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Background: Short-term exposure to particulate matter air pollution has been associated with the exacerbations of COPD, but its association with COPD mortality was not fully elucidated. We aimed to assess the association between short-term particulate matter exposure and the risk of COPD mortality in China using individual-level data., Methods: We derived 2.26 million COPD deaths from a national death registry database in Chinese mainland between 2013 and 2019. Exposures to fine particulate matter (PM 2.5 ) and coarse particulate matter (PM 2.5-10 ) were assessed by satellite-based models of a 1 × 1 km resolution and assigned to each individual based on residential address. The associations of PM 2.5 and PM 2.5-10 with COPD mortality were examined using a time-stratified case-crossover design and conditional logistic regressions with distributed lag models. We further conducted stratified analyses by age, sex, education level, and season., Findings: Short-term exposures to both PM 2.5 and PM 2.5-10 were associated with increased risks of COPD mortality. These associations appeared and peaked on the concurrent day, attenuated and became nonsignificant after 5 or 7 days, respectively. The exposure-response curves were approximately linear without discernible thresholds. An interquartile range increase in PM 2.5 and PM 2.5-10 concentrations was associated with 4.23% (95% CI: 3.75%, 4.72%) and 2.67% (95% CI: 2.18%, 3.16%) higher risks of COPD mortality over lag 0-7 d, respectively. The associations of PM 2.5 and PM 2.5-10 attenuated slightly but were still significant in the mutual-adjustment models. A larger association of PM 2.5-10 was observed in the warm season., Interpretation: This individual-level, nationwide, case-crossover study suggests that short-term exposure to PM 2.5 and PM 2.5-10 might act as one of the environmental risk factors for COPD mortality., Funding: This study is supported by the National Key Research and Development Program of China (2023YFC3708304 and 2022YFC3702701), the National Natural Science Foundation of China (82304090 and 82030103), the 3-year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.2-YQ31), and the Science and Technology Commission of Shanghai Municipality (21TQ015)., Competing Interests: Declaration of interests All authors declare no potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The pursuit of two-dimensional (2D) magnetism is promising for energy-efficient electronic devices, including magnetoelectric random access memory and radio frequency/microwave magnonics, and it is gaining fundamental insights into quantum sensing technology. The key challenge resides in overseeing magnetic exchange interactions through a precise chemical reduction process, wherein manipulation of the arrangement of atoms and electrons is essential for achieving room-temperature 2D magnetism tailoring in a manner compatible with device architectures. Here, we report an electrochemically crafted CrI 3 layered magnet─a van der Waals material─with precisely tailored lithiation and delithiation degrees. The crystalline and packing structure within the intralayer are preserved during the lithium intercalation within the interlayer, owing to weak interlayer coupling. Intrinsic ferromagnetism featuring a Curie temperature reaching 420 K has been unequivocally demonstrated, showcasing a coercivity of 1120 Oe at room temperature. The degree of lithiation through the reduction from Cr 3+ to Cr 2+ plays a crucial role in determining a 28.5% change in magnetization and a 0.29 eV shift in the bandgap. Room temperature ferromagnetism and magnetoelectricity are critical for noncontact, specifically photon-driven, dynamic magnetism control of 2D magnet-based magnonics devices.

Rationale & Objective: Proteinuria is a surrogate end point for predicting long-term kidney outcomes in IgA nephropathy (IgAN) with levels<1g/day identified as a therapeutic target. However, this threshold has not been sufficiently studied. We quantified the associations of progression of IgAN with various levels of proteinuria., Study Design: Observational cohort study., Setting & Participants: 1,530 patients with IgAN and at least 12 months of follow-up at Peking University First Hospital., Exposure: Proteinuria levels updated over time (time-varying proteinuria, TVP)., Outcome: A composite kidney outcome of a 50% reduction in the estimated glomerular filtration rate or end-stage kidney disease., Analytical Approach: Marginal structural models., Results: After a median follow-up period of 43.5 (IQR, 27.2-72.8) months, 254 patients (16.6%) developed the composite kidney outcome. A graded association was observed between TVP and composite kidney outcomes with higher risk among those with proteinuria of≥0.5g/day. Compared with TVP<0.3g/day, the HRs for proteinuria levels of 0.3 to<0.5g/day, 0.5 to<1.0g/day, 1.0 to<2.0g/day, and≥2.0g/day were 2.22 (95% CI, 0.88-5.58), 4.04 (95% CI, 1.93-8.46), 8.46 (95% CI, 3.80-18.83), and 38.00 (95% CI, 17.62-81.95), respectively. The trend was more pronounced in patients with baseline proteinuria of≥1.0g/day, among whom a higher risk was observed with TVP of 0.3 to<0.5g/day compared with TVP<0.3g/day (HR, 3.26 [95% CI, 1.07-9.92], P=0.04). However, in patients with baseline proteinuria levels of<1g/day, the risk of composite kidney outcome only began to increase when TVP was≥1.0g/day (HR, 3.25 [95% CI, 1.06-9.90])., Limitations: Single-center observational study, selection bias, and unmeasured confounders., Conclusions: This study showed that patients with IgAN and proteinuria levels of>0.5g/day, have an elevated risk of kidney failure especially among patients with proteinuria levels≥1.0g/day before initiating treatment. These data may serve to inform the selection of proteinuria targets in the treatment of IgAN., Plain-Language Summary: The presence of proteinuria has often been considered a surrogate end point and a possible therapeutic target in clinical trials in IgA nephropathy (IgAN). Some guidelines recommend a reduction in proteinuria to<1g/day as a treatment goal based on the results of previous longitudinal studies. However, these findings may have been biased because they did not properly adjust for time-dependent confounders. Using marginal structural models to appropriately account for these confounding influences, we observed that patients with IgAN and proteinuria levels≥0.5g/day have an elevated risk of kidney failure, especially among patients who had proteinuria levels of≥1.0g/day before initiating treatment. These data may serve to inform the selection of proteinuria targets in the treatment of IgAN., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The primary goal of this study was to investigate the expressions of TUFT1 (Tuftelin) and Rac1-GTP in the cancerous tissues of individuals with triple-negative breast cancer (TNBC). Additionally, we aimed to explore the correlation between TUFT1 and Rac1-GTP expressions and examine the associations of TUFT1 and Rac1-GTP expressions with the clinical and pathological indicators of the patients., Methods: Ninety-six patients diagnosed with TNBC, scheduled for surgery between May 2022 and November 2022, were enrolled in this study. Cancerous tissue specimens were collected from these patients, and immunohistochemistry was employed to evaluate the levels of TUFT1 and Rac1-GTP expressions in the cancerous tissues. Subsequent to data collection, a comprehensive analysis was conducted to examine the correlation between TUFT1 and Rac1-GTP expressions. Furthermore, we sought to assess the associations of TUFT1 and Rac1-GTP expressions with the clinical and pathological indicators of the patients., Results: The TUFT1 protein was expressed in both the membrane and cytoplasm of TNBC cancer cells, with notably higher expression observed in the cytoplasm. Rac1-GTP was primarily expressed in the cytoplasm. There was a positive correlation between the levels of TUFT1 and Rac1-GTP expressions (χ 2  = 9.816, P < 0.05). The levels of TUFT1 and Rac1-GTP protein expressions showed no correlation with patient age (χ 2  = 2.590, 2.565, P > 0.05); however, they demonstrated a positive correlation with tumor size (χ 2  = 5.592,5.118), histological grading (χ 2  = 6.730, 5.443), and lymph node metastasis (χ 2  = 8.221, 5.180) (all with a significance level of P < 0.05)., Conclusion: A significant correlation was identified between the levels of TUFT1 and Rac1-GTP expressions in the cancerous tissues of patients with TNBC, suggesting a close association with the progression of TNBC. The two molecules play significant roles in facilitating an early diagnosis and treatment of TNBC., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Short-term exposure to PM 2.5 or O 3 can increase mortality risk; however, limited studies have evaluated their interaction. A multicity time series study was conducted to investigate the synergistic effect of PM 2.5 and O 3 on mortality in China, using mortality data and high-resolution pollutant predictions from 272 cities in 2013-2015. Generalized additive models were applied to estimate associations of PM 2.5 and O 3 with mortality. Modification and interaction effects were explored by stratified analyses and synergistic indexes. Deaths attributable to PM 2.5 and O 3 were evaluated with or without modification of the other pollutant. The risk of total nonaccidental mortality increased by 0.70% for each 10 μg/m 3 increase in PM 2.5 when O 3 levels were high, compared to 0.12% at low O 3 levels. The effect of O 3 on total nonaccidental mortality at high PM 2.5 levels (1.26%) was also significantly higher than that at low PM 2.5 levels (0.59%). Similar patterns were observed for cardiovascular or respiratory diseases. The relative excess risk of interaction and synergy index of PM 2.5 and O 3 on nonaccidental mortality were 0.69% and 1.31 with statistical significance, respectively. Nonaccidental deaths attributable to short-term exposure of PM 2.5 or O 3 when considering modification of the other pollutant were 28% and 31% higher than those without considering modification, respectively. Our results found synergistic effects of short-term coexposure to PM 2.5 and O 3 on mortality and suggested underestimations of attributable risks without considering their synergistic effects.

