miR-21-5p Modulates Airway Inflammation and Epithelial-Mesenchymal Transition Processes in a Mouse Model of Combined Allergic Rhinitis and Asthma Syndrome.

INTRODUCTION: Combined allergic rhinitis and asthma syndrome (CARAS) is a concurrent allergic symptom of diseases of allergic rhinitis and asthma. However, the mechanism of CARAS remains unclear. The study aimed to investigate the impact of microRNA-21 (miR-21) on CARAS via targeting poly (ADP-ribose) polymerase-1 (PARP-1) and phosphoinositide 3-kinase (PI3K)/AKT pathways. METHODS: The levels of miR-21-5p and PARP-1 in CARAS patients were detected by quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). An ovalbumin-sensitized mouse model of CARAS was established. And knock down of miR-21-5p was constructed by intranasally administering with miR-21-5p shRNA-encoding adeno-associated virus vector. Airway resistance and airway inflammatory response were detected. ELISA was used to evaluate IL-4/IL-5/IL-13 levels in bronchoalveolar lavage fluid (BALF). Expression levels of E-cadherin, fibronectin, and α-SMA were determined using Western blotting. The levels of PARP-1 and the activation of PI3K/AKT were assayed. RESULTS: Downregulation of miR-21-5p relieved pathophysiological symptoms of asthma including airway hyperreactivity and inflammatory cell infiltration. Downregulation of miR-21-5p significantly reduced the levels of IL4, IL-5, and IL-13 in BALF. Additionally, downregulation of miR-21-5p inhibited the epithelial-mesenchymal transition (EMT) process in CARAS mice. Furthermore, miR-21-5p regulated PARP-1 and was involved in PI3K/AKT activation in CARAS mice. CONCLUSION: Downregulation of miR-21-5p ameliorated CARAS-associated lung injury by alleviating airway inflammation, inhibiting the EMT process, and regulating PARP-1/PI3K/AKT in a mouse model of CARAS.

Associations of perceived built environment characteristics using NEWS questionnaires with all-cause mortality and major cardiovascular diseases: The prospective urban rural epidemiology (PURE)-China study.

BACKGROUND: Despite increased literature focusing on the role of the built environment (BE) in health, few cohort studies have quantitatively analyzed neighborhood walkability environment in relation to the risk of death and cardiovascular disease (CVD). This longitudinal study aimed at evaluating the association between perceived BE attributeswith mortality and major CVD based on the Prospective Urban Rural Epidemiology study in China (PURE-China). METHODS: The PURE-China study recruited 47,931 participants aged 35-70 years from 12 provinces of China between 2005 and 2009. The perceived BE information, including land use, street, aesthetics, and safety, was collected using the neighborhood environment walkability scale (NEWS) questionnaire, with higher scores indicating a more favorable rating. Two primary outcomes are all-cause mortality and major CVD event. The Cox frailty model with random intercepts was used to assess the association between the perceived total BE/subscales score and outcomes. RESULTS: Of 32,163 participants included in this study, 19,253 (59.9 %) were women, and the mean (SD) age was 51.0 (9.5) years. After a median follow-up period of 11.7 years (IQR 9.4 - 12.2), we observed that one standard deviation higher of combined BE scores was related to a lower risk of all-cause mortality (HR = 0.85; 95 %CI, 0.80-0.90), and major CVD events (HR = 0.95; 95 %CI, 0.90-0.99). The subscales of perceived BE were related to a lower risk, although a few were not significant. Land use mix-diversity and safety from crime were the two most significant subscales. Stronger risks were observed among urban and female participants. CONCLUSION: Favorable perceived BE characteristics were linked with a lower risk of all-cause mortality and major CVD events in Chinese population, especially in urban areas and females. Our findings can be used by policymakers to take action to mitigate the adverse effect of poor community conditions on health, such as improving local amenities and transport connectivity, providing building paths for walking, running and cycling.

MiR-4454 in Combined Allergic Rhinitis and Asthma Syndrome (CARAS): Clinical significance and mechanistic insights into airway inflammation.

