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1.
J Med Genet ; 61(7): 677-688, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38443156

ABSTRACT

BACKGROUND: Epigenetics makes substantial contribution to the aetiology of autism spectrum disorder (ASD) and may harbour a unique opportunity to prevent the development of ASD. We aimed to identify novel epigenetic genes involved in ASD aetiology. METHODS: Trio-based whole exome sequencing was conducted on ASD families. Genome editing technique was used to knock out the candidate causal gene in a relevant cell line. ATAC-seq, ChIP-seq and RNA-seq were performed to investigate the functional impact of knockout (KO) or mutation in the candidate gene. RESULTS: We identified a novel candidate gene NASP (nuclear autoantigenic sperm protein) for epigenetic dysregulation in ASD in a Chinese nuclear family including one proband with autism and comorbid atopic disease. The de novo likely gene disruptive variant tNASP(Q289X) subjects the expression of tNASP to nonsense-mediated decay. tNASP KO increases chromatin accessibility, promotes the active promoter state of genes enriched in synaptic signalling and leads to upregulated expression of genes in the neural signalling and immune signalling pathways. Compared with wild-type tNASP, tNASP(Q289X) enhances chromatin accessibility of the genes with enriched expression in the brain. RNA-seq revealed that genes involved in neural and immune signalling are affected by the tNASP mutation, consistent with the phenotypic impact and molecular effects of nasp-1 mutations in Caenorhabditis elegans. Two additional patients with ASD were found carrying deletion or deleterious mutation in the NASP gene. CONCLUSION: We identified novel epigenetic mechanisms mediated by tNASP which may contribute to the pathogenesis of ASD and its immune comorbidity.


Subject(s)
Autism Spectrum Disorder , Autoantigens , Epigenesis, Genetic , Nuclear Proteins , Female , Humans , Male , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/immunology , Autistic Disorder/genetics , Autistic Disorder/pathology , Exome Sequencing , Genetic Predisposition to Disease , Mutation , Pedigree , Signal Transduction/genetics , Autoantigens/genetics , Nuclear Proteins/genetics
2.
J Allergy Clin Immunol ; 153(6): 1668-1680, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38191060

ABSTRACT

BACKGROUND: CLEC16A intron 19 has been identified as a candidate locus for common variable immunodeficiency (CVID). OBJECTIVES: This study sought to elucidate the molecular mechanism by which variants at the CLEC16A intronic locus may contribute to the pathogenesis of CVID. METHODS: The investigators performed fine-mapping of the CLEC16A locus in a CVID cohort, then deleted the candidate functional SNP in T-cell lines by the CRISPR-Cas9 technique and conducted RNA-sequencing to identify target gene(s). The interactions between the CLEC16A locus and its target genes were identified using circular chromosome conformation capture. The transcription factor complexes mediating the chromatin interactions were determined by proteomic approach. The molecular pathways regulated by the CLEC16A locus were examined by RNA-sequencing and reverse phase protein array. RESULTS: This study showed that the CLEC16A locus is an enhancer regulating expression of multiple target genes including a distant gene ATF7IP2 through chromatin interactions. Distinct transcription factor complexes mediate the chromatin interactions in an allele-specific manner. Disruption of the CLEC16A locus affects the AKT signaling pathway, as well as the molecular response of CD4+ T cells to immune stimulation. CONCLUSIONS: Through multiomics and targeted experimental approaches, this study elucidated the underlying target genes and signaling pathways involved in the genetic association of CLEC16A with CVID, and highlighted plausible molecular targets for developing novel therapeutics.


Subject(s)
Common Variable Immunodeficiency , Introns , Lectins, C-Type , Monosaccharide Transport Proteins , Humans , Lectins, C-Type/genetics , Introns/genetics , Monosaccharide Transport Proteins/genetics , Common Variable Immunodeficiency/genetics , Common Variable Immunodeficiency/immunology , Polymorphism, Single Nucleotide , Gene Expression Regulation , Female , Male , Signal Transduction/genetics , CD4-Positive T-Lymphocytes/immunology , Adult
3.
Anal Chem ; 96(3): 1112-1120, 2024 01 23.
Article in English | MEDLINE | ID: mdl-38181398

