Exposure to acrylamide and increased risk of depression mediated by inflammation, oxidative stress, and alkaline phosphatase: Evidence from a nationally representative population-based study.

BACKGROUND: The health risk associated with acrylamide exposure has emerged as a significant issue of public health, attracting global attention. However, epidemiologic evidence on whether and how daily acrylamide exposure increases depression risk of the general population is unclear. METHODS: The study included 3991 adults from the National Health and Nutrition Examination Survey. The urinary metabolites of acrylamide (N-Acetyl-S-(2-carbamoylethyl)-L-cysteine [AAMA] and N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine [GAMA]) identified as reliable indicators of acrylamide exposure were examined to determine their relationships with depressive symptoms that were evaluated using the 9-item Patient Health Questionnaire. Besides, the measurements of alkaline phosphatase (ALP) and biomarkers of inflammation (white blood cell [WBC] count) and anti-oxidative stress (albumin [ALB]) were conducted to investigate their mediation roles in above relationships. RESULT: AAMA, GAMA, and ΣUAAM (AAMA+GAMA) were linearly associated with increased risk of depressive symptoms. Each 2.7-fold increase in AAMA, GAMA, or ΣUAAM was associated with a 30 % (odds ratio: 1.30; 95 % confidence interval: 1.09, 1.55), 47 % (1.47; 1.16, 1.87), or 36 % (1.36; 1.13, 1.63) increment in risk of depressive symptoms, respectively. Increased WBC count (mediated proportion: 4.48-8.00 %), decreased ALB (4.88-7.78 %), and increased ALP (4.93-5.23 %) significantly mediated the associations between acrylamide metabolites and depressive symptoms. CONCLUSIONS: Acrylamide exposure of the general adult population was related to increased risk of depressive symptoms, which was mediated in part by inflammation, oxidative stress, and increased ALP. Our findings provided pivotal epidemiologic evidence for depression risk increment from exposure to acrylamide.

Mesoporous silica stabilized perovskite quantum dots for the preparation of ultra-stable green flexible film.

CsPbBr3 perovskite quantum dots (QDs) have attracted much attention in the optical field because of their low band gap, wide absorption spectrum and high color purity. However, their poor stability in extreme environments such as water, light and heat severely limits their application in optical fields. Here, we prepared m-SiO2/CsPbBr3 composite luminescent material using an aqueous phase method combined with high temperature calcination. The material can retain 87% of the initial photoluminescence quantum efficiency after 60 days of storage under ambient conditions (humidity ∼80%; temperature ∼25 °C), its photoluminescence intensity only decreased by 33% after immersion in water for 90 min. This indicates that the material retains good stability under a high humidity environment. Finally, PMMA@m-SiO2/CsPbBr3 flexible films were prepared by aqueous solution polymerization. The flexible film has excellent green light emission properties and exhibits (0.092, 0.625) CIE coordinates.

A systematic review of exosomes in remote ischemic conditioning.

BACKGROUND: Remote ischemic conditioning (RIC) is considered a promising non-pharmacological therapeutic strategy to mitigate ischemic injury. Although the precise mechanisms of RIC's protective effects remain elusive, existing data suggest that exosomes contribute significantly to these processes through cell-to-cell communication OBJECTIVE: This review aims to elucidate the role of exosomes in RIC-mediated multi-organ protection. METHODS: We systematically searched multiple databases through October 2023 for preclinical studies evaluating the effect of exosomes in ischemic models using RIC procedures. Key outcomes, such as improved organ function and reduced infarct size, were recorded. Articles were selected and data were extracted by independent pairs of reviewers. FINDINGS: A total of 16 relevant studies were identified in this review, showing that circulating exosomes derived from the plasma of RIC-treated animals exhibited protective effects akin to those of the RIC procedure itself. Exosome concentrations were measured in eight studies, six of which reported significant increases in the RIC group. Additional findings indicated that RIC might primarily modulate the expression of miRNAs and bioactive molecules delivered by exosomes, rather than directly altering circulating exosome levels. Notably, the expression of 11 distinct exosomal miRNAs was altered after RIC intervention, potentially involving multiple pathways. CONCLUSION: Exosomes appear to play a pivotal role in the protective effects induced by RIC. Clarifying their function in RIC under different pathological situations represents a grand challenge for future research.