Abnormal expression of non-coding microRNA is associated with the development of combined allergic rhinitis and asthma syndrome (CARAS). However, the function of miR-4454 in CARAS is unknown. Our study aimed to reveal the clinical significance and related mechanism of miR-4454 in CARAS. Blood samples from 38 cases of CARAS and 43 cases of healthy subjects were collected to detect the expression of miR-4454. House dust mite (HDM) sensitization and challenge-induced bronchial epithelial cells to simulate the asthma state model in vitro, miR-4454 mimics and inhibitor transfection to detect the expression level of pro-inflammatory cytokines, cell survival rate and migration ability, flow cytometry and western blot (WB) Detection of cell cycle, apoptosis and inflammation-related protein levels. Compared with healthy controls, the expression of miR-4454 in the blood of CARAS patients was significantly up-regulated, and IL-6 and IL-8 were significantly up-regulated in the HDM treatment group, indicating that the model induction was successful. After overexpression of miR-4454, cell proliferation and migration in the HDM-treated group were significantly inhibited, and the levels of early apoptosis and inflammation-related proteins (IL-17, IL-17RD, TNF-α, GCSF and NF-κB) were increased High; after inhibiting miR-4454, cell proliferation and migration were significantly enhanced, and the levels of apoptosis and inflammation-related proteins were decreased. This study found that inhibiting the expression of miR-4454 can improve HDM-induced cell injury, which may be related to miR-4454 regulating the activation of IL-17/NF-кB inflammatory axis.

Elucidation of the Molecular Mechanism of Compound Danshen Dripping Pills Against Angina Pectoris based on Network Pharmacology and Molecular Docking.

BACKGROUND: Compound Danshen dripping pills (CDDP), a traditional Chinese medicine, has had an extensive application in the treatment of angina pectoris (AP) in China. However, research on the bioactive ingredients and underlying mechanisms of CDDP in AP remains unclear. OBJECTIVE: In the present study, we explored the major chemical components and potential molecular mechanisms linked to the anti-angina effects of CDDP through the application of network pharmacology and molecular docking. METHODS: The potential targets of active ingredients in CDDP were sourced from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and the Swiss Target Prediction Database (STPD). Additionally, targets related to angina pectoris (AP) were retrieved from various databases, including Gene Cards, DisGeNET, Dis Genet, the Drug Bank database (DBD), and the Therapeutic Target Database (TDD). Protein- protein interaction [1] networks were also established, and core targets were identified based on their topological significance. GO enrichment analysis and KEGG pathway analysis were conducted using the R software. Interactions between active ingredients and potential targets selected through the above process were investigated through molecular docking. RESULTS: Seventy-six active ingredients were selected with the following criteria: OB ≥ 30%, DL ≥ 0.18. 383 targets of CDDP and 1488 targets on AP were gathered, respectively. Afterwards, 194 common targets of CDDP and anti-AP targets were defined, of which 12 were core targets. GO enrichment analysis indicated that CDDP acted on AP by response to lipopolysaccharide, regulating the reactive oxygen species and metal ion metabolism, and epithelial cell proliferation. In addition, KEGG enrichment analysis indicated that the signaling pathways were notably enriched in lipid and atherosclerosis, fluid shear stress and atherosclerosis, IL-17 signaling pathway, EGFR tyrosine kinase inhibitor resistance, PI3K-Akt signaling pathway, and TNF signaling pathway. Moreover, the molecular docking manifested excellent binding capacity between the active ingredients and targets on AP. CONCLUSION: This study comprehensively illustrated the bioactive, potential targets, and molecular mechanisms of CDDP against AP, offering fresh perspectives into the molecular mechanisms of CDDP in preventing and treating AP.

Effects of TrPLDs on the pathogenicity of Trichothecium roseum infected apple fruit.

Phospholipase D plays a critical regulatory role in the pathogenicity of filamentous fungi. However, the molecular mechanism of PLD regulating the pathogenicity of filamentous fungi has not been reported. In this research, the previously constructed TrPLD1 and TrPLD2 (TrPLDs) mutants were used as test strains. Firstly, the function of TrPLDs in Trichothecium roseum was studied. Then, the effects of TrPLDs on the pathogenicity of T. roseum and the quality of the inoculated apples were verified. The results suggested that the deletion of TrPLD1 delayed the spore germination of ΔTrPLD1 and inhibited germ tube elongation by down-regulating the expressions of TrbrlA, TrabaA and TrwetA. By down-regulating the extracellular enzyme-coding gene expressions, ΔTrPLD1 inhibited the degradation of apple fruit cell wall and the change of fatty acid content during infection, reduced the cell membrane permeability and malondialdehyde (MDA) content of apple fruit, thereby maintaining the integrity of fruit cell membrane, and reduced the pathogenicity of ΔTrPLD1 to apple and kept the quality of apple. However, ΔTrPLD2 did not have a significant effect on the infection process of apple fruit by the pathogen.

Ozone Application Suppressed the Blue Mold Development and Maintained the Main Active Ingredients Content of Postharvest Fresh Codonopsis pilosula during Storage.

