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Summary: Increasing cohort studies have examined the link between mitochondrial DNA copy number (mtDNA-CN) and cardiovascular disease (CVD), with inconsistent findings. We searched PubMed, EMBASE, and Web of Science up to July 11, 2023 and used a random-effects model to calculate summary hazard ratios (HRs) and 95% confidence intervals (CIs). This systematic review and meta-analysis included 8 articles encompassing 29 studies with 646,398 participants. Individuals with the lowest mtDNA-CN had a summary HR of 1.27 (95% CI 1.02–1.59) for CVD, 1.18 (95% CI 0.92–1.50) for coronary heart disease (CHD), 1.10 (95% CI 0.89–1.37) for stroke, and 1.30 (95% CI 1.07–1.56) for heart failure (HF). Decreased mtDNA-CN is linked to an increased risk of CVD and HF but not CHD and stroke. These findings suggest mtDNA-CN from leukocytes may be a potential early biomarker for CVD. However, more prospective studies with long follow-up are needed.

Exploring the energy evolution of fractured sandstone under true triaxial cyclic loading is helpful to clarify the law of rock damage and failure. The evolution characteristics of total absorbed energy, elastic energy, dissipated energy and plastic deformation energy during the test were systematically analyzed. A rock damage evaluation model was established, and the rock damage failure law was discussed in combination with the mesoscopic damage characteristics of the fracture surface. The results show as follows: with the increase of crack angle, the greater the peak strength of the sample during failure, the greater the total absorbed energy, they were 0.238, 0.276, 0.307 and 0.332 MJ/m3, respectively; the total absorbed energy, elastic energy and dissipated energy increase gradually during the whole test process, while the plastic deformation energy decreases first and then increases; based on hysteretic loop energy and total dissipated energy, an evaluation index was established to describe rock damage, and the results of the two evaluation methods are consistent, and it is found that the rock damage degree changes nonlinear with loading and unloading during the test; the number of cyclic loading and unloading during the failure of the sample has a significant influence on the internal damage of the sample. The more times of cyclic loading and unloading, the higher the degree of extrusion friction and the more complex the micromorphology of the fracture surface.

Objective To investigate the efficacy of single drug treatment of dapagliflozin and combination of dapagliflozin and sitagliptin in the treatment of type 2 diabetes mellitus (T2DM). Methods Sixty-two patients with T2DM admitted to Luhe District Hospital of Chinese Medicine from January 2022 to December 2023 were selected as research subjects, and the patients were randomly divided into two groups, with 31 cases in each group. The control group only received treatment with dapagliflozin (10 mg/d oral), while the observation group received both dapagliflozin (10 mg/d oral) and sitagliptin (100 mg/d oral) treatment. Both groups were treated for 3 months. The post-treatment blood glucose control effects ［fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c)］, blood glucose fluctuations, inflammatory markers ［C-reactive protein (CRP)］, and cardiac function ［left ventricular ejection fraction (LVEF)］ were compared between two groups. Results After 3 months of treatment, compared with before treatment, both groups showed a significant decrease in FPG and HbA1c after treatment (P＜0.05). Compared with the control group, FPG ［(6.96±0.87) mmol/L vs (7.91±0.96) mmol/L, t=4.083, P＜0.01］ and HbA1c ［(6.54±0.33)% vs (7.65±0.58)%, t=9.261, P＜0.01］ of patients in the observation group were significantly decreased, and the standard deviation of mean blood glucose (SDBG) and amplitude of postprandial blood glucose fluctuation (PPGE) were lower (P

Abstract Background This study used a bidirectional 2-sample Mendelian randomization study to investigate the potential causal links between mtDNA copy number and cardiometabolic disease (obesity, hypertension, hyperlipidaemia, type 2 diabetes [T2DM], coronary artery disease [CAD], stroke, ischemic stroke, and heart failure). Methods Genetic associations with mtDNA copy number were obtained from a genome-wide association study (GWAS) summary statistics from the UK biobank (n = 395,718) and cardio-metabolic disease were from largest available GWAS summary statistics. Inverse variance weighting (IVW) was conducted, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. We repeated this in the opposite direction using instruments for cardio-metabolic disease. Results Genetically predicted mtDNA copy number was not associated with risk of obesity (P = 0.148), hypertension (P = 0.515), dyslipidemia (P = 0.684), T2DM (P = 0.631), CAD (P = 0.199), stroke (P = 0.314), ischemic stroke (P = 0.633), and heart failure (P = 0.708). Regarding the reverse directions, we only found that genetically predicted dyslipidemia was associated with decreased levels of mtDNA copy number in the IVW analysis (β= − 0.060, 95% CI − 0.044 to − 0.076; P = 2.416e−14) and there was suggestive of evidence for a potential causal association between CAD and mtDNA copy number (β= − 0.021, 95% CI − 0.003 to − 0.039; P = 0.025). Sensitivity and replication analyses showed the stable findings. Conclusions Findings of this Mendelian randomization study did not support a causal effect of mtDNA copy number in the development of cardiometabolic disease, but found dyslipidemia and CAD can lead to reduced mtDNA copy number. These findings have implications for mtDNA copy number as a biomarker of dyslipidemia and CAD in clinical practice.

Summary: Skeletal muscle may mutually interact with gastrointestinal disease through metabolic homeostasis and nutritional status and therefore may be a marker for early risk detection. We conducted a prospective cohort analysis including 393,606 participants (mean age 56.0 years, 53.9% female) from the UK Biobank. The exposures were grip strength and skeletal muscle mass (SMM). The primary outcomes were 24 incident gastrointestinal diseases. During a mean follow-up of 12.1 years, we found that one sex-specific SD increase in grip strength and SMM were associated with reduced risk of 16 and 19 gastrointestinal diseases, respectively. For grip strength, the HRs ranged from 0.94 (for ulcerative colitis) to 0.80 (for liver cancers). For SMM, the HRs ranged from 0.92 (for colorectal cancer) to 0.51 (for non-alcoholic fatty liver disease). Our finding suggested that grip strength and SMM might be significant indicators for gastrointestinal diseases risk screen.

