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1.
Parasit Vectors ; 17(1): 284, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956725

RESUMO

BACKGROUND: Toxoplasma gondii infection affects a significant portion of the global population, leading to severe toxoplasmosis and, in immunocompromised patients, even death. During T. gondii infection, disruption of gut microbiota further exacerbates the damage to intestinal and brain barriers. Therefore, identifying imbalanced probiotics during infection and restoring their equilibrium can regulate the balance of gut microbiota metabolites, thereby alleviating tissue damage. METHODS: Vimentin gene knockout (vim-/-) mice were employed as an immunocompromised model to evaluate the influence of host immune responses on gut microbiota balance during T. gondii infection. Behavioral experiments were performed to assess changes in cognitive levels and depressive tendencies between chronically infected vim-/- and wild-type (WT) mice. Fecal samples were subjected to 16S ribosomal RNA (rRNA) sequencing, and serum metabolites were analyzed to identify potential gut probiotics and their metabolites for the treatment of T. gondii infection. RESULTS: Compared to the immunocompetent WT sv129 mice, the immunocompromised mice exhibited lower levels of neuronal apoptosis and fewer neurobehavioral abnormalities during chronic infection. 16S rRNA sequencing revealed a significant decrease in the abundance of probiotics, including several species of Lactobacillus, in WT mice. Restoring this balance through the administration of Lactobacillus murinus and Lactobacillus gasseri significantly suppressed the T. gondii burden in the intestine, liver, and brain. Moreover, transplantation of these two Lactobacillus spp. significantly improved intestinal barrier damage and alleviated inflammation and neuronal apoptosis in the central nervous system. Metabolite detection studies revealed that the levels of various Lactobacillus-related metabolites, including indole-3-lactic acid (ILA) in serum, decreased significantly after T. gondii infection. We confirmed that L. gasseri secreted much more ILA than L. murinus. Notably, ILA can activate the aromatic hydrocarbon receptor signaling pathway in intestinal epithelial cells, promoting the activation of CD8+ T cells and the secretion of interferon-gamma. CONCLUSION: Our study revealed that host immune responses against T. gondii infection severely disrupted the balance of gut microbiota, resulting in intestinal and brain damage. Lactobacillus spp. play a crucial role in immune regulation, and the metabolite ILA is a promising therapeutic compound for efficient and safe treatment of T. gondii infection.


Assuntos
Lesões Encefálicas , Microbioma Gastrointestinal , Camundongos Knockout , Toxoplasma , Animais , Camundongos , Toxoplasma/imunologia , Lesões Encefálicas/imunologia , Probióticos/administração & dosagem , Encéfalo/imunologia , Lactobacillus , Modelos Animais de Doenças , Hospedeiro Imunocomprometido , Toxoplasmose/imunologia , RNA Ribossômico 16S/genética , Masculino , Intestinos/imunologia
2.
Appl Microbiol Biotechnol ; 108(1): 417, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995388

RESUMO

Fertilizer input is one of the effective forest management practices, which improves soil nutrients and microbial community compositions and promotes forest productivity. However, few studies have explored the response of rhizosphere soil microbial communities to various fertilization regimes across seasonal dynamics. Here, we collected the rhizosphere soil samples from Phoebe bournei plantations to investigate the response of community assemblages and microbial interactions of the soil microbiome to the short-term application of four typical fertilizer practices (including chemical fertilizer (CF), organic fertilizer (OF), compound microbial fertilizer (CMF), and no fertilizer control (CK)). The amendments of organic fertilizer and compound microbial fertilizer altered the composition of rhizosphere soil bacterial and fungal communities, respectively. The fertilization regime significantly affected bacterial diversity rather than fungal diversity, and rhizosphere fungi responded more sensitively than bacteria to season. Fertilization-induced fungal networks were more complex than bacterial networks. Stochastic processes governed both rhizosphere soil bacterial and fungal communities, and drift and dispersal limitation dominated soil fungal and bacterial communities, respectively. Collectively, these findings demonstrate contrasting responses to community assemblages and interactions of rhizosphere bacteria and fungi to fertilizer practices. The application of organic fertilization strengthens microbial interactions and changes the succession of key taxa in the rhizosphere habitat. KEY POINTS: • Fertilization altered the key taxa and microbial interaction • Organic fertilizer facilitated the turnover of rhizosphere microbial communities • Stochasticity governed soil fungal and bacterial community assembly.


