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Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P < 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95% CI [1.16, 2.60]; P = 0.007). To assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95% CI [1.57, 3.6]; P < 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response.
Subject(s)
Clonal Hematopoiesis , Disease Susceptibility , Hepatitis , Liver Cirrhosis , Animals , Mice , Clonal Hematopoiesis/genetics , Hepatitis/genetics , Inflammation/genetics , Liver Cirrhosis/genetics , Non-alcoholic Fatty Liver Disease/genetics , Odds Ratio , Disease ProgressionABSTRACT
BACKGROUND: Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D). METHODS: This study included up to 11â 394 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Diet was assessed with two 24-hour dietary recalls at baseline. We examined associations of dietary fiber intake with gut microbiome measured by shotgun metagenomics (350 species/85 genera and 1958 enzymes; n=2992 at visit 2), serum metabolome measured by untargeted metabolomics (624 metabolites; n=6198 at baseline), and associations between fiber-related gut bacteria and metabolites (n=804 at visit 2). We examined prospective associations of serum microbial-associated metabolites (n=3579 at baseline) with incident T2D over 6 years. RESULTS: We identified multiple bacterial genera, species, and related enzymes associated with fiber intake. Several bacteria (eg, Butyrivibrio, Faecalibacterium) and enzymes involved in fiber degradation (eg, xylanase EC3.2.1.156) were positively associated with fiber intake, inversely associated with prevalent T2D, and favorably associated with T2D-related metabolic traits. We identified 159 metabolites associated with fiber intake, 47 of which were associated with incident T2D. We identified 18 of these 47 metabolites associated with the identified fiber-related bacteria, including several microbial metabolites (eg, indolepropionate and 3-phenylpropionate) inversely associated with the risk of T2D. Both Butyrivibrio and Faecalibacterium were associated with these favorable metabolites. The associations of fiber-related bacteria, especially Faecalibacterium and Butyrivibrio, with T2D were attenuated after further adjustment for these microbial metabolites. CONCLUSIONS: Among United States Hispanics/Latinos, dietary fiber intake was associated with favorable profiles of gut microbiota and circulating metabolites for T2D. These findings advance our understanding of the role of gut microbiota and microbial metabolites in the relationship between diet and T2D.
Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Humans , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/microbiology , Diet , Bacteria , Dietary FiberABSTRACT
BACKGROUND: Dietary acculturation, or adoption of dominant culture diet by migrant groups, influences human health. We aimed to examine dietary acculturation and its relationships with cardiovascular disease (CVD), gut microbiota, and blood metabolites among US Hispanic and Latino adults. METHODS: In the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), US exposure was defined by years in the United States (50 states and Washington, DC) and US nativity. A dietary acculturation pattern was derived from 14 172 participants with two 24-hour dietary recalls at baseline (2008-2011) using least absolute shrinkage and selection operator regression, with food groups as predictors of US exposure. We evaluated associations of dietary acculturation with incident CVD across ≈7 years of follow-up (n=211/14 172 cases/total) and gut microbiota (n=2349; visit 2, 2014 to 2017). Serum metabolites associated with both dietary acculturation-related gut microbiota (n=694) and incident CVD (n=108/5256 cases/total) were used as proxy measures to assess the association of diet-related gut microbiome with incident CVD. RESULTS: We identified an empirical US-oriented dietary acculturation score that increased with US exposure. Higher dietary acculturation score was associated with higher risk of incident CVD (hazard ratio per SD, 1.33 [95% CI, 1.13-1.57]), adjusted for sociodemographic, lifestyle, and clinical factors. Sixty-nine microbial species (17 enriched from diverse species, 52 depleted mainly from fiber-utilizing Clostridia and Prevotella species) were associated with dietary acculturation, driven by lower intakes of whole grains, beans, and fruits and higher intakes of refined grains. Twenty-five metabolites, involved predominantly in fatty acid and glycerophospholipid metabolism (eg, branched-chain 14:0 dicarboxylic acid** and glycerophosphoethanolamine), were associated with both diet acculturation-related gut microbiota and incident CVD. Proxy association analysis based on these metabolites suggested a positive relationship between diet acculturation-related microbiome and risk of CVD (r=0.70, P<0.001). CONCLUSIONS: Among US Hispanic and Latino adults, greater dietary acculturation was associated with elevated CVD risk, possibly through alterations in gut microbiota and related metabolites. Diet and microbiota-targeted interventions may offer opportunities to mitigate CVD burdens of dietary acculturation.