Synchronization bandwidth enhancement induced by a parametrically excited oscillator.

The synchronization phenomenon in nature has been utilized in sensing and timekeeping fields due to its numerous advantages, including amplitude and frequency stabilization, noise reduction, and sensitivity improvement. However, the limited synchronization bandwidth hinders its broader application, and few techniques have been explored to enhance this aspect. In this paper, we conducted theoretical and experimental studies on the unidirectional synchronization characteristics of a resonator with phase lock loop oscillation. A novel enhancement method for the synchronization bandwidth using a parametrically excited MEMS oscillator is proposed, which achieves a remarkably large synchronization bandwidth of 8.85 kHz, covering more than 94% of the hysteresis interval. Importantly, the proposed method exhibits significant potential for high-order synchronization and frequency stabilization compared to the conventional directly excited oscillator. These findings present an effective approach for expanding the synchronization bandwidth, which has promising applications in nonlinear sensing, fully mechanical frequency dividers, and high-precision time references.

Advancing stroke therapy: innovative approaches with stem cell-derived extracellular vesicles.

Stroke is a leading cause of mortality and long-term disability globally, with acute ischemic stroke (AIS) being the most common subtype. Despite significant advances in reperfusion therapies, their limited time window and associated risks underscore the necessity for novel treatment strategies. Stem cell-derived extracellular vesicles (EVs) have emerged as a promising therapeutic approach due to their ability to modulate the post-stroke microenvironment and facilitate neuroprotection and neurorestoration. This review synthesizes current research on the therapeutic potential of stem cell-derived EVs in AIS, focusing on their origin, biogenesis, mechanisms of action, and strategies for enhancing their targeting capacity and therapeutic efficacy. Additionally, we explore innovative combination therapies and discuss both the challenges and prospects of EV-based treatments. Our findings reveal that stem cell-derived EVs exhibit diverse therapeutic effects in AIS, such as promoting neuronal survival, diminishing neuroinflammation, protecting the blood-brain barrier, and enhancing angiogenesis and neurogenesis. Various strategies, including targeting modifications and cargo modifications, have been developed to improve the efficacy of EVs. Combining EVs with other treatments, such as reperfusion therapy, stem cell transplantation, nanomedicine, and gut microbiome modulation, holds great promise for improving stroke outcomes. However, challenges such as the heterogeneity of EVs and the need for standardized protocols for EV production and quality control remain to be addressed. Stem cell-derived EVs represent a novel therapeutic avenue for AIS, offering the potential to address the limitations of current treatments. Further research is needed to optimize EV-based therapies and translate their benefits to clinical practice, with an emphasis on ensuring safety, overcoming regulatory hurdles, and enhancing the specificity and efficacy of EV delivery to target tissues.

Anti-inflammatory Effect of Batroxobin Combined With Anticoagulation in Patients With Cerebral Venous Thrombosis.

Inflammation is pivotal in the pathogenesis and development of cerebral venous thrombosis (CVT). Herein, we aimed to assess the anti-inflammatory effects of batroxobin combined with anticoagulation in CVT. Participants were categorized into the batroxobin group (batroxobin combined with anticoagulation) and the control group (anticoagulation only). Regression analysis was employed to explore the association between the number of episodes of batroxobin administration and the fluctuation of inflammatory indicators, as well as the proportion of patients with inflammatory indicators that were reduced after batroxobin use. Twenty-three cases (age: 39.9 ± 13.8 years, female: 39.1%) in the batroxobin group and 36 cases (40.3 ± 9.6 years, 52.8%) in the control group were analyzed. Compared to the control group, batroxobin combined with anticoagulation significantly decreased fibrinogen (P < .001), platelet-lymphocyte ratio (PLR) (P = .016) and systemic immune-inflammation index (SII) (P = .008), and increased the proportion of the patients with lower fibrinogen (P < .001), neutrophil-lymphocyte ratio (NLR) (P = .005), PLR (P = .026), and SII (P = .006). Linear analysis showed that as the number of episodes of batroxobin administration increased, the fibrinogen (P < .001), the PLR (P = .001), and the SII (P = .020) significantly decreased. Logistic regression analysis showed as the number of episodes of batroxobin administration increased, the ratio of the patients with decreased NLR (P = .008) and PLR (P = .015), as well as SII (P = .013), significantly increased. Batroxobin could decrease NLR, PLR, and SII in CVT. The effect was related to the number of episodes of batroxobin administration. Besides reducing fibrinogen and indirect thrombolysis effects, this may be another critical benefit of batroxobin for CVT.

