ABSTRACT
Natriuretic peptide receptor-C (NPR-C) is highly expressed in adipose tissues, and regulates obesity related diseases, however the detailed mechanism remains unknown. In this research, we aimed to explore the potential role of NPR-C in cold exposure and high-fat/high-sugar (HF/HS) diet induced metabolic changes, especially in regulating white adipose tissue (WAT) mitochondrial function. Our findings showed that NPR-C expression, especially in epididymal WAT (eWAT), was reduced after cold exposure. Global Npr3 (gene encoding NPR-C protein) deficiency led to reduced body weight, increased WAT browning, thermogenesis, and enhanced expression of genes related to mitochondrial biogenesis. RNA-sequencing of eWAT showed that Npr3 deficiency enhanced expression of mitochondrial respiratory chain complex genes and promoted mitochondrial oxidative phosphorylation in response to cold exposure. In addition, Npr3 KO mice were able to resist obesity induced by HF/HS diet. Npr3 knockdown in stromal vascular fraction (SVF)-induced white adipocytes promoted the expression of proliferator-activated receptor gamma coactivator 1α (PGC1α), uncoupling protein 1 (UCP1) and mitochondrial respiratory chain complexes. Mechanistically, NPR-C inhibited cGMP and calcium signaling in an NPR-B-dependent manner but suppressed cAMP signaling in an NPR-B-independent manner. Moreover, Npr3 knockdown induced browning via AKT and p38 pathway activation, which were attenuated by Npr2 knockdown. Importantly, treatment with the NPR-C specific antagonist, AP-811, decreased WAT mass and increased PGC-1α, UCP1 and mitochondrial complex expression. These findings demonstrate that NPR-C deficiency enhances metabolic health by boosting energy expenditure in WAT, emphasizing the potential of NPR-C inhibition for treating obesity and related metabolic disorders.
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BACKGROUND: The global dementia prevalence is surging, necessitating research into contributing factors. We aimed to investigate the association between metabolic syndrome (MetS), its components, serum uric acid (SUA) levels, and dementia risk. METHODS: Our prospective study comprised 466,788 participants without pre-existing MetS from the UK Biobank. We confirmed dementia diagnoses based on the ICD-10 criteria (F00-03). To evaluate the dementia risk concerning MetS, its components, and SUA levels, we applied Cox proportional hazards models, while adjusting for demographic factors. RESULTS: Over a median follow-up of 12.7 years, we identified 6845 dementia cases. Individuals with MetS had a 25% higher risk of all-cause dementia (hazard ratio [HR] = 1.25, 95% confidence interval [CI] = 1.19-1.31). The risk increased with the number of MetS components including central obesity, dyslipidemia for high-density lipoprotein (HDL) cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides. Particularly for those with all five components (HR = 1.76, 95% CI = 1.51-2.04). Dyslipidemia for HDL cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides were independently associated with elevated dementia risk (p < 0.01). MetS was further linked to an increased risk of all-cause dementia (11%) and vascular dementia (VD, 50%) among individuals with SUA levels exceeding 400 µmol/L (all-cause dementia: HR = 1.11, 95% CI = 1.02-1.21; VD: HR = 1.50, 95% CI = 1.28-1.77). CONCLUSIONS: Our study provides robust evidence supporting the association between MetS, its components, and dementia risk. These findings emphasize the importance of considering MetS and SUA levels in assessing dementia risk, offering valuable insights for prevention and management strategies.
