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1.
Ecotoxicol Environ Saf ; 270: 115828, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38118331

RESUMO

BACKGROUND: Anemia seriously affects the health and quality of life of the older adult population and may be influenced by various types of environmental metal exposure. Current studies on metals and anemia are mainly limited to single metals, and the association between polymetals and their mixtures and anemia remains unclear. METHODS: We determined 11 urinary metal concentrations and hemoglobin levels in 3781 participants. Binary logistic regression and restricted cubic spline (RCS) model were used to estimate the association of individual metals with anemia. We used Bayesian kernel machine regression (BKMR) and Quantile g-computation (Q-g) regression to assess the overall association between metal mixtures and anemia and identify the major contributing elements. Stratified analyses were used to explore the association of different metals with anemia in different populations. RESULTS: In a single-metal model, nine urinary metals significantly associated with anemia. RCS analysis further showed that the association of arsenic (As) and copper (Cu) with anemia was linear, while cobalt, molybdenum, thallium, and zinc were non-linear. The BKMR model revealed a significant positive association between the concentration of metal mixtures and anemia. Combined Q-g regression analysis suggested that metals such as Cu, As, and tellurium (Te) were positively associated with anemia, with Te as the most significant contributor. Stratified analyses showed that the association of different metals with anemia varied among people of different sexes, obesity levels, lifestyle habits, and blood pressure levels. CONCLUSIONS: Multiple metals are associated with anemia in the older adult population. A significant positive association was observed between metal mixture concentrations and anemia, with Te being the most important factor. The association between urinary metal concentrations and anemia is more sensitive in the non-hypertensive populations.


Assuntos
Anemia , Arsênio , Humanos , Idoso , Estudos Transversais , Teorema de Bayes , Vida Independente , Qualidade de Vida , Metais/urina , Arsênio/urina , Anemia/epidemiologia , China/epidemiologia
2.
Pestic Biochem Physiol ; 201: 105879, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685245

RESUMO

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) (Lepidoptera, Noctuidae), is a highly polyphagous invasive pest that damages various crops. Pesticide control is the most common and effective strategy to control FAW. In this study, we evaluated the toxicity of metaflumizone and indoxacarb against third-instar FAW larvae using the insecticide-incorporated artificial diet method under laboratory conditions. Both metaflumizone and indoxacarb exhibited substantial toxicity against FAW, with LC50 values of 2.43 and 14.66 mg/L at 72 h, respectively. The sublethal effects of metaflumizone and indoxacarb on parental and F1 generation FAW were investigated by exposing third-instar larvae to LC10 and LC30 concentrations of these insecticides. Sublethal exposure to these two insecticides significantly shortened adult longevity, extended pupal developmental times and led to reduced pupal weight, pupation rates, and adult fecundity in the treated parental generation and F1 generation at LC10 or LC30 concentrations, in comparison to the control group. The larval developmental times were shortened in the parental generation but prolonged in the F1 generation, after being treated with sublethal concentrations of metaflumizone. Furthermore, larvae exposed to LC10 or LC30 concentrations of indoxacarb exhibited elevated activity levels of cytochrome P450 monooxygenase and glutathione S-transferase, which coincides with the observed synergistic effect of piperonyl butoxide and diethyl maleate. In conclusion, the high toxicity and negative impact of metaflumizone and indoxacarb on FAW provided significant implications for the rational utilization of insecticides against this pest.


Assuntos
Inseticidas , Larva , Oxazinas , Semicarbazonas , Spodoptera , Animais , Spodoptera/efeitos dos fármacos , Spodoptera/crescimento & desenvolvimento , Inseticidas/toxicidade , Inseticidas/farmacologia , Semicarbazonas/farmacologia , Larva/efeitos dos fármacos , Oxazinas/toxicidade , Longevidade/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Inativação Metabólica
3.
Int J Phytoremediation ; 26(9): 1453-1464, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505937

