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1.
Food Chem ; 367: 130727, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34371276

RESUMO

An electrochemical sensor was fabricated by modifying nanoporous gold (NPG)-coated glassy carbon electrode (NPG/GCE) with functionalized graphene oxide /chitosan/ionic liquid nanocomposites (fGO/CS/IL). The introduction of ionic liquid (IL) and chitosan (CS) induced higher dispersibility of functionalized graphene oxide (fGO), and was beneficial for the combination of fGO/CS/IL with NPG/GCE. As a result of the synergistic effect of NPG and fGO/CS/IL, the resulted functionalized graphene oxide/chitosan/ionic liquid nanocomposites/nanoporous gold /glassy carbon electrode (fGO/CS/IL/NPG/GCE) showed the highest redox peak current response signal of Amaranth (E123) due to ultrahigh surface area, electronic conductivity as well as the improvement of the surface structure. Under optimized conditions, the enhanced peak currents represented excellent analytical performance for detection of Amaranth in the concentration range from 8.0 to 1200.0 nM. Meanwhile, the fGO/CS/IL/NPG/GCE presented satisfactory sensitivity and selectivity, excellent reproducibility, and long-time stability. For practical applications, the fGO/CS/IL/NPG/GCE was validated for the determination of Amaranth in three types of drinks with satisfactory results.


Assuntos
Técnicas Biossensoriais , Quitosana , Grafite , Líquidos Iônicos , Nanocompostos , Nanoporos , Técnicas Eletroquímicas , Eletrodos , Ouro , Reprodutibilidade dos Testes
2.
Anesth Analg ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34748518

RESUMO

BACKGROUND: Results from previous studies evaluating the effects of remote ischemic preconditioning (RIPC) on morbidity and mortality after cardiac surgery are inconsistent. This meta-analysis of randomized controlled trials (RCTs) aims to determine whether RIPC improves cardiac and renal outcomes in adults undergoing cardiac surgery. METHODS: PubMed, EMBASE, and Cochrane Library were comprehensively searched to identify RCTs comparing RIPC with control in cardiac surgery. The coprimary outcomes were the incidence of postoperative myocardial infarction (MI) and the incidence of postoperative acute kidney injury (AKI). Meta-analyses were performed using a random-effect model. Subgroup analyses were conducted according to volatile only anesthesia versus propofol anesthesia with or without volatiles, high-risk patients versus non-high-risk patients, and Acute Kidney Injury Network (AKIN) or Kidney Disease Improving Global Outcomes (KDIGO) criteria versus other criteria for AKI diagnosis. RESULTS: A total of 79 RCTs with 10,814 patients were included. While the incidence of postoperative MI did not differ between the RIPC and control groups (8.2% vs 9.7%; risk ratio [RR] = 0.87, 95% confidence interval [CI], 0.76-1.01, P = .07, I2 = 0%), RIPC significantly reduced the incidence of postoperative AKI (22% vs 24.4%; RR = 0.86, 95% CI, 0.77-0.97, P = .01, I2 = 34%). The subgroup analyses showed that RIPC was associated with a reduced incidence of MI in non-high-risk patients, and that RIPC was associated with a reduced incidence of AKI in volatile only anesthesia, in non-high-risk patients, and in the studies using AKIN or KDIGO criteria for AKI diagnosis. CONCLUSIONS: This meta-analysis demonstrates that RIPC reduces the incidence of AKI after cardiac surgery. This renoprotective effect of RIPC is mainly evident during volatile only anesthesia, in non-high-risk patients, and when AKIN or KDIGO criteria used for AKI diagnosis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34793306

RESUMO

Currently, dialogue systems have attracted increasing research interest. In particular, background knowledge is incorporated to improve the performance of dialogue systems. Existing dialogue systems mostly assume that the background knowledge is correct and comprehensive. However, low-quality background knowledge is common in real-world applications. On the other hand, dialogue datasets with manual labeled background knowledge are often insufficient. To tackle these challenges, this article presents an algorithm to revise low-quality background knowledge, named background knowledge revising transformer (BKR-Transformer). By innovatively formulating the knowledge revising task as a sequence-to-sequence (Seq2Seq) problem, BKR-Transformer generates the revised background knowledge based on the original background knowledge and dialogue history. More importantly, to alleviate the effect of insufficient training data, BKR-Transformer introduces the ideas of parameter sharing and tensor decomposition, which could significantly reduce the number of model parameters. Furthermore, this work presents a background knowledge revising and incorporating dialogue model that combines the background knowledge revision with response selection in a unified model. Empirical analyses on real-world applications demonstrate that the proposed background knowledge revising and incorporating dialogue system (BKRI) could revise most low-quality background knowledge and substantially outperforms previous dialogue models.