Subject(s)
Dementia , Dyslipidemias , Hyperglycemia , Hypertension , Metabolic Syndrome , Humans , Uric Acid , Prospective Studies , Risk Factors , Hypertension/complications , Cholesterol, HDL , Triglycerides , Dyslipidemias/complications , Dementia/etiology , Dementia/complicationsABSTRACT
Interleukin-20 (IL-20), as an essential member of IL-10 family, plays vital roles in mammalian immunological response such as antimicrobial, inflammation, hematopoiesis, and immune diseases. In teleost, the study about immune antimicrobial function of IL-20 is largely scarce. In this article, we revealed the expression profiles and the immunological functions of the IL-20 (CsIL-20) in tongue sole Cynoglossus semilaevis. CsIL-20 is composed of 183 amino acid residues, with seven cysteine residues and a typical IL-10 domain which comprises six α-helices and two ß-sheets, and shares 34.4-71.2 % identities with other teleost IL-20. CsIL-20 was constitutively expressed in a variety of tissues and regulated by bacterial invasion, and the recombinant CsIL-20 (rCsIL-20) could bind to different bacteria. In vitro rCsIL-20 could interact with the membrane of peripheral blood leukocytes (PBLs), leading to the attenuation of reactive oxygen species (ROS) production and acid phosphatase activity in PBLs. In line with In vitro results, In vivo rCsIL-20 could obviously suppressed the host immune against bacterial infection. Furthermore, knockdown of CsIL-20 in vivo could markedly enhance the host antibacterial immunity. Collectively, these observations offer new insights into the negative effect of CsIL-20 on antibacterial immunity.
Subject(s)
Anti-Infective Agents , Fish Diseases , Flatfishes , Interleukins , Animals , Interleukin-10 , Amino Acid Sequence , Fish Proteins , Leukocytes/metabolism , Bacteria/metabolism , Anti-Bacterial Agents , Fishes/metabolism , Mammals/metabolismABSTRACT
Eukaryotic genomes are generally organized in multiple chromosomes. Here we have created a functional single-chromosome yeast from a Saccharomyces cerevisiae haploid cell containing sixteen linear chromosomes, by successive end-to-end chromosome fusions and centromere deletions. The fusion of sixteen native linear chromosomes into a single chromosome results in marked changes to the global three-dimensional structure of the chromosome due to the loss of all centromere-associated inter-chromosomal interactions, most telomere-associated inter-chromosomal interactions and 67.4% of intra-chromosomal interactions. However, the single-chromosome and wild-type yeast cells have nearly identical transcriptome and similar phenome profiles. The giant single chromosome can support cell life, although this strain shows reduced growth across environments, competitiveness, gamete production and viability. This synthetic biology study demonstrates an approach to exploration of eukaryote evolution with respect to chromosome structure and function.
Subject(s)
Chromosomes, Artificial, Yeast/genetics , Genetic Engineering/methods , Genetic Fitness/genetics , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/genetics , Synthetic Biology/methods , Artificial Gene Fusion/methods , Centromere/genetics , Evolution, Molecular , Meiosis , Microbial Viability/genetics , Saccharomyces cerevisiae/growth & development , Spores, Fungal/genetics , Telomere/genetics , TranscriptomeABSTRACT
PURPOSE: Patients with gynaecological cancer often experience psychological issues due to multiple stressors. Psychological disturbances have debilitating effects on patients with gynaecological cancer. In recent decades, digital psychosocial interventions have rapidly advanced and been incorporated into mental health interventions. Digital psychosocial interventions could provide patients with several benefits over traditional in-person interventions, including convenience, anonymity, flexible scheduling, and geographic mobility. The aim of this systematic review was to synthesize the effectiveness of digital psychosocial intervention in reducing psychological distress, depression, and anxiety and improving health-related quality of life in patients with gynaecological cancer. METHODS: Three-step extensive search was performed on 22 December 2022 from nine bibliographic databases, trial registries and grey literature. Experimental studies involving patients with gynaecological cancer utilizing digital psychosocial interventions for the improvement of mental health outcomes were included. Meta-analysis was conducted using RevMan 5.4 software. Heterogeneity was analysed by Cochran's Q test and I2. Subgroup analyses were attempted to evaluate relative effect sizes of subgroup features. RESULTS: Meta-analysis of nine studies revealed small effect size in reduction of depression post-intervention (d = 0.24, 95% CI - 0.46 to - 0.02) and medium effect size in reduction of psychological distress post-intervention (d = 0.51, 95% CI - 0.81 to - 0.21) and follow-up (d = 0.65, 95% CI - 1.25 to - 0.05) compared to the control group. The effects of digital psychosocial interventions on anxiety and health-related quality of life were not statistically significant. CONCLUSIONS: Digital psychosocial interventions probably reduced psychological distress and slightly reduced depression amongst patients with gynaecological cancer compared to the control group, which can be integrated into clinical practice. Additional trials with rigorous methodology and bigger sample sizes are needed to validate findings. TRIAL REGISTRATION: PROSPERO (CRD42023389502).