RESUMO

The improvement of biosorption efficiency for selective dye removal in a multi-dye aqueous system has become an increasingly significant research topic. However, the competitive effects of coexisting dyes and the target dye in such systems remain uncertain due to complex interactions between adsorbent and coexisting dyes. Therefore, in this research, response surface methodology (RSM) model was effectively employed to investigate the competitive effects of allura red (AR) and malachite green (MG) on methylene blue (MB) removal in a ternary dye aqueous system using three different parts of rape straw powders. In the current design of RSM, the initial concentrations of AR and MG dyes ranging from 0 mg·L-1 to 500 mg·L-1 were considered as influencing factors, while the removal rates of MB on adsorbents at an initial concentration of 500 mg·L-1 were established as response values. The RSM models exhibited high correlation coefficients with adjusted R2 values of 0.9908 (pith core), 0.9870 (seedpods), and 0.9902 (shells), respectively, indicating a close fitted between predicted and actual values. The proposed models indicated that the perturbation effects of initial AR and MG concentrations were observed on the removal rates of MB by three types of rape straw powders in a ternary dye aqueous system, resulting in a decrease in MB removal rates, particularly at higher initial AR concentration due to stronger competitive effects compared to initial MG concentration. The structures of rape straw powders, including pith core, seedpods and shell, were analyzed using scanning eletron microscoe (SEM), energy dispersive spectroscopy (EDS), N2 physisorption isotherm, frourier transform infared spectroscopy (FTIR), Zeta potential classes and fluorescence spectrum before and after adsorption of MB in various dye aqueous systems. The characteristics of rape straw powders suggested that similar adsorption mechanisms, such as electrostatic attraction, pore diffusion, and group complex formation for MB, AR, and MG, respectively, occurred on the surfaces of adsorbents during their respective adsorption processes. This leads to significant competitive effects on the removal rates of MB in a ternary dye aqueous system, which are particularly influenced by initial AR concentrations as confirmed through fluorescence spectrum analysis.


Impact of AR and MG on MB removal was analyzed using simple methodologies.Competitive behaviors between AR, MG and MB were understood through RSM.Intense restrain effects on MB removal were revealed by AR concentration.


Assuntos
Biodegradação Ambiental , Corantes , Azul de Metileno , Pós , Poluentes Químicos da Água , Adsorção , Corantes/química , Corantes de Rosanilina/química , Brassica rapa , Compostos Azo , Eliminação de Resíduos Líquidos/métodos
4.
Angew Chem Int Ed Engl ; : e202402880, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758629

RESUMO

Lysine-specific peptide and protein modification strategies are widely used to study charge-related functions and applications. However, these strategies often result in the loss of the positive charge on lysine, significantly impacting the charge-related properties of proteins. Herein, we report a strategy to preserve the positive charge and selectively convert amines in lysine side chains to amidines using nitriles and hydroxylamine under aqueous conditions. Various unprotected peptides and proteins were successfully modified with a high conversion rate. Moreover, the reactive amidine moiety and derived modification site enable subsequent secondary modifications. Notably, positive charges were retained during the modification. Therefore, positive charge-related protein properties, such as liquid-liquid phase separation behaviour of α-synuclein, were not affected. This strategy was subsequently applied to a lysine rich protein to develop an amidine-containing coacervate DNA complex with outstanding mechanical properties. Overall, our innovative strategy provides a new avenue to explore the characteristics of positively charged proteins.

