mBio
·
2024
·Vol. 15
·期 6
·
IF 5.1
Xiaolong Guo,Hua Yu,Junzhi Xiong,Qian Dai,Yuanyuan Li,Wei Zhang,Xiping Liao,Xiaomei He,Hongli Zhou,Kebin Zhang
Pseudomonas aeruginosa is one of the most common nosocomial pathogens worldwide, known for its virulence, drug resistance, and elaborate sensor-response network. The primary challenge encountered by pathogens during the initial stages of infection is the immune clearance arising from the host. The resident macrophages of barrier organs serve as the frontline defense against these pathogens. Central to our understanding is the mechanism by which bacteria modify their behavior to circumvent macrophage-mediated clearance, ensuring their persistence and colonization. To successfully evade macrophage-mediated phagocytosis, bacteria must possess an adaptive response mechanism. Two-component systems provide bacteria the agility to navigate diverse environmental challenges, translating external stimuli into cellular adaptive responses. Here, we report that the well-documented histidine kinase, LadS, coupled to a cognate two-component response regulator, PA0034, governs the expression of a vital adhesin called chaperone-usher pathway pilus cupA. The LadS/PA0034 system is susceptible to interference from the reactive oxygen species likely to be produced by macrophages and further lead to a poor adhesive phenotype with scantily cupA pilus, impairing the phagocytosis efficiency of macrophages during acute infection. This dynamic underscores the intriguing interplay: as macrophages deploy reactive oxygen species to combat bacterial invasion, the bacteria recalibrate their exterior to elude these defenses.
研究领域:
微生物学
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免疫学
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致病机理
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ELECTROCHEMISTRY
·
2024
·
IF 2.7
Yuzhi LI,Jinyu WANG,Shuai ZOU,Aihong WANG,Huize JIANG,Kaibo WANG
Cleverly designing and synthesizing bifunctional electrocatalysts with high activity and exceptional stability for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) hold profound importance in the realm of renewable energy technologies. Here we demonstrated the fabrication of FeCoP hollow nanocubes by precisely controlling the oxidation-phosphorization processing on Prussian blue analogues. Owing to the robust electronic interaction and hollow structure, the obtained FeCoP material, when utilized for catalyzing HER and OER in a 1 M KOH solution, requires overpotentials of merely 74 mV and 219 mV to achieve 10 mA cm−2, respectively. Importantly, when used as a bifunctional catalyst for overall water splitting, FeCoP can achieve a current density of 10 mA cm−2 at a low cell voltage of only 1.58 V and exhibits impressive durability. After a prolonged test of 52 hours under a constant current density, there is no significant degradation performance decay. The current method offers a broader avenue for the controllable synthesis of phosphide electrocatalysts in practical applications.
研究领域:
材料科学
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可再生能源技术
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电化学
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产品关联
DOI
高影响因子
Translational Andrology and Urology
·
2024
·Vol. 13
·期 9
·1971
·
IF 1.9
Jiahao Jiang,Fei Xiao,Lanxin Yang,Yan Zeng,Jing Chen,Hengcheng Zhu,Lingqi Liu
Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urological disease characterized by chronic pelvic pain and various discomforts. Astaxanthin (AST) has multiple functions, including anti-inflammatory property, but it is unclear whether AST plays a key role in CP/CPPS and how it works. This study aimed to investigate the protective effect of AST on CP/CPPS in rats and the underlying mechanism. Methods A CP/CPPS rat model was induced by intraprostatic injection of carrageenan and the blood specimens and prostates were harvested for further research after oral administration of AST for 4 weeks. Results Tactile allodynia test showed that AST ameliorated chronic pelvic pain in a dose-depended manner. In addition, histological evaluation indicated that AST alleviated CP/CPPS rat prostate histological inflammation. Meanwhile, AST suppressed the expression of proinflammatory cytokines, including interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNF-α). Besides, AST inhibited the activities of prostaglandin E2 (PGE2) and cyclooxygenase 2 (COX2). Furthermore, AST decreased the activation of the nuclear factor-κB (NF-κB) signaling pathway. Conclusions Our study has shown that AST exerts an anti-inflammatory and protective effect against CP/CPPS and the function is mediated at least through the suppression of NF-κB signaling pathway. These results provide evidence of AST as the potential agents for the treatment of CP/CPPS.
