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1.
Natl Sci Rev ; 11(5): nwae163, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38855727

RESUMO

China, one of the most populous countries in the world, has suffered the highest number of natural disaster-related deaths from fire. On local scales, the main causes of urban fires are anthropogenic in nature. Yet, on regional to national scales, little is known about the indicators of large-scale co-varying urban fire activity in China. Here, we present the China Fire History Atlas (CFHA), which is based on 19 947 documentary records and represents fires in urban areas of China over the twentieth century (1901-1994). We found that temperature variability is a key indicator of urban fire activity in China, with warmer temperatures being correlated with more urban fires, and that this fire-temperature relationship is seasonally and regionally explicit. In the early twentieth century, however, the fire-temperature relationship was overruled by war-related fires in large urban areas. We further used the fire-temperature relationship and multiple emissions scenarios to project fire activity across China into the twenty-first century. Our projections show a distinct increase in future urban fire activity and fire-related economic loss. Our findings provide insights into fire-climate relationships in China for densely-populated areas and on policy-relevant time scales and they contribute spatial coverage to efforts to improve global fire models.

2.
J Agric Food Chem ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867141

RESUMO

Thymol has efficient bactericidal activity against a variety of pathogenic bacteria, but the bactericidal mechanism against Vibrio parahemolyticus (V. parahemolyticus) has rarely been reported. In the current study, we investigated the bactericidal mechanism of thymol against V. parahemolyticus. The Results revealed that 150 µg/mL of thymol had 99.9% bactericidal activity on V. parahemolyticus. Intracellular bursts of reactive oxygen species (ROS), Fe2+accumulation, lipid peroxidation, and DNA breakage were checked by cell staining. The exogenous addition of H2O2 and catalase promoted and alleviated thymol-induced cell death to a certain extent, respectively, and the addition of the ferroptosis inhibitor Liproxstatin-1 also alleviated thymol-induced cell death, confirming that thymol induced Fenton-reaction-dependent ferroptosis in V. parahemolyticus. Proteomic analysis revealed that relevant proteins involved in ROS production, lipid peroxidation accumulation, and DNA repair were significantly upregulated after thymol treatment. Molecular docking revealed two potential binding sites (amino acids 46H and 42F) between thymol and ferritin, and thymol could promote the release of Fe2+ from ferritin proteins through in vitro interactions analyzed. Therefore, we hypothesized that ferritin as a potential target may mediate thymol-induced ferroptosis in V. parahemolyticus. This study provides new ideas for the development of natural inhibitors for controlling V. parahemolyticus in aquatic products.

3.
Int Immunopharmacol ; 137: 112424, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38878486

RESUMO

Colorectal cancer is a major global health burden, with limited efficacy of traditional treatment modalities in improving survival rates. However, recently advances in immunotherapy has improved treatment outcomes for patients with this cancer. To address the continuing need for improved treatment efficacy, this study introduced a novel tri-specific antibody, IMT030122, that targets EpCAM, 4-1BB, and CD3. We evaluated the pharmacological efficacy and mechanism of action of IMT030122 in vitro and in vivo. In in vitro studies, IMT030122 exhibited differential binding to antigens and cells expressing EpCAM, 4-1BB, and CD3. Moreover, IMT030122 relied on EpCAM-targeted activation of intracellular CD3 and 4-1BB signaling and mediated T cell cytotoxicity specific to HCT116 colorectal cancer cells. In vivo, IMT030122 demonstrated potent anti-tumor activity, significantly inhibiting the growth of colon cancer HCT116 and MC38-hEpCAM subcutaneous grafts. Further pharmacological analysis revealed that IMT030122 recruited lymphocytes from peripheral blood into colorectal cancer tissue and exerted durable anti-tumor activity, predominantly by promoting the activation, proliferation, and differentiation of CD8T cells. Notably, IMT030122 still exhibited anti-tumor efficacy even in the presence of significantly depleted lymphocytes in colorectal cancer tissue. The potent pharmacological activity and anti-tumor effects of IMT030122 suggest it may enhance treatment efficacy and substantially extend the survival of patients with colorectal cancer in the future.

