The efficacy and safety of continuous theta burst stimulation for auditory hallucinations: a systematic review and meta-analysis of randomized controlled trials.

Objective: Auditory hallucinations are the most frequently occurring psychotic symptom in schizophrenia. Continuous theta burst stimulation (cTBS) has been used as an adjuvant treatment for auditory hallucinations. This meta-analysis focused on randomized controlled clinical trials (RCTs) to assess the efficacy of adjuvant cTBS on auditory hallucinations in schizophrenia. Methods: We performed a comprehensive search of four international databases from their inception to January 14, 2024, to identify relevant RCTs that assessed the effects of adjuvant cTBS on auditory hallucinations. The key words included "auditory hallucinations", "continuous theta burst stimulation" and "transcranial magnetic stimulation". Inclusion criteria included patients with auditory hallucinations in schizophrenia or schizoaffective disorder. The Revised Cochrane risk-of-bias tool for randomized trials (RoB1) were used to evaluate the risk of bias and the Review Manager Software Version 5.4 was employed to pool the data. Results: A total of 4 RCTs involving 151 patients with auditory hallucinations were included in the analysis. The Cochrane risk of bias of these studies presented "low risk" in all items. Preliminary analysis showed no significant advantage of adjuvant cTBS over sham stimulation in reducing hallucinations [4 RCTs, n = 151; SMD: -0.45 (95%CI: -1.01, 0.12), P = 0.13; I2 = 61%]. Subgroup analysis revealed that patients treated with adjuvant cTBS for more than 10 stimulation sessions and total number of pulses more than 6000 [3 RCTs, n = 87; SMD: -4.43 (95%CI: -8.22, -0.63), P = 0.02; I2 = 47%] had a statistically significant improvement in hallucination symptoms. Moreover, the rates of adverse events and discontinuation did not show any significant difference between the cTBS and sham group. Conclusions: Although preliminary analysis did not revealed a significant advantage of adjuvant cTBS over sham stimulation, subgroup analysis showed that specific parameters of cTBS appear to be effective in the treatment of auditory hallucinations in schizophrenia. Further large-scale studies are needed to determine the standard protocol of cTBS for treating auditory hallucinations. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024534045.

Association between neutrophil to high-density lipoprotein cholesterol ratio (NHR) and depression symptoms among the United States adults: a cross-sectional study.

BACKGROUND: Depression acts as a noteworthy worldwide public health challenge. Identifying accessible biomarkers is crucial for early diagnosis and intervention. The relationship between depression in adult Americans and the neutrophil to high-density lipoprotein cholesterol ratio (NHR) was investigated in this research. METHODS: The relationship between NHR and depressive symptoms was analyzed utilizing National Health and Nutrition Examination Survey data from 2005 to 2018 and the Patient Health Questionnaire-9. The study included 33,871 participants with complete NHR and depression data. Adjusted multivariable logistic regression models were used to account for possible confounders, and subgroup analyses were conducted to investigate effect changes. RESULTS: Elevated NHR levels were positively correlated with a heightened risk of depression (OR = 1.03, 95% CI: 1.01-1.05, P < 0.0005). After the NHR was divided into tertiles, those in the top tertile had an 18% higher chance of developing depression than those in the bottom tertile (OR = 1.18; 95% CI: 1.05-1.32; P for trend = 0.0041). Subgroup analyses revealed variations in this association based on race and marital status. Additionally, the relationship between NHR and depression demonstrated a U-shaped pattern, with a significant breakpoint identified at an NHR of 6.97. CONCLUSION: These results imply that the NHR may be a potential biomarker for depression risk, with implications for early detection and personalized treatment. Further research is needed to elucidate the mechanisms underlying the NHR-depression link and establish causality.

Ion Transport in Multi-Nanochannels Regulated by pH and Ion Concentration.