4.
Cell Rep Med ; 2(11): 100448, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34723223

RESUMO

Activation of nucleic acid sensing Toll-like receptors (TLRs) in B cells is involved in antiviral responses by promoting B cell activation and germinal center responses. In order to take advantage of this natural pathway for vaccine development, synthetic pathogen-like antigens (PLAs) constructed of multivalent antigens with encapsulated TLR ligands can be used to activate B cell antigen receptors and TLRs in a synergistic manner. Here we report a PLA-based coronavirus disease 2019 (COVID-19) vaccine candidate designed by combining a phage-derived virus-like particle carrying bacterial RNA as TLR ligands with the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein as the target antigen. This PLA-based vaccine candidate induces robust neutralizing antibodies in both mice and non-human primates (NHPs). Using a NHP infection model, we demonstrate that the viral clearance is accelerated in vaccinated animals. In addition, the PLA-based vaccine induces a T helper 1 (Th1)-oriented response and a durable memory, supporting its potential for further clinical development.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34847074

RESUMO

Purpose: Our study aims to explore the impact of non-invasive ventilation (NIV) alone or combined with montelukast on clinical efficiency and pulmonary function (PF) in treating patients with bronchial asthma complicated by obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: A total of 386 patients with bronchial asthma underwent sleep monitoring. Patients were divided into 3 groups according to the different treatment methods. The changes in PF, apnea hypopnea index (AHI) score and the level of inflammatory factors in all patients before and after treatment were recorded, and the clinical effect following treatment was noted. Results: Following treatment, the clinical efficiency of Group 2 was significantly better than that of both Group 1and the control group, and the therapeutic effect in Group 1 was better than in the control group (P < .05). Before treatment, vital capacity (VC), peak expiratory flow (PEF), forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) and asthma control test (ACT) scores, AHI scores, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) index were compared between the 3 groups (P > .05). In contrast, after treatment the VC, PEF, FEV1/FVC and ACT, AHI, CRP and TNF-α scores and the IL-6 index in the 3 groups were improved compared with before treatment. The indices in Groups 1 and 2 were better than in the control group, and the VC, PEF, FEV1/FVC and ACT, AHI, CRP, and TNF-α scores and IL-6 index in Group 2 reported greater beneficial effect than in Group 1. Conclusion: The combination of NIV and montelukast exerts a beneficial effect in treating patients with bronchial asthma complicated with OSAHS, which holds the potential of effectively improving clinical symptoms and PF, reducing ACT and AHI scores and alleviating inflammatory reactions. Hence, the combination is valid and appropriate for clinical application.

6.
Front Med (Lausanne) ; 8: 745931, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805214

RESUMO

Purpose: This study aimed to develop a radiomics score (Rad-score) extracted from liver and spleen CT images in cirrhotic patients to predict the probability of esophageal variceal rebleeding. Methods: In total, 173 cirrhotic patients were enrolled in this retrospective study. A total of 2,264 radiomics features of the liver and spleen were extracted from CT images. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select features and generate the Rad-score. Then, the Rad-score was evaluated by the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Kaplan-Meier analysis was used to assess the risk stratification ability of the Rad-score. Results: Rad-scoreLiver, Rad-scoreSpleen, and Rad-scoreLiver-Spleen were independent risk factors for EV rebleeding. The Rad-scoreLiver-Spleen, which consisted of ten features, showed good discriminative performance, with C-indexes of 0.853 [95% confidence interval (CI), 0.776-0.904] and 0.822 (95% CI, 0.749-0.875) in the training and validation cohorts, respectively. The calibration curve showed that the predicted probability of rebleeding was very close to the actual probability. DCA verified the usefulness of the Rad-scoreLiver-Spleen in clinical practice. The Rad-scoreLiver-Spleen showed good performance in stratifying patients into high-, intermediate- and low-risk groups in both the training and validation cohorts. The C-index of the Rad-scoreLiver-Spleen in the hepatitis B virus (HBV) cohort was higher than that in the non-HBV cohort. Conclusion: The radiomics score extracted from liver and spleen CT images can predict the risk of esophageal variceal rebleeding and stratify cirrhotic patients accordingly.