4.
World J Gastrointest Oncol ; 16(5): 2168-2180, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38764810

RESUMO

BACKGROUND: Complement components could contribute to the tumor microenvironment and the systemic immune response. Nevertheless, their role in colorectal cancer (CRC) remains a contentious subject. AIM: To elucidate the relationship between complement components and CRC risk and clinical characteristics. METHODS: Searches were conducted in PubMed, the Cochrane Library, and the China National Knowledge Infrastructure database until June 1, 2023. We included cohort studies encompassing participants aged ≥ 18 years, investigating the association between complement components and CRC. The studies were of moderate quality or above, as determined by the Agency for Healthcare Research and Quality. The meta-analysis employed fixed-effects or random-effects models based on the I² test, utilizing risk ratio (RR) and their corresponding 95% confidence interval (CI) for outcomes. Sensitivity and subgroup analyses were performed to validate the robustness of the collective estimates and identify the source of heterogeneity. RESULTS: Data from 15 studies, comprising 1631 participants that met the inclusion criteria, were included in the meta-analysis. Our findings indicated that protein levels of cluster of differentiation 46 (CD46) (RR = 3.66, 95%CI: 1.75-7.64, P < 0.001), CD59 (RR = 2.86, 95%CI: 1.36-6.01, P = 0.005), and component 1 (C1) (RR = 5.88, 95%CI: 1.75-19.73, P = 0.004) and serum levels of C3 (standardized mean difference = 1.82, 95%CI: 0.06-3.58, P = 0.040) were significantly elevated in patients with CRC compared to healthy controls. Strong expression of CD55 or CD59 was associated with a higher incidence of lymph node metastasis, whereas strong CD46 expression correlated with a higher incidence of tumor differentiation compared to low CD46 expression (P < 0.05 for all). Although specific pooled results demonstrated notable heterogeneity, subgroup analyses pointed to regional differences as the primary source of inconsistency among the studies. CONCLUSION: Our analysis underscores that increased levels of specific complement components are associated with a heightened risk of CRC, emphasizing the potential significance of monitoring elevated complement component levels.

5.
Phytomedicine ; 129: 155683, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38701543

RESUMO

BACKGROUND: Peritoneal dialysis (PD) is a successful renal replacement therapy for end-stage renal disease. Long-term PD causes mesothelial-mesenchymal transition (MMT) of peritoneal mesothelial cells (PMCs), leading to peritoneal fibrosis (PF), which reduces the efficiency of PD. Macrophages are thought to play a role in the onset and perpetuation of peritoneal injury. However, the mechanisms by which macrophages-PMCs communication regulates peritoneal fibrosis are not fully understood resulting in a lack of disease-modifying drugs. Astragaloside IV (AS-IV) possessed anti-fibrotic effect towards PF in PD whereas the mechanistic effect of AS-IV in PD is unknown. METHODS: The primary macrophages were extracted and treated with LPS or AS-IV, then co-cultured with primary PMCs in transwell plates. The macrophage-derived exosomes were extracted and purified by differential centrifugation, then co-cultured with primary PMCs. Small RNA-seq was used to detect differential miRNAs in exosomes, and then KEGG analysis and q-PCR were performed for validation. In vivo PD rat models were established by inducing with high-glucose peritoneal dialysis fluid and different concentrations of AS-IV and exosomes were intraperitoneal injection. Through qRT-PCR, western blotting, and luciferase reporting, candidate proteins and pathways were validated in vivo and in vitro. The functions of the validated pathways were further investigated using the mimic or inhibition strategy. PF and inflammatory situations were assessed. RESULTS: We found AS-IV reversed the MMT of PMCs caused by LPS-stimulated macrophages and the improving effect was mediated by macrophage-derived exosomes in vitro. We also demonstrated that AS-IV significantly reduced the MMT of PMCs in vitro or PF in a rat PD model via regulating exosome-contained miR-204-5p which targets Foxc1/ß-catenin signaling pathway. CONCLUSION: AS-IV attenuates macrophage-derived exosomes induced fibrosis in PD through the miR-204-5p/Foxc1 pathway.


