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2.
Am J Transl Res ; 16(9): 4662-4670, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39398586

RESUMO

OBJECTIVE: To investigate the influence of intestinal flora imbalance on inflammatory factors in the serum and vascular endothelial functionality in individuals with preeclampsia (PE). METHODS: From January 2022 to December 2023, a total of 58 individuals with PE (PE group) and 60 healthy controls (CON group) were included in this study; they were matched for age and pre-pregnancy Body Mass Index (BMI). A comparison was made between the two groups in terms of the general data and the number of unique intestinal flora. Additionally, clinical blood measures, serum inflammatory factors, and vascular endothelial function were also assessed and compared between the groups. RESULTS: Age, gestational age, and pre-pregnancy BMI were similar between the PE and control group. However, diastolic and systolic blood pressure were significantly higher in the PE group. The abundance of Lactobacillus, Bifidobacterium, Enterobacter, and Enterococcus. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were considerably higher in the PE group compared to the CON group, but Interleukin-4 (IL-4) was noticeably lower, and the amount of White blood cells (WBC), neutrophil count (N) and lymphocyte count (L) in the PE group were significantly higher than those in the CON group. In the PE group, serum vascular endothelin (ET) and soluble endoglin (sEng) were higher than in the CON group, vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels were considerably lower than in the CON group, and the levels of TC, TG, LDL-C and HDL-C were significantly higher in the PE group than in the CON group. The presence of Lactobacillus and Bifidobacterium was inversely associated with levels of TNF-α, IL-6, Interleukin-10 (IL-10), ET, and sEng, and positively associated with levels of IL-4, VEGF, and NO. Nevertheless, there was a positive correlation between the abundance of Enterobacterium and Enterococcus with the levels of TNF-α, IL-6, IL-10, ET, and sEng. Conversely, there was a negative correlation between the abundance of Enterobacterium and Enterococcus and the levels of IL-4, VEGF, and NO. CONCLUSION: Patients with PE exhibited dysbiosis of intestinal flora, characterized by altered gut microbiota diversity, increased serum pro-inflammatory factors, and impaired vascular endothelial function.

3.
Angew Chem Int Ed Engl ; : e202414772, 2024 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-39370522

RESUMO

Fiber zinc-air batteries are explored as promising power systems for wearable and portable electronic devices due to their intrinsic safety and the use of ambient oxygen as cathode material. However, challenges such as limited zinc anode reversibility and sluggish cathode reaction kinetics result in poor cycling stability and low energy efficiency. To address these challenges, we design a polydopamine-based all-in-one gel electrolyte (PAGE) that simultaneously regulates the reversibility of zinc anodes and the kinetics of air cathodes through polydopamine interfacial and redox chemistry, respectively. The intrinsic catechol and carboxylate groups in PAGE regulate the transport and solvation structure of Zn2+, facilitating dendrite-free zinc deposition with a lamellar stacking morphology. Additionally, the oxidation of redox-active catechol groups in PAGE replaces the sluggish oxygen evolution reaction on the air cathode and reduces the energy barrier for charging, enabling fiber zinc-air batteries to achieve a significantly improved energy efficiency of 95% and a longer lifespan of 40 hours. Further integration into self-powered electronic textiles underscores its potential for next-generation wearable systems.