Sleep and liver function biomarkers in relation to risk of incident liver cancer: a nationwide prospective cohort study.

BACKGROUND: To assess the largely undetermined separate and joint effects of sleep and liver function biomarkers on liver cancer. METHODS: Data of 356,894 participants without cancer at baseline in the UK Biobank were analyzed. Sleep score was evaluated using five sleep traits (sleep duration, chronotype, insomnia, snoring, and excessive daytime sleepiness) and dichotomized into healthy or unhealthy sleep. Circulating liver function biomarkers were measured. Cox proportional hazard model was performed to investigate the independent and joint associations of sleep and liver function biomarkers with liver cancer incidence. RESULTS: After a median follow-up time of 13.1 years, 394 cases of incident liver cancer were documented. The multivariable-adjusted hazard ratio (HR) for liver cancer was 1.46 (95% confidence interval: 1.15-1.85) associated with unhealthy sleep (vs. healthy sleep), and was 1.17 (1.15-1.20), 1.20 (1.18-1.22), 1.69 (1.47-1.93), 1.06 (1.06-1.07), 1.08 (1.07-1.09), 1.81 (1.37-2.39), or 0.29 (0.18-0.46) associated with each 10-unit increase in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), or albumin (ALB), respectively. Individuals with unhealthy sleep and high (≥ median) ALT, AST, TBIL, GGT, ALP, or TP or low (< median) ALB level had the highest HR of 3.65 (2.43-5.48), 4.03 (2.69-6.03), 1.97 (1.40-2.77), 4.69 (2.98-7.37), 2.51 (1.75-3.59), 2.09 (1.51-2.89), or 2.22 (1.55-3.17) for liver cancer, respectively. Significant additive interaction of unhealthy sleep with high TP level on liver cancer was observed with relative excess risk due to an interaction of 0.80 (0.19-1.41). CONCLUSIONS: Unhealthy sleep was associated with an increased risk of liver cancer, especially in participants with lower ALB levels or higher levels of ALT, AST, TBIL, GGT, ALP, or particularly TP.

Exposure to ambient air pollutants during circadian syndrome and subsequent cardiovascular disease and its subtypes and death: A trajectory analysis.

BACKGROUND: The association between exposure to air pollutants and cardiovascular disease (CVD) trajectory in individuals with circadian syndrome remains inconclusive. METHODS: The individual exposure levels of air pollutants, including particulate matter (PM) with aerodynamic diameter ≤ 2.5 µm (PM2.5), PM with aerodynamic diameter ≤ 10 µm (PM10), PM2.5 absorbance, PM with aerodynamic diameter between 2.5 µm and 10 µm, nitrogen dioxide (NO2), nitrogen oxides (NOx), and air pollution score (overall air pollutants exposure), were estimated for 48,850 participants with circadian syndrome from the UK Biobank. Multistate regression models were employed to estimate associations between exposure to air pollutants and trajectories from circadian syndrome to CVD/CVD subtypes (including coronary heart disease [CHD], atrial fibrillation [AF], heart failure [HF], and stroke) and death. Mediation roles of CVD/CVD subtypes in the associations between air pollutants and death were evaluated. RESULTS: After a mean follow-up time over 12 years, 12,570 cases of CVD occurred, including 8192 CHD, 1693 AF, 1085 HF, and 1600 stroke cases. In multistate model, per-interquartile range increment in PM2.5 (hazard ratio: 1.08; 95 % confidence interval: 1.06, 1.10), PM10 (1.04; 1.01, 1.06), PM2.5 absorbance (1.04; 1.02, 1.06), NO2 (1.07; 1.03, 1.11), NOx (1.08; 1.04, 1.12), or air pollution score (1.06; 1.03, 1.08) was associated with trajectory from circadian syndrome to CVD. Significant associations between the above-mentioned air pollutants and trajectories from circadian syndrome and CVD to death were observed. CVD, particularly CHD, significantly mediated the associations of PM2.5, NO2, NOx, and air pollution score with death. CONCLUSIONS: Long-term exposure to air pollutants during circadian syndrome was associated with subsequent CVD and death. CHD emerged as the most prominent CVD subtype in CVD progression driven by exposure to air pollutants during circadian syndrome. Our study highlights the importance of controlling air pollutants exposure and preventing CHD in people with circadian syndrome.

