Associations of environmental cadmium exposure with kidney damage: Exploring mediating DNA methylation sites in Chinese adults.

Environmental exposure is widely recognized as the primary sources of Cadmium (Cd) in the human body, and exposure to Cd is associated with kidney damage in adults. Nevertheless, the role of DNA methylation in Cd-induced kidney damage remains unclear. This study aimed to investigate the epigenome-wide association of environmental Cd-related DNA methylation changes with kidney damage. We included 300 non-smoking adults from the China in 2019. DNA methylation profiles were measured with Illumina Infinium MethylationEPIC BeadChip array. Linear mixed-effect model was employed to estimate the effects of urinary Cd with DNA methylation. Differentially methylated positions (DMPs) associated with urinary Cd were then tested for the association with kidney damage indicators. The mediation analysis was further applied to explore the potential DNA methylation based mediators. The prediction model was developed using a logistic regression model, and used 1000 bootstrap resampling for the internal validation. We identified 27 Cd-related DMPs mapped to 20 genes after the adjustment of false-discovery-rate for multiple testing among non-smoking adults. 17 DMPs were found to be associated with both urinary Cd and kidney damage, and 14 of these DMPs were newly identified within the Chinese. Mediation analysis revealed that DNA methylation of cg26907612 and cg16848624 mediated the Cd-related reduced kidney damage. In addition, ten variables were selected using the LASSO regression analysis and were utilized to develop the prediction model. It found that the nomogram model predicted the risk of kidney damage caused by environmental Cd with a corrected C-index of 0.779. Our findings revealed novel DMPs associated with both environmental Cd exposure and kidney damage among non-smoking adults, and developed an easy-to-use nomogram-illustrated model using these novel DMPs. These findings could provide a theoretical basis for formulating prevention and control strategies for kidney damage from the perspective of environmental pollution and epigenetic regulation.

Hourly Air Pollution Exposure and Emergency Hospital Admissions for Stroke: A Multicenter Case-Crossover Study.

BACKGROUND: Daily exposure to ambient air pollution is associated with stroke morbidity and mortality; however, the association between hourly exposure to air pollutants and risk of emergency hospital admissions for stroke and its subtypes remains relatively unexplored. METHODS: We obtained hourly concentrations of fine particulate matter (PM2.5), respirable particulate matter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO) from the China National Environmental Monitoring Center. We conducted a time-stratified case-crossover study among 86 635 emergency hospital admissions for stroke across 10 hospitals in 3 cities (Jinhua, Hangzhou, and Zhoushan) in Zhejiang province, China, between January 1, 2016 and December 31, 2021. Using a conditional logistic regression combined with a distributed lag linear model, we estimated the association between hourly exposure to multiple air pollutants and risk of emergency hospital admissions for total stroke, ischemic stroke, hemorrhagic stroke, and undetermined type. RESULTS: Hourly exposure to PM2.5, PM10, NO2, and SO2 was associated with an increased risk of hospital admissions for total stroke and ischemic stroke. The associations were most pronounced during the concurrent hour of exposure and lasted for ≈2 hours. We found that the risk was more pronounced among male patients or those aged <65 years old. CONCLUSIONS: Our findings suggest that exposure to PM2.5, PM10, NO2, and SO2, but not CO and O3, is associated with emergency hospital admissions for total stroke or ischemic stroke shortly after exposure. Implementing targeted pollution emission reduction measures may have significant public health implications in controlling and reducing the burden of stroke.

Impact of Heavy PM2.5 Pollution Events on Mortality in 250 Chinese Counties.

We explored the impact of heavy PM2.5 pollution events on the health of residents in 250 counties in China. A time-series approach involving a two-stage analysis was applied to estimate the association between heavy PM2.5 pollution events and mortality from 2013 to 2018. The associations between heavy (PM2.5 ≥75 µg/m3 and <150 µg/m3) and extremely heavy (PM2.5 ≥150 µg/m3) PM2.5 pollution days with mortality were explored. The added effects of the heavy PM2.5 pollution events were evaluated by controlling PM2.5 concentration in the model. From 2013 to 2018, there were 57,279 county days of heavy PM2.5 pollution and 21,248 county days of extremely heavy PM2.5 pollution. The risks of mortality during this period of heavy PM2.5 pollution events increased by 1.22% (95% CI: 0.82-1.63%), 1.14% (95% CI: 0.74-1.53%), 1.09% (95% CI: 0.58-1.60%), and 1.30% (95% CI: 0.40-2.20%), for all-cause, nonaccidental, circulatory, and respiratory mortality, respectively. We also observed that heavy PM2.5 pollution events had an added effect on mortality risk associated with all-cause, nonaccidental, circulatory, and respiratory mortality, evident from an observed increase by 0.77% (95% CI: 0.29-1.24%), 0.73% (95% CI: 0.27-1.19%), 0.96% (95% CI: 0.37-1.55%), and 0.55% (95% CI: -0.52-1.63%), respectively. Heavy PM2.5 pollution events increased mortality risks and caused an independent added effect. The findings serve as a foundation for policymakers in developing early warning systems and policy interventions.

