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Abstract Here we retrieve global daily 1 km gapless PM2.5 concentrations via machine learning and big data, revealing its spatiotemporal variability at an exceptionally detailed level everywhere every day from 2017 to 2022, valuable for air quality monitoring, climate change, and public health studies. We find that 96%, 82%, and 53% of Earth’s populated areas are exposed to unhealthy air for at least one day, one week, and one month in 2022, respectively. Strong disparities in exposure risks and duration are exhibited between developed and developing countries, urban and rural areas, and different parts of cities. Wave-like dramatic changes in air quality are clearly seen around the world before, during, and after the COVID-19 lockdowns, as is the mortality burden linked to fluctuating air pollution events. Encouragingly, only approximately one-third of all countries return to pre-pandemic pollution levels. Many nature-induced air pollution episodes are also revealed, such as biomass burning.

Abstract Background Aberrant Wnt5a expression contributes to immunity, inflammation and tissue damage. However, it remains unknown whether Wnt5a is associated with liver injury in chronic hepatitis B virus (HBV) infection. We aimed to explore the potential role of Wnt5a expression in liver injury caused by chronic HBV infection. Methods Wnt5a mRNA levels in peripheral blood mononuclear cells (PBMCs) were analyzed in 31 acute-on-chronic hepatitis B liver failure (ACHBLF) patients, 82 chronic hepatitis B (CHB) patients, and 20 healthy controls using quantitative real-time polymerase chain reaction. Intrahepatic Wnt5a protein expression from 32 chronic HBV infection patients and 6 normal controls was evaluated by immunohistochemical staining. Results Wnt5a mRNA expression was increased in CHB patients and ACHBLF patients compared to healthy controls and correlated positively with liver injury markers. Additionally, there was a significant correlation between Wnt5a mRNA expression and HBV DNA load in all patients and CHB patients but not in ACHBLF patients. Furthermore, intrahepatic Wnt5a protein expression was elevated in chronic HBV infection patients compared to that in normal controls. Moreover, chronic HBV infection patients with higher hepatic inflammatory grades had increased intrahepatic Wnt5a protein expression compared with lower hepatic inflammatory grades. In addition, the cut-off value of 12.59 for Wnt5a mRNA level was a strong indicator in predicting ACHBLF in CHB patients. Conclusions We found that Wnt5a expression was associated with liver injury in chronic HBV infection patients. Wnt5a might be involved in exacerbation of chronic HBV infection.

Neurofibromatosis type 2 is an autosomal dominant multiple neoplasia syndrome and is usually caused by mutations in the neurofibromin 2 (NF2) gene, which encodes a tumor suppressor and initiates the Hippo pathway. However, the mechanism by which NF2 functions in the Hippo pathway isn't fully understood. Here we identified a NF2 c.770-784del mutation from a neurofibromatosis type 2 family. MD simulations showed that this mutation significantly changed the structure of the F3 module of the NF2-FERM domain. Functional assays indicated that the NF2 c.770-784del variant formed LLPS in the cytoplasm with LATS to restrain LATS plasma membrane localization and inactivated the Hippo pathway. Besides, this deletion partly caused a skipping of exon 8 and reduced the protein level of NF2, collectively promoting proliferation and tumorigenesis of meningeal cells. We identified an unrecognized mechanism of LLPS and splicing skipping for the NF2-induced Hippo pathway, which provided new insight into the pathogenesis of neurofibromatosis type 2.

AbstractFruit colour is a crucial factor influencing both the marketability and quality of pepper (Capsicum annuum), particularly ornamental varieties. Fruit colour is a complex multigenic trait in plant species. Previously, the Arabidopsis pseudo-response regulator 2 (APRR2) gene, one of the regulators that control fruit chlorophyll content and chloroplast development, thereby influencing fruit colour at the green immature stage in tomato (Solanum lycopersicum), cucumber (Cucumis sativus) and pepper, was reported. Functional molecular markers associated with this homologous gene in pepper could be employed to discern fruit colour at the seedling stage, thus improving the efficiency of green/white-fruited pepper breeding. In this study, a derived cleaved amplified polymorphic sequences (dCAPS) marker was developed based on the mutation site in the sequence of a CaAPRR2-like gene that was cloned from the inbred line B1-2, which exhibits milky white fruit at the green immature stage. The marker was subsequently validated in a CaAPRR2-like progeny segregation population. After digestion with the restriction endonuclease TaqI, the amplification product exhibited evident polymorphic bands, enabling it to distinguish between peppers with milky white and green fruit colours. The developed molecular marker displayed remarkable stability and repeatability, thus offering a straightforward and effective tool for enhancing fruit colour in pepper breeding programs.