Background and Objectives: Many studies suggested that short-term exposure to fine particulate matter (PM 2.5 ) and coarse particulate matter (PM 2.5-10 ) was linked to elevated risk of cerebrovascular disease. However, little is known about the potentially differential effects of PM 2.5 and PM 2.5-10 on various types of cerebrovascular disease., Methods: We collected individual cerebrovascular death records for all residents in Shanghai, China from 2005 to 2021. Residential daily air pollution data were predicted from a satellite model. The associations between particulate matters (PM) and cerebrovascular mortality were investigated by an individual-level, time-stratified, case-crossover design. The data was analyzed by the conditional logistic regression combined with the distributed lag model with a maximum lag of 7 days. Furthermore, we explored the effect modifications by sex, age and season., Results: A total of 388,823 cerebrovascular deaths were included. Monotonous increases were observed for mortality of all cerebrovascular diseases except for hemorrhagic stroke. A 10 μg/m 3 rise in PM 2.5 was related to rises of 1.35% [95% confidence interval (CI): 1.04%, 1.66%] in mortality of all cerebrovascular diseases, 1.84% (95% CI: 1.25%, 2.44%) in ischemic stroke, 1.53% (95% CI: 1.07%, 1.99%) in cerebrovascular sequelae and 1.56% (95% CI: 1.08%, 2.05%) in ischemic stroke sequelae. The excess risk estimates per each 10 μg/m 3 rise in PM 2.5-10 were 1.47% (95% CI: 1.10%, 1.84%), 1.53% (95% CI: 0.83%, 2.24%), 1.93% (95% CI: 1.38%, 2.49%) and 2.22% (95% CI: 1.64%, 2.81%), respectively. The associations of both pollutants with all cerebrovascular outcomes were robust after controlling for co-pollutants. The associations were greater in females, individuals > 80 years, and during the warm season., Conclusions: Short-term exposures to both PM 2.5 and PM 2.5-10 may independently increase the mortality risk of cerebrovascular diseases, particularly of ischemic stroke and stroke sequelae., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The connections between fine particulate matter (PM 2.5 ) and coarse particulate matter (PM 2.5-10 ) and daily mortality of viral pneumonia and bacterial pneumonia were unclear., Objectives: To distinguish the connections between PM 2.5 and PM 2.5-10 and daily mortality due to viral pneumonia and bacterial pneumonia., Methods: Using a comprehensive national death registry encompassing all areas of mainland China, we conducted a case-crossover investigation from 2013 to 2019 at an individual level. Residential daily particle concentrations were evaluated using satellite-based models with a spatial resolution of 1 km. To analyze the data, we employed the conditional logistic regression model in conjunction with polynomial distributed lag models., Results: We included 221,507 pneumonia deaths in China. Every interquartile range (IQR) elevation in concentrations of PM 2.5 (lag 0-2 d, 37.6 μg/m 3 ) was associated with higher magnitude of mortality for viral pneumonia (3.03%) than bacterial pneumonia (2.14%), whereas the difference was not significant (p-value for difference = 0.38). An IQR increase in concentrations of PM 2.5-10 (lag 0-2 d, 28.4 μg/m 3 ) was also linked to higher magnitude of mortality from viral pneumonia (3.06%) compared to bacterial pneumonia (2.31%), whereas the difference was not significant (p-value for difference = 0.52). After controlling for gaseous pollutants, their effects were all stable; however, with mutual adjustment, the associations of PM 2.5 remained, and those of PM 2.5-10 were no longer statistically significant. Greater magnitude of associations was noted in individuals aged 75 years and above, as well as during the cold season., Conclusion: This nationwide study presents compelling evidence that both PM 2.5 and PM 2.5-10 exposures could increase pneumonia mortality of viral and bacterial causes, highlighting the more robust effects of PM 2.5 and somewhat higher sensitivity of viral pneumonia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although epidemiological studies have demonstrated significant associations of long-term exposure to particulate matter (PM) air pollution with stroke, evidence on the long-term effects of PM exposure on cause-specific stroke incidence is scarce and inconsistent. We incorporated 33,282 and 33,868 individuals aged 35-75 years without a history of ischemic or hemorrhagic stroke at the baseline in 2014, who were followed up till 2021. Residential exposures to particulate matter with an aerodynamic diameter less than 2.5 μm (PM 2.5 ) and particulate matter with an aerodynamic diameter less than 10 μm (PM 10 ) for each participant were predicted using a satellite-based model with a spatial resolution of 1 × 1 km. We employed time-varying Cox proportional hazards models to assess the long-term effect of PM pollution on incident stroke. We identified 926 cases of ischemic stroke and 211 of hemorrhagic stroke. Long-term PM exposure was significantly associated with increased incidence of both ischemic and hemorrhagic stroke, with almost 2 times higher risk on hemorrhagic stroke. Specifically, a 10 μg/m³ increase in 3-year average concentrations of PM 2.5 was linked to a hazard ratio (HR) of 1.35 (95% confidence interval (CI): 1.18-1.54) for incident ischemic stroke and 1.79 (95% CI: 1.36-2.34) for incident hemorrhagic stroke. The HR related to PM 10 , though smaller, remained statistically significant, with a HR of 1.25 for ischemic stroke and a HR of 1.51 for hemorrhagic stroke. The excess risks are larger among rural residents and individuals with lower educational attainment. The present cohort study contributed to the mounting evidence on the increased risk of incident stroke associated with long-term PM exposures. Our results further provide valuable evidence on the heightened sensitivity of hemorrhagic stroke to air pollution exposures compared with ischemic stroke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Previous research indicates that coronavirus disease 2019 (COVID-19) infection may have a role in triggering immunoglobulin A (IgA) nephropathy. However, limited research has explored the clinical implications of COVID-19 infection in individuals already diagnosed with IgA nephropathy. This study aimed to determine whether COVID-19 infection independently affects the subsequent trajectory of kidney function in IgA nephropathy patients., Methods: This was a single-center cohort study. The study included 199 patients diagnosed with IgA nephropathy. The COVID-19 infection status was determined using a combined method: a questionnaire and the Health Code application, both administered at the end of 2022 in northern China. Kidney function trajectory was assessed by the estimated glomerular filtration rate (eGFR), calculated based on serum creatinine levels measured during follow-up outpatient visits. The primary endpoint of interest was the eGFR trajectory., Results: Out of the 199 participants, 75% ( n  = 181) reported a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, determined through antigen or polymerase chain reaction tests, accounting for 79% ( n  = 143) of the infected patients. A significant majority (98%) experienced mild to moderate symptoms. Over a median follow-up period of 10.7 months post-COVID-19 infection, notable clinical events included gross hematuria in 30 patients (16.6%), which normalized within an average of 3 days. Additionally, a 2-fold increase in proteinuria or progression to the nephrotic range was observed in 10 individuals (5.5%). No cases of acute kidney injury were noted. COVID-19 exposure was associated with an absolute change in eGFR of 2.98 mL/min/1.73 m 2 per month (95% confidence interval 0.46 to 5.50). However, in a fully adjusted model, the estimated changes in eGFR slope post-COVID-19 were -0.39 mL/min/1.73 m 2 per month (95% confidence interval -0.83 to 0.06, P  = .088) which included the possibility of no significant effect. Notably, a higher rate of kidney function decline was primarily observed in patients with a baseline eGFR <45 mL/min/1.73 m 2 [-0.56 mL/min/1.73 m 2 (-1.11 to -0.01), P  = .048]. In the cohort, there were few instances of severe COVID-19 cases. The absence of long-term follow-up outcomes was observed., Conclusions: Overall, mild to moderate COVID-19 infection does not appear to significantly exacerbate the subsequent decline in kidney function among IgA nephropathy patients, particularly in those with preserved baseline kidney function., Competing Interests: All the authors declared no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