Background: The main clinical manifestations of patients with Pierre Robin sequence (PRS) include micrognathia, the glossoptosis and dyspnoea. The difficulty of tracheal intubation (TI) in such patients is increased.Objective: The purpose of the study was to evaluate the reliability and efficacy of the PRS simulator.Methods: A PRS simulator was developed by using 3-dimensional (3D) printing technology under computer-aided design. A total of 12 anaesthesiologists each trained 5 times for TI on the PRS Training Simulator-1 and recorded the simulation time. After the training, they were randomly divided into three groups with a total of 12 nontrained anaesthesiologists, and the simulation was completed on PRS Simulator-2, 3 and 4. The simulation time was recorded, and the performance was evaluated by three chief anaesthesiologists. Then, all 24 anaesthesiologists completed the questionnaire.Results: A PRS simulator developed by 3D printing was used to simulate the important aspects of TI. The average number of years worked was 6.3 ± 3.1 years, and 66.7% were female. The time for the 12 anaesthesiologists to complete the training gradually decreased (p < 0.01). Compared with the trained anaesthesiologists, the simulation time of TI in the nontrained anaesthesiologists was much longer (all p < 0.01). In addition, the simulation performance of the trained anaesthesiologists was relatively better (all p < 0.01).Conclusion: The reliability and efficacy of the PRS simulator is herein preliminarily validated, and it has potential to become a teaching and training tool for anaesthesiologists.

Background: The real-world safety profile of COVID-19 mRNA vaccines remains incompletely elucidated. Methods: We performed a nationwide post-market safety surveillance analysis in Singapore, on vacinees aged 5 years and older, through mid-September 2022. Observed-over-expected (O/E) analyses were performed to identify potential safety signals among eight shortlisted adverse events of special interest (AESIs): strokes, cerebral venous thrombosis (CVT), acute myocardial infarction, myocarditis/pericarditis, pulmonary embolism, immune thrombocytopenia, convulsions and appendicitis. Self-controlled case series analyses (SCCS) were performed to validate signals of concern, occurring within 42 days of vaccination. Findings: Elevated risks were observed on O/E analyses for the following AESIs: myocarditis/pericarditis, [rate ratio (RR): 3.66, 95 % confidence interval (95 % CI): 2.71 to 4.94], appendicitis [RR: 1.14 (1.02 to 1.27)] and CVT [RR: 2.11 (1.18 to 3.77)]. SCCS analyses generated corroborative findings: myocarditis/pericarditis, [relative incidence (RI): 6.96 (3.95 to 12.27) at 1 to 7 days post-dose 2], CVT [RI: 4.30 (1.30 to 14.20) at 22 to 42 days post-dose 1] and appendicitis [RI: 1.31 (1.03 to 1.67) at 1 to 7 days post-dose 1]. Booster dose 1 continued to be associated with higher rates of myocarditis/pericarditis on O/E analysis [RR: 2.30, (1.39 to 3.80) and 1.69, (1.11 to 2.59)] at 21- and 42-days post-booster dose 1, respectively. Males aged 12 to 17 exhibited highest risks of both myocarditis/pericarditis [RI: 6.31 (1.36 to 29.3)] and appendicitis [RI: 2.01 (1.12 to 3.64)] after primary vaccination. Similarly, CVT was also predominantly observed in males aged above 50 (11 out of 16 cases), within 42-days of vaccination. Interpretation: Our data suggest that myocarditis/pericarditis, appendicitis and CVT are associated with primary vaccination using COVID-19 mRNA vaccines. Males at specific ages exhibit higher risks for all three AEs identified. The risk of myocarditis/pericarditis continues to be elevated after booster dose 1.

In this work, a series of novel compounds Spartinin C1-C24 were screened, synthesised and evaluated for inhibiting xanthine oxidase thus lowering serum uric acid level. The backbones were derived from the components of coastal marine source Spartina alterniflora and marketed drugs. The top hits Spartinin C10 & C22 suggested high inhibition percentages (78.54 and 93.74) at 10 μM dosage, which were higher than the positive control Allopurinol. They were low cytotoxic onto human normal hepatocyte cells. Treatment with Spartinin C10 could lower the serum uric acid level to 440.0 μM in the hyperuricemic model mice (723.0 μM), comparable with Allopurinol (325.8 μM). Spartinin C10 was more appreciated than Allopurinol on other serum indexes. The preliminary pharmacokinetics evaluation indicated that the rapid absorption, metabolism and elimination of Spartinin C10 should be further improved. The discovery of pharmaceutical molecules from coastal marine source here might inspire the inter-disciplinary investigations on public health.

ObjectivesTo conduct a systematic review and meta-analysis of prospective cohort studies to investigate the association between total, vegetable, fruit, cereal, soluble and insoluble fiber intake and risk of all causes, cardiovascular disease (CVD), and cancer mortality and quantitatively assess the dose–response relation.MethodsEligible studies were identified by searching PubMed, Embase and Web of science before August 2023. Random effects models were used to calculate summary relative risk (RR) and 95% confidence intervals (CI) and restricted cubic splines to model the linear/non-linear association.ResultsThe summary RR for all-cause, CVD and cancer mortality of dietary fiber was 0.90 (95% CI: 0.86,0.93), 0.87 (0.84,0.91), 0.91 (0.88,0.93), respectively. Significant association was observed for all-cause and CVD mortality with fruit, vegetable cereal and soluble fiber intake and cancer mortality with cereal fiber intake. No significant association was found for insoluble fiber, vegetable or fruit fiber intake and cancer mortality. Dose-response analysis showed a significant non-linear relation of dietary fiber intake with all-cause mortality, and linear relation for others.ConclusionsHigher dietary fiber including different type and food sources of fiber intake were associated with lower risk of mortality. Our findings provide more comprehensive evidence on dietary fiber intake with mortality.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier: CRD42022338837.