4.
Virulence ; 15(1): 2411540, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39359063

RESUMO

The ability to form robust biofilms and secrete a diverse array of virulence factors are key pathogenic determinants of Staphylococcus aureus, causing a wide range of infectious diseases. Here, we characterized cwrA as a VraR-regulated gene encoding a cell wall inhibition-responsive protein (CwrA) using electrophoretic mobility shift assays. We constructed cwrA deletion mutants in the genetic background of methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains. Phenotypic analyses indicated that deletion of cwrA led to impaired biofilm formation, which was correlated with polysaccharide intercellular adhesin (PIA). Besides, the results of real-time quantitative PCR (RT-qPCR) and ß-galactosidase activity assay revealed that CwrA promoted biofilm formation by influence the ica operon activity in S. aureus. Furthermore, cwrA deletion mutants released less extracellular DNA (eDNA) in the biofilm because of their reduced autolytic activity compared to the wild-type (WT) strains. We also found that cwrA deletion mutant more virulence than the parental strain because of its enhanced hemolytic activity. Mechanistically, this phenotypic alteration is related to activation of the SaeRS two-component system, which positively regulates the transcriptional levels of genes encoding membrane-damaging toxins. Overall, our results suggest that CwrA plays an important role in modulating biofilm formation and hemolytic activity in S. aureus.


Assuntos
Proteínas de Bactérias , Biofilmes , Parede Celular , Regulação Bacteriana da Expressão Gênica , Infecções Estafilocócicas , Staphylococcus aureus , Fatores de Virulência , Biofilmes/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Staphylococcus aureus/patogenicidade , Staphylococcus aureus/genética , Virulência , Parede Celular/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Infecções Estafilocócicas/microbiologia , Animais , Camundongos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Óperon , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Polissacarídeos Bacterianos/metabolismo , Polissacarídeos Bacterianos/genética , Deleção de Genes , Feminino , Proteínas Quinases
5.
Cont Lens Anterior Eye ; : 102291, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227202

RESUMO

PURPOSE: To evaluate the impact of short-term scleral lens (SL) wear on anterior chamber (AC) dimension and central corneal thickness (CCT) in healthy Chinese people. METHODS: This is a prospective, daily wear study. Eligible participants were dispensed SLs to correct refractive errors. Anterior segment (AS) parameters were measured by AS optical coherence tomography (AS-OCT) before, during, and after 2 and 4 hours of lens wear. Repeated-measures analysis of variance (ANOVA) was used to analyze the changes in AS parameters over time. RESULTS: Twelve subjects (10 females and 2 males) with a mean age of 25.3 ± 3.8 years (ranging from 21 to 34 years) were recruited. The AC parameters, including anterior chamber depth (ACD) from the endothelium (endo-ACD), angle opening distance at 500 µm (AOD500), and trabecular-iris space area at 500 µm (TISA500), significantly decreased after wearing SLs for 4 hours (P<0.05). CCT increased by 12 µm (2.29 %) after wearing SLs for 4 hours (P=0.013). CONCLUSION: This study suggests that SL wear has a significant impact on AS dimensions in patients with healthy corneas in the short term with SL in situ, but tend to recover quickly after SL removal. Further research is needed to determine whether the change in AS dimensions during SL wear affects aqueous humor (AH) outflow and causes changes in intraocular pressure (IOP).

6.
Angew Chem Int Ed Engl ; : e202412459, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261278

RESUMO

Inherently chiral calixarenes have garnered significant attention due to their distinctive properties, yet the development of efficient catalytic asymmetric synthesis methods remains a critical challenge. Herein, we report the asymmetric synthesis of calix[4]arenes featuring inherent or both inherent and axial chirality via a cobalt-catalyzed C-H activation/annulation strategy in high yield with excellent enantio- and diastereoselectivity (up to > 99% ee and > 20:1 dr). Electrooxidation was also suitable for this transformation to obviate the sacrificial metal oxidants, underscoring the environmentally friendly potential of this approach. A key octahedral cobaltacycle intermediate was synthesized and characterized, providing valuable insights into the mode of enantio- and diastereocontrol of this protocol. Noteworthy photoluminescence quantum yields of up to 0.94 were measured, underscoring the potential of these compounds in the domain of organic fluorescent materials.