7.
Chin Med J (Engl) ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34839316

RESUMO

BACKGROUND: Prospective analyses have yet to identify a consistent relationship between sleep duration and the incidence of gastrointestinal (GI) cancers. The effect of changes in sleep duration on GI cancer incidence has scarcely been studied. Therefore, we aimed to examine the association between baseline sleep duration and annual changes in sleep duration and GI cancer risk in a large population-based cohort study. METHODS: A total of 123,495 participants with baseline information and 83,511 participants with annual changes in sleep duration information were prospectively observed from 2006 to 2015 for cancer incidence. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and their confidence intervals (CIs) for GI cancers according to sleep duration and annual changes in sleep duration. RESULTS: In baseline sleep duration analyses, short sleep duration (≤5 h) was significantly associated with a lower risk of GI cancer in females (HR: 0.31, 95% CI: 0.10-0.90), and a linear relationship between baseline sleep duration and GI cancer was observed (P = 0.010), especially in males and in the >50-year-old group. In the annual changes in sleep duration analyses, with stable category (0 to -15 min/year) as the control group, decreased sleep duration (≤-15 min/year) was significantly associated with the development of GI cancer (HR: 1.29; 95% CI: 1.04-1.61), especially in the >50-year-old group (HR: 1.32; 95% CI: 1.01-1.71), and increased sleep duration (>0 min/year) was significantly associated with GI cancer in females (HR: 2.89; 95% CI: 1.14-7.30). CONCLUSIONS: Both sleep duration and annual changes in sleep duration were associated with the incidence of GI cancer.

8.
J Pain Res ; 14: 3573-3581, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815710

RESUMO

Purpose: Patients undergoing major laparoscopic surgery often experience significant pain and postoperative nausea and vomiting (PONV). Deep neuromuscular block (NMB) improves surgical conditions and facilitates the application of low intra-abdominal pressure (IAP), which may be beneficial for these patients. This study is designed to determine the effects of deep NMB combined with low IAP, as compared to moderate NMB combined with standard IAP, on patients' nociceptive recovery after major laparoscopic gastrointestinal surgery. Study Design and Methods: This single-center randomized controlled trial will include 220 patients scheduled for major laparoscopic gastrointestinal surgery (lasts for ≥ 90 minutes). Patients will be randomly assigned, with a 1:1 ratio, into a deep NMB + low IAP group (train of four = 0, post-tetanic count = 1-3, IAP = 8 mmHg) and a moderate NMB + standard IAP group (train of four = 1-3, IAP = 12 mmHg). If the surgical workspace is inadequate, the surgeons can request a step increase of 1 mmHg in IAP during 3-min intervals. The upper limit of IAP will be set at 15 mmHg. Postoperative recovery will be assessed using the postoperative quality recovery scale (PQRS). The primary outcome of this trial is the PQRS nociceptive recovery (including pain and PONV) at postoperative day (POD) 1. The secondary outcomes include recovery in other PQRS domains at POD 1, and recovery in all PQRS domains in a post-anesthesia care unit, at POD 3 in the surgical wards, at hospital discharge, and at postoperative 30 days. For the sample size estimation, 110 patients in each group (220 in total) would be needed to detect an absolute increase rate of 20% in the PQRS nociceptive domain in the deep NMB + low IAP group at POD 1. Discussion: This study investigates the effects of deep NMB combined with low IAP on postoperative PQRS nociceptive recovery in patients undergoing major laparoscopic gastrointestinal surgery. We expect that this deep NMB + low IAP strategy would improve postoperative pain and PONV following major laparoscopic gastrointestinal surgery.