5.
J Transl Med ; 21(1): 561, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37608254

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease that exhibits a high degree of heterogeneity, marked by unpredictable disease flares and significant variations in the response to available treatments. The lack of optimal stratification for RA patients may be a contributing factor to the poor efficacy of current treatment options. The objective of this study is to elucidate the molecular characteristics of RA through the utilization of mitochondrial genes and subsequently construct and authenticate a diagnostic framework for RA. Mitochondrial proteins were obtained from the MitoCarta database, and the R package limma was employed to filter for differentially expressed mitochondrial genes (MDEGs). Metascape was utilized to perform enrichment analysis, followed by an unsupervised clustering algorithm using the ConsensuClusterPlus package to identify distinct subtypes based on MDEGs. The immune microenvironment, biological pathways, and drug response were further explored in these subtypes. Finally, a multi-biomarker-based diagnostic model was constructed using machine learning algorithms. Utilizing 88 MDEGs present in transcript profiles, it was possible to classify RA patients into three distinct subtypes, each characterized by unique molecular and cellular signatures. Subtype A exhibited a marked activation of inflammatory cells and pathways, while subtype C was characterized by the presence of specific innate lymphocytes. Inflammatory and immune cells in subtype B displayed a more modest level of activation (Wilcoxon test P < 0.05). Notably, subtype C demonstrated a stronger correlation with a superior response to biologics such as infliximab, anti-TNF, rituximab, and methotrexate/abatacept (P = 0.001) using the fisher test. Furthermore, the mitochondrial diagnosis SVM model demonstrated a high degree of discriminatory ability in distinguishing RA in both training (AUC = 100%) and validation sets (AUC = 80.1%). This study presents a pioneering analysis of mitochondrial modifications in RA, offering a novel framework for patient stratification and potentially enhancing therapeutic decision-making.


Assuntos
Artrite Reumatoide , Doenças Autoimunes , Humanos , Inibidores do Fator de Necrose Tumoral , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Mitocôndrias , Infliximab
6.
J Med Virol ; 95(3): e28649, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36897027

RESUMO

Systemic lupus erythematosus (SLE) characterized by immune dysfunction is possibly more vulnerable to herpes simplex virus (HSV) infection. The infection has been intensively considered a common onset and exacerbation of SLE. This study is aimed at elucidating the causal association between SLE and HSV. A bidirectional two-sample Mendelian Randomization (TSMR) analysis was systematically conducted to explore the causal effect of SLE and HSV on each other. The causality was estimated by inverse variance weighted (IVW), MR-Egger and weighted median methods based on the summary-level genome-wide association studies (GWAS) data from a publicly available database. Genetically proxied HSV infection exhibited no causal association with SLE in the forward MR analysis using IVW method (odds ratio [OR] = 0.987; 95% confidence interval [CI]: 0.891-1.093; p = 0.798), nor did HSV-1 IgG (OR = 1.241; 95% CI: 0.874-1.762; p = 0.227) and HSV-2 IgG (OR = 0.934; 95% CI: 0.821-1.062; p = 0.297). Similar null results with HSV infection (OR = 1.021; 95% CI: 0.986-1.057; p = 0.245), HSV-1 IgG (OR = 1.003; 95% CI: 0.982-1.024; p = 0.788) and HSV-2 IgG (OR = 1.034; 95% CI: 0.991-1.080; p = 0.121) were observed in the reverse MR where SLE served as the exposure. Our study demonstrated no causal association between the genetically predicted HSV and SLE.


Assuntos
Herpes Simples , Lúpus Eritematoso Sistêmico , Humanos , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Herpes Simples/complicações , Herpes Simples/epidemiologia , Anticorpos Antivirais , Imunoglobulina G , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único
7.
Rheumatology (Oxford) ; 62(5): 1955-1963, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36165706

RESUMO

OBJECTIVES: Long non-coding RNAs (lncRNAs) play important roles in RA pathogenesis. However, specific lncRNAs that regulate gene expression in RA pathogenesis are poorly known. This study was undertaken to characterize a novel lncRNA (lnc-RNU12) that has a lower-than-normal expression level in RA patients. METHODS: We performed initial genome-wide lncRNA microarray screening in peripheral blood mononuclear cells from 28 RA cases and 18 controls. Multiple methods were used to validate the detected associations between lncRNAs and RA. Furthermore, we identified the source and characteristics of the highlighted lncRNAs, detected the target genes, and determined the functional effect on immune cells through lncRNA knock-down in Jurkat T cell lines. RESULTS: lnc-RNU12 was downregulated in peripheral blood mononuclear cells and T cell subtypes of RA patients and was genetically associated with RA risk. lnc-RNU12 mediates the effect of microbiome alterations on RA risk. Activation of T cells caused low expression of lnc-RNU12. Knock-down of lnc-RNU12 in Jurkat T cells caused cell cycle S-phase arrest and altered the expression of protein-coding genes related to the cell cycle and apoptosis (e.g. c-JUN, CCNL2, CDK6, MYC, RNF40, PKM, VPS35, DNAJB6 and FLCN). Finally, c-JUN and CCNL2 were identified as target genes of lnc-RNU12 at the mRNA and protein expression levels. RNA-binding protein immunoprecipitation assays verified the interaction between lnc-RNU12 and the two proteins (c-Jun and cyclin L2) in Jurkat cells. CONCLUSIONS: Our study suggested that lnc-RNU12 was involved in the pathogenesis of RA by influencing the T cell cycle by targeting c-JUN and CCNL2.