ABSTRACT

Oblique-incidence reflectivity difference (OIRD) is a novel real-time, label-free, and nondestructive optical detection method and exhibits encouraging application in the detection of antibody/DNA microarrays. In this study, for the first time, an OIRD label-free immunoassay was achieved by using adherent live cells as the probe. The cells were cultured on glass cells, and the affinity binding of antibodies targeted on the HLA class I antigen of the cell surface was detected with an OIRD. The results show that an OIRD is able to detect the binding process of anti-human HLA-A, B, and C antibodies on MDA-MB-231 cells and HUVEC cells. Control experiments and complementary fluorescence analysis confirmed the high detection specificity and good quantitative virtue of the OIRD label-free immunoassay. Label-free OIRD imaging analysis of cell microarrays was further demonstrated successfully, and the underlying optical mechanism was revealed by combining the theoretical modeling. This work explores the use of live cells as probes for an OIRD immunoassay, thus expanding the potential applications of the OIRD in the field of pathological analysis, disease diagnosis, and drug screening, among others.


Subject(s)
Antibodies , Glass , Oligonucleotide Array Sequence Analysis , Immunoassay
4.
Chembiochem ; 25(3): e202300575, 2024 02 01.
Article in English | MEDLINE | ID: mdl-37963820

ABSTRACT

Salmonella constitutes a prevalent alimentary pathogen, instigating zoonotic afflictions. Consequently, the prompt discernment of Salmonella in sustenance is of cardinal significance. Lateral flow assays utilizing colorimetric methodologies adequately fulfill the prerequisites of point-of-care diagnostics, however, their detection threshold remains elevated, generally permitting only qualitative discernment, an impediment to the preliminary screening of nascent pathogens. In response to this conundrum, we propose a lateral flow diagnostic predicated upon a streptavidin-biotin amplification system with recombinase polymerase amplification engineered for the expeditious and quantitative discernment of Salmonella enteritidis. Trace nucleic acids within a sample undergo exponential amplification via recombinase polymerase amplification to a level discernable, constituting the initial signal amplification. Subsequently, along the test line (T-line) of the lateral flow strip, the chromatic signal undergoes augmentation by securing a greater quantity of AuNPs through the magnification capacity of the streptavidin-biotin mechanism, affecting the second signal amplification. Quantitative results are procured via smartphone capture and transferred to computer software for precise calculation of the targeted quantity. The lateral flow strip exhibits a LOD at 19.41 CFU/mL for cultured S. enteritidis. The RSD of three varying concentrations were respectively 3.74 %, 5.96 %, and 4.25 %.


Subject(s)
Metal Nanoparticles , Salmonella enteritidis , Salmonella enteritidis/genetics , Biotin , Streptavidin , Recombinases , Gold , Nucleotidyltransferases , Nucleic Acid Amplification Techniques/methods , Sensitivity and Specificity
5.
Article in English | MEDLINE | ID: mdl-38317060

ABSTRACT

BACKGROUND: The genetic architecture of juvenile idiopathic arthritis (JIA) remains only partially comprehended. There is a clear imperative for continued endeavors to uncover insights into the underlying causes of JIA. METHODS: This study encompassed a comprehensive spectrum of endeavors, including conducting a JIA GWAS meta-analysis that incorporated data from 4,550 JIA cases and 18 446 controls. We employed in silico and genome-editing approaches to prioritize target genes. To investigate pleiotropic effects, we conducted phenome-wide association studies. Cell-type enrichment analyses were performed by integrating bulk and single-cell sequencing data. Finally, we delved into potential druggable targets for JIA. RESULTS: Fourteen genome-wide significant non-HLA loci were identified including four novel loci, each exhibiting pleiotropic associations with other autoimmune diseases or musculoskeletal traits. We uncovered strong genetic correlation between JIA and bone mineral density (BMD) traits at 52 genomic regions, including three GWAS loci for JIA. Candidate genes with immune functions were captured by in silico analyses at each novel locus, with additional findings identified through our experimental approach. Cell-type enrichment analysis revealed 21 specific immune cell types crucial for affected organs in JIA, indicating their potential contribution to the disease. Finally, 24 known or candidate druggable target genes were prioritized. CONCLUSIONS: Our identification of four novel JIA associated genes, CD247, RHOH, COLEC10 and IRF8, broadens novel potential drug repositioning opportunities. We established a new genetic link between COLEC10, TNFRSF11B and JIA/BMD. Additionally, the identification of RHOH underscores its role in positive thymocyte selection, thereby illuminating a critical facet of JIA's underlying biological mechanisms.