Assuntos
Bactérias , Fertilizantes , Fungos , Microbiota , Rizosfera , Microbiologia do Solo , Fertilizantes/análise , Fungos/classificação , Bactérias/classificação , Bactérias/metabolismo , Bactérias/genética , Interações Microbianas , Estações do Ano , Solo/química
3.
Nurse Educ Pract ; 79: 104027, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38959704

RESUMO

AIM: To investigate the perspectives of clinical nurse educators regarding the challenges and essential elements of teaching competence in blended learning environments during nursing internships to inform the development of a competency-based teaching model. BACKGROUND: Competency-based teaching and blended learning play important roles in enhancing the learning experience of nursing internship trainees. Internship trainees refer to nursing students undergoing supervised practical training in clinical settings. However, clinical nurse educators frequently encounter challenges in acquiring the necessary competence for successful implementation of blended learning strategies. DESIGN: A descriptive qualitative study. METHODS: This study used semi-structured interviews with 11 certified nurse educators (CNEs) from diverse clinical disciplines in a tertiary hospital in China. Purposive sampling ensured diversity across key characteristics. Ethical approval was obtained and interviews were digitally recorded, transcribed and analyzed thematically. Theoretical saturation guided data collection, with precise measures taken to ensure confidentiality and anonymity. Thematic analysis, employing a constant comparison technique, systematically identified various themes related to blended teaching competence. This approach provided valuable insights into CNEs' perspectives and practices. The analysis involved theoretical sampling, line-by-line coding and comparative evaluation with supporting text materials. RESULTS: The in-depth analysis of teaching competence among clinical nurse educators in blended learning settings during nurse internships revealed five key themes: professionalism, teaching literacy, subject expertise, information literacy and interpersonal communication. CONCLUSION: These themes recognized clinical nurse educators' perspectives towards establishing a competency-based nursing teaching model for a blended learning environment for nurse internships. Moreover, these perspectives are also crucial in enhancing teaching literacy through effective instructional methods, engagement strategies and the promotion of critical thinking skills. Identifying these themes contributes to efforts to improve teaching effectiveness and enhance learning outcomes for internship trainees in a blended learning context.

5.
Sci Total Environ ; 947: 174467, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969122

RESUMO

Although industrial activities are significant contributors to atmospheric releases of particulate matter (PM) and associated toxic substances that lead to adverse human health effects, a knowledge gap exists concerning the human health risk resulting from such activities owing to lack of evaluation of industrial emissions. Here, we comprehensively characterized and quantified PM from 118 full-scale industrial plants. The dominant (97.9 %) PM showed diameters of <2.5 µm; 79.0 % had diameters below 1 µm. Annual atmospheric releases of Fe and heavy metals (As, Cd, Cr, Cu, Ni, Pb, Zn) contained in fine PM from these global industrial activities are estimated to be 51,161 t and 69,591 t, respectively. Emissions of heavy metals from these industries cause increased cancer risk, estimated to range from 1461 % to 50,752 %. Five crystalline compounds (ZnO, PbSO4, Mn3O4, Fe3O4, Fe2O3) that can indicate specific industrial sources are identified. Global annual emissions of these toxic compounds in fine PM from the industrial sources are estimated to be 78,635 t. The Global South displayed higher emissions than the Global North. These results are significant for recognizing regional health risks of industrial emissions.

