Health impacts of lifestyle and ambient air pollution patterns on all-cause mortality: a UK Biobank cohort study.

BACKGROUND: Extensive evidence indicates that both lifestyle factors and air pollution are strongly associated with all-cause mortality. However, little studies in this field have integrated these two factors in order to examine their relationship with mortality and explore potential interactions. METHODS: A cohort of 271,075 participants from the UK Biobank underwent analysis. Lifestyles in terms of five modifiable factors, namely smoking, alcohol consumption, physical activity, diet, and sleep quality, were classified as unhealthy (0-1 score), general (2-3 score), and healthy (4-5 score). Air pollution, including particle matter with a diameter ≤ 2.5 µm (PM2.5), particulate matter with a diameter ≤ 10 µm (PM10), particulate matter with a diameter 2.5-10 µm (PM2.5-10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), was divided into three levels (high, moderate, and low) using Latent Profile Analysis (LPA). Cox proportional hazard regression analysis was performed to examine the links between lifestyle, air pollution, and all-cause mortality before and after adjustment for potential confounders. Restricted cubic spline curves featuring three knots were incorporated to determine nonlinear relationships. The robustness of the findings was assessed via subgroup and sensitivity analyses. RESULTS: With unhealthy lifestyles have a significantly enhanced risk of death compared to people with general lifestyles (HR = 1.315, 95% CI, 1.277-1.355), while people with healthy lifestyles have a significantly lower risk of death (HR = 0.821, 95% CI, 0.785-0.858). Notably, the difference in risk between moderate air pollution and mortality risk remained insignificant (HR = 0.993, 95% CI, 0.945-1.044). High air pollution, on the other hand, was independently linked to increased mortality risk as compared to low air pollution (HR = 1.162, 95% CI, 1.124-1.201). The relationship between NOx, PM10, and PM2.5-10 and all-cause mortality was found to be nonlinear (p for nonlinearity < 0.05). Furthermore, no significant interaction was identified between lifestyle and air pollution with respect to all-cause mortality. CONCLUSIONS: Exposure to ambient air pollution elevated the likelihood of mortality from any cause, which was impacted by individual lifestyles. To alleviate this hazard, it is crucial for authorities to escalate environmental interventions, while individuals should proactively embrace and sustain healthy lifestyles.

The screening, identification, design and clinical application of tumor-specific neoantigens for TCR-T cells.

Recent advances in neoantigen research have accelerated the development of tumor immunotherapies, including adoptive cell therapies (ACTs), cancer vaccines and antibody-based therapies, particularly for solid tumors. With the development of next-generation sequencing and bioinformatics technology, the rapid identification and prediction of tumor-specific antigens (TSAs) has become possible. Compared with tumor-associated antigens (TAAs), highly immunogenic TSAs provide new targets for personalized tumor immunotherapy and can be used as prospective indicators for predicting tumor patient survival, prognosis, and immune checkpoint blockade response. Here, the identification and characterization of neoantigens and the clinical application of neoantigen-based TCR-T immunotherapy strategies are summarized, and the current status, inherent challenges, and clinical translational potential of these strategies are discussed.

Secular trend of non-communicable chronic disease prevalence throughout the life span who endured Chinese Great Famine (1959-1961).

BACKGROUND: Famine is a risk factor for non-communicable chronic diseases (NCDs), which account for over 80% of deaths in China. The effect of famine on the prevalence of NCDs in terms of various age groups, time periods and cohorts is currently poorly understood. OBJECTIVE: This study aims to explore long-term trends in the impact of China's Great Famine (1959-1961) on NCDs in China. METHODS: This study used data from the 2010-2020 China Family Panel Longitudinal Survey across 25 provinces in China. The subjects were aged 18-85 years, and the total number of subjects was 174,894. The prevalence of NCDs was derived from the China Family Panel Studies database (CFPS). An age-period-cohort (APC) model was used to estimate the age, period and cohort effects of NCDs in 2010-2020 and the effect of famine on the risk of NCDs in terms of cohort effects. RESULTS: The prevalence of NCDs increased with age. Additionally, the prevalence did not clearly decrease over the survey period. Regarding the cohort effect, people born in the years adjacent to the famine period had a higher risk of NCDs; additionally, females, those born in rural areas, and those who lived in provinces with severe famine and post-famine had a higher likelihood of NCDs. CONCLUSIONS: Experiencing famine at an early age or the experience of famine in a close relative's generation (births after the onset of famine) are associated with an increased risk of NCDs. Additionally, more severe famine is associated with a higher risk of NCDs.

