Changes in Blood Pressure is Associated with Bone Loss in US Adults: A Cross-Sectional Study from NHANES 2005-2018.

Hypertension and osteoporosis are common geriatric diseases, sharing similar risk factors. This study aims to investigate this association and explore relatively mixed variables. Our study included 12,787 eligible participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Included participants had valid data on hypertension and osteoporosis, without tumors, liver diseases, gout or thyroid diseases. We explored the association between hypertension and osteoporosis by logistic regression and examined blood pressure and BMD/BMC by linear and non-linear regression. Moreover, we used machine learning models to predict the importance of various factors in the occurrence of osteoporosis and evaluated causality by mendelian randomization. Our study found that osteoporosis is significantly associated with hypertension [OR 2.072 (95% CI 2.067-2.077), p < 0.001]. After adjusting for co-variances, the association remained significant [OR 1.223 (95% CI 1.220-1.227), p < 0.001]. Our study showed that osteoporosis is positively associated with hypertension in the US population. A variety of factors influence this relationship. Specific regulatory mechanisms and confounding factors need to be further investigated.

Subacute exposure to dechlorane 602 dysregulates gene expression and immunity in the gut of mice.

Dechlorane 602 (Dec 602) has biomagnification potential. Our previous studies suggested that exposure to Dec 602 for 7 days induced colonic inflammation even after 7 days of recovery. To shed some light on the underlying mechanisms, disturbances of gut immunity and gene expression were further studied. Adult C57BL/6 mice were administered orally with Dec 602 for 7 days, then allowed to recover for another 7 days. Colonic type 3 innate lymphoid cells (ILC3s) in lamina propria lymphocytes (LPLs) and lymphocytes in mesenteric lymph nodes (MLNs) were examined by flow cytometry. Expressions of genes in the gut were determined by RNA-Seq. It was found that Dec 602 exposure up-regulated the percentage of CD4+ T cells in MLNs. The mean fluorescent intensity (MFI) of interleukin (IL)- 22 in LPLs was decreased, while the MFI of IL-17a as well as the percentage of IL-17a+ ILC3s in LPLs were increased after exposure to Dec 602. Genes involved in the formation of blood vessels and epithelial-mesenchymal transition were up-regulated by Dec 602. Ingenuity pathway analysis of differentially expressed genes predicted that exposure to Dec 602 resulted in the activation of liver X receptor/retinoid X receptor (LXR/RXR) and suppression of muscle contractility. Our results, on one hand, verified that the toxic effects of Dec 602 on gut immunity could last for at least 14 days, and on the other hand, these results predicted other adverse effects of Dec 602, such as muscle dysfunction. Overall, our studies provided insights for the further investigation of Dec 602 and other emerging environmental pollutants.

Association between thermal stress and cardiovascular mortality in the subtropics.

Hazardous thermal conditions resulting from climate change may play a role in cardiovascular disease development. We chose the Universal Thermal Climate Index (UTCI) as the exposure metric to evaluate the relationship between thermal conditions and cardiovascular mortality in Shenzhen, China. We applied quasi-Poisson regression non-linear distributed lag models to evaluate the exposure-response associations. The findings suggest that cardiovascular mortality risks were significantly increased under heat and cold stress, and the adverse effects of cold stress were stronger than heat stress. Referencing the 50th percentile of UTCI (25.4°C), the cumulative risk of cardiovascular mortality was 75% (RRlag0-21 =1.75, 95%CI: 1.32, 2.32) higher in the 1st percentile (3.5°C), and 40% (RRlag0-21=1.40, 95%CI: 1.09, 1.80) higher in the 99th percentile (34.1°C). We observed that individuals older than 65 years were more vulnerable to both cold and heat stress, and females were identified as more susceptible to heat stress than males. Moreover, increased mortality risks of hypertensive disease and cerebrovascular disease were observed under cold stress, while heat stress was related to higher risks of mortality for hypertensive disease and ischemic heart disease. We also observed a stronger relationship between cold stress and ischemic heart disease mortality during the cold season, as well as a significant impact of heat stress on cerebrovascular disease mortality in the warm season when compared to the analysis of the entire year. These results confirm the significant relationship between thermal stress and cardiovascular mortality, with age and sex as potential effect modifiers of this association. Providing affordable air conditioning equipment, increasing the amount of vegetation, and establishing comprehensive early warning systems that take human thermoregulation into account could all help to safeguard the well-being of the public, particularly vulnerable populations, in the event of future extreme weather.