7.
Carbohydr Polym ; 346: 122637, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39245502

RESUMO

Tumor vaccines have become a promising approach for cancer treatment by triggering antigen-specific responses against tumors. However, autophagy and immunosuppressive tumor microenvironment (TME) reduce antigen exposure and immunogenicity, which limit the effect of tumor vaccines. Here, we develop fucoidan (Fuc) based chlorin e6 (Ce6)-chloroquine (CQ) self-assembly hydrogels (CCFG) as in situ vaccines. Ce6 triggers immune response in situ by photodynamic therapy (PDT) induced immunogenic cell death (ICD) effect, which is further enhanced by macrophage polarization of Fuc and autophagy inhibition of CQ. In vivo studies show that CCFG effectively enhances antigen presentation under laser irradiation, which induces a powerful in situ vaccine effect and significantly inhibits tumor metastasis and recurrence. Our study provides a novel approach for enhancing tumor immunotherapy and inhibiting tumor recurrence and metastasis.


Assuntos
Autofagia , Vacinas Anticâncer , Clorofilídeos , Cloroquina , Hidrogéis , Imunoterapia , Macrófagos , Fotoquimioterapia , Polissacarídeos , Porfirinas , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Camundongos , Vacinas Anticâncer/farmacologia , Vacinas Anticâncer/imunologia , Porfirinas/química , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Autofagia/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Imunoterapia/métodos , Fotoquimioterapia/métodos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Cloroquina/farmacologia , Camundongos Endogâmicos C57BL , Microambiente Tumoral/efeitos dos fármacos , Células RAW 264.7 , Linhagem Celular Tumoral , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Camundongos Endogâmicos BALB C , Feminino
8.
BMC Genomics ; 25(1): 902, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39349998

RESUMO

BACKGROUND: Backfat serves as a vital fat reservoir in pigs, and its excessive accumulation will adversely impact pig growth performance, farming efficiency, and pork quality. The aim of this research is to integrate assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) to explore the molecular mechanisms underlying porcine backfat deposition. RESULTS: ATAC-seq analysis identified 568 genes originating from 698 regions exhibiting differential accessibility, which were significantly enriched in pathways pertinent to adipocyte differentiation and lipid metabolism. Besides, a total of 283 transcription factors (TFs) were identified by motif analysis. RNA-seq analysis revealed 978 differentially expressed genes (DEGs), which were enriched in pathways related to energy metabolism, cell cycle and signal transduction. The integration of ATAC-seq and RNA-seq data indicates that DEG expression levels are associated with chromatin accessibility. This comprehensive study highlights the involvement of critical pathways, including the Wnt signaling pathway, Jak-STAT signaling pathway, and fatty acid degradation, in the regulation of backfat deposition. Through rigorous analysis, we identified several candidate genes (LEP, CTBP2, EHHADH, OSMR, TCF7L2, BCL2, FGF1, UCP2, CCND1, TIMP1, and VDR) as potentially significant contributors to backfat deposition. Additionally, we constructed TF-TF and TF-target gene regulatory networks and identified a series of potential TFs related to backfat deposition (FOS, STAT3, SMAD3, and ESR1). CONCLUSIONS: This study represents the first application of ATAC-seq and RNA-seq, affording a novel perspective into the mechanisms underlying backfat deposition and providing invaluable resources for the enhancement of pig breeding programs.


Assuntos
Cromatina , Animais , Suínos/genética , Cromatina/genética , Cromatina/metabolismo , Tecido Adiposo/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Regulação da Expressão Gênica , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , RNA-Seq
9.
Adv Mater ; : e2409910, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39258364

RESUMO

Scalable fiber lithium-ion batteries (FLIBs) have garnered significant attention due to huge potential applications in wearable technology. However, their widespread applications have been limited by inadequate cycle and calendar life, primarily due to the high permeability of the encapsulation layer to water vapor in ambient air. To address this challenge, an ultra-high barrier composite tube is developed by blending polytrifluorochloroethylene (PCTFE) with organically modified montmorillonite (OMMT) for the continuous packaging of FLIBs. Due to the high crystallinity (≈40.21%) and small free volume (103.443 Å3), the PCTFE tube exhibited a low water vapor transmission rate (WVTR) of 0.123 mg day-1 pkg-1. Furthermore, through the melt extrusion, OMMT with its plate-like morphology are fully exfoliated and dispersed within the PCTFE matrix. This created more complex pathways for water, increasing the diffusion path length and thereby reducing WVTR to 0.006 mg day-1 pkg-1. This innovation enabled an ultra-long calendar life of 200 days and cycle life of 870 cycles for FLIBs, with over 80% capacity retention in ambient air. Additionally, 2%OMMT-PCTFE-FLIBs exhibited excellent flexibility, retaining an impressive 85.31% capacity after 10 000 bending cycles. This research presents a simple yet effective approach to enhance the lifetime and practicality of FLIBs through building a high-performance polymer-based encapsulation layer.