Dissociative neurological symptoms disorder (DNSD), or conversion disorder, frequently manifests with unexplained neurological symptoms, necessitating referral to psychiatry following preliminary diagnosis in neurology. We present a case of an adolescent female patient with gait disturbance as the predominant clinical presentation, and delve into the diagnosis and interdisciplinary intervention process. Given neuroimaging deviations detected and familial similar presentations, the organic etiology was confirmed. However, the aberrant gait remained unexplained ultimately prompting psychiatric consultation resulting in the diagnosis of DNSD. Interventions consisting of health education, suggestive therapy, and physiotherapy notably improved gait disturbance. However, at follow-up, the patient presented with a depressive episode. It was deduced that undiagnosed psychosocial factors, notably familial dynamics, likely contributed to this decline. Eventually, transformed relation patterns among family members as well as antidepressant treatment were instrumental in attaining symptom remission.

Abstract Perovskite films with large crystal size, preferred orientation, and facile fabrication process, combining advantages of single‐crystal and polycrystalline films, have gained considerable attention recently. However, there is little research on the facet properties of perovskite films. Here, (111)‐ and (001)‐oriented perovskite films with bandgaps ranging from 1.53 to 1.77 eV, and systematically investigated their orientation‐dependent properties are achieved. The (111)‐oriented films show electron‐dominated traps and the (001)‐oriented films show hole‐dominated traps, which are related to their atomic arrangement at the surface. Compared with the (001)‐oriented films, the (111)‐oriented films exhibit lower work function and superior water/oxygen robustness. For the wide‐bandgap films, the lattice of the (001)‐oriented film provides an unobstructed passage for ion migration. Comparably, the (111)‐oriented films exhibit suppressed ion migration and excellent phase stability. The optimized unencapsulated solar cells based on both (001) and (111) orientations show a similar high efficiency of ≈23%. The (111)‐oriented solar cell exhibits excellent stability, maintaining 95% of its initial efficiency after 1500 h maximum power point (MPP) tracking test, and 97% initial efficiency after 3000 h aging in ambient conditions. This work paves the way for the rational design, controllable synthesis, and targeted optimization of uniaxial‐oriented perovskite films for various electronic applications.

Background The health effects of particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5) might differ depending on compositional variations. Little is known about the joint effect of PM2.5 constituents on metabolic syndrome and cardiovascular disease (CVD). This study aims to evaluate the combined associations of PM2.5 components with CVD, identify the most detrimental constituent, and further quantify the mediation effect of metabolic syndrome. Methods and Results A total of 14 427 adults were included in a cohort study in Sichuan, China, and were followed to obtain the diagnosis of CVD until 2021. Metabolic syndrome was defined by the simultaneous occurrence of multiple metabolic disorders measured at baseline. The concentrations of PM2.5 chemical constituents within a 1‐km2 grid were derived based on satellite‐ and ground‐based detection methods. Cox proportional hazard models showed that black carbon, organic matter (OM), nitrate, ammonium, chloride, and sulfate were positively associated with CVD risks, with hazard ratios (HRs) ranging from 1.24 to 2.11 (all P

Background This study examines the association between traditional cardiovascular health (CVH) metrics and major adverse cardiovascular events (MACE) incidence in individuals with diverse sleep patterns. Methods and Results We analyzed data from 208 621 participants initially free of cardiovascular disease (CVD) in the UK Biobank study. Sleep patterns were assessed using scores for chronotype, duration, insomnia, snoring, and daytime dozing. Traditional CVH scores were derived from the Life's Simple 7 metrics. Cox proportional hazards multivariate regression assessed associations between distinct combinations of CVH and sleep scores and MACE, including nonfatal myocardial infarction, nonfatal stroke, and CVD mortality. Over a mean follow‐up of 12.73 years, 9253 participants experienced incident MACE. Individuals with both a healthy sleep pattern and ideal CVH levels had the lowest MACE risk compared with those with a poor sleep pattern and poor CVH levels (hazard ratio, 0.306 [95% CI, 0.257–0.365]; P