Cardiolipin function in the yeast S. cerevisiae and the lessons learned for Barth syndrome.

Cardiolipin (CL) is the signature phospholipid (PL) of mitochondria and plays a pivotal role in mitochondrial and cellular function. Disruption of the CL remodeling gene tafazzin (TAZ) causes the severe genetic disorder Barth syndrome (BTHS). Our current understanding of the function of CL and the mechanism underlying the disease has greatly benefited from studies utilizing the powerful yeast model Saccharomyces cerevisiae. In this review, we discuss important findings on the function of CL and its remodeling from yeast studies and the implications of these findings for BTHS, highlighting the potential physiological modifiers that may contribute to the disparities in clinical presentation among BTHS patients.

Short-term exposure to nitrogen dioxide and ischemic stroke incidence in Shenzhen, China: Modification effects by season and temperature.

BACKGROUND AND OBJECTIVES: China has experienced a serious public health burden because of the increased incidence of ischemic stroke. Evidence describing the association between short-term exposure to nitrogen dioxide (NO2) and ischemic stroke morbidity is limited, and few studies have focused on the effects of season and temperature. This study aimed to evaluate the acute effects of NO2 on ischemic stroke incidence in Shenzhen, a southeastern city of China, considering the modified effects of season and temperature. METHODS: A time-stratified case-crossover study was conducted between 2003 and 2014 among 98,482 ischemic stroke hospitalizations. Conditional quasi-Poisson regression was used to estimate the percentage changes in ischemic stroke admissions in relation to each 10 µg/m3 increment in NO2. RESULTS: NO2 was positively associated with ischemic stroke onset over the full year, as well as in the cold season (November through April) and on cold days (ambient temperature≤median temperature), with significant single-day effects within 3 days after the exposure, and significant cumulative effects within the delayed five days. The maximum percentage changes were obtained at lag0-5, with 1.81% (95% confidence interval (CI) was 0.86-2.76%) over the full year, 2.75% (1.48-4.03%) in the cold season, and 3.04% (1.74-4.35%) on cold days. Additionally, the effects of exposure were found to be greater in males and people with higher education, and were lasting longer in subgroups of older individuals. CONCLUSIONS: Our findings provide evidence that reductions in NO2 levels might decrease ischemic stroke morbidity, and enhance the understanding of ischemic stroke occurrence associated with NO2 modified by season and temperature.

Cardiolipin-deficient cells have decreased levels of the iron-sulfur biogenesis protein frataxin.

Cardiolipin (CL) is the signature phospholipid of mitochondrial membranes, where it is synthesized locally and plays an important role in mitochondrial bioenergetics. Previous studies in the yeast model have indicated that CL is required for optimal iron homeostasis, which is disrupted by a mechanism not yet determined in the yeast CL mutant, crd1Δ. This finding has implications for the severe genetic disorder, Barth syndrome (BTHS), in which CL metabolism is perturbed because of mutations in the CL-remodeling enzyme, tafazzin. Here, we investigate the effects of tafazzin deficiency on iron homeostasis in the mouse myoblast model of BTHS tafazzin knockout (TAZ-KO) cells. Similarly to CL-deficient yeast cells, TAZ-KO cells exhibited elevated sensitivity to iron, as well as to H2O2, which was alleviated by the iron chelator deferoxamine. TAZ-KO cells exhibited increased expression of the iron exporter ferroportin and decreased expression of the iron importer transferrin receptor, likely reflecting a regulatory response to elevated mitochondrial iron. Reduced activities of mitochondrial iron-sulfur cluster enzymes suggested that the mechanism underlying perturbation of iron homeostasis was defective iron-sulfur biogenesis. We observed decreased levels of Yfh1/frataxin, an essential component of the iron-sulfur biogenesis machinery, in mitochondria from TAZ-KO mouse cells and in CL-deleted yeast crd1Δ cells, indicating that the role of CL in iron-sulfur biogenesis is highly conserved. Yeast crd1Δ cells exhibited decreased processing of the Yfh1 precursor upon import, which likely contributes to the iron homeostasis defects. Implications for understanding the pathogenesis of BTHS are discussed.

