Nicotinamide deficiency promotes imidacloprid resistance via activation of ROS/CncC signaling pathway-mediated UGT detoxification in Nilaparvata lugens.

Metabolic alternation is a typical characteristic of insecticide resistance in insects. However, mechanisms underlying metabolic alternation and how altered metabolism in turn affects insecticide resistance are largely unknown. Here, we report that nicotinamide levels are decreased in the imidacloprid-resistant strain of Nilaparvata lugens, may due to reduced abundance of the symbiotic bacteria Arsenophonus. Importantly, the low levels of nicotinamide promote imidacloprid resistance via metabolic detoxification alternation, including elevations in UDP-glycosyltransferase enzymatic activity and enhancements in UGT386B2-mediated metabolism capability. Mechanistically, nicotinamide suppresses transcriptional regulatory activities of cap 'n' collar isoform C (CncC) and its partner small muscle aponeurosis fibromatosis isoform K (MafK) by scavenging the reactive oxygen species (ROS) and blocking the DNA binding domain of MafK. In imidacloprid-resistant N. lugens, nicotinamide deficiency re-activates the ROS/CncC signaling pathway to provoke UGT386B2 overexpression, thereby promoting imidacloprid detoxification. Thus, nicotinamide metabolism represents a promising target to counteract imidacloprid resistance in N. lugens.

Low-temperature NH3 abatement via selective oxidation over a supported copper catalyst with high Cu+ abundance.

Selective catalytic NH3-to-N2 oxidation (NH3-SCO) is highly promising for abating NH3 emissions slipped from stationary flue gas after-treatment devices. Its practical application, however, is limited by the non-availability of low-cost catalysts with high activity and N2 selectivity. Here, using defect-rich nitrogen-doped carbon nanotubes (NCNT-AW) as the support, we developed a highly active and durable copper-based NH3-SCO catalyst with a high abundance of cuprous (Cu+) sites. The obtained Cu/NCNT-AW catalyst demonstrated outstanding activity with a T50 (i.e. the temperature to reach 50% NH3 conversion) of 174°C in the NH3-SCO reaction, which outperformed not only the Cu catalyst supported on N-free O-functionalized CNTs (OCNTs) or NCNT with less surface defects, but also those most active Cu catalysts in open literature. Reaction kinetics measurements and temperature-programmed surface reactions using NH3 as a probe molecule revealed that the NH3-SCO reaction on Cu/NCNT-AW follows an internal selective catalytic reaction (i-SCR) route involving nitric oxide (NO) as a key intermediate. According to mechanistic investigations by X-ray photoelectron spectroscopy, Raman spectroscopy, and X-ray absorption spectroscopy, the superior NH3-SCO performance of Cu/NCNT-AW originated from a synergy of surface defects and N-dopants. Specifically, surface defects promoted the anchoring of CuO nanoparticles on N-containing sites and, thereby, enabled efficient electron transfer from N to CuO, increasing significantly the fraction of SCR-active Cu+ sites in the catalyst. This study puts forward a new idea for manipulating and utilizing the interplay of defects and N-dopants on carbon surfaces to fabricate Cu+-rich Cu catalysts for efficient abatement of slip NH3 emissions via selective oxidation.

Characterization of Neuropeptides from Spodoptera litura and Functional Analysis of NPF in Diet Intake.

Neuropeptides are involved in many biological processes in insects. However, it is unclear what role neuropeptides play in Spodoptera litura adaptation to phytochemical flavone. In this study, 63 neuropeptide precursors from 48 gene families were identified in S. litura, including two neuropeptide F genes (NPFs). NPFs played a positive role in feeding regulation in S. litura because knockdown of NPFs decreased larval diet intake. S. litura larvae reduced flavone intake by downregulating NPFs. Conversely, the flavone intake was increased if the larvae were treated with NPF mature peptides. The NPF receptor (NPFR) was susceptible to the fluctuation of NPFs. NPFR mediated NPF signaling by interacting with NPFs to regulate the larval diet intake. In conclusion, this study suggested that NPF signaling regulated diet intake to promote S. litura adaptation to flavone, which contributed to understanding insect adaptation mechanisms to host plants and provide more potential pesticidal targets for pest control.

Long-term ambient ozone exposure and incident cardiovascular diseases: National cohort evidence in China.