6.
Environ Sci Technol ; 58(28): 12356-12367, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38953388

RESUMO

Unhealthy lifestyles, obesity, and environmental pollutants are strongly correlated with the development of nonalcoholic fatty liver disease (NAFLD). Haloacetaldehyde-associated disinfection byproducts (HAL-DBPs) at various multiples of concentrations found in finished drinking water together with high-fat (HF) were examined to gauge their mixed effects on hepatic lipid metabolism. Using new alternative methods (NAMs), studying effects in human cells in vitro for risk assessment, we investigated the combined effects of HF and HAL-DBPs on hepatic lipid metabolism and lipotoxicity in immortalized LO-2 human hepatocytes. Coexposure of HAL-DBPs at various multiples of environmental exposure levels with HF increased the levels of triglycerides, interfered with de novo lipogenesis, enhanced fatty acid oxidation, and inhibited the secretion of very low-density lipoproteins. Lipid accumulation caused by the coexposure of HAL-DBPs and HF also resulted in more severe lipotoxicity in these cells. Our results using an in vitro NAM-based method provide novel insights into metabolic reprogramming in hepatocytes due to coexposure of HF and HAL-DBPs and strongly suggest that the risk of NAFLD in sensitive populations due to HAL-DBPs and poor lifestyle deserves further investigation both with laboratory and epidemiological tools. We also discuss how results from our studies could be used in health risk assessments for HAL-DBPs.


Assuntos
Hepatócitos , Metabolismo dos Lipídeos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Desinfecção , Fígado/metabolismo , Fígado/efeitos dos fármacos , Acetaldeído/toxicidade , Linhagem Celular
7.
AAPS J ; 26(4): 80, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38992280

RESUMO

Immunogenicity testing and characterization is an important part of understanding the immune response to administration of a protein therapeutic. Neutralizing antibody (NAb) assays are used to characterize a positive anti-drug antibody (ADA) response. Harmonization of reporting of NAb assay performance and results enables efficient communication and expedient review by industry and health authorities. Herein, a cross-industry group of NAb assay experts have harmonized NAb assay reporting recommendations and provided a bioanalytical report (BAR) submission editable template developed to facilitate agency filings. This document addresses key bioanalytical reporting gaps and provides a report structure for documenting clinical NAb assay performance and results. This publication focuses on the content and presentation of the NAb sample analysis report including essential elements such as the method, critical reagents and equipment, data analysis, study samples, and results. The interpretation of immunogenicity data, including the evaluation of the impact of NAb on safety, exposure, and efficacy, is out of scope of this publication.


Assuntos
Anticorpos Neutralizantes , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Humanos
8.
Artigo em Inglês | MEDLINE | ID: mdl-38870505

RESUMO

Objective: To observe the effect of cholangioscopy (CS) combined with minimally invasive abdominal surgery on prognosis stone recurrence in elderly patients (≥60 years old) with gallstones (GS). Methods: One hundred and fourteen GS patients admitted to The First Hospital of Nanchang between August 2018 and December 2021 were selected for the study, and they were randomly divided into the control group (n=57) and the observation group (n=57). The control group was treated with open surgery, while the observation group was given CS combined with minimally invasive stone removal surgery. Inter-group comparisons were made regarding operation time, intraoperative blood loss, postoperative intestinal function recovery, hospitalization time, clinical efficacy, and postoperative complication rate. Pain intensities before and, 4, 24, 48, and 72 hours after surgery were assessed using the Visual Analogue Score. After a 1-year post-discharge follow-up, the stone recurrence rate was counted, and the Gastrointestinal Quality-of-Life Index evaluated the quality of life. Results: There was no difference in operation time between the two groups (P > .05), but intraoperative blood loss, recovery time of intestinal function, hospitalization time, and complication rate were all lower in the observation group than in the control group (P < .05). In addition, the clinical efficacy of the observation group was better, and postoperative pain was lower (P < .05). In the prognostic follow-up, it was seen that the observation group had a lower stone recurrence rate (3.51%) and better quality of life (P < .05). Conclusions: CS combined with minimally invasive abdominal surgery is effective and safe in treating patients with GS and can validly reduce the prognosis risk of recurrent stones in patients, which deserves popularization in clinical use.

