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1.
J Am Chem Soc ; 146(9): 6037-6044, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38377954

RESUMO

Alkene hydroformylation is one of the largest industrial reactions on an industrial scale; however, the development of nonnoble heterogeneous catalysts is usually limited by their low activities and stabilities. Herein, we constructed a 1% Co2C/SiO2 catalyst featuring Co-Cvacancy-Co-C symmetry-breaking sites, which generated a polar surface exhibiting a moderate charge density gradient at the localized Co atoms. Comparatively, this catalyst exhibited notable enhancements in the adsorption and activation of the reactants, as well as in the polarity between intermediates. Significantly, the spatial distance between the adsorption sites of intermediates was reduced, thereby effectively decreasing the energy barrier of reaction processes. As the density of the symmetry-breaking sites increased, the turnover number for propene hydroformylation soared to 18 363, exceeding the activity of heterogeneous Co-based catalysts reported thus far by 1 or 2 orders of magnitude, and the catalyst exhibited high stability during the reaction. This study provides a methodology for constructing atomically active sites, which holds great potential for the design and development of highly efficient catalysts.

2.
Anal Chem ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38887964

RESUMO

Simultaneous detection of multiple breast cancer-associated miRNAs significantly raises the accuracy and reliability of early diagnosis. In this work, disposable carbon fiber paper serves as the biosensing interface, linking DNA probes via click chemistry to efficiently capture targets and signals efficiently. DNA probes have multiple recognition domains that trigger a cascade reaction through the helper probes and targets, resulting in two signals output. The signals are centrally encapsulated in the pore of the MIL-88(Fe)-NH2. The signal carriers are directed by signal probes to the recognition domains that correspond to the DNA probes. The biosensor is selective and stable, and it can quantify miRNA-21 and miRNA-155 simultaneously with detection limits of 0.64 and 0.54 fmol/L, respectively. Furthermore, it demonstrates satisfactory performance in tests conducted with normal human serum and cell lysate. Overall, this method makes a satisfactory exploration to realize an inexpensive and sensitive biosensor for multiple biomarkers.

3.
J Virol ; 97(8): e0075623, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37578227

RESUMO

During entry, non-enveloped viruses penetrate a host membrane to cause infection, although how this is accomplished remains enigmatic. Polyomaviruses (PyVs) are non-enveloped DNA viruses that penetrate the endoplasmic reticulum (ER) membrane to reach the cytosol en route to the nucleus for infection. To penetrate the ER membrane, the prototype PyV simian virus 40 (SV40) induces formation of ER-escape sites, called foci, composed of repeating units of multi-tubular ER junctions where the virus is thought to exit. How SV40 triggers formation of the ER-foci harboring these multi-tubular ER junctions is unclear. Here, we show that the ER morphogenic atlastin 2 (ATL2) and ATL3 membrane proteins play critical roles in SV40 infection. Mechanistically, ATL3 mobilizes to the ER-foci where it deploys its GTPase-dependent membrane fusion activity to promote formation of multi-tubular ER junctions within the ER-foci. ATL3 also engages an SV40-containing membrane penetration complex. By contrast, ATL2 does not reorganize to the ER-foci. Instead, it supports the reticular ER morphology critical for the integrity of the ATL3-dependent membrane complex. Our findings illuminate how two host factors play distinct roles in the formation of an essential membrane penetration site for a non-enveloped virus. IMPORTANCE Membrane penetration by non-enveloped viruses, a critical infection step, remains enigmatic. The non-enveloped PyV simian virus 40 (SV40) penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol en route for infection. During ER-to-cytosol membrane penetration, SV40 triggers formation of ER-associated structures (called ER-foci) that function as the membrane penetration sites. Here, we discover a role of the ATL ER membrane proteins-known to shape the ER morphology-during SV40-induced ER-foci formation. These findings illuminate how a non-enveloped virus hijacks host components to construct a membrane penetration structure.