Assuntos
Artrite Reumatoide , RNA Longo não Codificante , Humanos , Ciclo Celular , Ciclinas , Proteínas de Choque Térmico HSP40 , Leucócitos Mononucleares/metabolismo , Chaperonas Moleculares , Proteínas do Tecido Nervoso , RNA Longo não Codificante/genética , Linfócitos T/metabolismo , Fatores de Transcrição , Proteínas Proto-Oncogênicas c-jun/metabolismo
8.
Clin Genet ; 103(2): 219-225, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36155908

RESUMO

POPDC1 also known as BVES, is a highly conserved transmembrane protein, important for striated muscle function and homeostasis. Pathogenic variants in the POPDC1 gene are associated with limb-girdle muscular dystrophy type 25 (LGMDR25). In the present study, we performed trio-whole exome sequencing (WES) followed by Sanger sequencing on a single family having LGMD clinical features. Protein modeling of all POPDC1 missense variants (POPDC1Pro134Leu , POPDC1Ile193Ser , and POPDC1Ser201Phe ) associated with LGMDR25 were performed using Molecular Dynamics (MD) simulation. We identified a homozygous missense variant (c.401C>T; p.Pro134Leu) in the POPDC1 gene. Altered 3D structure, disruptive fluctuation, less compactness, and instability were observed in all the three variants of POPDC1 protein models. In comparison, POPDC1Ser201Phe protein dynamics were more unstable than other variants. Functional study of newly identified variant would add key answers to underlying mechanisms of the disease.


Assuntos
Distrofia Muscular do Cíngulo dos Membros , Humanos , Moléculas de Adesão Celular/genética , Homozigoto , Proteínas de Membrana/genética , Proteínas Musculares/genética , Músculo Esquelético/metabolismo , Distrofia Muscular do Cíngulo dos Membros/genética , Mutação de Sentido Incorreto/genética
9.
Opt Lett ; 48(7): 1590-1593, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37221717

RESUMO

Sub-diffraction-limit quasi-non-diffracting light sheets (SQLSs) are crucial for a resolution-enhanced and field of view (FOV)-enlarged light sheet microscope. However, it has aways been plagued by sidelobes inducing severe background noise. Here, a self-trade-off optimized method is proposed to generate sidelobe-suppressed SQLSs based on super-oscillatory lenses (SOLs). An SQLS thus obtained shows sidelobes of only 15.4%, first realizing the sub-diffraction-limit thickness, quasi-non-diffracting characteristic, and suppressed sidelobes simultaneously for static light sheets. Moreover, a window-like energy allocation is realized by the self-trade-off optimized method, successfully further suppressing the sidelobes. In particular, an SQLS with theoretical sidelobes of 7.6% is achieved within the window, which provides a new strategy to deal with sidelobes for light sheets and shows great potential in high signal-to-noise ratio light sheet microscopy (LSM).

10.
Phys Rev Lett ; 131(1): 013201, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37478442

RESUMO

The ion momentum distribution in the x-ray-induced dissociative photoionization of molecules is investigated, treating the ionization analytically under the Born-Oppenheimer approximation and simulating numerically the ion motion via the Schrödinger equation. The ion-photoelectron entanglement transfers information of the electronic interference to the ion dynamics. As a consequence, the ion momentum distributions of dissociative molecular photoionization present Young's double-slit interference when the photoelectron emission angle is fixed. We demonstrate that double-slit interference signatures persist in the ion longitudinal momentum shift even when the information of the correlated photoelectron is lost, which is the case for heteronuclear molecules when an additional photoelectron recoil momentum arises due to the different ion masses. For the case of sequential double ionization, we show that double-slit interference in the ion dynamics can be utilized for coherent control of the molecular dynamics.