RGD Peptides-Conjugated Pluronic Triblock Copolymers Encapsulated with AP-2α Expression Plasmid for Targeting Gastric Cancer Therapy in Vitro and in Vivo.

Gastric cancer, a high-risk malignancy, is a genetic disease developing from a cooperation of multiple gene mutations and a multistep process. Gene therapy is a novel treatment method for treating gastric cancer. Here, we developed a novel Arg-Gly-Asp (RGD) peptides conjugated copolymers nanoparticles-based gene delivery system in order to actively targeting inhibit the growth of gastric cancer cells. These transcription factor (AP-2α) expression plasmids were also encapsulated into pluronic triblock copolymers nanoparticles which was constituted of poly(ethylene glycol)-block-poly(propylene glycol)- block-poly(ethylene glycol) (PEO-block-PPO-block-PEO, P123). The size, morphology and composition of prepared nanocomposites were further characterized by nuclear magnetic resonance (NMR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). In MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide) analysis, these nanocomposites have minor effects on the proliferation of GES-1 cells but significantly decreased the viability of MGC-803, suggesting they own low cytotoxicity but good antitumor activity. The following in vivo evaluation experiments confirmed that these nanocomposites could prevent the growth of gastric cancer cells in the tumor xenograft mice model. In conclusion, these unique RGD peptides conjugated P123 encapsulated AP-2α nanocomposites could selectively and continually kill gastric cancer cells by over-expression of AP-2α in vitro and in vivo; this exhibits huge promising applications in clinical gastric cancer therapy.

Application value of DSMB-O scale in self-management of elderly patients with type 2 diabetes mellitus.

BACKGROUND: To enhance the self-management ability of elderly diabetes mellitus (DM) patients, priority should be given to the accurate evaluation of their current self-management ability, and then provide corresponding guidance. OBJECTIVE: To explore the application value of Diabetes Self-Management Behaviors among Older Koreans (DSMB-O) in self-management of elderly patients with type 2 diabetes mellitus (T2DM). METHODS: Using convenient sampling, this study retrospectively collected the clinical data of 215 elderly patients with T2DM who were admitted to our hospital from June 2020 to June 2022. Enrolled patients were divided into an effective-control group (n= 80) and an ineffective-control group (n= 135) based on whether the glycated hemoglobin (HbA1C) was < 7.5% for further comparison of the collected data. RESULTS: There were statistically significant differences in the comparison of the proportion of diabetes mellitus (DM) course (χ2= 26.000, P< 0.001), DSMB-O score (17.67 ± 4.07 VS 14.67 ± 4.70 points, t= 4.582, P< 0.001), and Summary Diabetes Self Care Activity (SDSCA) score (43.16 ± 11.17 VS 37.58 ± 12.47 points, t= 5.492, P< 0.001) between the two groups. The total score of DSMB-O was negatively correlated with both HbA1c (r=-0.281, P< 0.001) and complications (r=-0.193, P= 0.004); moreover, the total score of SDSCA was also negatively correlated with both HbA1c (r=-0.234, P< 0.001) and complications (r=-0.153, P= 0.025). Among various dimensions of DSMB-O, active exercise (OR= 0.699, 95%CI: 0.541 ∼ 0.902) and blood glucose monitoring (OR= 0.603, 95%CI: 0.431 ∼ 0.817) were protective factors for T2DM patients with HbA1c levels < 7.5%. The area under the curve (AUC) of SDSCA score and DSMB-O score predicting self-management level in elderly T2DM patients was 0.643 (95%CI: 0.611 ∼ 0.756) and 0.716 (95%CI: 0.689∼ 0.774), respectively. CONCLUSION: DSMB-O exhibits a higher accuracy in predicting the self-management level of elderly patients with T2DM than that of SDSCA. Regular exercise, medication, blood glucose monitoring, and reducing the risk of complications are all intimately associated with the control of blood glucose.

Temporal dynamic effects of meteorological factors and air quality on the physical health of the older adults in Shenzhen, China.

