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1.
Diagn Microbiol Infect Dis ; 110(1): 116385, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38848663

RESUMO

AIMS: To retrospectively analyze the diagnostic efficacy of Xpert MTB/RIF (Xpert) in lymph node tuberculosis (LNTB). METHODS: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of Xpert, pathological examination and culture for LNTB were calculated. RESULTS: 421 suspected LNTB cases were categorized into the LNTB group (377 cases) and non-LNTB group (44 cases). The sensitivities of Xpert, pathological examination, and culture were 72.15%, 20.69%, 30.24%, respectively, with NPVs of 29.53%, 12.83%, 14.33%. The AUC values were 0.861, 0.603, 0.651, respectively. The sensitivity of Xpert varied across sample types: tissue (64.73%), puncture fluid (74.42%), and pus (96.05%). For specific lymph node locations, the sensitivity was head-and-neck (72.51%), mediastinal (84.21%), and axillary (45.83%). CONCLUSIONS: Xpert demonstrates high diagnostic value for LNTB, particularly in pus samples. It also performs better in mediastinal and head-and-neck lymph node samples compared to axillary lymph node samples.

2.
Front Vet Sci ; 11: 1404539, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840632

RESUMO

Introduction: Stereotypic behaviours, especially oral stereotypic behaviours, are frequently expressed in farm animals. Tongue-rolling is the most common oral stereotypic behaviour in dairy cows (Bos taurus). If animals frequently display stereotypic behaviours, this is an indication of poor welfare. It has been suggested that animals express stereotypic behaviours as a way of coping with stress. As a result, animals with stereotypic behaviours may have lower levels of stress hormones than animals without stereotypic behaviours. Methods: In this study, 916 Holstein cows in the first lactation were subjected to scan sampling behavioural observations 200 times for 10 days. All cows were assigned to either a stereotypic behaviours group (SB) or a control group (CON). The SB group was further subdivided into a tongue-rolling group (TR) and an other-stereotypic behaviours group (OS). The TR group was also split into an only tongue-rolling group (OTR) and a mixed tongue-rolling and other stereotypic behaviours group (TROS). Some cows in the TR group belonged to an extreme tongue-rolling group (ETR). Hair and saliva samples were collected from 601 cows to test cortisol concentrations and dairy herd improvement (DHI) data were collected from a total of 762 cows. Results: There were no differences in hair or saliva cortisol concentrations between the groups (p>0.05), and the frequencies of tongue-rolling were not associated with cortisol concentrations (p>0.05). For DHI in cows, the milk protein percentage (p = 0.028), milk true protein percentage (p = 0.021) and milk crude protein percentage (p = 0.023) of cows in the ETR group were significantly lower than those in the CON group. For cows in ETR group, as the frequencies of tongue-rolling increased, the milk protein percentage (p = 0.034, r = 0.365), milk true protein percentage (p = 0.022, r = 0.393) and milk crude protein percentage (p = 0.035, r = 0.363) increased. Discussion: We investigated the relationship between stereotypic behaviours and stress by using a non-invasive sampling method to minimise harm to the cows. We suggest that tongue-rolling may not be a way for cows to cope with stress, at least in terms of cortisol concentrations.