Spartina alterniflora is native to the Atlantic coast of the United States, which is recognized as an alien species along the Pacific coast. S. alterniflora has attracted much attention in related fields for many years. In order to deepen the understanding of S. alterniflora related research, and explore the future research priorities, the paper analyzed its research progress quantitatively and protracted visual knowledge graph by VOSviewer software with the key words of S. alterniflora during 1972-2020 from Web of Science database by bibliometric analysis method. The number of published papers and citations of S. alterniflora has been rising during 1972-2020, and shown a rapid development trend since 2004. The research areas covered ecology, environmental science, marine and freshwater biology. The publications were mainly contributed by countries in America, Asia, Europe and Oceania, and the United States ranked the 1st followed by China. The topics of S. alterniflora focus on its effects on salt marsh ecosystem, biogeochemical cycle, physiology and interspecific interaction. S. alterniflora′s contributions to blue carbon and responses to global climate change is the current hot topic in coastal salt marshes.

Abstract Objectives Neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII), easily accessible systemic inflammation response parameters, were reported to associate with poor lung cancer prognosis. However, research on the effects of these markers on the risk of positive nodules (PNs) and lung cancer is limited. Methods Participants in this retrospective study were those who had their first computed tomography (CT) screening at Jiangsu Province Hospital's Health Promotion Center between January 1, 2017 and December 31, 2020. We identified PNs (≥6 mm in diameter) from free text of CT reports and lung cancer from medical records. Multivariate logistic analysis was used to assess the association between NLR, PLR, or SII and PNs or lung cancer. Results The detected rate of PNs was 9.60% among the 96,476 participants. Age, smoking and body mass index were possible influencing factors for PNs. We observed linear dose‐effect relationship between NLR, PLR, or SII and PNs (pnon‐linear > 0.05). Compared with low quintile, participants with top quintiles of NLR, PLR or SII had an increased risk of PNs, with the adjusted ORs of 1.19 (1.11–1.28), 1.11 (1.04–1.19) or 1.11 (1.03–1.18), respectively. Meanwhile, NLR showed the U‐shaped relationship with lung cancer, with adjusted ORs of 1.40 (1.08–1.81) comparing highest NLR quintile to the third quintile. The high PLR and SII showed significantly associated with lung cancer with adjusted ORs of 1.29 (0.99–1.68) and 1.35 (1.04–1.74) comparing to the lowest quintile. Conclusions The high levels of systemic inflammation markers were associated with the risk of positive pulmonary nodules and lung cancer, which suggested systemic immune response may be an important pre‐clinical feature for the early identification of diseases.

BackgroundHealthcare workers were at high risk of psychological problems during the COVID-19 pandemic, but it remains not well-investigated in the post-pandemic era of COVID-19, with regular epidemic prevention and control embedded in burdened healthcare work. This study aimed to investigate the prevalence and potential risk factors of the symptoms of depression and anxiety among healthcare workers at a tertiary hospital in Shenzhen.MethodOur cross-sectional study was conducted among 21- to 64-year-old healthcare workers in December 2021 at a tertiary hospital in Shenzhen, using a simple random sampling strategy. A wide range of socio-demographic characteristics, individual information, and psychological condition of the subjects were extracted. Healthcare workers' psychological conditions were tested with the Center for Epidemiologic Studies Depression (CESD-10), General Anxiety Disorder (GAD-7), Insomnia Severity Index (ISI), Work-Family Conflict Scale (WFCS), 10-item Connor-Davidson Resilience Scale (CD-RISC-10), and 17-item of Maslach's Burnout Inventory-Human Services Survey (MBI-HSS-17). Data were collected based on these questionnaires. Descriptive statistics were used to assess the difference between healthcare workers with depressive and anxiety symptoms among different groups. Hierarchical logistic regression analyses were conducted to investigate the association between focused variables and mental health outcomes.ResultsA total of 245 healthcare workers were enrolled. The proportion of depressive symptoms, anxiety symptoms and their co-occurrence were 34.7, 59.6, and 33.1%, respectively. Logistic regression showed that for the three outcomes, no history of receiving psychological help and self-rated good or higher health were protective factors, whereas more severe insomnia and job burnout were risk factors. Junior or lower job title and higher psychological resilience were related to a lower prevalence of depressive symptoms, while relatively longer working hours and larger work-family conflict were positively associated with the anxiety symptoms. Psychological resilience was inversely associated with the co-occurrence of depressive and anxiety symptoms.ConclusionsOur study revealed a high proportion of psychological problems and proved that several similar factors which were significant during the pandemic were also associated with the symptoms of depression and anxiety among healthcare workers in the post-pandemic era of COVID-19. These results provide scientific evidence for psychological interventions for healthcare workers.

We aimed to assess the association between fasting plasma glucose (FPG) change trajectory and incident hypertension among Chinese population. This cohort study included 11,791 adults aged 18–80 years without hypertension at first entry and who completed at least four follow-ups between 2009 and 2016. Logistic regression was used to estimate odds ratios (ORs) and 95% CIs for the association between FPG change trajectory and probability of hypertension. During a median follow-up of 5.10 years (total person– years 61,887.76), hypertension developed in 2177 participants. After adjusting for baseline potential confounders, the probability of hypertension increased with the increasing FPG change trajectory (adjusted OR (aOR) 1.22, 95% CI 1.07–1.40), bell-shape trajectory (aOR 1.15, 95% CI 1.02–1.30) and other-shape trajectory (aOR 1.13, 95% CI 1.02–1.25) which showed a higher variability of FPG compared to the decreasing group. In addition, the increasing FPG change trajectory was associated with a higher probability of hypertension compared with the decreasing group regardless of age and BMI bu t was only significant in males and in those with normal FPG at baseline. Our study indicates that the increasing FPG change trajectory determines the highest risk of hypertension, demonstrating the importance of maintaining low and stable levels of FPG, especially in males and in those with normal FPG.