Air pollution exposure, accelerated biological aging, and increased thyroid dysfunction risk: Evidence from a nationwide prospective study.

BACKGROUND: Long-term air pollution exposure is a major health concern, yet its associations with thyroid dysfunction (hyperthyroidism and hypothyroidism) and biological aging remain unclear. We aimed to determine the association of long-term air pollution exposure with thyroid dysfunction and to investigate the potential roles of biological aging. METHODS: A prospective cohort study was conducted on 432,340 participants with available data on air pollutants including particulate matter (PM2.5, PM10, and PM2.5-10), nitrogen dioxide (NO2), and nitric oxide (NO) from the UK Biobank. An air pollution score was calculated using principal component analysis to reflect joint exposure to these pollutants. Biological aging was assessed using the Klemera-Doubal method biological age and the phenotypic age algorithms. The associations of individual and joint air pollutants with thyroid dysfunction were estimated using the Cox proportional hazards regression model. The roles of biological aging were explored using interaction and mediation analyses. RESULTS: During a median follow-up of 12.41 years, 1,721 (0.40 %) and 9,296 (2.15 %) participants developed hyperthyroidism and hypothyroidism, respectively. All air pollutants were observed to be significantly associated with an increased risk of incident hypothyroidism, while PM2.5, PM10, and NO2 were observed to be significantly associated with an increased risk of incident hyperthyroidism. The hazard ratios (HRs) for hyperthyroidism and hypothyroidism were 1.15 (95 % confidence interval: 1.00-1.32) and 1.15 (1.08-1.22) for individuals in the highest quartile compared with those in the lowest quartile of air pollution score, respectively. Additionally, we noticed that individuals with higher pollutant levels and biologically older generally had a higher risk of incident thyroid dysfunction. Moreover, accelerated biological aging partially mediated 1.9 %-9.4 % of air pollution-associated thyroid dysfunction. CONCLUSIONS: Despite the possible underestimation of incident thyroid dysfunction, long-term air pollution exposure may increase the risk of incident thyroid dysfunction, particularly in biologically older participants, with biological aging potentially involved in the mechanisms.

The possible causal relationship between COVID-19 and imaging markers of cerebral small vessel disease: a Mendelian randomization study.

OBJECTIVES: Observational studies have suggested that SARS-CoV-2 infection may increase the burden of cerebral small vessel disease (CSVD). This study aims to explore the causal correlation between COVID-19 and the imaging markers of CSVD using Mendelian randomization (MR) methods. METHODS: Summary-level genome-wide association study (GWAS) statistics for COVID-19 susceptibility, hospitalization, and severity were utilized as proxies for exposure. Large-scale meta-analysis GWAS data on three neuroimaging markers of white matter hyperintensity, lacunar stroke, and brain microbleeds, were employed as outcomes. Our primary MR analysis employed the inverse variance weighted (IVW) approach, supplemented by MR-Egger, weighted median, and MR-PRESSO methods. We also conducted multivariable MR analysis to address confounding bias and validate the robustness of the established causal estimates. Comprehensive sensitivity analyses included Cochran's Q test, Egger-intercept analysis, MR-PRESSO, and leave-one-out analysis. RESULTS: The MR analysis revealed a significant causal correlation between the severity of COVID-19 and an increased risk of lacunar stroke, as demonstrated by the IVW method (ORivw = 1.08, 95% CI: 1.03-1.16, pivw = 0.005, FDR = 0.047). Nevertheless, no causal correlations were observed between COVID-19 susceptibility or hospitalization and any CSVD imaging markers. The robustness and stability of these findings were further confirmed by multivariable MR analysis and comprehensive sensitivity analyses. DISCUSSION: This study provides compelling evidence of a potential causal effect of severe COVID-19 on the incidence of lacunar stroke, which may bring fresh insights into the understanding of the comorbidity between COVID-19 and CSVD.

The causal relationship between sarcopenia-related traits and ischemic stroke: Insights from univariable and multivariable Mendelian randomization analyses.