Association of living arrangements with all-cause mortality among older adults: a propensity score-matched cohort study.

BACKGROUND: Many studies exist on the living arrangements and health status of older adults, but the findings have been inconsistent. Therefore, we examined the relationship between living arrangements and all-cause mortality in older adults. METHODS: This perspective study was based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2011 to 2018. We used a sample aged 65 years and over included in the study in 2011. Propensity score matching was performed to minimize bias and Cox proportional hazards regression models were conducted. RESULTS: A total of 7,963 participants were included. Of these, 1,383 were living alone, 6,424 were living with families, and 156 were living in nursing homes. In the propensity score-matched cohort, older adults living alone had a significantly lower risk of all-cause mortality than those living with families (hazard ratio 0.85; 95% confidence intervals 0.76 to 0.95). Living alone was prominently associated with a decline in mortality compared with living in nursing homes (hazard ratio 0.61; 95% confidence intervals 0.44 to 0.84). There was no significant difference in mortality between living in nursing homes and living with families (hazard ratio 1.19; 95% confidence intervals 0.89 to 1.60). Subgroup analyses indicated that there was no significant interaction with age, sex, education, or residence. CONCLUSIONS: The risk of all-cause mortality was significantly lower in older adults living alone than in those living with families or living in nursing homes. This article's findings suggest the need to adopt multiple approaches to meet the needs of senior care services.

Effects of common plastic products heat exposure on cognition: Mediated by gut microbiota.

Considering plastic exposure patterns in modern society, the effects of exposure to leachate from boiled-water treated plastic products on cognitive function was probed in mice through changes in gut microbiota diversity. In this study, Institute for Cancer Research (ICR) mice were used to establish drinking water exposure models of three popular kinds of plastic products, including non-woven tea bags, food-grade plastic bags and disposable paper cups. 16S rRNA was used to detect changes in the gut microbiota of mice. Behavioral, histopathology, biochemistry, and molecular biology experiments were used to evaluate cognitive function in mice. Our results showed that the diversity and composition of gut microbiota changed at genus level compared to control group. Nonwoven tea bags-treated mice were proved an increase in Lachnospiraceae and a decreased in Muribaculaceae in gut. Alistipes was increased under the intervention of food grade plastic bags. Muribaculaceae decreased and Clostridium increased in disposable paper cups group. The new object recognition index of mice in the non-woven tea bag and disposable paper cup groups decreased, and amyloid ß-protein (Aß) and tau phosphorylation (P-tau) protein deposition. Cell damage and neuroinflammation were observed in the three intervention groups. Totally speaking, oral exposure to leachate from boiled-water treated plastic results in cognitive decline and neuroinflammation in mammals, which is likely related to MGBA and changes in gut microbiota.

T cell epitope screening of Epstein-Barr virus fusion protein gB.

Glycoprotein B (gB) is an essential fusion protein for the Epstein-Barr virus (EBV) infection of both B cells and epithelial cells and is thus a promising target antigen for a prophylactic vaccine to prevent or reduce EBV-associated disease. T cell responses play key roles in the control of persistent EBV infection and in the efficacy of a vaccine. However, to date, T cell responses to gB have been characterized for only a limited number of human leukocyte antigen (HLA) alleles. Here, we screened gB T cell epitopes in 23 healthy EBV carriers and ten patients with nasopharyngeal cancer (NPC) using a peptide library spanning the entire gB sequence. We identified twelve novel epitopes in the context of seven new HLA restrictions that are common in Asian populations. Two epitopes, gB214-223 and gB840-849, restricted by HLA-B*58:01 and B*38:02, respectively, elicited specific CD8+ T cell responses to inhibit EBV-driven B cell transformation. Interestingly, gB-specific CD8+ T cells were more frequent in healthy viral carriers with EBV reactivation than in those without EBV reactivation, indicating that EBV reactivation in vivo stimulates both humoral (VCA-gp125-IgA) and cellular responses to gB. We further found that most gB epitopes are conserved among different EBV strains. Our study broadens the diversity and HLA restrictions of gB epitopes and suggests that gB is a common target of T cell responses in healthy viral carriers with EBV reactivation. In particular, the precisely mapped and conserved gB epitopes provide valuable information for prophylactic vaccine development.ImportanceT cells are crucial for the control of persistent EBV infection and the development of EBV-associated diseases. The EBV gB protein is essential for virus entry into B cells and epithelial cells and is thus a target antigen for vaccine development. Understanding T cell responses to gB is important for subunit vaccine design. Herein, we comprehensively characterized T cell responses to full-length gB. Our results expand the available gB epitopes and HLA restrictions, particularly those common in Asian populations. Furthermore, we showed that gB-specific CD8+ T cells inhibit B cell transformation ex vivo and that gB-specific CD8+ T cell responses in vivo may be associated with intermittent EBV reactivation in asymptomatic viral carriers. These gB epitopes are highly conserved among geographically separated EBV strains. Precisely mapped and conserved T cell epitopes may contribute to immune monitoring and to the development of a gB subunit vaccine.