9.
Cell Biochem Biophys ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888871

RESUMO

The target of rapamycin (TOR) proteins exhibits phylogenetic conservation across various species, ranging from yeast to humans, and are classified as members of the phosphatidylinositol kinase (PIK)-related kinase family. Multiple serine/threonine (Ser/Thr) protein phosphatases (PP)2A, PP4, and PP6, have been recognized as constituents of the TOR signaling pathway in mammalian cells. The protein known as TOR signaling pathway regulator-like (TIPRL) functions as a regulatory agent by impeding the activity of the catalytic subunits of PP2A. Various cellular contexts have been postulated for TIPRL, encompassing the regulation of mechanistic target of rapamycin (mTOR) signaling, inhibition of apoptosis and biogenesis, and recycling of PP2A. According to reports, there has been an observed increase in TIPRL levels in several types of carcinomas, such as non-small-cell lung carcinoma (NSCLC) and hepatocellular carcinomas (HCC). This review aims to comprehensively examine the significance of the Tor pathway in regulating apoptosis and proliferation of cancer cells, with a specific focus on the role of TOR signaling and TIPRL in cancer.

10.
Adv Sci (Weinh) ; : e2309972, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937990

RESUMO

Klebsiella pneumoniae, a major clinical pathogen known for causing severe infections, is attracting heightened attention due to its escalating antibiotic resistance. Phages are emerging as a promising alternative to antibiotics; however, their specificity to particular hosts often restricts their use. In this study, a collection of 114 phages is obtained and subjected to analysis against 238 clinical K. pneumoniae strains, revealing a spectrum of lytic behaviors. A correlation between putative tail protein clusters and lysis patterns leads to the discovery of six receptor-binding protein (RBP) clusters that determine host capsule tropism. Significantly, RBPs with cross-capsular lysis capabilities are identified. The newly-identified RBPs provide a toolbox for customizing phages to target diverse capsular types. Building on the toolbox, the engineered phages with altered RBPs successfully shifted and broadened their host capsule tropism, setting the stage for tunable phage that offer a precise and flexible solution to combat K. pneumoniae infections.

11.
Food Chem ; 458: 140241, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38944926

RESUMO

Tea is widely consumed in both beverages and food. Epigallocatechin gallate (EGCG) is the most crucial active ingredient in tea. Currently, knowledges on transformation processes of EGCG during tea processing are lacking. Understanding the chemical reactions of EGCG and its products during tea processing is important for assessing the safety of tea-containing food. Here, we revealed the formation of persistent free radicals (PFRs) from EGCG under the influence of heating and light irradiation, which was substantiated with evidence. These PFRs exhibited stability for >30 min in simulated gastric fluid. Furthermore, we observed potential effects of these PFRs on DNA damage and cell cytotoxicity in vitro. By combining electron paramagnetic resonance spectrometer with Fourier transform ion cyclotron resonance mass spectrometry, we elucidated the pathways involved in free radical formation. These findings are expected to contribute to a comprehensive understanding of free radical chemistry in tea-containing food.

12.
Water Res ; 261: 122008, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38944971

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by abnormal lipid deposition, with oxidative stress being a risk factor in its onset and progression. Haloacetamides (HAcAms), as unregulated disinfection by-products in drinking water, may alter the incidence and severity of NAFLD through the production of oxidative stress. We explored whether HAcAms at 1, 10, and 100-fold concentrations in Shanghai drinking water perturbed lipid metabolism in normal human liver LO-2 cells. CRISPR/Cas9 was used to construct a LO-2 line with stable NRF2 knock-down (NRF2-KD) to investigate the mechanism underlying abnormal lipid accumulation and hepatocyte damage caused by mixed exposure to HAcAms. At 100-fold real-world concentration, HAcAms caused lipid deposition and increased triglyceride accumulation in LO-2 cells, consistent with altered de novo lipogenesis. Differences in responses to HAcAms in normal and NRF2-KD LO-2 cells indicated that HAcAms caused hepatocyte lipid deposition and triglyceride accumulation by activation of the NRF2/PPARγ pathway and aggravated liver cell toxicity by inducing ferroptosis. These results indicate that HAcAms are important risk factors for NAFLD. Further observations and verifications of the effect of HAcAms on NAFLD in the population are warranted in the future.