BACKGROUND: Long-term ozone (O3) exposure has been associated with cardiovascular disease (CVD) mortality in mounting cohort evidence, yet its relationship with incident CVD was poorly understood, especially in low- and middle-income countries (LMICs) experiencing high ambient air pollution. METHODS: We carried out a nationwide perspective cohort study from 2010 through 2018 by dynamically enrolling 36948 participants across Chinese mainland. Warm-season (April-September) O3 concentrations were estimated using satellite-based machine-learning models with national coverage. Cox proportional hazards model with time-varying exposures was employed to evaluate the association of long-term O3 exposure with incident CVD (overall CVD, hypertension, stroke, and coronary heart disease [CHD]). Assuming causality, a counterfactual framework was employed to estimate O3-attributable CVD burden based on the exposure-response (E-R) relationship obtained from this study. Decomposition analysis was utilized to quantify the contributions of four key direct driving factors (O3 exposure, population size, age structure, and incidence rate) to the net change of O3-related CVD cases between 2010 and 2018. RESULTS: A total of 4428 CVD, 2600 hypertension, 1174 stroke, and 337 CHD events were reported during 9-year follow-up. Each 10-µg/m³ increase in warm-season O3 was associated with an incident risk of 1.078 (95% confidence interval [CI]: 1.050-1.106) for overall CVD, 1.098 (95% CI: 1.062-1.135) for hypertension, 1.073 (95% CI: 1.019-1.131) for stroke, and 1.150 (95% CI: 1.038-1.274) for CHD, respectively. We observed no departure from linear E-R relationships of O3 exposure with overall CVD (Pnonlinear= 0.22), hypertension (Pnonlinear= 0.19), stroke (Pnonlinear= 0.70), and CHD (Pnonlinear= 0.44) at a broad concentration range of 60-160 µg/m3. Compared with rural dwellers, those residing in urban areas were at significantly greater O3-associated incident risks of overall CVD, hypertension, and stroke. We estimated 1.22 million (10.6% of overall CVD in 2018) incident CVD cases could be attributable to ambient O3 pollution in 2018, representing an overall 40.9% growth (0.36 million) compared to 2010 (0.87 million, 9.7% of overall CVD in 2010). This remarkable rise in O3-attributable CVD cases was primary driven by population aging (+24.0%), followed by increase in O3 concentration (+10.5%) and population size (+6.7%). CONCLUSIONS: Long-term O3 exposure was associated with an elevated risk and burden of incident CVD in Chinese adults, especially among urban dwellers. Our findings underscored policy priorities of implementing joint control measures for fine particulate matter and O3 in the context of accelerated urbanization and population aging in China.

Probing the Alcoholysis Degree of Polyvinyl Alcohol by Synergistic Coordination-Regulated Fluorescence.

Polyvinyl alcohol (PVA) with abundant hydroxyl groups (-OH) has been widely used for membranes, hydrogels, and films, and its function is largely affected by the alcoholysis degree. Therefore, the development of rapid and accurate methods for alcoholysis degree determination in PVAs is important. In this contribution, we have proposed a novel fluorescence-based platform for probing the alcoholysis degree of PVA by using the (E)-N-(4-methoxyphenyl)-1-(quinolin-2-yl)methanimine (QPM)-Zn2+ complex as the reporter. The mechanism study disclosed that the strong coordination between -OH and Zn2+ induced the capture of the QPM-Zn2+ complex and promoted its subsequent immobilization into the noncrystalline area. The immobilization of the QPM-Zn2+ complex restricted its molecular rotation and reduced the nonirradiative transition, thus yielding bright emissions. In addition, the practical applications of this proposed method were further validated by the accurate alcoholysis degree determination of blind PVA samples with the confirmation of the National Standard protocol. It is expected that the developed fluorescence approach in this work might become an admissive strategy for screening the alcoholysis degree of PVA.

Chromosome-level genome of spider Pardosa pseudoannulata and cuticle protein genes in environmental stresses.

Spiders are representative arthropods of adaptive radiation. The high-quality genomes have only been reported in several web weaver spider species, leaving the wandering spiders' genomic information scarce. The pond wolf spider, Pardosa pseudoannulata, is a representative species in the retrolateral titial apophysis (RTA) clade. We present a chromosome-level P. pseusoannulata genome assembly of 2.42 Gb in size with a scaffold N50 of 169.99 Mb. Hi-C scaffolding assigns 94.83% of the bases to 15 pseudo-chromosomes. The repeats account for 52.79% of the assembly. The assembly includes 96.2% of the complete arthropod universal single-copy orthologs. Gene annotation predicted 24,530 protein-coding genes with a BUSCO score of 95.8% complete. We identified duplicate clusters of Hox genes and an expanded cuticle protein gene family with 243 genes. The expression patterns of CPR genes change in response to environmental stresses such as coldness and insecticide exposure. The high-quality P. pseudoannulata genome provides valuable information for functional and comparative studies in spiders.