Electronic and Steric Control of Rates and Selectivities in Rhodium-Catalyzed [2+2+2] Cycloadditions for Constructing Fused Tricyclic Hydronaphthofurans: A Density Functional Theory Study.

Fused tricyclic hydronaphthofurans with multiple chiral centers are very important skeletons for constructing natural products; however, their synthesis is challenging, and a detailed understanding of the final formation mechanism remains elusive. In this work, density functional theory computations were employed to characterize rhodium-catalyzed [2+2+2] cycloaddition of enyne with terminal alkynes. The putative mechanism involves an initial ligand exchange, followed by oxidative cyclization, olefin insertion, and reductive elimination processes. Oxidative cyclization is shown to be the rate- and selectivity-determining step of the full chemical transformation, where the R substituent on terminal alkynes has a significant influence on the reaction selectivities. When R is an electron-donating group (OMe and Me), the ortho-substituted tricyclic hydronaphthofurans (P1) are predicted to be dominant; on the contrary, meta-substituted compounds P2 emerge as the main products when R is an electron-withdrawing group (NO2, CF3, and CN). Computational predictions for selectivity are in good agreement with experimental product ratios. Free energy barriers of the rate-determining step for P1 and P2 are ∼22.3-23.6 kcal mol-1, which align well with their experimental yields of ∼79-92% at 313 K after 0.5 h. The results also accurately reproduce experimentally observed regio-, chemo-, and enantioselectivities, with steric hindrance as well as electronic properties of the substrate and ligand markedly influencing the reaction rates and selectivities. The influence of computational methods is also explored and discussed in detail.

The association between undiagnosed diabetes and cognitive function: findings from the China health and retirement longitudinal study.

BACKGROUND: The cognitive function of people with diabetes has gained an increasing interest in recent years, and this study focuses on exploring the relationship between undiagnosed diabetes and cognitive function among the middle-aged and elderly people in China. METHODS: The data came from the China Health and Retirement Longitudinal Study (CHARLS) which was conducted between July and October 2015. 9855 subjects were enrolled in the study. Executive function and episodic memory were used to assess cognitive function. The subjects were divided into three groups: no diabetes, diagnosed diabetes, and undiagnosed diabetes, and weighted multiple linear regression models were established to evaluate the association of undiagnosed diabetes with cognitive function. RESULTS: After controlling for covariates, undiagnosed diabetes was statistically associated with executive function (ß = -0.215, P < 0.01). In the age group of ≥65 years, undiagnosed diabetes was statistically associated with executive function (ß = -0.358, P < 0.01) and episodic memory (ß = -0.356, P < 0.01). When adjusting for confounders, no statistically significant associations were found between diagnosed diabetes and cognitive function except in 45-54 age group (ß = 0.374, P < 0.05). CONCLUSIONS: The cross-sectional study suggested that undiagnosed diabetes was linked to poor cognitive function, especially in the elderly population. Timely diagnosis and active treatment of diabetes are important to reduce the occurrence of cognitive impairment. Further prospective cohort studies are required to articulate the association between undiagnosed diabetes and cognitive function.

Inhibition of mTOR by temsirolimus overcomes radio-resistance in nasopharyngeal carcinoma.