3.
BMC Complement Med Ther ; 24(1): 226, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858650

RESUMO

OBJECTIVE: Previous studies have shown that fraxetin has antitumor activity in a variety of tumors, but its role in acute myeloid leukemia (AML) remains unclear. In this study, we aimed to evaluate the anti-AML effect of fraxetin through cell experiments and network pharmacology analysis. METHODS: The inhibitory and apoptotic effects of fraxetin on AML cells were determined by CCK-8 and flow cytometry experiments. Potential targets of fraxetin and AML-related targets were screened using public databases. PPI network, GO functional enrichment and KEGG pathway enrichment analyses were performed to predict the hub targets and signaling pathways by which fraxetin alleviates AML. Molecular docking was used to determine the fraxetin binding sites on hub targets. Using the GEPIA database, the expression of hub targets was analyzed in relation to the overall survival of AML patients. RESULTS: Cell experiments showed that fraxetin inhibits AML cell proliferation and induces apoptosis. To explore the potential mechanism of fraxetin, 29 shared targets of fraxetin and AML were obtained through screening online public databases. Among them, AKT1, TNF, SRC, etc., are related to AML cell apoptosis. The expression levels of SRC, NOS3, VAV1, LYN, and PTGS1 were associated with the overall survival of AML patients (p value < 0.05). The enrichment analysis results identified the main pathways, namely, focal adhesion and the PI3K-AKT signaling pathway, that affected the proliferation and apoptosis of AML cells. The analysis of hub targets of the PPI network showed that AKT1, TNF, CTNNB1, etc., were hub targets, which were related to the proliferation and apoptosis of AML cells. The results of molecular docking showed that the hub targets had good binding with fraxetin. CONCLUSION: Fraxetin may inhibit AML cell proliferation and induce AML cell apoptosis through multiple targets, such as AKT1, SRC, and EGFR, and multiple pathways, such as focal adhesion and the PI3K-AKT signaling pathway.


Assuntos
Apoptose , Proliferação de Células , Leucemia Mieloide Aguda , Simulação de Acoplamento Molecular , Farmacologia em Rede , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Cumarínicos/farmacologia , Transdução de Sinais/efeitos dos fármacos
4.
Small ; : e2402478, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778729

RESUMO

Direct electrolysis of seawater to generate hydrogen is an attractive approach for storing renewable energy. However, direct seawater splitting suffers from low current density and limited operating stability, which severely hinders its industrialization. Herein, a promising strategy is reported to obtain a nano needle-like array catalyst-CDs-Mn-CoxP on nickel foam, in which the Mn─O─C bond tightly binds Mn, Carbon dots (CDs), and CoxP together. The coordination engineering of CDs and Mn not only effectively regulates the electronic structure of CoxP, but also endows the as-prepared catalyst with selectivity and marked long-term stability at ampere-level current density. Low overpotentials of 208 and 447 mV are required to achieve 1000 mA cm-2 for hydrogen evolution reaction (HER) and Oxygen evolution reaction (OER) in simulated seawater, respectively. Cell potentials of 1.78 and 1.86 V are needed to reach 500 and 1000 mA cm-2 in alkaline seawater along with excellent durability for 350 h. DFT studies have verified that the introduction of Mn and CDs effectively shifts the d-band center of Co-3d toward higher energy, thereby strengthening the adsorption of intermediates and enhancing the catalytic activity. This study sheds light on the development of highly effective and stable catalysts for large-scale seawater electrolysis.

5.
J Thorac Dis ; 16(4): 2539-2549, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38738241

RESUMO

Background: A rapid and precise etiological diagnosis is crucial for the effective treatment of bloodstream infection (BSI). In this study, the performance of probe capture-based targeted next-generation sequencing (tNGS) was compared to that of blood culture and metagenomic next-generation sequencing (mNGS) in detecting potential pathogens in patients with BSI. Methods: A total of 80 patients with suspected BSI were prospectively enrolled from 24 November 2023 to 30 December 2023 at Zhongshan Hospital, Shanghai, China. All 80 participants underwent simultaneous blood culture, blood mNGS, and blood tNGS after admission when febrile, and the results were compared. Results: Among the 80 participants, 11 were clinically diagnosed with noninfectious fever, and 69 were diagnosed with BSI. Blood tNGS had a higher sensitivity for the diagnosis of BSI than blood culture (91.3% vs. 23.2%, P<0.001) and blood mNGS (91.3% vs. 69.6%, P=0.001). There was no significant difference in specificity between blood mNGS and tNGS (81.8% vs. 100.0%, P=0.13). Blood tNGS demonstrated a faster turnaround time than blood culture and blood mNGS. In 22 (31.9%) patients with BSI, targeted adjustment of the anti-infectious therapy according to the blood tNGS results resulted in clinical improvement. Conclusions: Blood tNGS may be a promising tool for detecting potential pathogens in patients with BSI. The application of blood tNGS for BSI could guide anti-infectious treatment strategies and might improve clinical outcomes.