Firm-level carbon risk perception and ESG performance.

In a sustainable economy, each firm perceives different levels of carbon risk, but there are few studies on the relationship between a firm's carbon risk perception and Environmental, Social, and Governance (ESG) performance. This paper examines the impact of firm-level carbon risk perception on ESG performance using Chinese A-share listed firms during 2011-2020. We find a positive relationship between firm-level perception of carbon risk and firm ESG performance. Further analysis shows that analyst coverage and media attention exert a substantial moderating effect on the link between carbon risk perception and ESG performance. We identify three channels through which carbon risk perception affects ESG performance. First, rising carbon risk perception enables firms to take measures to reduce pollutants and greenhouse gas emissions and increases environmental (E) scores. Second, this perception encourages firms to take responsibility for social employment and increases social (S) scores. Finally, it improves firm sustainable governance and further increases governance (G) scores. Our research has an important guiding role in promoting firm ESG practice.

Characterization and functional analysis of UDP-glycosyltransferases reveal their contribution to phytochemical flavone tolerance in Spodoptera litura.

Efficient detoxification is the key factor for phytophagous insect to adapt to phytochemicals. However, the role of uridine diphosphate (UDP)-glycosyltransferases (UGTs) in insect anti-defense to phytochemical flavone is largely unknown. In this study, 52 UGT genes were identified in Spodoptera litura and they presented evident gene duplication. UGT played a crucial part in larval tolerance to flavone because the enzyme activity and transcriptional level of 77 % UGT members were remarkably upregulated by flavone administration and suppression of UGT enzyme activity and gene expressions significantly increased larval susceptibility to flavone. Bacteria coexpressing UGTs had high survival rates under flavone treatment and flavone was dramatically metabolized by UGT recombinant cells, which indicated the involvement of UGTs in flavone detoxification. What's more, ecdysone pathway was activated by flavone. Topical application of 20-hydroxyecdysone highly upregulated UGT enzyme activity and more than half of UGT expressions. The effects were opposite when ecdysone receptor (EcR) and ultraspiracle (USP)-mediated ecdysone signaling pathway was inhibited. Furtherly, promoter reporter assays of 5 UGT genes showed that their transcription activities were notably increased by cotransfection with EcR and USP. In consequence, this study suggested that UGTs were involved in flavone detoxification and their transcriptional expressions were regulated by ecdysone pathway.

The clinical and imaging features of eosinophilic cystitis in children: a case series study.

BACKGROUND: Eosinophilic cystitis (EC) is rare in children and remains poorly understood. Our aim was to analyse the clinical and imaging features of eosinophilic cystitis in children. METHODS: A retrospective review of histologically confirmed eosinophilic cystitis between January 2008 and December 2022 was performed, including patient age, sex, symptoms, laboratory examination, radiology, treatment and outcome. RESULTS: Twelve children (two girls, 10 boys; age range: 3-12 years, mean age: 7.2 years) were included in the study. Urinary irritation symptoms (10/12), haematuria (5/12) and hypogastralgia (3/12) were the most common symptoms. Five patients had a history of allergies, six patients had elevated serum IgE, nine patients had elevated peripheral eosinophils and six patients had positive microscopic haematuria. Radiology revealed diffuse homogeneous or inhomogeneous thickening in seven patients, localised thickening in three patients, and solitary tumour-like lesions in the other two patients. Preservation of the mucosal line and bladder wall layering were observed in eleven patients, and perivesical exudation and small vessel dilatation were observed in ten patients. All four patients with delayed scans showed obvious delayed enhancement. One patient showed low signal intensity on T2-W imaging. All patients received antihistamine, antibiotic and/or corticosteroid therapy and two tumour-like patients underwent transurethral resection. Nine patients achieved complete response and three patients achieved partial response. CONCLUSION: The clinical and imaging manifestations of EC in children have relative characteristics; when urologist and radiologist confronted with similar cases, EC should be considered. The final diagnosis depends on pathological biopsy.

Using deep learning models in magnetic resonance cholangiopancreatography images to diagnose common bile duct stones.