In Great Britain, limited studies have employed machine learning methods to predict air pollution especially ozone (O 3 ) with high spatiotemporal resolution. This study aimed to address this gap by developing random forest models for four key pollutants (fine and inhalable particulate matter [PM 2.5 and PM 10 ], nitrogen dioxide [NO 2 ] and O 3 ) by integrating multiple-source predictors at a daily level and 1-km resolution. The out-of-bag R 2 (root mean squared error, RMSE) between predictions from models and measurements from monitoring stations in 2006-2013 was 0.85 (3.63 μg/m 3 ) for PM 2.5 , 0.77 (6.00 μg/m 3 ) for PM 10 , 0.85 (9.71 μg/m 3 ) for NO 2 , and 0.85 (9.39 μg/m 3 ) for maximum daily 8-h average (MDA8) O 3 at daily level, and the predicting accuracy was higher at monthly and annual level. The high-resolution predictions captured characterized spatiotemporal patterns of the four pollutants. Higher concentrations of PM 2.5 , PM 10 , and NO 2 were distributed in densely populated southern regions of Great Britain while O 3 showed an inverse spatial pattern in general, which could not be fully depicted by monitoring stations. Therefore, predictions produced in this study could improve exposure assessment with less exposure misclassification and flexible exposure windows for future epidemiological studies to investigate the impact of air pollution across Great Britain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: IgA nephropathy (IgAN) is the most prevalent form of glomerulonephritis. Unfortunately, molecular biomarkers for IgAN derived from omics studies are still lacking. This research aims to identify critical genes associated with IgAN through large-scale blood transcriptome analysis., Methods: We constructed novel blood transcriptome profiles from peripheral blood mononuclear cells (PBMCs) of 53 Chinese IgAN patients and 28 healthy individuals. Our analysis included GO, KEGG, and GSEA for biological pathways. We analyzed immune cell profiles with CIBERSORT and constructed PPI networks with STRING, visualized in Cytoscape. Key differentially expressed genes (DEGs) were identified using CytoHubba and MCODE. We assessed the correlation between gene expressions and clinical data to evaluate clinical significance and identified hub genes through machine learning, validated with an open-access dataset. Potential drugs were explored using the CMap database., Results: We identified 333 DEGs between IgAN patients and healthy controls, mainly related to immune response and inflammation. Key pathways included NK cell mediated cytotoxicity, complement and coagulation cascades, antigen processing, and B cell receptor signaling. Cytoscape revealed 16 clinically significant genes (including KIR2DL1, KIR2DL3, VISIG4, C1QB, and C1QC, associated with sub-phenotype and prognosis). Machine learning identified two hub genes (KLRC1 and C1QB) for a diagnostic model of IgAN with 0.92 accuracy, validated at 1.00 against the GSE125818 dataset. Sirolimus, calcifediol, and efaproxiral were suggested as potential therapeutic agents., Conclusion: Key DEGs, particularly VISIG4, KLRC1, and C1QB, emerge as potential specific markers for IgAN, paving the way for future targeted personalized treatment options., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The urban ambient air quality has been largely improved in the past decade. It is unknown whether childhood asthma prevalence is still increasing in ever top-ranking city of Shanghai, whether the improved air quality is beneficial for children's asthma and what time window of exposure plays critical roles., Methods: Using a repeat cross-sectional design, we analyzed the association between early life exposure to particles and wheezing/asthma in each individual and combined surveys in 2011 and 2019, respectively, in 11,825 preschool children in Shanghai., Results: A significantly lower prevalence of doctor-diagnosed asthma (DDA) (6.6% vs. 10.5%, p < 0.001) and wheezing (10.5% vs. 23.2%, p < 0.001) was observed in 2019 compared to 2011. Exposure to fine particulate matter (PM 2.5 ), coarse particles (PM 2.5-10 ) and inhalable particles (PM 10 ) was decreased in 2019 by 6.3%, 35.4%, and 44.7% in uterus and 24.3%, 20.2%, and 31.8% in infancy, respectively. Multilevel log-binomial regression analysis showed exposure in infancy had independent association with wheezing/DDA adjusting for exposure in uterus. For each interquartile range (IQR) increase of infancy PM 2.5 , PM 2.5-10 and PM 10 exposure, the odds ratios were 1.39 (95% confidence interval (CI): 1.24-1.56), 1.51 (95% CI:1.15-1.98) and 1.53 (95% CI:1.27-1.85) for DDA, respectively. The distributed lag non-linear model showed the sensitive exposure window (SEW) was 5.5-11 months after birth. Stratified analysis showed the SEWs were at or shortly after weaning, but only in those with <6 months of exclusive breastfeeding., Conclusions: Improved ambient PM benefits in decreasing childhood asthma prevalence. We firstly reported the finding of SEW to PM at or closely after weaning on childhood asthma., (© 2023 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

The exact pathogenesis of IgA nephropathy (IgAN) is complex and so far, not well defined. Since it has been shown that microbial infections could induce high levels of type I interferon (IFN-I) and there is an evident link between mucosal infection and gross hematuria in IgAN, we hypothesized that IFN-I may play a role in the pathogenic process. In this study, we investigated the type I interferon status in IgAN based on the expression of 17 IFN-regulated genes (IRGs) in whole blood from 59 IgAN patients in a cross-sectional study, of which 34 patients followed longitudinally. Analysis of the IFN-score showed that there was a significant elevated IFN-score in the IgAN patients compared with healthy controls (n = 28, p = 9.80 × 10 -3 ), and we observed an elevated IFN-score in the group with less tubular atrophy/interstitial fibrosis (p = 1.07 × 10 -2 ) and with a lower proportion of mesangial hypercellularity (p = 1.23 × 10 -2 ). In the longitudinal analysis, Cox regression analysis revealed that a higher IFN level was associated with a better renal outcome in IgAN after adjustments for gender and age (hazard ratio, 0.90; 95 % confidence interval, 0.81 to 0.97; p = 4.20 × 10 -2 ). In conclusion, our finding suggested that IFN score may represent a novel type of biomarker in IgAN, which requires further exploration on its mechanism and therapeutic targeting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ambient PM 2.5 exposure has been recognized as a major health risk and related to aging, cardiovascular, respiratory and neurologic diseases, and cancer. However, underlying mechanism of epigenetic alteration and regulated pathways still remained unclear. The study on methylome effect of PM 2.5 exposure was quite limited in Chinese population, and cohort-based study was absent. The study included blood-derived DNA methylation for 3365 Chinese participants from the NSPT cohort. We estimated individual PM 2.5 exposure level of short-medium-, medium- and long-term, based on a validated prediction model. We preformed epigenome-wide association studies to estimate the links between PM 2.5 exposure and DNA methylation change, as well as stratification and sensitive analysis to examined the robustness of the association models. A systematic review was conducted to obtain the previously published CpGs and examined for replication. We also conducted comparison on the DNA methylation variation corresponding to different time windows. We further conducted gene function analysis and pathway enrichment analysis to reveal related biological response. We identified a total of 177 CpGs and 107 DMRs associated with short-medium-term PM 2.5 exposure, at a strict genome-wide significance (P < 5 × 10 -8 ). The effect sizes on most CpGs tended to cease with the exposure of extended time scale. Associated markers and aligned genes were related to aging, immunity, inflammation and carcinogenesis. Enriched pathways were mostly involved in cell cycle and cell division, signal transduction, inflammatory pathway. Our study is the first EWAS on PM 2.5 exposure conducted in large-scale Han Chinese cohort and identified associated DNA methylation change on CpGs and regions, as well as related gene functions and pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The enhanced Coulomb interaction in two-dimensional semiconductors leads to tightly bound electron-hole pairs known as excitons. The large binding energy of excitons enables the formation of Rydberg excitons with high principal quantum numbers (n), analogous to Rydberg atoms. Rydberg excitons possess strong interactions among themselves as well as sensitive responses to external stimuli. Here, we probe Rydberg exciton resonances through photocurrent spectroscopy in a monolayer WSe 2 p-n junction formed by a split-gate geometry. We show that an external in-plane electric field not only induces a large Stark shift of Rydberg excitons up to quantum principal number 3 but also mixes different orbitals and brightens otherwise dark states such as 3p and 3d. Our study provides an exciting platform for engineering Rydberg excitons for new quantum states and quantum sensing.