Nanochannels are a powerful technique for detecting a wide range of biomolecules without labeling. The ion transport phenomena in nanochannel arrays differ from those in single nanochannels and are caused by interchannel communication. This study uses a fully coupled Poisson-Nernst-Planck (PNP) and Navier-Stokes model to investigate ion transport in nanochannel arrays. Instead of being set at a constant value, the surface charge density used in this study is established by the protonation and deprotonation of the silanol groups that are present on the walls of the silicon-based nanochannels. The surface charge density of the nanochannel walls varies with the number of nanochannels, the channel lateral distance, and the background solution properties, which consequently influence the ionic concentration distribution, flow velocity, and electric field strength. For example, in different numbers of nanochannel systems, the ion concentration in nanochannels is not much different, but it is different in reservoirs, especially near the openings of nanochannels. The number of nanochannels and the distance between nanochannels can also affect the formation of electro-convective vortex zones under certain conditions. These findings can aid in optimizing the nanochannel array design by regulating the number and distance of nanochannels and facilitating the construction of solid-state nanochannel arrays with any desired nanochannel dimensions.

Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

Objective: Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD. Method: 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations. Results: Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001). Conclusion: Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.

Corrigendum: Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

[This corrects the article DOI: 10.3389/fpsyt.2024.1354999.].

HiMIC-Monthly: A 1 km high-resolution atmospheric moisture index collection over China, 2003-2020.

Near-surface atmospheric moisture is a key environmental and hydro-climatic variable that has significant implications for the natural and human systems. However, high-resolution moisture data are severely lacking for fine-scale studies. Here, we develop the first 1 km high spatial resolution dataset of monthly moisture index collection in China (HiMIC-Monthly) over a long period of 2003~2020. HiMIC-Monthly is generated by the light gradient boosting machine algorithm (LightGBM) based on observations at 2,419 weather stations and multiple covariates, including land surface temperature, vapor pressure, land cover, impervious surface proportion, population density, and topography. This collection includes six commonly used moisture indices, enabling fine-scale assessment of moisture conditions from different perspectives. Results show that the HiMIC-Monthly dataset has a good performance, with R2 values for all six moisture indices exceeding 0.96 and root mean square error and mean absolute error values within a reasonable range. The dataset exhibits high consistency with in situ observations over various spatial and temporal regimes, demonstrating broad applicability and strong reliability.

Arctic amplification-induced decline in West and South Asia dust warrants stronger antidesertification toward carbon neutrality.

Dust loading in West and South Asia has been a major environmental issue due to its negative effects on air quality, food security, energy supply and public health, as well as on regional and global weather and climate. Yet a robust understanding of its recent changes and future projection remains unclear. On the basis of several high-quality remote sensing products, we detect a consistently decreasing trend of dust loading in West and South Asia over the last two decades. In contrast to previous studies emphasizing the role of local land use changes, here, we attribute the regional dust decline to the continuous intensification of Arctic amplification driven by anthropogenic global warming. Arctic amplification results in anomalous mid-latitude atmospheric circulation, particularly a deepened trough stretching from West Siberia to Northeast India, which inhibits both dust emissions and their downstream transports. Large ensemble climate model simulations further support the dominant role of greenhouse gases induced Arctic amplification in modulating dust loading over West and South Asia. Future projections under different emission scenarios imply potential adverse effects of carbon neutrality in leading to higher regional dust loading and thus highlight the importance of stronger anti-desertification counter-actions such as reforestation and irrigation management.

Anthropogenic forcing has increased the risk of longer-traveling and slower-moving large contiguous heatwaves.

Heatwaves are consecutive hot days with devastating impacts on human health and the environment. These events may evolve across both space and time, characterizing a spatiotemporally contiguous propagation pattern that has not been fully understood. Here, we track the spatiotemporally contiguous heatwaves in both reanalysis datasets and model simulations and examine their moving patterns (i.e., moving distance, speed, and direction) in different continents and periods. Substantial changes in contiguous heatwaves have been identified from 1979 to 2020, with longer persistence, longer traveling distance, and slower propagation. These changes have been amplified since 1997, probably due to the weakening of eddy kinetic energy, zonal wind, and anthropogenic forcing. The results suggest that longer-lived, longer-traveling, and slower-moving contiguous heatwaves will cause more devastating impacts on human health and the environment in the future if greenhouse gas emissions keep rising and no effective measures are taken immediately. Our findings provide important implications for the adaption and mitigation of globally connected extreme heatwaves.