Assuntos
Membranas Intracelulares , Chaperonas Moleculares , Membranas Intracelulares/metabolismo , Chaperonas Moleculares/metabolismo , Internalização do Vírus , Retículo Endoplasmático/metabolismo , Proteínas de Membrana/metabolismo
4.
Opt Express ; 32(4): 5397-5409, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439267

RESUMO

Active-polarization imaging holds significant promise for achieving clear underwater vision. However, only static targets were considered in previous studies, and a background region was required for image restoration. To address these issues, this study proposes an underwater dynamic polarization imaging method based on image pyramid decomposition and reconstruction. During the decomposition process, the polarized image is downsampled to generate an image pyramid. Subsequently, the spatial distribution of the polarization characteristics of the backscattered light is reconstructed by upsampling, which recovered the clear scene. The proposed method avoids dependence on the background region and is suitable for moving targets with varying polarization properties. The experimental results demonstrate effective elimination of backscattered light while sufficiently preserving the target details. In particular, for dynamic targets, processing times that fulfill practical requirements and yield superior recovery effects are simultaneously obtained.

5.
Int J Hyperthermia ; 41(1): 2295232, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38159557

RESUMO

OBJECTIVE: To investigate the factors which may cause thermal injury of abdominal skin in patients with uterine fibroids (UFs) who underwent ultrasound-guided focused ultrasound ablation surgery (FUAS). METHOD: A total of 123 patients were enrolled in the injury group. In contrast, 246 patients without thermal injury were assigned to the non-injury group. The relationship between patient and treatment parameters and injury were explored using univariate analysis and multiple logistic regression analyses. In addition, the factors influencing the degree of thermal injury were analyzed using Kruskal-Wallis H. RESULTS: (1) Abdominal scars (p = .007, OR = 2.187, 95% CI: 1.242-3.849), abdominal wall thickness (p < .001, OR = 1.042, 95% CI: 1.019-1.067), fundus fibroids (p = .038, OR = 1.790, 95% CI: 1.033-3.100), UFs with hyperintense/mixed T2-weighted imaging (T2WI) signals (p = .022, OR = 1.843, 95% CI: 1.091-3.115), average sonication power (AP) (p = .025, OR = 1.021, 95% CI: 1.003-1.039), and treatment time (TT) (p < .001, OR = 1.017, 95% CI: 1.011-1.023) were independent risk factors for thermal injury, while treatment volume (TV) (p = .002, OR = 0.775, 95% CI: 0.661-0.909) was a protective factor for injury. (2) Four groups were subdivided according to the degree of thermal injury(Group A: without skin injury. Group B: with changed T2WI signal in the abdominal wall, Group C: mild skin injury, Group D: severe skin injury), comparison of each with every other showed that the abdominal wall in Groups A and D was thinner than Groups B and C, with statistically significant differences (PAB<0.05, PAC<0.01, PDC<0.05, PDB<0.05); Group A was slightly thicker than D, however, without statistical difference. The ratio of sonication time (ST) to TV in Group A was the lowest of all (PAB, PAC, PAD all < 0.05). And as the level of thermal injury rose, the ratio gradually increased, however, without statistical difference. CONCLUSIONS: Based on our limited results, the following conclusion was made. (1) Abdominal scars, abdominal wall thickness, fundus fibroids, UFs with T2WI hyperintense/mixed signals, AP and TT were independent risk factor. (2) Neither too thick nor too thin abdominal walls would be recommended, as both might increase the risk of skin injury. (3) Noticeably, the risk of skin injury might increase considerably when the ST was longer and the sonication area was more fixed.


