ABSTRACT
Mechanical damage of LiMn2O4 active material caused by volume change, phase transition, and lithium diffusion-induced stress is the main degradation mechanism in lithium-ion batteries. Young's modulus is a key parameter of mechanical property, and its variation with lithium content x or state of charge (SOC) at the nanoscale is an important issue because such variation may have influences on the stress level and lithium-ion transport. In this study, we successfully developed bimodal atomic force microscopy (bimodal AFM) and related approaches to carry out surface topography imaging and Young's modulus mapping of LixMn2O4 nanosized particles. It was validated that the size of particles decreased with decreasing SOC due to delithiation during the charging cycle. The variation in Young's modulus with SOC was quantitatively determined using the silicon material as a reference, and the trend of the variation is consistent with the reported results of molecular dynamics simulation. Furthermore, spatially nonuniform distribution of Young's modulus on the nanosized particle surface was found even upon completion of charging. This phenomenon could be attributed to the coexistence of two phases during the charging process. Our experimental study reveals the correlation between Young's modulus of LiMn2O4 and SOC at the nanosized particle level, and we believe that the bimodal AFM will be widely used in the nanocharacterization of the electrode materials because lithium content- or SOC-dependent mechanical properties are common in battery electrode materials.
ABSTRACT
Studies on nitenpyram determination and behavior within tea remain limited despite its widespread use as a neonicotinoid. An organic-saving analytical approach tailored for the detection of nitenpyram in tea was established. Nitenpyram was extracted by boiling water and cleaned up by Cleanert PCX solid-phase. The average recoveries were 75.1-94.5 %, with relative standard deviations (RSDs) of 0.7-8.6 % for saving 34.5-88.6 % organic solvent. The limits of quantification (LOQs) were 0.002 mg·kg-1 in fresh tea shoots, 0.005 mg·kg-1 in made tea, and 0.001 mg·L-1 in tea brew, satisfying the current minimum Maximum Residue Limit (MRL). Nitenpyram dissipated rapidly with half-lives of 1.2-1.4 days at the recommended dosage (27 g a.i. ha-1) in two locations. Remarkably, 20-110 % of nitenpyram was leached out from made tea in different brewing modes. This work provides insights into nitenpyram's rational application in tea cultivation and offers considerations to institutions tasked with unestablished MRLs in tea.
Subject(s)
Food Contamination , Neonicotinoids , Pesticide Residues , Tea , Tea/chemistry , Pesticide Residues/analysis , Neonicotinoids/analysis , Food Contamination/analysis , Solid Phase Extraction/methods , Limit of Detection , Camellia sinensis/chemistryABSTRACT
Research on the potential association between life-ever gallstones and depressive symptoms is limited. This study aims to evaluate whether the presence of gallstone disease is associated with depressive symptoms. In this cross-sectional study, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 cycles. The presence of depressive symptoms and gallstone disease was assessed using questionnaire responses. Adjusted odds ratios (OR) were calculated using a multivariate logistic regression model, with adjustments made for age, sex, race, body mass index, history of cardiovascular disease, hypertension, arthritis, and pulmonary disease across different models. Subgroup and sensitivity analyses were conducted to ensure the stability of the results. This study included 6201 adults aged 20 years and above, with 539(8.7%) experiencing depressive symptoms. After adjusting for age, sex, race, body mass index, CVD history, hypertension, arthritis, pulmonary disease, depressive symptoms were possibly associated with life-ever gallstones (OR 1.37, 95% CI 0.91-2.08).When depressive symptoms were categorized as mild, moderate, moderately severe, and severe,life-ever gallstones was possibly associated with mild depressive symptoms (OR 1.12, 95% CI 0.81-1.56), moderate depressive symptoms (OR 1.37, 95% CI 0.89-2.12), moderately severe depressive symptoms (OR 1.93, 95% CI 0.93-3.99), and severe depressive symptoms (OR 0.67, 95% CI 0.16-2.88).As a continuous variable, life-ever gallstones was associated with the PHQ-9 score (OR 0.42, 95% CI 0.02-0.83). The results remained stable after multiple imputation for all missing data. This cross-sectional study demonstrates no significant association between life-ever gallstones and depressive symptoms in US adults.