Radio-resistance is a leading cause of nasopharyngeal carcinoma (NPC) treatment failure and identification of sensitising therapeutic targets is an unmet need to enhance clinical management. Given that the mammalian target of rapamycin (mTOR) signalling confers resistance to cancer therapy, we investigated whether mTOR contributes to radio-resistance in NPC and pharmacological inhibition of mTOR can overcome radio-resistance. We found that mTOR mRNA and protein levels, and phosphorylation of its downstream effector were increased in radio-resistant NPC compared with parental cells. mTOR inhibitor temsirolimus inhibits proliferation and induces apoptosis in a panel of NPC cell lines. Importantly, temsirolimus acts synergistically with radiation and is effective against radio-resistant cells. Using radio-resistant xenograft mouse model, we validated the efficacy of temsirolimus in preventing tumour formation and inhibiting tumour growth. Temsirolimus overcome radio-resistance in NPC via inhibiting mTOR signalling. Our work provides the pre-clinical evidence that the combination of radiation and mTOR inhibitor may be a therapeutic strategy in NPC. Our findings might accelerate the initiation of clinical trials on radio-resistant NPC patients using temsirolimus.

CircRNA CORO1C Regulates miR-654-3p/USP7 Axis to Mediate Laryngeal Squamous Cell Carcinoma Progression.

Circular RNAs have attracted the attention in the research on laryngeal squamous cell carcinoma (LSCC) development. But the function and mechanism of circRNA coronin-1C (circ_CORO1C) in LSCC progression are largely unknown. Circ_CORO1C, microRNA (miR)-654-3p, and ubiquitin-specific protease 7 (USP7) levels in LSCC tissues and cells were determined. Quantitative reverse transcription polymerase chain reaction and western blotting assays were conducted to determine the mRNA and protein levels of genes. Functional assays were further investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), EdU staining, flow cytometry, transwell and xenograft assays. The binding relationship was examined by dual-luciferase reporter assay. Circ_CORO1C expression was elevated in LSCC samples and cells. circ_CORO1C silencing constrained cell proliferation and promoted apoptosis via reducing cell proliferation, inducing cell cycle arrest, inhibiting epithelial-mesenchymal transition, and promoting apoptosis, as well as restraining cell migration and invasion. USP7 is highly expressed in LSCC tissues and cells, and its expression was suppressed by circ_CORO1C silencing. Besides, the up-regulation of USP7 attenuated the influence of circ_CORO1C silencing on LSCC cell progression. Both circ_CORO1C and USP7 could bind to miR-654-3p. circ_CORO1C regulated USP7 expression by modulating miR-654-3p. miR-654-3p knockdown mitigated the influence of circ_CORO1C silence on LSCC cell progression. Furthermore, circ_CORO1C silencing reduced tumor growth in vivo. In conclusion, circ_CORO1C is highly expressed in LSCC tissues and cells, and circ_CORO1C silencing repressed LSCC progression via regulating miR-654-3p/USP7 axis.

2,4-dichlorophenoxyacetic acid induces ROS activation in NLRP3 inflammatory body-induced autophagy disorder in microglia and the protective effect of Lycium barbarum polysaccharide.

The pesticide 2,4-dichlorophenoxyacetic acid (2,4-D) exerts neurotoxic effects; however, its action mechanism remains unclear. Here, we used BV2 cells as a model and divided them into six groups: control group (serum-free medium), lipopolysaccharide (LPS) (1 µg/mL), 2,4-D (1.2 µmol/mL), Lycium barbarum polysaccharide (LBP; 300 µg/mL LBP), LPS (1 µg/mL) + LBP (300 µg/mL), and 2,4-D (1.2 µmol/mL) + LBP (300 µg/mL) with dimethyl sulfoxide as the solvent. Our results showed that 2,4-D treatment decreased superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde content. The percentage of microglial activation (co-expression of ionized calcium-binding adaptor protein-1 + CD68) in the LPS and 2,4-D groups and the levels of tumor necrosis factor alpha, interleukin (IL) 1 beta, IL-6, and IL-18 in the cell supernatant were increased. The protein and mRNA levels of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein, caspase-1, IL-1ß, IL-18, and p62 increased, whereas those of LC3II/I and Beclin-1 decreased in the 2,4-D group. The protein expression and mRNA levels of NLRP3, cleaved caspase-1, IL-1ß, IL-18, and p62 decreased significantly, whereas the protein expression and mRNA levels of LC3II/I and Beclin-1 increased in small interfering RNA of NLRP3-treated BV2 cells stimulated with 2,4-D and LPS. In conclusion, 2,4-D enhanced cell migration, promoted oxidative stress, induced excessive release of mitochondrial reactive oxygen species, promoted microglial cell activation, released inflammatory factors, activated NLRP3 inflammasomes, and inhibited autophagy. Meanwhile, LBP reduced inflammation and the release of mitochondrial reactive oxygen species, inhibited NLRP3 inflammasome activation, and regulated autophagy, thereby playing a neuroprotective role.

