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1.
Gene ; 916: 148426, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38575101

RESUMO

Since late 2019, COVID-19 has significantly impacted the world. Understanding the evolution of SARS-CoV-2 is crucial for protecting against future infectious pathogens. In this study, we conducted a comprehensive chronological analysis of SARS-CoV-2 evolution by examining mutation prevalence from the source countries of VOCs: United Kingdom, India, Brazil, South Africa, plus two countries: United States, Russia, utilizing genomic sequences from GISAID. Our methodological approach involved large-scale genomic sequence alignment using MAFFT, Python-based data processing on a high-performance computing platform, and advanced statistical methods the Maximal Information Coefficient (MIC), and also Long Short-Term Memory (LSTM) models for correlation analysis. Our findings elucidate the dynamics of SARS-CoV-2 evolution, highlighting the virus's changing behaviour over various pandemic stages. Key results include the discovery of three temporal mutation patterns-lineage distinct, long-span, and competitive mutations-with varying levels of impact on the virus. Notably, we observed a convergence of advantageous mutations in the spike protein, especially in the later stages of the pandemic, indicating a substantial evolutionary pressure on the virus. One of the most significant revelations is the predominant role of natural immunity over vaccination-induced immunity in driving these evolutionary changes. This emphasizes the critical need for regular vaccine updates to maintain efficacy against evolving strains. In conclusion, our study not only sheds light on the evolutionary trajectory of SARS-CoV-2 but also underscores the urgency for robust, continuous global data collection and sharing. It highlights the necessity for rapid adaptations in medical countermeasures, including vaccine development, to stay ahead of pathogen evolution. This research provides valuable insights for future pandemic preparedness and response strategies.

2.
Front Psychiatry ; 15: 1309022, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628262

RESUMO

Depression is the most common psychiatric disorder that burdens modern society heavily. Numerous studies have shown that adverse childhood experiences can increase susceptibility to depression, and depression with adverse childhood experiences has specific clinical-biological features. However, the specific neurobiological mechanisms are not yet precise. Recent studies suggest that the gut microbiota can influence brain function and behavior associated with depression through the "microbe-gut-brain axis" and that the composition and function of the gut microbiota are influenced by early stress. These studies offer a possibility that gut microbiota mediates the relationship between adverse childhood experiences and depression. However, few studies directly link adverse childhood experiences, gut microbiota, and depression. This article reviews recent studies on the relationship among adverse childhood experiences, gut microbiota, and depression, intending to provide insights for new research.

3.
4.
Lipids Health Dis ; 23(1): 106, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616260

RESUMO

BACKGROUND: Dyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia. METHODS: In this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3' untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P < 0.05 indicating statistical significance. Assessment of linkage disequilibrium patterns and haplotype structures was conducted utilizing Haploview. RESULTS: Eleven distinct polymorphisms at LDLR 3' UTR were identified. Seven polymorphisms (rs1433099, rs14158, rs2738466, rs5742911, rs17249057, rs55971831, and rs568219285) were correlated with the baseline serum lipid levels (P < 0.05). In particular, four polymorphisms (rs14158, rs2738466, rs5742911, and rs17249057) were in strong linkage disequilibrium (r2 = 1), and patients with the AGGC haplotype had higher TC and LDL-C levels at baseline. Three polymorphisms (rs1433099, rs2738467, and rs7254521) were correlated with the therapeutic efficacy of atorvastatin (P < 0.05). Furthermore, carriers of the rs2738467 T allele demonstrated a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) levels post-atorvastatin treatment (P = 0.03), indicating a potentially crucial genetic influence on therapeutic outcomes. Two polymorphisms (rs751672818 and rs566918949) were neither correlated with the baseline serum lipid levels nor atorvastatin's efficacy. CONCLUSIONS: This research outlined the complex genetic architecture surrounding LDLR 3' UTR polymorphisms and their role in lipid metabolism and the response to atorvastatin treatment in adult Han Chinese patients with dyslipidemia, highlighting the importance of genetic profiling in enhancing tailored therapeutic strategies. Furthermore, this investigation advocates for the integration of genetic testing into the management of dyslipidemia, paving the way for customized therapeutic approaches that could significantly improve patient care. TRIAL REGISTRATION: This multicenter study was approved by the Ethics Committee of Xiangya Hospital Central South University (ethics number K22144). It was a general ethic. In addition, this study was approved by The First Hospital of Hebei Medical University (ethics number 20220418).