研究领域:
泌尿科
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药理学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
ELECTROCHEMISTRY
·
2024
·Vol. 92
·期 4
·043015-043015
·
IF 2.7
Yuxiang ZHONG,Yuanjia MA,Yangzhou HE,Xiao YANG
The authors focus on the development of a molten salt processing technology for extracting white phosphorus (P4) from sewage sludge ash, which is recognized as a potential secondary P source due to its composition of various metal phosphates. This work offers insights into the interaction between solid AlPO4 and molten CaCl2. The results show that solid AlPO4 exhibits favorable solubility in molten CaCl2, although at a slower rate compared to solid Ca3(PO4)2 due to the presence of stable Al–O bonds. The study also demonstrates the feasibility of extracting high-purity P4 from the molten mixture through electrolysis. The purity of the obtained electrolyzed P4 from AlPO4 is comparable to the commercially available high-purity-grade product. These findings underscore the potential of sewage sludge ash containing AlPO4 as a viable source for extracting high-purity P4. This research contributes to the advancement of sustainable P utilization technologies from secondary sources.
研究领域:
环境科学
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化学工程
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产品关联
DOI
高影响因子
mBio
·
2025
·
IF 4.7
Kaili Duan,Shaozhe Qin,Fangling Cui,Liangyuan Zhao,Yongqing Huang,Jin-Rong Xu,Guanghui Wang
Deoxynivalenol (DON), a mycotoxin primarily produced by Fusarium species, is commonly found in cereal grains and poses risks to human and animal health, as well as global grain trade. This study demonstrates that methyl jasmonate (MeJA), a natural plant hormone, inhibits the growth and conidiation of Fusarium graminearum. Importantly, MeJA significantly reduces DON production by suppressing TRI gene expression and toxisome formation. To explore the molecular mechanism, we identified MeJA-tolerant mutants, including a transcription factor MRT1 and cAMP-PKA pathway-related genes (FgGPA1 and FgSNT1). MeJA treatment reduced PKA activity and intracellular cAMP levels in F. graminearum, suggesting it targets the cAMP-PKA pathway. Notably, the MeJA-resistant mutant FgGPA1R178H enhanced fungal growth, DON production, and cAMP levels in the presence of MeJA. Exogenous cAMP alleviated MeJA’s inhibitory effects on DON production, further supporting this pathway’s involvement. Interestingly, MeJA had no effect on all three MAP kinase pathways (Mgv1, Gpmk1, and FgHog1). Truncated and phospho-mimicking mutations in Mrt1 or FgSnt1 conferred MeJA resistance, suggesting they may act downstream of the cAMP-PKA pathway. In conclusion, MeJA presents a promising approach to control F. graminearum growth and DON production.
研究领域:
植物病理学
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分子生物学
·
真菌学
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产品关联
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2025
·
IF 3.8
Heng Zhang,Yizheng Zhou,Hanmo Yang,Xinyi Tao,Yinping Chen,Fuqiang Dong,Yi Sun
The growing resistance of Aspergillus to azoles poses a significant challenge in treating invasive fungal infections. This study aimed to investigate the synergistic effect of berbamine hydrochloride (BBM) combined with azoles in treating Aspergillus fumigatus and explore the role of efflux pump inhibition in this synergy. The efficacy of combining BBM with itraconazole (ITC), voriconazole (VOR), and posaconazole (POS) was tested against 69 A. fumigatus strains that had been identified using the M38-A3 broth microdilution method. quantitative reverse transcription PCR (RT-qPCR) was used to measure gene expression related to synergy, while flow cytometry was employed to assess mitochondrial reactive oxygen species (ROS) levels, and Rhodamine 6G exocytosis assays were performed to quantify efflux pump activity. BBM alone showed no significant antifungal activity. BBM combined with POS exhibited synergy against 66 strains (95.7%), while two clinical isolates (Af05/Af08) and one defective strain (Δcdr1B) showed no synergy. Synergy with ITC was observed in three strains (4.3%), but not with VOR. In the non-synergistic Af05 and Af08 strains, the expression of the cdr1B gene was significantly lower compared to wild-type (WT) strains. ROS levels increased significantly in WT with POS and BBM combination therapy, but not in the defective strains. Glucose uptake was also reduced in the POS-BBM combination. BBM enhances azole sensitivity in A. fumigatus primarily by inhibiting the cdr1B-mediated efflux pump, supported by reduced Rhodamine 6G exocytosis and synergy loss in cdr1B-deficient strains. ROS accumulation and metabolic disruption may further contribute to this synergy. Targeting efflux pumps with BBM provides a novel strategy to combat azole resistance.
