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.

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.

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.

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 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.

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.

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.

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.

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.

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.

CVD growth of large-area monolayer WS2 film on sapphire through tuning substrate environment and its application for high-sensitive strain sensor.

Large-area, continuous monolayer WS2 exhibits great potential for future micro-nanodevice applications due to its special electrical properties and mechanical flexibility. In this work, the front opening quartz boat is used to increase the amount of sulfur (S) vapor under the sapphire substrate, which is critical for achieving large-area films during the chemical vapor deposition processes. COMSOL simulations reveal that the front opening quartz boat will significantly introduce gas distribute under the sapphire substrate. Moreover, the gas velocity and height of substrate away from the tube bottom will also affect the substrate temperature. By carefully optimizing the gas velocity, temperature, and height of substrate away from the tube bottom, a large-scale continues monolayered WS2 film was achieved. Field-effect transistor based on the as-grown monolayer WS2 showed a mobility of 3.76 cm2V-1 s-1 and ON/OFF ratio of 106. In addition, a flexible WS2/PEN strain sensor with a gauge factor of 306 was fabricated, showing great potential for applications in wearable biosensors, health monitoring, and human-computer interaction.

How does Internet use affect farmers' low-carbon agricultural technologies in southern China?

Agricultural low-carbon emission reduction is an essential part of China's ecological civilization construction. Farmers' low-carbon agricultural technology (LCAT) adoption has become an important means to achieve agricultural low-carbon emission reduction. Based on the survey data of 1080 farmers in Sichuan Province, farmers' LCAT adoption has been empirically studied using the combined estimate conditional mixed treatment model (CMP). The results show that the use of the Internet will substantially promote farmers' low-carbon tillage technology adoption and low-carbon fertilization technology adoption but has no significant impact on farmers' low-carbon pharmaceutical application technology adoption, low-carbon irrigation technology adoption, low-carbon agricultural film recycling technology adoption, and straw recycling technology adoption. Mechanism analysis shows that Internet use mainly affects farmers' low-carbon fertilization technology adoption through economic benefit cognition and affects farmers' low-carbon tillage technology adoption through ecological benefit cognition. This study can enhance our understanding of the relationship between Internet use and LCAT adoption and serve as a resource for rural digital infrastructure development and LCAT adoption-related policy design.

Cross-sectional and Longitudinal Associations Between Propylene Oxide Exposure and Lung Function Among Chinese Community Residents: Roles of Oxidative DNA Damage, Lipid Peroxidation, and Protein Carbonylation.

BACKGROUND: Toxicologic studies have reported propylene oxide (PO) exposure may harm the respiratory system, but the association between PO exposure and lung function and potential mechanism remains unclear. RESEARCH QUESTION: What is the association between PO exposure and lung function and potential mediating mechanism? STUDY DESIGN AND METHODS: Urinary PO metabolite [N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA)] as PO internal exposure biomarker and lung function were measured for 3,692 community residents at baseline and repeated at 3-year follow up. Cross-sectional and longitudinal associations between urinary 2HPMA and lung function were assessed by linear mixed model. Urinary 8-hydroxy-deoxyguanosine, urinary 8-iso-prostaglandin-F2α, and plasma protein carbonyls as biomarkers of oxidative DNA damage, lipid peroxidation, and protein carbonylation, respectively, were measured for all participants to explore their potential roles in 2HPMA-associated lung function decline by mediation analysis. RESULTS: After adjustment for potential covariates, each threefold increase in urinary 2HPMA was cross sectionally associated with a 26.18 mL (95% CI, -50.55 to -1.81) and a 21.83 mL (95% CI, -42.71 to -0.95) decrease in FVC and FEV1, respectively, at baseline (all P < .05). After 3 years of follow up, 2HPMA was observed to be longitudinally associated with FEV1/FVC decline. No significant interaction effect of smoking or passive smoking was observed (Pinteraction > .05), and the associations between 2HPMA and lung function indexes were persistent among participants who were not smoking and those who were not passive smoking in both baseline and follow-up evaluations. We observed urinary 8-hydroxy-deoxyguanosine partially mediated the associations of 2HPMA with FVC (mediation proportion, 5.48%) and FEV1 (mediation proportion, 6.81%), and plasma protein carbonyl partially mediated the association between 2HPMA and FEV1 (mediation proportion, 3.44%). INTERPRETATION: PO exposure was associated with lung function decline among community residents, and oxidative DNA damage and protein carbonylation partially mediated PO exposure-associated lung function decline. Further attention on respiratory damage caused by PO exposure is warranted.

Impact of outsourced machinery services on farmers' green production behavior: Evidence from Chinese rice farmers.

As an important part of agricultural socialization services, outsourced machinery services are of great significance for promoting the green development of agriculture. Using the field survey data of 1080 rice growers in Sichuan Province, this paper empirically analyzes outsourced machinery services' impact and role path on farmers' green production behavior. Further, it analyzes the difference in influence from the perspective of group heterogeneity. The research results show that: (1) The outsourced machinery services significantly impact farmers' adoption of no-tillage technology, organic fertilizer application technology, and straw returning technology. The conclusion is still stable after considering endogeneity. (2) The outsourced machinery services indirectly affect farmers' green production behavior by promoting off-farm employment and expanding the scale of farmland. (3) The impact of outsourced machinery services on farmers' green production behavior is not significant in the male group and the group whose households own agricultural machinery. In conclusion, the study proposes to increase assistance to outsourced machinery services providers and encourage service entities to actively publicize and popularize green production technologies while providing services, to play an influential role in guiding and educating farmers.