6.
Oncology ; 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37918372

ABSTRACT

In this study, clinical trials were generalized, summarized, and meta-analyzed to evaluate correlations between artificial sweeteners (ASs) and colorectal cancer (CRC). PubMed, Web of Science, EMBASE (Ovid platform), MEDLINE, and the Cochrane Library databases were searched from inception until July 24, 2023. The association between AS exposure and CRC incidence was assessed using odds ratios (ORs) and 95% confidence intervals (CIs). STATA software (version 12.0) was used to perform the meta-analysis. Ten studies (three case-control studies and seven cohort studies) involving 711,537 participants were identified. Results showed that the intake of ASs reduced the incidence of CRC (OR=0.93, 95% CI=[0.87-0.99]) and was not significantly associated with mortality (OR=0.93, 95% CI=[0.83-1.05]). Subgroup analyses showed that low doses of ASs were associated with lower CRC incidence (OR=0.90, 95% CI=[0.83-0.99]), and medium/high doses were not associated with CRC incidence (OR=1.11, 95% CI=[0.93-1.33]; OR=0.89, 95% CI=[0.79-1.00], respectively). Moreover, low, medium, and high exposures were not associated with an increased risk of mortality due to CRC (OR=0.95, 95% CI=[0.80-1.14]; OR=0.99, 95% CI=[0.88-1.11]; OR=0.93, 95% CI=[0.71-1.21], respectively). The results of our meta-analysis showed that a low intake of ASs may be associated with a lower risk of CRC.

7.
Plant Cell ; 31(9): 2107-2130, 2019 09.
Article in English | MEDLINE | ID: mdl-31227558

ABSTRACT

Abscisic acid (ABA) and reactive oxygen species (ROS) act as key signaling molecules in the plant response to salt stress; however, how these signals are transduced and amplified remains unclear. Here, a soybean (Glycine max) salinity-induced NAM/ATAF1/2/CUC2 (NAC) transcription factor encoded by SALT INDUCED NAC1 (GmSIN1) was shown to be a key component of this process. Overexpression of GmSIN1 in soybean promoted root growth and salt tolerance and increased yield under salt stress; RNA interference-mediated knockdown of GmSIN1 had the opposite effect. The rapid induction of GmSIN1 in response to salinity required ABA and ROS, and the effect of GmSIN1 on root elongation and salt tolerance was achieved by boosting cellular ABA and ROS contents. GmSIN1 upregulated 9-cis-epoxycarotenoid dioxygenase coding genes in soybean (GmNCED3s, associated with ABA synthesis) and Respiratory burst oxidase homolog B genes in soybean (GmRbohBs, associated with ROS generation) by binding to their promoters at a site that has not been described to date. Together, GmSIN1, GmNCED3s, and GmRbohBs constitute a positive feed-forward system that enables the rapid accumulation of ABA and ROS, effectively amplifying the initial salt stress signal. These findings suggest that the combined modulation of ABA and ROS contents enhances soybean salt tolerance.


Subject(s)
Cell Cycle Proteins/metabolism , Dioxygenases/metabolism , Glycine max/metabolism , Plant Proteins/metabolism , Plant Roots/metabolism , Ribonuclease III/metabolism , Salt Stress/physiology , Abscisic Acid/metabolism , Arabidopsis Proteins , Cell Cycle Proteins/genetics , Dioxygenases/genetics , Gene Expression Regulation, Plant/drug effects , Gene Knockdown Techniques , Plant Proteins/genetics , Plant Roots/growth & development , Plants, Genetically Modified , Reactive Oxygen Species/metabolism , Ribonuclease III/genetics , Salinity , Salt Stress/genetics , Salt Tolerance/genetics , Salt Tolerance/physiology , Glycine max/genetics , Stress, Physiological
8.
BMC Pulm Med ; 20(1): 19, 2020 Jan 21.
Article in English | MEDLINE | ID: mdl-31964358