Assuntos
Dislipidemias , Polimorfismo Genético , Adulto , Humanos , Atorvastatina/uso terapêutico , Regiões 3' não Traduzidas/genética , LDL-Colesterol , Dislipidemias/tratamento farmacológico , Dislipidemias/genética , China
5.
Artigo em Inglês | MEDLINE | ID: mdl-38569918

RESUMO

BACKGROUND: To access early and midterm outcomes of a gutter-plugging chimney stent-graft for treatment of Stanford type B aortic dissections (TBAD) in the clinical trial of Prospective Study for Aortic Arch Therapy with stENt-graft for Chimney technology (PATENCY). METHODS: Between October 2018 and March 2022, patients with TBAD were treated with the LonguetteTM chimney stent-graft in 26 vascular centers. The efficiency and the incidence of adverse event over 12 months were investigated. RESULTS: :A total of 150 patients were included. The technical success rate was 99.33% (149/150). The incidence of immediate postoperative endoleak was 5.33% (8/150, type I, n = 6; type II, n = 1; type IV, n = 1), neurologic complications (stroke or spinal cord ischemia) and 30-day mortality were 0.67% (1/150) and 1.33% (2/150), respectively. During the follow-up, the median follow-up time was 11.67 (5-16) months. The patent rate of Longuette graft is 97.87%. Two type I endoleak patients underwent reintervention. The follow-up rate of incidence of retrograde A type aortic dissection was 0.67% (1/150). There was no paraplegia, left arm ischemia, or stent migration. CONCLUSION: For revascularization of the left subclavian artery, the LonguetteTM chimney stent graft can provide an easily manipulated, safe, and effective endovascular treatment. It should be considered a more efficient technique to prevent type Ia endoleak. Longer follow-up and a larger cohort are needed to validate these results.

6.
Ann Vasc Surg ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38599492

RESUMO

OBJECTIVES: The Talos stent-graft has extended length to improve aortic remodeling, and distal porous design to decrease the rate of spinal cord ischemia. This study retrospectively analyzed its mid-term outcomes for uncomplicated type B aortic dissection in a multicenter study. METHODS: The primary safety endpoint was 30-day major adverse events, including all-cause mortality, dissection-related mortality, conversion to open surgery, and device-related adverse events. The primary efficacy endpoint was treatment success at 12 months post-operation, defined as no technical failure or secondary dissection-related reintervention. The survival status of the patients was visualized using the Kaplan-Meier curve. Aortic growth was assessed at four levels, and spinal cord ischemia was evaluated at 12 months. RESULTS: 113 patients participated with a mean age of 54.4 (11.1) years and 71.7% (81/113) were male. The 30-day mortality was 0.9% (1/113), no conversions to open surgery or device-related adverse events were recorded. The 12-month treatment success rate was 99.1% (112/113), with no dissection-related reinterventions. There was no spinal cord or visceral ischemia at 12 months. At a median of 34 months follow-up, 9 further deaths were recorded and the 3-year survival rate was 91.7%. The percentage of aortic growth was 1.8% (2/111) at the tracheal bifurcation, 3.6% (4/111) below the left atrium, 6.0% (5/83) above the celiac artery, and 12.1% (9/74) below the lower renal artery. The total thrombosis rate of the false lumen at the stented segment was 80.5% (91/113). CONCLUSIONS: The results showed satisfactory results of Talos stent-graft in terms of safety and efficacy. More data are needed to confirm the long-term performance.

7.
JCI Insight ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483541

RESUMO

Glioblastoma (GBM) remains an incurable disease, requiring more effective therapies. Through interrogation of publicly available CRISPR and RNAi library screens, we identified the alpha-ketoglutarate dehydrogenase (OGDH) gene, which encodes for an enzyme that is part of the tricarboxylic acid cycle (TCA cycle) as essential for GBM growth. Moreover, by combining a transcriptome and metabolite screening analyses we discovered that loss of function of OGDH by the clinically validated drug compound, CPI-613, was synthetically lethal with Bcl-xL inhibition (genetically and through the clinically validated BH3-mimetic, ABT263) in patient-derived xenograft as well neurosphere GBM cultures. CPI-613 mediated energy deprivation drove an integrated stress response with an up-regulation of the BH3-only domain protein, Noxa in an ATF4 dependent manner as demonstrated by genetic loss of function experiments. Consistently, silencing of Noxa attenuated cell death induced by CPI-613 in model systems of GBM. In patient-derived xenograft models of GBM in mice, the combination treatment of ABT263 and CPI-613 suppressed tumor growth and extended animal survival more potently than each compound on its own. Therefore, combined inhibition of Bcl-xL along with interference of the TCA-cycle might be a treatment strategy for GBM.