Assuntos
Exossomos , Macrófagos , MicroRNAs , Fibrose Peritoneal , Ratos Sprague-Dawley , Saponinas , Triterpenos , Fibrose Peritoneal/tratamento farmacológico , Animais , Exossomos/metabolismo , Exossomos/efeitos dos fármacos , Saponinas/farmacologia , Triterpenos/farmacologia , Ratos , MicroRNAs/metabolismo , Masculino , Macrófagos/efeitos dos fármacos , Diálise Peritoneal/efeitos adversos , Modelos Animais de Doenças , Células Cultivadas , Técnicas de Cocultura
6.
Foods ; 13(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38790773

RESUMO

Postharvest rot is an urgent problem affecting the storage of winter jujube. Therefore, the development of new technologies for efficient and safe preservation is very important. This study aimed to elucidate the fungal microbiota found on the epidermis of jujube during the storage period using high-throughput sequencing, as well as to monitor the changes in quality indexes throughout this period. Through internal transcribed spacer (ITS) sequencing, we identified two phyla (Basidiomycota and Ascomycota) and six genera (Cryptococcus, Bulleromyces, Sporidiobolus, Alternaria, Pseudozyma, and Sporobolomyces), which potentially contribute to the spoilage and deterioration of jujube, referred to as "core fungal taxa". A high correlation was further found between preservation indices (including decay rate, firmness, and total soluble solids) and the growth of multiple core fungi over time. These findings will provide insights and a theoretical basis for further research on preservation techniques related to biological control during date fruit storage.

7.
J Appl Toxicol ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581191

RESUMO

Isobavachalcone (IBC) is a flavonoid component of the traditional Chinese medicine Psoraleae Fructus, with a range of pharmacological properties. However, IBC causes some hepatotoxicity, and the mechanism of toxicity is unclear. The purpose of this paper was to investigate the possible mechanism of toxicity of IBC on HepG2 cells and zebrafish embryos. The results showed that exposure to IBC increased zebrafish embryo mortality and decreased hatchability. Meanwhile, IBC induced liver injury and increased expression of ALT and AST activity. Further studies showed that IBC caused the increase of ROS and MDA the decrease of CAT, GSH, and GSH-Px; the increase of Fe2+ content; and the changes of ferroptosis related genes (acsl4, gpx4, and xct) and iron storage related genes (tf, fth, and fpn) in zebrafish embryos. Through in vitro verification, it was found that IBC also caused oxidative stress and increased Fe2+ content in HepG2 cells. IBC caused depolarization of mitochondrial membrane potential (MMP) and reduction of mitochondrial ATP, as well as altered expression of ACSl4, SLC7A11, GPX4, and FTH1 proteins. Treatment of HepG2 cells with ferrostatin-1 could reverse the effect of IBC. Targeting the System Xc--GSH-GPX4 pathway of ferroptosis and preventing oxidative stress damage might offer a theoretical foundation for practical therapy and prevention of IBC-induced hepatotoxicity.

8.
PLoS One ; 19(4): e0302361, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38687802

RESUMO

Growing evidence has increasingly suggested a potential linkage between the oral microbiome and various diseases, including pancreatic ductal adenocarcinoma (PDAC). However, the utilization of gene-level information derived from the oral microbiome for diagnosing PDAC remains unexplored. In this study, we sought to investigate the novel potential of leveraging genomic signatures associated with antibiotic resistance genes (ARGs) within the oral microbiome for the diagnosis of PDAC. By conducting an analysis of oral microbiome samples obtained from PDAC patients, we successfully identified specific ARGs that displayed distinct sequence abundance profiles correlated with the presence of PDAC. In the healthy group, three ARGs were found to be enriched, whereas 21 ARGs were enriched in PDAC patients. Remarkably, these ARGs from oral microbiome exhibited promising diagnostic capabilities for PDAC (AUROC = 0.79), providing a non-invasive and early detection method. Our findings not only provide novel modal data for diagnosing PDAC but also shed light on the intricate interplay between the oral microbiome and PDAC.


Assuntos
Carcinoma Ductal Pancreático , Microbiota , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/microbiologia , Neoplasias Pancreáticas/diagnóstico , Microbiota/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/microbiologia , Carcinoma Ductal Pancreático/diagnóstico , Feminino , Masculino , Boca/microbiologia , Pessoa de Meia-Idade , Resistência Microbiana a Medicamentos/genética , Idoso , Genômica/métodos
9.
Microbiol Res ; 284: 127711, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38636240