This study uses integrated behavioral model as the guiding framework to examine the role of general and specific environmental education in promoting household pro-environmental behavior. The data collected from a convenience sample of 213 household representatives using self-administered questionnaires were analyzed using OLS and quantile regressions. The results show that specific knowledge, intention, and salience of behavior have positive effects on pro-environmental behavior, while environmental constraints have negative effects. The effects vary across different quantiles of pro-environmental behavior, which imply that different emphasis and strategies should be placed based on different levels of pro-environmental behavior to encourage such behavior. The result of the joint effect of general and specific environmental knowledge shows that specific knowledge is a significant factor of pro-environmental behavior, but not general environmental knowledge. Intention becomes more important in encouraging pro-environmental behavior as the gap between general and specific environmental knowledge widens. The overall result suggests that different strategies should be designed and implemented based on different levels of behavior in encouraging household pro-environmental behavior, especially for those with low-level of pro-environmental behavior but with high intention as they require improved specific environmental knowledge and skills, support and facilities, and recognition of their pro-environmental behavior.

Abstract Background Severe myocarditis is often accompanied by cardiac fibrosis, but the underlying mechanism has not been fully elucidated. CXCL4 is a chemokine that has been reported to have pro‐inflammatory and profibrotic functions. The exact role of CXCL4 in cardiac fibrosis remains unclear. Methods Viral myocarditis (VMC) models were induced by intraperitoneal injection of Coxsackie B Type 3 (CVB3). In vivo, CVB3 (100 TCID50) and CVB3‐AMG487 (CVB3: 100 TCID50; AMG487: 5 mg/kg) combination were administered in the VMC and VMC+AMG487 groups, respectively. Hematoxylin and eosin staining, severity score, Masson staining, and immunofluorescence staining were performed to measure myocardial morphology in VMC. Enzyme‐linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT‐PCR) were performed to quantify inflammatory factors (IL‐1β, IL‐6, TNF‐α, and CXCL4). Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase‐myocardial band (CK‐MB) levels were analyzed by commercial kits. CXCL4, CXCR3B, α‐SMA, TGF‐β1, Collagen I, and Collagen III were determined by Western blot and immunofluorescence staining. Results In vivo, CVB3‐AMG487 reduced cardiac injury, α‐SMA, Collagen I and Collagen III levels, and collagen deposition in VMC+AMG487 group. Additionally, compared with VMC group, VMC+AMG group decreased the levels of inflammatory factors (IL‐1β, IL‐6, and TNF‐α). In vitro, CXCL4/CXCR3B axis activation TGF‐β1/Smad2/3 pathway promote mice cardiac fibroblasts differentiation. Conclusion CXCL4 acts as a profibrotic factor in TGF‐β1/Smad2/3 pathway‐induced cardiac fibroblast activation and ECM synthesis, and eventually progresses to cardiac fibrosis. Therefore, our findings revealed the role of CXCL4 in VMC and unveiled its underlying mechanism. CXCL4 appears to be a potential target for the treatment of VMC.

This review highlighted the pivotal role of zyxin, an essential cell focal adhesions protein, in cellular biology and various diseases. Zyxin can orchestrate the restructuring and dynamic alterations of the cellular cytoskeleton, which is involved in cell proliferation, adhesion, motility, and gene transcription. Aberrant zyxin expression is closely correlated with tumor cell activity and cardiac function in both tumorigenesis and cardiovascular diseases. Moreover, in fibrotic and inflammatory conditions, zyxin can modulate cellular functions and inflammatory responses. Therefore, a comprehensive understanding of zyxin is crucial for deciphering signal transduction networks and disease pathogenesis. Investigating its role in diseases holds promise for novel avenues in early diagnosis and therapeutic strategies. Nevertheless, targeting zyxin as a therapeutic focal point presents challenges in terms of specificity, safety, drug delivery, and resistance. Nonetheless, in-depth studies on zyxin and the application of precision medicine could offer new possibilities for personalized treatment modalities.