8.
Eur J Pediatr ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38429545

RESUMO

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.

9.
Int J Cardiol ; 404: 131977, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38508322

RESUMO

PURPOSE: To evaluate the best endovascular treatment for de novo femoropopliteal lesions at long-term follow-up through network meta-analysis of randomized controlled trials. METHODS: Medical databases were searched on September 17, 2023. 17 trials and 7 treatments were selected. Outcomes were primary patency, target lesion revascularization (TLR), major amputation and all-cause mortality at 3 and/or 5 years. RESULTS: Regarding 3-year primary patency, drug-eluting stents (DES) was the best and better than balloon angioplasty (BA; odds ratio [OR], 4.96; 95% confidence interval [CI], 2.68-9.18), bare metal stents (BMS; OR, 2.81; 95% CI, 1.45-5.46), cryoplasty (OR, 6.75; 95% CI, 2.76-16.50), covered stents (CS; OR, 3.25; 95% CI, 1.19-8.87) and drug-coated balloons (DCB; OR, 2.04; 95% CI, 1.14-3.63). Regarding 5-year primary patency, DES was the best and better than BMS (OR, 2.34; 95% CI, 1.10-4.99). Regarding 3-year TLR, DES was the best and better than BA (OR, 0.24; 95% CI, 0.13-0.44). Regarding 5-year TLR, DES was the best and better than BA (OR, 0.20; 95% CI, 0.09-0.42) and balloon angioplasty with brachytherapy (OR, 0.21; 95% CI, 0.06-0.74). Regarding 3- and 5-year major amputation, DCB was the best. Regarding 3-year mortality, DES was the best and better than CS (OR, 0.09; 95% CI, 0.01-0.67). CONCLUSIONS: DES was the best treatment regarding 3-year primary patency, TLR and mortality, and DCB was the best regarding major amputation. DES was the best treatment regarding 5-year TLR, and DCB was the best regarding primary patency and major amputation. DES and DCB should be given priority in treating femoropopliteal lesions.


Assuntos
Angioplastia com Balão , Stents Farmacológicos , Doença Arterial Periférica , Humanos , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/cirurgia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/cirurgia , Metanálise em Rede , Resultado do Tratamento , Grau de Desobstrução Vascular , Ensaios Clínicos Controlados Aleatórios como Assunto , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/cirurgia , Materiais Revestidos Biocompatíveis
10.
Artigo em Inglês | MEDLINE | ID: mdl-38552594

RESUMO

Youkenafil is a novel Phosphodiesterase type 5 inhibitor used for treating erectile dysfunction. N-desethyl compound of youkenafil (M1) is its main active metabolite. In this study, two methods were developed and validated for the simultaneous determination of youkenafil and M1 by HPLC-MS/MS in human matrices including seminal plasma and plasma, in which the multiple reaction monitoring and electrospray ionization in positive mode were adopted, and the deuterated youkenafil (youkenafil-d5) was selected as the internal standard. The collected semen sample was kept at room temperature for approximately 30 min until fully liquefied. The volume of the liquefied semen was measured and then divided into two parts. One part was centrifuged to obtain the seminal plasma for the content detection of youkenafil and M1, while the other part was used for routine semen analysis. The chromatographic separation was accomplished with the column of Poroshell 120 EC-C18 (5 × 2.1 mm, 2.7 µm, Agilent). Protein precipitation with methanol was used for the pretreatment of seminal plasma and plasma. The intra-run and inter-run precisions were less than 6.4 % (relative standard deviation) and accuracies were all within -4.7 %-6.8 % (relative error) in both matrices. All other validated bioanalytical parameters were within the acceptance criteria set by the FDA. The methods were successfully applied to different clinical studies of youkenafil. In the clinical study of the acute effect of youkenafil on semen quality in healthy males, the content of youkenafil in seminal plasma was extremely low. Concentrations of youkenafil and M1 in seminal plasma were lower than those in plasma, at 20.7 % and 4.49 % of the plasma concentration, respectively. There was no significant acute effect of youkenafil on semen quality. In the pharmacokinetic study of youkenafil after single dose-escalation administration, the exposure to youkenafil and M1 was non-linear with the dose in the range of 100-400 mg.