Subject(s)
Depression , Gallstones , Humans , Gallstones/epidemiology , Gallstones/complications , Gallstones/psychology , Male , Female , Depression/epidemiology , Cross-Sectional Studies , Adult , Middle Aged , United States/epidemiology , Aged , Nutrition Surveys , Young Adult , Risk Factors , Odds RatioABSTRACT
Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity-associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small-molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO-regulated transcriptome-wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue-specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL-4/IL-13-treated epithelial cells and house dust mite (HDM)-induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF-α signaling via NF-κB and epithelial-mesenchymal transition-related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23-induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM-induced mice, potentially through diverse cellular processes and epithelial-mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.
Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO , Asthma , Inflammation , Animals , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Mice , Asthma/metabolism , Asthma/genetics , Inflammation/metabolism , Humans , Respiratory Mucosa/metabolism , Respiratory Mucosa/pathology , Epithelial Cells/metabolism , Mice, Inbred BALB C , Female , Hypersensitivity/metabolism , Hypersensitivity/drug therapy , Epithelial-Mesenchymal Transition/drug effects , Mice, Inbred C57BLABSTRACT
OBJECTIVES: To apply cardiac magnetic resonance imaging (CMR) for detailed myocardial characterization in uremic cardiomyopathy (UC), hypertensive cardiomyopathy (HTN), and hypertrophic cardiomyopathy (HCM) aiming to enrich the understanding of UC's etiology and further support the development of therapeutic strategies. METHODS: A total of 152 patients (age: 49.2 ± 9.9 years; 65.8% male) underwent routine CMR from June 2016 to March 2023. Retrospectively, 53 patients with UC, 39 patients with HTN, 30 patients with HCM, and 30 healthy controls were included. Functional analysis, feature tracking of the left ventricle and left atrium, and myocardial T1, T2, and T2* mapping were performed. Statistical analysis included Pearson correlation and ROC analysis to define correlations and discriminators between groups. RESULTS: UC patients demonstrated significantly higher native T1 (p < 0.001 for all) and T2 (p < 0.002 for all) values compared with the other three groups. UC patients revealed higher left atrial reservoir strain rate (p < 0.001 for all) and left atrial conduit strain rate (p < 0.001 for all) absolute values as compared with HTN and HCM patients. A significant correlation between T1 and T2 values in UC patients (r = 0.511, p < 0.001) was found. The combination of T1 values and strain parameters was the best discriminator between UC and HTN patients (AUC = 0.872, 95% CI: 0.801-0.943) and between UC and HCM patients (AUC = 0.840, 95% CI: 0.746-0.934). CONCLUSION: UC reveals distinguishing tissue characteristics as evidenced by T1 and T2 mapping, as well as distinguishing functional strain parameters as compared with other hypertrophic phenotypes such as HTN and HCM. CRITICAL RELEVANCE STATEMENT: The use of CMR imaging in UC patients offers incremental information to elucidate its complex etiology, contributing to ongoing discourse on effective treatment pathways. KEY POINTS: This study investigated uremic, hypertensive, and hypertrophic cardiomyopathies using cardiac MRI. UC patients have higher T1 and T2 values and better preserved cardiac function. Combined strain and T1 values distinguish UC from other cardiomyopathies.
ABSTRACT
Anthrones are key structural motifs in many natural products and pharmaceutical chemicals. However, due to its unique tricyclic aromatic structure, the synthetic space for the development of chiral anthrone derivatives is largely limited. By utilizing the potential of the copper-catalyzed remote asymmetric yne-allylic substitution reaction, we describe the first example of copper-catalyzed highly regio- and enantioselective remote yne-allylic substitution on various yne-allylic esters with anthrones under a mild reaction condition, which afforded a range of enantioenriched 1,3-enynes with exhibiting broad functional group tolerance across 51 examples.