9.
Front Surg ; 8: 757085, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778364

RESUMO

Background: The current study analyzed resected stage I-IIIA pulmonary lymphoepithelioma-like carcinoma (LELC) cases to define the clinical characteristics, prognosis and long-term outcomes of resected LELC, with the purpose of guiding clinical management for this rare tumor. Methods: Resected stage I-IIIA LELC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC) cases from our center were enrolled. Propensity score matching (PSM) was applied to minimize the selection bias. Overall survival (OS) and disease-free survival (DFS) were compared between groups. Multivariate analyses were performed to identify the prognostic factors, and a nomogram was developed. Results: A total of 159 LELCs, 2,757 ADCs, and 1,331 SCCs were included. LELC, dominated among younger patients and non-smokers. LELC was a poorly differentiated disease that lacked driver gene mutations and was positive for immunohistochemistry indicators of squamous cell lineage. Survival analyses revealed that OS was significantly better for LELC than for other common non-small cell lung cancers (NSCLCs) both before PSM (all P < 0.001) and after PSM (all P < 0.05). Further analyses revealed that early pathological node stage and preoperative albumin level ≥35 were identified as independent prognostic factors favoring OS and DFS. Conclusions: LELC, dominated among younger and non-smoking populations, lacked driver gene mutations and was positive for immunohistochemistry indicators of squamous cell lineage. The survival outcome of LELC was better than other common NSCLCs.

10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1577-1581, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627443

RESUMO

OBJECTIVE: To investigate the effect of enhanced autophagy in megakaryocyte to proplatelet formation in children with immune thrombocytopenia(ITP). METHODS: Giemsa staining and immunofluorescence staining were used to observe megakaryocyte morphology and proplatelet formation, Western blot was used to determine the expression of cytoskeleton protein and autophagy related protein. Autophagr regulation drugs Rap or 3-MA was used to regulate autophagy of megakaryocytes. RESULTS: Some vacuole-like structures was found in ITP megakaryocytes of the children, the expression of LC3II/I (ITP 1.32±0.18; Ctrl 0.49±0.16,P<0.05) and Atg5-Atg12 (ITP 0.69±0.17; Ctrl 0.12±0.08,P<0.05) was significantly higher in ITP children as compared with those in control group. The immu- nofluorescence staining showed that the cytoskeleton arrangement in megakaryocytes of ITP children was abnormal, and the phosphorylation of myosin light chain was also increased(ITP 0.74±0.09, Ctrl 0.05±0.02,P<0.05). In vitro, inducer or inhibitor of autophagy could regulate the production of proplatelet and the expression of cell cycle related protein, including CyclinD1(Veh 1.08±0.12; Rap 0.46±0.04; Rap+3-MA 0.70±0.03), CyclinD2(Veh 0.47±0.04; Rap 0.27±0.04; Rap+3-MA 0.41±0.03), P21(Veh 0.15±0.01; Rap 0.04±0.01; Rap+3-MA 0.05±0.01). CONCLUSION: Enhanced autophagy is the key factor of poor proplatelet formation in megakaryocytes of ITP children.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Autofagia , Plaquetas , Humanos , Megacariócitos
12.
Front Pharmacol ; 12: 720368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690763

RESUMO

The Na+/K+-ATPase α1 subunit (ATP1A1) is a potential target for hepatic carcinoma (HCC) treatment, which plays a key role in Na+/K+ exchange, metabolism, signal transduction, etc. In vivo, we found that Panax notoginseng saponins (PNS) could inhibit tumor growth and significantly downregulate the expression and phosphorylation of ATP1A1/AKT/ERK in tumor-bearing mice. Our study aims to explore the potential effects of PNS on the regulation of ATP1A1 and the possible mechanisms of antitumor activity. The effects of PNS on HepG2 cell viability, migration, and apoptosis were examined in vitro. Fluorescence, Western blot, and RT-PCR analyses were used to examine the protein and gene expression. Further analysis was assessed with a Na+/K+-ATPase inhibitor (digitonin) and sorafenib in vitro. We found that the ATP1A1 expression was markedly higher in HepG2 cells than in L02 cells and PNS exhibited a dose-dependent effect on the expression of ATP1A and the regulation of AKT/ERK signaling pathways. Digitonin did not affect the expression of ATP1A1 but attenuated the effects of PNS on the regulation of ATP1A1/AKT/ERK signaling pathways and enhanced the antitumor effect of PNS by promoting nuclear fragmentation. Taken together, PNS inhibited the proliferation of HepG2 cells via downregulation of ATP1A1 and signal transduction. Our findings will aid a data basis for the clinical use of PNS.