Assuntos
Sêmen , Espectrometria de Massas em Tandem , Masculino , Humanos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , 60705 , Análise do Sêmen , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos Testes
11.
Adv Sci (Weinh) ; : e2400444, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552156

RESUMO

Aortic root aneurysm is a potentially life-threatening condition that may lead to aortic rupture and is often associated with genetic syndromes, such as Marfan syndrome (MFS). Although studies with MFS animal models have provided valuable insights into the pathogenesis of aortic root aneurysms, this understanding of the transcriptomic and epigenomic landscape in human aortic root tissue remains incomplete. This knowledge gap has impeded the development of effective targeted therapies. Here, this study performs the first integrative analysis of single-nucleus multiomic (gene expression and chromatin accessibility) and spatial transcriptomic sequencing data of human aortic root tissue under healthy and MFS conditions. Cell-type-specific transcriptomic and cis-regulatory profiles in the human aortic root are identified. Regulatory and spatial dynamics during phenotypic modulation of vascular smooth muscle cells (VSMCs), the cardinal cell type, are delineated. Moreover, candidate key regulators driving the phenotypic modulation of VSMC, such as FOXN3, TEAD1, BACH2, and BACH1, are identified. In vitro experiments demonstrate that FOXN3 functions as a novel key regulator for maintaining the contractile phenotype of human aortic VSMCs through targeting ACTA2. These findings provide novel insights into the regulatory and spatial dynamics during phenotypic modulation in the aneurysmal aortic root of humans.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38491165

RESUMO

PURPOSE: To evaluate the safety and feasibility of left subclavian artery (LSA) revascularization techniques during thoracic endovascular aortic repair (TEVAR)-the in situ needle fenestration (ISNF) technique and the carotid-subclavian bypass (CS-Bp)-for complicated aortic pathologies. METHODS: A retrospective single-center observational study was conducted to identify all patients with thoracic aortic pathologies who underwent TEVAR with LSA revascularization using either CS-Bp or ISNFs from January 2014 to December 2020. RESULTS: One hundred and twelve consecutive patients who received TEVAR with LSA revascularization were included. Among them, 69 received CS-Bp and 43 received ISNF (29 using the Futhrough adjustable puncture needles, 14 using the binding stent-graft puncture systems). Technical success, defined as achieving aortic arch pathology exclusion and LSA preservation, was attained in 99.1% patients. Early mortality was 0.9%. Major adverse events within 30 days, including one cerebral hemorrhage, one cervical incision hemorrhage, one stroke and two paraplegia, were exclusively observed in the CS-Bp group. Immediate type I, II and III endoleaks occurred in 0%, 4.7% and 2.3% in the ISNF group, respectively, compared to 0%, 2.9% and 0% in the CS-Bp group.One hundred and eight (97.2%) patients were available for follow-up at a median 50 (maiximum of 103) months, revealing a LSA patency rates of 99.1%. Six patients died during follow-ups-five in the CS-Bp group and one in the ISNF group. Cause of death include one aortic-related stent-graft infection, three non-related and two with unknow causes. The survival exhibited no significantly different between the ISNF (97.7%) and CS-Bp (89.9%) groups (p = 0.22). CONCLUSIONS: Both CS-Bp and ISNF are feasible techniques for LSA reconstruction in TEVAR. ISNF, whether using Futhrough or BPS, seems to be competitive with CS-Bp.

14.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(1): 45-50, 2024 Feb 18.
Artigo em Chinês | MEDLINE | ID: mdl-38318895