ABSTRACT
Integrin α5ß1 is crucial for cell attachment and migration in development and tissue regeneration, and α5ß1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5ß1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5ß1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin and RGD peptide in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed fibronectin and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine.
ABSTRACT
Both melatonin and hydrogen sulfide (H2S) mitigate chromium (Cr) toxicity in plants, but the specific interaction between melatonin and H2S in Cr detoxification remains unclear. In this study, the interaction between melatonin and H2S in Cr detoxification was elucidated by measuring cell wall polysaccharide metabolism and antioxidant enzyme activity in maize. The findings revealed that exposure to Cr stress (100 µM K2Cr2O7) resulted in the upregulation of L-/D-cysteine desulfhydrase (LCD/DCD) gene expression, leading to a 77.8% and 27.3% increase in endogenous H2S levels in maize leaves and roots, respectively. Similarly, the endogenous melatonin system is activated in response to Cr stress. We found that melatonin had a significant impact on the relative expression of LCD/DCD, leading to a 103.3% and 116.7% increase in endogenous H2S levels in maize leaves and roots, respectively. In contrast, NaHS had minimal effects on the relative mRNA expression of serotonin-Nacetyltransferase (SNAT) and endogenous melatonin levels. The production of H2S induced by melatonin is accompanied by an increase in Cr tolerance, as evidenced by elevated gene expression, elevated cell wall polysaccharide content, increased pectin methylesterase activity, and improved antioxidant enzyme activity. The scavenging of H2S decreases the melatonin-induced Cr tolerance, while the inhibitor of melatonin synthesis, p-chlorophenylalanine (p-CPA), has minimal impact on H2S-induced Cr tolerance. In conclusion, our findings suggest that H2S serves as a downstream signaling molecule involved in melatonin-induced Cr tolerance in maize.
ABSTRACT
The Rab GTPase constitutes the largest family of small GTPases that regulate intracellular trafficking. Different eukaryotes possess varying numbers of Rab paralogs. However, limited knowledge exists regarding the evolutionary pattern of Rab family in most major eukaryotic supergroups. This study cloned 24 Rab genes from transcriptome data of Procambarus clarkii haemocytes. The multiple sequence alignment and phylogenetic tree analysis revealed a relatively high degree of conservation for PcRab. Furthermore, PcRab exhibited similarities in motif composition with all members showing presence of G, PM, RabF, and RabSF motifs. The tertiary structure indicated that PcRab proteins mainly consisted of α-helices and ß-strands, and most PcRab proteins shared similar tertiary structures, and it was indicated that they have similar protein characteristics. Protein-protein interaction prediction identified a total of 20 interacting proteins involved in vesicle trafficking, phagocytosis, and signal transduction with 193 interactions. Expression analysis showed wide expression patterns for PcRab in P. clarkii organs. Upon infection by white spot syndrome virus and Aeromonas veronii, significant induction was observed for PcRab gene expression levels, indicating their involvement in pathogen response mechanisms. The present study represents the pioneering effort in comprehensively identifying and cloning the Rab family genes in crustacean, followed by a systematic investigation into their evolutionary patterns and immune response upon pathogen infection. The results provided valuable insights for further investigation into the molecular mechanism underlying the response of P. clarkii to pathogen infection.
Subject(s)
Astacoidea , Evolution, Molecular , Phylogeny , rab GTP-Binding Proteins , Animals , Astacoidea/genetics , Astacoidea/immunology , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolism , Amino Acid Sequence , Multigene Family , Gene Expression Profiling , Transcriptome , White spot syndrome virus 1/immunology , Gene Expression Regulation , Sequence AlignmentABSTRACT
Chiral coumarins and their derivatives are ubiquitous structural motifs found in an array of biologically and therapeutically active natural products and drugs. Herein, a highly enantioselective dual remote copper-catalyzed vinylogous alkynylallylic substitution of yne-allylic esters with coumarins has been developed. The practicality of this method is exemplified by the use of readily available starting materials; mild reaction conditions; excellent regio-, enantio-, and stereoselectivities; and the very broad substrate scope (67 examples), while the scalability and further applications of this method are illustrated by the gram-scale reaction and the series of derivations of the products.