ABSTRACT

BACKGROUND: Previous studies demonstrated an important role for connexin 43 (Cx43) in the regulation of apoptosis by influencing mitochondrial functions. This study aimed to investigate the relationship between Cx43 and lipopolysaccharide (LPS)-induced oxidative stress and apoptosis in human umbilical vein endothelial cells (HUVECs). METHODS: Western blot was performed to determine mitochondrial Cx43 (MtCx43) protein level and phosphorylation (p-MtCx43). Gap19, a selective Cx43 inhibitor, was used to examine the effects of Cx43 on LPS-induced oxidative stress and apoptosis in HUVECs. Expression of regulatory genes associated with oxidative stress was examined by quantitative polymerase chain reaction (qPCR) and Western blot. Apoptosis was assessed by flow cytometry. RESULTS: LPS stimulation resulted in increased levels of MtCx43 and p-MtCx43. Interestingly, Gap19 antagonized the upregulation of glutathione S-transferase Zeta 1 (GSTZ1) and cytochrome b alpha beta (CYBB), and the downregulation of antioxidant 1 (ATOX1), glutathione synthetase (GSS) and heme oxygenase 1 (HMOX1) induced by LPS or Cx43 overexpression. Moreover, the increased production of reactive oxygen species (ROS) and apoptosis elicited by LPS or Cx43 overexpression were reduced following treatment with Gap19. CONCLUSIONS: Selective inhibition of Cx43 hemichannels protects HUVECs from LPS-induced apoptosis and this may be via a reduction in oxidative stress production.


Subject(s)
Apoptosis/drug effects , Connexin 43/antagonists & inhibitors , Mitochondria/drug effects , Oxidative Stress/drug effects , Apoptosis/genetics , Connexin 43/drug effects , Connexin 43/genetics , Connexin 43/metabolism , Copper Transport Proteins/drug effects , Copper Transport Proteins/genetics , Down-Regulation , Gene Knock-In Techniques , Glutathione Synthase/drug effects , Glutathione Synthase/genetics , Glutathione Transferase/drug effects , Glutathione Transferase/genetics , Heme Oxygenase-1/drug effects , Heme Oxygenase-1/genetics , Human Umbilical Vein Endothelial Cells , Humans , Lipopolysaccharides/pharmacology , Mitochondria/metabolism , Molecular Chaperones/drug effects , Molecular Chaperones/genetics , NADPH Oxidase 2/drug effects , NADPH Oxidase 2/genetics , Oxidative Stress/genetics , Reactive Oxygen Species/metabolism , Up-Regulation
9.
Bioorg Med Chem ; 27(20): 114918, 2019 10 15.
Article in English | MEDLINE | ID: mdl-31178269

ABSTRACT

Twelve N-hydroxycinnamoyl amino acid amide ethyl esters (CAES) were synthesized by using l-amino acid ethyl ester hydrochloride and corresponding cinnamic acid (ferulic acid, acetylferulic acid and caffeic acid) as raw materials in the presence of a catalytic amount of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide-hydrochloride (EDC) and 1-hydroxybenzotriene (HOBt). The 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activities of CAES were evaluated. The anti-tyrosinase activities of N-feruloyl amino acid ethyl esters and the hydroxyl (OH) free radical scavenging activities of N-caffeoyl amino acid ethyl esters were also examined. DPPH free radical scavenging activity was shown in all CAES, of which N-caffeoyl amino acid ethyl esters demonstrated higher radical scavenging activity than N-feruloyl amide derivatives, and (E) -N-(caffeic acid)-l-glycinate ethyl ester (c5) had the strongest ability to scavenge free radicals with an IC50 value of 18.6 µM. The acetylferuloyl amino acid esters exhibited the highest tyrosinase inhibition activity among the tested amides.


