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BACKGROUND: Streptococcus suis is an important zoonotic pathogen. Biofilm formation largely explains the difficulty in preventing and controlling S. suis. However, little is known about the molecular mechanism of S. suis biofilm formation. RESULTS: In this study, transcriptomic and metabolomic analyses of S. suis in biofilm and planktonic states were performed to identify key genes and metabolites involved in biofilm formation. A total of 789 differential genes and 365 differential metabolites were identified. By integrating transcriptomics and metabolomics, five main metabolic pathways were identified, including amino acid pathway, nucleotide metabolism pathway, carbon metabolism pathway, vitamin and cofactor metabolism pathway, and aminoacyl-tRNA biosynthesis metabolic pathway. CONCLUSIONS: These results provide new insights for exploring the molecular mechanism of S. suis biofilm formation.
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Biofilmes , Metabolômica , Streptococcus suis , Streptococcus suis/genética , Streptococcus suis/metabolismo , Biofilmes/crescimento & desenvolvimento , Redes e Vias Metabólicas/genética , Transcriptoma , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Metaboloma , MultiômicaRESUMO
Background: Rujin Jiedu decoction (RJJDD) is a classical prescription of Traditional Chinese Medicine that has long been applied to treat pneumonia caused by external infection, but whether and how it benefits influenza virus therapy remains largely unclear. The aim of this study was to investigate the anti-inflammatory effect of RJJDD on the mouse model of influenza and to explore its potential mechanism. Methods: The mice were mock-infected with PBS or infected with PR8 virus followed by treatment with RJJDD or antiviral oseltamivir. The weight loss and morbidity of mice were monitored daily. Network pharmacology is used to explore the potential pathways that RJJDD may modulate. qRT-PCR and ELISA were performed to assess the expression of inflammatory cytokines in the lung tissue and macrophages. The intestinal feces were collected for 16S rDNA sequencing to assess the changes in gut microbiota. Results: We demonstrate that RJJDD protects against IAV-induced pneumonia. Comprehensive network pharmacology analyses of the Mass Spec-identified components of RJJDD suggest that RJJDD may act through down-regulating key signaling pathways producing inflammatory cytokines, which was experimentally confirmed by cytokine expression analysis in IAV-infected mouse lung tissues and IAV single-strand RNA mimic R837-induced macrophages. Furthermore, gut microbiota analysis indicates that RJJDD prevented IAV-induced dysbiosis of host intestinal flora, thereby offering a mechanistic explanation for RJJDD's efficacy in influenza pneumonia. Conclusion: This study defines a previously uncharacterized role for RJJDD in protecting against influenza likely by maintaining homeostasis of gut microbiota, and provides a new therapeutic option for severe influenza.
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Endothelial cells (ECs) rely on glycolysis for energy production to maintain vascular homeostasis and the normalization of hyperglycolysis in tumor vessels has recently gained attention as a therapeutic target. We analyzed the TCGA database and found reduced Foxp1 expression in lung carcinoma. Immunostaining demonstrated reduced expression more restricted at tumor vascular ECs. Therefore, we investigated the function and mechanisms of Foxp1 in EC metabolism for tumor angiogenesis required for tumor growth. EC-Foxp1 deletion mice exhibited a significant increase of tumor and retinal developmental angiogenesis and Hif1α was identified as Foxp1 target gene, and Hk2 as Hif1α target gene. The Foxp1-Hif1α-Hk2 pathway in ECs is important in the regulation of glycolytic metabolism to govern tumor angiogenesis. Finally, we used genetic deletion of EC-Hif1α and RGD-peptide nanoparticles EC target delivery of Hif1α/Hk2-siRNAs to knockdown gene expression which reduced the tumor EC hyperglycolysis state and restricted angiogenesis for tumor growth. This study advances our understanding of EC metabolism for tumor angiogenesis, and meanwhile provides evidence for future therapeutic intervention of hyperglycolysis in tumor ECs for suppression of tumor growth.
