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1.
Food Res Int ; 188: 114488, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823841

ABSTRACT

Direct analysis in real time-mass spectrometry (DART-MS) has evolved as an effective analytical technique for the rapid and accurate analysis of food samples. The current advancements of DART-MS in food analysis are described in this paper. We discussed the DART principles, which include devices, ionization mechanisms, and parameter settings. Numerous applications of DART-MS in the fields of food and food products analysis published during 2018-2023 were reviewed, including contamination detection, food authentication and traceability, and specific analyte analysis in the food matrix. Furthermore, the challenges and limitations of DART-MS, such as matrix effect, isobaric component analysis, cost considerations and accessibility, and compound selectivity and identification, were discussed as well.


Subject(s)
Food Analysis , Food Contamination , Mass Spectrometry , Food Analysis/methods , Mass Spectrometry/methods , Food Contamination/analysis
2.
Article in English | MEDLINE | ID: mdl-38826133

ABSTRACT

Gastric cancer (GC) is a common gastrointestinal system malignancy. PACSIN1 functions as an oncogene in various cancers. This study aims to investigate the potential of PACSIN1 as a target in GC treatment. Gene expression is determined by RT-qPCR, immunofluorescence staining, and immunohistochemistry assay. FISH is performed to determine the colocalization of PACSIN1 and the major histocompatibility complex (MHC-I). Cytokine release and cell functions are analyzed by flow cytometry. In vivo assays are also conducted. Histological analysis is performed using H&E staining. The results show that PACSIN1 is overexpressed in GC patients, especially in those with immunologically-cold tumors. A high level of PACSIN1 is associated with poor prognosis. PACSIN1 deficiency inhibits autophagy but increases antigen presentation in GC cells. Moreover, PACSIN1 deficiency inhibits the lysosomal fusion and selective autophagy of MHC-I, increases CD8 + T-cell infiltration, and suppresses tumor growth and liver metastasis in vivo. Additionally, PACSIN1 knockout enhances the chemosensitivity of cells to immune checkpoint blockade. In summary, PACSIN1 mediates lysosomal fusion and selective autophagy of MHC-I and suppresses antigen presentation and CD8 + T-cell infiltration, thus inhibiting antitumor immunity in GC.

4.
J Chem Theory Comput ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38828925

ABSTRACT

Exclusively prioritizing the precision of energy prediction frequently proves inadequate in satisfying multifaceted requirements. A heightened focus is warranted on assessing the rationality of potential energy curves predicted by machine learning-based force fields (MLFFs), alongside evaluating the pragmatic utility of these MLFFs. This study introduces SWANI, an optimized neural network potential stemming from the ANI framework. Through the incorporation of supplementary physical constraints, SWANI aligns more cohesively with chemical expectations, yielding rational potential energy profiles. It also exhibits superior predictive precision compared with that of the ANI model. Additionally, a comprehensive comparison is conducted between SWANI and a prominent graph neural network-based model. The findings indicate that SWANI outperforms the latter, particularly for molecules exceeding the dimensions of the training set. This outcome underscores SWANI's exceptional capacity for generalization and its proficiency in handling larger molecular systems.

5.
Int J Gen Med ; 17: 2445-2453, 2024.
Article in English | MEDLINE | ID: mdl-38826508

ABSTRACT

Background: This investigation evaluated the prognostic significance of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), and introduced a combined NLR-PLR score to evaluate the correlation between NLR-PLR score and hepatocellular carcinoma (HCC) recurrence. Material/Methods: We enrolled 110 patients who underwent orthotopic liver transplantation (LT) for HCC. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were assessed, and appropriate cut-off values were established. The NLR-PLR score ranged from 0 to 2 as follows: score of 2, high NLR (≥3.37) and high PLR (≥105.96); score of 1, either high NLR or high PLR; score of 0, neither high NLR nor high PLR. Results: The median overall survival (OS) of patients with NLR-PLR score of 0, 1 and 2 was 27, 26.5, and 6 months, respectively. The median OS of patients with NLR-PLR score of 2 was shorter than those with 0 (P < 0.001) and 1 (P < 0.001). The median disease-free survival (DFS) time of patients with NLR-PLR score of 0, 1 and 2 was 24.5, 24, and 6 months, The median DFS of patients with NLR-PLR score of 2 was shorter than those with 0 (P = 0.001) and 1 (P = 0.015). Multivariate analysis showed that NLR-PLR score was an independent risk factor for prognosis and survival. Conclusion: NLR, PLR and NLR-PLR score can predict the long-term survival of patients, and NLR-PLR score, having more predictive value than NLR and PLR alone is an independent risk factor for patient survival. more predictive value than NLR and PLR alone.