13.
BMC Gastroenterol ; 24(1): 211, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918740

RESUMO

BACKGROUND: Crohn's disease (CD) is a chronic condition characterized by a high recurrence rate after surgery, which seriously affects the quality of life of patients. Many studies have explored the risk factors for the recurrence of CD after surgery, there is a lack of meta-analysis focusing on endoscopic postoperative recurrence (ePOR) as a clinical outcome. Therefore, this paper aims to identify the risk factors for ePOR in CD patients through systematic review and meta-analysis. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched for related literature from inception to 17th October 2023. Two researchers independently screened the literature and extracted information. Data analysis was performed using Stata18.0. RESULTS: Twenty-three papers were included, with 5 case-control studies and 18 cohort studies. The National Institutes of Health quality assessment tool rated 17 studies as good and 6 studies as fair. The sample size of the 23 studies ranged from 40 to 346, and the number of patients with ePOR ranged from 23 to 169. The results of multivariate meta-analysis showed that smoking [OR = 2.06, 95% CI (1.65, 2.57), P = 0.0001], previous ileocolonic resection [OR = 1.71, 95% CI (1.23, 2.38), P = 0.002], disease localization at ileocolic resection [OR = 2.68, 95% CI (1.38, 5.22), P = 0.004], perianal disease [OR = 1.47, 95% CI (1.07, 2.03), P = 0.017], and anastomotic scattered ulcer [OR = 3.39, 95% CI (1.83, 6.28), P = 0.001] were risk factors for ePOR in CD patients. Postoperative prophylactic medication [OR = 0.53, 95% CI (0.38,0.75), P = 0.0001] was a protective factor for ePOR in CD patients. CONCLUSIONS: This systematic review identified multiple factors for ePOR in CD patients, as well as a protective factor. However, the number of articles included was limited. More high-quality clinical studies are required to further validate the conclusions. TRIAL REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023483671).


Assuntos
Doença de Crohn , Metanálise como Assunto , Recidiva , Revisões Sistemáticas como Assunto , Doença de Crohn/cirurgia , Humanos , Fatores de Risco , Projetos de Pesquisa , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
14.
Life Sci ; 351: 122849, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38897346

RESUMO

EGFR tyrosine kinase inhibitor (TKI) resistance is a major challenge for EGFR-mutant non-small cell lung cancer (NSCLC) treatment. Our previous work revealed that overexpression of AXL promoted EGFR-TKI resistance through epithelial-mesenchymal transition (EMT) in a subset of NSCLC patients. Compared with erlotinib resistant and sensitive cells, RP11-874 J12.4 was upregulated in erlotinib-resistant NSCLC cells (HCC827-ER3). Interestingly, the expression of RP11-874 J12.4 positively correlated with AXL. Besides, RP11-874 J12.4 promotes NSCLC cell proliferation and metastasis in vitro. Mechanistically, RP11-874 J12.4 promoted AXL expression through sponge with miR-34a-5p, which was reported to inhibit the translation of AXL mRNA. Meanwhile, the expression of RP11-874 J12.4 in lung cancer tumors were higher than the adjacent tissue, and those patients with high expression of RP11-874 J12.4 showed a poor prognosis in clinical. High expression of RP11-874 J12.4 might be a biomarker for NSCLC patients with erlotinib resistance. These findings reveal a novel insight into the mechanism of erlotinib resistance in NSCLC, and it might be a promising target for the diagnosis and treatment of NSCLC.