Penicillium expansum is the predominant causal agent causing blue mold in postharvest fresh Codonopsis pilosula during storage. The pathogen reduces the yield and affects the quality of C. pilosula and even generates patulin, threatening human health. In this study, postharvest fresh, healthy C. pilosula was sprayed with P. expansum, and the control effect of ozone on postharvest diseases of C. pilosula was studied, and the effect of ozone on the contents in the main active ingredients of C. pilosula was compared; finally, the effect of ozone on reactive oxygen species (ROS) metabolism in C. pilosula was analyzed. The results showed that 2 mg L-1 ozone application significantly inhibited the occurrence of postharvest blue mold caused by P. expansum, reduced weight loss rate, controlled the accumulation of patulin and maintained the contents of the main active components in C. pilosula. The study will provide a theoretical basis for ozone treatment to control the occurrence of postharvest diseases of C. pilosula.

Effects of straw returning combined with blended controlled-release urea fertilizer on crop yields, greenhouse gas emissions, and net ecosystem economic benefits: A nine-year field trial.

Although straw returning combined with blended controlled-release urea fertilizer (BUFS) has been shown to improve wheat-maize rotation system productivity, their effects on greenhouse gas (GHG) emissions, carbon footprints (CF), and net ecosystem economic benefits (NEEB) are still unknown. Life cycle assessment was used to investigate a long-term (2013-2022) wheat-maize rotation experiment that included straw combined with two N fertilizer types [BUFS and (conventional urea fertilizer) CUFS] and straw-free treatments (BUF and CUF). The results showed that BUFS and CUFS treatments increased the annual yield by 13.8% and 11.5%, respectively, compared to BUF and CUF treatments. The BUFS treatment increased the yearly yield by 13.8% compared to the CUFS treatment. Since BUFS and CUFS treatments increased soil organic carbon (SOC) sink sequestration by 25.0% and 27.0% compared to BUF and CUF treatments, they reduced annual GHG emissions by 7.1% and 4.7% and CF per unit of yield (CFY) by 13.7% and 9.6%, respectively. BUFS treatment also increased SOC sink sequestration by 20.3%, reduced GHG emissions by 10.7% and CFY by 23.0% compared to CUFS treatment. It is worth noting that the BUFS and CUFS treatments increased the annual ecological costs by 41.6%, 26.9%, and health costs by 70.1% and 46.7% compared to the BUF and CUF treatments, but also increased the net yield benefits by 9.8%, 6.8%, and the soil nutrient cycling values by 29.2%, 27.3%, and finally improved the NEEB by 10.1%, 7.3%, respectively. Similar results were obtained for the BUFS treatment compared to the CUFS treatment, ultimately improving the NEEB by 23.1%. Based on assessing yield, GHG emissions, CF, and NEEB indicators, the BUFS treatment is recommended as an ideal agricultural fertilization model to promote sustainable and clean production in the wheat-maize rotation system and to protect the agroecological environment.

LINC00158 modulates the function of BEAS-2B cells via targeting BCL11B and ameliorates OVA-LPS-induced severe asthma in mice models.

Persistent type (T) 2 airway inflammation plays an important role in the development of severe asthma. However, the molecular mechanisms leading to T2 severe asthma have yet to be fully clarified. Human normal lung epithelial cells (BEAS-2B cells) were transfected with LINC00158/BCL11B plasmid/small interfering RNA (siRNA). Levels of epithelial-mesenchymal transition (EMT)-related markers were measured using real-time qPCR (RT-qPCR) and western blot. A dual luciferase reporter assay was used to validate the targeting relationship between LINC00158 and BCL11B. The effects of LINC00158-lentivirus vector-mediated overexpression and dexamethasone on ovalbumin (OVA)/lipopolysaccharide (LPS)-induced severe asthma were investigated in mice in vivo. Our study showed that overexpression of LINC00158/BCL11B inhibited the levels of EMT-related proteins, apoptosis, and promoted the proliferation of BEAS-2B cells. BCL11B was a direct target of LINC00158. And LINC00158 targeted BCL11B to regulate EMT, apoptosis, and cell proliferation of BEAS-2B cells. Compared with severe asthma mice, LINC00158 overexpression alleviated OVA/LPS-induced airway hyperresponsiveness and airway inflammation, including reductions in T helper 2 cells factors in lung tissue and BALF, serum total- and OVA-specific IgE, inflammatory cell infiltration, and goblet cells hyperplasia. In addition, LINC00158 overexpression alleviated airway remodeling, including reduced plasma TGF-ß1 and collagen fiber deposition, as well as suppression of EMT. Additionally, overexpression of LINC00158 enhanced the therapeutic effect of dexamethasone in severe asthmatic mice models. LINC00158 regulates BEAS-2B cell biological function by targeting BCL11B. LINC00158 ameliorates T2 severe asthma in vivo and provides new insights into the clinical treatment of severe asthma.