RESUMO

Microbial ferroptosis has been proved to combat drug-resistant pathogens, but whether this pattern can be applied to the prevention and control of Escherichia coli remains to be further explored. In this study, ferrous gluconate (FeGlu) showed remarkable efficacy in killing E. coli MG1655 with a mortality rate exceeding 99.9%, as well as enterotoxigenic E. coli H10407 (ETEC H10407) and enterohemorrhagic E. coli O157:H7 (EHEC O157:H7). Bacteria death was instigated by the infiltration of Fe2+, accompanied by a burst of intracellular reactive oxygen species (ROS) and lipid peroxidation. Notably, mitigating lipid peroxidation failed to alleviate death of E. coli. Further findings confirmed that FeGlu induced DNA damage, and ΔrecA mutant showed more sensitive, implicating that DNA damage was involved in the death of E. coli. The direct interaction of Fe2+ with DNA was demonstrated by fluorescent staining, gel electrophoresis, and circular dichroism (CD). Moreover, proteomic analysis unveiled 50 differentially expressed proteins (DEPs), including 18 significantly down-regulated proteins and 32 significantly up-regulated proteins. Among them, the down-regulation of SOS-responsive transcriptional suppressor LexA indicated DNA damage induced severely by FeGlu. Furthermore, FeGlu influenced pathways such as fatty acid metabolism (FadB, FadE), iron-sulfur cluster assembly (IscA, IscU, YadR), iron binding, and DNA-binding transcription, along with α-linolenic acid metabolism, fatty acid degradation, and pyruvate metabolism. These pathways were related to FeGlu stress, including lipid peroxidation and DNA damage. In summary, FeGlu facilitated ferroptosis in E. coli through mechanisms involving lipid peroxidation and DNA damage, which presents a new strategy for the development of innovative antimicrobial strategies targeting E. coli infections.


Assuntos
Dano ao DNA , Escherichia coli , Ferroptose , Compostos Ferrosos , Peroxidação de Lipídeos , Espécies Reativas de Oxigênio , Ferroptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Compostos Ferrosos/metabolismo , Compostos Ferrosos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Antibacterianos/farmacologia , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Proteômica , Escherichia coli O157/efeitos dos fármacos , Escherichia coli O157/genética , Escherichia coli O157/metabolismo
10.
Rejuvenation Res ; 27(3): 102-109, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38666697

RESUMO

Elevated substance P can be utilized to predict early mortality during the first week of cerebral infarction. Whether aprepitant, a substance P receptor blocker could be utilized to alleviate poststroke pneumonia which is investigated in this study. Intraluminal monofilament model of middle cerebral artery occlusion (MCAO) was constructed in C57BL/6J male mice, and the relative expression of substance P was detected in collected bronchoalveolar lavage fluid (BALF) and lung tissue homogenate at 24 hours, 48 hours, and 72 hours poststroke. On the other hand, different concentrations of aprepitant (0.5, 1, and 2 mg/kg) were atomized and inhaled into MCAO mice. Inflammation cytokines and bacterial load were detected in collected BALF and lung tissue homogenate at 72-hour poststroke, and lung injury was revealed by histological examination. Aprepitant administration decreased total proteins, total cells, neutrophils, and macrophages in BALF. The concentrations of interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, interferon γ, monocyte chemoattractant protein-1, and IL-10 in lung tissue homogenates were also diminished by the administration of aprepitant. In conclusion, aprepitant could attenuate poststroke pneumonia in mice suggesting its potential therapeutic use in the clinic.


Assuntos
Aprepitanto , Líquido da Lavagem Broncoalveolar , Citocinas , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média , Camundongos Endogâmicos C57BL , Pneumonia , Animais , Aprepitanto/farmacologia , Aprepitanto/uso terapêutico , Masculino , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Pneumonia/tratamento farmacológico , Pneumonia/complicações , Pneumonia/patologia , Líquido da Lavagem Broncoalveolar/química , Citocinas/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologia , Substância P/metabolismo , Pulmão/patologia , Pulmão/efeitos dos fármacos , Camundongos , Morfolinas/farmacologia , Morfolinas/uso terapêutico
11.
Angew Chem Int Ed Engl ; 63(26): e202405962, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644535