10.
mSphere ; : e0064324, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39311583

RESUMO

The widespread prevalence and dissemination of antibiotic-resistant bacteria, coupled with the diminishing supply of new antibiotics, emphasize the pressing necessity for the exploration of innovative antibacterial agents. Previously, we detailed the impact of the small-molecule compound CY-158-11 on S. aureus biofilm. By hindering adhesion and PIA-mediated biofilm formation, subinhibitory concentrations of CY-158-11 exhibit antibiofilm activity toward S. aureus. Here, we sought to elucidate the antibacterial activity and mode of action of this compound. Upon CY-158-11 treatment in culture, the inhibition of bacterial growth, coupled with MBC to MIC of >4, indicated that CY-158-11 exerted a bacteriostatic effect. Particularly, CY-158-11 showed strong antibacterial activity against a wide variety of S. aureus, including multidrug-resistant bacteria. We found that CY-158-11 promoted the permeability of cell membrane and propidium iodide absorption as well as caused the dissipation of membrane potential. The effect of CY-158-11 on the mammalian cytoplasmic membrane was measured using hemolytic and cytotoxicity assays, and the skin irritation and systemic toxicity of the drug were measured by injecting the compound into the skin and tail vein of mice. Moreover, CY-158-11 exhibited considerable efficacy in a subcutaneous abscess mouse model of S. aureus infection. In conclusion, CY-158-11 possesses antibacterial properties, including inhibition of bacterial growth, damage to cell membranes, and treatment of skin abscesses, which can be a promising therapeutic option for combating S. aureus. IMPORTANCE: The combination of the rising incidence of antibiotic resistance and the shrinking antibiotic pipeline has raised concern about the postantibiotic era. New antibacterial agents and targets are required to combat S. aureus-associated infections. In this study, we identified a maleimide-diselenide hybrid compound CY-158-11 exhibiting antibacterial activity against S. aureus in vitro and in vivo at relatively low concentrations. Furthermore, the investigation of its mode of action revealed that CY-158-11 can selectively perturb the cytoplasmic membrane of bacteria without harming mammalian cells or mouse organs. Thus, CY-158-11 is a compelling novel drug for development as a new therapy for S. aureus infections.

11.
ACS Appl Mater Interfaces ; 16(37): 49104-49113, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39234752

RESUMO

Photothermal therapy (PTT) shows promise in cancer treatments due to its good spatiotemporal selectivity and minimal invasiveness. However, PTT has some problems such as excessive heat damage to normal tissues, tumor thermo-resistance caused by heat shock proteins (HSPs), and limited efficacy of monotherapy. Here, we construct a patch named "partitioned microneedles" (PMN-SNAP/CuS), which separates the "catalyst" bovine serum albumin-based copper sulfide nanoparticles (CuS@BSA NPs) and the "reactant" S-nitroso-N-acetylpenicillamine (SNAP) into different regions of microneedles, for enhancing mild PTT (mPTT) of melanoma. PMN-SNAP/CuS showed an excellent photothermal effect, Fenton-like catalytic activity, and nitric oxide (NO) generation ability. The combination of NO and reactive oxygen species (ROS) produced by PMN-SNAP/CuS effectively blocked the synthesis of HSPs at the source and enhanced the efficacy of mPTT. Both in vitro and in vivo results proved that PMN-SNAP/CuS significantly enhanced the inhibition of melanoma under 808 nm laser irradiation. In conclusion, our partitioned microneedle strategy based on the combination of enhanced mPTT and gas therapy (GT) provides a promising approach to enhance the therapeutic effect on melanoma.