Assuntos
Parede Abdominal , Queimaduras , Ablação por Ultrassom Focalizado de Alta Intensidade , Leiomioma , Neoplasias Uterinas , Humanos , Feminino , Cicatriz/etiologia , Ablação por Ultrassom Focalizado de Alta Intensidade/efeitos adversos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Estudos Retrospectivos , Leiomioma/diagnóstico por imagem , Leiomioma/cirurgia , Queimaduras/etiologia , Imageamento por Ressonância Magnética/métodos , Neoplasias Uterinas/cirurgia , Resultado do Tratamento
6.
Biol Pharm Bull ; 47(1): 292-302, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38281773

RESUMO

Staphylococcus aureus (SAU) stands as the prevailing pathogen in post-traumatic infections, with the emergence of antibiotic resistance presenting formidable treatment hurdles. The pressing need is to explore novel antibiotics to address this challenge. ShangKeHuangShui (SKHS), a patented traditional Chinese herbal formula, has gained widespread use in averting post-traumatic infections, but its biological effects remain incomplete understanding. This study's primary objective was to delve into the antibacterial properties, potential antibacterial compounds within SKHS, and their associated molecular targets. In vitro SKHS antibacterial assays demonstrated that the minimum inhibitory concentration (MIC) was 8.625 mg/mL and the minimum bactericide concentration (MBC) was 17.25 mg/mL. Proteomic analysis based on tandem mass tag (TMT) showed significant changes in the expression level of 246 proteins in SKHS treated group compared to control group, with 79 proteins upregulated and 167 proteins downregulated (>1.5-fold, p < 0.05). Subsequently, thirteen target proteins related to various biological processes and multiple metabolic pathways were selected to conduct parallel reaction monitoring (PRM) and molecular docking screen. In protein tyrosine phosphatase PtpA (ptpA) docking screening, phellodendrine and obacunone can bind to ptpA with the binding energy of - 8.4 and - 8.3 kcal/mol, respectively. This suggests their potential impact on antibacterial activity by modulating the two-component system of SAU. The discovery lays a groundwork for future research endeavors for exploring new antibacterial candidates and elucidating specific active chemical components within SKHS that match target proteins. Further investigations are imperative to unveil the biological effects of these monomers and their potential synergistic actions.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Proteômica , Simulação de Acoplamento Molecular , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana
7.
Neurol Sci ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902569

RESUMO

OBJECTIVE: To describe the association between preoperative ictal scalp electroencephalogram (EEG) results and surgical outcomes in patients with focal epilepsies. METHODS: The data of consecutive patients with focal epilepsies who received surgical treatments at our center from January 2012 to December 2021 were retrospectively analyzed. RESULTS: Our data showed that 44.2% (322/729) of patients had ictal EEG recorded on video EEG monitoring during preoperative evaluation, of which 60.6% (195/322) had a concordant ictal EEG results. No significant difference of surgery outcomes between patients with and without ictal EEG was discovered. Among MRI-negative patients, those with concordant ictal EEG had a significantly better outcome than those without ictal EEG (75.7% vs. 43.8%, p = 0.024). Further logistic regression analysis showed that concordant ictal EEG was an independent predictor for a favorable outcome (OR = 4.430, 95%CI 1.175-16.694, p = 0.028). Among MRI-positive patients, those with extra-temporal lesions and discordant ictal EEG results had a worse outcome compared to those without an ictal EEG result (44.7% vs. 68.8%, p = 0.005). Further logistic regression analysis showed that discordant ictal EEG was an independent predictor of worse outcome (OR = 0.387, 95%CI 0.186-0.807, p = 0.011) in these patients. Furthermore, our data indicated that the number of seizures was not associated with the concordance rates of the ictal EEG, nor the surgical outcomes. CONCLUSIONS: The value of ictal scalp EEG for epilepsy surgery varies widely among patients. A concordant ictal EEG predicts a good surgical outcome in MRI-negative patients, whereas a discordant ictal EEG predicts a poor postoperative outcome in lesional extratemporal lobe epilepsy.