AIMS: The causal relationship between sarcopenia-related traits and ischemic stroke (IS) remains poorly understood. This study aimed to explore the causal impact of sarcopenia-related traits on IS and to identify key mediators of this association. METHODS: We conducted univariable, multivariable two-sample, and two-step Mendelian randomization (MR) analyses using genome-wide association study (GWAS) data. This included data for appendicular lean mass (ALM), hand grip strength (HGS), and usual walking pace (UWP) from the UK Biobank, and IS data from the MEGASTROKE consortium. Additionally, 21 candidate mediators were analyzed based on their respective GWAS data sets. RESULTS: Each 1-SD increase in genetically proxied ALM was associated with a 7.5% reduction in the risk of IS (95% CI: 0.879-0.974), and this correlation remained after controlling for levels of physical activity and adiposity-related indices. Two-step MR identified that six mediators partially mediated the protective effect of higher ALM on IS, with the most significant being coronary heart disease (CHD, mediating proportion: 39.94%), followed by systolic blood pressure (36.51%), hypertension (23.87%), diastolic blood pressure (15.39%), type-2 diabetes mellitus (T2DM, 12.71%), and low-density lipoprotein cholesterol (7.97%). CONCLUSION: Our study revealed a causal protective effect of higher ALM on IS, independent of physical activity and adiposity-related indices. Moreover, we found that higher ALM could reduce susceptibility to IS partially by lowering the risk of vascular risk factors, including CHD, hypertension, T2DM, and hyperlipidemia. In brief, we elucidated another modifiable factor for IS and implied that maintaining sufficient muscle mass may reduce the risk of such disease.

The first high-quality chromosome-level genome of Eretmochelys imbricata using HiFi and Hi-C data.

Eretmochelys imbricata, a critically endangered sea turtle inhabiting tropical oceans and protected across the world, had an unknown genome sequence until now. In this study, we used HiFi reads and Hi-C technology to assemble a high-quality, chromosome-level genome of E. imbricata. The genome size was 2,138.26 Mb, with contig N50 length of 123.49 Mb and scaffold N50 of 137.21 Mb. Approximately 97.52% of the genome sequence was anchored to 28 chromosomes. A total of 20,206 protein-coding genes were predicted. We also analyzed the evolutionary relationships, gene family expansions, and positive selection of E. imbricata. Our results revealed that E. imbricata diverged from Chelonia mydas 38 million years ago and had enriched olfactory receptors and aging-related genes. Our genome will be useful for studying E. imbricata and its conservation.

Identification of Colletotrichum aenigma as the new causal agent of leaf blight disease on Aucuba japonica Thunb., and screenings of effective fungicides for its sustainable management.

Aucuba japonica Thunb is an evergreen woody ornamental plant with significant economic and ecological values. It also produces aucubin, showing a variety of biological activities. It is widely planted in the southwest region of China, including karst landscape areas in Guizhou Province. In January 2022, a serious leaf blight disease was observed on the leaves of A. japonica in the outdoor gardens of Guizhou University, Guiyang, Guizhou, China. The causal agent was identified as Colletotrichum aenigma through amplification and sequencing of the internal transcribed spacer (ITS) region, translation of the chitin synthase (CHS) and actin (ACT) genes, and morphological characterizations. Koch's postulates were confirmed by its pathogenicity on healthy leaves, including re-isolation and identification. To our knowledge, this is the first report of C. aenigma causing leaf blight on A. japonica worldwide. To identify pathogen characteristics that could be utilized for future disease management, the effects of temperature and light on mycelial growth, conidia production, and conidial germination, and the effects of humidity on conidial germination were studied. Optimal temperatures for mycelial growth of C. aenigma BY827 were 25-30°C, while 15°C and 35°C were favorable for conidia production. Concurrently, alternating 10-h light and 14-h dark, proved to be beneficial for mycelial growth and conidial germination. Additionally, conidial germination was enhanced at 90% humidity. In vitro screenings of ten chemical pesticides to assess their efficacy in suppressing C. aenigma representative strain BY827. Among them, difenoconazole showed the best inhibition rate, with an EC50 (concentration for 50% of maximal effect) value of 0.0148 µg/ml. Subsequently, field experiment results showed that difenoconazole had the highest control efficiency on A. japonica leaf blight (the decreasing rate of disease incidence and decreasing rate of disease index were 44.60 and 47.75%, respectively). Interestingly, we discovered that C. aenigma BY827 may develop resistance to mancozeb, which is not reported yet among Colletotrichum spp. strains. In conclusion, our study provided new insights into the causal agent of A. japonica leaf blight, and the effective fungicides evaluated provided an important basis and potential resource for the sustainable control of A. japonica leaf blight caused by C. aenigma in the field.