Immunization with a Self-Assembled Nanoparticle Vaccine Elicits Potent Neutralizing Antibody Responses against EBV Infection.

Epstein-Barr virus (EBV) infection is a global health concern infecting over 90% of the population. However, there is no currently available vaccine. EBV primarily infects B cells, where the major glycoprotein 350 (gp350) is the main target of neutralizing antibodies. Given the advancement of nanoparticle vaccines, we describe rationally designed vaccine modalities presenting 60 copies of gp350 on self-assembled nanoparticles in a repetitive array. In a mouse model, gp350s on lumazine synthase (LS) and I3-01 adjuvanted with MF59 or aluminum hydroxide (Alhydrogel) elicited over 65- to 133-fold higher neutralizing antibody titers than the corresponding gp350 monomer to EBV. Furthermore, immunization with gp350D123-LS and gp350D123-I3-01 vaccine induced a Th2-biased response. For the nonhuman primate model, gp350D123-LS in MF59 elicited higher titers of total IgG and neutralizing antibodies than the monomeric gp350D123. Overall, these results support gp350D123-based nanoparticle vaccine design as a promising vaccine candidate for potent protection against EBV infection.

Association Between Parental Absence and Depressive Symptoms in Adolescence: Evidence From a National Household Longitudinal Survey.

Longitudinal evidence demonstrating the association between parental absence and depressive symptoms in adolescence is limited. The present study aimed to explore this relationship in a Chinese national representative sample. This research was based on the China Family Panel Studies and included 1481 subjects. Depressive symptoms were assessed using the self-reported Center for Epidemiologic Studies Depression questionnaire. A multiple logistic regression model with a generalized estimating equation was used to test the association between parental absence and adolescent depressive symptoms. In the baseline year, 2012, 29.03% and 43.75% of adolescents had maternal and paternal absence, respectively. The prevalence of depressive symptoms increased from 23.23% to 28.12% in subsequent years. After controlling for covariates, maternal absence was positively associated with depressive symptoms (odds ratio 1.69, 95% confidence interval 1.06-2.68). Maternal absence led to depression in adolescents. It may be beneficial for adolescents with depression to spend more time with their mothers.

Circulation weather types and hospital admissions for cardiovascular disease in Changchun, China.

Epidemiological studies have reported significant associations between weather situations and health. Cardiovascular disease is a serious chronic non-communicable disease which causes mortality and morbidity, bringing large economic burden to patients' families. This study explored the relationship between cardiovascular disease (CVD) and weather conditions in Changchun, northeast China. The frequency distributions of 13 main circulation weather types (CWTs) were analyzed, and a comparison between air mass classification and hospital admissions was performed for various groups using an admission index (AI). The results indicated that women had a lower risk of CVD than men did. The risk of CVD for older people (aged ≥ 65 years) was lower than that for young people (aged < 65 years). Younger men had the highest risk. The risks of CVD were higher in all groups (i.e., men, women, older, and younger) under southwesterly (SW) and northerly (N) CWTs and were lowest under the anticyclone (A) CWT. The risk of CVD among men was higher than that for women under these CWTs. N type circulation is characterized by cold, dry weather and was most closely associated with an increased incidence of CVD. The most significant effect of N type circulation on AI was observed with a delay of 2 days. SW type circulation is characterized by humid, hot weather and was the CWT that was second most closely associated with an increased incidence of CVD, with a peak in AI on the day that SW type circulation occurred. The results of this study could be provided to local health authorities as scientific guidelines for controlling and preventing CVD in Changchun, China.

Effects of 2,4-dichlorophenoxyacetic acid on the expression of NLRP3 inflammasome and autophagy-related proteins as well as the protective effect of Lycium barbarum polysaccharide in neonatal rats.