8.
BMC Nephrol ; 25(1): 209, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918687

RESUMO

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited cystic disease characterized by bilateral renal cyst formation and congenital liver fibrosis. Cardiovascular disorders such as noncompaction of ventricular myocardium (NVM) have not been reported with ARPKD. CASE PRESENTATION: A 5-month-old girl was examined after presenting with a fever and turbid urine for one day and was diagnosed as urinary tract infection. Urinary ultrasound showed multiple round, small cysts varying in size in both kidneys. Genetic testing revealed two heterozygous mutations and one exon deletion in the polycystic kidney and hepatic disease 1 gene, indicating a diagnosis of ARPKD. During hospitalization, she was found to have chronic heart failure after respiratory tract infection, with an ejection fraction of 29% and fraction shortening of 13%. When the patient was 15 months old, it was found that she had prominent trabeculations and deep intertrabecular recesses with the appearance of blood flow from the ventricular cavity into the intertrabecular recesses by echocardiography. The noncompaction myocardium was 0.716 cm and compaction myocardium was 0.221 cm (N/C = 3.27), indicating a diagnosis of NVM. Liver and kidney function remained normal during four-year follow-up. CONCLUSIONS: This is the first report of NVM in a patient with ARPKD. It is unsure if the coexistence of NVM and ARPKD is a coincidence or they are different manifestations of ciliary dysfunction in the heart and kidneys.


Assuntos
Rim Policístico Autossômico Recessivo , Humanos , Feminino , Rim Policístico Autossômico Recessivo/complicações , Rim Policístico Autossômico Recessivo/genética , Rim Policístico Autossômico Recessivo/diagnóstico por imagem , Lactente , Miocárdio Ventricular não Compactado Isolado/complicações , Miocárdio Ventricular não Compactado Isolado/genética , Miocárdio Ventricular não Compactado Isolado/diagnóstico por imagem , Ciliopatias/genética , Ciliopatias/complicações
9.
J Med Internet Res ; 26: e48527, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38252469

RESUMO

BACKGROUND: Machine learning is a potentially effective method for predicting the response to platinum-based treatment for ovarian cancer. However, the predictive performance of various machine learning methods and variables is still a matter of controversy and debate. OBJECTIVE: This study aims to systematically review relevant literature on the predictive value of machine learning for platinum-based chemotherapy responses in patients with ovarian cancer. METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we systematically searched the PubMed, Embase, Web of Science, and Cochrane databases for relevant studies on predictive models for platinum-based therapies for the treatment of ovarian cancer published before April 26, 2023. The Prediction Model Risk of Bias Assessment tool was used to evaluate the risk of bias in the included articles. Concordance index (C-index), sensitivity, and specificity were used to evaluate the performance of the prediction models to investigate the predictive value of machine learning for platinum chemotherapy responses in patients with ovarian cancer. RESULTS: A total of 1749 articles were examined, and 19 of them involving 39 models were eligible for this study. The most commonly used modeling methods were logistic regression (16/39, 41%), Extreme Gradient Boosting (4/39, 10%), and support vector machine (4/39, 10%). The training cohort reported C-index in 39 predictive models, with a pooled value of 0.806; the validation cohort reported C-index in 12 predictive models, with a pooled value of 0.831. Support vector machine performed well in both the training and validation cohorts, with a C-index of 0.942 and 0.879, respectively. The pooled sensitivity was 0.890, and the pooled specificity was 0.790 in the training cohort. CONCLUSIONS: Machine learning can effectively predict how patients with ovarian cancer respond to platinum-based chemotherapy and may provide a reference for the development or updating of subsequent scoring systems.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Bases de Dados Factuais , Aprendizado de Máquina , PubMed , Máquina de Vetores de Suporte
10.
J Soc Work End Life Palliat Care ; 20(2): 201-216, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38557360

RESUMO

Racial disparities in hospice use are a longstanding concern in the U.S. Asian Americans are among the least likely to receive hospice care and to be included in studies on this topic. This study examined the knowledge, attitudes, and preferences related to hospice care among older Chinese immigrants and associated factors. A sample of 262 Chinese immigrants age 60+ was recruited from six older adult centers in NYC. In-person interviews were conducted in Mandarin and Cantonese. Non-English-speaking older Chinese immigrants had very limited knowledge about hospice care. Only 26% of respondents had heard of hospice, and a few could correctly define any components. After receiving a comprehensive definition of hospice care, study participants expressed a positive attitude and a strong willingness to use hospice if near the end of life. Notably, some respondents still held misconceptions about hospice and were less positive in their attitude and preference for hospice care. These findings underscore the necessity for clear and accessible information about hospice among this population throughout the trajectory from good health to end of life. Further research is needed to identify the range of factors that influence the attitudes and preferences of older Chinese immigrants toward hospice care.