Associations between Individual Exposure to Fine Particulate Matter Elemental Constituent Mixtures and Blood Lipid Profiles: A Panel Study in Chinese People Aged 60-69 Years.

Dyslipidemia may be a potential mechanism linking fine particulate matter (PM2.5) to adverse cardiovascular outcomes. However, inconsistent associations between PM2.5 and blood lipids have resulted from the existing research, and the joint effect of PM2.5 elemental constituents on blood lipid profiles remains unclear. We aimed to explore the overall associations between PM2.5 elemental constituents and blood lipid profiles and to identify the significant PM2.5 elemental constituents in this association. Sixty-nine elderly people were recruited between September 2018 and January 2019. Each participant completed a survey questionnaire, 3 days of individual exposure monitoring, health examination, and biological sample collection at each follow-up visit. Bayesian kernel machine regression (BKMR) models were used to identify the joint effects of the 17 elemental constituents on blood lipid profiles. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) levels were significantly increased in older adults when exposed to the mixture of PM2.5 elemental constituents. Copper and titanium had higher posterior inclusion probabilities than other constituents, ranging from 0.76 to 0.90 (Cu) and 0.74 to 0.94 (Ti). Copper and titanium in the PM2.5 elemental constituent mixture played an essential role in changes to blood lipid levels. This study highlights the importance of identifying critical hazardous PM2.5 constituents that may cause adverse cardiovascular outcomes in the future.

Linking the Fasting Blood Glucose Level to Short-Term-Exposed Particulate Constituents and Pollution Sources: Results from a Multicenter Cross-Sectional Study in China.

Ambient PM2.5 (fine particulate matter with aerodynamic diameters ≤ 2.5 µm) is thought to be associated with the development of diabetes, but few studies traced the effects of PM2.5 components and pollution sources on the change in the fasting blood glucose (FBG). In the present study, we assessed the associations of PM2.5 constituents and their sources with the FBG in a general Chinese population aged over 40 years. Exposure to PM2.5 was positively associated with the FBG level, and each interquartile range (IQR) increase in a lag period of 30 days (18.4 µg/m3) showed the strongest association with an elevated FBG of 0.16 mmol/L (95% confidence interval: 0.04, 0.28). Among various constituents, increases in exposed elemental carbon, organic matter, arsenic, and heavy metals such as silver, cadmium, lead, and zinc were associated with higher FBG, whereas barium and chromium were associated with lower FBG levels. The elevated FBG level was closely associated with the PM2.5 from coal combustion, industrial sources, and vehicle emissions, while the association with secondary sources was statistically insignificant. Improving air quality by tracing back to the pollution sources would help to develop well-directed policies to protect human health.

Epigenetic age stratifies the risk of blood pressure elevation related to short-term PM2.5 exposure in older adults.

BACKGROUND: Exposure to fine particulate matter (PM2.5) is a prominent risk factor for cardiovascular aging in older adults and causes mild syndromes or other comorbidities in otherwise healthy older adults. Accordingly, a precise tool for PM2.5 exposure risk stratification is urgently needed. We aimed to address this need by comparing the performances of seven types of epigenetic age and chronological age to classify the effects of short-term PM2.5 exposure on blood pressure (BP), a typical clinical surrogate marker of cardiovascular aging. METHODS: We conducted a panel study of the Chinese healthy adults aged 60-69 years through five monthly visits. Personal PM2.5 exposures were measured using wearable monitoring devices for three consecutive days, and DNA methylation was determined by the Illumina MethylationEPIC BeadChip using blood samples collected at each visit. Systolic BP, diastolic BP, mean arterial pressure and pulse pressure were measured by the electronic BP monitor. Linear mixed models with interaction terms between PM2.5 and different ages were used to assess their potential usefulness for stratification. RESULTS: DNAmPhenoAge, Skin & blood clock, DNAmGrimAge acceleration, and DunedinPoAm had significant modifying effects on the relationship between PM2.5 and BP. For instance, a 10-µg/m3 increase in the 72-h moving mean PM2.5 was significantly associated with 0.30% (95% CI: 0.10%, 0.51%) and -0.07% (95% CI: -0.32%, 0.18%) increases in systolic BP at higher and lower DNAmPhenoAge acceleration, respectively. Joint models further revealed that using a combination of epigenetic ages could more precisely stratify the effect of PM2.5 on BP. CONCLUSIONS: Our research indicates that epigenetic age may be a useful tool for evaluating the effect of short-term PM2.5 exposure on cardiovascular aging status.