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Streptococcus suis is one of the major pathogens of pigs circulating worldwide, and the development of vaccines will help to effectively control streptococcosis in swine. In this study, we evaluated the potential of three membrane associated proteins, histidine kinase (HK), glycosyltransferase family 2 (Gtf-2) and phosphate binding protein (PsbP) of S. suis as subunit vaccines. Bioinformatics analysis shows that protein ABC is highly conserved in S. suis. To verify the protective effects of these proteins in animal models, recombinant protein HK, Gtf-2 and PsbP were used to immunize BALB/c mice separately. The results showed that these proteins immunization in mice can effectively induce strong humoral immune responses, protect mice from cytokine storms caused by S. suis infection, and have a significant protective effect against lethal doses of S. suis infection. Furthermore, antibodies with opsonic activity exist in the recombinant proteins antiserum to assist phagocytic cells in killing S. suis. Overall, these results indicated that these recombinant proteins all elicit good immune protective effect against S. suis infection and can be represent promising candidate antigens for subunit vaccines against S. suis.
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Anticorpos Antibacterianos , Proteínas de Bactérias , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Proteínas Recombinantes , Infecções Estreptocócicas , Vacinas Estreptocócicas , Streptococcus suis , Vacinas de Subunidades Antigênicas , Streptococcus suis/imunologia , Streptococcus suis/genética , Animais , Infecções Estreptocócicas/prevenção & controle , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Camundongos , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/genética , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/genética , Vacinas Estreptocócicas/imunologia , Vacinas Estreptocócicas/administração & dosagem , Vacinas Estreptocócicas/genética , Sorogrupo , Citocinas/metabolismo , Feminino , Proteínas de Membrana/imunologia , Proteínas de Membrana/genética , Imunidade Humoral , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/genética , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/imunologia , Doenças dos Suínos/microbiologia , Suínos , Biologia ComputacionalRESUMO
To address the limitations of the CRISPR/Cas12f1 system in clinical diagnostics, which require the complex preparation of single-stranded DNA (ssDNA) or in vitro transcripts (RNA), we developed a fluorescent biosensor named PDTCTR (PAM-dependent dsDNA Target-activated Cas12f1 Trans Reporter). This innovative biosensor integrates Recombinase Polymerase Amplification (RPA) with the Cas12f_ge4.1 system, facilitating the direct detection of double-stranded DNA (dsDNA). PDTCTR represents a significant leap forward, exhibiting a detection sensitivity that is a hundredfold greater than the original Cas12f1 system. It demonstrates the capability to detect Mycoplasma pneumoniae (M. pneumoniae) and Hepatitis B virus (HBV) with excellent sensitivity of 10 copies per microliter (16.8 aM) and distinguishes single nucleotide variations (SNVs) with high precision, including the EGFR (L858R) mutations prevalent in non-small cell lung cancer (NSCLC). Clinical evaluations of PDTCTR have demonstrated its high sensitivity and specificity, with rates ranging from 93%-100% and 100%, respectively, highlighting its potential to revolutionize diagnostic approaches for infectious diseases and cancer-related SNVs.This research underscores the substantial advancements in CRISPR technology for clinical diagnostics and its promising future in early disease detection and personalized medicine.
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Técnicas Biossensoriais , Sistemas CRISPR-Cas , RNA Guia de Sistemas CRISPR-Cas , Técnicas Biossensoriais/métodos , Humanos , RNA Guia de Sistemas CRISPR-Cas/genética , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , DNA/genética , DNA/química , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/isolamento & purificação , Proteínas Associadas a CRISPR/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/química , Pneumonia por Mycoplasma/diagnósticoRESUMO
Bordetella bronchiseptica is a significant contributor to respiratory disease in pigs, leading to substantial economic losses in the swine industry worldwide. We isolated 52 B. bronchiseptica strains from 542 samples collected from pigs with atrophic rhinitis and bronchopneumonia in central China. Multi-locus sequence typing identified two prevalent sequence types: ST6 (69.23%) and ST7 (30.77%). PCR-based detection of seven virulence genes (fhaB, prn, cyaA, dnt, bteA, fla, and bfrZ) revealed that six of these genes were present in over 90% of the isolates, with bfrZ being the exception at 59.62%. Antimicrobial susceptibility testing, performed using the K-B method, demonstrated high sensitivity to enrofloxacin, polymyxin, and doxycycline but a notable resistance to tylosin, trimethoprim, tobramycin, ciprofloxacin, and amikacin. Remarkably, 86.54% of the isolates exhibited a multidrug-resistant phenotype. Notably, we successfully screened a strain of B. bronchiseptica with a heteroresistance phenotype to gentamicin using population analysis profiling, which is a rare case. Biofilm-formation assays indicated that 96.15% of the isolates possessed biofilm-forming capabilities. These findings provide crucial insights into the prevalence of B. bronchiseptica in central China, facilitating the development of effective preventive measures to safeguard both animal and human health.