RESUMO

OBJECTIVE: To investigate the differences and similarities of parameters associated with anemia of inflammation between patients with stage Ⅲ periodontitis and periodontally healthy volunteers, and to explore the influence of periodontal initial therapy on those indicators. METHODS: Patients with stage Ⅲ periodontitis and periodontally healthy volunteers seeking periodontal treatment or prophylaxis at Department of Periodontology, Peking University School and Hospital of Stomatology from February 2020 to February 2023 were enrolled. Their demographic characteristics, periodontal parameters (including probing depth, clinical attachment loss, bleeding index), and fasting blood were gathered before periodontal initial therapy. Three months after periodontal initial therapy, the periodontal parameters of the patients with stage Ⅲ periodontitis were re-evaluated and their fasting blood was collected again. Blood routine examinations (including white blood cells, red blood cells, hemoglobin, packed cell volume, mean corpuscular volume of erythrocytes, and mean corpuscular hemoglobin concentration) were performed. And ferritin, hepcidin, erythropoietin (EPO) were detected with enzyme-linked immunosorbent assay (ELISA). All data analysis was done with SPSS 21.0, independent sample t test, paired t test, and analysis of covariance were used for comparison between the groups. RESULTS: A total of 25 patients with stage Ⅲ periodontitis and 25 periodontally healthy volunteers were included in this study. The patients with stage Ⅲ periodontitis were significantly older than those in periodontally healthy status [(36.72±7.64) years vs. (31.44±7.52) years, P=0.017]. The patients with stage Ⅲ periodontitis showed lower serum hemoglobin [(134.92±12.71) g/L vs. (146.52±12.51) g/L, P=0.002] and higher serum ferritin [(225.08±103.36) µg/L vs. (155.19±115.38) µg/L, P=0.029], EPO [(41.28±12.58) IU/L vs. (28.38±10.52) IU/L, P < 0.001], and hepcidin [(48.03±34.44) µg/L vs. (27.42±15.00) µg/L, P=0.009] compared with periodontally healthy volunteers. After adjusting the age with the covariance analysis, these parameters (hemoglobin, ferritin, EPO, and hepcidin) showed the same trends as independent-sample t test with statistical significance. Three months after periodontal initial therapy, all the periodontal parameters showed statistically significant improvement. The serum hemoglobin raised [(146.05±15.48) g/L vs. (133.77± 13.15) g/L, P < 0.001], while the serum ferritin [(128.52±90.95) µg/L vs. (221.22±102.15) µg/L, P < 0.001], EPO [(27.66±19.67) IU/L vs. (39.63± 12.48) IU/L, P=0.004], and hepcidin [(32.54±18.67) µg/L vs. (48.18±36.74) µg/L, P=0.033] decreased compared with baseline. CONCLUSION: Tendency of iron metabolism disorder and anemia of inflammation was observed in patients with stage Ⅲ periodontitis, which can be attenuated by periodontal initial therapy.


Assuntos
Anemia , Periodontite Crônica , Periodontite , Humanos , Hepcidinas , Anemia/etiologia , Anemia/terapia , Periodontite/complicações , Periodontite/terapia , Hemoglobinas/análise , Inflamação , Ferritinas , Perda da Inserção Periodontal
15.
Heliyon ; 10(4): e26209, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38390181

RESUMO

The investigation of peptide drugs has become essential in the development of innovative medications for hypertension. In this study, a sensitive high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to determine the plasma concentration and stability of the antihypertensive peptide FR-6 in rats. An isotopically labeled peptide (with an unchanged sequence) was utilized as an internal standard (IS) for validation purposes. Subsequently, this assay was employed to examine the pharmacokinetics of different administration methods (tail vein and gavage) in Sprague Dawley (SD) rats. Extracted plasma samples underwent sample preparation through methanol protein precipitation, followed by elution of FR-6 on Wondasil C18 Superb column (4.6 × 150 mm, 5 µm), using a mobile phase consisting of formic acid (0.1%) in water (A) and formic acid (0.125%)-ammonium formate (2 mM) in methanol (B). Ion pairs corresponding to FR-6 and IS were monitored via multiple reaction monitoring (MRM) under positive ion mode: m/z 400.7 â†’ 285.1 for FR-6 and m/z 406.1 â†’ 295.1 for IS detection respectively. The method exhibited excellent linearity with respect to FR-6 concentrations. In addition, the inter-day and intra-day precision were 0.61-6.85% and 1.76-11.75%; the inter-day and intra-day accuracy were -7.28-0.13% and -7.20-2.28%, respectively. In conclusion, the matrix effect, extraction recovery, and stability data were validated according to FDA recommended acceptance criteria for bioanalytical methods. This validated method serves as a reliable tool for determining the concentration of antihypertensive peptide FR-6, and has been successfully applied in pharmacokinetic studies involving rats.