Association between serum insulin-like growth factor 1 levels and the improvements of cognitive impairments in a subgroup of schizophrenia: Preliminary findings.

BACKGROUND: Numerous studies have implicated abnormal insulin-like growth factor 1 (IGF-1) in the pathophysiology of schizophrenia, but findings have been inconsistent. METHODS: We conducted a meta-analysis to compare IGF-1 levels in schizophrenia patients with healthy controls and explored factors contributing to variability between estimates. In an independent sample (58 chronic schizophrenia patients and 30 healthy controls), we investigated differences in IGF-1 levels among schizophrenia subgroups with distinct cognitive profiles, identified using k-means clustering based on five cognitive domains from The Repeatable Battery for the Assessment of Neuropsychological Status. Associations between serum IGF-1 levels and clinical and neurocognitive improvements were also examined. RESULTS: The meta-analysis revealed significantly lower serum IGF-1 levels in schizophrenia patients compared to healthy controls, albeit with high heterogeneity. Medication status, BMI, and severity of negative symptoms were identified as potential contributors to this heterogeneity. In our independent study, antipsychotic treatment led to a significant increase in IGF-1 levels, and lower pre-treatment serum IGF-1 levels correlated with greater improvement in cognitive deficits, particularly in a subgroup with more severe cognitive symptoms. CONCLUSIONS: Our findings support the "IGF-1 deficiency hypothesis" in the pathogenesis of schizophrenia. Further research is crucial to elucidate the role of IGF-1 in the cognitive impairments associated with schizophrenia.

[Predictive value of HACOR score on the clinical outcome of non-invasive positive pressure ventilation in the treatment of chronic obstructive pulmonary disease with pulmonary encephalopathy].

OBJECTIVE: To explore the predictive value of HACOR score [heart rate (H), acidosis (A), consciousness (C), oxygenation (O), and respiratory rate (R)] on the clinical outcome of non-invasive positive pressure ventilation in patients with pulmonary encephalopathy due to chronic obstructive pulmonary disease (COPD). METHODS: A prospective study was conducted. The patients with COPD combined with pulmonary encephalopathy who were admitted to Henan Provincial People's Hospital from January 1, 2017 to June 1, 2021 and initially received non-invasive positive pressure ventilation were enrolled. Besides non-invasive positive pressure ventilation, standard medical treatments were delivered to these patients according to guidelines. The need for endotracheal intubation was judged as failure of non-invasive ventilation treatment. Early failure was defined as the need for endotracheal intubation within 48 hours of treatment, and late failure was defined as the need for endotracheal intubation 48 hours and later. The HACOR score at different time points after non-invasive ventilation, the length of intensive care unit (ICU) stay, the total length of hospital stay, and the clinical outcome were recorded. The above indexes of patients with non-invasive ventilation were compared between successful and failed groups. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive effect of HACOR score on the failure of non-invasive positive pressure ventilation in the treatment of COPD with pulmonary encephalopathy. RESULTS: A total of 630 patients were evaluated, and 51 patients were enrolled, including 42 males (82.35%) and 9 females (17.65%), with a median age of 70.0 (62.0, 78.0) years old. Among the 51 patients, 36 patients (70.59%) were successfully treated with non-invasive ventilation and discharged from the hospital eventually, and 15 patients (29.41%) failed and switched to invasive ventilation, of which 10 patients (19.61%) were defined early failure, 5 patients (9.80%) were late failure. The length of ICU and the total length of hospital stay of the non-invasive ventilation successful group were significantly longer than those of the non-invasive ventilation failure group [length of ICU stay (days): 13.0 (10.0, 16.0) vs. 5.0 (3.0, 8.0), total length of hospital stay (days): 23.0 (12.0, 28.0) vs. 12.0 (9.0, 15.0), both P < 0.01]. The HACOR score of patients at 1-2 hours in the non-invasive ventilation failure group was significantly higher than that in the successful group [10.47 (6.00, 16.00) vs. 6.00 (3.25, 8.00), P < 0.05]. However, there was no significant difference in HACOR score before non-invasive ventilation and at 3-6 hours between the two groups. The ROC curve showed that the area under the ROC curve (AUC) of 1-2 hour HACOR score after non-invasive ventilation for predicting non-invasive ventilation failure in COPD patients with pulmonary encephalopathy was 0.686, and the 95% confidence interval (95%CI) was 0.504-0.868. When the best cut-off value was 10.50, the sensitivity was 60.03%, the specificity was 86.10%, positive predictive value was 91.23%, and negative predictive value was 47.21%. CONCLUSIONS: Non-invasive positive pressure ventilation could prevent 70.59% of COPD patients with pulmonary encephalopathy from intubation. HACOR score was valuable to predict non-invasive positive pressure ventilation failure in pulmonary encephalopathy patients due to COPD.