Subject(s)
Acculturation , Cardiovascular Diseases , Diet , Gastrointestinal Microbiome , Hispanic or Latino , Humans , Male , Female , Cardiovascular Diseases/blood , Cardiovascular Diseases/ethnology , Middle Aged , United States/epidemiology , Adult , Diet/adverse effects , Risk Factors , IncidenceABSTRACT
While polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived polygenic transcriptome risk score (PTRS) to improve cross-ethnic portability of risk prediction. We constructed the PTRS using summary statistics from application of PrediXcan on large-scale GWASs of lung function (forced expiratory volume in 1 s [FEV1] and its ratio to forced vital capacity [FEV1/FVC]) in the UK Biobank. We examined prediction performance and cross-ethnic portability of PTRS through smoking-stratified analyses both on 29,381 multi-ethnic participants from TOPMed population/family-based cohorts and on 11,771 multi-ethnic participants from TOPMed COPD-enriched studies. Analyses were carried out for two dichotomous COPD traits (moderate-to-severe and severe COPD) and two quantitative lung function traits (FEV1 and FEV1/FVC). While the proposed PTRS showed weaker associations with disease than PRS for European ancestry, the PTRS showed stronger association with COPD than PRS for African Americans (e.g., odds ratio [OR] = 1.24 [95% confidence interval [CI]: 1.08-1.43] for PTRS versus 1.10 [0.96-1.26] for PRS among heavy smokers with ≥ 40 pack-years of smoking) for moderate-to-severe COPD. Cross-ethnic portability of the PTRS was significantly higher than the PRS (paired t test p < 2.2 × 10-16 with portability gains ranging from 5% to 28%) for both dichotomous COPD traits and across all smoking strata. Our study demonstrates the value of PTRS for improved cross-ethnic portability compared to PRS in predicting COPD risk.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Transcriptome , Humans , Lung , National Heart, Lung, and Blood Institute (U.S.) , Pulmonary Disease, Chronic Obstructive/genetics , Risk Factors , United States/epidemiologyABSTRACT
RATIONALE: Genetic variation has a substantial contribution to chronic obstructive pulmonary disease (COPD) and lung function measurements. Heritability estimates using genome-wide genotyping data can be biased if analyses do not appropriately account for the nonuniform distribution of genetic effects across the allele frequency and linkage disequilibrium (LD) spectrum. In addition, the contribution of rare variants has been unclear. OBJECTIVES: We sought to assess the heritability of COPD and lung function using whole-genome sequence data from the Trans-Omics for Precision Medicine program. METHODS: Using the genome-based restricted maximum likelihood method, we partitioned the genome into bins based on minor allele frequency and LD scores and estimated heritability of COPD, FEV1% predicted and FEV1/FVC ratio in 11 051 European ancestry and 5853 African-American participants. MEASUREMENTS AND MAIN RESULTS: In European ancestry participants, the estimated heritability of COPD, FEV1% predicted and FEV1/FVC ratio were 35.5%, 55.6% and 32.5%, of which 18.8%, 19.7%, 17.8% were from common variants, and 16.6%, 35.8%, and 14.6% were from rare variants. These estimates had wide confidence intervals, with common variants and some sets of rare variants showing a statistically significant contribution (P-value < 0.05). In African-Americans, common variant heritability was similar to European ancestry participants, but lower sample size precluded calculation of rare variant heritability. CONCLUSIONS: Our study provides updated and unbiased estimates of heritability for COPD and lung function, and suggests an important contribution of rare variants. Larger studies of more diverse ancestry will improve accuracy of these estimates.