Assuntos
Receptor Tirosina Quinase Axl , Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Cloridrato de Erlotinib , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas , Receptores Proteína Tirosina Quinases , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Humanos , Cloridrato de Erlotinib/farmacologia , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , MicroRNAs/genética , MicroRNAs/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Animais , Camundongos
15.
Eur J Med Chem ; 275: 116605, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38885550

RESUMO

C-X-C chemokine receptor type 4 (CXCR4) exerts considerable influence on the pathogenesis of inflammatory disorders and offers a potent avenue for drug intervention. This research utilizes a hybrid virtual screening methodology constructed using computer-aided drug design to discover novel CXCR4 inhibitors for the treatment of inflammation. First, a compound library was screened by Lipinski's five rules and adsorption, distribution, metabolism, excretion and toxicity properties. Second, the HypoGen algorithm was used in constructing a 3D-QSAR pharmacophore model and verify it layer by layer, and the obtained optimal pharmacophore 1 (Hypo 1) was used as a 3D query for compound screening. Then, hit compounds were obtained through molecular docking (Libdock and CDOCKER). The toxicity of the compounds to MDA-MB-231 cells was evaluated in vitro, and their binding affinity to the target was evaluated according to how they compete with 12G5 antibody for CXCR4 on the surfaces of the MDA-MB-231 cells. Compound Hit14 showed the strongest binding affinity among the hit compounds and inhibited cell migration and invasion in Matrigel invasion and wound healing assay at a concentration of 100 nM, demonstrating a better effect than AMD3100. Western Blot experiments further showed that Hit14 blocked the CXCR4/CXCL12-mediated phosphorylation of Akt. Meanwhile, cellular thermal displacement assay analysis showed that CXCR4 protein bound to Hit14 had high thermal stability. Finally, through in vivo experiments, we found that Hit14 inhibited mouse ear inflammation and reduced ear swelling and damage. Therefore, Hit14 is a promising drug for the further development of CXCR4 inhibitors for inflammation treatment.


Assuntos
Inflamação , Simulação de Acoplamento Molecular , Receptores CXCR4 , Receptores CXCR4/antagonistas & inibidores , Receptores CXCR4/metabolismo , Humanos , Animais , Camundongos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Descoberta de Drogas , Movimento Celular/efeitos dos fármacos , Estrutura Molecular , Avaliação Pré-Clínica de Medicamentos , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Relação Quantitativa Estrutura-Atividade , Masculino
16.
Nat Commun ; 15(1): 4737, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834556

RESUMO

Hexachlorobutadiene (HCBD) is a concerning chemical that is included in the United States Toxic Substances Control Act, and the Stockholm Convention. Knowledge of the sources of HCBD is insufficient and is pivotal for accurate inventory and implementing global action. In this study, unintentional HCBD release and source emission factors of 121 full-scale industrial plants from 12 industries are investigated. Secondary copper smelting, electric arc furnace steelmaking, and hazardous waste incineration show potential for large emission reductions, which are found of high HCBD emission concentrations of > 20 ng/g in fine particulate matter in this study. The highest HCBD emission concentration is observed for the secondary copper smelting industry (average: 1380 ng/g). Source emission factors of HCBD for the 12 industries range from 0.008 kg/t for coal fire power plants to 0.680 kg/t for secondary lead smelting, from which an estimation of approximately 8452.8 g HCBD emissions annually worldwide achieved. The carcinogenic risks caused by HCBD emissions from countries and regions with intensive 12 industrial sources are 1.0-80 times higher than that without these industries. These results will be useful for formulating effective strategies of HCBD control.