11.
Proteome Sci ; 21(1): 17, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37828502

RESUMO

µ-Conotoxin GIIIB (µ-CTX GIIIB) is a polypeptide containing three disulfide bridges, produced by the sea snail Conus geographus. This study was aimed to explored the cytotoxic effects of µ-CTX GIIIB on mouse skeletal musculoblast (Sol8). Sol8 cells were exposed to ouabain and veratridine to establish the cell injury model, and then treated with µ-CTX GIIIB. CCK-8 was adopted to evaluate the cytotoxicity of µ-CTX GIIIB. Then, proteomics and transcriptome were conducted, and the explore the differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) affected by µ-CTX GIIIB were found. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to investigate the affected signaling pathways. µ-CTX GIIIB increased the cell survival rate of injured Sol8 cells. We found and identified 1,663 DEGs and 444 DEPs influenced by µ-CTX GIIIB. 106 pairs of correlated DEGs and DEPs were selected by combining transcriptome and proteome data. The results of KEGG and GO analysis showed that µ-CTX GIIB affected the cell cycle, apoptosis, DNA damage and repair, lipid metabolism and other biological processes of Sol8 cells. µ-CTX GIIIB could affected cell cycle regulation, DNA damage repair, and activation of tumor factors, with potential carcinogenic effects. Our results provide an important basis for the study of in vitro toxicity, the mechanism of toxicity and injury prevention by µ-CTX GIIIB.

12.
Mol Cell Biochem ; 478(10): 2297-2307, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36735210

RESUMO

Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of replication-competent HBV DNA in the liver, with or without HBV DNA in the blood, in individuals who tested negative for HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Several advances have been made toward clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host's immune control and epigenetic factors. Although the underlying mechanisms describing the genesis of OBI are not completely known, the presence of viral cccDNA, which remains in a low state of replication due to the host's strong immune suppression of HBV replication and gene expression, appears to be the causative factor. Through this review, we have provided an updated account on the role of HBV cccDNA in regulating OBI. We have comprehensively described the HBV cell cycle, cccDNA kinetics, current regulatory mechanisms, and the therapeutic methods of cccDNA in OBI-related diseases.


Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Vírus da Hepatite B/genética , DNA Circular/genética , DNA Viral/genética , DNA Viral/metabolismo , Hepatite B/genética , Antígenos de Superfície da Hepatite B/genética , Replicação Viral
13.
Analyst ; 149(1): 188-195, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38010128

RESUMO

Herein, the electrodeposition of paracetamol oxide (PA ox) for the intelligent portable ratiometric detection of nicotine (NIC) and ethyl vanillin ß-D-glucoside (EVG) is reported. PA ox electrodeposited on a screen-printed carbon electrode (SPCE) was used as a new fixed state ratiometric reference probe. A portable electrochemical workstation combined with a smart phone was applied as an intelligent portable electrochemical sensing platform. The sensor was studied by scanning electron microscopy (SEM), Fourier transform infrared spectrophotometry (FT-IR), ultraviolet-visible spectrophotometry (UV-vis), theoretical calculation, chronoamperometry, cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and square wave voltammetry (SWV). Under optimized conditions, the detection range of NIC is 10-200 µmol L-1, and the detection limit is 0.256 µmol L-1. The detection range of EVG was 10-180 µmol L-1, and the detection limit was 0.058 µmol L-1. The sensor can realize the real-time detection of NIC and EVG concentration in cigarette samples quickly and accurately, and has good anti-interference, repeatability and stability.