Role of the gut-microbiota-metabolite axis in the rotenone model of early-stage Parkinson's Disease.

Gastrointestinal symptoms are common in the early-stage Parkinson's disease (PD), but its potential pathogenesis remains unclear. Therefore, in the present study, we used the 16S ribosomal RNA gene sequencing and gas chromatography coupled with mass spectrometry-based metabolomics to investigate the alterations of gut microbiome and serum amino acid levels in the early-stage PD mice model induced with rotenone. The results demonstrated that the microbial taxa at phylum, family and genus levels remarkably altered in rotenone-induced mice relative to vehicle-induced mice. The rotenone-induced mice had higher relative abundance of Flavobacteriaceae, Staphylococcaceae, and Prevotellaceae as well as lower relative abundance of Lachnospiraceae_UCG-001, Ruminiclostridium, and Prevotellaceae_NK3B31_group than vehicle-induced mice. The evaluation of serum amino acids revealed the alterations in several classes of amino acids, including L-proline, L-alanine, L-serine, L-asparagine, L-threonine, L-glutamine, L-methionine, and L-4-hydroxyproline. Notably, the altered serum amino acid levels were significantly associated with the abundance of gut microbiota, especially Ruminococcaceae and Ruminiclostridium. Our study explored the possible role of the gut-microbiota-metabolite axis in the early-stage PD and provided the possibility of prevention and treatment of PD by gut-microbiota-metabolite axis in the future.

Alterations of gut microbiota and metabolome with Parkinson's disease.

Gut microbiota and amino acids that are one of their metabolites play important roles in the mechanism of pathology of Parkinson's disease (PD). It has been reported that the level of amino acids in vivo participate in neurodegeneration by regulating adaptive immune response, while the current researches on alteration of amino acids in gut microbiota are still insufficient. We hypothesized that alterations in gut microbiota might be accompanied by altered concentrations of amino acids, leading to the occurrence of PD. In this study, we collected stool samples from PD and healthy controls to analyse fecal microbiome and targeted metabolome by 16S ribosomal RNA (16S rRNA) gene sequencing and gas chromatography coupled to mass spectrometry (GC-MS). At the genus level, there was a greater abundance of Alistipes, Rikenellaceae_RC9_gut_group, Bifidobacterium, Parabacteroides, while Faecalibacterium was decreased in fecal samples from PD patients. Moreover, fecal branched chain amino acids (BCAAs) and aromatic amino acids concentrations were significantly reduced in PD patients compared to controls. Our study not only finds the abundance of certain gut microbiota in PD,but also reveals that it is related to BCAAs and aromatic amino acids. These findings are beneficial to identifying new therapeutic targets for PD by regulating diet and/or gut microbiota.

Repetitive Transcranial Magnetic Stimulation (rTMS) Modulates Thyroid Hormones Level and Cognition in the Recovery Stage of Stroke Patients with Cognitive Dysfunction.