Gene-environment interaction in long-term effects of polychlorinated biphenyls exposure on glucose homeostasis and type 2 diabetes: The modifying effects of genetic risk and lifestyle.

The longitudinal relationships of polychlorinated biphenyls (PCBs) exposure with glucose homeostasis and type 2 diabetes (T2D) risk among Chinese population have not been assessed, and interactions of PCB exposure with genetic susceptibility and lifestyle are unclear. In this prospective cohort study, fasting plasma glucose (FPG) and insulin (FPI) and seven serum indicator-PCBs were measured for each participant. We constructed polygenic risk score (PRS) of T2D and healthy lifestyle score. Each 1-unit increment of ln-transformed PCB-118 was related with a 0.141 mmol/L, 11.410 pmol/L, 0.661, and 74.5% increase in FPG, FPI, homeostasis model assessment of insulin resistance, and incident T2D risk over 6 years, respectively. Each 1-unit increment in T2D-PRS was related with a 0.169 mmol/L elevation of FPG and 65.5% elevation of incident T2D risk during 6 years. Compared with participants who had low T2D-PRS and low PCB-118, participants with high T2D-PRS and high PCB-118 showed a significant increase in FPG (0.162 mmol/L; P for interaction <0.001) and incident T2D risk [hazard ratio (HR)= 2.222]. Participants with low PCB-118, low PRS, and healthy lifestyle had the lowest incident T2D risk (HR=0.232). Our findings highlighted the significance of reducing PCB exposure and improvement in lifestyle for T2D prevention and management, especially for individuals with higher genetic risk of T2D.

Genomic Evidence for the Nonpathogenic State in HIV-1-Infected Northern Pig-Tailed Macaques.

HIV-1 is a highly host-specific retrovirus that infects humans but not most nonhuman primates. Thus, the lack of a suitable primate model that can be directly infected with HIV-1 hinders HIV-1/AIDS research. In the previous study, we have found that the northern pig-tailed macaques (NPMs) are susceptible to HIV-1 infection but show a nonpathogenic state. In this study, to understand this macaque-HIV-1 interaction, we assembled a de novo genome and longitudinal transcriptome for this species during the course of HIV-1 infection. Using comparative genomic analysis, a positively selected gene, Toll-like receptor 8, was identified with a weak ability to induce an inflammatory response in this macaque. In addition, an interferon-stimulated gene, interferon alpha inducible protein 27, was upregulated in acute HIV-1 infection and acquired an enhanced ability to inhibit HIV-1 replication compared with its human ortholog. These findings coincide with the observation of persistently downregulated immune activation and low viral replication and can partially explain the AIDS-free state in this macaque following HIV-1 infection. This study identified a number of unexplored host genes that may hamper HIV-1 replication and pathogenicity in NPMs and provided new insights into the host defense mechanisms in cross-species infection of HIV-1. This work will facilitate the adoption of NPM as a feasible animal model for HIV-1/AIDS research.

Acrolein Exposure Impaired Glucose Homeostasis and Increased Risk of Type 2 Diabetes: An Urban Adult Population-Based Cohort Study with Repeated Measures.