ROS mediated by TrPLD3 of Trichothecium roseum participated cell membrane integrity of apple fruit by influencing phosphatidic acid metabolism.

Trichothecium roseum is a typical necrotrophic fungal pathogen that not only bring about postharvest disease, but contribute to trichothecenes contamination in fruit and vegetables. Phospholipase D (PLD), as an important membrane lipid degrading enzyme, can produce phosphatidic acid (PA) by hydrolyzing phosphatidylcholine (PC) and phosphatidylinositol (PI). PA can promote the production of reactive oxygen species (ROS) by activating the activity of NADPH oxidase (NOX), thereby increasing the pathogenicity to fruit. However, the ROS mediated by TrPLD3 how to influence T. roseum infection to fruit by modulating phosphatidic acid metabolism, which has not been reported. In this study, the knockout mutant and complement strain of TrPLD3 were constructed through homologous recombination, TrPLD3 was tested for its effect on the colony growth and pathogenicity of T. roseum. The experimental results showed that the knockout of TrPLD3 inhibited the colony growth of T. roseum, altered the mycelial morphology, completely inhibited the sporulation, and reduced the accumulation of T-2 toxin. Moreover, the knockout of TrPLD3 significantly decreased pathogenicity of T. roseum on apple fruit. Compared to inoculated apple fruit with the wide type (WT), the production of ROS in apple infected with ΔTrPLD3 was slowed down, the relative expression and enzymatic activity of NOX, and PA content decreased, and the enzymatic activity and gene expression of superoxide dismutase (SOD) increased. In addition, PLD, lipoxygenase (LOX) and lipase activities were considerably decreased in apple fruit infected with ΔTrPLD3, the changes of membrane lipid components were slowed down, the decrease of unsaturated fatty acid content was alleviated, and the accumulation of saturated fatty acid content was reduced, thereby maintaining the cell membrane integrity of the inoculated apple fruit. We speculated that the decreased PA accumulation in ΔTrPLD3-inoculated apple fruit further weakened the interaction between PA and NOX on fruit, resulting in the reduction of ROS accumulation of fruits, which decreased the damage to the cell membrane and maintained the cell membrane integrity, thus reducing the pathogenicity to apple. Therefore, TrPLD3-mediated ROS plays a critical regulatory role in reducing the pathogenicity of T. roseum on apple fruit by influencing phosphatidic acid metabolism.

Biodegradation of microplastics derived from controlled release fertilizer coating: Selective microbial colonization and metabolism in plastisphere.

Coated controlled-release fertilizers (CRFs) are widely used in agriculture, and the persistent presence of residual polymer coating has raised environmental concerns. This study investigates the underlying degradation dynamics of microplastics (MPs) derived from three typical materials used in CRFs, including polyethylene (PE), epoxy (EP), and polyurethane (PU), through a soil degradation test. The formation of surface biofilm, the succession process, and metabolic characteristics of microbial community are revealed by laser scanning confocal microscope, 16S rRNA sequencing, and non-targeted metabolomics analysis. The weight loss rates of PE, EP, and PU after 807 days of degradation were 16.70 %, 2.79 %, and 4.86 %, respectively. Significant secondary MPs were produced with tears and holes appeared in the coating cross sections and pyrolysis products were produced such as ethers, acids, and esters for PE; alkanes, olefins and their branched-chain derivatives for EP; and short-chain fatty acids and benzene molecules for PU. The coating surface selectively recruited the bacteria of Chujaibacter and Ralstonia and fungus of Fusarium and Penicillium, forming biofilm composed of lipids, proteins, and living cells. The metabolism of amino acids and polymers was enhanced to protect against MP-induced stress. The metabolites or intermediates of organic acids and derivatives, oxygen-contained organic compounds, and benzenoids on CRF surface increased significantly compared with soil, but there were no significant differences among different coating types. This study provides insights to the underlying mechanisms of biodegradation and microenvironmental changes of MPs in soil.

A Robust Framework for One-Shot Key Information Extraction via Deep Partial Graph Matching.