The pesticide 2,4-dichlorophenoxyacetic acid (2,4-D) has neurotoxic effects, but its mechanism is not clear. In this study, a 2,4-D (75 mg/kg. b.w) exposure model was established in SD rats with colostrum. Lipopolysaccharide (1 mg/kg b.w) was used as the positive control, and Lycium barbarum polysaccharide (LBP, 50 mg/kg b.w) was used as an intervention factor to explore the neurotoxic effect of 2,4-D and the neuroprotective effect of LBP. Our research results show that 2,4-D causes a decrease in the number of hippocampal CA3 pyramidal cells and pyknosis in nuclei with a triangular or irregular shape and that rats show signs of anxiety or depression. In rat serum, superoxide dismutase, and glutathione peroxidase activity decreased, while malondialdehyde content increased. Protein and mRNA levels of TNFα, IL-6, IL-1ß, IL-18, NLRP3, ASC, caspase-1, IL-1ß, IL-18, and p62 increased, while those of LC3-II/LC3-I and Beclin-1 decreased in hippocampal tissues. In conclusion, 2,4-D increased the oxidative stress level, induced neuroinflammatory response, and decreased the autophagy level in experimental rats. LBP may have upregulated the autophagy level in the body by inhibiting the activation of the NLRP3 inflammasome, thus playing a neuroprotective role.

Persistent pollution episodes, transport pathways, and potential sources of air pollution during the heating season of 2016-2017 in Lanzhou, China.

As one of the most important industrial cities in Northwest China, Lanzhou currently suffers from serious air pollution. This study analyzed the formation mechanism and potential source areas of persistent air pollution in Lanzhou during the heating period from November 1, 2016 to March 31, 2017 based on the air pollutant concentrations and relevant meteorological data. Our findings indicate that particulate pollution was extremely severe during the study period. The daily PM2.5 and PM10 concentrations had significantly negative correlations with daily temperature, wind speed, maximum daily boundary layer height, while the daily PM2.5 and PM10 concentrations showed significantly positive correlations with daily relative humidity. Five persistent pollution episodes were identified and classified as either stagnant accumulation or explosive growth types according to the mechanism of pollution formation and evolution. The PM2.5 and PM10 concentrations and PM2.5/PM10 ratio followed a growing "saw-tooth cycle" pattern during the stagnant accumulation type event. Dust storms caused abrupt peaks in PM10 and a sharp decrease in the PM2.5/PM10 ratio in explosive growth type events. The potential sources of PM10 were mainly distributed in the Kumtag Desert in Xinjiang Uygur Autonomous Region, the Qaidam Basin and Hehuang Valley in Qinghai Province, and the western and eastern Hexi Corridor in Gansu Province. The contributions to PM10 were more than 120 µg/m3. The important potential sources of PM2.5 were located in Hehuang Valley in Qinghai and Linxia Hui Autonomous Prefecture in Gansu; the concentrations of PM2.5 were more than 60 µg/m3.

The relationship between sleep onset time and cardiometabolic biomarkers in Chinese communities: a cross-sectional study.

BACKGROUND: Late sleep onset time (SOT) is a common social phenomenon in modern society, and it was associated with a higher risk of obesity. However, the literature gap exists about the SOT and cardiometabolic biomarkers which closely associated with obesity. The present study aimed to explore the association of SOT with cardiometabolic biomarkers in Chinese communities. METHODS: A cross-sectional study enrolled a total of 2418 participants was conducted in Ningxia province of China. The cardiometabolic biomarkers included triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein and fasting plasma glucose were measured quantitatively using the standard method. The SOT and sleep duration were acquired by a self-report questionnaire. The multiple mixed-effect linear regression model was employed to examine the association. RESULTS: Binary analysis found an inverse association of SOT with high-density lipoprotein (ß = - 0.05, 95%CI: - 0.06, - 0.03), with 1 h delayed in SOT the high-density lipoprotein decreased 0.05 mmol/L. After controlling for demographic variables, health-related behaviors, and physical health covariates, late SOT was associated with a higher level of triglyceride (ß = 0.12, 95%CI: 0.06, 0.18), a higher level of low-density lipoprotein (ß = 0.06, 95% CI: 0.02, 0.09), and a lower level of high-density lipoprotein (ß = - 0.05, 95% CI: - 0.06, - 0.03). when stratified by sleep duration (less than eight hours vs. eight and longer hours), a positive association between SOT and LDL (ß = 0.08, 95% CI: 0.04, 0.12) was found among participants with sleep duration eight hours and longer. CONCLUSION: Late sleep onset time with the negative effect on the cardiometabolic biomarkers, and individuals with late SOT coupled with longer sleep duration may take risk of a higher level of low-density lipoprotein which in turn lead to increase the risk of cardiovascular disease.