RESUMO

Nature-inspired supramolecular self-assemblies are attractive photocatalysts, but their quantum yields are limited by poor charge separation and transportation. A promising strategy for efficient charge transfer is to enhance the built-in electric field by symmetry breaking. Herein, an unsymmetric protonation, N-heterocyclic π-conjugated anthrazoline-based supramolecular photocatalyst SA-DADK-H+ was developed. The unsymmetric protonation breaks the initial structural symmetry of DADK, resulting in ca. 50-fold increase in the molecular dipole, and facilitates efficient charge separation and transfer within SA-DADK-H+. The protonation process also creates numerous active sites for H2O adsorption, and serves as crucial proton relays, significantly improving the photocatalytic efficiency. Remarkably, SA-DADK-H+ exhibits an outstanding hydrogen evolution rate of 278.2 mmol g-1 h-1 and a remarkable apparent quantum efficiency of 25.1 % at 450 nm, placing it among the state-of-the-art performances in organic semiconductor photocatalysts. Furthermore, the versatility of the unsymmetric protonation approach has been successfully applied to four other photocatalysts, enhancing their photocatalytic performance by 39 to 533 times. These findings highlight the considerable potential of unsymmetric protonation induced symmetry breaking strategy in tailoring supramolecular photocatalysts for efficient solar-to-fuel production.

12.
BMC Genomics ; 25(1): 229, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429670

RESUMO

BACKGROUND: Alfalfa (Medicago sativa. L) is one of the best leguminous herbage in China and even in the world, with high nutritional and ecological value. However, one of the drawbacks of alfalfa is its sensitivity to dry conditions, which is a global agricultural problem. The objective of this study was to investigate the regulatory effects of endogenous nitric oxide (NO) on endogenous hormones and related miRNAs in alfalfa seedling leaves under drought stress. The effects of endogenous NO on endogenous hormones such as ABA, GA3, SA, and IAA in alfalfa leaves under drought stress were studied. In addition, high-throughput sequencing technology was used to identify drought-related miRNAs and endogenous NO-responsive miRNAs in alfalfa seedling leaves under drought stress. RESULT: By measuring the contents of four endogenous hormones in alfalfa leaves, it was found that endogenous NO could regulate plant growth and stress resistance by inducing the metabolism levels of IAA, ABA, GA3, and SA in alfalfa, especially ABA and SA in alfalfa. In addition, small RNA sequencing technology and bioinformatics methods were used to analyze endogenous NO-responsive miRNAs under drought stress. It was found that most miRNAs were enriched in biological pathways and molecular functions related to hormones (ABA, ETH, and JA), phenylpropane metabolism, and plant stress tolerance. CONCLUSION: In this study, the analysis of endogenous hormone signals and miRNAs in alfalfa leaves under PEG and PEG + cPTIO conditions provided an important basis for endogenous NO to improve the drought resistance of alfalfa at the physiological and molecular levels. It has important scientific value and practical significance for endogenous NO to improve plant drought resistance.


Assuntos
MicroRNAs , Plântula , Plântula/genética , Plântula/metabolismo , Medicago sativa/genética , Óxido Nítrico/metabolismo , Secas , MicroRNAs/genética , MicroRNAs/metabolismo , Hormônios/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas
13.
BMC Genomics ; 25(1): 316, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549050

RESUMO

BACKGROUND: Alfalfa is a perennial forage crop of high importance, but its cultivation is often affected by drought stress. Currently, the investigation of drought-related small RNAs is a popular research topic to uncover plant drought resistance mechanisms. Among these small RNAs, microRNA166 (miR166) is associated with drought in numerous plant species. Initial small RNA sequencing studies have shown that miR166 is highly responsive to exogenous nitric oxide (NO) and drought. Therefore, analyzing the expression of Msa-miR166 under nitric oxide and drought treatment is significant. RESULT: Bioinformatics analysis revealed that the miR166 family is widely distributed among plants, ranging from mosses to eudicots, with significant distribution differences between species. The evolutionary degree of Msa-miR166s is highly similar to that of Barrel medic (Medicago truncatula) and Soybean (Glycine max), but significantly different from the model plant Arabidopsis (Arabidopsis thaliana). It is suggested that there are no significant differences in miR166s within the species, and members of Msa-miR166s can form a typical stem-loop. The lowest level of exogenous nitric oxide was observed in Msa-miR166s under drought stress, followed by individual drought, and the highest level was observed after removing endogenous nitric oxide. CONCLUSION: In response to short-term drought, Msa-miR166s down-regulate expression in alfalfa (Medicago sativa L.). Exogenous nitric oxide can reduce the expression of Msa-miR166s in response to short-term drought. These findings suggest that Msa-miR166e-5p is responsive to environmental changes. The expression levels of target genes showed an opposite trend to Msa-miR166s, verifying the accuracy of Degradome sequencing in the early stage. This suggests that alfalfa experiences drought stress when regulated by exogenous nitric oxide, targeting HD ZIP-III, FRI, and CoA ligase genes. Additionally, the expression of Msa-miR166s in response to drought stress varies between leaves and roots, indicating spatiotemporal specificity.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , MicroRNAs , Medicago sativa/genética , Proteínas de Plantas/genética , Óxido Nítrico/metabolismo , Secas , Sequência de Bases , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética , Proteínas de Arabidopsis/genética , MicroRNAs/genética , MicroRNAs/metabolismo
14.
Infect Drug Resist ; 17: 1051-1071, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505247