13.
Cell Chem Biol ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34715056

RESUMO

Efforts to target glucose metabolism in cancer have been limited by the poor potency and specificity of existing anti-glycolytic agents and a poor understanding of the glucose dependence of cancer subtypes in vivo. Here, we present an extensively characterized series of potent, orally bioavailable inhibitors of the class I glucose transporters (GLUTs). The representative compound KL-11743 specifically blocks glucose metabolism, triggering an acute collapse in NADH pools and a striking accumulation of aspartate, indicating a dramatic shift toward oxidative phosphorylation in the mitochondria. Disrupting mitochondrial metabolism via chemical inhibition of electron transport, deletion of the malate-aspartate shuttle component GOT1, or endogenous mutations in tricarboxylic acid cycle enzymes, causes synthetic lethality with KL-11743. Patient-derived xenograft models of succinate dehydrogenase A (SDHA)-deficient cancers are specifically sensitive to KL-11743, providing direct evidence that TCA cycle-mutant tumors are vulnerable to GLUT inhibitors in vivo.

14.
Phytomedicine ; 93: 153779, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34638030

RESUMO

BACKGROUND: Gansui-Banxia Decoction (GSBXD) is a classic formula of traditional Chinese medical (TCM) sage Zhang Zhongjing to treat stagnation of evil heat and obstruction of qi. At present GSBXD is wildly used to treat cancerous ascites, pleural effusion, peritoneal effusion, pericardial effusion, cranial cavity effusion and several types of cancers, such as hepatocellular carcinoma (HCC) and esophageal cancer. Myeloid-derived suppressor cells (MDSCs) are a kind of immature and heterogeneous cells which can suppress lymphocytes activation by forming a suppressive environment. MDSCs accumulation in peripheral blood and tumors are closely related to the cancer stage and low survival rate of clinical patients. The antitumor immune effect of GSBXD has not received widespread attention. PURPOSE: To investigate the effects of GSBXD on MDSCs accumulation and the mediators including AKT/STAT3/ERK signaling pathways. METHODS: The chemical components of GSBXD were analyzed by UHPLC-MS, and the putative pathways of GSBXD based on Network pharmacology were predicted. Mice were vaccinated with Hepatoma 22 (H22) to establish tumor growth model, which were then administrated with GSBXD ethanol extraction (0.49 mg/kg/day, 1.75 mg/kg/day), sorafenib (60 mg/kg) or saline for 14 days. The cell morphology was evaluated by hematoxylin and eosin (H&E) staining, and immunity cells were determined through flowcytometry analysis. The levels of cytokines production in blood were evaluated by using ELISA kits. STAT3, ERK and AKT/mTOR signaling transduction associated proteins were determined by Western blot. RESULTS: GSBXD could inhibit tumor growth and splenomegaly in H22 tumor model mice. Importantly, GSBXD reduced MDSCs accumulation and differentiation, and inhibited proliferation of F4/80+ CD11b+ macrophages and apoptosis of T cells and B cells, and increased the percentage of CD 3- NK1.1+ NK cells. To better understand the active component of GSBXD, the ethanol-extraction powdered GSBXD was prepared and analyzed by UHPLC-MS. Combined with these main chemical compounds, we predicted that the anti-tumor effect of GSBXD mainly mediated PI3K-AKT and RAS-MAPK signal pathways based on Network Pharmacology. Western blot analysis of tumor tissues and MDSCs cells demonstrated that phosphorylation of AKT, ERK and STAT3 were significantly reduced, specially the activation of ERK. The levels of IL-1ß and IFN-γ were significantly decreased by ELISA analysis. CONCLUSION: GSBXD exhibited antitumor immune activity by reducing the accumulation of MDSCs in vivo, which is possible via down-regulation of AKT/STAT3/ERK signaling pathway and suppression of IL-1ß and IFN-γ.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Supressoras Mieloides , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Células Supressoras Mieloides/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3 , Transdução de Sinais
16.
JAMA Netw Open ; 4(10): e2128886, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34648009