Introduction: IgA nephropathy (IgAN) is a leading cause of end-stage renal disease. The exact pathogenesis of IgAN is not well defined, but some genetic studies have led to a novel discovery that the (immuno)proteasome probably plays an important role in IgAN., Methods: We firstly analyzed the association of variants in the UBE2L3 region with susceptibility to IgAN in 3,495 patients and 9,101 controls, and then analyzed the association between lead variant and clinical phenotypes in 1,803 patients with regular follow-up data. The blood mRNA levels of members of the ubiquitin-proteasome system including UBE2L3 were analyzed in peripheral blood mononuclear cells from 53 patients and 28 healthy controls. The associations between UBE2L3 and the expression levels of genes involved in Gd-IgA1 production were also explored., Results: The rs131654 showed the most significant association signal in UBE2L3 region (OR: 1.10, 95% CI: 1.04-1.16, p = 2.29 × 10 -3 ), whose genotypes were also associated with the levels of Gd-IgA1 ( p = 0.04). The rs131654 was observed to exert cis- eQTL effects on UBE2L3 in various tissues and cell types, particularly in immune cell types in multiple databases. The UBE2L3 , LUBAC , and proteasome subunits were highly expressed in patients compared with healthy controls. High expression levels of UBE2L3 were not only associated with higher proteinuria ( r = 0.34, p = 0.01) and lower eGFR ( r = -0.28, p = 0.04), but also positively correlated with the gene expression of LUBAC and other proteasome subunits. Additionally, mRNA expression levels of UBE2L3 were also positively correlated with IL-6 and RELA , but negatively correlated with the expression levels of the key enzyme in the process of glycosylation including C1GALT1 and C1GALT1C1 ., Conclusion: In conclusion, by combined genetic association and differed expression analysis of UBE2L3 , our data support a role of genetically conferred dysregulation of the (immuno)proteasome in regulating galactose-deficient IgA1 in the development of IgAN., Competing Interests: All the authors have nothing to disclose., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Alveolar nitric oxide is a non-invasive indicator of small-airway inflammation, a key pathophysiologic mechanism underlying lower respiratory diseases. However, no epidemiological studies have investigated the impact of fine particulate matter (PM 2.5 ) exposure on the concentration of alveolar nitric oxide (CANO). To explore the associations between PM 2.5 exposure in multiple periods and CANO, we conducted a nationwide cross-sectional study in 122 Chinese cities between 2019 and 2021. Utilizing a satellite-based model with a spatial resolution of 1 × 1 km, we matched long-term, mid-term, and short-term PM 2.5 exposure for 28,399 individuals based on their home addresses. Multivariable linear regression models were applied to estimate the associations between PM 2.5 at multiple exposure windows and CANO. Stratified analyses were also performed to identify potentially vulnerable subgroups. We found that per interquartile range (IQR) unit higher in 1-year average, 1-month average, and 7-day average PM 2.5 concentration was significantly associated with increments of 17.78% [95% confidence interval (95%CI): 12.54%, 23.26%], 8.76% (95%CI: 7.35%, 10.19%), and 4.00% (95%CI: 2.81%, 5.20%) increment in CANO, respectively. The exposure-response relationship curves consistently increased with the slope becoming statistically significant beyond 20 μg/m 3 . Males, children, smokers, individuals with respiratory symptoms or using inhaled corticosteroids, and those living in Southern China were more vulnerable to PM 2.5 exposure. In conclusion, our study provided novel evidence that PM 2.5 exposure in long-term, mid-term, and short-term periods could significantly elevate small-airway inflammation represented by CANO. Our results highlight the significance of CANO measurement as a non-invasive tool for early screening in the management of PM 2.5 -related inflammatory respiratory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Epidemiological and epigenetic studies have acknowledged ambient ozone exposure associated with inflammatory and cardiovascular disease. However, the molecular mechanisms still remained unclear, and epigenome-wide analysis in cohort were lacking, especially in Chinese. We included blood-derived DNA methylation for 3365 Chinese participants from the NSPT cohort and estimated individual ozone exposure level of short-, intermediate- and long-term, based on a validated prediction model. We performed epigenome-wide association studies which identified 59 CpGs and 30 DMRs at a strict genome-wide significance (P < 5 ×10 -8 ). We also conducted comparison on the DNA methylation alteration corresponding to different time windows, and observed an enhanced differentiated methylation trend for intermediate- and long-term exposure, while the short-term exposure associated methylation changes did not retain. The targeted genes of methylation alteration were involved in mechanism related to aging, inflammation disease, metabolic syndrome, neurodevelopmental disorders, and oncogenesis. Underlying pathways were enriched in biological activities including telomere maintenance process, DNA damage response and megakaryocyte differentiation. In conclusion, our study is the first EWAS on ozone exposure conducted in large-scale Han Chinese cohort and identified associated DNA methylation change on CpGs and regions, as well as related gene functions and pathways., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Kawasaki disease (KD) is an acute, systemic vasculitis that primarily affects children aged under the age of 5. While environmental factors have been linked to the development of KD, the specific role of ozone (O 3 ) pollution in triggering the disease onset remains uncertain. This study aimed to examine the associations between short-term O 3 exposure and KD onset in children. Utilizing a satellite-based model with a spatial resolution of 1 × 1 km, we matched 1808 KD patients (out of a total of 6115 eligible individuals) to pre-onset ozone exposures based on their home addresses in East China between 2013 and 2020. Our findings revealed a significant association of O 3 exposure with KD onset on the day of onset (lag 0 day). However, this association attenuated and became statistically insignificant on lag 1 and lag 2 days. Each interquartile range (52.32 μg/m 3 ) increase in O 3 concentration at lag 0 day was associated with a 16.2% (95% CI: 3.6%, 30.3%) increased risk of KD onset. The E-R curve for O 3 exhibited a plateau at low concentrations and then increased rapidly at concentrations ≥75 μg/m 3 . Notably, these associations were stronger in male children, younger children (<2 years of age) and patients experiencing KD onset during the warm season. This study provides novel epidemiological evidence indicating that short-term O 3 exposure is associated with an increased risk of childhood KD onset. These findings emphasized the importance of considering this environmental risk factor in KD prevention strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Immunoglobulin A nephropathy (IgAN) has been reported to coexist with hepatitis B virus (HBV) infection. Despite the clinical significance of this association, there is a lack of comprehensive research investigating the impact of various common conditions following HBV infection and the potential influence of anti-HBV therapy on the progression of IgAN., Methods: We investigated 3 distinct states of HBV infection, including chronic HBV infection, resolved HBV infection, and the deposition of hepatitis B antigens in renal tissue, in a follow-up database of 1961 patients with IgAN. IgAN progression was defined as a loss of estimated glomerular filtration rate (eGFR) >40%. Multivariable cause-specific hazards models to analyze the relationship between HBV states and IgAN progression., Results: Chronic HBV infection was identified as an independent risk factor for IgAN progression, supported by both prematching analysis (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.06-2.44; P  = 0.024) and propensity-score matching analysis (HR, 1.74; 95% CI 1.28-2.37; P  < 0.001). Conversely, resolved HBV infection showed no significant association with IgAN progression (HR, 1.01; 95% CI 0.67-1.52; P  = 0.969). Moreover, the presence of HBV deposition in the kidneys and the utilization of anti-HBV therapy did not appear to be significant risk factors for renal outcomes ( P > 0.05)., Conclusion: Chronic HBV infection is an independent risk factor for IgAN progression, whereas resolved HBV infection is not. In patients with IgAN, management of concurrent chronic HBV infection should be enhanced. The presence of HBV deposition in the kidneys and the use of anti-HBV medications do not impact the kidney disease progression in patients with IgAN with concurrent HBV infection., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5 th edition of the World Health Organization Classification of Tumours of the Digestive System., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