RESUMO

Purpose: Bloodstream infection(BSI) is linked with high mortality, underscoring the significance of prompt etiological diagnosis for timely and precise treatment. This study aims to investigate the diagnostic value of droplet digital polymerase chain reaction(ddPCR) in combination with conventional inflammatory markers [interleukin-6(IL-6) and procalcitonin(PCT)] concerning disease progression and treatment prognosis in BSI patients. Furthermore, the study aims to explore a more efficient clinical application strategy. Patients and Methods: This prospective case seried study centers on 176 patients suspected of or confirmed with BSI. Blood samples were collected to extract nucleic acids for identifying pathogens (bacteria, fungi, and viruses) and determining copy loads via ddPCR. Results: The sensitivity of ddPCR was markedly higher compared to the culture method (74.71% vs 31.03%). A positive correlation existed between bacterial load and levels of inflammatory markers [IL-6 (P=0.0182), PCT (P=0.0029), and CRP (P=0.0005)]. In suspected BSI cases, the combination of ddPCR and inflammatory markers could predict sepsis risk [ROC: Area under the curve(AUC)=0.6071, P=0.0383]. Within confirmed BSI patients, the ddPCR bacterial load of those with SOFA<7 was lower than that of the SOFA≥7 (P=0.0334). ddPCR (OR: 1.789, P=0.035) monitoring combined with PCT (OR: 1.787, P=0.035) holded predictive value for SOFA progression (AUC=0.7913, P=0.0003). Similarly, BSI survivors displayed a lower burden than non-survivors (P=0.0170). Additionally, ddPCR combinated with IL-6 provided a more accurate and expedited insight into clinical outcomes prediction for BSI confirmed patients (AUC=0.7352, P=0.0030). Serial monitoring of bacterial load by ddPCR effectively mirrored the clinical course of BSI in patients. Notably, patients with positive ddPCR virus infection exhibited significantly reduced lymphocyte counts (P=0.0003). Conclusion: In a clinical context, qualitative ddPCR results and quantitative continuous monitoring can more precisely assess sepsis progression and treatment prognosis in BSI patients. Furthermore, ddPCR results offer quicker and more accurate reference points for clinical antibacterial and antiviral interventions.