Assuntos
Asiático , Emigrantes e Imigrantes , Conhecimentos, Atitudes e Prática em Saúde , Cuidados Paliativos na Terminalidade da Vida , Humanos , Feminino , Masculino , Idoso , Emigrantes e Imigrantes/psicologia , Emigrantes e Imigrantes/estatística & dados numéricos , Cuidados Paliativos na Terminalidade da Vida/psicologia , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Asiático/psicologia , Asiático/estatística & dados numéricos , Pessoa de Meia-Idade , Estados Unidos , Idoso de 80 Anos ou mais , China/etnologia , Preferência do Paciente/etnologia , Fatores Socioeconômicos , Entrevistas como Assunto , Cidade de Nova Iorque , População do Leste Asiático
11.
J Clin Ultrasound ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38895932

RESUMO

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is rare, particularly in children, and is potentially fatal. This article presents two cases of pediatric mitral-aortic intervalvular fibrosa pseudoaneurysm: one secondary to infective endocarditis and the other confirmed to be congenital in nature. The characteristic echocardiographic manifestations of mitral-aortic intervalvular fibrosa pseudoaneurysm demonstrated in this study will enhance diagnostic efficacy and guide early clinical intervention.

12.
J Am Chem Soc ; 145(3): 1847-1854, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36635072

RESUMO

To solve the serious environmental problem and huge resource waste of plastic pollution, we report a tandem catalytic conversion of low-density polyethylene (LDPE) into naphtha, the key feedstock for renewable plastic production. Using ß zeolite and silicalite-1-encapsulated Pt nanoparticles (Pt@S-1), a naphtha yield of 89.5% is obtained with 96.8% selectivity of C5-C9 hydrocarbons at 250 °C. The acid sites crack long-chain LDPE into olefin intermediates, which diffuse within the channels of Pt@S-1 to encounter Pt nanoparticles. The hydrogenation over confined metal matches cracking steps by selectively shipping the olefins with right size, and the rapid diffusion boosts the formation of narrow-distributed alkanes. A conceptual upgrading indicates it is suitable for closing the plastic loop, with a significant energy saving of 15% and 30% reduced greenhouse gas emissions.

13.
Ann Surg Oncol ; 30(3): 1744-1754, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36404379

RESUMO

BACKGROUND: Patients undergoing gastrectomy for gastric cancer are more likely to develop gallstones than the general population. Prophylactic cholecystectomy remains controversial. METHODS: Studies from 2000-2022 were systematically searched in the PubMed, EMBASE, and Cochrane Library databases. The search included simultaneous cholecystectomy or risk factors for gallstone formation with gastrectomy alone. Major prognostic factors included complications and mortality, and risk factor analyses included age, sex, TNM stage, gastrectomy type, lymph node dissection, diabetes, and duodenal exclusion. Random effects regression models were used to analyze risk estimates and data were presented as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS: There were no significant differences in postoperative morbidity (OR 1.12, 95% CI 0.90-1.39; p = 0.33, I2 = 11%) and mortality (OR 1.23, 95% CI 0.62-2.43; p = 0.56, I2 = 0%) between gastrectomy alone and simultaneous cholecystectomy. Older age (OR 1.48, 95% CI 1.36-1.59; p < 0.001, I2 = 59%), male sex (OR 1.38, 95% CI 1.10-1.71; p = 0.004, I2 = 77%), total gastrectomy (OR 1.50, 95% CI 1.25-1.81; p < 0.001, I2 = 72%), diabetes mellitus (OR 1.38, 95% CI 1.17-1.63; p < 0.001, I2 = 8%), and duodenal exclusion (OR 1.77, 95% CI 1.47-2.15; p < 0.001, I2 = 30%) were risk factors for cholecystolithiasis. CONCLUSIONS: Simultaneous cholecystectomy did not increase the incidence of postoperative complications or mortality. Older age, male sex, total gastrectomy, duodenal exclusion, and diabetes were risk factors for gallstone development after gastrectomy.