Subject(s)
Genetic Predisposition to Disease , Pulmonary Disease, Chronic Obstructive , Humans , Polymorphism, Single Nucleotide/genetics , Pulmonary Disease, Chronic Obstructive/genetics , Genome-Wide Association Study , PhenotypeABSTRACT
Metal-organic frameworks (MOFs) are a new variety of solid crystalline porous functional materials. As an extension of inorganic porous materials, it has made important progress in preparation and application. MOFs are widely used in various fields such as gas adsorption storage, drug delivery, sensing, and biological imaging due to their high specific surface area, porosity, adjustable pore size, abundant active sites, and functional modification by introducing groups. In this paper, the types of MOFs are classified, and the synthesis methods and functional modification mechanisms of MOFs materials are summarized. Finally, the application prospects and challenges of metal-organic framework materials in the biomedical field are discussed, hoping to promote their application in multidisciplinary fields.
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RATIONALE & OBJECTIVE: Biomarkers that enable better identification of persons with chronic kidney disease (CKD) who are at higher risk for disease progression and adverse events are needed. This study sought to identify urine and plasma metabolites associated with progression of kidney disease. STUDY DESIGN: Prospective metabolome-wide association study. SETTING & PARTICIPANTS: Persons with CKD enrolled in the German CKD Study (GCKD) with metabolite measurements; with external validation within the Atherosclerosis Risk in Communities Study. EXPOSURES: 1,513 urine and 1,416 plasma metabolites (Metabolon, Inc.) measured at study entry using untargeted mass spectrometry. OUTCOMES: Main endpoints were kidney failure (KF), and a composite endpoint of KF, eGFR <15 mL/min/1.73m2, or 40% decline in eGFR (CKE). Death from any cause was a secondary endpoint. After a median of 6.5 years follow-up, 500 persons experienced KF, 1,083 experienced CKE and 680 died. ANALYTICAL APPROACH: Time-to-event analyses using multivariable proportional hazard regression models in a discovery-replication design, with external validation. RESULTS: 5,088 GCKD participants were included in analyses of urine metabolites and 5,144 in analyses of plasma metabolites. Among 182 unique metabolites, 30 were significantly associated with KF, 49 with CKE, and 163 with death. The strongest association with KF was observed for plasma hydroxyasparagine (hazard ratio: 1.95, 95% confidence interval: 1.68-2.25). An unnamed metabolite measured in plasma and urine was significantly associated with KF, CKE, and death. External validation of the identified associations of metabolites with KF or CKE revealed direction-consistency for 88% of observed associations. Selected associations of 18 metabolites with study outcomes have not been previously reported. LIMITATIONS: Use of observational data and semi-quantitative metabolite measurements at a single time point. CONCLUSIONS: The observed associations between metabolites and KF, CKE or death in persons with CKD confirmed previously reported findings and also revealed several associations not previously described. These findings warrant confirmatory research in other study cohorts.
ABSTRACT
Chronic obstructive pulmonary disease (COPD) is associated with age and smoking, but other determinants of the disease are incompletely understood. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-related state in which somatic mutations in clonal blood populations induce aberrant inflammatory responses. Patients with CHIP have an elevated risk for cardiovascular disease, but the association of CHIP with COPD remains unclear. We analyzed whole-genome sequencing and whole-exome sequencing data to detect CHIP in 48 835 patients, of whom 8444 had moderate to very severe COPD, from four separate cohorts with COPD phenotyping and smoking history. We measured emphysema in murine models in which Tet2 was deleted in hematopoietic cells. In the COPDGene cohort, individuals with CHIP had risks of moderate-to-severe, severe, or very severe COPD that were 1.6 (adjusted 95% confidence interval [CI], 1.1-2.2) and 2.2 (adjusted 95% CI, 1.5-3.2) times greater than those for noncarriers. These findings were consistently observed in three additional cohorts and meta-analyses of all patients. CHIP was also associated with decreased FEV1% predicted in the COPDGene cohort (mean between-group differences, -5.7%; adjusted 95% CI, -8.8% to -2.6%), a finding replicated in additional cohorts. Smoke exposure was associated with a small but significant increased risk of having CHIP (odds ratio, 1.03 per 10 pack-years; 95% CI, 1.01-1.05 per 10 pack-years) in the meta-analysis of all patients. Inactivation of Tet2 in mouse hematopoietic cells exacerbated the development of emphysema and inflammation in models of cigarette smoke exposure. Somatic mutations in blood cells are associated with the development and severity of COPD, independent of age and cumulative smoke exposure.