Assuntos
Acetaminofen , Nicotina , Óxidos , Espectroscopia de Infravermelho com Transformada de Fourier , Galvanoplastia , Glucosídeos , Eletrodos , Técnicas Eletroquímicas/métodos
14.
Fish Shellfish Immunol ; 132: 108471, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36509413

RESUMO

This study aimed to evaluate antioxidant capacity and protection from white spot syndrome virus (WSSV) challenge of Procambarus clarkii fed trans-vp19 and trans-vp (19 + 28) genes of Synechococcus sp. PCC7942 (Syn7942). P. clarkii were fed transgenic cyanobacteria continuously for 7 days, and then infected with WSSV after 12 h starvation. The daily mortality in each group was measured for 10 days and hepatopancreas and muscle of P. clarkii were examined for enzymes phenoloxidase (PO) activity, catalase (CAT) activity, glutathione peroxidase (GSH-px) activity, and malondialdehyde (MDA) concentration after immunization and viral challenge at different times. Compared with the WSSV-infected crayfish in positive control group (challenge and no vaccination) and wild type group (challenge, feeding wild-type Syn7942), vp19 group (challenge, feeding Syn7942 trans-vp19 gene) and vp (19 + 28) group [challenge, feeding Syn7942 trans-vp (19 + 28) genes] significantly improved the survival rate from 0% to 60% and 56.7%, respectively. Consistently, significantly greater PO, CAT, and GSH-px activity and significantly lower MDA concentration in the vp19 and vp (19 + 28) groups compared to the control group. These results demonstrate that the trans-vp19 and trans-vp (19 + 28) gene of Syn7942 significantly facilitated the immune and antioxidant capacity of crayfish. Therefore, the trans-vp19 and trans-vp (19 + 28) genes of Syn7942 could provide protection for crayfish as an anti-WSSV oral medication.


Assuntos
Synechococcus , Vírus da Síndrome da Mancha Branca 1 , Animais , Antioxidantes , Astacoidea , Vírus da Síndrome da Mancha Branca 1/fisiologia , Synechococcus/genética , Administração Oral
15.
J Pept Sci ; 29(3): e3454, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36181422

RESUMO

Considering the fact that site-selective late-stage diversification of peptides and proteins remains a challenge for biochemistry, strategies targeting low-abundance natural amino acids need to be further developed. As an extremely oxidation-sensitive and low-abundance amino acid, methionine emerges as a promising target for chemo- and site-selective modification. Herein we report an efficient and highly selective modification on methionine residues by one-pot O- and N-transfer reaction, generating sulfoximine-modified peptides with near-perfect conversion within 10 min. Moreover, the great tolerance to other natural amino acids has been demonstrated in reactions with various peptide substrates. To demonstrate the generality of this protocol, we have modified natural peptides and obtained sulfoximination products with high conversion rates. This methodology provides a novel strategy as the expansion of the methionine-based peptide functionalization toolbox.


Assuntos
Metionina , Proteínas , Metionina/química , Metionina/metabolismo , Proteínas/química , Peptídeos/química , Racemetionina/metabolismo , Estresse Oxidativo
16.
Bioorg Chem ; 131: 106320, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36527991

RESUMO

Xanthine oxidase (XO) is a crucial target for the treatment of hyperuricemia and gout. A series of derivatives based on natural 3,4-dihydroxychalcone, obtained from Carthamus tinctorious and Licorice, were designed and synthesized. Nine derivatives (9a-e, 10b,c, and 15a,b) exhibited apparent XO inhibitory activity in vitro (IC50 values varied from 0.121 to 7.086 µM), 15b presented the most potent inhibitory activity (IC50 = 0.121 µM), which was 27.47-fold higher than that of allopurinol (IC50 = 3.324 µM). The SAR analysis indicated that introducing hydroxyl groups at 3'/4'/5'-position on ring A was more beneficial to the inhibition of XO than at 2'/6'-position; the removal of 3­hydroxyl group on ring B could weaken the inhibitory potency of hydroxychalcones on XO, but it was beneficial to the XO inhibitory potency of methoxychalcones. Molecule modeling studies afforded insights into the binding mode of 15b with XO and supported the findings of SAR analysis. Additionally, kinetics studies demonstrated that 15b presented a reversible and competitive XO inhibitor, which spontaneously combined with XO through hydrophobic force, and finally changed the secondary conformation of XO. Furthermore, the acute hyperuricemia model was employed to investigate the hypouricemic effect of 15b, which could effectively reduce the serum uric acid levels of rats at an oral dose of 10 mg/kg. ADMET prediction suggested that compound 15b possessed good pharmacokinetic properties. Briefly, compound 15b emerges as an interesting XO inhibitor for the treatment of hyperuricemia and gout with beneficial effects on serum uric acid levels regulating. Meanwhile, the XO inhibitors with chalcone skeleton will deserve further attention and discussion.