Background: In chronic kidney disease, current guidelines recommend systolic blood pressure (SBP) below 120 mmHg. However, the renoprotective effect of intensive blood-pressure (BP) lowering on immunoglobulin A nephropathy (IgAN) remains undetermined. We aimed to determine the effect of intensive BP control on the progression of IgAN., Methods: At Peking University First Hospital, 1530 patients with IgAN were enrolled. An examination of the relationship between baseline and time-updated BP and composite kidney outcomes, defined as development of end-stage kidney disease (ESKD) or a 30% decline in estimated glomerular filtration rate (eGFR), was conducted. Baseline and time-updated BPs were modeled using multivariate causal hazards models and marginal structural models (MSMs)., Results: In a median follow-up of 43.5 (interquartile range 27.2, 72.7) months, 367 (24.0%) patients experienced the composite kidney outcomes. No significant associations were found between baseline BP and the composite outcomes. Using MSMs with time-updated SBP for analysis, a U-shaped association was found. In reference to SBP 110-119 mmHg, hazard ratios (95% confidence intervals) for the SBP categories <110, 120-129, 130-139 and ≥140 mmHg were 1.48 (1.02-2.17), 1.13 (0.80-1.60), 2.21 (1.54-3.16) and 2.91 (1.94-4.35), respectively. The trend was more prominent in patients with proteinuria ≥1 g/day and eGFR ≥60 mL/min/1.73 m2. After analyzing time-updated diastolic BP, no similar trend was observed., Conclusions: In patients with IgAN, intensive BP control during the treatment period may retard the kidney disease progression, but the potential risk of hypotension still needs to be considered., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Objectives: Air pollution has been suggested as an important risk factor for chronic obstructive pulmonary disease (COPD); however, evidence of interactive effects on COPD between different factors was sparse, especially for young adults. We aimed to assess the combined effects of ambient ozone (O 3 ) and household air pollution on COPD in young individuals., Methods: We conducted a population-based study of residents aged 15-50 years in the low-income and middle-income regions of western China. We used multivariable logistic regression models to examine the associations between long-term ozone exposure and COPD in young individuals., Results: A total of 6537 young cases were identified among the participants, with a COPD prevalence rate of 7.8 (95% CI 7.2% to 8.5%), and most young COPD individuals were asymptomatic. Exposure to household air pollution was associated with COPD in young patients after adjustment for other confounding factors (OR 1.82, 95% CI 1.41 to 2.37). We also found positive associations of COPD with O 3 per IQR increase of 20 ppb (OR 1.92, 95% CI 1.59 to 2.32). The individual effects of household air pollution and O 3 were 1.68 (95% CI 1.18 to 2.46) and 1.55 (95% CI 0.99 to 2.43), respectively, while their joint effect was 3.28 (95% CI 2.35 to 4.69) with the relative excess risk due to interaction of 1.05 (95% CI 0.33 to 1.78)., Conclusions: This study concludes that exposure to ambient O 3 and household air pollution might be important risk factors for COPD among young adults, and simultaneous exposure to high levels of the two pollutants may intensify their individual effects., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Compared to distal gastrectomy (DG), pylorus-preserving gastrectomy (PPG), a peristaltic function-preserving surgery for early gastric cancer (EGC), is advantageous as it leads to a more improved nutritional status and quality of life (QOL) of patients. In recent years, total laparoscopic PPG (TLPPG), an anastomosis which is performed intracorporeally, has increasingly replaced laparoscopic-assisted PPG (LAPPG) due to its minimal invasiveness., Aim: To evaluate the safety and feasibility of TLPPG in terms of perioperative efficacy., Patients: Three patients underwent TLPPG in the Affiliated Hospital of Changzhi Medical College from September 2021 to March 2022., Methods: Surgical safety analysis: Our three cases (TLPPG group) were compared to data from the CLASS-02 study, which collected data from multiple centers across China for the laparoscopic total gastrectomy (LTG group). The CLASS-02 study provides data from the most invasive type of gastric surgery, providing solid comparative data to our own.Postoperative short-term efficacy analysis: Patient questionnaire responses provided data on postoperative nutritional and QOL status. Results from our three cases were compared to the Japanese multicenter data PGSAS-37 (PGSAS group)., Results: There were no complications or deaths occurred during or after operation in our cases. Compared to the PGSAS group, our cases scored lower for abdominal pain, dyspepsia, and weight loss., Conclusion: Although more case information is needed, our findings demonstrate that TLPPG may be a possible and effective treatment for EGC in China, similar to that in Japan., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Juntendo Medical Society.)

The associations between air pollution and diabetes mortality of different subtypes and complications were largely unclear. We performed an individual-level, time-stratified case-crossover study among over 0.9 million diabetes deaths from all administrative regions of Chinese mainland during 2013-2019. Daily concentrations of fine particles (PM 2.5 ), coarse particles (PM 2.5-10 ), nitrogen dioxide (NO 2 ) and ozone (O 3 ) were obtained for each decedent using high-resolution prediction models. Conditional logistic regression models were utilized to analyze the data. Each interquartile range increment in PM 2.5 , PM 2.5-10 , NO 2 and O 3 concentrations on lag 0-2 d increased the risks of overall diabetes mortality by 2.81 %, 1.92 %, 3.96 % and 2.15 %, respectively. Type 2 diabetes had stronger associations with air pollution than type 1 diabetes. Air pollutants were associated with diabetic ketoacidosis and diabetic nephropathy, but not other complications. The exposure-response curves were approximately linear with a plateau at higher concentrations of PM 2.5 , PM 2.5-10 , and NO 2 , while the associations for O 3 appear to be statistically significant beyond 60 μg/m 3 . This nationwide study reinforces the evidence of higher risks of acute diabetic events following short-term air pollution exposure. We identified differential effects of air pollutants on various subtypes and complications of diabetes, which require further mechanistic investigations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Backgroud: The current diagnostic criteria for refractory Mycoplasma pneumoniae pneumonia (RMPP) among Mycoplasma pneumoniae Pneumonia (MPP) are insufficient for early identification, and potentially delayed appropriate treatment. This study aimed to develop an effective individualized diagnostic prediction nomogram for pediatric RMPP., Methods: A total of 517 hospitalized children with MPP, including 131 with RMPP and 386 without RMPP (non-RMPP), treated at Lianyungang Maternal and Child Health Care Hospital from January 2018 to December 2021 were retrospectively enrolled as a development (modeling) cohort to construct an RMPP prediction nomogram. Additionally, 322 pediatric patients with MPP (64 with RMPP and 258 with non-RMPP, who were treated at the Affiliated Hospital of Xuzhou Medical University from June 2020 to May 2022 were retrospectively enrolled as a validation cohort to assess the prediction accuracy of model. Univariable and multivariable logistic regression analyses were used to identify RMPP risk factors among patients with MPP. Nomogram were generated based on these risk factors using the rms package of R, and the predictive performance was evaluated based on receiver operating characteristic (ROC) curves and using decision curve analysis (DCA)., Results: Multivariate analysis revealed five significant independent predictors of RMPP among patients with MPP: age (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.08-1.33, P = 0.038), fever duration (HR 1.34, 95%CI 1.20-1.50, P < 0.001), lymphocyte count (HR 0.45, 95%CI 0.23-0.89, P = 0.021), serum D-dimer (D-d) level (HR 1.70, 95%CI 1.16-2.49, P = 0.006), and pulmonary imaging score (HR 5.16, 95%CI 2.38-11.21, P < 0.001). The area under the ROC curve was 90.7% for the development cohort and 96.36% for the validation cohort. The internal and external verification calibration curves were almost linear with slopes of 1, and the DCA curve revealed a net benefit with the final predictive nomogram., Conclusion: This study proposes a predictive nomogram only based on five variables. The nomogram can be used for early identification of RMPP among pediatric patients with MPP, thereby facilitating more timely and effective intervention., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Currently, clinical analysis of male infertility mainly relies on parameters of semen and sperm cells. However, the high diagnostic failure rates indicate that the current assessment methods are not sufficient and a new approach to evaluating sperm function still needs to be developed. Here we explored the feasibility of single-cell inductively coupled plasma mass spectrometry (sc-ICP-MS)-derived profiles to determine the elemental characteristics in viable capacitated sperm under normal and deficient conditions. To validate the measurements, we used male sterile Pmca4-knockout (KO) mice with impaired calcium clearance, known to be dysregulated due to loss of calcium efflux capacity during sperm capacitation. Consistently, we observed significantly increased calcium intensities in Pmca4-KO sperm upon capacitation stimulation compared with control sperm from the caudaepididymides of wild-type control (WT) mice. More importantly, we explored that the characteristic signatures of calcium intensities in individual spikes derived from sc-ICP-MS was consistent with the dynamics of relative calcium levels in single sperm reported in the literature. Prominent alterations were also observed in the dynamic signatures of sc-ICP-MS-derived profiles of essential elements, particularly the redox-labile elements including copper, iron, manganese, selenium, and zinc in Pmca4-KO sperm compared to WT controls. Therefore, our study demonstrates that elementomics of sc-ICP-MS-derived signals can reveal ionic dysregulation in plasma membrane Ca2+-ATPase isoform 4 protein deficient sperm, and that sc-ICP-MS assay can be applied for functional analysis of viable sperm in functional activities, such as capacitation stimulation. We propose that cell elementomics can be used as an alternative approach to assessing sperm quality and male fertility at the single-cell level., (© The Author(s) 2023. Published by Oxford University Press.)

The spatial disparity of air pollutants is one of the key influential factors for environmental inequality. We quantitatively evaluated the evolution of PM 2.5 spatial disparity in China during 2013-2020, and investigated the associations between PM 2.5 spatial disparity and economic indicators. Differences in PM 2.5 between more- and less-polluted cities declined over time, suggesting decreased absolute disparity. However, the more polluted cities in 2013 remained so in 2017 and 2020, and vice versa, indicating persistent relative disparity. PM 2.5 pollution levels increased with higher GDP per capita in less-developed areas of China, but such negative effects weakened over time, while economic development tended to promote cleaner air in developed areas of China. Therefore, policies to improve air quality and promote economic development simultaneously are needed in China to reduce the disparity of air pollution and promote all people to enjoy environmental equality., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors.)