Assuntos
Cobre , Melanoma , Óxido Nítrico , Terapia Fototérmica , Animais , Óxido Nítrico/metabolismo , Cobre/química , Cobre/farmacologia , Camundongos , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/metabolismo , Melanoma/terapia , Agulhas , Linhagem Celular Tumoral , Soroalbumina Bovina/química , S-Nitroso-N-Acetilpenicilamina/química , S-Nitroso-N-Acetilpenicilamina/farmacologia , Humanos , Espécies Reativas de Oxigênio/metabolismo
12.
J Hazard Mater ; 480: 135923, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39316916

RESUMO

Low permeability barrier has emerged as a promising, cost-effective technology for anti-seepage and pollution mitigation in geotechnical engineering. However, its efficacy in organic pollution sites, particularly those contaminated with chlorinated hydrocarbons (CHCs) pales in comparison to its performance in areas contaminated by heavy metals. In order to rectify this deficiency, a novel bentonite backfill, modified with dihexadecyl dimethyl ammonium chloride (DDAC) and designated as DDAC-LPB, is proposed for use in low permeability barriers to contain CHCs in groundwater at contaminated sites. A series of rigid-wall permeability tests, mechanical properties tests, and diffusion tests were conducted to investigate the impact of CHCs solution on hydraulic conductivity, unconfined compression strength and adsorption properties of the LPB, respectively. The results reveal that LPB containing 10 % DDAC modified bentonite exhibits excellent impermeability and mechanical workability, with a 2-5 fold increase in adsorption capacity, primarily driven by the hydrophobic interaction between CHCs and DDAC. Moreover, this study has innovatively applied computational fluid dynamics simulation to the field of solute transport modeling to evaluate the performance of DDAC-LPB in containing CHCs within lateral flowing groundwater. This novel approach was benchmarked against the widely embraced convection-diffusion equation modeling method, demonstrating a significant improvement in predictive accuracy. In a typical field scenario, the breakthrough time for CHCs using the DDAC-LPB technique ranged from 25.3 to 25.5 years, with a barrier thickness of 1 m. This duration satisfactorily aligns with the expected service life of real-world projects. Overall, the DDAC-LPB has demonstrated superior performance and practical applicability in enhancing the containment of CHCs in contaminated groundwater.

13.
Arch Oral Biol ; 167: 106068, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39151326

RESUMO

OBJECTIVES: The aim of this study was to investigate the role and molecular mechanism of proline/arginine-rich end leucine-rich repeat protein (PRELP), a secreted protein in extracellular matrix, in oral squamous cell carcinoma (OSCC) progression. DESIGN: PRELP expression in OSCC was analyzed in the Gene Set Enrichment (GSE) 138206, GSE37991, and GSE23558 datasets as well as cell lines. Also, PRELP expression and its relationship with prognosis and immune infiltration in head and neck squamous cell carcinoma (HNSCC) were confirmed by bioinformatics analysis. The proliferation, apoptosis, invasion, epithelial-to-mesenchymal transition (EMT) and NF-κB activation were detected after alteration of PRELP expression in OSCC cells using CCK-8, EdU, flow cytometry, Transwell, real-time PCR, immunofluorescence and Western blot. Additionally, an NF-κB inhibitor PDTC was used to confirm the regulation mechanism of PRELP. RESULTS: The expression of PRELP in OSCC tissues, cells and in HNSCC samples was low. HNSCC patients with higher PRELP expression was associated with longer overall survival. A positive correlation between PRELP expression and immune cell infiltration was found in HNSCC. Upregulation of PRELP inhibited, whereas PRELP silencing promoted, the proliferation, invasion and EMT of OSCC cells. Also, overexpression of PRELP promoted cell apoptosis. Mechanistically, PRELP suppressed p65 phosphorylation and nuclear translocation. And PDTC treatment partially reversed the influences of PRELP knockdown on the malignant behaviors in OSCC cells. CONCLUSION: PRELP suppressed OSCC progression via inactivation of the NF-κB pathway. Targeting PRELP may be a potential approach for OSCC treatment.