Text field labelling plays a key role in Key Information Extraction (KIE) from structured document images. However, existing methods ignore the field drift and outlier problems, which limit their performance and make them less robust. This paper casts the text field labelling problem into a partial graph matching problem and proposes an end-to-end trainable framework called Deep Partial Graph Matching (dPGM) for the one-shot KIE task. It represents each document as a graph and estimates the correspondence between text fields from different documents by maximizing the graph similarity of different documents. Our framework obtains a strict one-to-one correspondence by adopting a combinatorial solver module with an extra one-to-(at most)-one mapping constraint to do the exact graph matching, which leads to the robustness of the field drift problem and the outlier problem. Finally, a large one-shot KIE dataset named DKIE is collected and annotated to promote research of the KIE task. This dataset will be released to the research and industry communities. Extensive experiments on both the public and our new DKIE datasets show that our method can achieve state-of-the-art performance and is more robust than existing methods.

Application of metagenomic next-generation sequencing (mNGS) in diagnosing pneumonia of adults.

INTRODUCTION: Accurate identification of pathogens that cause pulmonary infections is essential for effective treatment and hastening recovery in adults diagnosed with pneumonia. At present, despite metagenomic next-generation sequencing (mNGS) technology has been widely used in clinical practice for pathogen identification, the clinical significance and necessity of detecting pathogen in bronchoalveolar lavage fluid (BALF) for pneumonia-stricken adults remain ambiguous. METHODOLOGY: In this study, 80 patients suffering from pulmonary infection were enrolled, who were admitted to the Affiliated Changzhou Second People's Hospital of Nanjing Medical University between January 2020 and September 2022. The diagnostic performances of mNGS and conventional methods (CM) were systematically analyzed based on BALF samples, and we further investigated the influence of mNGS and CM in diagnosis modification and treatment. RESULTS: We found a significantly higher positive rate for the mNGS method in contrast to CM. Bacteria were the most common pathogens, and Streptococcus pneumoniae was the most commonly identified pathogen. Candida albicans and Epstein-Barr virus were the most frequently identified fungus and virus. Atypical pathogens such as Mycobacterium tuberculosis, virus Nontuberculous mycobacteria, and Chlamydia psittaci were also identified. A total of 77 patients were identified with mixed infections by mNGS. As the disease progressed and recurrent antibiotic treatment persisted, significant dynamic changes in the clinical manifestation from the BALF samples could be found by mNGS. CONCLUSIONS: This study underscores the efficacy of mNGS in detecting pathogens in BALF samples from patients suffering pulmonary infections. Compared with the CM, mNGS significantly enhanced the positive diagnosis ratio, particularly in diagnosing Mycobacterium tuberculosis, atypical pathogens, and viral or fungal infections.

RNA Sequencing and Bioinformatics Analysis to Reveal Potential Biomarkers in Patients with Combined Allergic Rhinitis and Asthma Syndrome.

Introduction: Combined allergic rhinitis and asthma syndrome (CARAS) is a concurrent clinical or subclinical allergic symptom of diseases of the upper and lower respiratory tract. This study is the first to explore the expression profiles of mRNA, lncRNA, and circRNA in CARAS using RNA sequencing, which may provide insight into the mechanisms underlying CARAS. Material and Methods: Whole blood samples from nine participants (three CARAS patients, three AR patients, and three normal control participants) were subjected to perform RNA sequencing, followed by identification of differentially expressed lncRNAs (DElncRNAs), circRNAs (DEcircRNAs) and mRNAs (DEmRNAs). Then, lncRNA/circRNA-mRNA regulatory pairs were constructed, followed by functional analysis, immune infiltration analysis, drug prediction, and expression validation with RT-qPCR and ELISA. Results: The results showed that 61 DEmRNAs, 23 DElncRNAs and 3 DEcircRNAs may be related to the occurrence and development of CARAS. KRT8 may be implicated in the development of AR into CARAS. Three immunity-related mRNAs (IDO1, CYSLTR2, and TEC) and two hypoxia-related mRNAs (TKTL1 and VLDLR) were associated with the occurrence and development of CARAS. TEC may be considered a drug target for Dasatinib in treating CARAS. Several lncRNA/circRNA-mRNA regulatory pairs were identified in CARAS, including LINC00452/MIR4280HG/hsa_circ_0007272/hsa_circ_0070934-CLC, HEATR6-DT/LINC00639/LINC01783/hsa_circ_0008903-TEC, RP11-71L14.3-IDO1/SMPD3, RP11-178F10.2-IDO1/HRH4, and hsa_circ_0008903-CYSLTR2, which may indicate potential regulatory effects of lncRNAs/circRNAs in CARAS. Dysregulated levels of immune cell infiltration may be closely related to CARAS. Conclusion: The regulating effect of lncRNA/circRNA-immunity/hypoxia-related mRNA regulatory pairs may be involved in the occurrence and development of CARAS.