Assuntos
Diabetes Mellitus , Cálculos Biliares , Neoplasias Gástricas , Humanos , Masculino , Cálculos Biliares/complicações , Cálculos Biliares/cirurgia , Cálculos Biliares/epidemiologia , Neoplasias Gástricas/patologia , Gastrectomia/efeitos adversos , Colecistectomia/efeitos adversos , Diabetes Mellitus/cirurgia
14.
Microb Pathog ; 183: 106310, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37604214

RESUMO

Brucella abortus is facultative intracellular pathogen that causes chronic persistent infections and results in abortion and infertility in food animals. Recurrent infections can be one of the results of persister cells formation that transiently displays phenotypic tolerance to high dose of antibiotics treatment. We examined persister cells formation of B. abortus strain A19 in stationary phase and investigated a potential role for the (p)ppGpp synthetase Rsh in this process. We found that B. abortus stationary phase cells can produce higher levels of multi-drugs tolerant persister cells in vitro under high dose of antibiotics (20 × MIC) exposure than do exponential phase cells. Persister cell formation was also induced with environmental stressors pH 4.5, 0.01 M PBS (pH7.0), 2% NaCl and 25 °C, upon exposure to ampicillin, enrofloxacin and rifampicin. Persister cells were not formed following exposure to 1 mM H2O2. The numbers of persister cells were significantly increased following uptake of B. abortus stationary phase cells by RAW264.7 macrophages in contrast with cultures in TSB liquid medium. Environmental stressors to B. abortus significantly increased expression of rsh mRNA level. The rsh null mutant (Δrsh) formed significantly fewer persister cells than the complemented (CΔrsh) and wildtype (WT) strains under high dose of rifampicin in vitro. These data for the first time demonstrate that B. abortus can produce multi-drug tolerant persister cells in stationary phase. The (p)ppGpp synthetase Rsh is necessary for persister cell formation in B. abortus in the presence of rifampicin. On this basis, a new understanding of the recurrent infections of Brucella was advanced, thus provided a new basis for revelation of pathogenic mechanism of the chronic persistent infection in Brucella.


Assuntos
Brucella abortus , Rifampina , Feminino , Gravidez , Animais , Brucella abortus/genética , Rifampina/farmacologia , Peróxido de Hidrogênio , Reinfecção , Antibacterianos/farmacologia
15.
Respir Res ; 24(1): 212, 2023 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-37635231

RESUMO

BACKGROUND: Previous studies have shown that IL-25 levels are increased in patients with asthma with fixed airflow limitation (FAL). However, the mechanism by which IL-25 contributes to airway remodeling and FAL remains unclear. Here, we hypothesized that IL-25 facilitates pro-fibrotic phenotypic changes in bronchial epithelial cells (BECs) and circulating fibrocytes (CFs), orchestrates pathological crosstalk from BECs to CFs, and thereby contributes to airway remodeling and FAL. METHODS: Fibrocytes from asthmatic patients with FAL and chronic asthma murine models were detected using flow cytometry, multiplex staining and multispectral imaging analysis. The effect of IL-25 on BECs and CFs and on the crosstalk between BECs and CFs was determined using cell culture and co-culture systems. RESULTS: We found that asthmatic patients with FAL had higher numbers of IL-25 receptor (i.e., IL-17RB)+-CFs, which were negatively correlated with forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC). The number of airway IL-17RB+-fibrocytes was significantly increased in ovalbumin (OVA)- and IL-25-induced asthmatic mice versus the control subjects. BECs stimulated with IL-25 exhibited an epithelial-mesenchymal transition (EMT)-like phenotypic changes. CFs stimulated with IL-25 produced high levels of extracellular matrix (ECM) proteins and connective tissue growth factors (CTGF). These profibrotic effects of IL-25 were partially blocked by the PI3K-AKT inhibitor LY294002. In the cell co-culture system, OVA-challenged BECs facilitated the migration and expression of ECM proteins and CTGF in CFs, which were markedly blocked using an anti-IL-17RB antibody. CONCLUSION: These results suggest that IL-25 may serve as a potential therapeutic target for asthmatic patients with FAL.