Assuntos
Carcinoma de Células Escamosas , Transição Epitelial-Mesenquimal , Proteínas da Matriz Extracelular , Glicoproteínas , Neoplasias Bucais , NF-kappa B , Humanos , Apoptose , Western Blotting , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Citometria de Fluxo , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/genética , NF-kappa B/metabolismo , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Glicoproteínas/genética , Glicoproteínas/metabolismo
14.
Am J Ophthalmol ; 269: 60-68, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39197509

RESUMO

PURPOSE: Spectacle lenses with highly aspherical lenslets (HAL) have been shown to effectively retard myopia progression in myopic children. This study aimed to investigate the impact of spectacle lenses with HAL on refractive and axial length (AL) changes in Chinese children with low amount of hyperopia. DESIGN: Randomized controlled trial. METHODS: A total of 108 Chinese children aged 6.0 to 9.9 years and spherical equivalent refractive error (SERE) from 0.00 to +2.00 D were randomly allocated into two groups: the HAL group and the single vision spectacle lens (SVL) group. Cycloplegic refraction, AL, and uncorrected visual acuity were measured at baseline, 6 and 12 months after lens dispensing. The duration of spectacle lens wear was monitored using a wearable device attached to the spectacle frame and by questionnaire logs provided by participants at each follow-up visit. RESULTS: The 1-year SERE change was -0.19 (-0.32, 0.03) D and -0.23 (-0.36, 0.05) D in the SVL and HAL groups (P = .883). The 1-year AL elongation was 0.24 (0.18, 0.34) mm and 0.19 (0.12, 0.27) mm in the SVL and HAL groups (P = .057). In the HAL group, changes in AL and SERE were significantly correlated to lens wearing time (P < .001 and P = .024, respectively). Participants in the HAL group who wore their lenses for more than 30 hours per week had significantly slower AL elongation (0.11 [0.05, 0.17] mm) compared to their SVL counterparts (0.27 [0.21, 0.33] mm) (P < .001). CONCLUSIONS: Spectacle lenses with HAL significantly reduced AL elongation in low hyperopic children who wore lenses for over 30 hours per week. A dose-response relationship was evident with longer lens wearing time associated with less AL change.

15.
mSystems ; 9(9): e0066424, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39158330

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) sequence type 630 (ST630) is a rarely reported lineage worldwide. This study aimed to trace the dissemination of the emerging MRSA ST630 clones in China and investigate their virulence potential. We collected 22 ST630-MRSA isolates from across China and performed whole-genome sequencing analysis and virulence characterization on these isolates. Epidemiological results showed that MRSA ST630 isolates were primarily isolated from pus/wound secretions, mainly originating from Jiangxi province, and carried diverse virulence and drug resistance genes. Staphylococcal cassette chromosome mec type V (SCCmec V) predominated (11/22, 50.0%) among the MRSA ST630 isolates. Interestingly, nearly half (45.5%) of the 22 ST630-MRSA isolates tested lacked intact SCCmec elements. Phylogenetic analysis demonstrated that ST630-MRSA could be divided into two distinct clades, with widespread dissemination mainly in Chinese regions. Five representative isolates were selected for phenotypic assays, including hemolysin activity, real-time fluorescence quantitative PCR, western blot analysis, hydrogen peroxide killing assay, blood killing assay, cell adhesion and invasion assay, and mouse skin abscess model. The results showed that, compared to the USA300-LAC strain, ST630 isolates exhibited particularly strong invasiveness and virulence in the aforementioned phenotypic assays. This study described the emergence of a highly virulent ST630-MRSA lineage and improved our insight into the molecular epidemiology of ST630 clones in China.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) sequence type 630 (ST630) is an emerging clone with an increasing isolation rate in China. This study raises awareness of the hypervirulent MRSA ST630 clones in China and alerts people to their widespread dissemination. ST630-staphylococcal cassette chromosome mec V is a noteworthy clone in China, and we present the first comprehensive genetic and phenotypic analysis of this lineage. Our findings provide valuable insights for the prevention and control of infections caused by this emerging MRSA clone.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Filogenia , Infecções Estafilocócicas , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , China/epidemiologia , Humanos , Animais , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/epidemiologia , Virulência/genética , Camundongos , Fenótipo , Sequenciamento Completo do Genoma , Genoma Bacteriano , Feminino , Masculino , Fatores de Virulência/genética
16.
Nat Commun ; 15(1): 7009, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39147753