Introduction: Meteorological and environmental factors can affect people's lives and health, which is crucial among the older adults. However, it is currently unclear how they specifically affect the physical condition of older adults people. Methods: We collected and analyzed the basic physical examination indicators of 41 older adults people for two consecutive years (2021 and 2022), and correlated them with meteorological and environmental factors. Partial correlation was also conducted to exclude unrelated factors as well. Results: We found that among the physical examination indicators of the older adults for two consecutive years, five indicators (HB, WBC, HbAlc, CB, LDL-C) showed significant differences across the population, and they had significantly different dynamic correlation patterns with six meteorological (air pressure, temperature, humidity, precipitation, wind speed, and sunshine duration) and seven air quality factors (NO2, SO2, PM10, O3-1h, O3-8h, CO, PM2.5). Discussion: Our study has discovered for the first time the dynamic correlation between indicators in normal basic physical examinations and meteorological factors and air quality indicators, which will provide guidance for the future development of policies that care for the healthy life of the older adults.

Chlorate and perchlorate in tea leaves from major producing regions in China and related human exposure risk.

Chlorate and perchlorate are emerging pollutants that may interfere with thyroid function. Since they are highly water soluble, chlorate and perchlorate in tea leaves cause health concerns but have scarcely been studied. In this study, chlorate and perchlorate concentrations in 216 tea samples from different regions of China were determined. Perchlorate was detected in all the samples with a median concentration of 44.1 µg kg-1, while the chlorate detection frequency was 15.7%. We observed regional differences in perchlorate contents in tea leaves, with the highest quantity found in the central region of China. Except for dark tea, the concentration of perchlorate in tea infusions decreased with the increased number of times the tea leaves were brewed. The hazard quotients (HQs) of chlorate and perchlorate in all the samples were less than 1, suggesting negligible health risks caused by these pollutants from tea consumption. To the best of our knowledge, this is the first study to investigate chlorate and perchlorate contamination in tea infusions by simulating brewing behavior.

Concentrations, sources and health risk of bisphenols in red swamp crayfish (Procambarus clarkii) from South-Eastern China.

Bisphenol analogs (BPs) are extensively employed in commercial and industrial products and they have been found in a variety of environmental matrices and human samples. The red swamp crayfish (Procambarus clarkii) has been a trendy food in China in recent decades. However, the levels of BPs in Chinese crayfish and the associated hazards of human exposure remain unknown. Thus, in this study, the levels of eight BPs in crayfish gathered from five major provinces engaged in crayfish within the Yangtze River Basin were analyzed. Additionally, the health risks for humans by ingesting crayfish were calculated. BPs were frequently detected in crayfish tissues, indicating the wide occurrence of these chemicals. In comparison to other substitutions, BPA remains the dominant bisphenol analog. Most of the BPs were observed to accumulate in the hepatopancreas compared to the muscle, so consuming the hepatopancreas of crayfish is not recommended. With the exception of BPS, the Estimated Daily Intakes (EDIs) of the remaining BPs exceeded the Tolerable Daily Intake (TDI) specified by the European Food Safety Authority (EFSA) by a factor of 1.75-69.0. The mean hazard index (HI) values exceeded 1 for both hepatopancreas and muscle in all provinces, and the mean HI values for hepatopancreas were significantly higher than those for muscle, indicating potential health risks for local consumers.

[Effect of carbon disulfide on mitochondrial respiratory chain in spermatogenic cells in male rats].

OBJECTIVE: To investigate the effect of carbon disulfide (CS(2)) on the mitochondrial respiratory chain in testicular spermatogenic cells in male rats and to explore the possible mechanism of reproductive system damage caused by CS(2) in male rats. METHODS: Twenty-four male Sprague-Dawley rats (clean grade) were randomly divided into four groups: three CS(2) exposure groups (CS(2) concentrations: 50, 250, and 1250 mg/m(3)) and a control group. The rats in CS(2) exposure groups were exposed to CS(2) by static inhalation for 10 weeks (2 h/d, 5 d/w), while the rats in control group were exposed to air. Then, all rats were sacrificed by decapitation; testicular tissues were collected, and mitochondrial protein in spermatogenic cells were extracted; the levels of mitochondrial respiratory chain enzyme complex I∼V were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, all CS(2) exposure groups had significantly increased levels of mitochondrial respiratory chain enzyme complex I∼V in spermatogenic cells (P < 0.05). There were no significant differences in the levels of respiratory chain enzyme complex I∼IV between the CS(2) exposure groups (P < 0.05), but the level of respiratory chain enzyme complex V rose significantly as the concentration of CS(2) increased (P<0.05). CONCLUSION: Various levels of CS(2) exposure may increase the levels of mitochondrial respiratory chain enzyme complex in testicular spermatogenic cells among male rats, thus affecting the normal oxidative phosphorylation in mitochondria.