6.
Asia Pac Allergy ; 14(2): 70-76, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38827263

ABSTRACT

Background: Histones have been associated with human diseases. However, the implication of extranuclear histone proteins and their potential mechanism in the pathophysiology of chronic rhinosinusitis (CRS) have not been thoroughly investigated. This study was designed to evaluate the role of histones in patients with CRS by comparing histone expression between patients and controls. Methods: Nasal polyp (NP) tissues were obtained, and their comprehensive gene expression profiles were investigated by microarray analysis. Differences in expression were verified by reverse transcriptase polymerase chain reaction and immunohistochemical staining. Cell culture and flow cytometry were used to evaluate the role of histones in the pathogenesis of polyps. Results: Significant differences in the microarray analysis were observed between the patient and control groups (P < 0.01). It was found by flow cytometry that the histone (H2BK) can promote cell apoptosis in NPs. Conclusion: Our results indicate that reduced expression of H2BK may contribute to the imbalance process of cell proliferation and apoptosis in CRS with NP.

7.
Int J Chron Obstruct Pulmon Dis ; 19: 1197-1206, 2024.
Article in English | MEDLINE | ID: mdl-38831891

ABSTRACT

Background: Malnutrition adversely affects prognosis in various medical conditions, but its implications in older adults with Chronic Obstructive Pulmonary Disease (COPD) in the ICU are underexplored. The geriatric nutritional risk index (GNRI) is a novel tool for assessing malnutrition risk. This study investigates the association between GNRI and 90-day mortality in this population. Methods: We selected older adults with COPD admitted to the ICU from Medical Information Mart for Intensive Care (MIMIC)-IV 2.2 database. A total of 666 patients were categorized into four groups based on their GNRI score: normal nutrition (>98), mild malnutrition (92-98), moderate malnutrition (82-91), and severe malnutrition (≤81) groups. We employed a restricted cubic spline (RCS) analysis to assess the presence of a curved relationship between them and to investigate any potential threshold saturation effect. Results: In multivariate Cox regression analyses, compared with individuals had normal nutrition (GNRI in Q4 >98), the adjusted HR values for GNRI in Q3 (92-98), Q2 (82-91), and Q1 (≤81) were 1.81 (95% CI: 1.27-2.58, p=0.001), 1.23 (95% CI: 0.84-1.79, p=0.296), 2.27 (95% CI: 1.57-3.29, p<0.001), respectively. The relationship between GNRI and 90-day mortality demonstrates an L-shaped curve (p=0.016), with an approximate inflection point at 101.5. Conclusion: These findings imply that GNRI is a useful prognostic tool in older adults with COPD in the ICU. An L-shaped relationship was observed between GNRI and 90-day mortality in these patients.


