 0.74, respectively. CONCLUSION: Therefore, these results provided quantitative evidence that Pb exposure may contribute to the development of ALS. Bayesian networks may be used to predict the ALS early onset with blood Pb levels.

Disruption and recovery of outdoor bioaerosols before, during, and after the COVID-19 outbreak at a campus in Central China: pathogen composition, particle size distribution, influencing factors, and exposure risk.

Before (2019), during (2020), and after (2021) the COVID-19 outbreak, different response methods and measures were taken on campuses to control the spread of COVID-19 within schools. These response methods may have changed the outdoor bioaerosol characteristics, which may affect staff and student health. Therefore, we analyzed the bacterial concentrations, particle size distribution, microbial populations, exposure risks, and environmental influences of bioaerosols at a campus before, during, and after the COVID-19 outbreak. This study used eight-stage Andersen samplers to collect and analyze culturable bacteria in bioaerosols from various locations, high-throughput sequencing to analyze microbial species, principal component analysis to compare differences in samples, RDA to investigate the effects of environmental factors on bioaerosols, and hazard quotient (HQ) and BugBase to evaluate human health risks. The study findings revealed that average bacterial concentrations before, during, and after COVID-19 were 75 CFU m-3, 136 CFU m-3, and 78 CFU m-3, respectively. Moreover, the average percentage of bacteria attached to PM2.5 was 49.2%, 42.7%, and 29.9%, respectively. High-throughput sequencing revealed that species composition changed significantly during the three years of COVID-19. The proportion of Pantoea and Bacillus increased with the development of COVID-19 and these became the dominant strains after COVID-19, whereas Pseudomonas had the maximum proportion during COVID-19. Both risk assessment and BugBase phenotype prediction results indicated that the potential pathogenic risk was the highest in the outdoor environment of the campus during COVID-19 and that bioaerosol contamination was the most severe compared to the outdoor bioaerosol characteristics of the campus recovered after COVID-19.

U-shaped relationship between ozone exposure and preterm birth risk associated with preconception telomere length.

There are conflicting findings regarding the association of ozone (O3) exposure with preterm birth (PTB) occurrence. In the present study, two cohorts were combined to explore the relationship between maternal O3 exposure during pregnancy and PTB risk, and analyze the underlying mechanisms of this relationship in terms of alterations in the preconception telomere length. Cohort 1 included mothers who participated in the National Free Preconception Health Examination Project in Henan Province from 2014 to 2018 along with their newborns (n = 1,066,696). Cohort 2 comprised mothers who conceived between 2016 and 2018 and their newborns (n = 1871) from six areas in Henan Province. The telomere length was assessed in the peripheral blood of mothers at the preconception stage. Data on air pollutant concentrations were collected from environmental monitoring stations and individual exposures were assessed using an inverse distance-weighted model. O3 concentrations (100.60 ± 14.13 µg/m3) were lower in Cohort 1 than in Cohort 2 (114.09 ± 15.17 µg/m3). Linear analyses showed that PTB risk decreased with increasing O3 exposure concentrations in Cohort 1 but increased with increasing O3 exposure concentrations in Cohort 2. Nonlinear analyses revealed that PTB risk tended to decrease and then increase with increasing O3 exposure concentrations in both cohorts. Besides, PTB risk was reduced by 88% for each-unit increase in telomere length in those exposed to moderate O3 concentrations (92.4-123.7 µg/m3, P < 0.05). While no significant association was observed between telomere length and PTB at extreme O3 concentration exposure during entire pregnancy (<92.4 or >123.7 µg/m3, P > 0.05) in Cohort 2. These findings reveal a nonlinear (U-shaped) relationship between O3 exposure and PTB risk. Furthermore, telomere with elevated length was associated with decreased risk of PTB only when exposed to moderate concentrations of O3, but not when exposed to extreme concentrations of O3 during pregnancy.

Effect of zinc intake on association between fluoride exposure and abnormal sex steroid hormones among US pubertal males: NHANES, 2013-2016.