17.
Heliyon ; 10(9): e29845, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707354

RESUMO

Objectives: To develop and validate a risk prediction model by identifying the preoperative factors associated with an increased risk of pneumonia after spinal surgery. Methods: This study included patients with spinal disease from two hospitals between January 2021 and June 2023. The patients were divided into the training and validation sets, which were categorized as postoperative pneumonia (POP) or non-POP, respectively. This study identified the independent risk variables for POP using a multivariate logistic regression analysis. A nomogram prediction model was developed and validated using risk factors, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) to assess predictive performance. Results: Following exclusion, 2223 patients from Changzheng Hospital were enrolled in the training set and 357 patients from the No. 905 Hospital of PLA Navy were enrolled in the validation set. Univariate and multivariate logistic regression analyses revealed that operation time, American Society of Anesthesiologists (ASA) grade, smoking, non-wearing of medical masks, lack of preoperative respiratory training, chronic obstructive pulmonary disease (COPD), underlying diseases, and spinal section were risk factors for POP development in patients with spinal diseases. The area under the ROC curve of the training set was 0.950, whereas that of the validation set was 0.879. The model calibration curves demonstrated good agreement, and the DCA indicated a high expected net benefit value. Conclusion: The POP risk prediction model has high accuracy and efficiency in predicting POP in patients with spinal diseases. POP development is influenced by factors such as operation length, ASA grade, smoking, non-wearing of medical masks, lack of preoperative respiratory training, COPD, underlying diseases, and lumbar surgery.

18.
PLoS Biol ; 22(5): e3002628, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38814940

RESUMO

The peptidoglycan (PG) layer is a critical component of the bacterial cell wall and serves as an important target for antibiotics in both gram-negative and gram-positive bacteria. The hydrolysis of septal PG (sPG) is a crucial step of bacterial cell division, facilitated by FtsEX through an amidase activation system. In this study, we present the cryo-EM structures of Escherichia coli FtsEX and FtsEX-EnvC in the ATP-bound state at resolutions of 3.05 Å and 3.11 Å, respectively. Our PG degradation assays in E. coli reveal that the ATP-bound conformation of FtsEX activates sPG hydrolysis of EnvC-AmiB, whereas EnvC-AmiB alone exhibits autoinhibition. Structural analyses indicate that ATP binding induces conformational changes in FtsEX-EnvC, leading to significant differences from the apo state. Furthermore, PG degradation assays of AmiB mutants confirm that the regulation of AmiB by FtsEX-EnvC is achieved through the interaction between EnvC-AmiB. These findings not only provide structural insight into the mechanism of sPG hydrolysis and bacterial cell division, but also have implications for the development of novel therapeutics targeting drug-resistant bacteria.


Assuntos
Trifosfato de Adenosina , Divisão Celular , Proteínas de Escherichia coli , Escherichia coli , Peptidoglicano , Peptidoglicano/metabolismo , Hidrólise , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/química , Escherichia coli/metabolismo , Escherichia coli/genética , Trifosfato de Adenosina/metabolismo , Microscopia Crioeletrônica , Parede Celular/metabolismo , Conformação Proteica , Modelos Moleculares , N-Acetil-Muramil-L-Alanina Amidase/metabolismo , N-Acetil-Muramil-L-Alanina Amidase/genética , Proteínas da Membrana Bacteriana Externa , Transportadores de Cassetes de Ligação de ATP , Regulador de Condutância Transmembrana em Fibrose Cística , Lipoproteínas , Proteínas de Ciclo Celular
19.
Med Phys ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38820428

RESUMO

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is a frequently encountered clinical condition that poses a diagnostic challenge due to its nonspecific symptoms. PURPOSE: To enhance the diagnosis of CCH and non-CCH through Magnetic Resonance Imaging (MRI), offering support in clinical decision-making and recommendations to ultimately elevate diagnostic accuracy and optimize patient treatment outcomes. METHODS: In the retrospective research, we collected 204 routine brain magnetic resonance imaging (MRI) from March 1 to September 10 2022, as training and testing cohorts. And a validation cohort with 108 samples was collected from November 14 2022 to August 4 2023. MRI sequences were processed to obtain T1-weighted (T1WI) and T2-weighted (T2WI) sequence images for each patient. We propose CCH-Network (CCHNet), an end-to-end deep learning model, integrating convolution and Transformer modules to capture local and global structural information. Our novel adversarial training method improves feature knowledge capture, enhancing both generalization ability and efficiency in predicting CCH risk. We assessed the classification performance of the proposed model CCHNet by comparing it with existing state-of-the-art deep learning algorithms, including ResNet34, DenseNet121, VGG16, Convnext, ViT, Coat, and TransFG. To better validate model performance, we compared the results of the proposed model with eight neurologists to evaluate their consistency. RESULTS: CCHNet achieved an AUC of 91.6% (95% CI: 86.8-99.1), with an accuracy (ACC) of 85.0% (95% CI: 75.6-95.2). It demonstrated a sensitivity (SE) of 80.0% (95% CI: 71.6-95.6) and a specificity (SP) of 90.0% (95% CI: 82.3-97.8) in the testing cohort. In the validation cohort, the model demonstrated an AUC of 86.0% (95% CI: 80.3-93.0), an ACC of 84.2% (95% CI: 70.2-93.6), a SE of 83.3% (95% CI: 68.3-95.5), and a SP of 84.7% (95% CI: 70.3-96.8). CONCLUSIONS: The model improved the diagnostic performance of MRI with high SE and SP, providing a promising method for the diagnosis of CCH.