6.
BMC Plant Biol ; 24(1): 232, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561659

RESUMO

BACKGROUND: Chrysanthemum, one of the four major cut flowers all over the world, is very sensitive to salinity during cultivation. DNA binding with one finger (DOF) transcription factors play important roles in biological processes in plants. The response mechanism of CmDOF18 from chrysanthemum to salt stress remains unclear. RESULTS: In this study, CmDOF18 was cloned from Chrysanthemum morifolium, and its expression was induced by salinity stress. The gene encodes a 291-amino acid protein with a typical DOF domain. CmDOF18 was localized to the nucleus in onion epidermal cells and showed transcriptional activation in yeast. CmDOF18 transgenic plants were generated to identify the role of this gene in resistance to salinity treatment. Chrysanthemum plants overexpressing CmDOF18 were more resistant to salinity stress than wild-type plants. Under salinity stress, the malondialdehyde content and leaf electrolyte conductivity in CmDOF18-overexpressing transgenic plants were lower than those in wild-type plants, while the proline content, chlorophyll content, superoxide dismutase activity and peroxidase activity were higher than those in wild-type plants. The opposite findings were observed in gene-silenced plants compared with wild-type plants. The gene expression levels of oxidoreductase increased in CmDOF18-overexpressing transgenic plants but decreased in CmDOF18-SRDX gene-silenced transgenic plants. CONCLUSION: In summary, we analyzed the function of CmDOF18 from chrysanthemum, which may regulate salinity stress in plants, possibly due to its role in the regulation of oxidoreductase.


Assuntos
Chrysanthemum , Oxirredutases , Oxirredutases/metabolismo , Tolerância ao Sal/genética , Chrysanthemum/genética , Chrysanthemum/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Saccharomyces cerevisiae/metabolismo , Salinidade , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética
7.
Environ Int ; 186: 108578, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38522230

RESUMO

Southeast Asia has been experiencing severe air pollution due to its substantial local emissions and transboundary air pollution (TAP), causing significant health impacts. While literature focused on air pollution episodes in Southeast Asia, we have yet to fully understand the contributions of local emission sectors and TAP to air quality in the region annually. Herein we employed air quality modeling with the species tagging method to first assess the contributions of source sectors and locations to fine particulate matter (PM2.5) and ozone (O3) in Southeast Asia and to hence quantify the resultant health impacts. Our results show that air pollutant exposure was associated with âˆ¼ 900 thousand premature mortalities in Southeast Asia every year. Of which, 77 % and 23 % were due to local emissions and TAP in the region, respectively. âˆ¼ 87 % of the premature mortalities due to local emissions were induced by PM2.5 exposure, whereas the remaining were due to O3 exposure. PM2.5-related health impacts were dominated by industrial (45 %) and residential (17 %) emissions, and O3-related impacts were mainly due to biogenic (40 %) and road transport (24 %) emissions. Furthermore, the health impacts of TAP were particularly adverse in Brunei, East Timor, Singapore, Laos, and border regions.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Material Particulado , Ozônio/análise , Material Particulado/análise , Sudeste Asiático , Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Humanos , Monitoramento Ambiental , Exposição Ambiental
8.
Small ; 20(1): e2304512, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37653588

RESUMO

The development of high performance electrocatalysts for effective hydrogen production is urgently needed. Herein, three hybrid catalysts formed by WS2 and Co-based metal-organic frameworks (MOFs) derivatives are constructed, in which the small amount of W in the MOFs derivatives acts as a bridge to provide the charge transfer channel and enhance the stability. In addition, the effects of the surface charge distribution on the catalytic performance are fully investigated. Due to the optimal interfacial electron coupling and rearrangement as well as its unique porous morphology, WS2 @W-CoPx exhibits superior bifunctional performance in alkaline media with low overpotentials in hydrogen evolution reaction (HER) (62 mV at 10 mA cm-2 ) and oxygen evolution reaction (OER) (278 mV at 100 mA cm-2 ). For overall water splitting (OWS), WS2 @W-CoPx only requires a cell voltage of 1.78 V at 50 mA cm-2 and maintains good stability within 72 h. Density functional theory calculations verify that the combination of W-CoPx with WS2 can effectively enhance the activity of OER and HER with weakened OH (or O) adsorption and enhanced H atom adsorption. This work provides a feasible idea for the design and practical application of WS2 or phosphide-based catalysts in OWS.