Subject(s)
Anxiety , Depression , Genital Neoplasms, Female , Psychological Distress , Psychosocial Intervention , Quality of Life , Humans , Female , Genital Neoplasms, Female/psychology , Genital Neoplasms, Female/therapy , Anxiety/etiology , Anxiety/therapy , Anxiety/psychology , Depression/etiology , Depression/therapy , Depression/psychology , Psychosocial Intervention/methods , Stress, Psychological/therapy , Stress, Psychological/etiology , Stress, Psychological/psychology , Stress, Psychological/prevention & controlABSTRACT
Lakes and wetlands play pivotal roles in global organic matter storage, receiving significant inputs of organic material. However, the co-metabolic processes governing the decomposition of these organic materials and their impact on greenhouse gas emissions remain inadequately understood. This study aims to assess the effects of mixed decomposition involving macrophytes and cyanobacteria on carbon emissions. A series of microcosms was established to investigate the decomposition of macrophyte residues and algae over a period of 216 days. A two-component kinetic model was utilized to estimate methane (CH4) production rates. Gas isotope technology was employed to discern the contributions of CH4 produced by macrophyte residues or algae. Quantitative PCR and analysis of 16S rRNA gene amplicons were employed to assess changes in functional genes and microbial communities. There were significant differences in the cumulative carbon release from the decomposition of different plant types due to the addition of carbon sources. After adding algae, the cumulative emission of CH4 increased significantly. The δ13C-CH4 partitioning indicated that CH4 originated exclusively from the fresh organic carbon of macrophyte residues, while it shifted to algae source after adding algae. The synergistic effect of the mixed decomposition on the CH4 emissions was greater than the sum of the individual decompositions. The microbial community richness was higher in the single plant residue treatment compared to the mixed treatment with algae addition, while microbial evenness in the sediment increased steadily in each treatment. Our findings emphasize the pronounced co-metabolic effect observed during the mixed decomposition of macrophytes and cyanobacteria.
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BACKGROUND: Breast cancer (BC) ranks as the third most fatal malignant tumor worldwide, with a strong reliance on fatty acid metabolism. CLDN6, a candidate BC suppressor gene, was previously identified as a regulator of fatty acid biosynthesis; however, the underlying mechanism remains elusive. In this research, we aim to clarify the specific mechanism through which CLDN6 modulates fatty acid anabolism and its impact on BC growth and metastasis. METHODS: Cell function assays, tumor xenograft mouse models, and lung metastasis mouse models were conducted to evaluate BC growth and metastasis. Human palmitic acid assay, triglyceride assay, Nile red staining, and oil red O staining were employed to investigate fatty acid anabolism. Reverse transcription polymerase chain reaction (RT-PCR), western blot, immunohistochemistry (IHC) assay, nuclear fractionation, immunofluorescence (IF), immunoprecipitation and acyl-biotin exchange (IP-ABE), chromatin immunoprecipitation (ChIP), dual luciferase reporter assay, and co-immunoprecipitation (Co-IP) were applied to elucidate the underlying molecular mechanism. Moreover, tissue microarrays of BC were analyzed to explore the clinical implications. RESULTS: We identified that CLDN6 inhibited BC growth and metastasis by impeding RAS palmitoylation both in vitro and in vivo. We proposed a unique theory suggesting that CLDN6 suppressed RAS palmitoylation through SREBP1-modulated de novo palmitic acid synthesis. Mechanistically, CLDN6 interacted with MAGI2 to prevent KLF5 from entering the nucleus, thereby restraining SREBF1 transcription. The downregulation of SREBP1 reduced de novo palmitic acid synthesis, hindering RAS palmitoylation and subsequent endosomal sorting complex required for transport (ESCRT)-mediated plasma membrane localization required for RAS oncogenic activation. Besides, targeting inhibition of RAS palmitoylation synergized with CLDN6 to repress BC progression. CONCLUSIONS: Our findings provide compelling evidence that CLDN6 suppresses the palmitic acid-induced RAS palmitoylation through the MAGI2/KLF5/SREBP1 axis, thereby impeding BC malignant progression. These results propose a new insight that monitoring CLDN6 expression alongside targeting inhibition of palmitic acid-mediated palmitoylation could be a viable strategy for treating oncogenic RAS-driven BC.