ABSTRACT
Proteins which bind intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) with high affinity and specificity could have considerable utility for therapeutic and diagnostic applications. However, a general methodology for targeting IDPs/IDRs has yet to be developed. Here, we show that starting only from the target sequence of the input, and freely sampling both target and binding protein conformation, RFdiffusion can generate binders to IDPs and IDRs in a wide range of conformations. We use this approach to generate binders to the IDPs Amylin, C-peptide and VP48 in a range of conformations with Kds in the 3 -100nM range. The Amylin binder inhibits amyloid fibril formation and dissociates existing fibers, and enables enrichment of amylin for mass spectrometry-based detection. For the IDRs G3bp1, common gamma chain (IL2RG) and prion, we diffused binders to beta strand conformations of the targets, obtaining 10 to 100 nM affinity. The IL2RG binder colocalizes with the receptor in cells, enabling new approaches to modulating IL2 signaling. Our approach should be widely useful for creating binders to flexible IDPs/IDRs spanning a wide range of intrinsic conformational preferences.
ABSTRACT
Microbial fuel cells (MFCs) have the dual advantage of mitigating Cr(â ¥) wastewater ecological threats while generating electricity. However, the low electron transfer efficiency and the limited enrichment of active electrogens are barriers to MFCs advancement. This study describes the synthesis of the TP-PDA-RGO@CC negative electrode using tea polyphenol as a reducing agent and polydopamine-doped graphene, significantly enhances the roughness and hydrophilicity of the anode. The charge transfer resistance was reduced by 94%, and the peak MFC power was 1375.80 mW m-2. Under acidic conditions, the Cr(â ¥) reduction rate reached 92% within 24 h, with a 52% increase in coulombic efficiency. Biodiversity analysis shows that the TP-PDA-RGO@CC anode could enrich electrogens, thereby boosting the electron generation mechanism at the anode and enhancing the reduction efficiency of Cr(â ¥) in the cathode chamber. This work emphasizes high-performance anode materials for efficient pollutant removal, energy conversion, and biomass reuse.
Subject(s)
Bioelectric Energy Sources , Chromium , Electrodes , Graphite , Indoles , Polymers , Polyphenols , Tea , Polyphenols/chemistry , Polymers/chemistry , Indoles/chemistry , Chromium/chemistry , Graphite/chemistry , Tea/chemistry , Wastewater/chemistry , Water Pollutants, Chemical/chemistry , Oxidation-ReductionABSTRACT
Infection with Mycobacterium bovis precipitates a spectrum of pathologies in bovines, notably necrotic pneumonia, mastitis, and arthritis, impinging upon the health and nutritional assimilation of these animals. A pivotal factor, lipocalin 2 (Lcn2), is responsive to microbial invasion, inflammatory processes, and tissue damage, the extent of which Lcn2 modulates the gut environment, however, remains unclear in response to M. bovis-induced alterations. To explore the role of Lcn2 in shaping the gut milieu of mice during a 5-week period post-M. bovis infection, Lcn2 knockout Lcn2-/- mice were scrutinized for changes in the gut microbiota and metabolomic profiles. Results showed that Lcn2-/- mice infected with M. bovis exhibited notable shifts in the operational taxonomic units (OTUs) of gut microbiota, alongside significant disparities in α and ß diversity. Concomitantly, a marked increase was observed during the 5-week period in the abundance of Akkermansia, Oscillospira, and Bacteroides, coupled with a substantial decrease in Ruminococcus within the microbiome of Lcn2 knockout mice. Notably, Akkermansia muciniphila was significantly enriched in the gut flora of Lcn2-/- mice. Furthermore, the absence of Lcn2 significantly altered the gut metabolomic landscape, evidenced by elevated levels of metabolites such as taurodeoxycholic acid, 10-undecenoic acid, azelaic acid, and dodecanedioic acid in Lcn2-/- mice. Our findings demonstrated that the lack of Lcn2 in the context of M. bovis infection profoundly affected the regulation of gut microbiota and metabolomic components, culminating in a transformed gut environment. Our results revealed that Lcn2 may regulate gut microbiota and metabolome components, changing the intestinal environment, thereby affecting the infection status of M. bovis. IMPORTANCE: Our study addresses the critical knowledge gap regarding the specific influence of lipocalin 2 (LCN2) in the context of Mycobacterium bovis infection, particularly focusing on its role in the gut environment. Utilizing LCN2 knockout (Lcn2-/-) mice, we meticulously assessed changes in the gut microbiota and metabolic components following M. bovis infection. Our findings reveal alterations in the gut microbial community, emphasizing the potentially crucial role of LCN2 in maintaining stability. Furthermore, we observed significant shifts in specific microbial communities, including the enrichment of Akkermansia muciniphila, known for its positive impact on intestinal health and immune regulation. The implications of our study extend beyond understanding the dynamics of the gut microbiome, offering insights into the potential therapeutic strategies for gut-related health conditions and microbial dysbiosis.