研究领域:
医学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
mSystems
·
2024
·
IF 5
Hong Xue,Yitian Wang,Chunfeng Mei,Lili Han,Mengxiong Lu,Xuan Li,Ting Chen,Fengyun Wang,Xudong Tang
Lactose intolerance (LI) is a prevalent condition characterized by gastrointestinal symptoms that arise following lactose consumption. Recent evidence suggests that the gut microbiome may influence lactose levels in the gut. However, there is limited understanding regarding the alterations in microbiota and metabolism between individuals with LI and non-LI. This study conducted a paired-sample investigation utilizing data from the American Gut Project (AGP) and performed metagenomic and untargeted metabolomic analyses in a Chinese cohort to explore the interaction between the gut microbiome and serum metabolites. In addition, fecal microbiota transplantation (FMT) experiments were conducted to further examine the impact of the LI-associated gut microbiome on inflammatory outcomes. We identified 14 microbial genera that significantly differed between LI and controls from AGP data. Using a machine learning approach, group separation was predicted based on seven species and nine metabolites in the Chinese cohort. Notably, increased levels of Escherichia coli in the LI group were negatively correlated with several metabolites, including PC (22:6/0:0), indole, and Lyso PC, while reduced levels of Faecalibacterium prausnitzii and Eubacterium rectale were positively correlated with indole and furazolidone. FMT-LI rats displayed visceral hypersensitivity and an altered gut microbiota composition compared to FMT-HC rats. Metagenomic and metabolomic analyses revealed an enrichment of MAPK signaling in LI, which was confirmed by FMT-LI rats showing higher expression of ERK and RAS, along with increased concentrations of proinflammatory cytokines. This study provides valuable insights into the disrupted microbial and metabolic traits associated with LI, emphasizing potential microbiome-based approaches for its prevention and treatment.
研究领域:
微生物学
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代谢组学
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胃肠病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
·
2024
·
IF 3.9
Yujia Chen,Wei Li,Li Wang,Bingmei Wang,Jian Suo
In confronting the significant challenge posed by multidrug-resistant (MDR) pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), the development of innovative anti-infective strategies is essential. Our research focuses on sortase A (SrtA), a vital enzyme for anchoring surface proteins in S. aureus. We discovered that plantamajoside (PMS), a phenylpropanoid glycoside extracted from Plantago asiatica L. (Plantaginaceae), acts as an effective and reversible inhibitor of SrtA, with a notable IC50 value of 22.93 µg/mL. This breakthrough provides a novel approach to combat both resistance and virulence in MRSA. PMS significantly inhibits S. aureus adhesion to fibrinogen, reducing biofilm formation and hindering the anchoring of staphylococcal protein A to the cell wall. Live-dead cell assays demonstrated increased survival rates in PMS-treated MRSA-infected A549 cells. Fluorescence quenching experiments revealed a robust interaction between PMS and SrtA, with mechanistic analyses pinpointing the critical R197 amino acid residue as the target site. In vivo, PMS was highly effective in a Galleria mellonella infection model, reducing mortality rates in MRSA-infected larvae. Additionally, PMS demonstrated therapeutic efficacy in a mouse pneumonia model, improved survival rates, reduced the bacterial load in pulmonary tissues, and mitigated lung damage. These results validate PMS as a promising compound to mitigate MRSA virulence and thwart resistance by targeting SrtA. This study highlights PMS as a leading candidate for controlling MRSA infections, showing the potential of targeting specific bacterial mechanisms in the fight against MDR infections.