Acrolein is an identified high-priority hazardous air pollutant ubiquitous in daily life and associated with cardiometabolic risk that attracts worldwide attention. However, the etiology role of acrolein exposure in glucose dyshomeostasis and type 2 diabetes (T2D) is unclear. This repeated-measurement prospective cohort study included 3522 urban adults. Urine/blood samples were repeatedly collected for determinations of acrolein metabolites (N-acetyl-S-(3-hydroxypropyl)-l-cysteine, N-acetyl-S-(2-carboxyethyl)-l-cysteine; acrolein exposure biomarkers), glucose homeostasis, and T2D at baseline and a three-year follow-up. We found that each 3-fold increment in acrolein metabolites was cross-sectionally associated with 5.91-6.52% decrement in homeostasis model assessment-insulin sensitivity (HOMA-IS) and 0.07-0.14 mmol/L, 4.02-4.57, 5.91-6.52, 19-20, 18-19, and 23-31% increments in fasting glucose (FPG), fasting insulin (FPI), HOMA-insulin resistance (HOMA-IR), risks of prevalent IR, impaired fasting glucose (IFG), and T2D, respectively; longitudinally, participants with sustained-high acrolein metabolite levels had increased risks of incident IR, IFG, and T2D by 63-80, 87-99, and 120-154%, respectively (P < 0.05). In addition, biomarkers of heme oxygenase-1 activity (exhaled carbon monoxide), lipid peroxidation (8-iso-prostaglandin-F2α), protein carbonylation (protein carbonyls), and oxidative DNA damage (8-hydroxy-deoxyguanosine) mediated 5.00-38.96% of these associations. Our study revealed that acrolein exposure may impair glucose homeostasis and increase T2D risk via mediating mechanisms of heme oxygenase-1 activation, lipid peroxidation, protein carbonylation, and oxidative DNA damage.

Carbon disulfide exposure induced lung function reduction partly through oxidative protein damage: A cross-sectional and longitudinal analysis.

Carbon disulfide (CS2) exposure has been associated with lung function reduction in occupational population. However, evidence on the general population with relatively low CS2 exposure is lacking and the mechanism involved remains largely unknown. Urinary CS2 metabolite (2-mercaptothiazolidine-4-carboxylic acid, TTCA) and lung function were determined in the urban adults from the Wuhan-Zhuhai cohort at baseline in 2011-2012 and were repeated every 3 years. Cross-sectional and longitudinal associations between TTCA and lung function were estimated using linear mixed models. Inflammation and oxidative damage biomarkers in blood/urine were measured to evaluate their potential mediating roles involved. Cross-sectionally, participants in the highest quartile of TTCA level showed a 0.64% reduction in FEV1/FVC and a -308.22 mL/s reduction in PEF, compared to those in the lowest quartile. Longitudinally, participants with consistently high TTCA level had annually -90.27 mL/s decline in PEF, compared to those with consistently low TTCA level. Mediation analysis revealed that plasma protein carbonyl mediated 49.89% and 22.10% of TTCA-associated FEV1/FVC and PEF reductions, respectively. Conclusively, there was a cross-sectional and longitudinal association between CS2 exposure and lung function reduction in the general urban adults, and protein carbonylation (oxidative protein damage) partly mediated lung function reduction from CS2 exposure.

The potential role of plasma miR-4301 in PM2.5 exposure-associated lung function reduction.

The effect of PM2.5 exposure on lung function reduction has been well-documented, but the underlying mechanism remains unclear. MiR-4301 may be involved in regulating pathways related to lung injury/repairment, and this study aimed to explore the potential role of miR-4301 in PM2.5 exposure-associated lung function reduction. A total of 167 Wuhan community nonsmokers were included in this study. Lung function was measured and personal PM2.5 exposure moving averages were evaluated for each participant. Plasma miRNA was determined by real-time polymerase chain reaction. A generalized linear model was conducted to assess the relationships among personal PM2.5 moving average concentrations, lung function, and plasma miRNA. The mediation effect of miRNA on the association of personal PM2.5 exposure with lung function reduction was estimated. Finally, we performed pathway enrichment analysis to predict the underlying pathways of miRNA in lung function reduction from PM2.5 exposure. We found that each 10 µg/m3 increase in the 7-day personal PM2.5 moving average concentration (Lag0-7) was related to a 46.71 mL, 1.15%, 157.06 mL/s, and 188.13 mL/s reductions in FEV1, FEV1/FVC, PEF, and MMF, respectively. PM2.5 exposure was negatively associated with plasma miR-4301 expression levels in a dose‒response manner. Additionally, each 1% increase in miR-4301 expression level was significantly associated with a 0.36 mL, 0.01%, 1.14 mL/s, and 1.28 mL/s increases in FEV1, FEV1/FVC, MMF, and PEF, respectively. Mediation analysis further revealed that decreased miR-4301 mediated 15.6% and 16.8% of PM2.5 exposure-associated reductions in FEV1/FVC and MMF, respectively. Pathway enrichment analyses suggested that the wingless related-integration site (Wnt) signaling pathway might be one of the pathways regulated by miR-4301 in the reduction of lung function from PM2.5 exposure. In brief, personal PM2.5 exposure was negatively associated with plasma miR-4301 or lung function in a dose‒response manner. Moreover, miR-4301 partially mediated the lung function reduction associated with PM2.5 exposure.