Assuntos
Chalcona , Chalconas , Gota , Hiperuricemia , Ratos , Animais , Relação Estrutura-Atividade , Ácido Úrico , Chalconas/farmacologia , Chalconas/uso terapêutico , Xantina Oxidase , Chalcona/farmacologia , Chalcona/uso terapêutico , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Inibidores Enzimáticos/química , Gota/tratamento farmacológico
17.
Anesth Analg ; 136(1): 34-42, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36534715

RESUMO

BACKGROUND: Surgery is accompanied by a systemic inflammatory response that may presage delirium in susceptible individuals. Little is known about the trajectory of plasma proinflammatory cytokines and their potential associations with postoperative delirium (POD). The current study longitudinally assessed both pro and anti-inflammatory plasma cytokine response and development of POD in older surgical patients to investigate associations with individual and/or clusters of cytokines that may indicate pathogenic mechanisms. METHODS: A prospective longitudinal study sought to enroll patients >60 years old who were scheduled for major lower limb surgery under general anesthesia. Blood was obtained preoperatively and postoperatively from day 1 through postoperative day 4 for measurement of plasma interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6, soluble IL-6 receptor (sIL-6R), IL-10, and tumor necrosis factor-α (TNF-α). Participants were assessed for POD twice daily for 4 days using the confusion assessment method. Trajectory of postoperative changes in plasma cytokines was determined by a group-based trajectory modeling analysis that was informed by distinct cytokines identified by time-dependent Cox regression model. RESULTS: One hundred eighty-eight patients were assessed for eligibility of whom 129 underwent major surgery and 126 had complete datasets for final analysis. POD was diagnosed in 31 of 126 patients (24.6%). Time-dependent Cox regression model identified that higher IL-6 and sIL-6R levels were associated with higher risk of developing POD. A two-cluster model (stable lower and fluctuating higher levels) was considered to be the most statistically appropriate model for IL-6 and sIL-6R trajectory. More participants with fluctuating higher IL-6 were delirious (73.3% vs 18.0%, P = .001) as were those with fluctuating higher sIL-6R (81.3% vs 16.4%, P = .001). CONCLUSIONS: As higher IL-6 and sIL-6R levels were significantly associated with higher risk of POD and the combination is required for IL-6 trans-signaling, it is possible that activation of this pathway may be associated with POD. Furthermore, it will be important to determine whether high levels of the combination of IL-6 and sIL-6R can be an early biomarker for the subsequent development of POD.


Assuntos
Citocinas , Delírio do Despertar , Humanos , Idoso , Pessoa de Meia-Idade , Interleucina-6 , Estudos Prospectivos , Estudos Longitudinais , Extremidade Inferior
18.
Ecotoxicol Environ Saf ; 259: 114966, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37182299