Subject(s)
Amides/pharmacology , Antioxidants/pharmacology , Cinnamates/pharmacology , Enzyme Inhibitors/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Agaricales/enzymology , Amides/chemical synthesis , Amides/chemistry , Antioxidants/chemical synthesis , Antioxidants/chemistry , Benzothiazoles/antagonists & inhibitors , Cinnamates/chemical synthesis , Cinnamates/chemistry , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Molecular Structure , Monophenol Monooxygenase/metabolism , Structure-Activity Relationship , Sulfonic Acids/antagonists & inhibitors
10.
Plant Physiol ; 172(3): 1804-1820, 2016 11.
Article in English | MEDLINE | ID: mdl-27670816

ABSTRACT

Functional divergence is thought to be an important evolutionary driving force for the retention of duplicate genes. We reconstructed the evolutionary history of soybean (Glycine max) membrane-bound NAC transcription factor (NTL) genes. NTLs are thought to be components of stress signaling and unique in their requirement for proteolytic cleavage to free them from the membrane. Most of the 15 GmNTL genes appear to have evolved under strong purifying selection. By analyzing the phylogenetic tree and gene synteny, we identified seven duplicate gene pairs generated by the latest whole-genome duplication. The members of each pair were shown to have variously diverged at the transcriptional (organ specificity and responsiveness to stress), posttranscriptional (alternative splicing), and protein (proteolysis-mediated membrane release and transactivation activity) levels. The dormant (full-length protein) and active (protein without a transmembrane motif) forms of one pair of duplicated gene products (GmNTL1/GmNLT11) were each separately constitutively expressed in Arabidopsis (Arabidopsis thaliana). The heteroexpression of active but not dormant forms of these proteins caused improved tolerance to abiotic stresses, suggesting that membrane release was required for their functionality. Arabidopsis carrying the dormant form of GmNTL1 was more tolerant to hydrogen peroxide, which induces its membrane release. Tolerance was not increased in the line carrying dormant GmNTL11, which was not released by hydrogen peroxide treatment. Thus, NTL-release pattern changes may cause phenotypic divergence. It was concluded that a variety of functional divergences contributed to the retention of these GmNTL duplicates.


Subject(s)
Cell Membrane/metabolism , Evolution, Molecular , Genes, Plant , Glycine max/genetics , Plant Proteins/genetics , Transcription Factors/genetics , Alternative Splicing/genetics , Arabidopsis/genetics , Base Sequence , Conserved Sequence/genetics , Endoplasmic Reticulum/metabolism , Exons/genetics , Gene Expression Profiling , Gene Expression Regulation, Plant , Genes, Duplicate , Introns/genetics , Likelihood Functions , Models, Biological , Multigene Family , Nucleotide Motifs/genetics , Phylogeny , Plant Proteins/metabolism , Plants, Genetically Modified , Protein Binding , Stress, Physiological/genetics , Subcellular Fractions/metabolism , Synteny/genetics , Transcriptional Activation/genetics
11.
Int J Phytoremediation ; 17(9): 879-84, 2015.
Article in English | MEDLINE | ID: mdl-25581317

ABSTRACT

Monoculture and intercrop of hyperaccumulator Solanum nigrum L. with low accumulation Welsh onion Renbentieganchongwang were conducted. The results showed that the remove ratio of S. nigrum to Cd was about 7% in intercrop plot when top soil (0-20 cm) Cd concentration was 0.45-0.62 mg kg(-1), which did not significantly impact the yield of low accumulation Welsh onion compared to the monoculture. The consistency of remove ratio in practice and theory indicated the remediation of S. nigrum to Cd was significant. The Cd concentration and yield of Welsh onion were not affected by the growth of S. nigrum either in intercrop plot. The Cd concentration in edible parts of Welsh onion was available either. In short, inter-planting hyperaccumulator with low accumulation crop could normally remediate contaminated soil and produce crop (obtain economic benefit), which may be one practical pathway of phytoremediating heavy metal contaminated soil in the future.


Subject(s)
Cadmium/metabolism , Onions/metabolism , Soil Pollutants/metabolism , Solanum nigrum/metabolism , Biodegradation, Environmental
12.
Int J Phytoremediation ; 17(7): 657-61, 2015.
Article in English | MEDLINE | ID: mdl-25976879

ABSTRACT

Multiple crop experiment of hyperaccumulator Solanum nigrum L. with low accumulation Chinese cabbage Fenyuanxin 3 were conducted in a cadmium (Cd) contaminated vegetable field. In the first round, the average removal rate of S. nigrum to Cd was about 10% without assisted phytoextraction reagent addition for the top soil (0-20 cm) with Cd concentration at 0.53-0.97 mg kg(-1) after its grew 90 days. As for assisted phytoextraction reagent added plots, efficiency of Cd remediation might reach at 20%. However, in the second round, Cd concentration in Chinese cabbage was edible, even in the plots with assisted phytoextraction reagent added. Thus, multiple cropping hyperaccumulator with low accumulation crop could normally remediate contaminated soil and produce crop (obtain economic benefit) in one year, which may be one practical pathway of phytoremediating heavy metal contaminated soil in the future.