Excessive fluoride exposure can disturb the balance of sex hormones. Zinc is essential for sex hormone synthesis and spermatogenesis. But it is not clear how zinc affects the relationship of fluoride exposure with abnormal sex steroid hormones. Here, a total of 1008 pubertal males from the National Health and Nutrition Examination Survey (NHANES) in two cycles (2013-2014, 2015-2016) were enrolled. The concentrations of water fluoride and plasma fluoride and the levels of serum testosterone, estradiol, and sex hormone binding globulin (SHBG) were measured. Two 24-h dietary recall interviews were conducted to assess the dietary zinc intake. The relationships of fluoride exposure and zinc intake with sex hormones were examined using linear regression and logistic regression models, while the generalized additive model was used to evaluate their non-linear relationship. Our findings revealed that for every two-fold increase in plasma fluoride concentration, testosterone levels decreased by 7.27% (95% CI - 11.49%, - 2.86%) and estradiol levels decreased by 8.73% (95% CI - 13.61%, - 3.57%). There was also significant non-linear association observed between zinc intake and SHBG levels. Being in the first tertile of plasma fluoride had a 60% lower risk of high SHBG (OR = 0.40, 95% CI 0.18, 0.89) compared with being in the second tertile. When compared to the first tertile, being in the second tertile of zinc intake was associated with a 63% (OR = 0.37, 95% CI 0.14, 0.98) lower risk of high SHBG. Furthermore, we observed an interactive effect between the plasma fluoride and zinc intake on estradiol and SHBG, as well as the risk of high SHBG (P-interaction < 0.10). These findings suggest that fluoride exposure and zinc intake can affect sex steroid hormone levels and the risk of high SHBG. Notably, zinc intake may alleviate the increased risk of high SHBG and the abnormal changes of estradiol and SHBG caused by higher fluoride exposure.

Monocyte-to-lymphocyte ratio and gastrointestinal disorder-related hospitalization in patients on maintenance hemodialysis.

INTRODUCTION: To explore the association between monocyte-to-lymphocyte ratio (MLR) and the risk of hospitalization due to gastrointestinal (GI) disorder in hemodialysis (HD) patients. METHODS: In this multicenter, observational cohort study, 1626 patients were enrolled in 2019 and followed up to 2 years. Cox regression models were performed to estimate the association of MLR with GI disorder-related hospitalization risk. Receiver-operating characteristic (ROC) analyses were conducted to evaluate the cutoff value of MLR in identifying GI disorder-related hospitalization. RESULTS: During a median follow-up of 24 months, GI disorder-related hospitalization occurred in 107 patients. Higher MLR was independently associated with greater risks of GI disorder-related hospitalization. Furthermore, a cut-off value of 0.42 differentiated patients with GI disorder-related hospitalization from those without GI involvement. CONCLUSION: MLR was associated with the occurrence of GI disorder-related hospitalization in HD patients. The blood MLR could be monitored as a useful marker to predict GI disorder-related hospitalization.

Proteomics Sequencing Reveals the Role of TGF-ß Signaling Pathway in the Peripheral Blood of Offspring Rats Exposed to Fluoride.

The underlying mechanism of fluorosis has not been fully elucidated. The purpose of this study was to explore the mechanism of fluorosis induced by sodium fluoride (NaF) using proteomics. Six offspring rats exposed to fluoride without dental fluorosis were defined as group A, 8 offspring rats without fluoride exposure were defined as control group B, and 6 offspring rats exposed to fluoride with dental fluorosis were defined as group C. Total proteins from the peripheral blood were extracted and then separated using liquid chromatography-tandem mass spectrometry. The identified criteria for differentially expressed proteins were fold change > 1.2 or < 0.83 and P < 0.05. Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the oeCloud tool. The 177 upregulated and 22 downregulated proteins were identified in the A + C vs. B group. KEGG pathway enrichment analysis revealed that transforming growth factor-ß (TGF-ß) signaling pathway significantly enriched. PPI network constructed using Cytoscape confirmed RhoA may play a crucial role. The KEGG results of genes associated with fluoride and genes associated with both fluoride and inflammation in the GeneCards database also showed that TGF-ß signaling pathway was significantly enriched. The immunofluorescence in HPA database showed that the main expression sites of RhoA are plasma membrane and cytosol, while the main expression site of Fbn1 is the Golgi apparatus. In conclusion, long-term NaF intake may cause inflammatory response in the peripheral blood of rats by upregulating TGF-ß signaling pathway, in which RhoA may play a key role.

T-2 toxin induces mitochondrial dysfunction in chondrocytes via the p53-cyclophilin D pathway.

Kashin-Beck disease is an endemic joint disease characterized by deep chondrocyte necrosis, and T-2 toxin exposure has been confirmed its etiology. This study investigated mechanism of T-2 toxin inducing mitochondrial dysfunction of chondrocytes through p53-cyclophilin D (CypD) pathway. The p53 signaling pathway was significantly enriched in T-2 toxin response genes from GeneCards. We demonstrated the upregulation of the p53 protein and p53-CypD complex in rat articular cartilage and ATDC5 cells induced by T-2 toxin. Transmission electron microscopy showed the damaged mitochondrial structure of ATDC5 cells induced by T-2 toxin. Furthermore, it can lead to overopening of the mitochondrial permeability transition pore (mPTP), decreased mitochondrial membrane potential, and increased reactive oxygen species generation in ATDC5 cells. Pifithrin-α, the p53 inhibitor, alleviated the increased p53-CypD complex and mitochondrial dysfunction of chondrocytes induced by T-2 toxin, suggesting that p53 played an important role in T-2 toxin-induced mitochondrial dysfunction. Mechanistically, T-2 toxin can activate the p53 protein, which can be transferred to the mitochondrial membrane and form a complex with CypD. The increased binding of p53 and CypD mediated the excessive opening of mPTP, changed mitochondrial membrane permeability, and ultimately induced mitochondrial dysfunction and apoptosis of chondrocytes.