[Effect of carbon disulfide on mitochondrial apoptosis-related proteins in cytoplasm of testicular tissue among male rats].

OBJECTIVE: To investigate the role of mitochondrial pathway in the apoptosis of spermatogenic cells induced by inhalation of carbon disulfide in male rats. METHODS: Twenty-four male Sprague-Dawley rats (clean grade) were divided into four groups according to their body weights: three CS(2) exposure groups (CS(2) concentrations: 50, 250, and 1250 mg/m(3)) and a control group. The rats in CS(2) exposure groups were exposed to CS(2) by static inhalation for 10 weeks (2 h/d, 5 d/w), while the rats in control group were exposed to air. Then, all rats were sacrificed by decapitation; testicular tissues were collected, and cytoplasmic proteins were extracted; the levels of apoptosis-inducing factor (AIF), cytochrome c (cyto c), Bcl-2, Bax, procaspase-9, and procaspase-3 were measured by Western blot, and the activities of caspase-9 and caspase-3 were measured using a test kit. RESULTS: Compared with the control group, all CS(2) exposure groups had significantly increased levels of cyto c in the cytoplasm of testicular tissue (P<0.05); in the 250 mg/m(3) CS(2) exposure group, the Bax/Bcl-2 ratio and activities of caspase-9 and caspase-3 increased significantly (P<0.05), and the content of procaspase-9 and procaspase-3 decreased significantly (P<0.05); in the 1250 mg/m(3) CS(2) exposure group, the relative expression levels of Bax and AIF in cytoplasm increased significantly (P<0.05), and the expression level of Bcl-2 decreased significantly (P<0.05). CONCLUSION: Mitochondrial pathway plays an important role in the CS(2)-induced apoptosis of spermatogenic cells in testicular tissue among male rats.

Screw Pullout Strength After Pedicle Screw Reposition: A Finite Element Analysis.

RESEARCH DESIGN: Finite element analysis based on computed tomography images from the lumbar spine. OBJECTIVE: Determined the pullout strength of unsatisfactorily placed screws and repositioned screws after unsatisfactory place in lumbar spine surgery. BACKGROUND: Pedicle screws are widely used to stabilize the spinal vertebral body. Unsatisfactory screws could lead to surgical complications, and may need to be repositioned. Screw removal and reposition, however, may decrease pullout strength. METHODS: We conducted a three-dimensional finite element analysis based on high-resolution computed tomography images from a 39-year-old healthy woman. Pullout strength was determined with the screw placed in different orientations at the same entry point (as selected by the Magerl method), as well as after removal and reposition. The material properties of the vertebral body and the screw were simulated by using grayscale values and verified data, respectively. A load along the screw axis was applied to the end of the screw to simulate the pullout. RESULTS: The pullout strength was 1840.0 N with the Magerl method. For unsatisfactorily placed screws, the pullout strength was 1500.8 N at 20% overlap, 1609.6 N at 40% overlap, 1628.9 N at 60% overlap, and 1734.7 N at 80% overlap with the hypothetical screw path of the Magerl method. For repositioned screws, the pullout strength was 1763.6 N, with 20% overlap, 1728.3 N at 40% overlap, 1544.0 N at 60% overlap, and 1491.1 N at 80% overlap, with the original path. Comparison of repositioned screw with unsatisfactorily placed screw showed 14.04% decrease in pullout strength at 80% overlap, 5.21% decrease at 60% overlap, 7.37% increase at 40% overlap, and 17.51% increase at 20% overlap, with the screw path of the Magerl method. CONCLUSIONS: Removal and reposition increased the pullout strength at 20% and 40% overlap, but decreased the pullout strength at 60% and 80% overlap. For clinical translation, we recommend removal and reposition of the screw when the overlap is in the range of 20% to 40% or less. In vitro specimen studies are needed to verify these preliminary findings.