BACKGROUNDS AND AIMS: Magnetic resonance cholangiopancreatography (MRCP) plays a significant role in diagnosing common bile duct stones (CBDS). Currently, there are no studies to detect CBDS by using the deep learning (DL) model in MRCP. This study aimed to use the DL model You Only Look Once version 5 (YOLOv5) to diagnose CBDS in MRCP images and verify its validity compared to the accuracy of radiologists. METHODS: By collecting the thick-slab MRCP images of patients diagnosed with CBDS, 4 submodels of YOLOv5 were used to train and validate the performance. Precision, recall rate, and mean average precision (mAP) were used to evaluate model performance. Analyze possible reasons that may affect detection accuracy by validating MRCP images in 63 CBDS patients and comparing them with radiologist detection accuracy. Calculate the correctness of YOLOv5 for detecting one CBDS and multiple CBDS separately. RESULTS: The precision of YOLOv5l (0.970) was higher than that of YOLOv5x (0.909), YOLOv5m (0.874), and YOLOv5s (0.939). The mAP did not differ significantly between the 4 submodels, with the following results: YOLOv5l (0.942), YOLOv5x (0.947), YOLO5s (0.927), and YOLOv5m (0.946). However, in terms of training time, YOLOv5s was the fastest (4.8 h), detecting CBDS in only 7.2 milliseconds per image. In 63 patients the YOLOv5l model detected CBDS with an accuracy of 90.5% compared to 92.1% for radiologists, analyzing the difference between the positive group successfully identified and the unidentified negative group not. The incorporated variables include common bile duct diameter > 1 cm (p = .560), combined gallbladder stones (p = .706), maximum stone diameter (p = .057), combined cholangitis (p = .846), and combined pancreatitis (p = .656), and the number of CBDS (p = .415). When only one CBDS was present, the accuracy rate reached 94%. When multiple CBDSs were present, the recognition rate dropped to 70%. CONCLUSION: YOLOv5l is the model with the best results and is almost as accurate as the radiologist's detection of CBDS and is also capable of detecting the number of CBDS. Although the accuracy of the test gradually decreases as the number of stones increases, it can still be useful for the clinician's initial diagnosis.

Long-term ozone exposure and all-cause mortality: Cohort evidence in China and global heterogeneity by region.

BACKGROUND: Cohort evidence linking long-term ozone (O3) exposure to mortality remained largely mixed worldwide and was extensively deficient in densely-populated Asia. This study aimed to assess the long-term effects of O3 exposure on all-cause mortality among Chinese adults, as well as to examine potential regional heterogeneity across the globe. METHODS: A national dynamic cohort of 42153 adults aged 16+ years were recruited from 25 provinces across Chinese mainland and followed up during 2010-2018. Annual warm-season (April-September) O3 and year-round co-pollutants (i.e., nitrogen dioxide [NO2] and fine particulate matter [PM2.5]) were simulated through validated spatial-temporal prediction models and were assigned to each enrollee in each calendar year. Cox proportional hazards models with time-varying exposures were employed to assess the O3-mortality association. Concentration-response (C-R) curves were fitted by natural cubic spline function to investigate the potential nonlinear association. Both single-pollutant model and co-pollutant models additionally adjusting for PM2.5 and/or NO2 were employed to examine the robustness of the estimated association. The random-effect meta-analysis was adopted to pool effect estimates from the current and prior population-based cohorts (n = 29), and pooled C-R curves were fitted through the meta-smoothing approach by regions. RESULTS: The study population comprised of 42153 participants who contributed 258921.5 person-years at risk (median 6.4 years), of whom 2382 death events occurred during study period. Participants were exposed to an annual average of 51.4 ppb (range: 22.7-74.4 ppb) of warm-season O3 concentration. In the single-pollutant model, a significantly increased hazard ratio (HR) of 1.098 (95% confidence interval [CI]: 1.023-1.179) was associated with a 10-ppb rise in O3 exposure. Associations remained robust to additional adjustments of co-pollutants, with HRs of 1.099 (95% CI: 1.023-1.180) in bi-pollutant model (+PM2.5) and 1.093 (95% CI: 1.018-1.174) in tri-pollutant model (+PM2.5+NO2), respectively. A J-shaped C-R relationship was identified among Chinese general population, suggesting significant excess mortality risk at high ozone exposure only. The combined C-R curves from Asia (n = 4) and North America (n = 17) demonstrated an overall increased risk of all-cause mortality with O3 exposure, with pooled HRs of 1.124 (95% CI: 0.966-1.307) and 1.023 (95% CI: 1.007-1.039) per 10-ppb rise, respectively. Conversely, an opposite association was observed in Europe (n = 8, HR: 0.914 [95% CI: 0.860-0.972]), suggesting significant heterogeneity across regions (P < 0.01). CONCLUSIONS: This study provided national evidence that high O3 exposure may curtail long-term survival of Chinese general population. Great between-region heterogeneity of pooled O3-mortality was identified across North America, Europe, and Asia.