Socioeconomic disparity in mortality and the burden of cardiovascular disease: analysis of the Prospective Urban Rural Epidemiology (PURE)-China cohort study.

BACKGROUND: Although socioeconomic inequality in cardiovascular health has long been a public health focus, the differences in cardiovascular-disease burden and mortality between people with different socioeconomic statuses has yet to be adequately addressed. We aimed to assess the effects of socioeconomic status, measured via three socioeconomic-status indicators (ie, education, occupation, and household wealth and a composite socioeconomic-status disparity index, on mortality and cardiovascular-disease burden (ie, incidence, mortality, and admission to hospital) in China. METHODS: For this analysis, we used data from the Prospective Urban Rural Epidemiology (PURE)-China cohort study, which enrolled adults aged 35-70 years from 115 urban and rural areas in 12 provinces in China between Jan 1, 2005, and Dec 31, 2009. Final follow-up was on Aug 30, 2021. Indicators of socioeconomic status were education, occupation, and household wealth; these individual indicators were also used to create an integrated socioeconomic-status index via latent class analysis. Standard questionnaires administered by trained researchers were used to obtain baseline data and were supplemeted by physical measurements. The primary outcomes were all-cause mortality, cardiovascular-disease mortality, non-cardiovascular-disease mortality, major cardiovascular disease, and cardiovascular-disease admission to hospital. Hazard ratios (HRs) and average marginal effects were used to assess the association between the primary outcomes and socioeconomic status. FINDINGS: Of 47 931 participants enrolled in the PURE-China study, 47 278 (98·6%) had complete information on sex and follow-up. After excluding 1189 (2·5%) participants with missing data on education, household wealth, and occupation at baseline, 46 089 participants were included in this analysis. Median follow-up was 11·9 years (IQR 9·5-12·6); 26 860 (58·3%) of 46 089 participants were female and 19 229 (41·7%) were male. Having no or primary education, unskilled occupation, or being in the lowest third of household wealth was associated with a higher risk of all-cause mortality, cardiovascular-disease mortality, non-cardiovascular-disease mortality, major cardiovascular disease, and cardiovascular-disease admission to hospital compared with having higher education, a professional or managerial occupation, or more household wealth. After adjustment for confounders, people categorised as having low integrated socioeconomic status based on the index had a higher risk of all-cause mortality (HR 1·65 [95% CI 1·42-1·92]), cardiovascular-disease mortality (2·19 [1·68-2·85]), non-cardiovascular disease mortality (1·43 [1·18-1·72]), major cardiovascular disease (1·43 [1·27-1·61]) and cardiovascular-disease admission to hospital (1·14 [1·01-1·28]) compared with people categorised as having high integrated socioeconomic status. INTERPRETATION: Socioeconomic-status inequalities in mortality and cardiovascular-disease outcomes exist in China. Targeted policies of equal health-care resource allocation should be promoted to equitably benefit people with fewer years of education and less household wealth. FUNDING: Funding sources are listed at the end of the Article.

Isolation and Identification of Pathogens Causing Blue Mold of Lanzhou Lily during Postharvest Storage and Control of Disease and Mycotoxin Accumulation by Ozone Treatment.

Blue mold (penicilliosis) is a common disease of Lanzhou lily (Lilium davidii var. willmottiae) during postharvest storage, which not only seriously affects the appearance and reduces the quality of lily bulbs, but also leads to the accumulation of mycotoxins in rotten lily tissues, seriously endangering human health. Therefore, it is of great significance to clarify the main isolates causing postharvest blue mold of fresh Lanzhou lily and put forward effective measures to control the disease caused by these pathogens. In this study, pathogens were isolated and purified from the naturally diseased blue-mold tissue of Lanzhou lily, and then morphological and molecular biology techniques were applied to identify the isolates, verify the pathogenicity, determine the disease index and disease incidence, and finally, to analyze the control effect of ozone treatment on the blue mold of lily scale and mycotoxin accumulation. The results indicated that the main isolates causing postharvest blue mold of lily were Talaromyces adpressus, Penicillium gladioli, T. calidominioluteus, and P. polonicum. The pathogenicity test showed that P. gladioli and P. polonicum had a higher disease index than T. calidominioluteus and T. adpressus. Ozone treatment significantly reduced the incidence of disease caused by P. gladioli and P. polonicum, and effectively controlled the accumulation of patulin. This study characterized the main pathogens causing blue mold of postharvest Lanzhou lily during storage, and confirmed ozone application has a significant inhibitory effect on blue mold development and patulin accumulation in Lanzhou lily, which could be helpful in commercially controlling blue mold of postharvest Lanzhou lily during storage.