RESUMO

Importance: Postoperative ileus is common after abdominal surgery, and small clinical studies have reported that intraoperative administration of dexmedetomidine may be associated with improvements in postoperative gastrointestinal function. However, findings have been inconsistent and study samples have been small. Further examination of the effects of intraoperative dexmedetomidine on postoperative gastrointestinal function is needed. Objective: To evaluate the effects of intraoperative intravenous dexmedetomidine vs placebo on postoperative gastrointestinal function among older patients undergoing abdominal surgery. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at the First Affiliated Hospital of Anhui Medical University in Hefei, China (lead site), and 12 other tertiary hospitals in Anhui Province, China. A total of 808 participants aged 60 years or older who were scheduled to receive abdominal surgery with an expected surgical duration of 1 to 6 hours were enrolled. The study was conducted from August 21, 2018, to December 9, 2019. Interventions: Dexmedetomidine infusion (a loading dose of 0.5 µg/kg over 15 minutes followed by a maintenance dose of 0.2 µg/kg per hour) or placebo infusion (normal saline) during surgery. Main Outcomes and Measures: The primary outcome was time to first flatus. Secondary outcomes were postoperative gastrointestinal function measured by the I-FEED (intake, feeling nauseated, emesis, physical examination, and duration of symptoms) scoring system, time to first feces, time to first oral feeding, incidence of delirium, pain scores, sleep quality, postoperative nausea and vomiting, hospital costs, and hospital length of stay. Results: Among 808 patients enrolled, 404 were randomized to receive intraoperative dexmedetomidine, and 404 were randomized to receive placebo. In total, 133 patients (60 in the dexmedetomidine group and 73 in the placebo group) were excluded because of protocol deviations, and 675 patients (344 in the dexmedetomidine group and 331 in the placebo group; mean [SD] age, 70.2 [6.1] years; 445 men [65.9%]) were included in the per-protocol analysis. The dexmedetomidine group had a significantly shorter time to first flatus (median, 65 hours [IQR, 48-78 hours] vs 78 hours [62-93 hours], respectively; P < .001), time to first feces (median, 85 hours [IQR, 68-115 hours] vs 98 hours [IQR, 74-121 hours]; P = .001), and hospital length of stay (median, 13 days [IQR, 10-17 days] vs 15 days [IQR, 11-18 days]; P = .005) than the control group. Postoperative gastrointestinal function (as measured by the I-FEED score) and delirium incidence were similar in the dexmedetomidine and control groups (eg, 248 patients [72.1%] vs 254 patients [76.7%], respectively, had I-FEED scores indicating normal postoperative gastrointestinal function; 18 patients [5.2%] vs 12 patients [3.6%] had delirium on postoperative day 3). Conclusions and Relevance: In this randomized clinical trial, the administration of intraoperative dexmedetomidine reduced the time to first flatus, time to first feces, and length of stay after abdominal surgery. These results suggest that this therapy may be a viable strategy to enhance postoperative recovery of gastrointestinal function among older adults. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800017232.

17.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(5): 493-500, 2021 Oct 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34636195

RESUMO

YAP/TAZ are wild over-activated in head and neck squamous cell carcinoma (HNSCC) with high potential as a direct therapy target for HNSCC treatments. However, the efforts on the directly targeting-YAP/TAZ therapies over the past decade, have very limited impacts, mainly caused by: 1. There is still none effective and specific YAP/TAZ inhibitor with clinical potential; 2. YAP/TAZ might not be directly targeted, because of their multiple important biological functions, such as: regulation of cell proliferation and survival, stem cell maintain, regulation of organ development, organ size control, and tissue regeneration. Interestingly, the over-activation of YAP/TAZ in HNSCC mainly be regulated by upstream abnormal molecular or biological events, instead of genes alteration of YAP/TAZ. Therefore, exploring the alternative molecular events regulating YAP/TAZ activation and molecular mechanism in HNSCC might help to uncover novel indirect targets of YAP/TAZ therapies for HNSCC prevention and treatment.