Subject(s)
Geriatric Assessment , Malnutrition , Nutrition Assessment , Nutritional Status , Predictive Value of Tests , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/mortality , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Aged , Male , Female , Retrospective Studies , Risk Factors , Malnutrition/mortality , Malnutrition/diagnosis , Risk Assessment , Geriatric Assessment/methods , Time Factors , Aged, 80 and over , Prognosis , Age Factors , Databases, Factual , Intensive Care Units/statistics & numerical data
8.
Biofactors ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38696072

ABSTRACT

The deubiquitinating enzyme 26S proteasome non-ATPase regulatory subunit 14 (PSMD14), a member of the JAB1/MPN/Mov34 metalloenzyme (JAMM) family, has been shown to function as an oncogene in various human cancers. However, the function of PSMD14 in glioma and the underlying mechanism remain unclear. In this study, our findings reveal a dramatic upregulation of PSMD14 in GBMs, which is associated with poor survival outcomes. Knocking down PSMD14 is associated with decreased proliferation and invasion of GBM cells in vitro and inhibited tumor growth in a xenograft mouse model. Mechanistically, PSMD14 directly interacts with ß-catenin, leading to a decrease in the K48-linked ubiquitination of ß-catenin and subsequent ß-catenin stabilization. Increased ß-catenin expression significantly reverses the inhibitory effects of PSMD14 knockdown on the migration, invasion, and tumor growth of GBM cells. Moreover, we observed a significant correlation between PSMD14 and ß-catenin expression in human GBM samples. In summary, our results reveal that PSMD14 is a crucial deubiquitinase that is responsible for stabilizing the ß-catenin protein, highlighting its potential for use as a therapeutic target for GBM.

9.
Clin Nucl Med ; 49(6): e288-e289, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38704655

ABSTRACT

ABSTRACT: Solitary mixed squamous cell and glandular papilloma of the lung is an extremely rare benign neoplasm. We describe FDG PET/CT findings in a case of solitary mixed squamous cell and glandular papilloma of the lung with high serum carcinoembryonic antigen level (63.3 ng/mL; reference, <5 ng/mL). The tumor showed intense FDG uptake with SUVmax of 23.8 mimicking lung cancer.


Subject(s)
Carcinoembryonic Antigen , Fluorodeoxyglucose F18 , Lung Neoplasms , Papilloma , Positron Emission Tomography Computed Tomography , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Papilloma/diagnostic imaging , Carcinoembryonic Antigen/blood , Male , Middle Aged , Female , Tomography, X-Ray Computed
10.
Front Pediatr ; 12: 1308931, 2024.
Article in English | MEDLINE | ID: mdl-38720947

ABSTRACT

Background: Idiopathic scoliosis significantly affects the physical and mental health of children and adolescents, with varying prevalence rates in different regions. The occurrence of idiopathic scoliosis is associated with genetic regulation and biochemical factors, but the changes in exosome-derived miRNA profiles among idiopathic scoliosis patients remain unclear. This study aimed to determine the prevalence of idiopathic scoliosis in Yunnan Province, China, and identify key exosome-derived miRNAs in idiopathic scoliosis through a cohort study. Methods: From January 2018 to December 2020, a cross-sectional study on idiopathic scoliosis in children and adolescents was conducted in Yunnan Province. A total of 84,460 students from 13 cities and counties in Yunnan Province participated in a scoliosis screening program, with ages ranging from 7 to 19 years. After confirmation through screening and imaging results, patients with severe idiopathic scoliosis and normal control individuals were selected using propensity matching. Subsequently, plasma exosome-derived miRNA sequencing and RT-qPCR validation were performed separately. Based on the validation results, diagnostic performance analysis and target gene prediction were conducted for differential plasma exosome-derived miRNAs. Results: The overall prevalence of idiopathic scoliosis in children and adolescents in Yunnan Province was 1.10%, with a prevalence of 0.87% in males and 1.32% in females. The peak prevalence was observed at age 13. Among patients diagnosed with idiopathic scoliosis, approximately 12.8% had severe cases, and there were more cases of double curvature than of single curvature, with thoracolumbar curvature being the most common in the single-curvature group. Sequencing of plasma exosome-derived miRNAs associated with idiopathic scoliosis revealed 56 upregulated and 153 downregulated miRNAs. Further validation analysis confirmed that hsa-miR-27a-5p, hsa-miR-539-5p, and hsa-miR-1246 have potential diagnostic value. Conclusions: We gained insights into the epidemiological characteristics of idiopathic scoliosis in Yunnan Province and conducted further analysis of plasma exosome-derived miRNA changes in patients with severe idiopathic scoliosis. This study has provided new insights for the prevention and diagnosis of idiopathic scoliosis, paving the way for exploring clinical biomarkers and molecular regulatory mechanisms. However, further validation and elucidation of the detailed biological mechanisms underlying these findings will be required in the future.