BackgroundEvidence highlighted the likelihood of unmet mental health needs (UMHNs) among LGBTQ+ than non-LGBTQ+ populations during COVID-19. However, there lacks evidence to accurately answer to what extent the gap was in UMHN between LGBTQ+ and non-LGBTQ+ populations. We aim to evaluate the difference in UMHN between LGBTQ+ and non-LGBTQ+ during COVID-19.MethodsCross-sectional data from Household Pulse Survey between 21 July 2021 and 9 May 2022 were analyzed. LGBTQ+ was defined based on self-reported sex at birth, gender, and sexual orientation identity. UMHN was assessed by a self-reported question. Multivariable logistic regressions generated adjusted odds ratios (AODs) of UMHN, both on overall and subgroups, controlling for a variety of socio-demographic and economic-affordability confounders.Findings81267 LGBTQ+ and 722638 non-LGBTQ+ were studied. The difference in UMHN between LGBTQ+ and non-LGBTQ+ (as reference) varied from 4.9% (95% CI 1.2–8.7%) in Hawaii to 16.0% (95% CI 12.2–19.7%) in Utah. In multivariable models, compared with non-LGBTQ+ populations, LGBTQ+ had a higher likelihood to report UMHN (AOR = 2.27, 95% CI 2.18–2.39), with the highest likelihood identified in transgender (AOR = 3.63, 95% CI 2.97–4.39); compared with LGBTQ+ aged 65+, LGBTQ+ aged 18–25 had a higher likelihood to report UMHN (AOR = 1.34, 95% CI 1.03–1.75); compared with White LGBTQ+ populations, Black and Hispanic LGBTQ+ had a lower likelihood to report UMHN (AOR = 0.72, 95% CI 0.63–0.82; AOR = 0.85, 95% CI 0.75–0.97, respectively).InterpretationDuring the COVID-19, LGBTQ+ had a substantial additional risk of UMHN than non-LGBTQ+. Disparities among age groups, subtypes of LGBTQ+, and geographic variance were also identified.

Abstract Background Mental health is affected by both genetic and environmental factors. However, previous studies have showed conflict findings about the role of lifestyle and little is known about the situation of the Chinese population. The purpose of this study was to explore the relationship between the frequency of food consumption, physical exercise condition and mental health, as well as factors related to mental stress in Chinese. Methods We recruited 8160 residents who had health examinations in a public hospital during June 2016 to May 2018. Demographic characteristics, the frequency of food consumption, physical exercise condition and mental health status was collected by a questionnaire. We estimated the association using the odds ratio (OR) and 95% confidence interval (CI) based on Binary or ordinal logistic regression models. A classification and regression tree (CART) demonstrated the prediction of the value of a target variable based on other values. Results The logistic regression model and classification tree model both found that the frequency of fresh vegetables or fruit and fried foods consumption and the current state of drinking alcohol were related to mental stress. The degree of mental stress reduced significantly with increasing consumption of fish (OR = 0.80, 95% CI: 0.71–0.90) and regular exercise (OR = 0.55, 95% CI:0.48–0.64) in females and increased consumption of fish (OR = 0.55, 95% CI: 0.48–0.64) and cereal crop (OR = 0.77, 95% CI: 0.68–0.89), fish (OR = 0.87, 95%CI:0.77–0.96) and regular exercise (OR = 0.61, 95%CI:0.53–0.70) in males. On the contrary, the frequency of consumption of desserts (OR = 1.43, 95% CI: 1.26–1.62) and the current of drinking alcohol (OR = 1.47, 95%CI:1.21–1.79) in females and meat (OR = 1.47, 95%CI: 1.31–1.65), pickled and smoked food (OR = 1.18, 95%CI:1.05–1.32) and the current state of drinking alcohol (OR = 1.25, 95%CI:1.12–1.40) in males were related to an increased risk of mental health. Conclusions Our study showed that both the frequency of some food consumption and physical exercise condition were associated with mental health and affected the degree of stress, which provided novel insights into interventions.

BackgroundNeurocognitive impairments are prevalent among older people in China. It is more problematic among older people living with HIV. ObjectiveThis study aims to compare neurocognitive performance between older people living with HIV and HIV-negative controls, and to explore whether the association between HIV status and neurocognitive performance was mediated by depressive symptoms and level of physical activity. MethodsA cross-sectional study was conducted in Yongzhou, China. All people living with HIV aged ≥50 years listed in the registry were invited. Frequency matching was used to sample HIV-negative controls from the general population according to the distribution of age, sex, and years of formal education of older people living with HIV. A total of 315 older people living with HIV and 350 HIV-negative controls completed the face-to-face interview and comprehensive neuropsychological assessment of seven domains (learning, memory, working memory, verbal fluency, processing speed, executive function, and motor skills). ResultsAs compared to HIV-negative controls, older people living with HIV performed worse in global score and all seven domains (P

BackgroundSarcopenia is known to be the risk factor of non-alcoholic fatty liver disease (NAFLD). However, studies evaluating the association of skeletal muscle mass (SMM) with liver fibrosis by transient elastography are limited. Here, we investigated the association of SMM with hepatic steatosis and fibrosis assessed in Chinese adults.MethodsPatients who underwent liver ultrasonography at the Health Promotion Center of the First Affiliated Hospital of Nanjing Medical University between January 2020 to June 2021 were enrolled. We used transient elastography to evaluate the degree of hepatic fat and liver stiffness. Appendicular skeletal muscle mass was determined by bioelectrical impedance and was adjusted for body weight to derive the skeletal muscle mass index (SMI).ResultsOf 3,602 finally enrolled individuals, 1,830 had NAFLD and 1,772 did not have NAFLD. SMI gradually decreased as the severity of hepatic steatosis increased (40.47 ± 3.94% vs. 39.89 ± 3.57% vs. 39.22 ± 3.46% vs. 37.81 ± 2.84%, P < 0.001). Individuals with F3-F4 and F2 liver fibrosis groups had significantly lower SMI than individuals with F0-F1 stages (37.51 ± 3.19% vs. 38.06 ± 3.51% vs. 39.36 ± 3.38%, P < 0.001). As the SMI increased, the percentages of subjects with mild and severe NAFLD, and the percentages of subjects in F2 and F3-F4 stage were gradually decreased. SMI was independently associated with the severity of hepatic steatosis and fibrosis by logistic regression analysis. Moreover, decreased SMI was an independent risk factor for NAFLD and fibrosis.ConclusionSMI is closely associated with liver fat content and liver fibrosis in Chinese adults with NAFLD.