Assuntos
Remodelação das Vias Aéreas , Asma , Animais , Camundongos , Fosfatidilinositol 3-Quinases , Células Epiteliais , Inibidores da Angiogênese , Proteínas da Matriz Extracelular
16.
BMC Cancer ; 23(1): 698, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37495975

RESUMO

INTRODUCTION: The overall survival of patients with mesothelioma is poor and heterogeneous. At present, the prediction model for Chinese patients needs to be improved. We sought to investigate predictors of survival in malignant pleural mesothelioma and develop prognostic prediction models. METHODS: This Two-center retrospective cohort study recruited patients with pathologically diagnosed mesothelioma at Beijing Chao-Yang Hospital and Beijing Tong-Ren Hospital. We developed a new prognostic prediction model based on COX multivariable analysis using data from patients who were recruited from June 1, 2010 to July 1, 2021 in Beijing Chao-Yang Hospital (n = 95, development cohort) and validated this model using data from patients recruited from July 18, 2014 to May 9, 2022 in Beijing Tong-Ren Hospital (n = 23, validation cohort). Receiver operating characteristic analysis was used to estimate model accuracy. RESULTS: The parameters in this new model included PLT > 289.5(10^9/L) (1 point), Lymphocyte > 1.785(10^9/L) (-1point), Age > 73 years old (1 point), Calcium > 2.145(mmol/L) (-1point), Eastern Cooperative Oncology Group performance status (ECOG PS) > 2 (2 points). When the sum of scores < 0, it is recognized as a low-risk group; when the score is 0 ~ 3, it is recognized as a high-risk group. The survival rate of patients in the high-risk group was significantly lower than that in the low-risk group (hazard ratio [HR], 3.878; 95% confidence interval [CI], 2.226-6.755; P < 0.001). The validation group had similar results (HR,3.574; 95%CI,1.064-12.001; P = 0.039). Furthermore, the areas under the curve 6 months after diagnosis in the two cohorts were 0.900 (95% CI: 0.839-0.962) and 0.761 (95% CI: 0.568-0.954) for development and validation cohorts, respectively. CONCLUSION: We developed a simple, clinically relevant prognostic prediction model for PLACE by evaluating five variables routinely tested at the time of diagnosis. The predictive model can differentiate patients of Chinese ethnicity into different risk groups and further guide prognosis.


Assuntos
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Idoso , Prognóstico , Estudos Retrospectivos , Neoplasias Pleurais/patologia , Mesotelioma/patologia
17.
BMC Cancer ; 23(1): 526, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291499

RESUMO

NEDD4 family represent an important group of E3 ligases, which regulate various cellular pathways of cell proliferation, cell junction and inflammation. Emerging evidence suggested that NEDD4 family members participate in the initiation and development of tumor. In this study, we systematically investigated the molecular alterations as well as the clinical relevance regarding NEDD4 family genes in 33 cancer types. Finally, we found that NEDD4 members showed increased expression in pancreas cancer and decreased expression in thyroid cancer. NEDD4 E3 ligase family genes had an average mutation frequency in the range of 0-32.1%, of which HECW1 and HECW2 demonstrated relatively high mutation rate. Breast cancer harbors large amount of NEDD4 copy number amplification. NEDD4 family members interacted proteins were enriched in various pathways including p53, Akt, apoptosis and autophagy, which were confirmed by further western blot and flow cytometric analysis in A549 and H1299 lung cancer cells. In addition, expression of NEDD4 family genes were associated with survival of cancer patients. Our findings provide novel insight into the effect of NEDD4 E3 ligase genes on cancer progression and treatment in the future.