Subject(s)
Breast Neoplasms , Cell Proliferation , Claudins , Lipoylation , Sterol Regulatory Element Binding Protein 1 , Humans , Animals , Female , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 1/genetics , Mice , Claudins/metabolism , Claudins/genetics , Cell Proliferation/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Mice, Nude , Neoplasm Metastasis , ras Proteins/metabolism , ras Proteins/genetics , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/secondaryABSTRACT
Gefitinib is the first-generation drug of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) metabolised by the cytochrome P450 and transported by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). In the present study, the pharmacokinetics of gefitinib in healthy Chinese volunteers was investigated and the effect of genetic polymorphisms on its variability was evaluted.Forty-five healthy volunteers were administered a single dose of gefitinib and the blood samples were used for quantifying the concentration of gefitinib and genotyping fifteen single-nucleotide polymorphisms of cytochrome P450 enzymes (CYP3A4, CYP3A5, CYP2D6, CYP2C9 and CYP2C19) and drug transporters (ABCB1 and ABCG2).CYP3A5*3 (rs776746) polymorphism showed a significant influence, with higher gefitinib AUC0-t in carrier of CC genotype than in CT/TT genotype (BH-adjusted p value <0.05). For CYP2C9*3 (rs1057910), significant differences in pharmacokinetics of gefitinib were detected between carriers of AA and AC genotypes, with higher AUC0-t, AUC0-∞ and Cmax in carrier of AC genotype than in AA gen-otype (BH-adjusted p value <0.05). No associations were found between SNPs in CYP3A4, CYP2D6, CYP2C19, ABCB1, ABCG2 and the pharmacokinetics of gefitinib.The SNPs in CYP3A5*3 (rs776746) and CYP2C9*3 (rs1057910) were found to be associated with altered gefitinib pharmacokinetics in healthy Chinese volunteers.
Subject(s)
Cytochrome P-450 CYP2D6 , Cytochrome P-450 CYP3A , Humans , Cytochrome P-450 CYP3A/genetics , Cytochrome P-450 CYP3A/metabolism , Gefitinib , ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP2C19/metabolism , Cytochrome P-450 CYP2D6/metabolism , Healthy Volunteers , Cytochrome P-450 CYP2C9/genetics , Cytochrome P-450 CYP2C9/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Polymorphism, Single Nucleotide , Genotype , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , ChinaABSTRACT
Seven new monoterpene alkaloids (1 - 7), along with 16 known analogues, were isolated from an aqueous decoction of the hook-bearing stems of Uncaria rhynchophylla (Gou-teng). Their structures were determined by spectroscopic data analysis, single crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are stereoisomers belonging to a novel type of pseudoindoxyl monoterpene alkaloids, 3 is the first monoterpene furoindole alkaloid from nature, and 4 - 7 are derivatives of the known monoterpene alkaloids featuring different structures.
Subject(s)
Alkaloids , Uncaria , Indole Alkaloids/chemistry , Uncaria/chemistry , MonoterpenesABSTRACT
BACKGROUND: The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment. METHODS: Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology. RESULTS: (1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P < 0.05), and the remaining alpha diversity index did not significantly differ between the 2 groups (P > 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P < 0.05). (2) The core flora existed in both the pre- and posttreatment groups, and the proportion of their flora abundance could be altered depending on the caries status of the children in both groups. Leptotrichia abundance was significantly (P < 0.05) lower at 7 days posttreatment in both the single- and multiappointment groups. Corynebacterium and Corynebacterium_matruchotii were significantly more abundant in the C1_1M and C1_3M groups than in the C1 and C1_7D groups (P < 0.05). Streptococcus, Haemophilus and Haemophilus_parainfluenzae were significantly more abundant in the C1_7D group than in the other groups (P < 0.05). CONCLUSION: A single session of treatment under general anaesthesia can cause dramatic changes in the microbial community structure and composition within 7 days after treatment, whereas treatment over multiple appointments may cause slow changes in oral flora diversity.