Temporal and spatial distributions, source identification, and health risk assessment of polycyclic aromatic hydrocarbons in PM2.5 from 2016 to 2021 in Shenzhen, China.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants in the atmosphere that have drawn intense attention due to their carcinogenicity and mutagenicity. In this work, 1424 air samples were collected between January 2016 and December 2021 in three areas of Shenzhen, China to determine the concentrations of PM2.5 and PAHs and their spatiotemporal variation. Human health risks due to the daily intake and uptake of PAHs and the resulting incremental lifetime cancer risk (ILCR) were also evaluated. PAHs were detected frequently in the samples at concentrations between 0.28 and 32.7 ng/m3 (median: 1.04 ng/m3). PM2.5 and PAH concentrations decreased from 2016 to 2021, and the Yantian area had lower median concentrations of PM2.5 (23.0 µg/m3) and PAHs (0.02 ng/m3) than the Longgang and Nanshan areas. The concentrations of PM2.5 and PAHs were significantly higher in winter than in summer. Analysis of diagnostic ratios indicated that petroleum combustion was the dominant source of airborne PAHs in Shenzhen. The estimated daily intake (EDI) and uptake (EDU) of PAHs by local residents decreased gradually with increasing age, indicating that infants are at particular risk of PAH exposure. However, the incremental lifetime cancer risks (ILCRs) were below the threshold value of 10-6, indicating that inhalation exposure to PAHs posed a negligible carcinogenic risk to Shenzhen residents. While promising, these results may underestimate actual PAH exposure levels, so further analysis of health risks due to PAHs in Shenzhen is needed.

Trace elements in aquatic products from Shenzhen, China and their implications for human exposure.

Aquatic organisms in industrially polluted areas can accumulate large quantities of heavy metals. To assess the resulting health risks, 11 trace elements in 184 aquatic products representing 14 species of fish, crustaceans, and bivalves collected from Shenzhen, China were determined. Aluminum (Al), chromium (Cr), nickel (Ni), selenium (Se), antimony (Sb), manganese (Mn), copper (Cu), arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) were determined by inductively coupled plasma mass spectrometry. The pollution levels of each product and the human health risk resulting from their consumption were then assessed. The concentrations of As in 57 % of samples and Cd in 11 % of samples exceeded the upper limits stipulated by the Chinese National Food Safety Standards (GB 2762-2017), which was mainly due to high concentrations of trace elements in crustaceans and bivalves. The Nemerow integrated pollution index indicated that the aquatic products accumulated high levels of As and Cd. Health risk assessments using the target hazard quotient (THQ) and hazard index (HI) suggested that As and Cd exposure due to consumption of aquatic products presents a potential health risk for residents of Shenzhen.

A nationwide investigation of trace elements in rice and wheat flour in China: Levels, spatial distributions and implications for human exposure.

Rises in trace element contents in rice and wheat flour, which are staple foods for almost all the Chinese population, associated with rapid economic development have raised major concerns. This study aimed to assess trace element concentrations in these foods nationwide in China and associated human exposure risks. For these purposes, nine trace elements were measured in 260 rice samples and 181 wheat flour samples with 17 and 12 widely scattered geographical origins in China, respectively. Mean concentrations (mg kg-1) of the trace elements declined in the following orders: Zn > Cu > Ni > Pb > As > Cr > Cd > Se > Co in rice, and Zn > Cu > Ni > Se > Pb > Cr > Cd > As > Co in wheat flour. Significant regional differences in levels of trace elements in both rice and wheat flour were detected (p < 0.05), which may be related to local economic indicators. The hazard index (HI) of trace elements in rice samples from all origins exceeded 1, mainly due to the contribution of As, suggesting a potential non-carcinogenic risk. The total carcinogenic risk (TCR) for rice and wheat flour of all origins exceeded the safe level.

Increased emergency cases for out-of-hospital cardiac arrest due to cold spells in Shenzhen, China.