Subject(s)
Gastrointestinal Microbiome , Lipocalin-2 , Metabolome , Mice, Knockout , Mycobacterium bovis , Animals , Lipocalin-2/genetics , Lipocalin-2/metabolism , Mice , Mice, Inbred C57BL , Tuberculosis/microbiology , Tuberculosis/genetics , Tuberculosis/metabolism , Tuberculosis/immunology , FemaleABSTRACT
Residual pesticides in agricultural environments, including soil and irrigation water, can be taken up by plants, and thus pose a potential risk to food safety. Although tolfenpyrad has been widely used in tea plantations, limited information is available on its root uptake and fate in tea plants (Camellia sinensis L.). Exploring the mechanisms involved is crucial for understanding the migration and accumulation of tolfenpyrad in tea plants, particularly in the edible parts. In this study, root uptake of tolfenpyrad and its subsequent translocation, distribution, and metabolism in tea seedlings were investigated. The results indicated that the passive transport and apoplastic pathway dominated the root uptake of tolfenpyrad. After uptake, tolfenpyrad distributed predominantly in the cell walls (90.8-92.0 %) of roots, resulting in limited upward translocation in water-soluble fractions through transpirational pull, with translocation factor values far <1 (TFstem/root = 0.115-0.453 and TFleaf/stem = 0.039-0.184). Similar accumulation patterns were observed for the carboxylated metabolite PT-CA as well as hydroxylated metabolite PT-OH. Interestingly, the subcellular distribution of PT-CA in stems was much different from that of the parent tolfenpyrad: PT-CA mainly distributed in the stem cell walls (41.72 %) and cell organelles (56.18 %) at 3 h, then gradually transferred into the cell-soluble fractions (33.07 %) after 120 h. Results from the present study indicated limited upward translocation of tolfenpyrad with its main metabolites to leaves. This finding helps to alleviate concerns about environmental residual tolfenpyrad in tea consumption and provides valuable information for the safety evaluation of tolfenpyrad.
Subject(s)
Camellia sinensis , Plant Roots , Soil Pollutants , Camellia sinensis/metabolism , Plant Roots/metabolism , Soil Pollutants/metabolism , Soil Pollutants/analysisABSTRACT
Cough is one of the most common symptoms observed in patients presenting with COVID-19, persisting for an extended duration following SARS-CoV-2 infection. We aim to describe the distribution of airway microbiota and explore its role in patients with post-COVID-19 chronic cough. A total of 57 patients experiencing persistent cough after infection were recruited during the Omicron wave of SARS-CoV-2 in China. Airway microbiota profiling is assessed in nasopharyngeal swab, nasal lavage, and induced sputum samples at 4 and 8 weeks after SARS-CoV-2 infection. Our findings reveal that bacterial families Staphylococcaceae, Corynebacteriaceae, and Enterobacteriaceae are the most prevalent in the upper airway, while Streptococcaceae, Lachnospiraceae, and Prevotellaceae emerge as the most prevalent bacterial families in the lower airway. An increase in the abundance of Staphylococcus in nasopharyngeal swab samples and of Streptococcus in induced sputum samples is observed after one month. Furthermore, the abundance of Staphylococcus identified in nasopharyngeal swab samples at the baseline period emerges as an insightful predictor for improvement in cough severity. In conclusion, dynamic alterations in the airway microbial composition may contribute to the post-COVID-19 chronic cough progression, while the compositional signatures of nasopharyngeal microbiota could reflect the improvement of this disease.