Subject(s)
Dental Caries , Dental Plaque , Humans , Dental Plaque/microbiology , Dental Caries/microbiology , Dental Caries/therapy , Child, Preschool , Male , Female , Microbiota , Anesthesia, General , RNA, Ribosomal, 16SABSTRACT
Assembling different 2D nanomaterials into heterostructures with strong interfacial interactions presents a promising approach for novel artificial photocatalytic materials. Chemically implementing the 2D nanomaterials' construction/stacking modes to regulate different interfaces can extend their functionalities and achieve good performance. Herein, based on different fundamental principles and photochemical processes, multiple construction modes (e.g., face-to-face, edge-to-face, interface-to-face, edge-to-edge) are overviewed systematically with emphasis on the relationships between their interfacial characteristics (e.g., point, linear, planar), synthetic strategies (e.g., in situ growth, ex situ assembly), and enhanced applications to achieve precise regulation. Meanwhile, recent efforts for enhancing photocatalytic performances of 2D/2D heterostructures are summarized from the critical factors of enhancing visible light absorption, accelerating charge transfer/separation, and introducing novel active sites. Notably, the crucial roles of surface defects, cocatalysts, and surface modification for photocatalytic performance optimization of 2D/2D heterostructures are also discussed based on the synergistic effect of optimization engineering and heterogeneous interfaces. Finally, perspectives and challenges are proposed to emphasize future opportunities for expanding 2D/2D heterostructures for photocatalysis.
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Rice panicles, a major component of yield, are regulated by phytohormones and nutrients. How mineral nutrients promote panicle architecture remains largely unknown. Here, we report that NIN-LIKE PROTEIN3 and 4 (OsNLP3/4) are crucial positive regulators of rice panicle architecture in response to nitrogen (N). Loss-of-function mutants of either OsNLP3 or OsNLP4 produced smaller panicles with reduced primary and secondary branches and fewer grains than wild-type, whereas their overexpression plants showed the opposite phenotypes. The OsNLP3/4-regulated panicle architecture was positively correlated with N availability. OsNLP3/4 directly bind to the promoter of OsRFL and activate its expression to promote inflorescence meristem development. Furthermore, OsRFL activates OsMOC1 expression by binding to its promoter. Our findings reveal the novel N-responsive OsNLP3/4-OsRFL-OsMOC1 module that integrates N availability to regulate panicle architecture, shedding light on how N nutrient signals regulate panicle architecture and providing candidate targets for the improvement of crop yield.
Subject(s)
Oryza , Oryza/metabolism , Inflorescence/genetics , Promoter Regions, Genetic/genetics , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly. Dysregulation of intracellular Ca2+ homeostasis plays a critical role in the pathological development of AD. Dauricine (DAU) is a bisbenzylisoquinoline alkaloid isolated from Menispermum dauricum DC., which can prevent the influx of extracellular Ca2+ and inhibit the release of Ca2+ from the endoplasmic reticulum. DAU has a potential for anti-AD. However, it is unclear whether DAU can exert its anti-AD effect in vivo by regulating the Ca2+ related signaling pathways. Here, we investigated the effect and mechanism of DAU on D-galactose and AlCl3 combined-induced AD mice based on the Ca2+/CaM pathway. The results showed that DAU (1â¯mg/kg and 10â¯mg/kg for 30â¯days) treatment attenuated learning and memory deficits and improved the nesting ability of AD mice. The HE staining assay showed that DAU could inhibit the histopathological alterations and attenuate neuronal damage in the hippocampus and cortex of AD mice. Studies on the mechanism indicated that DAU decreased the phosphorylation of CaMKII and Tau and reduced the formation of NFTs in the hippocampus and cortex. DAU treatment also reduced the abnormally high expression of APP, BACE1, and Aß1-42, which inhibited the deposition of Aß plaques. Moreover, DAU could decrease Ca2+ levels and inhibit elevated CaM protein expression in the hippocampus and cortex of AD mice. The molecular docking results showed that DAU may have a high affinity with CaM or BACE1. DAU has a beneficial impact on pathological changes in AD mice induced by D-galactose and AlCl3 and may act by negative regulation of the Ca2+/CaM pathway and its downstream molecules such as CaMKII and BACE1.