BACKGROUND This single-center study aimed to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on modulation of thyroid hormone levels and cognition in the recovery stage of patients with cognitive dysfunction following stroke. MATERIAL AND METHODS Seventy post-stroke patients who had cognitive impairment were randomly assigned to either the rTMS group or the control (sham) group. Both groups were administered basic treatment, with the rTMS group receiving rTMS (1 Hz, 90% MT, 1000 pulse/20 min, once a day for 5 days, for a total of 20 times), the stimulation site was the contralateral dorsolateral prefrontal cortex (DLPFC), and the sham group receiving sham stimulation which had the same stimulation parameters and site, except that the coil plane was placed perpendicular to the surface of the scalp. Cognitive function assessment and thyroid function tests were performed before and after 4 weeks of treatment. RESULTS Serum levels of triiodothyronine (T3), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) showed a positive correlation with Montreal Cognitive Assessment (MoCA) scale score of stroke patients in the recovery phase. The post-treatment change in the scores of MoCA and Modified Barthel Index (MBI) and scores of 3 cognitive domains (visuospatial function, memory, and attention), as well as serum T3, FT3, and TSH levels, were improved more significantly in the rTMS group, and T3 and FT3 levels significantly affected the MoCA scores within the reference range. CONCLUSIONS Serum T3, FT3, and TSH levels of stroke patients in the recovery phase were positively correlated with MoCA score. rTMS increased T3, FT3, and TSH levels and also improved MoCA and MBI of patients in the recovery phase of stroke.

Research on the Establishment and Application of the Environmental Health Indicator System of Atmospheric Pollution in China.

To understand the health impact represented by exposure to current atmospheric pollution in China, an environmental health indicators (EHIs) system of atmospheric pollution was established. The EHIs were based on comprehensive consideration of environment, population, economy and diseases associated with atmospheric pollution. An EHIs evaluation system of atmospheric pollution, based on corresponding EHIs data collection and weighting coefficients determined using principal component analysis, was applied to major provinces and regions in China to evaluate the environmental health status. Results showed that the EHIs of atmospheric pollution in Central and East China were low, indicating a serious environmental health condition. Prevention and management of atmospheric pollution in these regions should be strengthened and protective measures taken to improve human health. Compared with other methods, the EHIs evaluation system was more intuitive, which facilitated users to identify the environmental health status and provided support for health management and pollution prevention.

Calcipotriol and iBRD9 reduce obesity in Nur77 knockout mice by regulating the gut microbiota, improving intestinal mucosal barrier function.

OBJECTIVE: The orphan nuclear receptor Nur77 is an important factor regulating metabolism. Nur77 knockout mice become obese with age, but the cause of obesity in these mice has not been fully ascertained. We attempted to explain the cause of obesity in Nur77 knockout mice from the perspective of the gut microbiota and to investigate the inhibitory effect of calcipotriol combined with BRD9 inhibitor (iBRD9) on obesity. METHODS: Eight-week-old wild-type mice and Nur77 knockout C57BL/6J mice were treated with calcipotriol combined with iBRD9 for 12 weeks. Mouse feces were collected and the gut microbiota was assessed by analyzing 16S rRNA gene sequences. The bacterial abundance difference was analyzed, and the intestinal mucosal tight junction protein, antimicrobial peptide, and inflammatory cytokine mRNA levels of the colon and serum LPS and inflammatory cytokine levels were measured. RESULTS: Calcipotriol combined with iBRD9 treatment reduced the body weight and body fat percentage in Nur77 knockout mice. In the gut microbiota of Nur77 knockout mice, the relative abundances of Lachnospiraceae and Prevotellaceae decreased, and Rikenellaceae increased; while Rikenellaceae decreased after treatment (p < 0.05). Correspondingly, the mRNA levels of intestinal mucosal tight junction proteins (occludin (Ocln), claudin3 (Cldn3)) in the colons of Nur77 knockout mice were significantly decreased, and they increased significantly after treatment (p < 0.001). The mRNA levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß)) were significantly increased in Nur77 knockout mice, and TNF-α and IL-6 levels were significantly decreased after treatment (p < 0.05, <0.01, or <0.001). The levels of serum LPS, TNF-α, and IL-1ß in Nur77 knockout mice were significantly increased (p < 0.05). Serum LPS, TNF-α, and IL-6 levels were significantly decreased after treatment (p < 0.05 or <0.01). CONCLUSIONS: Calcipotriol combined with iBRD9 can regulate the gut microbiota, improve intestinal mucosal barrier function, reduce LPS absorption into the blood, and alleviate obesity in Nur77 knockout mice.

Depression and Anxiety Associated with Exposure to Fine Particulate Matter Constituents: A Cross-Sectional Study in North China.