Subject(s)
Brassica rapa/metabolism , Cadmium/metabolism , Refuse Disposal , Soil Pollutants/metabolism , Solanum nigrum/metabolism , Biodegradation, Environmental
13.
Am J Transl Res ; 16(5): 1880-1890, 2024.
Article in English | MEDLINE | ID: mdl-38883384

ABSTRACT

This meta-analysis aims to explore the correlation between obesity and mortality in patients with sepsis. Data were gathered from various sources, including PubMed, the Cochrane Library, and Embase (no language restrictions). Clinical studies, both retrospective and prospective ones, were selected to analyze mortality due to sepsis in patients with or without obesity. The Newcastle-Ottawa Scale was used to assess the quality of the studies included. In data synthesis, odds ratio (OR) and 95% confidence interval (CI) were meta-analyzed using the DerSimonian-Laird random-effects model, followed by sensitivity and heterogeneity analyses. Two cohort studies were included to investigate survival in inpatients with obesity and sepsis, with pooled analysis indicating a lowered mortality rate (OR=0.88; 95% CI: 0.81-0.95; I2=0.00%; P=0.000). This meta-analysis lends support to the obesity paradox, suggesting a reduced mortality from sepsis in obese patients. However, further prospective trials and research on mechanisms are needed to test this hypothesis.

14.
Talanta ; 276: 126201, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38718653

ABSTRACT

Oblique-incidence reflectivity difference (OIRD) is a dielectric constant-sensitive technique and exhibits intriguing applications in label-free and high-throughput detection of protein microarrays. With the outstanding advantage of being compatible with arbitrary substrates, however, the effect of the substrate, particularly its dielectric constant on the OIRD sensitivity has not been fully disclosed. In this paper, for the first time we investigated the dependence of OIRD sensitivity on the dielectric constant of the substrate under top-incident OIRD configuration by combining theoretical modeling and experimental evaluation. Optical modeling suggested that the higher dielectric constant substrate exhibits a higher intrinsic sensitivity. Experimentally, three substrates including glass, fluorine-doped tin oxide (FTO) and silicon (Si) with different dielectric constants were selected as microarray substrates and their detection performances were evaluated. In good agreement with the modeling, high dielectric constant Si-based microarray exhibited the highest sensitivity among three chips, reaching a detection limit of as low as 5 ng mL-1 with streptavidin as the model target. Quantification of captured targets on three chips with on-chip enzyme-linked immunosorbent assay (ELISA) further confirmed that the enhanced performance originates from the high dielectric constant enhanced intrinsic OIRD sensitivity. This work thus provides a new way to OIRD-based label-free microarrays with improved sensitivity.


Subject(s)
Protein Array Analysis , Silicon , Tin Compounds , Protein Array Analysis/methods , Silicon/chemistry , Tin Compounds/chemistry , Glass/chemistry , Limit of Detection , Enzyme-Linked Immunosorbent Assay/methods , Fluorine/chemistry , Streptavidin/chemistry
15.
Front Immunol ; 15: 1336586, 2024.
Article in English | MEDLINE | ID: mdl-38504987

ABSTRACT

Introduction: Sepsis represents a critical medical condition that arises due to an imbalanced host reaction to infection. Central to its pathophysiology are cytokines. However, observational investigations that explore the interrelationships between circulating cytokines and susceptibility to sepsis frequently encounter challenges pertaining to confounding variables and reverse causality. Methods: To elucidate the potential causal impact of cytokines on the risk of sepsis, we conducted two-sample Mendelian randomization (MR) analyses. Genetic instruments tied to circulating cytokine concentrations were sourced from genome-wide association studies encompassing 8,293 Finnish participants. We then evaluated their links with sepsis and related outcomes using summary-level data acquired from the UK Biobank, a vast multicenter cohort study involving over 500,000 European participants. Specifically, our data spanned 11,643 sepsis cases and 474,841 controls, with subsets including specific age groups, 28-day mortality, and ICU-related outcomes. Results and Discussion: MR insights intimated that reduced genetically-predicted interleukin-10 (IL-10) levels causally correlated with a heightened sepsis risk (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.52-0.90, P=0.006). An inverse relationship emerged between monocyte chemoattractant protein-1 (MCP-1) and sepsis-induced mortality. Conversely, elevated macrophage inflammatory protein 1 beta (MIP1B) concentrations were positively linked with both sepsis incidence and associated mortality. These revelations underscore the causal impact of certain circulating cytokines on sepsis susceptibility and its prognosis, hinting at the therapeutic potential of modulating these cytokine levels. Additional research is essential to corroborate these connections.