Assuntos
Neoplasias de Cabeça e Pescoço , Fosfoproteínas , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Humanos , Fosfoproteínas/metabolismo , Transativadores/metabolismo , Fatores de Transcrição
18.
J Fungi (Basel) ; 7(10)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34682279

RESUMO

Magnaporthe oryzae, a fungal pathogen that causes rice blast, which is the most destructive disease of rice worldwide, has the potential to perform both asexual and sexual reproduction. MAT loci, consisting of MAT genes, were deemed to determine the mating types of M. oryzae strains. However, investigation was rarely performed on the development and molecular mechanisms of the sexual reproduction of the fungus. In the present work, we analyzed the roles of two MAT loci and five individual MAT genes in the sex determination, sexual development and pathogenicity of M. oryzae. Both of the MAT1-1 and MAT1-2 loci are required for sex determination and the development of sexual structures. MAT1-1-1, MAT1-1-3 and MAT1-2-1 genes are crucial for the formation of perithecium. MAT1-1-2 impacts the generation of asci and ascospores, while MAT1-2-2 is dispensable for sexual development. A GFP fusion experiment indicated that the protein of MAT1-1-3 is distributed in the nucleus. However, all of the MAT loci or MAT genes are dispensable for vegetative growth, asexual reproduction, pathogenicity and pathogenicity-related developments of the fungus, suggesting that sexual reproduction is regulated relatively independently in the development of the fungus. The data and methods of this work may be helpful to further understand the life cycle and the variation of the fungus.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34704324

RESUMO

The construction of single-atom catalysts (SACs) with high single atom densities, favorable electronic structures and fast mass transfer is highly desired. We have utilized metal-triazolate (MET) frameworks, a subclass of metal-organic frameworks (MOFs) with high N content, as precursors since they can enhance the density and regulate the electronic structure of single-atom sites, as well as generate abundant mesopores simultaneously. Fe single atoms dispersed in a hierarchically porous N-doped carbon matrix with high metal content (2.78 wt %) and a FeN4 Cl1 configuration (FeN4 Cl1 /NC), as well as mesopores with a pore:volume ratio of 0.92, were obtained via the pyrolysis of a Zn/Fe-bimetallic MET modified with 4,5-dichloroimidazole. FeN4 Cl1 /NC exhibits excellent oxygen reduction reaction (ORR) activity in both alkaline and acidic electrolytes. Density functional theory calculations confirm that Cl can optimize the adsorption free energy of Fe sites to *OH, thereby promoting the ORR process. The catalyst demonstrates great potential in zinc-air batteries. This strategy selects, designs, and adjusts MOFs as precursors for high-performance SACs.

20.
Signal Transduct Target Ther ; 6(1): 328, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471088

RESUMO

Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- and interleukin 6 (IL-6)-secreting cells and C-X-C motif chemokine receptor 3 (CXCR3)+ cells in lung tissue of old RMs. This pathological pattern, which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens, was significantly correlated with the systemic accumulation of CXCR3+ cells in lungs, spleens, and peripheral blood. Furthermore, the ratio of CXCR3+ to T-box protein expression in T cell (T-bet)+ (CXCR3+/T-bet+ ratio) in CD8+ cells may be used as a predictor of severe COVID-19. These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+ cells in predicting severe COVID-19.


Assuntos
Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Microambiente Celular/imunologia , Pulmão/imunologia , Receptores CXCR3/imunologia , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/imunologia , Animais , Linfócitos T CD8-Positivos/patologia , COVID-19/patologia , Modelos Animais de Doenças , Inflamação/imunologia , Inflamação/patologia , Interferon-alfa/imunologia , Interleucina-6/imunologia , Pulmão/patologia , Pulmão/virologia , Macaca mulatta , Masculino
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