Hsa_circ_0043603 promotes the progression of esophageal squamous cell carcinoma by sponging miR-1178-3p and regulating AADAC expression.

This study aims to investigate the regulatory impact of hsa_circ_0043,603, a circular RNA, on the progression of esophageal squamous cell carcinoma (ESCC), which ranks as the sixth leading cause of global mortality. We evaluated the expression, origin, and localization of hsa_circ_0043,603 in ESCC tumors using qRT-PCR, bioinformatics, and FISH analysis. Functional studies were conducted by manipulating the hsa_circ_0043,603 expression in Eca109 cells through overexpression and silencing plasmids. Additionally, xenografts derived from circ_0043,603-overexpressing Eca109 cells enabled us to investigate tumor growth, proliferation, and apoptosis. Through Starbase analysis, we identified miR-1178-3p as a target of circ_0043,603, which was validated using RIP and luciferase assays. Furthermore, we predicted arylacetamide deacetylase (AADAC) as a target of miR-1178-3p and examined its expression in ESCC tissues using Western blot. Lastly, we performed AADAC silencing and overexpression in Eca109 cells to study their impact on cellular phenotypic features, apoptosis, and their interaction with miR-1178-3p mimics and inhibitors. The low expression of hsa_circ_0043,603 in ESCC tissue was associated with poor prognosis. Overexpression of hsa_circ_0043,603 inhibited ESCC growth, invasion, migration, and proliferation, while promoting apoptosis in vitro and suppressing tumor growth in vivo. hsa_circ_0043,603 achieved these effects by targeting the oncogenic miR-1178-3p. Furthermore, AADAC was identified as a target of miR-1178-3p, and its reduced expression was confirmed in ESCC tissues. Overexpression of AADAC in Eca109 cells resulted in suppressed cell growth, proliferation, migration, and invasion by regulating miR-1178-3p. hsa_circ_0043,603 acts as a sponge for miR-1178-3p, leading to the regulation of AADAC expression and inhibition of ESCC development. These results suggest the potential of hsa_circ_0043,603 as a therapeutic and diagnostic target for ESCC.

Household Air Pollution and Adult Lung Function Change, Respiratory Disease, and Mortality across Eleven Low- and Middle-Income Countries from the PURE Study.

BACKGROUND: Globally, household air pollution (HAP) is a major environmental hazard that affects respiratory health. However, few studies have examined associations between HAP and lung function decline and respiratory disease and mortality. METHODS: We used data from the Prospective Urban and Rural Epidemiology study and examined adults residing in 240 rural communities in 11 low- and middle-income countries where HAP from cooking with solid fuels is common. Spirometry was conducted for 28,574 individuals at baseline and 12,489 individuals during follow-up (mean of 8 y between spirometry measures). In cross-sectional analyses, we compared lung function measurements [forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio] in those who used solid fuels for cooking in comparison with clean fuels. Using repeated measurements of lung function, we examined the percent change in lung function measures per year, comparing individuals by baseline fuel type and individuals who used solid fuels at baseline but switched to clean fuels during follow-up. We also examined associations with prospective health events (any respiratory diseases, respiratory disease hospitalizations, and all-cause mortality). RESULTS: In adjusted cross-sectional models, use of solid fuel in comparison with clean fuels was associated with lower FEV1 of -17.5mL (95% CI: -32.7, -2.3) and FVC of -14.4mL (95% CI: -32.0, 3.2), but not FEV1/FVC. In longitudinal analyses, individuals who switched from solid fuels to clean cooking fuels during follow-up (n=3,901, 46% of those using solid fuel at baseline), showed no differences in the annual rate of change in FEV1 or FVC, but had small improvements in FEV1/FVC change (0.2% per year, 95% CI: 0.03, 0.3). Individuals who switched from solid to clean fuels had a decreased hazard ratio for respiratory events of 0.76 (95% CI: 0.57, 1.00) in comparison with persistent solid fuel users, which was not attenuated by lung function measures. CONCLUSION: We observed modest associations between HAP exposure and lung function, lung function change, and respiratory disease and mortality. https://doi.org/10.1289/EHP11179.

Noise-resilient deep learning for integrated circuit tomography.