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Accurate estimates of fossil fuel CO2 (FFCO2) emissions are of great importance for climate prediction and mitigation regulations but remain a significant challenge for accounting methods relying on economic statistics and emission factors. In this study, we employed a regional data assimilation framework to assimilate in situ NO2 observations, allowing us to combine observation-constrained NOx emissions coemitted with FFCO2 and grid-specific CO2-to-NOx emission ratios to infer the daily FFCO2 emissions over China. The estimated national total for 2016 was 11.4 PgCO2·yr-1, with an uncertainty (1σ) of 1.5 PgCO2·yr-1 that accounted for errors associated with atmospheric transport, inversion framework parameters, and CO2-to-NOx emission ratios. Our findings indicated that widely used "bottom-up" emission inventories generally ignore numerous activity level statistics of FFCO2 related to energy industries and power plants in western China, whereas the inventories are significantly overestimated in developed regions and key urban areas owing to exaggerated emission factors and inexact spatial disaggregation. The optimized FFCO2 estimate exhibited more distinct seasonality with a significant increase in emissions in winter. These findings advance our understanding of the spatiotemporal regime of FFCO2 emissions in China.
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Dióxido de Carbono , Monitoramento Ambiental , Combustíveis Fósseis , Dióxido de Nitrogênio , Dióxido de Carbono/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Dióxido de Nitrogênio/análise , Estações do AnoRESUMO
The chemisorption energy of reactants on a catalyst surface, [Formula: see text], is among the most informative characteristics of understanding and pinpointing the optimal catalyst. The intrinsic complexity of catalyst surfaces and chemisorption reactions presents significant difficulties in identifying the pivotal physical quantities determining [Formula: see text]. In response to this, the study proposes a methodology, the feature deletion experiment, based on Automatic Machine Learning (AutoML) for knowledge extraction from a high-throughput density functional theory (DFT) database. The study reveals that, for binary alloy surfaces, the local adsorption site geometric information is the primary physical quantity determining [Formula: see text], compared to the electronic and physiochemical properties of the catalyst alloys. By integrating the feature deletion experiment with instance-wise variable selection (INVASE), a neural network-based explainable AI (XAI) tool, we established the best-performing feature set containing 21 intrinsic, non-DFT computed properties, achieving an MAE of 0.23 eV across a periodic table-wide chemical space involving more than 1,600 types of alloys surfaces and 8,400 chemisorption reactions. This study demonstrates the stability, consistency, and potential of AutoML-based feature deletion experiment in developing concise, predictive, and theoretically meaningful models for complex chemical problems with minimal human intervention.
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Background: Biofilm formation is considered to be one of reasons for difficulty in the prevention and control of Streptococcus suis. Aims: To explore the potential genes involved in the biofilm formation of S. suis. Methods: Transposon mutagenesis technology was used to screen biofilm-defective strains of S. suis, and the potential genes related to biofilm were identified. Results: A total of 19 genes were identified that were involved in bacterial metabolism, peptidoglycan-binding protein, cell wall synthesis, ABC transporters, and so on. Conclusion: This study constructed 979 transposon mutation libraries of S. suis. A total of 19 gene loci related to the formation of S. suis biofilm were identified, providing a reference for exploring the mechanism of S. suis biofilm formation in the future.
Streptococcus suis is an important pathogen (this is a microorganism that causes, or can cause, disease) that can be transmitted between animals and humans. The ability to form a protective community, called a biofilm, is one of the reasons why we can have difficulty in preventing and treating S. suis infection. The main purpose of this study was to screen potential genes that may determine biofilm formation in S. suis. The results revealed 19 genes that may affect the biofilm formation of S. suis.
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Infecções Estreptocócicas , Streptococcus suis , Humanos , Streptococcus suis/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Mutação , Mutagênese , Biofilmes , Infecções Estreptocócicas/microbiologiaRESUMO
Air pollution exerts crucial influence on crop yields and impacts regional and global food supplies. Here we employ a statistical model using satellite-based observations and flexible functional forms to analyse the synergistic effects of reductions in ozone and aerosols on China's food security. The model consistently shows that ozone is detrimental to crops, whereas aerosol has variable effects. China's maize, rice and wheat yields are projected to increase by 7.84%, 4.10% and 3.43%, respectively, upon reaching two air quality targets (60 µg m-3 for peak-season ozone and 35 µg m-3 for annual fine particulate matter). Average calories produced from these crops would surge by 4.51%, potentially allowing China to attain grain self-sufficiency 2 years earlier than previously estimated. These results show that ozone pollution control should be a high priority to increase staple crop edible calories, and future stringent air pollution regulations would enhance China's food security.