11.
Environ Monit Assess ; 196(6): 512, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38704803

ABSTRACT

To gain a comprehensive understanding of the hydrochemical characteristics, controlling factors, and water quality of groundwater in the main stream area of Yishu River (MSYR), a study was conducted using water quality data collected during both the dry and wet seasons. Through statistical analysis, hydrochemical methods, fuzzy comprehensive evaluation, and health risk evaluation modeling, the water chemical characteristics of the main stream area of Yishu River were studied, and the water quality of the area was comprehensively evaluated. The findings indicate that HCO3- and Ca2+ are the predominant anions and cations in the MSYR during the dry and wet seasons, respectively. Moreover, anion concentration in groundwater follows HCO3- > SO42- > NO3- > Cl-, while cations are ranked as Ca2+ > Na+ > Mg2+ > K+. Overall, the groundwater manifests as weakly alkaline and is predominantly classified as hard-fresh water. During the wet season, there is greater groundwater leaching and filtration, with rock and soil materials more readily transferred to groundwater, and the concentrations of main chemical components in groundwater are higher than those during the dry season, and the hydrochemical types are primarily characterized as HCO3-Ca·Mg and SO4·Cl-Ca·Mg types. These results also suggest that the chemical composition of the groundwater in the MSYR is influenced mainly by water-rock interaction. The primary ions originate from the dissolution of silicate rock and carbonate rock minerals, while cation exchange plays a critical role in the hydrogeochemical process. Groundwater in the MSYR is classified mostly as class II water, indicating that it is generally of good quality. However, areas with high levels of class IV and V water are present locally, and NO3- concentration is a crucial factor affecting groundwater quality. In the wet season, more groundwater and stronger mobility lead to greater mobility of NO3- and wider diffusion. Therefore, the risk evaluation model shows that nitrate health risk index is higher in the wet season than it is in the dry season, with children being more vulnerable to health risks than adults. To study groundwater in this area, its hydrochemical characteristics, water quality, and health risk assessment are of great practical significance for ensuring water safety for residents and stable development of social economy.


Subject(s)
Environmental Monitoring , Groundwater , Rivers , Water Pollutants, Chemical , Water Quality , Groundwater/chemistry , Water Pollutants, Chemical/analysis , Rivers/chemistry , China , Seasons
12.
Small ; : e2401394, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709222

ABSTRACT

Transition metal silicates (TMSs) are attempted for the electrocatalyst of oxygen evolution reaction (OER) due to their special layered structure in recent years. However, defects such as low theoretical activity and conductivity limit their application. Researchers always prefer to composite TMSs with other functional materials to make up for their deficiency, but rarely focus on the effect of intrinsic structure adjustment on their catalytic activity, especially anion structure regulation. Herein, applying the method of interference hydrolysis and vacancy reserve, new silicate vacancies (anionic regulation) are introduced in cobalt silicate hydroxide (CoSi), named SV-CoSi, to enlarge the number and enhance the activity of catalytic sites. The overpotential of SV-CoSi declines to 301 mV at 10 mA cm-2 compared to 438 mV of CoSi. Source of such improvement is verified to be not only the increase of active sites, but also the positive effect on the intrinsic activity due to the enhancement of cobalt-oxygen covalence with the variation of anion structure by density functional theory (DFT) method. This work demonstrates that the feasible intrinsic anion structure regulation can improve OER performance of TMSs and provides an effective idea for the development of non-noble metal catalyst for OER.