16.
J Med Virol ; 96(2): e29447, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38305064

RESUMO

With the emergence of the Omicron variant, the number of pediatric Coronavirus Disease 2019 (COVID-19) cases requiring hospitalization and developing severe or critical illness has significantly increased. Machine learning and multivariate logistic regression analysis were used to predict risk factors and develop prognostic models for severe COVID-19 in hospitalized children with the Omicron variant in this study. Of the 544 hospitalized children including 243 and 301 in the mild and severe groups, respectively. Fever (92.3%) was the most common symptom, followed by cough (79.4%), convulsions (36.8%), and vomiting (23.2%). The multivariate logistic regression analysis showed that age (1-3 years old, odds ratio (OR): 3.193, 95% confidence interval (CI): 1.778-5.733], comorbidity (OR: 1.993, 95% CI:1.154-3.443), cough (OR: 0.409, 95% CI:0.236-0.709), and baseline neutrophil-to-lymphocyte ratio (OR: 1.108, 95% CI: 1.023-1.200), lactate dehydrogenase (OR: 1.993, 95% CI: 1.154-3.443), blood urea nitrogen (OR: 1.002, 95% CI: 1.000-1.003) and total bilirubin (OR: 1.178, 95% CI: 1.005-3.381) were independent risk factors for severe COVID-19. The area under the curve (AUC) of the prediction models constructed by multivariate logistic regression analysis and machine learning (RandomForest + TomekLinks) were 0.7770 and 0.8590, respectively. The top 10 most important variables of random forest variables were selected to build a prediction model, with an AUC of 0.8210. Compared with multivariate logistic regression, machine learning models could more accurately predict severe COVID-19 in children with Omicron variant infection.


Assuntos
COVID-19 , Criança Hospitalizada , Humanos , Criança , Lactente , Pré-Escolar , COVID-19/diagnóstico , Modelos Logísticos , SARS-CoV-2 , Tosse , Aprendizado de Máquina , Estudos Retrospectivos
17.
CNS Neurosci Ther ; 30(2): e14611, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38353051

RESUMO

AIMS: Basolateral amygdala (BLA), as a center for stress responses and emotional regulation, is involved in visceral hypersensitivity of irritable bowel syndrome (IBS) induced by stress. In the present study, we aimed to investigate the role of EphB2 receptor (EphB2) in BLA and explore the underlying mechanisms in this process. METHODS: Visceral hypersensitivity was induced by water avoidance stress (WAS). Elevated plus maze test, forced swimming test, and sucrose preference test were applied to assess anxiety- and depression-like behaviors. Ibotenic acid or lentivirus was used to inactivate BLA in either the induction or maintenance stage of visceral hypersensitivity. The expression of protein was determined by quantitative PCR, immunofluorescence, and western blot. RESULTS: EphB2 expression was increased in BLA in WAS rats. Inactivation of BLA or downregulation of EphB2 in BLA failed to induce visceral hypersensitivity as well as anxiety-like behaviors. However, during the maintenance stage of visceral pain, visceral hypersensitivity was only partially relieved but anxiety-like behaviors were abolished by inactivation of BLA or downregulation of EphB2 in BLA. Chronic WAS increased the expression of EphB2, N-methyl-D-aspartate receptors (NMDARs), and postsynaptic density protein (PSD95) in BLA. Downregulation of EphB2 in BLA reduced NMDARs and PSD95 expression in WAS rats. However, activation of NMDARs after the knockdown of EphB2 expression still triggered visceral hypersensitivity and anxiety-like behaviors. CONCLUSIONS: Taken together, the results suggest that EphB2 in BLA plays an essential role in inducing visceral hypersensitivity. In the maintenance stage, the involvement of EphB2 is crucial but not sufficient. The increase in EphB2 induced by WAS may enhance synaptic plasticity in BLA through upregulating NMDARs, which results in IBS-like symptoms. These findings may give insight into the treatment of IBS and related psychological distress.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Síndrome do Intestino Irritável , Dor Visceral , Animais , Ratos , Complexo Nuclear Basolateral da Amígdala/metabolismo , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/psicologia , Ratos Sprague-Dawley , Receptor EphB2/metabolismo , Estresse Psicológico/psicologia , Dor Visceral/metabolismo , Água/metabolismo
18.
Angew Chem Int Ed Engl ; : e202403926, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38414401