Role of the epsilon glutathione S-transferases in xanthotoxin tolerance in Spodoptera litura.

Spodoptera litura, a polyphagous lepidopteran pest, demonstrates a remarkable capacity to adapt to varying host plants by efficiently detoxifying phytochemicals. However, the underlying mechanism for this adaptation is not well understood. Herein, twenty eplison glutathione S-transferase genes (GSTes) were characterized and their roles in phytochemical tolerance were analyzed in S. litura. Most of the GSTe genes were mainly expressed in the larval midgut and fat body. Exposure to the phytochemicals, especially xanthotoxin, induced the expression of most GSTe genes. Molecular docking analysis revealed that xanthotoxin could form stable bonds with six xanthotoxin-responsive GSTes, with binding free energies ranging from -36.44 to -68.83 kcal mol-1. Knockdown of these six GSTe genes increased the larval susceptibility to xanthotoxin. Furthermore, xanthotoxin exposure significantly upregulated the expression of two transcription factor genes CncC and MafK. Silencing of either CncC or MafK reduced the expression of GSTe16, which exhibited the largest change in response to xanthotoxin. Additionally, analysis of the promoter sequence of GSTe16 revealed the presence of seven CncC/Maf binding sites. Luciferase reporter assays showed that CncC and MafK enhanced the expression of GSTe16, leading to the increased xanthotoxin tolerance in S. litura. These findings provide insight into the functions and transcriptional regulatory mechanisms of GSTes, thereby enhancing our understanding of the role of GSTs in the adaptation of lepidopteran pests to phytochemicals.

CYP321A Subfamily P450s Contribute to the Detoxification of Phytochemicals and Pyrethroids in Spodoptera litura.

Although the induction of cytochrome P450 monooxygenases involved in insect detoxification has been well documented, the underlying regulatory mechanisms remain obscure. In Spodoptera litura, CYP321A subfamily members were effectively induced by exposure to flavone, xanthotoxin, curcumin, and λ-cyhalothrin, while knockdown of the CYP321A genes increased larval susceptibility to these xenobiotics. Homology modeling and molecular docking analyses showed that these four xenobiotics could stably bind to the CYP321A enzymes. Furthermore, two transcription factor genes, CncC and MafK, were significantly induced by the xenobiotics. Knockdown of CncC or MafK reduced the expression of four CYP321A genes and increased larval susceptibility to the xenobiotics. Dual-luciferase reporter assays showed that cotransfection of reporter plasmids carrying the CYP321A promoter with CncC and/or MafK-expressing constructs significantly magnified the promoter activity. These results indicate that the induction of CYP321A subfamily members conferring larval detoxification capability to xenobiotics is mediated by the activation of CncC and MafK.

Characterization of ginsenosides from Panax japonicus var. major (Zhu-Zi-Shen) based on ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry and desorption electrospray ionization-mass spectrometry imaging.