研究领域:
微生物学
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药理学
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传染病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Translational Andrology and Urology
·
2024
·Vol. 13
·期 9
·2055
·
IF 1.9
Shoubin Li,Chunhong Yu,Helong Xiao,Qingle Xu,Bo Gao,Liuxiong Guo,Zhanxin Sun,Junjiang Liu
Background Benign prostatic hyperplasia (BPH) is a common disease among older men characterized by non-malignant proliferation of epithelial cells and inflammation. Nitric oxide synthase traffic inducer (NOSTRIN) is a pleiotropic regulator of endothelial cell function and signaling and exerts anti-inflammatory, anti-proliferation, and modulating nuclear factor-kappa B (NF-κB) signaling effects. Its expression and function in BPH tissues and prostate epithelial cells are unknown. The study aims to investigate the expression and functions of NOSTRIN in BPH, and its possible molecular mechanism. Methods The BPH model was constructed in male Institute of Cancer Research (ICR) mice using 5 mg/kg/day testosterone propionate (TP) for 30 days, and the model was evaluated by detecting prostate index, prostate epithelial thickness, and prostate-specific antigen (PSA) expression. Dihydrotestosterone (DHT, 10 nM)-induced in vitro model of human prostate epithelial cells (RWPE-1) was established. We generated lentivirus-harboring human NOSTRIN . The mRNA expression was detected by real-time quantitative polymerase chain reaction (PCR) assay; the protein expression or localization was detected by western blot assay, immunohistochemistry, or immunofluorescence staining. Cell proliferation was assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and 5-ethynyl-2'-deoxyuridine (EdU) staining. Reactive oxygen species (ROS) production was observed by dihydroethidium staining. Nitric oxide (NO) and malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were detected using commercial kits. Enzyme-linked immunosorbent assay (ELISA) was used to determine levels of interleukin 1 beta (IL1B), interleukin 6 (IL6), interferon gamma (IFNG), and tumor necrosis factor (TNF). Results NOSTRIN expression was significantly inhibited in the TP-induced ICR mouse BPH model and DHT-induced model of RWPE-1 proliferation. Protein expression of the BPH-related and proliferation markers PSA and proliferating cell nuclear antigen (PCNA) was suppressed in NOSTRIN-overexpressing RWPE-1 cells exposed to DHT. NOSTRIN overexpression notably inhibited the RWPE-1 cell proliferation in vitro , as evidenced by MTT and EdU staining. NOSTRIN overexpression significantly decreased the expression of cell cycle-related proteins cyclin dependent kinase 4 (CDK4) and cyclin D1 (CCND1) in vitro . The production of ROS, NO, and lipid peroxidation products MDA was inhibited by NOSTRIN overexpression in vitro , while the SOD activity was increased. NOSTRIN overexpression reduced the mRNA expression of inflammatory mediator nitric oxide synthase 2 (NOS2) and inhibited the mRNA expression and secretion of pro-inflammatory cytokines IL1B, IL6, IFNG, and TNF in vitro . The mechanistic studies revealed an increased phosphorylation of NF-κB p65 in vivo and in vitro . Remarkably, NOSTRIN overexpression notably inhibited the protein expression of phospho-NF-κB p65 in vitro . Conclusions NOSTRIN is involved in BPH by inhibiting proliferation, oxidative stress, and inflammation in prostate epithelial cells. These functions may act through the inhibition of NF-κB signaling.
研究领域:
泌尿学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
·
2024
·
IF 4.1
Junyao Wang,Xi Liu,Yuxin Song,Zhonghua Liu,Xing Tang,Huaxin Tan
Antibiotic resistance has become a critical concern in recent years, and antimicrobial peptides may function as innovative antibacterial agents to address this issue. In this work, we identified a novel antimicrobial peptide, LC-AMP-I1, derived from the venom of Lycosa coelestis, demonstrating substantial antibacterial properties and minimal hemolytic activity. LC-AMP-I1 was subjected to additional assessment for antibacterial efficacy, anti-biofilm properties, drug resistance, stability, and cytotoxicity in vitro. It exhibited comparable antibacterial efficacy to melittin against six common clinical multidrug-resistant bacteria, effectively inhibiting biofilm formation and disrupting established biofilms. Additionally, LC-AMP-I1 demonstrated minimal bacterial resistance, excellent stability, negligible mammalian cell toxicity, low hemolytic activity, and appropriate selectivity for both normal and tumor cells. When combined with traditional antibiotics, LC-AMP-I1 exhibited additive or synergistic therapeutic effects. In a neutropenic mouse thigh infection model, LC-AMP-I1 exhibited a therapeutic effect in inhibiting bacterial proliferation in vivo. The mechanistic investigation indicated that LC-AMP-I1 could influence bacterial cell membrane permeability at low concentrations and directly disrupt structure-function at high concentrations. The results of this work indicate that LC-AMP-I1 may function as a viable alternative to traditional antibiotics in addressing multidrug-resistant bacteria.