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Poluição do Ar , Ozônio , Melhoria de Qualidade , Poluição do Ar/prevenção & controle , Ozônio/análise , Produtos Agrícolas , China , Segurança AlimentarRESUMO
Streptococcus suis is an emerging zoonotic pathogen that is widespread in swine populations. The control of S. suis infection and its associated diseases is a daunting challenge worldwide. Biofilm formation appears to be the main reason for the persistence of S. suis. In this review we gather existing knowledge on S. suis biofilm, describing the role of biofilm formation in S. suis virulence and drug resistance, the regulatory factors of S. suis biofilm formation, and the research progress of inhibiting S. suis biofilm formation, with the aim of providing guidance for future studies related to the field of S. suis biofilms.
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Infecções Estreptocócicas , Streptococcus suis , Doenças dos Suínos , Animais , Suínos , Virulência , Biofilmes , Infecções Estreptocócicas/veterináriaRESUMO
Regulatory T (Treg) cells play an essential role in maintaining immune balance across various physiological and pathological conditions. However, the mechanisms underlying Treg homeostasis remain incompletely understood. Here, we report that RIPK1 is crucial for Treg cell survival and homeostasis. We generated mice with Treg cell-specific ablation of Ripk1 and found that these mice developed fatal systemic autoimmunity due to a dramatic reduction in the Treg cell compartment caused by excessive cell death. Unlike conventional T cells, Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking FADD-dependent apoptosis. However, simultaneous removal of both Fadd and Ripk3 completely restored the homeostasis of Ripk1-deficient Treg cells by blocking two cell death pathways. Thus, our study highlights the critical role of RIPK1 in regulating Treg cell homeostasis by controlling both apoptosis and necroptosis, thereby providing novel insights into the mechanisms of Treg cell homeostasis.
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Apoptose , Linfócitos T Reguladores , Animais , Camundongos , Morte Celular , HomeostaseRESUMO
BACKGROUND: Activating signal cointegrator 3 (ASCC3) has been identified as an oncogenic factor that impairs host immune defense. However, the underlying mechanisms of carcinogenesis and its impact on the antitumor immune response remain unclear. In this study, we aimed to investigate the molecular mechanisms of ASCC3 in the progression of non-small cell lung cancer (NSCLC). METHODS: Single-cell sequencing data from the Gene Expression Omnibus and gene expression profiles from The Cancer Genome Atlas database were analyzed. The expression, clinical relevance and biological functions of ASCC3 in NSCLC were explored. Then, RNA sequencing, immunoprecipitation, mass spectrometry, immunofluorescence, and flow cytometry analyses were conducted to explore the underlying molecular mechanisms. In addition, in vivo experiments in mouse models were conducted to explore the probability of ASCC3 knockdown to improve the efficacy of anti-Programmed Death-1 (PD-1) therapy in NSCLC. RESULTS: ASCC3 was significantly upregulated in NSCLC and correlated with poor pathological characteristics and prognosis in patients with NSCLC. Overexpression of ASCC3 promoted malignant phenotypes of NSCLC cells and induced an immunosuppressive tumor microenvironment, which was characterized by a decrease in CD8+ T cells, natural killer cells and dendritic cells but an increase in regulatory T(Treg) cells. Mechanistically, ASCC3 stabilized signal transducer and activator of transcription (STAT)3 signaling by recruiting Cullin-associated and neddylation dissociated 1 (CAND1), which inhibited ubiquitin-mediated degradation of STAT3, thereby impairing the type I interferon response of tumor cells and promoting the immunosuppression and progression of NSCLC. Furthermore, high expression of ASCC3 impaired the efficacy of anti-PD-1 therapy, and an anti-PD-1 antibody combined with ASCC3 knockdown exerted promising synergistic efficacy in a preclinical mouse model. CONCLUSION: ASCC3 could stabilize the STAT3 pathway via CAND1, reshaping the tumor microenvironment and inducing resistance to anti-PD-1 therapy, which promotes the progression of NSCLC. It is a reliable prognostic indicator and can be a target in combination therapy for NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfócitos T CD8-Positivos , Proteínas Culina/genética , Terapia de Imunossupressão , Ubiquitinação , Microambiente Tumoral , Fatores de Transcrição/metabolismo , Fator de Transcrição STAT3/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismoRESUMO
In mammals, the most remarkable T cell variations with aging are the shrinking of the naïve T cell pool and the enlargement of the memory T cell pool, which are partially caused by thymic involution. However, the mechanism underlying the relationship between T-cell changes and aging remains unclear. In this study, we find that T-cell-specific Rip1 KO mice show similar age-related T cell changes and exhibit signs of accelerated aging-like phenotypes, including inflammation, multiple age-related diseases, and a shorter lifespan. Mechanistically, Rip1-deficient T cells undergo excessive apoptosis and promote chronic inflammation. Consistent with this, blocking apoptosis by co-deletion of Fadd in Rip1-deficient T cells significantly rescues lymphopenia, the imbalance between naïve and memory T cells, and aging-like phenotypes, and prolongs life span in T-cell-specific Rip1 KO mice. These results suggest that the reduction and hyperactivation of T cells can have a significant impact on organismal health and lifespan, underscoring the importance of maintaining T cell homeostasis for healthy aging and prevention or treatment of age-related diseases.
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Senilidade Prematura , Linfócitos T , Animais , Camundongos , Envelhecimento/genética , Senilidade Prematura/genética , Apoptose , Inflamação , MamíferosRESUMO
Ever-increasing ambient ozone (O3) pollution in China has been exacerbating cardiopulmonary premature deaths. However, the urban-rural exposure inequity has seldom been explored. Here, we assess population-scale O3 exposure and mortality burdens between 1990 and 2019 based on integrated pollution tracking and epidemiological evidence. We find Chinese population have been suffering from climbing O3 exposure by 4.3 ± 2.8 ppb per decade as a result of rapid urbanization and growing prosperity of socioeconomic activities. Rural residents are broadly exposed to 9.8 ± 4.1 ppb higher ambient O3 than the adjacent urban citizens, and thus urbanization-oriented migration compromises the exposure-associated mortality on total population. Cardiopulmonary excess premature deaths attributable to long-term O3 exposure, 373,500 (95% uncertainty interval [UI]: 240,600-510,900) in 2019, is underestimated in previous studies due to ignorance of cardiovascular causes. Future O3 pollution policy should focus more on rural population who are facing an aggravating threat of mortality risks to ameliorate environmental health injustice.
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Long noncoding RNAs (lncRNAs) are a distinct subtype of RNA that lack protein-coding capacity but exert significant influence on various cellular processes. In non-small cell lung cancer (NSCLC), dysregulated lncRNAs act as either oncogenes or tumor suppressors, contributing to tumorigenesis and tumor progression. LncRNAs directly modulate gene expression, act as competitive endogenous RNAs by interacting with microRNAs or proteins, and associate with RNA binding proteins. Moreover, lncRNAs can reshape the tumor immune microenvironment and influence cellular metabolism, cancer cell stemness, and angiogenesis by engaging various signaling pathways. Notably, lncRNAs have shown great potential as diagnostic or prognostic biomarkers in liquid biopsies and therapeutic strategies for NSCLC. This comprehensive review elucidates the significant roles and diverse mechanisms of lncRNAs in NSCLC. Furthermore, we provide insights into the clinical relevance, current research progress, limitations, innovative research approaches, and future perspectives for targeting lncRNAs in NSCLC. By summarizing the existing knowledge and advancements, we aim to enhance the understanding of the pivotal roles played by lncRNAs in NSCLC and stimulate further research in this field. Ultimately, unraveling the complex network of lncRNA-mediated regulatory mechanisms in NSCLC could potentially lead to the development of novel diagnostic tools and therapeutic strategies.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , MicroRNAs/genética , Oncogenes , Regulação Neoplásica da Expressão Gênica , Microambiente TumoralRESUMO
Purpose: The purpose of this study was to investigate the in vivo morphologic features of the cornea in patients with unilateral posterior interstitial keratitis. Methods: Seven eyes of 7 patients with unilateral posterior interstitial keratitis were examined by slit-lamp biomicroscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy (IVCM). The imaging features of the cornea were evaluated and analyzed. Results: By slit-lamp examination, the posterior corneal stromal opacities were observed in all 7 eyes, and deep neovascularization in 4 eyes. The posterior stromal opacities showed higher reflectivity with an intact overlying epithelium by AS-OCT and did not invade the Bowman's layer in all cases. IVCM revealed highly reflective dispersed microdots, needle-shaped bodies, and increased reflectivity of keratocytes in the lesion site in all patients. Active Langerhans cells and an attenuated subbasal nerve plexus were observed in 5 eyes. After treatment, the active Langerhans cells disappeared; however, highly reflective microdots and needle-shaped bodies remained. Conclusion: The three-dimensional evaluation of slit-lamp biomicroscopy, AS-OCT, and IVCM may help in the early diagnosis of patients with posterior interstitial keratitis.