Establishment of recombinant Catharanthus roseus stem cells stably overexpressing ORCA4 for terpenoid indole alkaloids biosynthesis.

Catharanthus roseus is a perennial herb of the Apocynaceae family, from which about 200 kinds of alkaloids have been characterized. Most alkaloids from C. roseus are terpenoid indole alkaloids (TIAs), such as vinblastine and vincristine, which are widely used in the clinic for their good antitumor activity. However, they were only biosynthesized in C. roseus, and their content in C. roseus is extremely low. The access to these valuable compounds is by plant extraction or chemical semisynthesis from their precursors catharanthine and vindoline. Since catharanthine and vindoline are also obtained from C. roseus, the supply of vinblastine and vincristine makes it difficult to meet market demands. Therefore, how to improve the yield of TIAs is an attractive issue. In this study, we compared the regulatory effect of two critical transcription factors, octadecanoid-derivative responsive Catharanthus AP2-domain protein 3 (ORCA3) and octadecanoid-derivative responsive Catharanthus AP2-domain protein 4 (ORCA4), on the biosynthesis of TIAs in C. roseus. The results showed that overexpressing both two transcription factors could increase the accumulation of TIAs. The effect was more significant when ORCA4 was overexpressed. To acquire C. roseus TIAs on a continuous and consistent basis, we then created and acquired C. roseus stem cells stably overexpressing ORCA4. This is the first time a recombinant C. roseus stem cell system with stable ORCA4 overexpression has been developed, which not only provides new ideas for future research in this area but also breaches new life into the industrial application of using plant cell culture to obtain natural products.

Epithelial-mesenchymal transition-related lncRNAs associated with prognosis and immune cell infiltration in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) remains the most common type of lung cancer and is associated with distant metastasis and poor prognosis. Epithelial-mesenchymal transition (EMT) plays crucial roles in carcinogenesis, embryogenesis, and wound healing. EMT-related molecules may be adopted for early diagnosis and prognosis of cancer and targeting them may constitute an attractive strategy for treatment. This study aims to identify the EMT-related long non-coding RNAs (lncRNAs) and develop a risk signature to accurately predict the prognosis of LUAD patients. METHODS: The RNA-seq data and corresponding clinical profiles were obtained from LUAD cohort of The Cancer Genome Atlas (TCGA) database. EMT-related lncRNAs significantly associated with prognosis were identified by Pearson correlation analysis and univariate regression analysis. Subsequently, an EMT-related prognostic risk signature was developed through LASSO and multivariate regression analyses. Kaplan Meier and receiver operating characteristic curve analysis were implemented to assess the predictive performance of the signature. The nomogram was constructed to predict the 1-year, 3-year, and 5-year overall survival of LUAD patients. Additionally, enrichment analyses were carried out to identify probable biologic processes and cellular pathways involved in the signature. The correlation of immune cell infiltration and risk score was also evaluated by CIBERSORT algorithm. Finally, we constructed a ceRNA network to further study possible downstream targets and molecular mechanisms of EMT-related lncRNAs in LUAD. RESULTS: Eight EMT-related lncRNAs were identified to develop a prognostic risk signature in LUAD. Patients with high-risk scores had worse survival outcomes than those with low-risk scores. The signature showed robust predictive potential, and was verified to be an independent prognostic factor. Moreover, the risk score based on the signature was significantly correlated with immune cell infiltration in LUAD. CONCLUSIONS: We established and validated a prognostic signature that reflects the tumor microenvironment characteristics and predicts the outcomes for LUAD.