20.
Complement Ther Med ; 83: 103053, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38801910

RESUMO

OBJECTIVE: Shenmai injection is a classic herbal prescription, and is often recommended for the treatment of anthracycline-induced cardiotoxicity. However, the efficacy and safety of Shenmai injection for the treatment of anthracycline-induced cardiotoxicity have not been reported. MATERIALS AND METHODS: We conducted a comprehensive search of eight literature databases and two clinical trial registries, retrieving all randomized controlled trials (RCTs) related to the treatment of anthracycline-induced cardiotoxicity with Shenmai injection from the establishment of the databases to July 1, 2023. Data analysis was performed using the Meta package in RStudio and RevMan 5.4. The GRADE pro3.6.1 software was utilized for assessing the quality of evidence. RESULTS: A total of 16 RCTs including 2140 patients were included in this study. Meta-analysis showed that Shenmai injection had an advantage in improving ST-T segment changes (RR = 0.28; 95 % CI, 0.20 to 0.39; P < 0.0001) (P < 0.01), creatine kinase isoenzyme (SMD = -3.49; 95 % CI, -5.24 to -1.74; P < 0.0001), Prolonged QT interval (RR = 0.46; 95 % CI, 0.28 to 0.75; P = 0.0018), Low QRS Voltage (RR = 0.44; 95 % CI, 0.27 to 0.71; P = 0.0007), sinus tachycardia (RR = 0.41; 95 % CI, 0.28 to 0.60; P < 0.0001), atrial premature beats (RR = 0.55; 95 % CI, 0.35 to 0.87; P = 0.01), Premature Ventricular Contractions (RR = 0.39; 95 % CI, 0.26 to 0.59; P < 0.0001) and creatine kinase (SMD = -1.43; 95 % CI, -2.57 to -0.29; P < 0.0001) in patients with anthracycline-induced cardiotoxicity. advantage, which was supported by sensitivity analyses, but not in improving left ventricular ejection fraction (MD = 16.01; 95 % CI, -3.10 to 35.12; P = 0.10) and atrioventricular block (RR = 0.49; 95 % CI, 0.24 to 1.03; P = 0.06). The literature included in the study did not refer to data regarding the safety aspects of Shenmai injection, so we do not yet know the safety of Shenmai injection. The results of subgroup analyses suggested that heterogeneity was not related to the administered dose and chemotherapy regimen. The publication bias test showed no publication bias. The quality of evidence for the results ranged from "very low" to "moderate." CONCLUSION: This study suggests that Shenmai injection is effective in treating anthracycline-induced cardiotoxicity and is a potential treatment for anthracycline-induced cardiotoxicity. However, due to the poor methodological quality of the included RCTs, we recommend rigorous, high-quality, large-sample trials to confirm our findings.


Assuntos
Antraciclinas , Cardiotoxicidade , Combinação de Medicamentos , Medicamentos de Ervas Chinesas , Humanos , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Cardiotoxicidade/etiologia , Antraciclinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
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