ABSTRACT
Hickory is an abundant source of phenolic compounds that exhibit a diverse range of bioactivities. In this study, phenolic compounds were extracted and purified from hickory green husk (HG), hickory nutshell (HN), and hickory seed coat (HS) using solid-phase extraction and ultrasonication (SPE-US). The effects of the SPE-US treatment on the structure and properties of the phenolic compounds were then investigated, including their composition, antioxidant activity, and antimicrobial activity. The dominant phenolic substances in the different extracts after SPE-US treatment were: ellagic acid and trans ferulic acid (HS); ellagic acid and sinapic acid (HN); and rutin (HG). The HS-SPE-US1 extract exhibited the highest total polyphenol content (416 ± 11 mg GAE/g DW), total flavonoid content (47.51 ± 0.68 mg RE/g DW), Fe3+ reduction ability (74.2 ± 1.0 mmol Fe2+/g DW), radical (DPPH and ABTS) scavenging ability, and antimicrobial activity against Staphylococcus aureus.
Subject(s)
Antioxidants , Phenols , Plant Extracts , Solid Phase Extraction , Staphylococcus aureus , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/isolation & purification , Phenols/chemistry , Phenols/pharmacology , Phenols/isolation & purification , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/isolation & purification , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Sonication , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Waste Products/analysisABSTRACT
The present study aimed to identify and verify new plasma protein markers to predict the female fecundability level. A nested case-control study was conducted involving couples who participated in the Chinese National Free Preconception Check-up Project. Women who successfully conceive within one year were defined as the high fecundability group, and those unable to conceive were defined as the low fecundability group. In the training cohort, potential protein biomarkers were identified using proteomics technology and were further tested in a validation cohort by the Western blotting assay, enzyme-linked immunosorbent assay, and biochemical tests. Meanwhile, receiver operating characteristic curve analysis were used to evaluate the predictive value. Cox proportional hazard regression analyses were conducted to calculate hazard ratios; restricted cubic spline analysis was used to assess the linear relationship between the the protein level and hazard ratios for fecundability. Pyruvate, a key product of glycolysis, was significantly increased in the high fecundability group (P < 0.01) compared to the low fecundability group, and its area under the curve value was 0.68 (P < 0.05). There was a linear positive dose-response association between the pyruvate level and fecundability possibility (hazard ratios = 1.66, 95% CI: 1.07-2.59, p for trend = 0.025, nonlinearity, p-value = 0.2927).
Subject(s)
Biomarkers , Fertility , Proteomics , Humans , Female , Case-Control Studies , Biomarkers/blood , Proteomics/methods , Adult , Pyruvic Acid/blood , ROC Curve , Blood Proteins/analysis , Proportional Hazards ModelsABSTRACT
Aims: Vitamin D deficiency (VDD) is prevalent in the population, with inadequate intake, impaired absorption and metabolism as the main causative factors. VDD increases the risk of developing chronic diseases such as type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), but the molecular mechanisms underlying this phenomenon are not known. The aim of this study was to investigate the association and potential mechanisms of vitamin D levels with the progression of DN by analyzing general clinical data and using bioinformatics methods. Methods: The study included 567 diabetes mellitus type 2 (T2DM) patients from the Rocket Force Characteristic Medical Center as the case group and 221 healthy examinees as the normal control group. T2DM patients were categorized into T2DM, early diabetic nephropathy (EDN), and advanced diabetic nephropathy (ADN) based on the progression of diabetic nephropathy. The renal RNA-seq and scRNA-seq data of patients with DN were mined from public databases, and the differential expression of vitamin D-related genes in normal-EDN-ADN was analyzed by bioinformatics method, protein interaction network was constructed, immune infiltration was evaluated, single cell map was drawn, and potential mechanisms of VD and DN interaction were explored. Results: Chi-square test showed that vitamin D level was significantly negatively correlated with DN progression (p < 0.001). Bioinformatics showed that the expression of vitamin D-related cytochrome P450 family genes was down-regulated, and TLR4 and other related inflammatory genes were abnormally up-regulated with the progression of DN. Vitamin D metabolism disturbance up-regulate "Nf-Kappa B signaling pathway," B cell receptor signaling pathway and other immune regulation and insulin resistance related pathways, and inhibit a variety of metabolic pathways. In addition, vitamin D metabolism disturbance are strongly associated with the development of diabetic cardiomyopathy and several neurological disease complications. Conclusion: VDD or vitamin D metabolism disturbance is positively associated with the severity of renal injury. The mechanisms may involve abnormal regulation of the immune system by vitamin D metabolism disturbance, metabolic suppression, upregulation of insulin resistance and inflammatory signalling pathways.