RESUMO

The solar-driven photocatalytic production of hydrogen peroxide (H2 O2 ) from water and oxygen using semiconductor catalysts offers a promising approach for converting solar energy into storable chemical energy. However, the efficiency of photocatalytic H2 O2 production is often restricted by the low photo-generated charge separation, slow surface reactions and inadequate stability. Here, we developed a mixed-linker strategy to build a donor-acceptor-acceptor (D-A-A) type covalent organic framework (COF) photocatalyst, FS-OHOMe-COF. The FS-OHOMe-COF structure features extended π-π conjugation that improves charge mobility, while the introduction of sulfone units not only as active sites facilitates surface reactions with water but also bolsters stability through increased interlayer forces. The resulting FS-OHOMe-COF has a low exciton binding energy, long excited-state lifetime and high photo-stability that leads to high performance for photocatalytic H2 O2 production (up to 1.0 mM h-1 ) with an H2 O2 output of 19 mM after 72 hours of irradiation. Furthermore, the catalyst demonstrates high stability, which sustained activity over 192 hours of photocatalytic experiment.

19.
Small ; : e2310359, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385806

RESUMO

Electrowetting displays (EWDs) based on microfluidics are highly sought after in the fields of electronic devices, smart homes, and information communication. However, the power supply of the EWD systems for visually engaging multi-color displays remains a big challenge. Herein, self-powered colorful dynamic display systems are developed by integrating the triboelectric nanogenerator (TENG) with the EWD device. The TENG is designed with a nanotube-patterned surface and can generate open-circuit voltages ranging from 30 to 295 V by controlling the contact area. The wetting property of the micro-droplet exhibits a response to the applied voltage, enabling the triboelectricity-triggered electrowetting-on-dielectric. Driven by the voltage of 160 V, the monochromatic EWD exhibits bright color switching from magenta to transparent with a pixel aperture ratio of 78%, and the recovery process can be rapidly completed. Furthermore, the self-powered colorful dynamic EWD system can be achieved. By selectively applying the voltage to the pixels in the three monochromatic layers that constitute the colorful EWD, the wetting properties of the fluids can be controlled, allowing for colorful dynamic display. This work contributes to the advancement of color display technology for portable and wearable electronic ink displays, indoor and outdoor sports equipment, and information communication.

20.
Ecotoxicol Environ Saf ; 273: 116115, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38377781

RESUMO

Triclosan (TCS) is a widely used synthetic, with broad-spectrum antibacterial properties found in both pharmaceuticals and personal care products. More specifically, it is hepatotoxic in rodents and exhibits differential effects in mice and humans. However, the mechanisms underlying TCS-induced liver toxicity have not been elucidated. This study examined the role of the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB)/ nod-like receptor protein 3 (NLRP3) pathway in TCS-exposed liver toxicity by established a long-life TCS-exposed mice liver injury model. The 24 C57BL/6 pregnant mice exposed to TCS (0, 50 and 100 mg/kg) every day during the gestation and nursing period. After weaning, the male mice were left to continue administrate with TCS until 8 weeks of age. Then, mice in each group were sacrificed for investigation. Long-life exposure to TCS resulted in a reduction of body weight in growth mice. TCS exposure caused the increase of serum ALT, AST and ALP. The situation of inflammatory cell infiltration, macrophage recruitment and collagen fiber deposition in TCS-exposed mice liver tissues were performed by histological analysis including hematoxylin-eosin, Masson, Sirius red, and immunohistochemistry staining. Protein expression levels in TLR4/NF-κB/NLRP3 pathway was measured through Western blot, and the NLRP3 inflammasome activation was measured using real-time quantitative PCR (RT-qPCR). The results showed that exposure to TCS elevated TLR4, myeloid differentiation factor 88 (Myd88), TNF receptor associated factor 6 (TRAF6), enhanced NF-κB activation, and affected NLRP3 inflammasome activation in mice liver. Collectively, these findings indicate that long-life exposure to TCS-induced mice by upregulating the TLR4-Myd88-TRAF6 pathway, activating the NF-κB signaling cascade, initiating the NLRP3 inflammasome pathway, and ultimately leading to liver injury, including inflammation, hepatocyte pyroptosis and hepatofibrosis. Henceforth, the TLR4/NF-κB/NLRP3 pathway may now provide a theoretical basis and valuable therapeutic targets for overcoming TCS-induced liver toxicity.


Assuntos
NF-kappa B , Triclosan , Humanos , Camundongos , Masculino , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Triclosan/toxicidade , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismo
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