Subject(s)
Clonal Hematopoiesis , Pulmonary Disease, Chronic Obstructive/genetics , Animals , Female , Humans , Male , Mice , Middle Aged , Odds Ratio , Pulmonary Disease, Chronic Obstructive/etiology , Risk Factors , Smoking/adverse effects , Exome SequencingABSTRACT
BACKGROUND: Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma. METHODS: Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non-case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non-case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta-analyzed using inverse-variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with atopy (n = 207), asthma without atopy (n = 554), atopy without asthma (n = 147), compared to neither (n = 948)). RESULTS: Meta-analysis of 4860 proteins identified 115 significantly (FDR<0.05) associated with asthma. Multiple signaling pathways related to airway inflammation and pulmonary injury were enriched (FDR<0.05) among these proteins. A proteomic score generated using machine learning provided predictive value for asthma (AUC = 0.77, 95% CI = 0.75-0.79 in training set; AUC = 0.72, 95% CI = 0.69-0.75 in validation set). Twenty proteins are targeted by approved or investigational drugs for asthma or other conditions, suggesting potential drug repurposing. The combined asthma-atopy phenotype showed significant associations with 20 proteins, including five not identified in the overall asthma analysis. CONCLUSION: This first large-scale proteomics study identified over 100 plasma proteins associated with current asthma in adults. In addition to validating previous associations, we identified many novel proteins that could inform development of diagnostic biomarkers and therapeutic targets in asthma management.
Subject(s)
Asthma , Hypersensitivity, Immediate , Adult , Humans , Proteomics/methods , Asthma/metabolism , Biomarkers , Phenotype , Blood Proteins/geneticsABSTRACT
Photosynthesis, converting sustainable solar energy into chemical energy, has emerged as a promising craft to achieve diverse organic transformations due to its mild reaction conditions, sustainability, and high efficiency. The synthesis of sulfonated compounds has drawn significant attention in the pharmaceuticals, agrochemicals, and materials industries due to the unique structure and electronic properties of the sulfonyl groups. Over the past decades, many photocatalytic sulfonylation reactions have been developed. In this review, the recent advances in photocatalyzed sulfonylation have been reviewed since 2020, with a primary focus on discussing reaction design and mechanism.
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Fungal keratitis (FK) is an infectious keratopathy can cause serious damage to vision. Its severity is related to the virulence of fungus and response of inflammatory. Rosmarinic acid (RA) extracted from Rosmarinus officinalis exhibits antioxidant, anti-inflammatory and anti-viral properties. The aim of this study was to investigate the effect of RA on macrophage autophagy and its therapeutic effect on FK. In this study, we demonstrated that RA reduced expression of proinflammatory cytokine, lessened the recruitment of inflammatory cells in FK. The relative contents of autophagy markers, such as LC3 and Beclin-1, were significantly up-regulated in RAW 264.7 cells and FK. In addition, RA restored mitochondrial membrane potential (MMP) of macrophage to normal level. RA not only reduced the production of intracellular reactive oxygen species (ROS) but also mitochondria ROS (mtROS) in macrophage. At the same time, RA induced macrophage to M2 phenotype and down-regulated the mRNA expression of IL-6, IL-1ß, TNF-α. All the above effects could be offset by the autophagy inhibitor 3-Methyladenine (3-MA). Besides, RA promote phagocytosis of RAW 264.7 cells and inhibits spore germination, biofilm formation and conidial adherence, suggesting a potential therapeutic role for RA in FK.