The association between fine particulate matter (PM2.5) exposure and mental disorders is attracting increasing attention, but the roles of specific PM2.5 chemical constituents have yet to be explored. We conducted a multicenter cross-sectional study in nine cities located in the Beijing-Tianjin-Hebei region in China to assess the effects of PM2.5 and chemical constituents on depression and anxiety. The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scale were used to quantify the depression and anxiety status, atmospheric monitoring data from fixed stations was used to calculate exposure concentrations. We performed multiple logistic regression models to assess the associations of PM2.5 chemical constituents exposure over the preceding 2 weeks with depression and anxiety. Overall, anxiety and depression were significantly associated with organic carbon (OC), elemental carbon (EC), copper (Cu), cadmium (Cd), nickel (Ni), and zinc (Zn). Subgroup analysis showed a stronger effect of PM2.5 constituents on depression during the heating period. This study provide evidence for the possible link between PM2.5 constituents and mental disorders among middle-aged and elderly Chinese adults, which requires further validation of the causal correlation. Our findings support the need for a stricter regulation on emissions of certain specific constituents, in addition to targeting control of total PM2.5 emission concentration.

Modification Effects of Temperature on the Ozone-Mortality Relationship: A Nationwide Multicounty Study in China.

Both ozone exposure and extreme temperatures are found to be significantly associated with mortality; however, inconsistent results have been obtained on the modification effects of temperature on the ozone-mortality association. In the present study, we conducted a nationwide time-series analysis in 128 counties from 2013-2018 to examine whether temperature modifies the association between short-term ozone exposure with nonaccidental and cause-specific mortality in China. First, we analyzed the effects of ozone exposure on mortality at different temperature levels. Then, we calculated the pooled effects through a meta-analysis across China. We found that high-temperature conditions (>75th percentile in each county) significantly enhanced the effects of ozone on nonaccidental, cardiovascular, and respiratory mortality, with increases of 0.44% (95% confidence interval (CI): 0.36 and 0.51%), 0.42% (95% CI: 0.32 and 0.51%) and 0.50% (95% CI: 0.31 and 0.68%), respectively, for a 10 µg/m3 increase in ozone at high temperatures. Stronger effects on nonaccidental and cardiovascular mortality were observed at high temperatures among elderly individuals aged 65 years and older compared with the younger people. Our findings provide evidence that health damage because of ozone may be influenced by the impacts of increasing temperatures, which point to the importance of mitigating ozone exposure in China under the context of climate change to further reduce the public health burden.

Plasma 25-Hydroxyvitamin D Concentrations Are Inversely Associated with All-Cause Mortality among a Prospective Cohort of Chinese Adults Aged ≥80 Years.

BACKGROUND: High concentrations of plasma 25-hydroxyvitamin D [25(OH)D], a marker of circulating vitamin D, have been associated with a lower risk of mortality in epidemiologic studies of multiple populations, but the association for Chinese adults aged ≥80 y (oldest old) remains unclear. OBJECTIVE: We investigated the association between plasma [25(OH)D] concentration and all-cause mortality among Chinese adults aged ≥80 y. DESIGN: The present study is a prospective cohort study of 2185 Chinese older adults (median age: 93 y). Prospective all-cause mortality data were analyzed for survival in relation to plasma 25(OH)D using Cox proportional hazards regression models, with adjustments for potential sociodemographic and lifestyle confounders and biomarkers. The associations were measured with HR and 95% CIs. RESULTS: The median plasma 25(OH)D concentration was 34.4 nmol/L at baseline. Over the 5466 person-year follow-up period, 1100 deaths were identified. Men and women were analyzed together as no effect modification by sex was found. After adjusting for multiple potential confounders, the risk of all-cause mortality decreased as the plasma 25(OH)D concentration increased (P-trend <0.01). Compared with the lowest age-specific quartile of plasma 25(OH)D, the adjusted HRs for mortality for the second, third, and fourth age-specific quartiles were 0.72 (95% CI: 0.57, 0.90), 0.73 (95% CI: 0.58, 0.93), and 0.61 (95% CI: 0.47, 0.81), respectively. The observed associations were broadly consistent across age and other subgroups. Sensitivity analyses generated similar results after excluding participants who died within 2 y of follow-up or after further adjustment for ethnicity and chronic diseases. CONCLUSIONS: A higher plasma 25-hydroxyvitamin D concentration was associated with a reduced risk of all-cause mortality among Chinese adults aged ≥80 y. This observed inverse association warrants further investigation in randomized controlled trials testing vitamin D supplementation in this age group.

Health-risk perception and its mediating effect on protective behavioral adaptation to heat waves.