Multiple genome-wide association studies (GWASs) have reproducibly identified the MTMR3/HORMAD2/LIF/OSM locus to be associated with IgA nephropathy (IgAN). However, the causal variant(s), implicated gene(s), and altered mechanisms remain poorly understood. Here, we performed fine-mapping analyses based on GWAS datasets encompassing 2762 IgAN cases and 5803 control individuals, and identified rs4823074 as the candidate causal variant that intersects the MTMR3 promoter in B-lymphoblastoid cells. Mendelian randomization studies suggested the risk allele may modulate disease susceptibility by affecting serum IgA levels through increased MTMR3 expression. Consistently, elevated MTMR3 expression in peripheral blood mononuclear cells was observed in patients with IgAN. Further mechanistic studies in vitro demonstrated that MTMR3 increased IgA production dependent upon its phosphatidylinositol 3-phosphate binding domain. Moreover, our study provided the in vivo functional evidence that Mtmr3-/- mice exhibited defective Toll Like Receptor 9-induced IgA production, glomerular IgA deposition, as well as mesangial cell proliferation. RNA-seq and pathway analyses showed that MTMR3 deficiency resulted in an impaired intestinal immune network for IgA production. Thus, our results support the role of MTMR3 in IgAN pathogenesis by enhancing Toll Like Receptor 9-induced IgA immunity., (Copyright © 2023 International Society of Nephrology. All rights reserved.)

Moiré superlattices of semiconducting transition metal dichalcogenides enable unprecedented spatial control of electron wavefunctions, leading to emerging quantum states. The breaking of translational symmetry further introduces a new degree of freedom: high symmetry moiré sites of energy minima behaving as spatially separated quantum dots. We demonstrate the superposition between two moiré sites by constructing a trilayer WSe 2 /monolayer WS 2 moiré heterojunction. The two moiré sites in the first layer WSe 2 interfacing WS 2 allow the formation of two different interlayer excitons, with the hole residing in either moiré site of the first layer WSe 2 and the electron in the third layer WSe 2 . An electric field can drive the hybridization of either of the interlayer excitons with the intralayer excitons in the third WSe 2 layer, realizing the continuous tuning of interlayer exciton hopping between two moiré sites and a superposition of the two interlayer excitons, distinctively different from the natural trilayer WSe 2 ., (© 2023. Springer Nature Limited.)

Background: Immunoglobulin A nephropathy (IgAN) is one of the leading causes of end-stage kidney disease (ESKD). Many studies have shown the significance of pathological manifestations in predicting the outcome of patients with IgAN, especially T -score of Oxford classification. Evaluating prognosis may be hampered in patients without renal biopsy., Methods: A baseline dataset of 690 patients with IgAN and an independent follow-up dataset of 1,168 patients were used as training and testing sets to develop the pathology T -score prediction ( T pre ) model based on the stacking algorithm, respectively. The 5-year ESKD prediction models using clinical variables (base model), clinical variables and real pathological T -score (base model plus T bio ), and clinical variables and T pre (base model plus T pre ) were developed separately in 1,168 patients with regular follow-up to evaluate whether T pre could assist in predicting ESKD. In addition, an external validation set consisting of 355 patients was used to evaluate the performance of the 5-year ESKD prediction model using T pre ., Results: The features selected by AUCRF for the T pre model included age, systolic arterial pressure, diastolic arterial pressure, proteinuria, eGFR, serum IgA, and uric acid. The AUC of the T pre was 0.82 (95% CI: 0.80-0.85) in an independent testing set. For the 5-year ESKD prediction model, the AUC of the base model was 0.86 (95% CI: 0.75-0.97). When the T bio was added to the base model, there was an increase in AUC [from 0.86 (95% CI: 0.75-0.97) to 0.92 (95% CI: 0.85-0.98); P = 0.03]. There was no difference in AUC between the base model plus T pre and the base model plus T bio [0.90 (95% CI: 0.82-0.99) vs . 0.92 (95% CI: 0.85-0.98), P = 0.52]. The AUC of the 5-year ESKD prediction model using T pre was 0.93 (95% CI: 0.87-0.99) in the external validation set., Conclusion: A pathology T -score prediction ( T pre ) model using routine clinical characteristics was constructed, which could predict the pathological severity and assist clinicians to predict the prognosis of IgAN patients lacking kidney pathology scores., Competing Interests: Authors DZ, HW, LW, RC and GC were employed by company WeGene. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JZ declared a shared parent affiliation with the authors LX, SS, LL, X-HZ, JL, X-JZ, and HZ to the handling editor at the time of review., (Copyright © 2023 Xu, Zhang, Weng, Wang, Chen, Chen, Shi, Liu, Zhong, Hong, Duan, Lv, Zhou and Zhang.)

Limited studies investigated the effects of long-term ozone exposure on cardiometabolic health. We aimed to examine the association of long-term ozone exposure with a range of cardiometabolic diseases, as well as the subclinical indicators in Eastern China. The study included 202,042 adults living in 11 prefecture-level areas in Zhejiang Province between 2014 and 2021. Using a satellite-based model with a 1 × 1 km spatial resolution, we estimated residential 5-year average ozone exposures for each subject. Mixed-effects logistic and linear regression models were applied to explore the associations of ozone exposure with cardiometabolic diseases and subclinical indicators, respectively. We found that a 9% [95% confidence interval (95% CI): 7-12%] higher in odds of cardiometabolic disease per 10 μg/m 3 increase in ozone exposure. Specifically, we also found higher prevalence of cardiovascular diseases (15%), stroke (19%), hypertension (7%), dyslipidemia (15%), and hypertriglyceridemia (9%) associated with ozone exposure. However, we did not find significant associations between ozone exposure and coronary heart disease, myocardial infarction, or diabetes mellitus. Long-term ozone exposures were also significantly associated with adverse changes in systolic blood pressure, diastolic blood pressure, total serum cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glucose concentration, and body mass index. Our results showed that people with lower education levels, those over 50 years old, and those who were overweight or obese were more susceptible to the effects of ozone on cardiometabolic diseases. Our findings demonstrated the detrimental effects of long-term ozone exposure on cardiometabolic health, emphasizing the need for ozone control strategies to reduce the burden of cardiometabolic diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Transition metal dichalcogenide (TMDC) moiré superlattices, owing to the moiré flatbands and strong correlation, can host periodic electron crystals and fascinating correlated physics. The TMDC heterojunctions in the type-II alignment also enable long-lived interlayer excitons that are promising for correlated bosonic states, while the interaction is dictated by the asymmetry of the heterojunction. Here we demonstrate a new excitonic state, quadrupolar exciton, in a symmetric WSe 2 -WS 2 -WSe 2 trilayer moiré superlattice. The quadrupolar excitons exhibit a quadratic dependence on the electric field, distinctively different from the linear Stark shift of the dipolar excitons in heterobilayers. This quadrupolar exciton stems from the hybridization of WSe 2 valence moiré flatbands. The same mechanism also gives rise to an interlayer Mott insulator state, in which the two WSe 2 layers share one hole laterally confined in one moiré unit cell. In contrast, the hole occupation probability in each layer can be continuously tuned via an out-of-plane electric field, reaching 100% in the top or bottom WSe 2 under a large electric field, accompanying the transition from quadrupolar excitons to dipolar excitons. Our work demonstrates a trilayer moiré system as a new exciting playground for realizing novel correlated states and engineering quantum phase transitions., (© 2023. The Author(s).)