ABSTRACT
Effect modification of integrated neighborhood environment on associations of air pollution with mortality remained unclear. We analyzed data from UK biobank prospective study (n = 421,650, median 12.5 years follow-up) to examine disparities of mortality risk associated with air pollution among varied neighborhood settings. Fine particulate matter (PM2.5), PM10 and nitrogen dioxide (NO2) were measured and assigned to each participants' address. Diverse ecological and societal settings of neighborhoods were integrated with principal component analysis and categorized into disadvantaged, intermediate and advantaged levels. We estimated mortality risk associated with air pollution across diverse neighborhoods using Cox regression. We calculated community-level proportions of mortality attributable to air pollutants. There was evidence of higher all-cause and respiratory disease mortality risk associated with PM2.5 and NO2 among those in disadvantaged neighborhoods. In disadvantaged communities, air pollutants explained larger proportions of deaths and such disparities persisted over past decades. Across 2010-2021, reducing PM2.5 and NO2 to 10 µg/m3 (World Health Organization limits) would save 87,000 (52,000-120,000) and 91,000 (37,000-145,000) deaths of populations aged ≥ 40 years, with 150 000 deaths occurred in disadvantaged neighborhood settings. These findings suggested that disadvantaged neighborhoods can exacerbate mortality risk associated with air pollution.
Subject(s)
Air Pollutants , Air Pollution , Nitrogen Dioxide , Particulate Matter , Humans , Prospective Studies , Particulate Matter/analysis , Middle Aged , Nitrogen Dioxide/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Male , Female , Air Pollutants/analysis , Air Pollutants/adverse effects , Air Pollutants/toxicity , Aged , Adult , Residence Characteristics , Mortality/trends , Environmental Exposure/adverse effects , United Kingdom , Neighborhood CharacteristicsABSTRACT
The Rab proteins primarily regulate vesicular transport between membrane-bound organelles and are important for innate immune. However, there is currently a lack of studies on crustaceans regarding Rab proteins, particularly core Rabs. We identified a Rab11 gene from Procambarus clarkii (PcRab11) and evaluated its potential involvement in immune response. The results showed PcRab11 was 1789 bp long, with an open reading frame of 645 bp encoding 211 amino acids and an estimated molecular weight of 23.8 kDa. Sequence analysis revealed its remarkable evolutionary conservation. The PcRab11 was widely expressed in various tissues, with highest levels in hepatopancreas, and localized within the cell cytoplasm. Upon infection with white spot syndrome virus (WSSV) or Aeromonas veronii, the expression of PcRab11 in immune organs was significantly induced. Furthermore, silencing PcRab11 reduced phagocytosis-related genes expression and haemocytes' phagocytic activity to FITC-labeled A. veronii, as well as decreased mortality and death time in WSSV or A. veronii infected P. clarkii. Additionally, the potential protein interaction between PcRab11 and 14-3-3ε was identified in haemocytes. Overall, our findings provided evidence for the involvement of Rab11 in P. clarkii's immune response, establishing a foundation to explore the immune role of core Rab proteins in crustaceans' innate immune system.