BACKGROUND: Panax japonicus var. major (PJM) belongs to the well-known ginseng species used in west China for hundreds of years, which has the effects of lung tonifying and yin nourishing, and exerts the analgesic, antitussive, and hemostatic activities. Compared with the other Panax species, the chemical composition and the spatial tissue distribution of the bioactive ginsenosides in PJM have seldom been investigated. METHODS: Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS) and desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) were integrated for the systematic characterization and spatial tissue distribution studies of ginsenosides in the rhizome of PJM. Considering the great difficulty in exposing the minor saponins, apart from the conventional Auto MS/MS (M1), two different precursor ions list-including data-dependent acquisition (PIL-DDA) approaches, involving the direct input of an in-house library containing 579 known ginsenosides (M2) and the inclusion of the target precursors screened from the MS1 data by mass defect filtering (M3), were developed. The in situ spatial distribution of various ginsenosides in PJM was profiled based on DESI-MSI with a mass range of m/z 100-1500 in the negative ion mode, with the imaging data processed by the High Definition Imaging (HDI) software. RESULTS: Under the optimized condition, 272 ginsenosides were identified or tentatively characterized, and 138 thereof were possibly not ever reported from the Panax genus. They were composed by 75 oleanolic acid type, 22 protopanaxadiol type, 52 protopanaxatriol type, 16 octillol type, 19 malonylated, 35 C-17 side-chain varied, and 53 others. In addition, the DESI-MSI experiment unveiled the differentiated distribution of saponins, but the main location in the cork layer and phloem of the rhizome. The abundance of the oleanolic acid ginsenosides was high in the rhizome slice of PJM, which was consistent with the results obtained by UHPLC/QTOF-MS. CONCLUSION: Comprehensive characterization of the ginsenosides in the rhizome of PJM was achieved, with a large amount of unknown structures unveiled primarily. We, for the first time, reported the spatial tissue distribution of different subtypes of ginsenosides in the rhizome slice of PJM. These results can benefit the quality control and further development of PJM and the other ginseng species.

Short-term effects of fine particulate matter constituents on myocardial infarction death.

Existing evidence suggested that short-term exposure to fine particulate matter (PM2.5) may increase the risk of death from myocardial infarction (MI), while PM2.5 constituents responsible for this association has not been determined. We collected 12,927 MI deaths from 32 counties in southern China during 2011-2013. County-level exposures of ambient PM2.5 and its 5 constituents (i.e., elemental carbon (EC), organic carbon (OC), sulfate (SO42-), ammonium (NH4+), and nitrate (NO3-)) were aggregated from gridded datasets predicted by Community Multiscale Air Quality Modeling System. We employed a space-time-stratified case-crossover design and conditional logistic regression models to quantify the association of MI mortality with short-term exposure to PM2.5 and its constituents across various lag days. Over the study period, the daily mean PM2.5 mass concentration was 77.8 (standard deviation (SD) = 72.7) µg/m3. We estimated an odds ratio of 1.038 (95% confidence interval (CI): 1.003-1.074), 1.038 (1.013-1.063) and 1.057 (1.023-1.097) for MI mortality associated with per interquartile range (IQR) increase in the 3-day moving-average exposure to PM2.5 (IQR = 76.3 µg/m3), EC (4.1 µg/m3) and OC (9.1 µg/m3), respectively. We did not identify significant association between MI death and exposure to water-soluble ions (SO42-, NH4+ and NO3-). Likelihood ratio tests supported no evident violations of linear assumptions for constituents-MI associations. Subgroup analyses showed stronger associations between MI death and EC/OC exposure in the elderly, males and cold months. Short-term exposure to PM2.5 constituents, particularly those carbonaceous aerosols, was associated with increased risks of MI mortality.

Incident risk and burden of cardiovascular diseases attributable to long-term NO2 exposure in Chinese adults.

BACKGROUND: A number of studies suggested a nexus between long-term exposure to nitrogen dioxide (NO2) and the incidence of cardiovascular disease (CVD), while population-based cohort evidence in low- and middle-income countries was extensively sparse. METHODS: We carried out an 8-year longitudinal study (2010-2018) in a nationwide dynamic cohort of 36,948 Chinese adult participants, who were free of CVD at baseline. Annual average estimates of NO2 exposure were predicted using a well-validated spatiotemporal model and assigned to study participants based on their residential counties. Considering death as a competing risk event, Fine-Gray competing risk models with time-varying exposures at an annual scale were used to quantify incident risks of overall CVD, hypertension, and stroke associated with a 10-µg/m3 rise in NO2 exposure. Using the meta-analysis approach, we performed a pooled analysis of hazard ratio (HR) drawn from this and prior multinational cohort studies for the assessment of attributable burden. NO2-attributable overall CVD incidents in China were evaluated by city and province for years 2010 and 2018, referring to a counterfactual exposure level of 10 µg/m3 (2021 World Health Organization [WHO] air quality guidelines). A decomposition method was used to decompose net change in NO2-attributable CVD incidents during 2010 and 2018 into 3 primary contributions of driving factors (i.e., changes in NO2 exposure, population size, and incidence rate). RESULTS: A total of 4428 overall CVD events (hypertension 2448, stroke 1044) occurred during a median follow-up period of 6.1 years. Annual mean NO2 concentration from 2010 to 2018 was 20.0 µg/m3 (range: 6.9-57.4 µg/m3). An increase of 10-µg/m3 in NO2 was associated with an HR of 1.558 (95% confidence interval [CI]: 1.477, 1.642) for overall CVD, 1.521 (95% CI: 1.419, 1.631) for hypertension, and 1.664 (95% CI: 1.485, 1.865) for stroke. Longitudinal associations of NO2 exposure with incident CVD were nearly linear over the exposure range, suggesting no discernible thresholds. Subgroup analyses indicated significantly higher NO2-associated risks of incident CVD among urban residents and overweight/obese individuals. According to pooled HR of NO2-CVD association (1.108, 95% CI: [1.007, 1.219]) from 10 multinational cohort studies, we estimated totally 1.44 million incident CVD cases attributable to NO2 exposure in 2018, representing a substantial decrease of 0.41 million compared to the estimate in 2010 (1.85 million) in mainland of China. Nationally, from 2010 to 2018, the attributable incident cases greatly dropped by 22.4%, which was dominantly driven by declined NO2 concentration (-47.1%) that had offset far from the rise of CVD incidence rate (+19.6%) and population growth (+5.1%). CONCLUSIONS: This study provided nationwide cohort evidence for elevated risks of CVD incidence associated with long-term ambient NO2 exposure among Chinese adults, particularly in urban areas and among overweight/obese individuals. Our findings highlighted that reducing NO2 exposure below 2021 WHO guideline could help prevent a substantial portion of incident CVD cases in China.