Mesoporous silica induces hippocampal neurons cell autophagy through AMPK/mTOR/P70S6K signaling pathway.

Mesoporous silica is a drug carrier with strong targeting, large loading capacity, and easy modification of its surface while its toxicity draws increasing attention recently. In this study, we evaluated the impact of SBA-15 nanomaterials on hippocampal neurons. We found that SBA-15 induces oxidative damage to hippocampal neurons HT22, which further activates autophagy. Treatment with the mammalian target of rapamycin (mTOR) inhibitor AZD8055, the phosphorylation level of mTOR and P70S6K reduced and increased levels of p-AMPK meaning that the adenosine-activated protein kinase (AMPK)/mTOR/P70S6K pathway is involved in SBA-15 induced autophagy of HT22. These results suggested that mesoporous silica material SBA-15 might affect central nervous cells via oxidative stress activation of the AMPK/mTOR/P70S6K pathway, which provides a theoretical basis for safe administration of such materials in patients.

[Meta-analysis on association between interleukin-6-174C/G and -634C/G polymorphisms and pneumoconiosis susceptibility].

OBJECTIVE: To explore the association between the interleukin-6-174 C/G and-634 C/G polymorphisms and pneumoconiosis susceptibility. METHODS: Taking pneumoconiosis, interleukin-6, and polymorphism as keywords, Chinese literatures were retrieved among the Sinomed, Wanfang Medicine, CNKI and VIP databases, and foreign language literatures were retrieved among the Pubmed, Embase, Cochrane Library and Web of Science databases. Taking pneumoconiosis, susceptibility, and interleukin-6 as keywords, Revman 5. 2 software was employed to combine the genetic effects and evaluate the quality of the included literatures. RESULTS: A total of seven literatures(containing nine case-control studies) were included, including 660 cases and 848 controls with IL-6-174 C/G polymorphism, and 344 cases and 362 controls with IL-6-634 C/G polymorphism. Meta-analysis shows that IL-6-174 C/G polymorphism is not associated with pneumoconiosis susceptibility(CC νs. CG+GG, OR=1. 05(95%CI 0. 76-1. 45), CG νs. GG+CC, OR=0. 79(95%CI 0. 40-1. 55), C νs. G, OR=0. 95(95% CI 0. 80-1. 14)), while IL-6-634 C/G polymorphism is associated with pneumoconiosis susceptibility(CC νs. CG+GG, OR=2. 12(95%CI 1. 56-2. 88), CG νs. GG+CC, OR=0. 40(95%CI 0. 27-0. 58), C νs. G, OR=1. 67(95%CI 1. 33-2. 11)). CONCLUSION: There exists an association between the IL-6-634 C/G polymorphism and pneumoconiosis susceptibility, while there isn't an association between the IL-6-174 C/G polymorphism and the susceptibility of pneumoconiosis. IL-6-634 C/C genotype is pneumoconiosis-susceptible genotype.

Intranasal immunization with Mycobacterium tuberculosis Rv3615c induces sustained adaptive CD4+ T-cell and antibody responses in the respiratory tract.

Sustained adaptive immunity to pathogens provides effective protection against infections, and effector cells located at the site of infection ensure rapid response to the challenge. Both are essential for the success of vaccine development. To explore new vaccination approach against Mycobacterium tuberculosis (M.tb) infection, we have shown that Rv3615c, identified as ESX-1 substrate protein C of M.tb but not expressed in BCG, induced a dominant Th1-type response of CD4+ T cells from patients with tuberculosis pleurisy, which suggests a potential candidate for vaccine development. But subcutaneous immunization with Rv3615c induced modest T-cell responses systemically, and showed suboptimal protection against virulent M.tb challenge at the site of infection. Here, we use a mouse model to demonstrate that intranasal immunization with Rv3615c induces sustained capability of adaptive CD4+ T- and B-cell responses in lung parenchyma and airway. Rv3615c contains a dominant epitope of mouse CD4+ T cells, Rv3615c41-50 , and elicits CD4+ T-cell response with an effector-memory phenotype and multi-Th1-type cytokine coexpressions. Since T cells resident at mucosal tissue are potent at control of infection at early stage, our data show that intranasal immunization with Rv3615c promotes a sustained regional immunity to M.tb, and suggests a potency in control of M.tb infection. Our study warranties a further investigation of Rv3615c as a candidate for development of effective vaccination against M.tb infection.