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Fleet electrification is one of the most promising strategies to mitigate carbon emissions and improve air quality. This study provides a comprehensive analysis of the currently unclear CO2 mitigation and human health benefits from electric vehicle (EV) adoption and energy decarbonization in the Yangtze River Delta (YRD) region by integrating fleet modeling, emission projection, air quality modeling and health risk assessment. Based on future socioeconomic trajectories, we project that the total vehicle stock in the YRD region will peak at 107-117 million around 2045-2050. The transition to EVs combined with largely renewable energy in the YRD region can potentially reduce CO2 emissions by 870 Tg in 2060 and brings along substantial health co-benefits with â¼360 avoided premature deaths per million from reduced PM2.5 and O3 concentrations. This study further explores the NO2-attributable burden from road transportation and reveals that fleet electrification could yield greater NO2-attributable health benefits than those from reduced PM2.5 and O3, especially in traffic-dense urban areas. Those findings indicate that China's near-term energy development plans (35% renewable energy) have created the conditions for large-scale EV adoption. Our results imply that the benefits of EVs exhibit substantial spatial heterogeneity, underscoring the importance of region-specific EV incentive policies, and hint that policymakers should prioritize densely populated megacities to maximize the potential for public health gains.
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The Mulibrey (Muscle-liver-brain-eye) nanism caused by loss-of-function variants in TRIM37 gene is an autosomal recessive disorder characterized by severe growth failure and constrictive pericarditis. These patients also suffer from severe respiratory infections, co-incident with an increased mortality rate. Here, we revealed that TRIM37 variants were associated with recurrent infection. Trim37 FINmajor (a representative variant of Mulibrey nanism patients) and Trim37 knockout mice were susceptible to influenza virus infection. These mice showed defects in follicular helper T (TFH) cell development and antibody production. The effects of Trim37 on TFH cell differentiation relied on its E3 ligase activity catalyzing the K27/29-linked polyubiquitination of Bcl6 and its MATH domain-mediated interactions with Bcl6, thereby protecting Bcl6 from proteasome-mediated degradation. Collectively, these findings highlight the importance of the Trim37-Bcl6 axis in controlling the development of TFH cells and the production of high-affinity antibodies, and further unveil the immunologic mechanism underlying recurrent respiratory infection in Mulibrey nanism.
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Posterior capsule opacification (PCO) is a common postoperative complication of extracapsular cataract surgery, which is caused by the proliferation and migration of lens epithelial cells and can affect long-term visual outcomes significantly. The most effective treatment for PCO is neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy; however, this treatment is associated with posterior segment complication and can break the stability of capsular bag, affecting the position and function of trifocal or toric intraocular lenses (IOLs). Advances in surgical procedures, IOL design, and pharmacy have reduced the rate of PCO in recent years, concentrating on the inhibition of proliferative lens epithelial cells (LECs). This protocol aimed to clear LECs more thoroughly during phacoemulsification and IOL implantation. The first several steps, including clear corneal incision, continuous circular capsulorhexis, hydrodissection, hydrodelineation, and phacoemulsification, were completed as conventional procedures. After placing the IOL into the capsular bag, rotation of the IOL by at least 360° was performed using an irrigation/aspiration tip or a hook, with slight stress on the posterior capsule. Some residuals occurred in the originally transparent capsular bag after rotation of the IOLs. Then, these materials and the viscoelastic were cleared completely using an irrigation/aspiration system. A clear posterior capsule was observed after the surgery in patients undergoing this method. This method of rotating IOLs is a simple, effective, and safe way to prevent PCO by clearing residual LECs and can be carried out without extra tools or skills.