Sex disparity in cognitive aging related to later-life exposure to ambient air pollution.

BACKGROUND: Sex difference in the association between ambient air pollution and cognitive aging remained unclear. This current study aimed to assess the impacts of long-term exposure to major air pollutants on cognitive performance among Chinese middle-aged and older adults, and explore whether these associations could be modified by sex. METHODS: By deriving longitudinal data from four waves of the China Health and Retirement Longitudinal Study, we included 13,507 participants aged 45+ years who had at least two cognitive tests recorded from 2011 to 2018. We used a standardized questionnaire consisting of five domain-specific functions to measure global cognitive score. Based on well-validated spatiotemporal datasets, annual average concentrations of ambient fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) were assigned to each enrollee at prefectural city level and at the simulated residential addresses through Monte Carlo simulation approach. Linear mixed-effects models were applied to assess the impacts of major air pollutants on cognitive function with multiple adjustments. Sex-stratified analyses were performed to examine the potential effect modification on these associations. To enhance the interpretability of our results, we also compared the estimated effects of air pollutants with the effect of aging on cognitive function. RESULTS: We evaluated 38,950 records of cognitive function tests, of which 44.0% were from women. An increase of 10-µg/m3 in PM2.5, NO2 and O3 exposure were associated with 0.36 (95% confidence interval: -0.40, -0.31), 0.51 (-0.60, -0.43) and 0.26 (-0.47, -0.06) points decline in global cognitive score, respectively, equivalent to the effect of aging by 2.8-5.0 years. Sex-stratified analyses suggested significantly greater cognitive impairment associated with air pollutants in women than men. We found reversely J-shaped concentration-response relationships between ambient air pollutants and cognitive decline in both sexes. Main findings on sex-specific associations were robust to the adjustments for covariates, inclusion criteria, and co-pollutant analyses, as well as sensitivity analyses based on simulation-based exposure for PM2.5 and NO2. CONCLUSIONS: Later-life exposure to ambient air pollution may accelerate cognitive aging of middle-aged and older adults, suggesting significant sex disparity with higher vulnerability in women.

Ambient ozone exposure and depression among middle-aged and older adults: Nationwide longitudinal evidence in China.