Subject(s)
Aspergillosis , Aspergillus fumigatus , Autophagy , Cinnamates , Depsides , Eye Infections, Fungal , Macrophages , Reactive Oxygen Species , Rosmarinic Acid , Depsides/pharmacology , Animals , Autophagy/drug effects , Mice , Aspergillosis/drug therapy , Aspergillosis/microbiology , Aspergillosis/metabolism , Eye Infections, Fungal/microbiology , Eye Infections, Fungal/drug therapy , Macrophages/drug effects , Macrophages/metabolism , Macrophages/microbiology , Cinnamates/pharmacology , Reactive Oxygen Species/metabolism , Membrane Potential, Mitochondrial/drug effects , Keratitis/microbiology , Keratitis/drug therapy , Keratitis/metabolism , Disease Models, Animal , RAW 264.7 Cells , Cytokines/metabolism , Phagocytosis/drug effectsABSTRACT
Fungal keratitis (FK) is a refractory keratitis caused by excessive inflammation and fungal damage. Excessive inflammation can lead to tissue damage and corneal opacity, resulting in a poor prognosis for FK. Oxymatrine (OMT) is a natural alkaloid, which has rich pharmacological effects, such as antioxidant and anti-inflammation. However, its antifungal activity and the mechanism of action in FK have not been elucidated. This study confirmed that OMT suppressed Aspergillus fumigatus growth, biofilm formation, the integrity of fungal cell and conidial adherence. OMT not only effectively reduced corneal fungal load but also inflammation responses. OMT lessened the recruitment of neutrophils and macrophages in FK. In addition, OMT up-regulated the expression of Nrf2 and down-regulated the expression of IL-18, IL-1ß, caspase-1, NLRP3 and GSDMD. Pre-treatment with Nrf2 inhibitor up-regulated the expression of IL-1ß, IL-18, caspase-1, NLRP3 and GSDMD supressed by OMT. In conclusion, OMT has efficient anti-inflammatory and antifungal effects by suppressing fungal activity and restricting pyroptosis via Nrf2 pathway. OMT is considered as a potential option for the treatment of FK.
Subject(s)
Aspergillosis , Corneal Ulcer , Eye Infections, Fungal , Keratitis , Matrines , Animals , Mice , Aspergillus fumigatus/physiology , NLR Family, Pyrin Domain-Containing 3 Protein , Interleukin-18 , Aspergillosis/drug therapy , Aspergillosis/metabolism , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Pyroptosis , NF-E2-Related Factor 2 , Keratitis/microbiology , Inflammation , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/metabolism , Caspase 1/metabolism , Mice, Inbred C57BLABSTRACT
BACKGROUND: Understanding seasonal variations in stroke can help stakeholders identify underlying causes in seasonal trends, and tailor resources appropriately to times of highest needs. We sought to evaluate the seasonal occurrence of stroke and its subtypes. METHODS: We conducted a retrospective cohort study using administrative data from January 1st, 2003, to December 31st, 2017, in Ontario, Canada's most populous province. We evaluated seasonal variations in stroke occurrence by subtype, via age/sex standardized rates and adjusted rate ratios using Poisson regressions. In those with stroke, we evaluated 30-day case fatality risks by season, adjusted for age, sex, stroke type, and comorbid conditions, and then used Cox proportional hazard models to estimate the effect of season on the fatality. The administrative data used in this study were from the Canadian Institute for Health Information's Discharge Abstract Database, the National Ambulatory Care Reporting System Database, the Ontario Registered Persons Database, and the 2006 and 2011 Canada Census and linked administrative databases. RESULTS: During our study period, we observed 394,145 strokes or TIA events, with a decrease in monthly hospitalization/emergency department visits per 100,000 people between January 2003 and December 2017 from 24.22 to 17.43. Compared to the summer, overall stroke occurrence was similar in the spring but slightly lower in the fall (adjusted rate ratio [aRR] 0.97, 95% confidence interval [CI] 0.96-0.98) and winter (aRR 0.94, 95% CI: 0.94-0.95). There were minor variations by stroke subtype. Winter was associated with the highest risk of stroke case fatality compared to the summer (12.4% vs. 11.4%, adjusted hazard ratio 1.10, 95% CI: 1.07-1.13). CONCLUSIONS: We found seasonal variations in stroke occurrence and case fatality, although the absolute differences were small. Further work is needed to better understand how environmental or meteorological factors might affect stroke risk.