Alexithymia is common among patients with generalized anxiety disorder (GAD) and may negatively affect the efficacy of treatment. This case report described a sole short-term psychotherapy focusing on alexithymia for a GAD patient. The intervention extends over 3 weekly 50-minute sessions and incorporates components of: (a) understanding the basic categories of emotions and the importance of processing them consciously and building one’s own vocabulary of emotions; (b) developing skills in identifying and labeling emotions and learning to register both positive and negative emotions in daily life; (c) observing and interpreting emotion-related body sensations and learning to get in touch with, be empathetic to, and take care of one’s own inner feelings in daily life. The Hamilton Rating Scale for Depression (HRSD), Hamilton Anxiety Rating Scale (HAMA), and Toronto Alexithymia Scale (TAS) were used to evaluate depression, anxiety, and alexithymia before and after the sessions. The results suggested that the treatment was not only effective in reducing alexithymia helping the patient to clarify, identify and describe her feelings, but also effective in reducing anxiety and depression.

ObjectiveEvidence regarding the effects of particulate matter (PM) pollutants on cardiovascular disease (CVD) mortality remains limited in Shanghai, China. Our objective was to thoroughly evaluate associations between PM pollutants and CVD mortality.MethodsDaily data on CVD mortality, PM (PM10 and PM2.5) pollutants, and meteorological variables in Shanghai, China were gathered from 2003 to 2020. We utilized a time-series design with the generalized additive model to assess associations between PM pollutants and CVD mortality. Additionally, we conducted stratified analyses based on sex, age, education, and seasons using the same model.ResultsWe found that PM pollutants had a significant association with CVD mortality during the study period. Specifically, there was a 0.29% (95%CI: 0.14, 0.44) increase in CVD mortality for every 10 μg/m3 rise in a 2-day average (lag01) concentration of PM10. A 0.28% (95% CI: 0.07, 0.49) increase in CVD mortality was associated with every 10 μg/m3 rise in PM2.5 concentration at lag01. Overall, the estimated effects of PM10 and PM2.5 were larger in the warm period compared with the cold period. Furthermore, males and the older adult exhibited greater susceptibility to PM10 and PM2.5 exposure, and individuals with lower education levels experienced more significant effects from PM10 and PM2.5 than those with higher education levels.ConclusionOur findings suggested that PM pollutants have a substantial impact on increasing CVD mortality in Shanghai, China. Moreover, the impacts of air pollution on health may be altered by factors such as season, sex, age, and educational levels.

Background: Studies have shown that short- and long-term exposure to particulate matter (PM) can increase the risk of asthma morbidity and mortality. However, the effect of medium-term exposure remains unknown. We aim to examine the effect of medium-term exposure to size-fractioned PM on asthma exacerbations among asthmatics with poor medication adherence. Methods: We conducted a longitudinal study in China based on the National Mobile Asthma Management System Project that specifically and routinely followed asthma exacerbations in asthmatics with poor medication adherence from April 2017 to May 2019. High-resolution satellite remote-sensing data were used to estimate each participant's medium-term exposure (on average 90 days) to size-fractioned PM (PM1, PM2.5, and PM10) based on the residential address and the date of the follow-up when asthma exacerbations (e.g., hospitalizations and emergency room visits) occurred or the end of the follow-up. The Cox proportional hazards model was employed to examine the hazard ratio of asthma exacerbations associated with each PM after controlling for sex, age, BMI, education level, geographic region, and temperature. Results: Modelling results revealed nonlinear exposure-response associations of asthma exacerbations with medium-term exposure to PM1, PM2.5, and PM10. Specifically, for emergency room visits, we found an increased hazard ratio for PM1 above 22.8 µg/m3 (1.060, 95 % CI: 1.025–1.096, per 1 µg/m3 increase), PM2.5 above 38.2 µg/m3 (1.032, 95 % CI: 1.010–1.054), and PM10 above 78.6 µg/m3 (1.019, 95 % CI: 1.006–1.032). For hospitalizations, we also found an increased hazard ratio for PM1 above 20.3 µg/m3 (1.055, 95 % CI: 1.001–1.111) and PM2.5 above 39.2 µg/m3 (1.038, 95 % CI: 1.003–1.074). Furthermore, the effects of PM were greater for a longer exposure window (90–180 days) and among participants with a high BMI. Conclusion: This study suggests that medium-term exposure to PM is associated with an increased risk of asthma exacerbations in asthmatics with poor medication adherence, with a higher risk from smaller PM.