Data Mining and Network Pharmacology Analysis of Kidney-Tonifying Herbs on the Treatment of Renal Osteodystrophy Based on the Theory of "Kidney Governing Bones" in Traditional Chinese Medicine.

Background: Renal osteodystrophy (ROD) secondary to chronic kidney disease is closely associated with osteoporosis and fractures. Based on the theory of "kidney governing bones" in traditional Chinese medicine (TCM), treating bone diseases from the perspective of the kidney has become a basic principle of treating ROD. However, there are many kidney-tonifying herbs and their mechanisms of treating ROD are not clear. Therefore, our study intends to use data mining and network pharmacology to study the commonly used kidney-tonifying herbs, as well as their active ingredients and mechanisms of treating ROD. Methods: We established a clinical ROD database by searching PubMed, CNKI, and other databases and screened out a core herbal combination of treating ROD. Furthermore, by using databases such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and GeneCards, we obtained active ingredients and targets of the core herbal combination and ROD targets. The STRING website and Cytoscape software were then used to obtain information on key active ingredients and key targets. Finally, we conducted GO and KEGG analyses using the Metascape website and molecular docking using the AutoDock Vina software. Results: Our study eventually included 58 prescriptions and 116 herbs of treating ROD. Through data mining, we found that yin-yang-huo, du-zhong, and bu-gu-zhi (YDB) constituted a core herbal combination to treat ROD. Network pharmacology showed that YDB mainly acted on targets such as estrogen receptor alpha through active ingredients such as quercetin by mitogen-activated protein kinase and other signaling pathways. Conclusion: Many ingredients, targets, and pathways are involved in the treatment of YDB for ROD. Specifically, the flavonoids contained in YDB have great potential for ROD treatment.

Long-term trends of atmospheric hot-and-polluted episodes (HPE) and the public health implications in the Pearl River Delta region of China.

Air pollution and extreme heat have been responsible for more than a million deaths in China every year, especially in densely urbanized regions. While previous studies intensively evaluated air pollution episodes and extreme heat events, a limited number of studies comprehensively assessed atmospheric hot-and-polluted-episodes (HPE) - an episode with simultaneously high levels of air pollution and temperature - which have potential adverse synergic impacts on human health. This study focused on the Pearl River Delta (PRD) region of China due to its high temperature in summer and poor air quality throughout a year. We employed geostatistical downscaling to model meteorology at a spatial resolution of 1 km, and applied a machine learning algorithm (XGBoost) to estimate a high-resolution (1 km) daily concentration of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) and ozone (O3) for June to October over 20 years (2000-2019). Our results indicate an increasing trend (∼50%) in the frequency of HPE occurrence in the first decade (2000-2010). Conversely, the annual frequency of HPE occurrence reduced (16.7%), but its intensity increased during the second decade (2010-2019). The northern cities in the PRD region had higher levels of PM2.5 and O3 than their southern counterparts. During HPEs, regional daily PM2.5 exceeded the World Health Organization (WHO) and Chinese guideline levels by 75% and 25%, respectively, while the O3 exceeded the WHO O3 standard by up to 69%. Overall, 567,063 (95% confidence interval (CI): 510,357-623,770) and 52,231 (95%CI: 26,116-78,346) excessive deaths were respectively attributable to exposure to PM2.5 and O3 in the PRD region. Our findings imply the necessity and urgency to formulate co-benefit policies to mitigate the region's air pollution and heat problems.

Autophagy promotes membrane trafficking of NR2B to alleviate depression by inhibiting AQP4 expression in mice.