Subject(s)
Alzheimer Disease , Benzylisoquinolines , Cognitive Dysfunction , Neurodegenerative Diseases , Mice , Animals , Alzheimer Disease/chemically induced , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Galactose/toxicity , Galactose/metabolism , Amyloid Precursor Protein Secretases/adverse effects , Amyloid Precursor Protein Secretases/metabolism , Neurodegenerative Diseases/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Molecular Docking Simulation , Aspartic Acid Endopeptidases/adverse effects , Aspartic Acid Endopeptidases/metabolism , Benzylisoquinolines/adverse effects , Hippocampus , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Disease Models, Animal , Amyloid beta-Peptides/metabolism , Mice, TransgenicABSTRACT
As one of the most abundant epigenetic modifications in RNA, N6-methyladenosine (m6A) affects RNA transcription, splicing, stability, and posttranscriptional translation. Methyltransferase-like 3 (METTL3), a key component of the m6A methyltransferase complex, dynamically regulates target genes expression through m6A modification. METTL3 has been found to play a critical role in tumorigenesis, tumor growth, metastasis, metabolic reprogramming, immune cell infiltration, and tumor drug resistance. As a result, the development of targeted drugs against METTL3 is becoming increasingly popular. This review systematically summarizes the factors that regulate METTL3 expression and explores the specific mechanisms by which METTL3 affects multiple tumor biological behaviors. We aim to provide fundamental support for tumor diagnosis and treatment, at the same time, to offer new ideas for the development of tumor-targeting drugs.
Subject(s)
Gene Expression Regulation, Neoplastic , Methyltransferases , Methyltransferases/genetics , RNAABSTRACT
Polyurethane (PU) is a versatile plastic that boasts high environmental resistance. The biodegradation of PU has become a hot topic of research aimed at finding ways to potentially solve PU pollutants. Identifying microorganisms capable of efficiently degrading PU plastics is pivotal for the development of a green recycling process for PU. This study aimed to isolate and characterize PU-degrading fungi from the soil of a waste transfer station in Luoyang, China. We isolated four different fungal strains from the soil. Among the isolates, the P2072 and P2073 strains were identified as Rhizopus oryzae (internal transcribed spacer identity, 99.66%) and Alternaria alternata (internal transcribed spacer identity, 99.81%), respectively, through microscopic, morphologic, as well as 18S rRNA sequencing. The degradation ability of strains P2072 and P2073 was analyzed through measurement of weight loss, and they exhibited a degradation rate of 2.7% and 3.3%, respectively, for the PU films after 2 months' growth in mineral salt medium (MSM) with PU films as the sole carbon source. In addition, the P2073 strain exhibited protease activity in the presence of PU. To our knowledge, R. oryzae has never been reported as a PU-degrading fungus. This study provides a new perspective on the biodegradation of PU.