RESUMO

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes severe viral hemorrhagic fever and thrombocytopenia syndrome with a fatality rate of up to 30%. No licensed vaccines or therapeutics are currently available for humans. Here, we develop seven monoclonal antibodies (mAbs) against SFTSV surface glycoprotein Gn. Mechanistic studies show that three neutralizing mAbs (S2A5, S1G3, and S1H7) block multiple steps during SFTSV infection, including viral attachment and membrane fusion, whereas another neutralizing mAb (B1G11) primarily inhibits the viral attachment step. Epitope binning and X-ray crystallographic analyses reveal four distinct antigenic sites on Gn, three of which have not previously been reported, corresponding to domain I, domain II, and spanning domain I and domain II. One of the most potent neutralizing mAbs, S2A5, binds to a conserved epitope on Gn domain I and broadly neutralizes infection of six SFTSV strains corresponding to genotypes A to F. A single dose treatment of S2A5 affords both pre- and post-exposure protection of mice against lethal SFTSV challenge without apparent weight loss. Our results support the importance of glycoprotein Gn for eliciting a robust humoral response and pave a path for developing prophylactic and therapeutic antibodies against SFTSV infection.


Assuntos
Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Antivirais , Epitopos , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Phlebovirus/imunologia , Camundongos , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Febre Grave com Síndrome de Trombocitopenia/imunologia , Febre Grave com Síndrome de Trombocitopenia/virologia , Febre Grave com Síndrome de Trombocitopenia/prevenção & controle , Humanos , Epitopos/imunologia , Feminino , Camundongos Endogâmicos BALB C , Proteínas do Envelope Viral/imunologia , Cristalografia por Raios X , Chlorocebus aethiops , Glicoproteínas/imunologia , Células Vero
18.
Front Cell Infect Microbiol ; 14: 1433359, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39185087

RESUMO

Introduction: Alveolar echinococcosis (AE) is a life-threatening disease in humans caused by the larval stage of Echinococcus multilocularis. Domestic animals, dogs, foxes, and small mammals constitute the circular chain of AE. To evaluate the infection, distribution, and genetic polymorphism of AE in the Ili Prefecture (Nilka, Xinyuan and Zhaosu), we conducted this survey. Methods: In June and July 2018, 267 small mammals were captured using water-infusion and mousetrap methods. Combined pathogenic and molecular biological methods were used to observe the histopathology of Echinococcus carried by rodents, amplify the mitochondrial nad1 gene of the pathogen, and investigate the genotype and haplotype diversity of Echinococcus in rodents in Ili Prefecture. Results: Morphological identification revealed that these captured small mammals belonged to three species, with Microtus gregalis being the dominant species (183/267). Pathological and molecular biological results confirmed that E. multilocularis was the pathogen of echinococcosis in small mammals, with an infection rate of 15.73% (42/267). Among the three areas sampled, the highest infection rate of rodents was 25.45% (14/55) in Nilka County. However, there was no significant difference in the infection rates between regions (χ2 = 5.119, p > 0.05). Of the three captured rodent species, M. gregalis had the highest infection rate of 17.49% (32/183), but there was no significant difference in infection rates between the rodent species (χ2 = 1.364, p > 0.05). Phylogenetic analyses showed that the nad1 gene sequences obtained in this study clustered in the same clade as isolates from China. These isolates contained 21 haplotypes (Hap_1-21); Hap_2 was the most common haplotype (9/42). Furthermore, haplotype diversity (0.925 ± 0.027) and nucleotide diversity (0.01139 ± 0.00119) were higher in the Ili Prefecture than in other regions, indicating that population differentiation was high. Tajima's D and Fu's Fs tests were negative (p > 0.10), indicating that the population had expanded. The low fixation index (Fst) ranged from 0.00000 to 0.16945, indicating that the degree of genetic differentiation was different among different populations. Discussion: In summary, Ili Prefecture is a high incidence area of AE, and Microtus spp. may play an important role in the transmission of AE in this area. The results of this study provide basic data for further study of the molecular epidemiology, genetic differences, and control of E. multilocularis in the Ili Prefecture, Xinjiang.