RESUMO

BACKGROUND: Environmental metal exposure is associated with elevated triglycerides (TG) and the development of chronic kidney disease (CKD). However, the relationship between metal exposure and glomerular filtration rate (GFR) remains uncertain, and the mediating effect of TG between the two is unclear. METHODS: This study measured the concentrations of 14 metals in urine samples from 3752 elderly people in the community. The most relevant metals were screened by least absolute shrinkage and selection operator (LASSO) regression. The relationship between combined exposure to multiple metals and abnormal estimated glomerular filtration rate (eGFR) was explored using multivariate logistic regression analysis and Bayesian kernel machine regression (BKMR) analysis. Generalized linear regression models and the Karlson-Holm-Breen (KHB) method were used to assess the mediating effects of TG. RESULTS: In the single-metal model, calcium (Ca), iron (Fe), selenium (Se), strontium (Sr), and thallium (Tl) showed significant negative correlations with the prevalence of abnormal eGFR (all P < 0.05). In the multi-metals model, Ca, Se, and Tl continued to show significant negative correlations, while vanadium (V) and zinc (Zn) showed significant positive correlations with abnormal eGFR (all P < 0.05). The BKMR model showed a negative joint effect of the mixture of Ca, V, Zn, Se, and Tl on the prevalence of abnormal eGFR. The generalized linear regression model showed a significant positive correlation between the concentrations of Ca (ß = 0.07), Zn (ß = 0.07), Se (ß = 0.09), and TG levels (all P < 0.05). In the mediation analysis, TG masked a 4.30% and 5.21% correlation between Ca and Se and the prevalence of eGFR abnormalities, respectively. CONCLUSIONS: Urinary concentration of multiple metals is significantly associated with eGFR abnormalities, and Ca, and Se may be among the potential protective factors. TG masked some of the protective effects of Ca and Se.


Assuntos
Taxa de Filtração Glomerular , Metais , Triglicerídeos , Idoso , Humanos , Teorema de Bayes , Cálcio , População do Leste Asiático , Vida Independente , Selênio , Zinco , Metais/urina
19.
Nano Lett ; 22(8): 3372-3379, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35343229

RESUMO

Simulation of biological visual perception has gained considerable attention. In this paper, an optoelectrical In2O3 transistor array with a negative photoconductivity behavior is designed using a side-gate structure and a screen-printed ion-gel as the gate insulator. This paper is the first to observe a negative photoconductivity in electrolyte-gated oxide devices. Furthermore, an artificial visual perception system capable of self-adapting to environmental lightness is mimicked using the proposed device array. The transistor device array shows a self-adaptive behavior of light under different levels of light intensity, successfully demonstrating the visual adaption with an adjustable threshold range to the external environment. This study provides a new way to create an environmentally adaptive artificial visual perception system and has far-reaching significance for the future of neuromorphic electronics.


Assuntos
Eletrólitos , Eletrônica , Eletrólitos/química , Óxidos
20.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614218

RESUMO

The xyloglucan endotransglucosylase/hydrolase (XET/XEH, also named XTH) family is a multigene family, the function of which plays a significant role in cell-wall rebuilding and stress tolerance in plants. However, the specific traits of the XTH gene family members and their expression pattern in different tissues and under stress have not been carried out in sweet potato. Thirty-six XTH genes were identified in I. batatas, all of which had conserved structures (Glyco_hydro_16). Based on Neighbor-Joining phylogenetic analysis the IbXTHs can be divided into three subfamilies-the I/II, IIIA, and IIIB subfamilies, which were unevenly distributed on 13 chromosomes, with the exception of Chr9 and Chr15. Multiple cis-acting regions related to growth and development, as well as stress responses, may be found in the IbXTH gene promoters. The segmental duplication occurrences greatly aided the evolution of IbXTHs. The results of a collinearity analysis showed that the XTH genes of sweet potato shared evolutionary history with three additional species, including A. thaliana, G. max, and O. sativa. Additionally, based on the transcriptome sequencing data, the results revealed that the IbXTHs have different expression patterns in leaves, stems, the root body (RB), the distal end (DE), the root stock (RS), the proximal end (PE), the initiative storage root (ISR), and the fibrous root (FR), and many of them are well expressed in the roots. Differentially expressed gene (DEG) analysis of FRs after hormone treatment of the roots indicated that IbXTH28 and IbXTH30 are up-regulated under salicylic acid (SA) treatment but down-regulated under methyl jasmonate (MeJA) treatment. Attentionally, there were only two genes showing down-regulation under the cold and drought treatment. Collectively, all of the findings suggested that genes from the XTH family are crucial for root specificity. This study could provide a theoretical basis for further research on the molecular function of sweet potato XTH genes.


Assuntos
Ipomoea batatas , Ipomoea batatas/genética , Ipomoea batatas/metabolismo , Filogenia , Glicosiltransferases/metabolismo , Hidrolases/metabolismo , Regulação da Expressão Gênica de Plantas
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