9.
Sci Total Environ ; 912: 169051, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38061644

RESUMO

While previous studies have investigated haze events over Southeast Asia (SEA), local and transboundary contributions of various emission sources to haze months over the entire SEA have yet to be assessed comprehensively and systematically. We utilized the Particle Source Apportionment Technique (PSAT) to quantify the spatial local, transboundary, and sectoral contributions to PM2.5 over SEA during the haze months of 2015-2019. Results show that local emission contributions accounted for 56.1 % ~ 94.2 % of PM2.5 in Indonesia, Philippines, Vietnam, and Thailand. Transboundary contributions (23.1 % ~ 57.6 %) from Indonesia notably influenced maritime SEA. Vietnam (15.6 % ~ 39.1 %) and super-regional (17.0 % ~ 34.3 %) contributions outside the SEA exerted remarkable impacts on mainland SEA. Among different sectors, fire emissions contributed the most to PM2.5 over maritime SEA (23.0 % ~ 68.6 %) during the studied haze months, whereas residential and other emissions were the main contributors to mainland SEA (27.2 % ~ 36.7 %). Regarding the source species, primary PM2.5 accounted for the majority of PM2.5. VOC and SO2 composed most of the secondary PM2.5 due to massive VOC emissions in the region and the priority reaction of NH3 with sulfuric acid (H2SO4) to form ammonium sulfate. Besides, the intensified haze months in Oct 2015 and Sep 2019 were characterized by more intensive fire emissions in the region and the climatic variability-induced meteorological effects that provided favorable condition for transboundary air pollution (56.9 % and 44.9 %, respectively, for maritime SEA, as well as 46.0 % and 37.7 %, respectively, for mainland SEA in the two studied haze months). The haze months can be attributed to the notable drought conditions amidst global climatic phenomena such as El Niño and positive Indian Ocean Dipole (IOD) in Oct 2015 and Sep 2019, respectively.

10.
J Clin Microbiol ; 62(1): e0092323, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38112450

RESUMO

IMPORTANCE: In this study, we successfully established a new One-Pot method, named TB One-Pot, for detecting Mtb in sputum by combining CRISPR-cas12b-mediated trans-cleavage with cross-priming amplification (CPA). Our study evaluated the diagnostic performance of TB One-Pot in clinical sputum samples for tuberculosis. The findings provide evidence for the potential of TB One-Pot as a diagnostic tool for tuberculosis.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Mycobacterium tuberculosis/genética , Escarro/microbiologia , Apresentação Cruzada , Sistemas CRISPR-Cas , Sensibilidade e Especificidade , Técnicas de Amplificação de Ácido Nucleico/métodos , Tuberculose/diagnóstico , Tuberculose/microbiologia
11.
Patient Prefer Adherence ; 17: 2773-2787, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37936716

RESUMO

Background: Lung cancer patients will have lung damage after surgery, need rehabilitation exercise. Common-sense model has shown the impact of patients' perception of illness on health behaviors. However, for patients with lung cancer after thoracoscopic surgery, there has been no relevant exploration of disease perception. Objective: The purpose of this study was to investigate the clinical status of patients with lung cancer patients who have undergone thoracoscopic surgery, and to explore the correlation between frailty, disease perception, and lung functional exercise compliance. Methods: The cross-sectional study included 218 patients with lung cancer after thoracoscopic surgery. We collected participants' frailty, disease perception, exercise adherence, and relevant clinical information. T-test, Chi-square, Linear regression, Pearson's correlation, and mediation analysis were used for statistical analysis of patient data. Results: We analyzed the data by disease perception with high and low median scores and found significant differences in lymphatic dissection, stool within three days, pain, thoracic drainage tube placement time. Linear regression results show that, after controlling for confounding factors, frailty and disease perception were significantly associated with pulmonary function exercise compliance. The higher the frailty score, the worse the compliance, and the higher the disease perception negative score, the less exercise. Illness perception played a partially mediating role in the association between frailty and lung functional exercise adherence. Conclusion: Frailty and disease perception have an impact on exercise adherence, therefore, we need to consider these factors in the intervention to improve exercise compliance after thoracoscopic surgery for lung cancer.