Subject(s)
Environmental Pollutants , Polyurethanes , Polyurethanes/metabolism , Soil , Soil Microbiology , Fungi/genetics , Fungi/metabolism , Biodegradation, Environmental , Environmental Pollutants/metabolismABSTRACT
PURPOSE: Activation of mitogen-activated protein kinases (MAPKs) by pathological stimuli participates in cardiovascular diseases. Dysfunction of adventitial fibroblast has emerged as a critical regulator in vascular remodeling, while the potential mechanism remains unclear. In this study, we sought to determine the effect of different activation of MAPKs in adventitial fibroblast contributing to neointima formation. METHODS: Balloon injury procedure was performed in male 12-week-old Sprague-Dawley rats. After injury, MAPK inhibitors were applied to the adventitia of injured arteries to suppress MAPK activation. Adventitial fibroblasts were stimulated by platelet-derived growth factor-BB (PDGF-BB) with or without MAPK inhibitors. RNA sequencing was performed to investigate the change of pathway and cell function. Wound healing, transwell assay, and flow cytometry were used to analyze adventitial fibroblast function. RESULTS: Phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular regulated kinases 1/2 (ERK1/2) was increased in injured arteries after balloon injury. In primary culture of adventitial fibroblasts, PDGF-BB increased phosphorylation of p38, JNK, ERK1/2, and extracellular regulated kinase 5 (ERK5) in a short time, which was normalized by their inhibitors respectively. Compared with the injury group, perivascular administration of four MAPK inhibitors significantly attenuated neointima formation by quantitative analysis of neointimal area, intima to media (I/M) ratio, and lumen area. RNA sequencing of adventitial fibroblasts treated with PDGF-BB with or without four inhibitors demonstrated differentially expressed genes involved in multiple biological processes, including cell adhesion, proliferation, migration, and inflammatory response. Wound healing and transwell assays showed that four inhibitors suppressed PDGF-BB-induced adventitial fibroblast migration. Cell cycle analysis by flow cytometry demonstrated that JNK, ERK1/2, and ERK5 but not p38 inhibitor blocked PDGF-BB-induced G1 phase release associated with decrease expression of cell cycle protein Cyclin D1 and transcription factor GATA4. Moreover, four inhibitors decreased macrophage infiltration into adventitia and monocyte chemoattractant protein-1 (MCP-1) expression. CONCLUSION: These results suggest that MAPKs differentially regulate activation of adventitial fibroblast through GATA4/Cyclin D1 axis that participates in neointima formation.
ABSTRACT
The KEOPS complex is an evolutionarily conserved protein complex in all three domains of life (Bacteria, Archaea, and Eukarya). In budding yeast Saccharomyces cerevisiae, the KEOPS complex (ScKEOPS) consists of five subunits, which are Kae1, Bud32, Cgi121, Pcc1, and Gon7. The KEOPS complex is an ATPase and is required for tRNA N6-threonylcarbamoyladenosine modification, telomere length maintenance, and efficient DNA repair. Here, recombinant ScKEOPS full complex and Kae1-Pcc1-Gon7 and Bud32-Cgi121 subcomplexes were purified and their biochemical activities were examined. KEOPS was observed to have ATPase and GTPase activities, which are predominantly attributed to the Bud32 subunit, as catalytically dead Bud32, but not catalytically dead Kae1, largely eliminated the ATPase/GTPase activity of KEOPS. In addition, KEOPS could hydrolyze ADP to adenosine or GDP to guanosine, and produce PPi, indicating that KEOPS is an ADP/GDP nucleotidase. Further mutagenesis characterization of Bud32 and Kae1 subunits revealed that Kae1, but not Bud32, is responsible for the ADP/GDP nucleotidase activity. In addition, the Kae1V309D mutant exhibited decreased ADP/GDP nucleotidase activity in vitro and shortened telomeres in vivo, but showed only a limited defect in t6A modification, suggesting that the ADP/GDP nucleotidase activity of KEOPS contributes to telomere length regulation.
Subject(s)
Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Adenosine Triphosphatases/metabolism , Adenosine Diphosphate/metabolism , GTP Phosphohydrolases/metabolismABSTRACT
Since the public long-term care insurance (LTCI) system was piloted in Chengdu, China, in October 2017, there has been considerable growth of LTC institutions in China. This study aimed to evaluate the health value effect of LTCI in older patients with severe disabilities in an LTC institution. This prospective study was based on data from 985 severe disability patients with or without LTCI from October 2017 to May 2021 in the Eighth People's Hospital, Chengdu, China. The Cox proportional hazard model estimated LTCI's health value, including survival probability and risk of pneumonia/pressure ulcers. Subgroup analysis was performed for sex, age, Charlson Comorbidity Index (CCI), and the number of drugs. In the analysis, 519 and 466 patients in LTCI and non-LTCI groups were included, respectively. In adjusted Cox analyses, the LTCI group had a significantly elevated survival rate compared with the non-LTCI groups at 12 months (P < .001, hazard ratio (HR) = 1.758, 95% confidence interval (CI) 1.300-2.376). At 40 months, the adjusted survival rate was 62.6% in the LTCI group, which was significantly higher (53.7%; P = .003, HR = 1.438, 95% CI 1.131-1.831). The subgroups of patients aged 60 to 79 years (interaction P = .007) and with CCI ≥ 3 (interaction P = .026) were more significantly associated with survival improvement than those aged >80 years and with CCI< 3. The LTCI group was also at lower risk for hospital-acquired pneumonia (P = .016, HR 0.622, 95% CI 0.422-0.917) and pressure ulcers (P = .008, HR 0.695, 95% CI 0.376-0.862). The improved survival of LTCI remained stable in sensitivity analyses. For older patients with severe disabilities, in a LTC institution, LTCI significantly improved their health profile and longevity after a year, suggesting the large role and development potentiality of institution care in the LTCI system of China.