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A Gram-stain-negative, aerobic, rod-shaped and halotolerant bacterium, designated as strain ASW11-75T, was isolated from intertidal sediments in Qingdao, PR China, and identified using a polyphasic taxonomic approach. Growth of strain ASW11-75T occurred at 10-45â°C (optimum, 37â°C), pH 6.5-9.0 (optimum, pH 8.0) and 0.5-18.0â% NaCl concentrations (optimum, 2.5â%). Phylogenetic analyses based on 16S rRNA gene sequences and 1179 single-copy orthologous clusters indicated that strain ASW11-75T is affiliated with the genus Marinobacter. Strain ASW11-75T showed highest 16S rRNA gene sequence similarity to 'Marinobacter arenosus' CAU 1620T (98.5â%). The digital DNA-DNA hybridization and average nucleotide identity values between strain ASW11-75T and its closely related strains (Marinobacter salarius R9SW1T, Marinobacter similis A3d10T, 'Marinobacter arenosus' CAU 1620T, Marinobacter sediminum R65T, Marinobacter salinus Hb8T, Marinobacter alexandrii LZ-8T and Marinobacter nauticus ATCC 49840T) were 19.8-24.5â% and 76.6-80.7â%, respectively. The predominant cellular fatty acids were C16â:â0, C18â:â1 ω9c and C16â:â0 N alcohol. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminophospholipid and two unidentified lipids. The major isoprenoid quinone was ubiquinone-9. The genomic DNA G+C content was 62.2âmol%. Based on genomic and gene function analysis, strain ASW11-75T had lower protein isoelectric points with higher ratios of acidic residues to basic residues and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt. The results of polyphasic characterization indicated strain ASW11-75T represents a novel Marinobacter species, for which the name Marinobacter qingdaonensis sp. nov. with the type strain ASW11-75T is proposed. The type strain is ASW11-75T (=KCTC 82497T=MCCC 1K05587T).
Subject(s)
Fatty Acids , Marinobacter , Fatty Acids/chemistry , Phospholipids/chemistry , Seawater/microbiology , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Base Composition , DNA, Bacterial/genetics , Bacterial Typing TechniquesABSTRACT
2,1,3-Benzothiadiazole is widely used as a privileged scaffold in pharmaceuticals and organic functional materials. Nonetheless, many current methods for the functionalization of 2,1,3-benzothiadiazole rely on preactivation, transition metal catalysts/promoters, or an elevated reaction temperature. Herein we disclose a transition-metal-free visible-light-induced photocatalytic method for the direct C-H alkylation of 2,1,3-benzothiadiazole using readily accessible carboxylic acid derivatives, i.e., N-hydroxyphthalimide esters (NHPEs), as alkylating reagents under room temperature. This mild and scalable method is highlighted by the late-stage installation of the benzothiadiazole scaffold in drugs and natural products.
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The palladium-catalyzed sequential cross-coupling/annulation of ortho-vinyl bromobenzenes with aryl bromides generating phenanthrenes was characterized by density functional theory (DFT). The Pd(II)-Pd(IV) pathway (Path V) is shown to be less probable than the bimetallic pathway (Path I), the latter proceeding via the following six steps: oxidative addition, vinyl-C(sp2)-H activation, Pd(II)-Pd(II) transmetalation, C-C coupling, aryl-C(sp2)-H activation, and reductive elimination. The aryl-C(sp2)-H activation process acts as the rate-determining step (RDS) of the entire chemical transformation, with an activation free energy barrier of ca. 27.4-28.8 kcal·mol-1, in good agreement with the corresponding experimental data (phenanthrenes' yields of ca. 65-90% at 130 °C after 5 h of reaction). The K2CO3 additive effectively reduces the activation free energy barrier of the RDS through direct participation in the reaction while preferentially modulating the charge distributions and increasing the stability of corresponding intermediates and complexes along the reaction path. Furthermore, bonding and electronic structure analyses of the key structures indicate that the chemo- and regioselectivities of the reaction are strongly influenced by both electronic effects and steric hindrance.
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Tosyl cyanide is a commonly used reagent for cyanation and sulfonylation in organic synthesis and pharmaceutical chemistry. The photocatalytic transformations of tosyl cyanide are generally conducted under mild conditions. This minireview summarizes the recent progress of radical-involved transformations of tosyl cyanide via photo-induced cyanation or sulfonylcyanation.