BACKGROUND: Epidemiological studies have linked long-term ozone (O3) exposure with depression in developed countries. However, available literature is sparse and exists great heterogeneities. We aimed to investigate the association of long-term O3 exposure with depression among Chinese middle-aged and older adults. METHODS: We designed a repeated measurement study based on longitudinal data from four waves (2011, 2013, 2015, and 2018) of the China Health and Retirement Longitudinal Study (CHARLS). Annual mean O3 concentrations assessed through machine learning-based spatiotemporal models were assigned to each participant at city level. Depression score was measured using the 10-item Center for Epidemiologic Studies Depression scale (CES-D-10), with scores above the cut-off point of ten defined as depressive symptom. Mixed-effects models were used to evaluate the impact of O3 on depression score and depressive symptom, and quantify the concentration-response (C-R) relationships. Subgroup analyses were performed to examine the potential effect modifications. RESULTS: A total of 19,582 participants with 60,125 visits were included in our analysis, with mean depression score of 8.1 (standard deviation: 6.3). Multivariable-adjusted mixed-effects model estimated a 6.34% (95% confidence interval [CI]: 3.34%, 9.43%) increase in depression score and an odds ratio (OR) of 1.29 (95% CI: 1.16, 1.45) for depressive symptom associated with per 10-µg/m3 rise in annual mean O3 exposure. Significantly elevated risks were identified only at high concentrations (approximately ≥90 µg/m3). Participants who suffered from chronic diseases had a significant increased risk of depression (% Change in depression score: 8.42% [95% CI: 4.79%, 12.17%], and OR: 1.42 [95% CI: 1.24, 1.62]), and an evident effect modification was identified for depressive symptom (P = 0.01). FINDINGS: Our study provided novel evidence that long-term O3 exposure could be a risk factor for depression among Chinese middle-aged and older adults. Our findings may have significant implications for formulating policies in reducing disease burden of depression by controlling air pollution.

Plasma-derived exosomal let-7c-5p, miR-335-3p, and miR-652-3p as potential diagnostic biomarkers for stable coronary artery disease.

Objectives: Circulating exosomal microRNAs (miRNAs) have been identified as promising biomarkers for diagnosis of cardiovascular diseases. Nevertheless, the diagnostic potential of miRNAs in circulating exosomes for stable coronary artery disease (SCAD) remains unclear. We aim here to analyze the exosomal differentially expressed miRNAs (DEmiRNAs) in plasma of SCAD patients and investigate their diagnostic potential as SCAD biomarkers. Methods: Plasma was collected from SCAD patients and healthy controls, and exosomes were isolated by ultracentrifugation. Exosomal DEmiRNAs were analyzed by small RNA sequencing and were further validated by quantitative real-time PCR (qRT-PCR) in a larger set of plasma samples. Relationships between plasma exosomal let-7c-5p, miR-335-3p, miR-652-3p, genders and Gensini Scores in patients with SCAD were analyzed using correlation analyses. Moreover, we conducted receiver operating characteristic (ROC) curves for these DEmiRNAs and analyzed their possible functions and signaling pathways. Results: Vesicles isolated from plasma displayed all characteristics of exosomes. In the small RNA sequencing study, a total of 12 DEmiRNAs were identified, among which seven were verified to be statistically significant by qRT-PCR. The areas under the ROC curves of exosomal let-7c-5p, miR-335-3p, and miR-652-3p were 0.8472, 0.8029, and 0.8009, respectively. Exosomal miR-335-3p levels were positively correlated with Gensini scores of patients with SCAD. Bioinformatics analysis revealed that these DEmiRNAs may be involved in the pathogenesis of SCAD. Conclusion: Our findings indicated that plasma exosomal let-7c-5p, miR-335-3p, and miR-652-3p can be used as promising biomarkers for diagnosis of SCAD. In addition, plasma exosomal miR-335-3p levels coordinated with severity of SCAD.

Nuclear receptors potentially regulate phytochemical detoxification in Spodoptera litura.

Phytochemicals are a class of potential pesticides for pest control. Our previous studies have demonstrated that the development of Spodoptera litura is suppressed by two phytochemicals, flavone and xanthotoxin. Generally, phytochemical is metabolized by insect detoxification enzyme systems. Nuclear receptor (NR) is the ligand-activated transcription factor that involved in the regulation of detoxification gene expressions. To explore how NR responds to phytochemical to mediate detoxification gene expression, in the present study, 19 NRs were firstly identified in S. litura genome. The transcriptional levels of most NRs were significantly induced in the midgut of S. litura larvae after exposure to flavone and xanthotoxin. RNAi-mediated knockdown of FTZF1, EcR, Dsf, and HR3 remarkably reduced the larval tolerance to flavone or xanthotoxin. In addition, many crucial detoxification genes were downregulated by dsNR administrations, which might be responsible for the high sensitivity of S. litura to phytochemicals. Molecular docking indicated that phytochemicals as the potential ligands had high affinity to bind to NRs. This study suggested that NR potentially regulated the transcriptional expression of detoxification genes in response to phytochemical stresses, which partially elucidated the mechanism of extensive host adaptation in S. litura and provided the theoretical evidences for the development of NR-targeted insecticides.