15.
Phytomedicine ; 129: 155564, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38554577

RESUMO

BACKGROUND: The incidence of ulcerative colitis (UC) is on the rise globally and the development of drugs targeting UC is urgent. Finding the target of action of natural products is important for drug discovery, elucidation of drug action mechanism, and disease mechanism. San-Ye-Qing (SYQ), is an ancient herbal medicine, but whether the powder of its rhizome has pharmacological effects against UC and its mechanism of action are not clear. PURPOSE: To evaluate the therapeutic effectiveness of rhizome powder of SYQ in treating UC, and conduct an isolation and characterization of the chemical constituents of the powder. Further, screen the most potent compounds among them and determine the potential mechanism for treating UC. METHODS: In vivo, the therapeutic effect of SYQ's rhizome powder on UC was assessed by mice's body weight, DAI score, colon length, tissue MPO activity, serum inflammatory markers, etc. Additionally, HPLC was used to isolate and identify the specific chemical components of SYQ's rhizome powder. Then, the most effective compounds and their therapeutic targets were analysed and screened in SYQ rhizome powder using network pharmacology, combined with CCK-8 assay, NO release assay and molecular docking assay, in conjunction with CETSA, DARTS, SPR and enzyme activity assay. Finally, the biological effects of the key compound on the targets were validated using Western blot and ELISA. RESULTS: In vivo, SYQ rhizome powder effectively restored mice's body weight, lowered DAI and pathological score, downregulated the expression of inflammatory biomarkers, and restored colon length, as well as the colonic epithelial and mucus barriers. Afterward, 9 compounds were isolated and identified from the powder of the rhizomes of SYQ by HPLC. Nicotiflorin is the primary compound in SYQ with the highest concentration. According to both CCK-8 and NO release tests, Nicotiflorin is also the most efficacious compound. Combined with network pharmacological prediction, molecular docking analysis, CETSA, DARTS, SPR and enzyme activity assay, Nicotiflorin may ultimately suppress inflammation by targeting p65 and inhibiting the NF-κB pathway, thereby attenuating the activation of NLRP3 inflammasome. To verify this conclusion, Western blot and ELISA experiments were conducted. CONCLUSIONS: Our results suggest that the extract from SYQ rhizomes has therapeutic properties for UC. Its active ingredient Nicotiflorin exerted potent anti-UC effects by binding to p65 and inhibiting the activation of NF-κB and NLRP3 inflammasomes.


Assuntos
Anti-Inflamatórios , Colite Ulcerativa , Medicamentos de Ervas Chinesas , Rizoma , Colite Ulcerativa/tratamento farmacológico , Animais , Rizoma/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Camundongos , Anti-Inflamatórios/farmacologia , Masculino , Simulação de Acoplamento Molecular , Colo/efeitos dos fármacos , Células RAW 264.7 , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , NF-kappa B/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Farmacologia em Rede
16.
Environ Res ; 249: 118466, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38354882

RESUMO

Global outbreaks and the spread of viral diseases in the recent years have led to a rapid increase in the usage of antiviral drugs (ATVs), the residues and metabolites of which are discharged into the natural environment, posing a serious threat to human health. There is an urgent need to develop sensitive and rapid detection tools for multiple ATVs. In this study, we developed a highly sensitive electrochemical sensor comprising a glassy carbon electrode (GCE) modified with graphitized hydroxylated multi-walled carbon nanotubes (G-MWCNT-OH) and 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6, IL) for the detection of six ATVs including famciclovir (FCV), remdesivir (REM), favipiravir (FAV), hydroxychloroquine sulfate (HCQ), cepharanthine (CEP) and molnupiravir (MOL). The morphology and structure of the G-MWCNT-OH/IL nanocomposites were characterized comprehensively, and the electroactive surface area and electron conductivity of G-MWCNT-OH/IL/GCE were determined using cyclic voltammetry and electrochemical impedance spectroscopy. The thermodynamic stability and non-covalent interactions between the G-MWCNT-OH and IL were evaluated through quantum chemical simulation calculations, and the mechanism of ATV detection using the G-MWCNT-OH/IL/GCE was thoroughly examined. The detection conditions were optimized to improve the sensitivity and stability of electrochemical sensors. Under the optimal experimental conditions, the G-MWCNT-OH/IL/GCE exhibited excellent electrocatalytic performance and detected the ATVs over a wide concentration range (0.01-120 µM). The limit of detections (LODs) were 42.3 nM, 55.4 nM, 21.9 nM, 15.6 nM, 10.6 nM, and 3.2 nM for FCV, REM, FAV, HCQ, CEP, and MOL, respectively. G-MWCNT-OH/IL/GCE was also highly stable and selective to the ATVs in the presence of multiple interfering analytes. This sensor exhibited great potential for enabling the quantitative detection of multiple ATVs in actual water environment.