Assuntos
Neoplasias , Ubiquitina-Proteína Ligases , Humanos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Ubiquitina-Proteína Ligases Nedd4/genética , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Neoplasias/genética , Proteínas do Tecido Nervoso/genética
18.
Inorg Chem ; 62(8): 3637-3645, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36792148

RESUMO

Urea degradation is one of the most crucial links in the natural nitrogen cycle. Exploring the real active species in the urea electro-oxidation process is of great significance for understanding the urea electro-oxidation mechanism and designing catalysts. A highly active and stable Prussian blue analogue catalyst (PBA@NiFe/NF) loaded on nickel foam was synthesized for electro-oxidation of urea. In situ Raman spectra revealed that Ni in PBA@NiFe/NF was able to maintain a stable divalent nickel (Ni(II)) state for up to 3.5 h during the initial urea oxidation process, which is rarely reported in previous research studies. In addition, with the participation of iron, the Ni-Fe bimetallic center significantly improves the electro-oxidation of urea. Our work provides a new idea for prolonging the Ni(II) activity in electrocatalytic oxidation of urea.

19.
Cell Biol Toxicol ; 39(5): 2165-2181, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35226250

RESUMO

N6-methyladenosine (m6A) messenger RNA methylation is the most widespread gene regulatory mechanism affecting liver functions and disorders. However, the relationship between m6A methylation and arsenic-induced hepatic insulin resistance (IR), which is a critical initiating event in arsenic-induced metabolic syndromes such as type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD), remains unclear. Here, we showed that arsenic treatment facilitated methyltransferase-like 14 (METTL14)-mediated m6A methylation, and that METTL14 interference reversed arsenic-impaired hepatic insulin sensitivity. We previously showed that arsenic-induced NOD-like receptor protein 3 (NLRP3) inflammasome activation contributed to hepatic IR. However, the regulatory mechanisms underlying the role of arsenic toward the post-transcriptional modification of NLRP3 remain unclear. Here, we showed that NLRP3 mRNA stability was enhanced by METTL14-mediated m6A methylation during arsenic-induced hepatic IR. Furthermore, we demonstrated that arsenite methyltransferase (AS3MT), an essential enzyme in arsenic metabolic processes, interacted with NLRP3 to activate the inflammasome, thereby contributing to arsenic-induced hepatic IR. Also, AS3MT strengthened the m6A methylase association with NLRP3 to stabilize m6A-modified NLRP3. In summary, we showed that AS3MT-induced m6A modification critically regulated NLRP3 inflammasome activation during arsenic-induced hepatic IR, and we identified a novel post-transcriptional function of AS3MT in promoting arsenicosis.


Assuntos
Arsênio , Resistência à Insulina , Humanos , Arsênio/toxicidade , Arsênio/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Inflamassomos/metabolismo , Fígado , Metiltransferases/genética , Metiltransferases/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR/metabolismo
20.
Anal Bioanal Chem ; 415(27): 6647-6661, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37848579

RESUMO

Detection of human-generated volatile organic compounds (VOCs) is a new pathway for assessing health. Herein, a polyvinylidene fluoride (PVDF)-based colorimetric sensor array was designed for detecting disease-related VOCs (DVOCs) within 15 min, using a complex of Cu metal-organic framework, graphene aerogel, and dyes as response materials. Fingermaps derived from 28 DVOCs were obtained for further data processing. Pattern recognition was successfully employed in the correct discrimination of 28 DVOCs in low (10 µM), medium (100 µM), and high (300 µM) concentrations. Importantly, the sensor array also presented excellent discrimination ability and application potential when detecting VOCs produced by human cancer and normal cells. In general, VOC acquisition is noninvasive and harmless, and the PVDF-based sensor arrays are simple and visual. Such advantages expand their further application potential.


Assuntos
Neoplasias , Compostos Orgânicos Voláteis , Humanos , Colorimetria , Polivinil , Neoplasias/diagnóstico
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