Subject(s)
Insurance, Long-Term Care , Pressure Ulcer , Humans , Aged , Prospective Studies , China , Outcome Assessment, Health Care , Long-Term CareABSTRACT
The application of reservoirs in the upper reaches of rivers will change the hydrological rhythm of river-connected wetlands in the lower reaches, causing changes in the distribution of wetland vegetation. The differences of carbon and nitrogen sequestration and emission potential in different vegetations may lead to the dynamics of greenhouse gas emissions from wetlands during hydrological periods. For a wetland connected to the Yangzi River, China, the dynamic changes of vegetation and water areas were identified by remote sensing, and the water level, the emission fluxes of greenhouse gases and the functional bacteria of carbon and nitrogen in soil were measured in-situ. Compared with drought period, the area of phragmites zone in flooding period increased by 28.2%, while the areas of carex and phalaris zones decreased by 42.9%. The carbon and nitrogen accumulation in the soil of phragmites zone is the highest, while the cumulative amount of phalaris is the lowest. The emission fluxes of CH4 and N2O in mud/water and various vegetations were positively correlated with water level and reached the maximum during flooding period. Although the global warming potential of mud/water was highest than that of vegetations, carex zone had the highest warming potential among vegetation zones. CH4 contributes 8-37 times as much as N2O to global warming potential in the wetland. The increase of flooding time promoted the emissions of CH4 and N2O in the wetland. The anaerobic condition caused by flooding stimulated the activities of denitrifying and methanogenic bacteria, thus increasing the emission of greenhouse gases. The sequestrations and emissions of carbon and nitrogen regulated by a reservoir in the upstream suggest that the operation of water conservancies should be considered to alleviate the greenhouse gas emission from river-connected wetland.
Subject(s)
Greenhouse Gases , Greenhouse Gases/analysis , Wetlands , Rivers , Carbon Dioxide/analysis , Environmental Monitoring , Methane/analysis , Nitrous Oxide/analysis , Poaceae , Soil , Nitrogen , CarbonABSTRACT
Artificial ecosystems with high biological complexity are generally considered to be efficient in metabolizing substances and resistant to temperature shock. In this study, a novel near-natural system (BCT system), which consisted of simple biofilter, constructed wetland and trophic biology pond, was conducted to treat rural sewage in situ for irrigation into farmland. Water quality related to carbon and nutrients and microbial community were analyzed along the system to reveal the effect of each unit. The annual average removals of BCT system for TN, NH4+-N, TP and COD could reach 46.53%, 52.18%, 41.48%, and 53.21%, respectively. There was no significant decrease for removal efficiencies from high temperature period (HTP, ≥15 °C) to low temperature period (LTP, <15 °C). In LTP, the trophic pond (TRP) removed 34.85% of TN, 33.93% of NH4+-N, 13.71% of TP and 18.77% of COD, while the removal efficiencies of constructed wetland fluctuated greatly. The TRP facilitated the BCT system to maintain the removal capability during low temperature period. The relative abundance of denitrification functional genes in TRP increased nearly tenfold from HTP to LTP. The effluent quality from the system can meet the agricultural irrigation standards, demonstrating the effect of BCT system on sewage treatment and agricultural irrigation in rural area.