13.
J Chem Theory Comput ; 20(10): 4308-4324, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38720441

ABSTRACT

The climbing-image nudged elastic band (CI-NEB) method serves as an indispensable tool for computational chemists, offering insight into minimum-energy reaction paths (MEPs) by delineating both transition states (TSs) and intermediate nonstationary structures along reaction coordinates. However, executing CI-NEB calculations for reactions with extensive reaction coordinate spans necessitates a large number of images to ensure a reliable convergence of the MEPs and TS structures, presenting a computationally demanding optimization challenge, even with mildly costly electronic-structure methods. In this study, we advocate for the utilization of physically inspired prior mean function-based Gaussian processes (GPs) to expedite MEP exploration and TS optimization via the CI-NEB method. By incorporating reliable prior physical approximations into potential energy surface (PES) modeling, we demonstrate enhanced efficiency in multidimensional CI-NEB optimization with surrogate-based optimizers. Our physically informed GP approach not only outperforms traditional nonsurrogate-based optimizers in optimization efficiency but also on-the-fly learns the reaction path valley during optimization, culminating in significant advancements. The surrogate PES derived from our optimization exhibits high accuracy compared to true PES references, aligning with our emphasis on leveraging reliable physical priors for robust and efficient posterior mean learning in GPs. Through a systematic benchmark study encompassing various reaction pathways, including gas-phase, bulk-phase, and interfacial/surface reactions, our physical GPs consistently demonstrate superior efficiency and reliability. For instance, they outperform the popular fast inertial relaxation engine optimizer by approximately a factor of 10, showcasing their versatility and efficacy in exploring reaction mechanisms and surface reaction PESs.

14.
Article in English | MEDLINE | ID: mdl-38729522

ABSTRACT

BACKGROUND & AIMS: Dysfunction of the intestinal epithelial barrier comprising the junctional complex of tight junctions and adherent junctions leads to increased intestinal permeability, which is a major cause of uncontrolled inflammation related to inflammatory bowel disease (IBD). The NAD+-dependent deacetylase SIRT1 is implicated in inflammation and the pathologic process of IBD. We aimed to elucidate the protective role and underlying mechanism of SIRT1 in cell-cell junction and intestinal epithelial integrity. METHODS: The correlation of SIRT1 expression and human IBD was analyzed by GEO or immunohistochemical analyses. BK5.mSIRT1 transgenic mice and wild-type mice were given dextran sodium sulfate (DSS) and the manifestation of colitis-related phenotypes was analyzed. Intestinal permeability was measured by FITC-dextran and cytokines expression was analyzed by quantitative polymerase chain reaction. The expression of the cell junction-related proteins in DSS-treated or SIRT1-knockdown Caco2 or HCT116 cells was analyzed by Western blotting. The effects of nicotinamide mononucleotide in DSS-induced mice colitis were investigated. Correlations of the SIRT1-ß-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway with human IBD samples were analyzed. RESULTS: Reduced SIRT1 expression is associated with human IBD specimens. SIRT1 transgenic mice exhibit much-reduced manifestations of DSS-induced colitis. The activation of SIRT1 by nicotinamide mononucleotide bolsters intestinal epithelial barrier function and ameliorates DSS-induced colitis in mice. Mechanistically, DSS downregulates SiRT1 expression, leading to destabilization of ß-TrCP1 and upregulation of Snail1, accompanied by reduced expression of E-cadherin, Occludin, and Claudin-1, consequently resulting in increased epithelial permeability and inflammation. The deregulated SIRT1-ß-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway correlates with human IBD. CONCLUSIONS: SIRT1 is pivotal in maintaining the intestinal epithelial barrier integrity via modulation of the ß-TrCP1-Snail1-E-cadhein/Occludin/Claudin-1 pathway.