Subject(s)
Cytokines , Sepsis , Humans , Cohort Studies , Genome-Wide Association Study , Mendelian Randomization Analysis , Sepsis/genetics
16.
Heliyon ; 10(3): e24409, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38322900

ABSTRACT

Background: SQSTM1/p62 is an autophagy-related receptor protein that participates in regulating tumorigenesis and multiple signaling pathways. Gastric cancer (GC) is a common tumor in the digestive tract and continues to pose a significant threat to human health. Therefore, this study aims to investigate the impact of p62 on gastric cancer. Methods: Immunohistochemistry and Western blotting were employed to assess the expression level of the p62 protein in gastric cancer tissues and its correlation with prognosis. Subsequently, in vitro cell experiments were conducted to determine the role of p62 in gastric cancer cell proliferation, migration, and metastasis. Result: The expression of p62 in gastric cancer tissues was significantly higher than in normal tissues. The expression of p62 was positively correlated with poor prognosis in gastric cancer patients. In vitro cell experiments indicated that p62 promotes gastric cancer cell proliferation and migration. Mechanistically, elevated p62 expression induced epithelial-mesenchymal transition (EMT), leading to upregulation of E-cadherin and downregulation of N-cadherin and vimentin. Conclusion: This study provides novel and robust evidence for the mechanism by which elevated p62 expression promotes the progression of gastric cancer. It offers promising therapeutic targets for anti-tumor treatment strategies in gastric cancer patients.

17.
Environ Sci Pollut Res Int ; 30(54): 115820-115838, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37897572

ABSTRACT

This study aims to investigate the water resource carrying capacity (WRCC) of Henan Province, identify its main obstacles, and provide suggestions for optimizing its WRCC. The article constructs a WRCC evaluation system with 20 indicators for the four subsystems of water resources, economy, society, and ecology based on literature and the actual situation of Henan Province. The entropy weighted TOPSIS method is used to calculate the WRCC of Henan Province from 2005 to 2021. The coupling coordination model is used to explore the degree of coupling coordination among internal systems, while the obstacle model is used to study its restrictive influencing factors. The study found that (1) the WRCC fluctuated in a U-shaped pattern around 0.5 during the study period; (2) the coupling and coordination degree of each subsystem is generally good, except for 2012 and 2013, which showed basic coordination; (3) currently, the main obstacles to the WRCC are ecosystems and water resources. The main indicators are afforestation area, proportion of the tertiary industry, fertilizer usage, and urban sewage treatment rate. Therefore, Henan Province should take measures such as reducing fertilizer usage, standardizing urban sewage treatment, improving water efficiency, and optimizing industrial structure to optimize its WRCC and promote comprehensive utilization of water resources.


Subject(s)
Conservation of Natural Resources , Water Resources , Ecosystem , Entropy , Fertilizers , Sewage , China , Cities
18.
Bioresour Technol ; 367: 128242, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36332855

ABSTRACT

In this study, an ammonia fiber expansion (AFEX)-assisted deep eutectic solvent (DES) pretreatment method was developed for the rapid separation of wheat straw fractions, which reduced the pretreatment time for DES and improved the pretreatment efficiency. This study describes the feasibility of the AFEX-assisted DES pretreatment in terms of both progressive and parallel relationships and analyzes the subsequent enzymatic effect in generating glucose from cellulose. Ammonia fiber expansion-assisted DES one-pot pretreatment at 120 °C, for 1.5 h resulted in an enzymatic efficiency of 98.0 ± 3.1 %. Moreover, the enzyme efficiency remained greater than 85 % after three recovery cycle experiments. The comparison between regenerated-lignin (d-lignin) and alkaline-lignin showed that regenerated lignin has a lower molecular weight and belongs to para-hydroxy-phenyl-guaiacyl-syringyl (H-G-S) type lignin. This study developed is a green and efficient pretreatment process with great potential in the separation and utilization of biomass fractions.