研究领域:
微生物学
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分子生物学
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药物开发
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感染性疾病
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产品关联
DOI
PubMed
高影响因子
mSphere
·
2024
·
IF 3.7
Wenxuan Liu,Fulong Nan,Fengjun Liu,Xiaoli Yang,Zonghui Li,Shasha Jiang,Xianjuan Zhang,Jun Li,Meng Yu,Yunyang Wang,Bin Wang
Hyperuricemia has become the second most prevalent metabolic disease after diabetes, but the limitations of urate-lowering treatment (ULT) drugs and patient nonadherence make ULT far less successful. Thus, more ULT approaches urgently need to be explored. Uric acid-degrading bacteria have potential application value in ULT. In this study, we isolated 44XBT, a uric acid-degrading bacterium, from black-headed gull (Chroicocephalus ridibundus) feces. Using a polyphasic taxonomic approach, strain 44XBT was identified as a novel genus within the family Bacillaceae; subsequently, the name Aciduricibacillus chroicocephali was proposed. Strain 44XBT had a unique uric acid-dependent phenotype and utilized uric acid and allantoin as the sole carbon and nitrogen sources, but not common carbon sources or complex media. In the genome, multiple copies of genes involved in uric acid metabolic pathway (pucL, pucM, uraD, and allB) were found. Six copies of pucL (encoding urate oxidase) were detected. Of these, five pucL copies were in a tandem arrangement and shared 70.42%–99.70% amino acid identity. In vivo experiments revealed that 44XBT reduced serum uric acid levels and attenuated kidney damage in hyperuricemic mice through uric acid catalysis in the gut and gut microbiota remodeling. In conclusion, our findings discover a strain for studying bacterial uric acid metabolism and may provide valuable insights into ULT.
研究领域:
微生物学
·
代谢疾病
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药理学
·
基因组学
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产品关联
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2024
·
IF 3.7
Yvhao Xie,Xinxin Li,Qingshi Meng,Jinjun Li,Xin Wang,Liying Zhu,Weiwei Wang,Xiaoqiong Li
Tryptophan (TRP) metabolites have been identified as potent biomarkers for complications of type 2 diabetes mellitus (T2DM). However, it remains unclear whether the therapeutic effect of metformin in T2DM is related to the modulation of TRP metabolic pathway. This study aims to investigate whether metformin affects TRP metabolism in T2DM mice through the gut microbiota. A liquid chromatography-tandem mass spectrometry method was established to determine 16 TRP metabolites in the serum, colon content, urine, and feces of T2DM mice, and the correlations between metabolites and the T2DM mice gut microbiota were performed. The method demonstrated acceptable linearity (R2 > 0.996), with the limit of quantification ranging from 0.29 to 69.444 nmol/L for 16 analytes, and the limit of detection ranging from 0.087 to 20.833 nmol/L. In T2DM mice, metformin treatment effectively restored levels of indole-3-lactic acid (ILA), indole-3-propionic acid (IPA), and the ILA/IPA ratio, along with several aryl hydrocarbon receptor ligands in the serum, with a notable impact in the colon but not in the urine. This restoration was accompanied by a shift in the relative abundance of Dubosiella, Turicibacter, RF39, Clostridia_UCG-014, and Alistipes. Spearman’s correlation analysis revealed positive correlations between Turicibacter and Alistipes with IPA and indole-3-acetic acid. Conversely, these genera displayed negative correlations with ILA and kynurenine. In addition, our study revealed the presence of endogenous indole pathway in germ-free mice, and the impact of metformin on endogenous TRP metabolism in T2DM mice cannot be disregarded. Further research is needed to investigate the regulation of TRP metabolism by metformin.
研究领域:
药理学
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微生物学
·
代谢组学
·
糖尿病研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）