Abstract Background The triglyceride-glucose index (TyG) is a reliable predictor of non-alcoholic fatty liver disease (NAFLD). Its association with the severity of hepatic steatosis and liver fibrosis in NAFLD is poorly understood. This study evaluated the relationship between these factors in NAFLD. Methods A total of 4784 participants who underwent ultrasonography were enrolled. Anthropometric and biochemical measurements were assessed. Participants with NAFLD were diagnosed by ultrasound. The degree of hepatic steatosis and liver stiffness was evaluated with transient elastography. Results The TyG index was significantly correlated with the severity of hepatic steatosis and the presence of liver fibrosis in patients with NAFLD. TyG quartile values correlated with increasing prevalence of NAFLD (Q1 30.9%, Q2 53.3%, Q3 71.7%, and Q4 86.4%, P

Abstract Background The discordance of the low-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with alterative lipid parameters may explain the inconsistent association of CIMT with the LDL-C/HDL-C ratio. Therefore, this study aimed to explore the associations between LDL-C/HDL-C ratio discordance with alternative lipid parameters and elevated carotid intima-media thickness (CIMT) risk in a large cohort in Beijing, China. Methods In total, 13,612 adults who didn’t have elevated CIMT at baseline and who participated in at least one follow-up of annual examination between 2009 and 2016 were included in this cohort study. A multivariable Cox regression model was utilized to evaluate the associations of discordance of the LDL-C/HDL-C ratio with TC, TGs, LDL-C and HDL-C with elevated CIMT risk. Results During 37,999 person-years of follow-up, 2004 individuals (1274 men and 730 women) developed elevated CIMT. Among individuals with normal TC and TGs, 16.6 and 15.2% individuals had a discordantly high LDL-C/HDL-C ratio, respectively, and the risk of elevated CIMT increased by 1.54 (95% CI 1.33, 1.77) and 1.53 (95% CI 1.33, 1.76), respectively, comparing to individuals with a concordantly low LDL-C/HDL-C ratio. A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with LDL-C and HDL-C (P

Background We aimed to evaluate the association between the Chinese visceral adiposity index (CVAI) and its dynamic change and risk of carotid plaque based on a large Chinese cohort. Methods and Results This cohort included 23 522 participants aged 20 to 80 years without elevated carotid intima‐media thickness and carotid plaque at baseline and who received at least 2 health checkups. CVAI was calculated at baseline and at every checkup. The dynamic change in CVAI was calculated by subtracting CVAI at baseline from that at the last follow‐up. Cox proportional hazard regression model was used to estimate hazard ratios (HRs) and 95% CIs. The restricted cubic spline was applied to model the dose‐response association between CVAI and carotid plaque risk. During the 82 621 person‐years of follow‐up, 5987 cases of carotid plaque developed (7.25/100 person‐years). We observed a significant positive correlation between CVAI and carotid plaque risk (HR, 1.53; 95% CI, 1.48–1.59 [P

Epithelial-mesenchymal transition (EMT) is a dedifferentiation program in which polarized, differentiated epithelial cells lose their cell-cell adhesions and transform into matrix-producing mesenchymal cells. EMT of retinal pigment epithelial (RPE) cells plays a crucial role in many retinal diseases, including age-related macular degeneration, proliferative vitreoretinopathy, and diabetic retinopathy. This dynamic process requires complex metabolic reprogramming to accommodate the demands of this dramatic cellular transformation. Both transforming growth factor-beta 2 (TGFβ2) and tumor necrosis factor-alpha (TNFα) have the capacity to induce EMT in RPE cells; however, little is known about their impact on the RPE metabolome. Untargeted metabolomics using high-resolution mass spectrometry was performed to reveal the metabolomic signatures of cellular and secreted metabolites of primary human fetal RPE cells treated with either TGFβ2 or TNFα for 5 days. A total of 638 metabolites were detected in both samples; 188 were annotated as primary metabolites. Metabolomics profiling showed distinct metabolomic signatures associated with TGFβ2 and TNFα treatment. Enrichment pathway network analysis revealed alterations in the pentose phosphate pathway, galactose metabolism, nucleotide and pyrimidine metabolism, purine metabolism, and arginine and proline metabolism in TNFα-treated cells compared to untreated control cells, whereas TGFβ2 treatment induced perturbations in fatty acid biosynthesis metabolism, the linoleic acid pathway, and the Notch signaling pathway. These results provide a broad metabolic understanding of the bioenergetic rewiring processes governing TGFβ2- and TNFα-dependent induction of EMT. Elucidating the contributions of TGFβ2 and TNFα and their mechanistic differences in promoting EMT of RPE will enable the identification of novel biomarkers for diagnosis, management, and tailored drug development for retinal fibrotic diseases.