12.
Front Aging Neurosci ; 15: 1244191, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37876876

RESUMO

Objective: To investigate the effects of brain-derived neurotrophic factor (BDNF) gene polymorphism on cognitive function, neuroimaging and blood biological markers in patients with subcortical ischaemic vascular dementia (SIVD). Methods: A total of 81 patients with SIVD were included. According to their BDNF gene polymorphism, the participants were divided into the Val/Val (n = 26), Val/Met (n = 35), and Met/Met (n = 20) groups. A comprehensive neuropsychological evaluation and multimodal brain MRI scan were performed. MRI markers for small vessel disease were visually rated or quantitatively analysed. Moreover, 52 patients were further evaluated with blood marker assays, including amyloid beta (Aß), phosphorylated tau at threonine-181 (P-tau181), glial fibrillary acidic protein (GFAP), total tau (T-tau) and neurofilament light chain (NfL). Results: There were no significant differences in demographics, disease duration or MRI markers of small vessel disease between the three groups. Compared with the Val/Val and Val/Met groups, the Met/Met group showed worse performance in the verbal fluency test and higher levels of plasma NfL. Conclusion: The rs6265 polymorphism of the BDNF gene is associated with semantic language fluency in patients with SIVD. The Met genotype may be a risk factor for cognitive impairment and neuronal injury.

13.
J Int Med Res ; 51(10): 3000605231202573, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37818767

RESUMO

Despite the widespread use of early revascularization and drugs to regulate the neuroendocrine system, the impact of such measures on alleviating the development of heart failure (HF) after myocardial infarction (MI) remains limited. Therefore, it is important to discuss the development of new therapeutic strategies to prevent or reverse HF after MI. This requires a better understanding of the potential mechanisms involved. HF after MI is the result of complex pathophysiological processes, with adverse ventricular remodeling playing a major role. Adverse ventricular remodeling refers to the heart's adaptation in terms of changes in ventricular size, shape, and function under the influence of various regulatory factors, including the mechanical, neurohormonal, and cardiac inflammatory immune environments; ischemia/reperfusion injury; energy metabolism; and genetic correlation factors. Additionally, unique right ventricular dysfunction can occur secondary to ischemic shock in the surviving myocardium. HF after MI may also be influenced by other factors. This review summarizes the main pathophysiological mechanisms of HF after MI and highlights sex-related differences in the prognosis of patients with acute MI. These findings provide new insights for guiding the development of targeted treatments to delay the progression of HF after MI and offering incremental benefits to existing therapies.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Remodelação Ventricular/fisiologia , Insuficiência Cardíaca/complicações , Miocárdio/metabolismo
14.
Protein Pept Lett ; 30(9): 734-742, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37622714

RESUMO

INTRODUCTION: Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of nicotinamide with S-adenosine-L-methionine (SAM) as the methyl donor. Abnormal expression of NNMT is associated with many diseases (such as multiple cancers and metabolic and liver diseases), making NNMT a potential therapeutic target. Limited studies concerning the enzymesubstrate/ inhibitor interactions could be found to fully understand the detailed reaction mechanism. METHODS: The binding affinity and ligand binding epitopes of nicotinamide or SAH for binding NNMT and its mutants were determined using saturated transfer difference (STD) nuclear magnetic resonance (NMR) techniques combined with site-directed mutagenesis. RESULTS: The average dissociation constant of WT NNMT with nicotinamide and S-adenosine homocysteine (SAH) was 5.5 ± 0.9 mM and 1.2 ± 0.3 mM, respectively, while the mutants Y20F and Y20G with nicotinamide were up to nearly 4 times and 20 times that of WT and with SAH nearly 2 times and 5 times that of WT. The data suggested that WT had the highest binding affinity for nicotinamide or SAH, followed by Y20F and Y20G, which was consistent with its catalytic activity. CONCLUSION: The binding affinity of nicotinamide and SAH to NNMT and its mutants were obtained by STD NMR in this study. It was found that nicotinamide and SAH bind to WT in a particular orientation, and Y20 is critical for their binding orientation and affinity to NNMT.