Ensuring spontaneously adjusting behaviors of the public in their daily life in response to heat waves is an important aspect of successful public health intervention under climate change. However, the current response behavior guidance released by the government is insufficient because of the limited understanding of public perceptions of heat-related risk and the motivating factors for the public's diverse adaptive behaviors. Here, we conducted a survey on the behavioral adaptations of 3065 urban residents in response to heat waves in Jinan, which is a typical city suffering from a hot climate. We provided evidence on the current state of residents' perception of heat waves and the mechanism of how risk perception mediates individual behavioral intentions upon exposure to high ambient temperatures. We found that the mediating effects of risk perception varied significantly with respect to different types of adaptive behaviors. Concern behaviors appeared be motivated completely by the mediating effects of perceived concern (b = 0.45, p < 0.01 for concerns about health guidelines; b = 0.36, p < 0.01 for concerns about the weather forecast) and severity (b = 0.11, p < 0.01 for concerns about health guidelines), while outdoor activity could be consciously adjusted according to temperature changes without those mediating effects (p > 0.05). Indoor cooling behaviors and transportation behaviors are partially mediated by risk perception (b = -0.04, p < 0.01; b = 0.08, p < 0.01; b = 0.08, p < 0.01 for indoor fan usage, use of air-conditioned buses, and use of private cars, respectively). The conclusions could help determine more targeted and detailed interventions to enhance public behavioral adjustments, including participation in adaption to and emergency preparedness for extreme temperature under the ongoing climate changes.

Identification of Recent Trends in Research on Vitamin D: A Quantitative and Co-Word Analysis.

BACKGROUND In recent years, many studies on vitamin D have been published. We combed these data for hot spot analyses and predicted future research topic trends. MATERIAL AND METHODS Articles (4625) concerning vitamin D published in the past 3 years were selected as a study sample. Bibliographic Items Co-occurrence Matrix Builder (BICOMB) software was used to screen high-frequency Medical Subject Headings (MeSH) terms and construct a MeSH terms-source article matrix and MeSH terms co-occurrence matrix. Then, Graphical Clustering Toolkit (gCLUTO) software was employed to analyze the matrix by double-clustering and visual analysis to detect the trends on the subject. RESULTS Ninety high-frequency major MeSH terms were obtained from 4625 articles and divided into 5 clusters, and we generated a visualized matrix and a mountain map. Strategic coordinates were established by the co-occurrence matrix of the MeSH terms based on the above classification, and the 5 clusters described above were further divided into 7 topics. We classified the vitamin D-related diseases into 12 categories and analyzed their distribution. CONCLUSIONS The analysis of strategic coordinates revealed that the epidemiological study of vitamin D deficiency and vitamin D-related diseases is a hot research topic. The use of vitamin D in the prevention and treatment of some diseases, especially diabetes, was found to have a significant potential future research value.

Neuroprotective effects of sulforaphane on cholinergic neurons in mice with Alzheimer's disease-like lesions.

Alzheimer's disease (AD) is a common neurodegenerative disease in elderly individuals, and effective therapies are unavailable. This study was designed to investigate the neuroprotective effects of sulforaphane (an activator of NF-E2-related factor 2) on mice with AD-like lesions induced by combined administration of aluminum and D-galactose. Step-down-type passive avoidance tests showed sulforaphane ameliorated cognitive impairment in AD-like mice. Immunohistochemistry results indicated sulforaphane attenuated cholinergic neuron loss in the medial septal and hippocampal CA1 regions in AD-like mice. However, spectrophotometry revealed no significant difference in acetylcholine level or the activity of choline acetyltransferase or acetylcholinesterase in the cerebral cortex among groups of control and AD-like mice with and without sulforaphane treatment. Sulforaphane significantly increased the numbers of 5-bromo-2'-deoxyuridine-positive neurons in the subventricular and subgranular zones in AD-like mice which were significantly augmented compared with controls. Atomic absorption spectrometry revealed significantly lower aluminum levels in the brains of sulforaphane-treated AD-like mice than in those that did not receive sulforaphane treatment. In conclusion, sulforaphane ameliorates neurobehavioral deficits by reducing cholinergic neuron loss in the brains of AD-like mice, and the mechanism may be associated with neurogenesis and aluminum load reduction. These findings suggest that phytochemical sulforaphane has potential application in AD therapeutics.

Association between exposure to chemical mixtures and epigenetic ageing biomarkers: Modifying effects of thyroid hormones and physical activity.