Subject(s)
Ammonia , Lignin , Triticum , Deep Eutectic Solvents , Hydrolysis , Carbohydrates , Biomass , Dietary Fiber , Solvents
19.
Lab Chip ; 23(10): 2477-2486, 2023 05 16.
Article in English | MEDLINE | ID: mdl-37097479

ABSTRACT

Oblique-incidence reflectivity difference (OIRD) is a compelling technique for real-time, label-free and non-destructive detection of antibody microarray chips, but its sensitivity needs essential improvement for clinical diagnosis. In this study, we report an innovative high-performance OIRD microarray by using poly[oligo(ethylene glycol) methacrylate-co-glycidyl methacrylate] (POEGMA-co-GMA) brush grafted fluorine-doped tin oxide (FTO) as the chip substrate. The polymer brush enhances the interfacial binding reaction efficiency of targets from the complicated sample matrix due to its high antibody loading and excellent anti-fouling merits; the FTO-polymer brush layered structure, on the other hand, excites the interference enhancement effect of OIRD to achieve enhanced intrinsic optical sensitivity. Synergistically, the sensitivity of this chip is significantly improved compared to rival chips, achieving a limit of detection (LOD) as low as 25 ng mL-1 for the model target C-reactive protein (CRP) in 10% human serum. This work explores the tremendous influence of the chip interfacial structure on the OIRD sensitivity and proposes a rational interfacial engineering strategy to boost the performance of the label-free OIRD based microarray and other bio-devices.


Subject(s)
Fluorine , Polymers , Humans , Polymers/chemistry , Antibodies , Microarray Analysis/methods
20.
Environ Sci Pollut Res Int ; 30(14): 41435-41444, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36631619

ABSTRACT

Bidens pilosa L. has been confirmed to be a potential Cd hyperaccumulator by some researchers, but the dynamic and real-time uptake of Cd2+ influx by B. pilosa root apexes was a conundrum up to now. The aim of our study was to investigate the effects of salinity and pH variations on the characteristics of Cd2+ influx around the root apexes of B. pilosa. The tested seedlings of B. pilosa were obtained by sand culture experiments in a greenhouse after 1 month from germination, and the Cd2+ influxes from the root apex of B. pilosa under Cd treatments with different salinity and pH levels were determined with application of non-invasive micro-test technology (NMT). The results showed that Cd2+ influxes at 300 µm from the root tips decreased under Cd treatments with 5 mM and 10 mM NaCl, as compared to Cd stress alone. However, Cd treatments with 2.5 mM NaCl had little effect on the net Cd2+ influxes, as compared to Cd treatments alone. Importantly, Cd treatments at pH = 4.0 markedly increased Cd2+ influxes in roots, and Cd treatment at pH = 7.0 had no significant effect on the net Cd2+ influxes compared to Cd treatments at pH = 5.5. Results also showed that Cd treatments with 10 mM NaCl significantly decreased concentrations of chlorophyll (Chl) a and b in leaves and root vigor of B. pilosa relative to Cd treatments alone, while there were no significant differences between Cd treatments with 2.5 mM NaCl and Cd treatments alone. But root vigor was inhibited significantly under Cd treatments with 5 mM and 10 mM NaCl. A significant increase of root vigor was observed in Cd treatments at pH = 4.0, as compared to pH = 5.5. The Cd treatments with high and medium concentrations of NaCl inhibited the uptake of Cd by B. pilosa roots and affected the Chl and root vigor further. But the Cd treatments at pH = 4.0 could promote the Cd uptake and root vigor. Our results revealed the uptake mechanisms of B. pilosa as a potential phytoremediator under different salinity and pH levels combined with Cd contamination and provided a new idea for screening ideal hyperaccumulator and constructing evaluation system.


Subject(s)
Bidens , Soil Pollutants , Cadmium/analysis , Sodium Chloride , Salinity , Biodegradation, Environmental , Soil Pollutants/analysis , Hydrogen-Ion Concentration , Plant Roots/chemistry
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