Abstract Introduction Prenatal stress (PS) can cause depression in offspring. However, the underlying biological mechanism of these influences is still unclear. This work was implemented to investigate the molecular mechanisms of depressive‐like behavior of offspring rats insulted with PS. Methods Relative quantitative phosphoproteomics of the hippocampus of PS susceptibility (PS‐S) and control (CON) rat offspring was performed using liquid chromatography‐tandem mass spectrometry to confirm known pathways and to identify new mechanisms involved in depression. Results A total of 6790 phosphopeptides, 9817 phosphorylation sites, and 2978 phosphoproteins were detected. Among the 2978 phosphoproteins, 1760 (59.09%) had more than two phosphorylated sites, the ENSRNOP00000023460 protein had more than 117 phosphorylated sites, and the average distribution of modification sites per 100 amino acids was 2.97. There were 197 different phosphopeptides, including 140 increased phosphopeptides and 57 decreased phosphopeptides in the PS‐S offspring rats, compared to the CON offspring rats. These differential phosphopeptides corresponded to 100 upregulated and 44 downregulated phosphoproteins, respectively. Gene ontology enrichment analysis revealed that these different phosphoproteins in the top five enriched terms in the cellular component, molecular function, and biological proces categories were involved in a total of 35 different phosphoproteins, and these phosphoproteins were mainly related to myelin‐, microtubule‐ and synapse‐associated proteins. The enrichment of Kyoto Encyclopedia of Genes and Genome pathways was found to be involved in many essential biological pathways, and the top five pathways included amphetamine addiction, insulin secretion, Cushing syndrome, and the circadian entrainment signaling pathway. These first five pathways were related to nine phosphoproteins, including Adcy9, Apc, Cacna1c, Camk2a, Camk2b, Camk2g, Ctnnd2, Grin2a, and Stx1a. The full data are available via ProteomeXchange with identifier PXD019117. Conclusion We preliminarily identified 144 different phosphoproteins involved in myelin, microtubule, and synapse formation and plasticity in the hippocampus of susceptible offspring rats exposed to PS.

ObjectiveThe association between non-alcoholic fatty liver disease (NAFLD) and thyroid hormones in euthyroid subjects is unclear. We investigated the relationship between thyroid function and the severity of hepatic steatosis and liver fibrosis in a large cohort of euthyroid Chinese adults.MethodsA total of 3496 participants were enrolled. Liver ultrasonography was used to define the presence of NAFLD (n=2172) or the absence of NAFLD (n=1324). Anthropometric and biochemical measurements were made and thyroid function parameters including free triiodothyronine (FT3), free thyroxine (FT4), thyroid‐stimulating hormone (TSH) were measured. The severity of hepatic steatosis and liver stiffness was assessed by transient elastography.ResultsLevels of FT3 were significantly higher in the severe NAFLD group and moderate NAFLD group than in the mild NAFLD group (5.18 ± 0.58 vs 5.11 ± 0.57 vs 4.98 ± 0.60 pmol/L, P

Myocardial ischemia/reperfusion injury is a common clinical problem and can result in severe cardiac dysfunction. Previous studies have demonstrated the protection of electroacupuncture against myocardial ischemia/reperfusion injury. However, the role of X-box binding protein I (XBP1) signaling pathway in the protection of electroacupuncture was still elusive. Thus, we designed this study and demonstrated that electroacupuncture significantly improved cardiac function during myocardial ischemia/reperfusion injury and reduced cardiac infarct size. Electroacupuncture treatment further inhibited cardiac injury manifested by the decrease of the activities of serum lactate dehydrogenase and creatine kinase-MB. The results also revealed that electroacupuncture elevated the expressions of XBP1, glucose-regulated protein 78 (GRP78), Akt, and Bcl-2 and decreased the Bax and cleaved Caspase 3 expressions. By using the inhibitor of XBP1 in vitro, the results revealed that suppression of XBP1 expression could markedly increase the activities of lactate dehydrogenase and creatine kinase-MB and cell apoptosis, thus exacerbating stimulated ischemia/reperfusion-induced H9c2 cell injury. Compared with stimulated ischemia/reperfusion group, inhibition of XBP1 inhibited the downstream GRP78 and Akt expressions during stimulated ischemia/reperfusion injury. Collectively, our data demonstrated that electroacupuncture treatment activated XBP1/GRP78/Akt signaling to protect hearts from myocardial ischemia/reperfusion injury. These findings revealed the underlying mechanisms of electroacupuncture protection against myocardial ischemia/reperfusion injury and may provide novel therapeutic targets for the clinical treatment of myocardial ischemia/reperfusion injury.

Abstract Background Lipid ratios, for example total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C), are associated with type 2 diabetes mellitus (T2DM). However, the predictive values of lipid ratios in prediabetes remain unclear. The aims of this study were: 1) to investigate the association between lipid ratios and abnormal glucose tolerance; 2) to compare the predictive significance of lipid ratios with commonly used indicators of lipid variables in clinical practice in a Chinese population. Methods The cross-sectional study enrolled 2680 participants from the Health Promotion Center of the First Affiliated Hospital of Nanjing Medical University. All participants received a 75 g oral glucose tolerance test. Blood samples were obtained at baseline and 120 min after glucose ingestion. Participants were classified as normal glucose tolerance (NGT), impaired glucose regulation (IGR), and T2DM. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression model. The receiver operating characteristic (ROC) curve was used to identify the cutoff points of lipid and lipid ratios. The area under the receiver operating characteristic curve (AUROC), sensitivity and specificity were calculated to estimate their diagnostic values. Results TC, TG, TC/HDL-C, TG/HDL-C and non-HDL-C were significantly correlated with both prediabetes and T2DM after adjustment for other risk factors such as blood glucose, whereas LDL-C was only positively correlated with prediabetes. TG and TG/HDL-C showed higher diagnostic values for prediabetes and T2DM than TC, LDL-C, HDL-C, TC/HDL-C and non-HDL-C, with the AUC values over 0.70. For predicting prediabetes, the optimal cutoff point was 1.36 mmol/l for TG and 1.13 for TG/HDL-C. For predicting T2DM, the optimal cutoff point was 1.46 mmol/l for TG and 1.22 for TG/HDL-C. Conclusions Both TG and TG/HDL-C are promising biomarkers for distinguishing individuals with abnormal glucose tolerance, and can be used to predict prediabetes and T2DM in Chinese population.