Decreased Intracellular to Total Body Water Ratio and Depressive Symptoms in Patients with Maintenance Hemodialysis.

Objective: Depression is a common psychiatric disorder and related to poor outcomes in patients undergoing maintenance hemodialysis (MHD). Previous studies have reported some associations between sarcopenia and depressive symptoms. Recently, intracellular water (ICW) and total body water (TBW) have been found to reflect muscle function and muscle mass. ICW/TBW ratio is a marker of sarcopenia that is simple to assess. However, the relationship between ICW/TBW ratio and depression has not been explored in MHD patients. Methods: In our cross-sectional and multi-center study, 3300 adult MHD patients were included from June 1, 2021, to August 30, 2021. Depressive symptoms were evaluated using the Beck Depression Inventory-II (BDI-II). TBW and ICW were measured by Body Composition Monitor (BCM). Multivariable logistic regression, stratified analyses, and interactive analyses were conducted to assess the relationship between ICW/TBW ratio and depression. Results: About 16.5% of the 3300 MHD patients were found to have depressive symptoms. The prevalence of depression increased with decreasing quartiles of ICW/TBW ratios, and decreased ICW/TBW ratio was independently associated with depression after adjusting for potential confounders. Patients in Quartile 1 of ICW/TBW ratios were more likely to have depressive symptoms (odds ratio 1.55, 95% confidence interval 1.07-2.22; p=0.002) than those in Quartile 4. History of diabetes and education status had interactive roles in the relationship between depression and ICW/TBW ratios (p < 0.05). The association of ICW/TBW ratios and depression existed in patients of both genders and different education levels, but only in non-diabetic patients. Conclusion: In MHD patients, the decreased ratio of ICW/TBW was independently related to high depression rates.

Low Lean Tissue Index and Muscle Strength Combined with High Fat Tissue Index Are Associated with Cardiovascular Disease-Related Hospitalisation in Patients on Haemodialysis.

INTRODUCTION: The combined clinical impact of muscle mass, muscle function, and adipose mass on hospitalisation events, especially those that have exact causes, such as cardiovascular diseases (CVDs), had been rarely studied in patients on haemodialysis (HD). This study aimed to determine the influence of lean tissue index (LTI), fat tissue index (FTI), and hand grip strength (HGS) on the risk of CVD-related hospitalisation in patients undergoing chronic HD. METHODS: This multi-centre observational study enrolled a total of 2,041 clinically stable patients aged >18 years and who had undergone HD for at least 3 months at 17 HD units in 2019. The follow-up period was up to 2 years. LTI and FTI were assessed using a body composition monitoring machine, and HGS was measured by a CAMRY® dynamometer. Cox regression models were fit to estimate the associations of body composition and HGS with CVD-related hospitalisation risk. RESULTS: During a mean follow-up of 22.6 months, CVD-related hospitalisation occurred in 492 patients. Compared with the non-CVD group, patients with CVD-related hospitalisation were older; had lower diastolic blood pressure; were more likely to have a history of diabetes; had worse activity status scores and lower levels of LTI, HGS, serum uric acid, and serum creatinine; and had higher FTI levels, body mass index, and extracellular water/intracellular water ratio. In the Cox regression models, low LTI and high FTI were independently associated with CVD-related hospitalisation in both men and women. In men, low HGS was an independent risk factor for CVD-related hospitalisation. When patients were further stratified into four distinct groups according to the sex-specific median values of LTI and FTI, the combination of low LTI and high FTI was an independent risk factor for CVD-related hospitalization (hazard ratio [HR] = 1.79 in men, 95% confidence interval 1.26-2.55; HR = 2.48 in women, 95% confidence interval 1.66-3.71; reference: high LTI/low FTI group). CONCLUSIONS: Among patients on chronic HD, low LTI, and high FTI were associated with CVD-related hospitalisation in men and women, whereas HGS was an independent risk factor for CVD-related hospitalisation in men but not in women. Combining low LTI and high FTI increased the association with hospitalisation risk and was an independent predictor of CVD-related hospitalisation.