Cold spells have been associated with specific diseases. However, there is insufficient scientific evidence on the effects of cold spells on out-of-hospital cardiac arrest (OHCA). Data on OHCA cases and on meteorological factors and air pollutants were collected between 2013 and 2020. We adopted a quasi-Poisson generalized additive model with a distributed lag nonlinear model (DLNM) to estimate the effect of cold spells on daily OHCA incidence. Backward attributable risk within the DLNM framework was calculated to quantify the disease burden. We compared the effects and OHCA burden of cold spells using nine definitions. The risks of different cold spells on OHCA increased at higher intensities and longer durations. Based on Akaike's information criterion for the quasi-Poisson regression model and the attributable risk, the optimal cold spell was defined as a period in the cold month when the daily mean temperature was below the 10th percentile of the temperature distribution in the study period for at least 2 days. The single-day effect of the optimal cold spell on OHCA occurred immediately and lasted for approximately 1 week. The maximum single-day effect was 1.052 (95% CI: 1.018-1.087) at lag0, while the maximum cumulative effect was 1.433 (95% CI:1.148-1.788) after a 14-day lag. Men were more susceptible to cold spells. Young and middle-aged people were affected by cold spells similar to the elderly. Cold spells can increase the risk of OHCA with an approximately 1-week lag effect. Health regulators should take more targeted measures to protect susceptible populations during cold weather.

Mediating oxidative stress through the Palbociclib/miR-141-3p/STAT4 axis in osteoporosis: a bioinformatics and experimental validation study.

Osteoporosis is a common bone disease characterized by loss of bone mass, reduced bone strength, and deterioration of bone microstructure. ROS-induced oxidative stress plays an important role in osteoporosis. However, the biomarkers and molecular mechanisms of oxidative stress are still unclear. We obtained the datasets from the Gene Expression Omnibus (GEO) database, and performed differential analysis, Venn analysis, and weighted correlation network analysis (WGCNA) analysis out the hub genes. Then, the correlation between inflammatory factors and hub genes was analyzed, and a Mendelian randomization (MR) analysis was performed on cytokines and osteoporosis outcomes. In addition, "CIBERSORT" was used to analyze the infiltration of immune cells and single-cell RNA-seq data was used to analyze the expression distribution of hub genes and cell-cell communications. Finally, we collected human blood samples for RT-qPCR and Elisa experiments, the miRNA-mRNA network was constructed using the miRBase database, the 3D structure was predicted using the RNAfold, Vfold3D database, and the drug sensitivity analysis was performed using the RNAactDrug database. We obtained three differentially expressed genes associated with oxidative stress: DBH, TAF15, and STAT4 by differential, WGCNA clustering, and Venn screening analyses, and further analyzed the correlation of these 3 genes with inflammatory factors and immune cell infiltration and found that STAT4 was significantly and positively correlated with IL-2. Single-cell data analysis showed that the STAT4 gene was highly expressed mainly in dendritic cells and monocytes. In addition, the results of RT-qPCR and Elisa experiments verified that the expression of STAT4 was consistent with the previous analysis, and a significant causal relationship between IL-2 and STAT4 SNPs and osteoporosis was found by Mendelian randomization. Finally, through miRNA-mRNA network and drug sensitivity analysis, we analyzed to get Palbociclib/miR-141-3p/STAT4 axis, which can be used for the prevention and treatment of osteoporosis. In this study, we proposed the Palbociclib/miR-141-3p/STAT4 axis for the first time and provided new insights into the mechanism of oxidative stress in osteoporosis.

Anomalous peroxidase activity of cytochrome c is the primary pathogenic target in Barth syndrome.

Barth syndrome (BTHS) is a life-threatening genetic disorder with unknown pathogenicity caused by mutations in TAFAZZIN (TAZ) that affect remodeling of mitochondrial cardiolipin (CL). TAZ deficiency leads to accumulation of mono-lyso-CL (MLCL), which forms a peroxidase complex with cytochrome c (cyt c) capable of oxidizing polyunsaturated fatty acid-containing lipids. We hypothesized that accumulation of MLCL facilitates formation of anomalous MLCL-cyt c peroxidase complexes and peroxidation of polyunsaturated fatty acid phospholipids as the primary BTHS pathogenic mechanism. Using genetic, biochemical/biophysical, redox lipidomic and computational approaches, we reveal mechanisms of peroxidase-competent MLCL-cyt c complexation and increased phospholipid peroxidation in different TAZ-deficient cells and animal models and in pre-transplant biopsies from hearts of patients with BTHS. A specific mitochondria-targeted anti-peroxidase agent inhibited MLCL-cyt c peroxidase activity, prevented phospholipid peroxidation, improved mitochondrial respiration of TAZ-deficient C2C12 myoblasts and restored exercise endurance in a BTHS Drosophila model. Targeting MLCL-cyt c peroxidase offers therapeutic approaches to BTHS treatment.