15.
Langmuir ; 40(21): 11251-11262, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38748644

ABSTRACT

Artificial photosynthesis for high-value hydrogen peroxide (H2O2) through a two-electron reduction reaction is a green and sustainable strategy. However, the development of highly active H2O2 photocatalysts is impeded by severe carrier recombination, ineffective active sites, and low surface reaction efficiency. We developed a dual optimization strategy to load dense Ni nanoparticles onto ultrathin porous graphitic carbon nitride (Ni-UPGCN). In the absence and presence of sacrificial agents, Ni-UPGCN achieved H2O2 production rates of 169 and 4116 µmol g-1 h-1 with AQY (apparent quantum efficiency) at 420 nm of 3.14% and 17.71%. Forming a Schottky junction, the surface-modified Ni nanoparticles broaden the light absorption boundary and facilitate charge separation, which act as active sites, promoting O2 adsorption and reducing the formation energy of *OOH (reaction intermediate). This results in a substantial improvement in both H2O2 generation activity and selectivity. The Schottky junction of dual modulation strategy provides novel insights into the advancement of highly effective photocatalytic agents for the photosynthesis of H2O2.

16.
iScience ; 27(5): 109732, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38706862

ABSTRACT

In Drosophila, long noncoding RNA Hsrω rapidly assembles membraneless organelle omega speckles under heat shock with unknown biological function. Here, we identified the distribution of omega speckles in multiple tissues of adult Drosophila melanogaster and found that they were selectively distributed in differentiated enterocytes but not in the intestinal stem cells of the midgut. We mimicked the high expression level of Hsrω via overexpression or intense heat shock and demonstrated that the assembly of omega speckles nucleates TBPH for the induction of ISC differentiation. Additionally, we found that heat shock stress promoted cell differentiation, which is conserved in mammalian cells through paraspeckles, resulting in large puncta of TDP-43 (a homolog of TBPH) with less mobility and the differentiation of human induced pluripotent stem cells. Overall, our findings confirm the role of Hsrω and omega speckles in the development of intestinal cells and provide new prospects for the establishment of stem cell differentiation strategies.

17.
Clin Pharmacol Ther ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711244

ABSTRACT

Gene expression networks associated with placebo effects are understudied; in this study, we identified transcriptomic profiles associated with placebo responsivity. Participants suffering from chronic pain underwent a verbal suggestion and conditioning paradigm with individually tailored thermal painful stimulations to elicit conditioned placebo effects. Participants reported pain intensity on a visual analog scale (VAS) anchored from zero = no pain to 100 = maximum imaginable pain. RNA was extracted from venous blood and RNA sequencing and validation tests were performed to identify differentially expressed genes (DEGs) associated with placebo effects, controlling for sex and level of pain. Unbiased enrichment analyses were performed to identify biological processes associated with placebo effects. Of the 10,700 protein-coding genes that passed quality control filters, 667 were found to be associated with placebo effects (FDR <0.05). Most genes (97%) upregulated were associated with larger placebo effects. The 17 top transcriptome-wide significant genes were further validated via RT-qPCR in an independent cohort of chronic pain participants. Six of them (CCDC85B, FBXL15, HAGH, PI3, SELENOM, and TNFRSF4) showed positive and significant (P < 0.05) correlation with placebo effects in the cohort. The overall DEGs were highly enriched in regulation of expression of SLITs and ROBOs (R-HSA-9010553, FDR = 1.26e-33), metabolism of RNA (R-HSA-8953854, FDR = 1.34e-30), Huntington's disease (hsa05016, FDR = 9.84e-31), and ribosome biogenesis (GO:0042254, FDR = 2.67e-15); alternations in these pathways might jeopardize the proneness to elicit placebo effects. Future studies are needed to replicate this finding and better understand the unique molecular dynamics of people who are more or less affected by pain and placebo.