Plastic pollution is a common concern of global environmental pollution. Polystyrene (PS) and polyethylene (PE) account for almost one-third of global plastic production. However, so far, there have been few reports on microbial strains capable of simultaneously degrading PS and PE. In this study, Microbacterium esteraromaticum SW3, a non-pathogenic microorganism that can use PS or PE as the only carbon source in the mineral salt medium (MM), was isolated from plastics-contaminated soil and identified. The optimal growth conditions for SW3 in MM were 2% (w/v) PS or 2% (w/v) PE, 35°C and pH 6.3. A large number of bacteria and obvious damaged areas were observed on the surface of PS and PE products after inoculated with SW3 for 21 d. The degradation rates of PS and PE by SW3 (21d) were 13.17% and 5.39%, respectively. Manganese peroxidase and lipase were involved in PS and PE degradation by SW3. Through Fourier infrared spectroscopy detection, different functional groups such as carbonyl, hydroxyl and amidogen groups were produced during the degradation of PS and PE by SW3. Moreover, PS and PE were degraded into alkanes, ketones, carboxylic acids, esters and so on detected by GC-MS. Collectively, we have isolated and identified SW3, which can use PS or PE as the only carbon source in MM as well as degrade PS and PE products. This study not only provides a competitive candidate strain with broad biodegradability for the biodegradation of PS and/or PE pollution, but also provides new insights for the study of plastic biodegradation pathways.

Evidence of the potential causal links between long-term exposure to particulate matters (PM, i.e., PM1, PM2.5, and PM1–2.5) and T2DM mortality based on large cohorts is limited. In contrast, the existing evidence usually suffers from inherent bias with the traditional association assessment.A prospective cohort of 580,757 participants in the southern region of China were recruited during 2009 and 2015 and followed up through December 2020. PM exposure at each residential address was estimated by linking to the well-established high-resolution simulation dataset. Hazard ratios (HRs) were calculated using time-varying marginal structural Cox models, an established causal inference approach, after adjusting for potential confounders.During follow-up, a total of 717 subjects died from T2DM. For every 1 μg/m3 increase in PM2.5, the adjusted HRs and 95% confidence interval (CI) for T2DM mortality was 1.036 (1.019–1.053). Similarly, for every 1 μg/m3 increase in PM1 and PM1–2.5, the adjusted HRs and 95% CIs were 1.032 (1.003–1.062) and 1.085 (1.054–1.116), respectively. Additionally, we observed a generally more pronounced impact among individuals with lower levels of education or lower residential greenness which as measured by the Normalized Difference Vegetation Index (NDVI). We identified substantial interactions between NDVI and PM1 (P-interaction = 0.003), NDVI and PM2.5 (P-interaction = 0.019), as well as education levels and PM1 (P-interaction = 0.049).The study emphasizes the need to consider environmental and socio-economic factors in strategies to reduce T2DM mortality. We found that PM1, PM2.5, and PM1–2.5 heighten the peril of T2DM mortality, with education and green space exposure roles in modifying it.