TiO2-based ultraviolet photodetectors have drawn great attention and are intensively explored. However, the construction of TiO2-based nanocomposites with excellent ultraviolet responses remains challenging. Herein, a TiO2 nanorod array was successfully prepared on fluorine-doped tin oxide (FTO) conductive glass by a one-step hydrothermal method. Then, polypyrrole (PPy)-TiO2 nanorod array composites were designed via subsequent in situ oxidative polymerization. The morphologies, structures, and photocurrent responses of the nanocomposites were systematically investigated. The results demonstrated that polypyrrole-TiO2 exhibited a stronger photocurrent response than pure TiO2 due to the p-n junction formed between n-type TiO2 nanorod arrays and p-type polypyrrole. The PPy-TiO2 composite obtained by deposition three times had the best photoelectric properties, exhibiting good performance with a sensitivity of 41.7 and responsivity of 3.5 × 10−3 A/W. Finally, the mechanism of the photoelectrical response of PPy-TiO2 composites was discussed, guiding the design of high-performance TiO2-based ultraviolet photodetectors.

Background: Insulin resistance (IR) is a significant risk factor for cardiovascular disease (CVD). In this study, the association of the triglyceride glucose (TyG) index, a simple surrogate marker of IR, with arterial stiffness and 10-year CVD risk was evaluated.Methods: A total of 13,706 participants were enrolled. Anthropometric and cardiovascular risk factors were determined in all participants, while serum insulin levels were only measured in 955 participants. Arterial stiffness was measured through brachial-ankle pulse wave velocity (baPWV), and 10-year CVD risk was evaluated using the Framingham risk score.Results: All participants were classified into four groups according to the quartile of the TyG index. BaPWV and the percentage of participants in the 10-year CVD risk categories significantly increased with increasing quartiles of the TyG index. Logistic regression analysis showed that the TyG index was independently associated with a high baPWV and 10-year CVD risk after adjusting for traditional CVD risk factors. The area under the receiver operating characteristics curve (AUROC) of the TyG index for predicting a high baPWV was 0.708 (95%CI 0.693–0.722, P < 0.001) in women, higher than that in men. However, the association of the homeostatic model assessment of IR (HOMA-IR) with a high baPWV and the 10-year CVD risk was absent when adjusting for multiple risk factors in 955 participants.Conclusions: The TyG index is independently associated with arterial stiffness and 10-year CVD risk.

To date, there is a paucity of information regarding the effect of COVID-19 or lockdown on mental disorders. We aimed to quantify the medium-term impact of lockdown on referrals to secondary care mental health clinical services. We conducted a controlled interrupted time series study using data from Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), UK (catchment population ~0.86 million). The UK lockdown resulted in an instantaneous drop in mental health referrals but then a longer-term acceleration in the referral rate (by 1.21 referrals per day per day, 95% confidence interval [CI] 0.41–2.02). This acceleration was primarily for urgent or emergency referrals (acceleration 0.96, CI 0.39–1.54), including referrals to liaison psychiatry (0.68, CI 0.35–1.02) and mental health crisis teams (0.61, CI 0.20–1.02). The acceleration was significant for females (0.56, CI 0.04–1.08), males (0.64, CI 0.05–1.22), working-age adults (0.93, CI 0.42–1.43), people of White ethnicity (0.98, CI 0.32–1.65), those living alone (1.26, CI 0.52–2.00), and those who had pre-existing depression (0.78, CI 0.19–1.38), severe mental illness (0.67, CI 0.19–1.15), hypertension/cardiovascular/cerebrovascular disease (0.56, CI 0.24–0.89), personality disorders (0.32, CI 0.12–0.51), asthma/chronic obstructive pulmonary disease (0.28, CI 0.08–0.49), dyslipidemia (0.26, CI 0.04–0.47), anxiety (0.21, CI 0.08–0.34), substance misuse (0.21, CI 0.08–0.34), or reactions to severe stress (0.17, CI 0.01–0.32). No significant post-lockdown acceleration was observed for children/adolescents, older adults, people of ethnic minorities, married/cohabiting people, and those who had previous/pre-existing dementia, diabetes, cancer, eating disorder, a history of self-harm, or intellectual disability. This evidence may help service planning and policy-making, including preparation for any future lockdown in response to outbreaks.

Background. Conflicting findings have been reported regarding the sex-specific association between serum uric acid (SUA) level and type 2 diabetes mellitus (T2DM) risk, and no study has explored the association between the change in hyperuricemia status and T2DM risk. The study was aimed at exploring the sex-specific association of baseline SUA and changes in hyperuricemia status with T2DM risk. Methods. We included 37,296 eligible adults without T2DM at the first examination who attended the baseline examination and at least one follow-up annual examination. Cox and logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) for T2DM risk associated with baseline SUA and the change in hyperuricemia status, respectively. Results. During a median follow-up of 3.09 years, of 37,296 eligible adults, 2,263 developed T2DM. Compared with the first SUA quartile, higher quartiles were associated with an increased risk of T2DM in women (HR 1.78, 95% CI 1.17-2.71 for Q3 and 1.93, 1.27-2.93 for Q4; Ptrend