Assuntos
Niacinamida , Nicotinamida N-Metiltransferase , Nicotinamida N-Metiltransferase/genética , Nicotinamida N-Metiltransferase/química , Ligantes , Niacinamida/química , Niacinamida/metabolismo , Adenosina , Espectroscopia de Ressonância Magnética
15.
Heliyon ; 9(8): e18949, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37600371

RESUMO

Objectives: The diagnosis of tuberculosis pleural effusion (TPE) remains challenging, traditional diagnostic tests have limited diagnostic efficacy. This study aimed to assess the diagnostic performance of pleural fluid (PF) lipoarabinomannan (LAM) in TPE. Methods: A diagnostic method for PF LAM (LAM-PF) was established using LEDBIO's AIMLAM kit. The diagnostic performance of LAM-PF was evaluated in 162 HIV-negative patients with suspected TPE. Results: The LAM-PF method established in this study exhibited good linearity and recovery rate, with a limit of detection (LOD) of 2.90 pg/mL. Using a cut-off value of 5.33 pg/mL, the sensitivity and specificity of LAM-PF in diagnosing TPE (n = 128) were 47.7% and 100.0%, respectively. The sensitivity in patients with probable TPE (n = 29) and definite TPE (n = 99) were 41.4% and 49.5%, respectively. LAM-PF displayed a significantly higher sensitivity in probable TPE compared to other tuberculosis detection methods. Combined testing of adenosine deaminase (ADA)and LAM increased the detection sensitivity of TPE to 68.0%, and the area under the curve was 0.84 (0.77-0.89). Conclusion: This study successfully established a method for detecting LAM in PF, which exhibited favorable diagnostic performance for TPE, particularly in challenging cases of probable TPE. Combined detection of LAM and ADA in PF significantly improves TPE diagnostic efficiency.

16.
Molecules ; 28(12)2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37375160

RESUMO

The main protease (Mpro) is a promising drug target for inhibiting the coronavirus due to its conserved properties and lack of homologous genes in humans. However, previous studies on Mpro's kinetic parameters have been confusing, hindering the selection of accurate inhibitors. Therefore, obtaining a clear view of Mpro's kinetic parameters is necessary. In our study, we investigated the kinetic behaviors of Mpro from SARS-CoV-2 and SARS-CoV using both FRET-based cleavage assay and the LC-MS method, respectively. Our findings indicate that the FRET-based cleavage assay could be used for preliminary screening of Mpro inhibitors, while the LC-MS method should be applied to select the effective inhibitors with higher reliability. Furthermore, we constructed the active site mutants (H41A and C145A) and measured the kinetic parameters to gain a deeper understanding of the atomic-level enzyme efficiency reduction compared to the wild type. Overall, our study provides valuable insights for inhibitor screening and design by offering a comprehensive understanding of Mpro's kinetic behaviors.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Antivirais/farmacologia , Reprodutibilidade dos Testes , Inibidores de Proteases/farmacologia , Inibidores de Proteases/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteínas não Estruturais Virais , Peptídeo Hidrolases
17.
STAR Protoc ; 4(2): 102254, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37115666

RESUMO

Engineered microorganisms hold potential for disease diagnosis and treatment. Here, we present a protocol to engineer E. coli Nissle 1917 strain (iROBOT) using genome insertion and plasmid construction to diagnose, record, and ameliorate inflammatory bowel disease in mice. We describe steps for constructing and administering iROBOT, diagnosing and recording colitis, preparing samples, and analyzing fluorescence and base editing ratios of iROBOT. We detail a colitis ameliorating assay using the disease activity index, colon length, tissue pathological section, and cytokine analysis. For complete details of the use and execution of this protocol, please refer to Zou et al.1.