IntroductionEarly detection of neuropsychiatric systemic lupus erythematosus (NPSLE) remains a challenge in clinical settings. Previous studies have found different autoantibodies as markers for NPSLE. This study aimed to describe the distribution of psychiatric syndromes in a group of patients with systemic lupus erythematosus (SLE) and to investigate the association between psychiatric syndromes and specific autoantibodies.MethodsThis retrospective study was conducted at a single medical center in China. We reviewed medical records of hospitalized patients with SLE who were consulted by psychiatrists due to potential mental disorders. Results of serum autoantibodies and general laboratory tests were collected. The correlation between clinical variables was examined. Binary logistic regression analyses were used to determine factors related to NPSLE and different psychiatric diagnoses.ResultsAmong the 171 psychiatric manifestations in 160 patients, 141 (82.4%) were attributed to SLE. Acute confusional state (ACS) had the highest prevalence (57.4%). Anti-cardiolipin (ACL) antibody (X2 = 142.261, p < 0.001) and anti-β2 glycoprotein I (-β2GP1) antibody (X2 = 139.818, p < 0.001) varied significantly between groups, with the highest positive rate found in patients with mood disorders (27.3% and 18.2%). SLE disease activity index – 2000 (SLEDAI-2K) score excluding item ACS and item psychosis was a predictor of NPSLE (OR 1.172 [95% CI 1.105 - 1.243]).ConclusionsDisease activity reflected by SLEDAI-2K score is a predictor for NPSLE. Antiphospholipid antibodies are associated with mood disorders in SLE. Further separate investigation of neuropsychiatric disorders is needed in order to better comprehend NPSLE’s pathological mechanism.

Introduction:Diabetic kidney disease (DKD) necessitates innovative therapeutic strategies. This study delves into the role of DNA damage-inducing transcription factor 4 (DDIT4) within the VDR-mTOR pathway, aiming to identify a novel target for DKD drug discovery.Methods:Transcriptome data from the Gene Expression Omnibus Database were analyzed to assess the expression of mTOR and VDR expression in human renal tissues. Clinical samples from DKD patients and minimal change disease (MCD) controls were examined, and a DKD animal model using 20-week-old db/db mice was established. DDIT4 plasmid transfection was employed to modulate the VDR-mTOR pathway, with its components evaluated using immunohistochemistry, real-time quantitative PCR (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA).Results:Changes in the expression of the VDR-mTOR pathway were observed in both DKD patients and the animal model. Overexpression of DDIT4 increased VDR expression and decreased levels of mTOR, p70s6k, and 4E-BP1. Furthermore, DDIT4 treatment regulated autophagy by upregulating LC3I expression and downregulating LC3II expression. Notably, DDIT4 alleviated oxidative stress by reducing the levels of lipid peroxidation product MDA, while simultaneously increasing the levels of superoxide dismutase (SOD) and glutathione (GSH), underscoring the role of DDIT4 in the pathological process of DKD and its potential as a therapeutic target.Conclusion:Unraveling DDIT4’s involvement in the VDR-mTOR pathway provides insights for innovative DKD drug discovery, emphasizing its potential as a therapeutic target for future interventions.

Nitrogen fertilizer supports agricultural intensification, but its manufacturing results in substantial contaminated sites. Ammonia nitrogen is the main specific pollutant in retired nitrogen fertilizer sites with potential human health and odor risks. However, few studies focus on ammonia nitrogen risk assessment at contaminated sites, particularly considering its solid-liquid partitioning process (Kd) and ammonium/ammonia equilibrium process (R) in the soil. This study took a closed nitrogen fertilizer factory site as an example and innovatively introduced Kd and R to scientifically assess the human health and odor risk of ammonia nitrogen. The risk control values (RCVs) of ammonia nitrogen based on human health and odor risk were also derived. The maximum concentration of ammonia nitrogen was 3380 mg/kg in the unsaturated soil, which was acceptable for human health because the health RCVs were 5589 ∼ 137,471 mg/kg in various scenarios. However, odor risk was unacceptable for RCVs were 296 ∼ 1111 mg/kg under excavation scenarios and 1118 ∼ 35,979 mg/kg under non-excavation scenarios. Of particular concern, introducing Kd and R in calculation increased the human health and odor RCVs by up to 27.92 times. Despite the advancements in ammonia risk assessment due to the introduction of Kd and R, odor risk during excavation remains a vital issue. These findings inform a more scientific assessment of soil ammonia risk at contaminated sites and provide valuable insights for the management and redevelopment of abandoned nitrogen fertilizer plant sites.