Assuntos
Equinococose , Echinococcus multilocularis , Haplótipos , Polimorfismo Genético , Roedores , Animais , China/epidemiologia , Equinococose/epidemiologia , Equinococose/parasitologia , Equinococose/veterinária , Roedores/parasitologia , Echinococcus multilocularis/genética , Echinococcus multilocularis/isolamento & purificação , Echinococcus multilocularis/classificação , Genótipo , Filogenia , Echinococcus/genética , Echinococcus/classificação , Echinococcus/isolamento & purificação
19.
Neurol Sci ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39190170

RESUMO

PURPOSE: A network meta-analysis was utilized to compare the rehabilitative effectiveness of different exercise interventions on motor function in cerebral palsy(CP) patients. METHODS: Computer searches were conducted across 9 databases, including PubMed, Cochrane Library, Scopus, Web of Science, Embase, and others, to identify randomized controlled trials focusing on different exercise interventions aimed at enhancing motor function in CP patients. The search spanned from the inception of the databases to January 31, 2024. RESULTS: 20 articles, encompassing 570 patients and evaluating three types of exercise interventions, were included in the analysis. Results showed that aerobic training, resistance training, and mixed training exhibited superior outcomes compared to the control group, as evidenced by improvements in Gross Motor Function Measure scores, muscle strength, gait speed, and 10-Meter Walk Test scores (P < 0.05). Furthermore, the network meta-analysis revealed that resistance training ranked highest in enhancing gross motor function and gait speed among CP patients, while mixed training was deemed most effective in improving muscle strength and 10-Meter Walk Test scores. CONCLUSION: Exercise interventions have been shown to significantly improve motor function in CP patients. Among these, resistance training and mixed training stand out for their effectiveness in enhancing walking capabilities. Resistance training is specifically aimed at improving gross motor function, while mixed training focuses on increasing muscle strength.

20.
Opt Lett ; 49(16): 4481-4484, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39146083

RESUMO

This study introduces an innovative optical coherence tomography (OCT) imaging system dedicated to high-throughput screening applications using ex vivo tissue culture. Leveraging OCT's non-invasive, high-resolution capabilities, the system is equipped with a custom-designed motorized platform and tissue detection ability for automated, successive imaging across samples. Transformer-based deep-learning segmentation algorithms further ensure robust, consistent, and efficient readouts meeting the standards for screening assays. Validated using retinal explant cultures from a mouse model of retinal degeneration, the system provides robust, rapid, reliable, unbiased, and comprehensive readouts of tissue response to treatments. This fully automated OCT-based system marks a significant advancement in tissue screening, promising to transform drug discovery, as well as other relevant research fields.


Assuntos
Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Animais , Camundongos , Retina/diagnóstico por imagem , Automação , Processamento de Imagem Assistida por Computador/métodos , Degeneração Retiniana/diagnóstico por imagem
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