Assuntos
Antivirais , Técnicas Eletroquímicas , Líquidos Iônicos , Nanotubos de Carbono , Antivirais/análise , Antivirais/química , Nanotubos de Carbono/química , Líquidos Iônicos/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Limite de Detecção , Eletrodos , Grafite/química
18.
Adv Mater ; 36(24): e2400764, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38415407

RESUMO

Supported metal catalysts have been exploited in various applications. Among them, cocatalyst supported on photocatalyst is essential for activation of photocatalysis. However, cocatalyst decoration in a controllable fashion to promote intrinsic activity remains challenging. Herein, a versatile method is developed for cocatalyst synthesis using an ice-templating (ICT) strategy, resulting in size control from single-atom (SA), and atomic clusters (AC) to nanoparticles (NP). Importantly, the coordination numbers (CN) of decorated AC cocatalysts are highly controllable, and this ICT method applies to various metals and photocatalytic substrates. Taking narrow-band gap Ga-doped La5Ti2Cu0.9Ag0.1O7S5 (LTCA) photocatalyst as an example, supported Ru AC/LTCA catalysts with regulable Ru CNs have been prepared, delivering significantly enhanced activities compared to Ru SA and Ru NPs supported on LTCA. Specifically, Ru(CN = 3.4) AC/LTCA with an average CN of Ru─Ru bond measured to be ≈3.4 exhibits excellent photocatalytic H2 evolution rate (578 µmol h-1) under visible light irradiation. Density functional theory calculation reveals that the modeled Ru(CN = 3) atomic cluster cocatalyst possesses favorable electronic properties and available active sites for the H2 evolution reaction.

19.
J Psychiatr Res ; 170: 253-261, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176353

RESUMO

OBJECTIVE: Insomnia is a significant health issue associated with various systemic diseases. Transcranial alternating current stimulation (tACS) has been proposed as a potential intervention for insomnia. However, the efficacy and mechanisms of tACS in chronic insomnia remain unclear. Accordingly, this study aimed to investigate the efficacy of tACS in treating chronic insomnia in adults and assess the impact of age on its effectiveness using a large sample from two centers. METHODS: A total of 120 participants with chronic insomnia underwent 20 daily sessions of tACS (duration: 40 min, frequency: 77.5 Hz, and intensity: 15 mA) or sham tACS targeting the forehead and both mastoid areas over 4 weeks. Assessments were conducted at baseline, post-treatment, and 4-week follow-up. Primary outcomes included sleep quality and efficiency, onset latency, total sleep time, and daily disturbances. Secondary outcomes included depression, anxiety, and clinical impression. RESULTS: Compared with the control group, the tACS group demonstrated improved sleep quality and efficiency, increased total sleep time, and reduced daily disturbance (all ps < 0.01). Moreover, tACS had a significant effect on clinical impression (p < 0.001), but not depression and anxiety scores. Subgroup analyses revealed that older participants experienced significant benefits from tACS in sleep quality, efficiency, and overall insomnia reduction at post-treatment and follow-up (p < 0.001). Notably, improved insomnia correlated with attenuated depressive and anxiety symptoms. CONCLUSIONS: These findings suggest that tACS may be an effective intervention for chronic insomnia within an eight-week timeframe, and age affects the response to tACS in terms of insomnia improvement.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Estimulação Transcraniana por Corrente Contínua , Adulto , Humanos , Transtornos de Ansiedade , Método Duplo-Cego , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do Tratamento
20.
Integr Cancer Ther ; 23: 15347354231225961, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38229425

RESUMO

BACKGROUND: In China, traditional Chinese medicines (TCMs), as a complementary therapy combined with chemotherapy, is widely used in the treatment of gastric cancer (GC). In order to systematically evaluate and synthesize existing evidence to provide a scientific basis for the efficacy and safety of this complementary therapy, we present an overview of systematic reviews (SRs) and meta-analyses (MAs) on the topic of TCMs as a complementary therapy in combination with chemotherapy for the treatment of GC. METHODS: SRs/MAs on TCMs combined with chemotherapy for GC were comprehensively searched in 8 databases. Methodological quality, risk of bias, reporting quality, and quality of evidence were assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020), as well as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Thirteen published SRs/MAs were included in our study. In terms of methodology, all SRs/MAs were considered to be of very low quality. Only 3 SRs/MAs has been assessed as low risk of bias. None of the SRs/MAs has been fully reported on the checklist. A total of 97 outcome indicators extracted from the included SRs/MAs were evaluated, and only 1 item was assessed as high quality. CONCLUSIONS: TCMs may be an effective and safe complementary therapy in combination with chemotherapy for the treatment of GC. However, this conclusion must be treated with caution as the quality of the evidence provided by SRs/MAs is generally low.


Assuntos
Terapia por Acupuntura , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Medicina Tradicional Chinesa , China , Bases de Dados Factuais
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