Depression is a high-incidence mental illness that seriously affects human health. AQP4 has been reported to be closely associated with depression, while the underlying mechanism is still unclear. This work aimed to investigate the functional role of AQP4 in depression. Depression mouse model was constructed by administration of chronic social defeat stress (CSDS). We found that AQP4 was highly expressed in the hippocampal tissues of CSDS mice. AQP4 knockdown alleviated depression and enhanced the expression of NR2B and PSD95 in CSDS mice. Moreover, primary hippocampal neurons were treated with N-methyl-d-aspartate (NMDA) to induce neuron injury. AQP4 overexpression repressed cell viability and promoted apoptosis of NMDA-treated primary hippocampal neurons. AQP4 up-regulation repressed the expression of NR2B (surface), and enhanced the expression of NR2B (intracellular), P-NR2B, CaMK II and CK2 in the NMDA-treated primary hippocampal neurons. The influence conferred by AQP4 up-regulation was abolished by KN-93 (CaMK II inhibitor) or TBB (CK2 inhibitor) treatment. Rapamycin treatment enhanced the expression of NR2B (surface), and repressed the expression of AQP4, NR2B (intracellular) and P-NR2B in the primary hippocampal neurons by activating autophagy. The activated autophagy alleviated depression in CSDS mice by repressing AQP4 expression. In conclusion, our data demonstrated that autophagy ameliorated depression by repressing AQP4 expression in mice, and AQP4 knockdown promoted membrane trafficking of NR2B and inhibited phosphorylation of NR2B via CaMK II/CK2 pathway. Thus, our work suggests that AQP4 may be a promising molecular target for the development of antidepressant drugs.

Association of Depression, Antidepressants With Atrial Fibrillation Risk: A Systemic Review and Meta-Analysis.

Background: Depression is a possible influence factor for the increased risk of incident atrial fibrillation (AF). Although several investigations have assessed their association, the results are still controversial. Therefore, we conducted a meta-analysis to evaluate the association between depression or using antidepressants and AF. Methods: We systemically performed the literature retrieval from two electronic databases PubMed and EMBASE until March 2022 to extract relevant data. The hazard ratios (HRs) and odds ratios (OR) from included studies with 95% confidence intervals (CIs) were adjusted into the risk ratio (RR) and pooled by using the random-effects model. Results: Totally 9 studies about the associations between depression or antidepressants and incident AF risk were included in this meta-analysis. Among them, 5 studies specifically analyzed the impact of antidepressants on the risk of AF. The outcomes of our analysis indicated that depression or depressive symptoms could increase AF risk (RR = 1.15, 95% CI, 1.03-1.27, P < 0.01). In addition, the use of antidepressants can also increase AF risk (RR = 1.16, 95% CI, 1.07-1.25, P < 0.001). These results remained unchanged when we remove the source of heterogeneity or adjust the analysis model into the fixed-effects model. Conclusions: Based on existing investigations, both depression and the use of antidepressants are closely related to the increase of incident AF risk.

Seasonal changes in the recent decline of combined high PM2.5 and O3 pollution and associated chemical and meteorological drivers in the Beijing-Tianjin-Hebei region, China.

China suffers from combined air pollution (CAP) comprising dual high O3 and PM2.5, particularly in the Beijing-Tianjin-Hebei (BTH) region, which is an urban agglomeration in the North China Plain. To characterize the seasonal changes in regional CAP, 82 CAP days were identified during the study period from 2015 to 2019 with the co-occurring pollution of O3 and PM2.5 in the BTH. It is found that CAP seasonality has undergone distinct changes with a declining trend in the interannual variations in CAP over recent years. It is also revealed that the monthly CAP peaks have recently shifted from summer to early spring (March and April), indicating seasonal changes in CAP in the BTH. Furthermore, the of chemical and meteorological roles in CAP changes was investigated using environmental and meteorological observation data. The recent reduction in PM2.5 and O3 concentrations had enhanced O3 production and atmospheric oxidizability, thereby causing increments in secondary PM2.5 proportion. The interaction between O3 and PM2.5 was responsible for changing the CAP of dual high O3 and PM2.5 to the transition/spring season in the context of mitigation of air pollutant emissions. Furthermore, principal component analysis in the T-mode (T-PCA) was applied to identify four synoptic circulation patterns that regulate CAP occurrence. The results show that the CAP occurrence was regulated by the dominant patterns of synoptic circulation in the BTH. Warm temperature and strong downward ultraviolet radiation anomalies were observed in the BTH, indicating the importance of meteorological drivers in O3 photochemical production on the CAP. The frequency of key synoptic circulation patterns during the spring season increased annually, thereby inducing seasonal changes in the atmospheric environment with CAP in the BTH in recent years.