X-ray tomography is a non-destructive imaging technique that reveals the interior of an object from its projections at different angles. Under sparse-view and low-photon sampling, regularization priors are required to retrieve a high-fidelity reconstruction. Recently, deep learning has been used in X-ray tomography. The prior learned from training data replaces the general-purpose priors in iterative algorithms, achieving high-quality reconstructions with a neural network. Previous studies typically assume the noise statistics of test data are acquired a priori from training data, leaving the network susceptible to a change in the noise characteristics under practical imaging conditions. In this work, we propose a noise-resilient deep-reconstruction algorithm and apply it to integrated circuit tomography. By training the network with regularized reconstructions from a conventional algorithm, the learned prior shows strong noise resilience without the need for additional training with noisy examples, and allows us to obtain acceptable reconstructions with fewer photons in test data. The advantages of our framework may further enable low-photon tomographic imaging where long acquisition times limit the ability to acquire a large training set.

CuO nanorod-decorated hemin-graphene with enhanced peroxidase-mimicking performance for the colorimetric and electrochemical determination of 4-aminophenol with a smartphone.

The detection of 4-aminophenol (4-AP) is of critical importance due to its high toxicity, and the development of accurate, sensitive, and portable methods for this purpose is essential. Here, a facile colorimetric and electrochemical dual-mode sensor based on a CuO nanorod-decorated hemin-functionalized graphene nanocomposite (CuO/H-Gr) is successfully constructed for the detection of 4-AP. CuO/H-Gr exhibited superior peroxidase-mimicking activity, catalyzing the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 and generating a colorimetric signal. The catalytic system was found to contain hydroxyl radicals, as revealed by reactive oxygen species trials. Meanwhile, TMB was found to be an electroactive indicator that could be oxidized on a glassy carbon electrode. In the presence of CuO/H-Gr and H2O2, an enhanced electrochemical signal of TMB was generated. Upon the addition of 4-AP, the catalytic performance of CuO/H-Gr in the oxidation of TMB was significantly reduced, leading to a decrease in colorimetric and electrochemical signals. Based on this, a dual-mode sensor for the detection of 4-AP was developed. The linear response ranges for colorimetric and electrochemical sensors are 1.00-200 µM and 0.0100-300 µM, with detection limits of 0.687 µM and 0.00756 µM, respectively. Real water samples were tested to estimate the feasibility of the dual-mode sensor, and the recoveries were found to be consistent with those obtained by high-performance liquid chromatography. In addition, a smartphone-based assay was used to evaluate the levels of 4-AP, which opened a new path for on-site detection.

Associations of outdoor fine particulate air pollution and cardiovascular disease: Results from the Prospective Urban and Rural Epidemiology Study in China (PURE-China).

BACKGROUND: Evidence on whether an excess risk of incidence and mortality of cardiovascular disease (CVD) among people exposed to a high level of ambient PM2.5 in low- and middle-income countries (LMICs) is lacking. This study aimed to investigate the associations between long-term exposure to ambient fine particulate matter<2.5 µm (PM2.5) concentrations and the risk of incidence and mortality of CVD in a large cohort study from 115 communities. METHODS: In this cohort study, we followed 42 160 adults aged 35-75 years at baseline who enrolled in the Prospective Urban and Rural Epidemiology Study conducted in China (PURE-China) between 2005 and 2009 with ambient PM2.5 estimates, and followed up until August 2021. Cox proportional hazards frailty models were used to estimate the associations between long-term mean outdoor PM2.5 concentrations and CVD events, CVD mortality, and all-cause mortality. FINDINGS: During a median follow-up period of 11.8 years, we documented 2 190 deaths, including 732 CVD deaths. There were 4 559 (10.8 %) of 42 160 participants who experienced incident total CVD, among them there were 861 myocardial infarctions (MI) and 2 338 S. The 3-year median concentration of ambient PM2.5 before the cohort commencement was 52.7 µg/m3 (interquartile range [IQR] 30.3-74.6). In full adjusted model, a 10 µg/m3 increase in PM2.5 was associated with a hazard ratio (HR) of 1.12 (95 % CI 1.11-1.14) for major CVD and 1.03 (95 % CI 1.01-1.05) for all-cause mortality. Besides, long-term PM2.5 concentrations had a significantly positive gradient association with total CVD and a similar pattern of associations with other CVD outcomes was observed. INTERPRETATION: This study demonstrated that long-term ambient PM2.5 concentrations is positively associated with increased risks of CVD in adults aged 35-70 years from China. This finding reinforces the need for policymakers to adopt more effective strategies to improve air quality.