Background: Evidence of the association between particles with a diameter of 2.5 μm or less (PM 2.5 ) in long term and ovarian cancer (OC) mortality is limited., Methods: This prospective cohort study analyzed data collected between 2015 and 2020 from 610 newly diagnosed OC patients, aged 18-79 years. The residential average PM 2.5 concentrations 10 years before the date of OC diagnosis were assessed by random forest models at a 1 km × 1 km resolution. Cox proportional hazard models fully adjusted for the covariates (including age at diagnosis, education, physical activity, kitchen ventilation, FIGO stage, and comorbidities) and distributed lag non-linear models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of PM 2.5 and all-cause mortality of OC., Results: During a median follow-up of 37.6 months (interquartile: 24.8-50.5 months), 118 (19.34 %) deaths were confirmed among 610 OC patients. One-year PM 2.5 exposure levels before OC diagnosis was significantly associated with an increase in all-cause mortality among OC patients (single-pollutant model: HR = 1.22, 95 % CI: 1.02-1.46; multi-pollutant models: HR = 1.38, 95 % CI: 1.10-1.72). Furthermore, during 1 to 10 years prior to diagnosis, the lag-specific effect of long-term PM 2.5 exposure on the all-cause mortality of OC had a risk increase for lag 1-6 years, and the exposure-response relationship was linear. Of note, significant interactions between several immunological indicators as well as solid fuel use for cooking and ambient PM 2.5 concentrations were observed., Conclusion: Higher ambient PM 2.5 concentrations were associated with an increased risk of all-cause mortality among OC patients, and there was a lag effect in long-term PM 2.5 exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Hydroxychloroquine (HCQ) is recommended as a treatment for IgA nephropathy (IgAN) to control proteinuria. The long-term effects of HCQ compared to systemic corticosteroid therapy remain unclear., Methods: We conducted a retrospective case‒control study at Peking University First Hospital. Thirty-nine patients with IgAN who received HCQ for at least 24 months without corticosteroids (CSs) or other immunosuppressive agents were included. Thirty-nine matched patients who received systemic CS therapy were selected using propensity score matching. Clinical data over a 24-month period were compared., Results: In the HCQ group, the level of proteinuria decreased from 1.72 [1.44, 2.35] to 0.97 [0.51, 1.37] g/d (-50.5 [-74.0, -3.4] %, P < 0.001) at 24 months. A significant decline in proteinuria was also found in the CS group, but no significant differences were found between the HCQ group and CS group in the levels of proteinuria (0.97 [0.51, 1.37] vs. 0.53 [0.25, 1.81] g/d, P = 0.707) and change rates (-50.5% [-74.0%, -3.4%] vs. -63.7% [-78.5%, -24.2%], P = 0.385) at 24 months. In addition, the decline rates of eGFR between the HCQ and CS groups were comparable (-7.9% [-16.1%, 5.8%] vs. -6.6% [-14.9%, 5.3%], P = 0.758). More adverse events were observed in the CS group., Conclusions: Long-term use of HCQ can maintain stable renal function with minimal side effects. In patients who cannot tolerate corticosteroids, HCQ might be an effective and safe supportive therapy for IgAN., (© 2023. The Author(s).)

Background: The associations between fine and coarse particulate matter (PM2.5 and PM2.5-10) air pollution and hospital admissions for full-spectrum respiratory diseases were rarely investigated, especially for age-specific associations. We aim to estimate the age-specific associations of short-term exposures to PM2.5 and PM2.5-10 with hospital admissions for full-spectrum respiratory diseases in China., Methods: We conducted an individual-level case-crossover study based on a nationwide hospital-based registry including 153 hospitals across 20 provincial regions in China in 2013-20. We applied conditional logistic regression models and distributed lag models to estimate the exposure- and lag-response associations., Results: A total of 1 399 955 hospital admission records for various respiratory diseases were identified. The associations of PM2.5 and PM2.5-10 with total respiratory hospitalizations lasted for 4 days, and an interquartile range increase in PM2.5 (34.5 μg/m3) and PM2.5-10 (26.0 μg/m3) was associated with 1.73% [95% confidence interval (95% CI): 1.34%, 2.12%)] and 1.70% (95% CI: 1.31%, 2.10%) increases, respectively, in total respiratory hospitalizations over lag 0-4 days. Acute respiratory infections (i.e. pneumonia, bronchitis and bronchiolitis) were consistently associated with PM2.5 or PM2.5-10 exposure across different age groups. We found the disease spectrum varied by age, including rarely reported findings (i.e. acute laryngitis and tracheitis, and influenza) among children and well-established associations (i.e. chronic obstructive pulmonary disease, asthma, acute bronchitis and emphysema) among older populations. Besides, the associations were stronger in females, children and older populations., Conclusions: This nationwide case-crossover study provides robust evidence that short-term exposure to both PM2.5 and PM2.5-10 was associated with increased hospital admissions for a wide range of respiratory diseases, and the spectra of respiratory diseases varied by age. Females, children and older populations were more susceptible., (© The Author(s) 2023; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: A large gap exists between the latest Global Air Quality Guidelines (AQG 2021) and Chinese air quality standards for NO 2 . Assessing whether and to what extent air quality standards for NO 2 should be tightened in China requires a comprehensive understanding of the spatiotemporal characteristics of population exposure to ambient NO 2 and related health risks, which have not been studied to date., Objective: We predicted ground NO 2 concentrations with high resolution in mainland China, explored exposure characteristics to NO 2 pollution, and assessed the mortality burden attributable to NO 2 exposure., Methods: Daily NO 2 concentrations in 2019 were predicted at 1-km spatial resolution in mainland China using random forest models incorporating multiple predictors. From these high-resolution predictions, we explored the spatiotemporal distribution of NO 2 , population and area percentages with NO 2 exposure exceeding criterion levels, and premature deaths attributable to long- and short-term NO 2 exposure in China., Results: The cross-validation R 2 and root mean squared error of the NO 2 predicting model were 0.80 and 7.78 μg/m 3 , respectively,at the daily level in 2019.The percentage of people (population number) with annual NO 2 exposure over 40 μg/m 3 in mainland China in 2019 was 10.40 % (145,605,200), and it reached 99.68 % (1,395,569,840) with the AQG guideline value of 10 μg/m 3 . NO 2 levels and population exposure risk were elevated in urban areas than in rural. Long- and short-term exposures to NO 2 were associated with 285,036 and 121,263 non-accidental deaths, respectively, in China in 2019. Tightening standards in steps gradually would increase the potential health benefit., Conclusion: In China, NO 2 pollution is associated with significant mortality burden. Spatial disparities exist in NO 2 pollution and exposure risks. China's current air quality standards may no longer objectively reflect the severity of NO 2 pollution and exposure risk. Tightening the national standards for NO 2 is needed and will lead to significant health benefits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Exposure to particulate matter (PM) has been a major public health threat, but the potentially differential effects on asthma of PM remain largely unknown in high altitude settings. We evaluated the effects of ambient PM on asthma in high altitude settings., Methods: The study recruited a representative sample from high altitude settings using a multistage stratified sampling procedure. Asthma was defined by a self-reported history of diagnosis by a physician or by wheezing symptoms in the preceding 12 months. The annual mean PM 2.5 and PM 10 concentrations were calculated for each grid cell at 1-km spatial resolution based on the geographical coordinates., Results: We analyzed data for participants (mean age 39.1 years, 51.4% female) and 183 (3.7%, 95% confidence interval (CI): 3.2-4.2) of the participants had asthma. Prevalence was higher in women (4.3%, 95% CI 3.5-5.1) than in men (3.1%, 2.4-3.8) and increasing with higher concentration of PM exposures. For an interquartile range (IQR) difference (8.77 μg/m 3 ) in PM 2.5 exposure, the adjusted odds ratio (OR) was 1.64 (95% CI 1.46-1.83, P < 0.001) for risk of asthma. For PM 10 , there was evidence for an association with risk of asthma (OR 2.34, 95% CI: 1.75-3.15, P < 0.001 per IQR of 43.26 μg/m 3 ). Further analyses showed that household mold or damp exposure may aggravate PM exposure associated risks of asthma., Conclusions: This study identified that PM exposure could be a dominate environmental risk factor for asthma but largely unconsidered in the high-altitude areas. The association between PM exposure and asthma should be of interest for planners of national policies and encourage programs for prevention of asthma in residents living at high altitudes., (© 2023 The Authors.)

Recent evidence advises particles with a diameter of 2.5 µm or less (PM 2.5 ) might be a prognostic factor for ovarian cancer (OC) survival. The oxidative balance score (OBS) incorporates diet-lifestyle factors to estimate individuals' anti-oxidant exposure status which may be relevant to cancer prognosis. We aimed to investigate the roles of PM 2.5 , and OBS and their interaction in OC prognosis. 663 patients with OC were enrolled in the current study. Satellite-derived annual average exposures to PM 2.5 based on patients' residential locations. The OBS was calculated based on 16 different diet-lifestyle components derived using an acknowledged self-reported questionnaire. The Cox regression model was performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS). We also assessed the effect of modification between PM 2.5 and OS by OBS via interaction terms. During a median follow-up of 37.57 (interquartile:35.27-40.17) months, 123 patients died. Compared to low-concentration PM 2.5 exposure, high PM 2.5 during 1 year before diagnosis was associated with worse OC survival (HR= 1.19, 95% CI = 1.01-1.42). We observed an improved OS with the highest compared with the lowest OBS (HR = 0.46, 95% CI = 0.27-0.79, P for trend < 0.05). Notably, we also found an additive interaction between low OBS and high exposure to PM 2.5 , with the corresponding associations of PM 2.5 being more pronounced among participants with lower OBS (HR = 1.42, 95% CI = 1.09-1.86). PM 2.5 may blunt OC survival, but high OBS represented an antioxidative performance that could alleviate the adverse association of PM 2.5 and OS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The non-toxic and stable chalcogenide perovskite BaZrS 3 fulfills many key optoelectronic properties for a high-efficiency photovoltaic material. It has been shown to possess a direct band gap with a large absorption coefficient and good carrier mobility values. With a reported band gap of 1.7-1.8 eV, BaZrS 3 is a good candidate for tandem solar cell materials; however, its band gap is significantly larger than the optimal value for a high-efficiency single-junction solar cell (∼1.3 eV, Shockley-Queisser limit)─thus doping is required to lower the band gap. By combining first-principles calculations and machine learning algorithms, we are able to identify and predict the best dopants for the BaZrS 3 perovskites for potential future photovoltaic devices with a band gap within the Shockley-Queisser limit. It is found that the Ca dopant at the Ba site or Ti dopant at the Zr site is the best candidate dopant. Based on this information, we report for the first time partial doping at the Ba site in BaZrS 3 with Ca (i.e., Ba 1- x Ca x ZrS 3 ) and compare its photoluminescence with Ti-doped perovskites [i.e., Ba(Zr 1- x Ti x )S 3 ]. Synthesized (Ba,Ca)ZrS 3 perovskites show a reduction in the band gap from ∼1.75 to ∼1.26 eV with <2 atom % Ca doping. Our results indicate that for the purpose of band gap tuning for photovoltaic applications, Ca-doping at the Ba-site is superior to Ti-doping at the Zr-site reported previously.