Abstract Background The steroid hormone estrogen (17-β-estradiol, E2) provides neuroprotection against cerebral ischemic injury by activating estrogen receptors. The novel estrogen receptor G protein-coupled receptor 30 (GPR30) is highly expressed in the brain and provides acute neuroprotection against stroke. However, the underlying mechanisms remain unclear. Methods In this study, ovariectomized female mice were subjected to middle cerebral artery occlusion (MCAO), and E2, G1, and ICI182780 were administered immediately upon reperfusion. The infarction volume, neurological scores, and neuronal injuries were examined. Primary microglial cells were subjected to oxygen-glucose deprivation (OGD), and the drugs were administered immediately upon reintroduction. The pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in penumbra and microglia were assessed by ELISA. The cell viability and lactose dehydrogenase (LDH) release of neurons co-cultured with microglia were analyzed using cell counting kit-8 (CCK8) and LDH release assays. Microglial activation as well as GPR30, Iba1, and Toll-like receptor 4 (TLR4) protein expression and TLR4 mRNA expression were detected. Additionally, NF-κB activity was detected in lipopolysaccharide (LPS)-activated microglia after the activation of GPR30. Results GPR30 was highly expressed in microglia and significantly increased after ischemic injury. The activation of GPR30 significantly reduced the infarction volume, improved the neurological deficit, and alleviated neuronal injuries. Moreover, GPR30 activation significantly reduced the release of TNF-α, IL-1β, and IL-6 from ischemic penumbra and microglia subjected to OGD and alleviated neuronal injury as assessed using the CCK8 and LDH assays. Finally, the activation of GPR30 relieved microglial activation, reduced Iba1 and TLR4 protein expression and TLR4 mRNA levels, and inhibited NF-κB activity. Conclusions Microglial GPR30 exerts acute neuroprotective effects by inhibiting TLR4-mediated microglial inflammation, which indicates that GPR30 may be a potential target for the treatment of ischemic stroke.

Modified nucleosides in tRNAs are critical for protein translation. N1-methylguanosine-37 and N1-methylinosine-37 in tRNAs, both located at the 3'-adjacent to the anticodon, are formed by Trm5. Here we describe Arabidopsis thaliana AtTRM5 (At3g56120) as a Trm5 ortholog. Attrm5 mutant plants have overall slower growth as observed by slower leaf initiation rate, delayed flowering and reduced primary root length. In Attrm5 mutants, mRNAs of flowering time genes are less abundant and correlated with delayed flowering. We show that AtTRM5 complements the yeast trm5 mutant, and in vitro methylates tRNA guanosine-37 to produce N1-methylguanosine (m1G). We also show in vitro that AtTRM5 methylates tRNA inosine-37 to produce N1-methylinosine (m1I) and in Attrm5 mutant plants, we show a reduction of both N1-methylguanosine and N1-methylinosine. We also show that AtTRM5 is localized to the nucleus in plant cells. Proteomics data showed that photosynthetic protein abundance is affected in Attrm5 mutant plants. Finally, we show tRNA-Ala aminoacylation is not affected in Attrm5 mutants. However the abundance of tRNA-Ala and tRNA-Asp 5' half cleavage products are deduced. Our findings highlight the bifunctionality of AtTRM5 and the importance of the post-transcriptional tRNA modifications m1G and m1I at tRNA position 37 in general plant growth and development.

This paper presents experimental results showing reduced phase noise in a very high frequency band microelectromechanical systems (MEMS) oscillator. This has been achieved by engineering the embedded MEMS resonator with phononic crystal structures. The aluminum nitride on silicon MEMS resonator with phononic crystal tethers achieves an unloaded quality factor (Qu) 2.3 times of the same resonator with a simple tether design. The increase in Qu leads to a measured 6dB close-to-carrier phase noise reduction in an MEMS-based oscillator that sustained by a transimpedance amplifier implemented in 65nm CMOS process. The 141 MHz MEMS-CMOS oscillator with phononic crystal tethers has a phase noise better than -83dBc/Hz at 1 kHz offset and -134dBc/Hz at the far-from-carrier range while consuming less than 3mW.

A newly isolated phosphate-solubilizing fungus from the topsoil of Spartina alterniflora habitats in Yancheng coastal salt marsh was cultivated. Scanning electron microscopy observation revealed that the sporangia are nearly spherical, peach-shaped, and the spores formed on the top of sporangia. The spores are ellipsoidal with raised white nubbins on the surface. Based on a polyphasic study and the genetic distance analysis referring to the sequence analysis of ITS (ITS1 + 5.8S + ITS2) and 28S rDNA (D1/D2 domains) genes, the novel species belongs to the genus Apophysomyces and is named as A. jiangsuensis. The optimum growth temperature and salinity of the new species were 28 °C and 1.15% NaCl, respectively. A study of its phosphate-solubilizing ability revealed that the fungus had an obvious decomposition effect on lecithin, Ca3(PO4)2, and AlPO3, respectively. The pH of the fermented liquid progressively decreased from 6.85 to 2.27 after 7 days of incubation, indicating that the low molecular weight organic acids excreted into the culture liquor were oxalic, succinic, and malic acids and a trace amount of citric acid. Among these, oxalic acid was the major organic acid, and its amount reached 652.5 mg/L. These results indicated that the main mechanism underlying the dissolved phosphorus was related to the secretion of large amounts of organic acids.

In this study, a donkey-specific primer pair and probe were designed from mitochondrial cytochrome b gene for the detection of raw donkey meat and different processed meat mixtures. The PCR product size for donkey DNA was 99 bp, and primer specificity was verified using 20 animal species. The limit of detection (LOD) was examined by serially diluting donkey DNA. Using real-time PCR, 0.001 ng of donkey DNA could be detected. In addition, binary meat mixtures with various percentages of donkey meat (0.001%, 0.01%, 0.1%, 1%, 10%, and 100%) in beef were analyzed to determine the sensitivity of this real-time PCR assay. At least 0.001% of donkey meat was detected in raw, boiled, roasted, dried, grinded, fried, and autoclaved meat mixtures. The developed real-time PCR method showed sufficient specificity and sensitivity in identification of donkey meat and could be a useful tool for the identification of donkey meat in processed products.

In this paper, we prepared the nanoparticle drug carrier system between nanoparticles — chitosan and Epigallocatechin-3-O-gallate (EGCG) for breast cancer cell inhibiting application. For this drug carrier system, chitosan acts as a carrier and EGCG as a drug. Which were systematically characterized and thoroughly evaluated in terms of their inhibition rate and biocompatibility. We also did a cell scratch test and the result indicated that the chitosan-EGCG nanoparticles have inhibitory effect on the growth of breast cancer cells. The inhibition rate could reach up to 21.91%. This work revealed that the modification of nanoparticles paved a way for specific biomedical applications.