18.
J Hazard Mater ; 445: 130614, 2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-37056003

RESUMO

Heavy metals (HMs) discharged from smelting production may pose a major threat to human health and soil ecosystems. In this study, the spatial distribution characteristics of HMs in the soil of a non-ferrous metal smelting site were assessed. This study employed the geodetector (GD) by optimizing the classification condition and supplementing the correlation analysis (CA). The contribution of driving factors, such as production workshop distributions, hydrogeological conditions, and soil physicochemical properties, to the distribution of HMs in soil in the horizontal and vertical dimensions was assessed. The results showed that the main factors underlying the spatial distribution of As, Cd, Hg, Pb, Sb, and Zn in the horizontal direction were the distance from the sintering workshop (the maximum q value of that factor, q=0.28), raw material yard (q=0.14), and electrolyzer (q=0.29), while those in the vertical direction were the soil moisture content (q=0.17), formation lithology (q=0.12), and soil pH (q=0.06). The findings revealed that the CA is a simple and effective method to supplement the GD analysis underlying the spatial distribution characteristics of HMs at site scale. This study provides useful suggestions for environmental management to prevent HMs pollution and control HMs in the soil of non-ferrous metal smelting sites.

19.
Int J Geriatr Psychiatry ; 38(3): e5900, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36862560

RESUMO

OBJECTIVES: Cognitive and neuroimaging assessments are still the main clinical practice methods for screening and diagnosing vascular dementia (VaD) patients. This study aimed to establish the neuropsychological characteristics of mild-to-moderate subcortical ischaemic vascular dementia (SIVD) patients, find an optimal cognitive marker for differentiating them from Alzheimer's disease (AD) patients, and explore the correlation between cognitive function and total small vessel disease (SVD) burden. METHODS: SIVD (n = 60) and AD (n = 30) patients and cognitively unimpaired healthy controls (HCs; n = 30) were recruited from our longitudinal MRI AD and SIVD study (ChiCTR1900027943) and received a comprehensive neuropsychological assessment and a multimodal MRI scan. Cognitive performance and MRI SVD markers were compared between groups. Combined cognitive scores were established for differentiating between SIVD and AD patients. Correlations between cognitive function and total SVD scores were analysed in dementia patients. RESULTS: SIVD patients showed poorer performance in information processing speed and better performance in memory, language, and visuospatial function than AD patients, although all cognitive domains were impaired in both groups compared with HCs. Combined cognitive scores showed an area under the curve of 0.727 (95%CI 0.62-0.84, p < 0.001) for differentiating SIVD and AD patients. Auditory Verbal Learning Test recognition scores were negatively correlated with total SVD scores in SIVD patients. CONCLUSIONS: Our results suggested that neuropsychological assessments, specifically combined tests including episodic memory, information processing speed, language and visuospatial ability, are useful in the clinical differentiation between SIVD and AD patients. Moreover, cognitive dysfunction was partly correlated with MRI SVD burden in SIVD patients.


Assuntos
Doença de Alzheimer , Isquemia Encefálica , Demência Vascular , Humanos , Demência Vascular/diagnóstico por imagem , Doença de Alzheimer/diagnóstico , Cognição , Isquemia Encefálica/psicologia , Neuroimagem , Testes Neuropsicológicos , Imageamento por Ressonância Magnética
20.
Front Cell Dev Biol ; 11: 1153174, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36968196

RESUMO

Metabolic syndrome (MetS) is a complex pathological condition that involves disrupted carbohydrate, protein, and fat metabolism in the human body, and is a major risk factor for several chronic diseases, including diabetes, cardiovascular disease, and cerebrovascular disease. While the exact pathogenesis of metabolic syndrome is not yet fully understood, there is increasing evidence linking mitochondrial dysfunction, which is closely related to the mitochondrial genome and mitochondrial dynamics, to the development of this condition. Recent advancements in genetic sequencing technologies have allowed for more accurate detection of mtDNA mutations and other mitochondrial abnormalities, leading to earlier diagnosis and intervention in patients with metabolic syndrome. Additionally, the identification of specific mechanisms by which reduced mtDNA copy number and gene mutations, as well as abnormalities in mtDNA-encoded proteins and mitochondrial dynamics, contribute to metabolic syndrome may promote the development of novel therapeutic targets and interventions, such as the restoration of mitochondrial function through the targeting of specific mitochondrial defects. Additionally, advancements in genetic sequencing technologies may allow for more accurate detection of mtDNA mutations and other mitochondrial abnormalities, leading to earlier diagnosis and intervention in patients with MetS. Therefore, strategies to promote the restoration of mitochondrial function by addressing these defects may offer new options for treating MetS. This review provides an overview of the research progress and significance of mitochondrial genome and mitochondrial dynamics in MetS.

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