The onset of various kidney diseases has been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, detailed clinical and pathological features are lacking. We screened and analyzed patients with newly diagnosed kidney diseases after inactivated SARS-CoV-2 vaccination in Peking University First Hospital from January 2021 to August 2021, and compared them with the reported cases in the literature. We obtained samples of blood, urine and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observations, were described. The SARS-CoV-2 spike protein and nucleoprotein were stained using the immunofluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay. The study group included 17 patients with a range of conditions including immune-complex-mediated kidney diseases (IgA nephropathy, membranous nephropathy and lupus nephritis), podocytopathy (minimal change disease and focal segmental glomerulosclerosis) and others (antineutrophil-cytoplasmic-antibody-associated vasculitis, anti-glomerular basement membrane nephritis, acute tubulointerstitial nephritis and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and ten (58.82%) after the second dose. The kidney disease spectrum as well as clinicopathological features are similar across different types of SARS-CoV-2 vaccines. We found no definitive evidence of SARS-CoV-2 spike protein or nucleoprotein deposition in the kidney biopsy samples. Seropositive markers implicated abnormal immune responses in predisposed individuals. Treatment and follow-up (median = 86 days) showed that biopsy diagnosis informed treatment and prognosis in all patients. In conclusion, we observed various kidney diseases following SARS-CoV-2 vaccine administration, which show a high consistency across different types of SARS-CoV-2 vaccines. Our findings provide evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of SARS-CoV-2 vaccine renal safety., (© The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Zona incerta (ZI) is an integrative subthalamic region in nociceptive neurotransmission. Previous studies demonstrated that the rostral ZI (ZIR) is an important gamma-aminobutyric acid-ergic (GABAergic) source to the thalamic paraventricular nucleus (PVT), but whether the ZIR-PVT pathway participates in nociceptive modulation is still unclear. Therefore, our investigation utilized anatomical tracing, fiber photometry, chemogenetic, optogenetic and local pharmacological approaches to investigate the roles of the ZIR GABA+ -PVT pathway in nociceptive neurotransmission in mice. We found that projections from the GABAergic neurons in ZIR to PVT were involved in nociceptive neurotransmission. Furthermore, chemogenetic and optogenetic activation of the ZIR GABA+ -PVT pathway alleviates pain, whereas inhibiting the activities of the ZIR GABA+ -PVT circuit induces mechanical hypersensitivity and partial heat hyperalgesia. Importantly, in vivo pharmacology combined with optogenetics revealed that the GABA-A receptor (GABA A R) is crucial for GABAergic inhibition from ZIR to PVT. Our data suggest that the ZIR GABA+ -PVT pathway acts through GABA A R-expressing glutamatergic neurons in PVT mediates nociceptive neurotransmission.

Background: Discontinuation of renin-angiotensin system (RAS) inhibitors is common in patients with chronic kidney disease (CKD), and the potential danger has been reported in several studies. However, a comprehensive analysis has not been conducted., Objectives: This study sought to evaluate the effects of discontinuation of RAS inhibitors in CKD., Method: Relevant studies up to November 30, 2022, were identified in the PubMed, Embase, Web of Science, and Cochrane Library databases. Efficacy outcomes included the composite of all-cause mortality, cardiovascular events, and end-stage kidney disease (ESKD). Results were combined using a random-effects or fixed-effects model, and sensitivity analysis used the leave-one-out method., Results: Six observational studies and one randomized clinical trial including 244,979 patients met the inclusion criteria. Pooled data demonstrated that discontinuation of RAS inhibitors was associated with an increased risk of all-cause mortality (HR 1.42, 95% CI 1.23-1.63), cardiovascular event risk (HR 1.25, 95% CI 1.17-1.22), and ESKD (HR 1.23, 95% CI 1.02-1.49). In sensitivity analyses, the risk for ESKD was reduced. Subgroup analysis showed that the risk of mortality was more pronounced in patients with eGFR above 30 mL/min/m2 and in patients with hyperkalemia-related discontinuation. In contrast, patients with eGFR below 30 mL/min/m2 were at great risk of cardiovascular events., Conclusions: The discontinuation of RAS inhibitors in patients with CKD was associated with a significantly increased risk of all-cause mortality and cardiovascular events. These data suggest that RAS inhibitors should be continued in CKD if the clinical situation allows., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Including data of different time intervals during model development influences the predicting accuracy of PM 2.5 but has not been widely discussed. Therefore, we included modeling data with multiple time windows to identify optimized modeling time windows for capturing the long-term variation of PM 2.5 in China during 2005-2019. In general, we incorporated PM 2.5 measurements, aerosol optical depth (AOD), meteorological parameters, land use data, and other predictors to train random forest models. The study period was separated into two phases (2013-2019 and 2005-2012) according to the availability of PM 2.5 measurements. First, we trained models with two strategies of choosing time windows to compare model performance in predicting PM 2.5 from 2013 to 2019, when measurements were available. Strategy 1a (ST1a) refers to training one model with all available data, and Strategy 1b (ST1b) refers to training multiple models each with one-year data. Second, we trained models with additional ten strategies (ST2a-ST2j) based on data from different time windows during 2013-2019 to compare the accuracy in predicting PM 2.5 before 2013, when measurements were unavailable. The internal and external cross-validation (CV) indicated that the model performance of ST1b was better than ST1a. Predictions based on ST1a tended to underestimate PM 2.5 levels in 2013 and 2014 when PM 2.5 concentrations were high, and overestimate after 2017 when PM 2.5 dropped dramatically. The external CV of predicting historical PM 2.5 was the most robust in ST2i (averaged predictions from two models developed by 2013 and 2014 data, respectively). Models with data closer to historical years and PM 2.5 levels performed better in predicting historical PM 2.5 concentrations. Our results suggested that training models with data of current-years performed better during 2013-2019, and with data of 2013 and 2014 performed better in predicting historical PM 2.5 before 2013 in China. The comparison provided evidence for choosing optimized time windows when predicting long-term PM 2.5 concentrations in China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Frequent application of chemical fumigants has contributed to the development of resistance in stored-product pests. Essential oils provide a novel and environmentally friendly alternative to conventional chemical pesticides. In this work, the fumigant activity of Taxodium 'zhongshansha' essential oil (TZEO) and main active components against Sitophilus zeamais were evaluated. In addition, the molecular mechanisms mediating the fumigant activity of limonene were assessed., Results: TZEO showed strong fumigant activity against Sitophilus zeamais, with a 50% lethal concentration (LC 50 ) of 22.90 μL L -1 air in 24 h. The main components of TZEO were identified using gas chromatography-mass spectrometry, the main active ingredient (limonene) showed an LC 50 of 9.93 μL L -1 air in 24 h which had a serious dose-time-effect. The LC 50 value of the positive control (aluminum phosphide) was 1.91 μL L -1 . In total, 3982 up-regulated and 3067 down-regulated genes were sequenced in limonene-fumigated Sitophilus zeamais, the genes related to metabolic detoxification were significantly enriched. The mortality rate of 7 day-old Sitophilus zeamais adult mediated with knockdown of SzCYP6MS5 and SzCYP6MS6 raised up to 65.67% and 67.65% after fumigation with limonene in 24 h, respectively. The results showed that SzCYP6MS5 and SzCYP6MS6 are closely involved to the detoxification of limonene., Conclusion: In this study, candidate genes affected by limonene treatment in Sitophilus zeamais were identified. These findings provided insights into the systemic metabolic response of Sitophilus zeamais to limonene and established a basis for the development of limonene as a botanical pesticide for the control of stored-product pests. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)