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Microwave irradiation (MW) and ionic liquids (ILs) are two of the most promising relatively greener synthetic approaches to preparing value-added chemicals. Herein, a series of 2-acylbenzothiazole derivatives were synthesized for the first time from commercially available α-bromoacetophenones and disulfane-diyl-dianilines through the cooperation of ionic liquids and microwave irradiation under metal- and extra-additives-free conditions. A plausible mechanism involving the successive IL-induced enolation has been proposed.
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Manure application is a global approach for enhancing soil organic carbon (SOC) sequestration. However, the response of SOC decomposition in manure-applied soil to abrupt warming, often occurring during diurnal temperature fluctuations, remains poorly understood. We examined the effects of long-term (23 years) continuous application of manure on SOC chemical composition, soil respiration, and microbial communities under temperature shifts (15 vs 25 °C) in the presence of plant residues. Compared to soil without fertilizer, manure application reduced SOC recalcitrance indexes (i.e., aliphaticity and aromaticity) by 17.45 and 21.77%, and also reduced temperature sensitivity (Q10) of native SOC decomposition, plant residue decomposition, and priming effect by 12.98, 15.98, and 52.83%, respectively. The relative abundances of warm-stimulated chemoheterotrophic bacteria and fungi were lower in the manure-applied soil, whereas those of chemoautotrophic Thaumarchaeota were higher. In addition, the microbial network of the manure-applied soil was more interconnected, with more negative connections with the warm-stimulated taxa than soils without fertilizer or with chemical fertilizer applied. In conclusion, our study demonstrated that the reduced loss of SOC to abrupt warming by manure application arises from C chemistry modification, less warm-stimulated microorganisms, a more complex microbial community, and the higher CO2 intercepting capability by Thaumarchaeota.
Subject(s)
Carbon , Manure , Microbiota , Soil Microbiology , Soil , Soil/chemistry , Fertilizers , TemperatureABSTRACT
BACKGROUND: Rifampicin resistant tuberculosis (RR-TB) poses a growing threat to individuals and communities. This study utilized a seasonal autoregressive integrated moving average (SARIMA) model to quantitatively predict the monthly incidence of RR-TB in Yunnan Province which could guide government health administration departments and the centers for disease control and prevention (CDC) in preventing and controlling the RR-TB epidemic. METHODS: The study utilized routine surveillance reporting data from the infectious Disease Network Surveillance and Reporting System. Monthly incidence rates of RR-TB were collected from January 2019 to December 2022. A time series SARIMA model was used to predict the number of monthly RR-TB cases in Yunnan Province in 2023, and the model was validated using time series plots, seasonal and non-seasonal differencing, autocorrelation and partial autocorrelation analysis, and white noise tests. RESULTS: From 2019 to 2022, the incidence of RR-TB decreases as the incidence of all TB decreases (P < 0.05). There was no significant change in the proportion of RR-TB among all TB cases, which remained within 2.5% (P>0.05). The time series decomposition shows that it presented obvious seasonality, periodicity and randomness after being decomposed. Time series analysis was performed on the original series after 1 non-seasonal difference and 1 seasonal difference, the ADF test showed P < 0.05. According to ACF and PACF, the SARIMA (1, 1, 1) (1, 1, 0)12 model was chosen and statistically significant model parameter estimates (P < 0.05). The predicted seasonal trend of RR-TB incidence in 2019 to 2023 was similar to the actual data. The percentage accuracy in the prediction excesses 80% in 2019 to 2022 and is all within 95% CI. However there was a certain gap between the actual incidence and the predicted value in 2023, and the acutual incidence had increased by 12.4% compared to 2022. The percentage of accuracy in the prediction was only 70% in 2023. CONCLUSIONS: We found the incidence of RR-TB was based on that of all TB in Yunnan. The SARIMA model successfully predicted the seasonal incidence trend of RR-TB in Yunnan Province in 2019 to 2023, but the prediction precision could be influenced by factors such as new infectious disease outbreaks or pandemics, social issues, environmental challenges or other unknown risks. Hence CDCs should pay special attention to the post epidemic effects of new infectious disease outbreaks or pandemics, carry out monitoring and early warning, and better optimize disease prediction models.