Evidence on the effects of internal chemical mixture exposures on biological age is limited. It also remains unclear whether hormone homeostasis and lifestyle factors can modify such a relationship. Based on the Biomarkers for Air Pollutants Exposure (BAPE) study, which involved healthy older adults aged 60-69 years in China, we found that chemical mixture exposures, including metals, polycyclic aromatic hydrocarbons (PAHs), per- and polyfluoroalkyl substances (PFASs), phthalates (PAEs), and organophosphate esters (OPEs), were significantly associated with shortened DNAmTL and accelerated SkinBloodClock, in which PFASs and OPEs in blood were the primary contributors to DNAmTL, while metals and PAEs had relatively higher contributions in urine. Furthermore, lower levels of thyroxin appeared to exacerbate the adverse effects of environmental chemicals on epigenetic ageing but relatively higher levels of physical activity had the beneficial impact. These findings may have important implications for the development of healthy ageing strategy and aged care policy, particularly in light of the global acceleration of population ageing.

Influence of maximum diameter on fine-needle aspiration biopsy outcomes in ACR TI-RADS 5 thyroid nodules.

Introduction: Fine needle aspiration (FNA) biopsy is a widely accepted method for diagnosing thyroid nodules. However, the influence of maximum diameter (MD) of ACR TIRADS 5 (TR5) thyroid nodules on the FNA outcomes remains debated. This study examined the influence of MD on the FNA outcomes and investigated the optimal MD threshold for FNA in TR5 nodules. Methods: We conducted a retrospective analysis of 280 TR5 thyroid nodules from 226 patients who underwent FNA from January to June 2022 in our department. Probably malignant (PM) group was defined as Bethesda V in cytopathology with confirmed BRAF V600E mutation or Bethesda VI, the other cytopathology outcomes were defined as probably benign (PB) group. We examined factors influencing malignant cytopathology outcomes and determined the optimal MD threshold for FNA in TR5 nodules using logistic regression and restricted cubic spline (RCS) analysis. Results: Among these nodules, 58.2% (163/280) had PM outcomes. The PM group had a significantly larger MD than the PB group [6.5mm (range 5.0-8.4) vs. 5.3mm (range 4.0-7.0), p < 0.001]. In multivariate logistic regression fully adjusted for confounders, MD was significantly associated with PM outcomes [odds ratio 1.16, 95%CI 1.05-1.31; p = 0.042]. The highest quartile of MD had a greater likelihood of PM outcomes compared to the lowest quartile [odds ratio 4.71, 95% CI 1.97-11.69, p = 0.001]. The RCS analysis identified 6.2 mm as the optimal MD threshold for FNA in TR5 nodules. Conclusion: MD significantly affects the probability of malignant outcomes in FNA of TR5 thyroid nodules. A MD threshold of ≥6.2mm is suggested for FNA in these nodules.

Regression equation for predicting dietary phosphorus intake based on estimated dietary protein intake: A multicenter cross-sectional study in China.

BACKGROUND: Protein and phosphorus intake, which affect chronic kidney disease (CKD), is assessed using cumbersome food diaries. Therefore, more straightforward and accurate methods of assessing protein and phosphorus intake are needed. We decided to investigate the nutrition status and dietary protein and phosphorus intake of patients with stages 3, 4, 5, or 5D CKD. METHODS: This cross-sectional survey included outpatients with CKD at seven class A tertiary hospitals in Beijing, Shanghai, Sichuan, Shandong, Liaoning, and Guangdong in China. Protein and phosphorus intake levels were calculated using 3-day food records. Protein levels and calcium and phosphorus serum concentrations were measured; urinary urea nitrogen was determined using a 24-h urine test. Protein and phosphorus intakes were calculated using the Maroni and Boaz formulas, respectively. The calculated values were compared with the recorded dietary intakes. An equation that regressed phosphorus intake on protein intake was constructed. RESULTS: The average recorded energy and protein intake was 1637.5 ± 595.74 kcal/day and 56.97 ± 25.25 g/day, respectively. Overall, 68.8% of patients had a good nutrition status (grade A on the Subjective Global Assessment). The correlation coefficient between protein intake and calculated intake was 0.145 (P = 0.376) and that between phosphorus intake and calculated intake was 0.713 (P < 0.001). CONCLUSION: Protein and phosphorus intakes correlated linearly. Chinese patients with stage 3-5 CKD had low daily energy intake but high protein intake. Malnutrition was present in 31.2% of patients with CKD. The phosphorus intake could be estimated from the protein intake.