18.
Animals (Basel) ; 14(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38731290

ABSTRACT

Streptococcus suis (S. suis) is a zoonotic pathogen with a global distribution, which causes serious diseases in both humans and animals and economic losses in the swine industry. As antibiotic resistance increases, there is an urgent imperative to explore novel antibacterial alternatives. In the present study, we selected the anticancer drug 5-fluorouracil (5-FU) approved by the Food and Drug Administration (FDA) as a candidate drug to treat S. suis infections. The results showed that various pathogens, especially S. suis, are more sensitive to 5-FU. Moreover, the cytotoxicity of 5-FU is relatively low. Extensive in vitro assays demonstrated the pronounced bacteriostatic and bactericidal efficacy of 5-FU against susceptible and multidrug-resistant S. suis strains. Its mechanisms of action include damage to the bacterial cell walls and membranes, resulting in the leakage of intracellular components, and the inhibition of thymidylate synthase (TS), leading to a depletion of deoxythymidine triphosphate (dTTP) pools, ultimately causing thymine-less death and lethal DNA damage in bacteria. Gene-knockout experiments further showed that 5-FU played a role by inhibiting the thyA gene-encoding thymidine synthase. Finally, we determined that S. suis infections can be alleviated by 5-FU in the mouse infection model. This study emphasizes the antibacterial potential of 5-FU against S. suis and provides evidence for its targeting of bacterial membrane damage and DNA damage. In summary, 5-FU can control S. suis infection and is expected to become a new alternative to antibiotics.

19.
Animals (Basel) ; 14(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38731305

ABSTRACT

Bordetella bronchiseptica is a significant contributor to respiratory disease in pigs, leading to substantial economic losses in the swine industry worldwide. We isolated 52 B. bronchiseptica strains from 542 samples collected from pigs with atrophic rhinitis and bronchopneumonia in central China. Multi-locus sequence typing identified two prevalent sequence types: ST6 (69.23%) and ST7 (30.77%). PCR-based detection of seven virulence genes (fhaB, prn, cyaA, dnt, bteA, fla, and bfrZ) revealed that six of these genes were present in over 90% of the isolates, with bfrZ being the exception at 59.62%. Antimicrobial susceptibility testing, performed using the K-B method, demonstrated high sensitivity to enrofloxacin, polymyxin, and doxycycline but a notable resistance to tylosin, trimethoprim, tobramycin, ciprofloxacin, and amikacin. Remarkably, 86.54% of the isolates exhibited a multidrug-resistant phenotype. Notably, we successfully screened a strain of B. bronchiseptica with a heteroresistance phenotype to gentamicin using population analysis profiling, which is a rare case. Biofilm-formation assays indicated that 96.15% of the isolates possessed biofilm-forming capabilities. These findings provide crucial insights into the prevalence of B. bronchiseptica in central China, facilitating the development of effective preventive measures to safeguard both animal and human health.

20.
Arab J Gastroenterol ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38755047

ABSTRACT

BACKGROUND AND STUDY AIMS: The integration of traditional Chinese medicine and Western medicine holds promise for the treatment of gastrointestinal disorders, which are influenced by intestinal microbiota and metabolites. This study reports a possible mechanism for the combination of Simo Decoction and Golden Bifid in functional dyspepsia (FD) by regulating intestinal microbiota and short-chain fatty acids (SCFAs). PATIENTS AND METHODS: A mouse model of food stagnation was constructed and treated with Simo Decoction combined with different concentrations of Golden Bifid. Meta-genomics sequencing was conducted to analyze the cecum contents of the mice. Following analyses of the composition and abundance of intestinal microbiota, gas chromatography-mass spectrometry was performed to measure SCFAs in the colonic content of mice. Finally, ELISA was utilized to determine the levels of pro-inflammatory factors in the duodenal mucosa of mice and the infiltration of eosinophils in the duodenum was observed by immunohistochemical staining. RESULTS: Combination of Simo Decoction and Golden Bifid more significantly alleviated dyspepsia in mice with food stagnation compared with Simo Decoction alone. The optimal ratio of combined treatment was 0.0075 mL/g (body weight) Simo Decoction and 0.0032 mg/g (body weight) Golden Bifid. The combined treatment increased the abundance of Bifidobacterium and Bacteroides in the intestine. The levels of SCFAs in the colonic contents of mice were increased after the combined treatment, contributing to diminished pro-inflammatory factors in the duodenal mucosa and reduced eosinophil infiltration. CONCLUSION: Combination of Simo Decoction and Golden Bifid increases the abundance of Bacteroides and Bifidobacterium and promotes the production of SCFAs, which is instrumental for alleviation of FD.

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