Association of ambient carbon monoxide exposure with hospitalization risk for respiratory diseases: A time series study in Ganzhou, China.

Background: Ambient carbon monoxide (CO) exposure is associated with increased mortality and hospitalization risk for total respiratory diseases. However, evidence on the risk of hospitalization for specific respiratory diseases from ambient CO exposure is limited. Methods: Data on daily hospitalizations for respiratory diseases, air pollutants, and meteorological factors from January 2016 to December 2020 were collected in Ganzhou, China. A generalized additive model with the quasi-Poisson link and lag structures was used to estimate the associations between ambient CO concentration and hospitalizations of total respiratory diseases, asthma, chronic obstructive pulmonary disease (COPD), upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), and influenza-pneumonia. Possible confounding co-pollutants and effect modification by gender, age, and season were considered. Results: A total of 72,430 hospitalized cases of respiratory diseases were recorded. Significant positive exposure-response relationships were observed between ambient CO exposure and hospitalization risk from respiratory diseases. For each 1 mg/m3 increase in CO concentration (lag0-2), hospitalizations for total respiratory diseases, asthma, COPD, LRTI, and influenza-pneumonia increased by 13.56 (95% CI: 6.76%, 20.79%), 17.74 (95% CI: 1.34%, 36.8%), 12.45 (95% CI: 2.91%, 22.87%), 41.25 (95% CI: 18.19%, 68.81%), and 13.5% (95% CI: 3.41%, 24.56%), respectively. In addition, the associations of ambient CO with hospitalizations for total respiratory diseases and influenza-pneumonia were stronger during the warm season, while women were more susceptible to ambient CO exposure-associated hospitalizations for asthma and LRTI (all P < 0.05). Conclusion: In brief, significant positive exposure-response relationships were found between ambient CO exposure and hospitalization risk for total respiratory diseases, asthma, COPD, LRTI, and influenza-pneumonia. Effect modification by season and gender was found in ambient CO exposure-associated respiratory hospitalizations.

A Novel Vpu Adaptive Mutation of HIV-1 Degrades Tetherin in Northern Pig-Tailed Macaques (Macaca leonina) Mainly via the Ubiquitin-Proteasome Pathway and Increases Viral Release.

Tetherin prevents viral cross-species transmission by inhibiting the release of multiple enveloped viruses from infected cells. With the evolution of simian immunodeficiency virus of chimpanzees (SIVcpz), a pandemic human immunodeficiency virus type 1 (HIV-1) precursor, its Vpu protein can antagonize human tetherin (hTetherin). Macaca leonina (northern pig-tailed macaque [NPM]) is susceptible to HIV-1, but host-specific restriction factors limit virus replication in vivo. In this study, we isolated the virus from NPMs infected with strain stHIV-1sv (with a macaque-adapted HIV-1 env gene from simian-human immunodeficiency virus SHIV-KB9, a vif gene replaced by SIVmac239, and other genes originating from HIV-1NL4.3) and found that a single acidic amino acid substitution (G53D) in Vpu could increase its ability to degrade the tetherin of macaques (mTetherin) mainly through the proteasome pathway, resulting in an enhanced release and resistance to interferon inhibition of the mutant stHIV-1sv strain, with no influence on the other functions of Vpu. IMPORTANCE HIV-1 has obvious host specificity, which has greatly hindered the construction of animal models and severely restricted the development of HIV-1 vaccines and drugs. To overcome this barrier, we attempted to isolate the virus from NPMs infected with stHIV-1sv, search for a strain with an adaptive mutation in NPMs, and develop a more appropriate nonhuman primate model of HIV-1. This is the first report identifying HIV-1 adaptations in NPMs. It suggests that while tetherin may limit HIV-1 cross-species transmission, the Vpu protein in HIV-1 can overcome this species barrier through adaptive mutation, increasing viral replication in the new host. This finding will be beneficial to building an appropriate animal model for HIV-1 infection and promoting the development of HIV-1 vaccines and drugs.