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1.
J Environ Manage ; 325(Pt A): 116597, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36308785

RESUMO

Currently, the influence of elevated atmospheric CO2 concentration (eCO2) on ammonia oxidation to nitrite, the rate-limiting step of nitrification in paddy soil, is poorly known. Previous studies that simulate the effect of eCO2 on nitrification are primarily based on an abrupt increase of atmospheric CO2 concentration. However, paddy ecosystems are experiencing a gradual increase of CO2 concentration. To better understand how the nitrification potential, abundance and communities of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) respond to eCO2 in paddy ecosystems, a field experiment was conducted using the following two treatments: a gradual increase of CO2 (EC, increase of 40 ppm per year until 200 ppm above ambient) and ambient CO2 (CK). The results demonstrated that the EC treatment significantly (P < 0.05) stimulated the soil potential nitrification rate (PNR) at the jointing and milky stages, which increased by 127.83% and 27.35%, respectively, compared with CK. Furthermore, the EC treatment significantly (P < 0.05) stimulated the AOA and AOB abundance by 56.60% and 133.84%, respectively, at the jointing stage. Correlation analysis showed that the PNR correlated well with the abundance of AOB (R2 = 0.7389, P < 0.001). In addition, the EC treatment significantly (P < 0.05) altered the community structure of AOB, while it had little effect on that of AOA. A significant difference in the proportion of Nitrosospira was observed between CO2 treatments. In conclusion, the gradual increase of CO2 positively influenced the PNR and abundance of ammonia oxidizers, and AOB could be more important than AOA in nitrification under eCO2.


Assuntos
Betaproteobacteria , Nitrificação , Amônia , Dióxido de Carbono , Microbiologia do Solo , Ecossistema , Archaea , Solo/química , Oxirredução , Filogenia
2.
Bioact Mater ; 22: 180-200, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36246664

RESUMO

Rare earth elements (REEs) have been long applied in magnesium alloys, among which the mischmetal-containing WE43 alloy has already got the CE mark approval for clinical application. A considerable amount of REEs (7 wt%) is needed in that multi-phased alloy to achieve a good combination of mechanical strength and corrosion resistance. However, the high complex RE addition accompanied with multiple second phases may bring the concern of biological hazards. Single-phased Mg-RE alloys with simpler compositions were proposed to improve the overall performance, i.e., "Simpler alloy, better performance". The single-phased microstructure can be successfully obtained with typical high-solubility REEs (Ho, Er or Lu) through traditional smelting, casting and extrusion in a wide compositional range. A good corrosion resistance with a macroscopically uniform corrosion mode was guaranteed by the homogeneously single-phased microstructure. The bimodal-grained structure with plenty of sub-grain microstructures allow us to minimize the RE addition to <1 wt%, without losing mechanical properties. The single-phased Mg-RE alloys show comparable mechanical properties to the clinically-proven Mg-based implants. They exhibited similar in-vitro and in-vivo performances (without local or systematic toxicity in SD-rats) compared to a high purity magnesium. In addition, metal elements in our single-phased alloys can be gradually excreted through the urinary system and digestive system, showing no consistent accumulation of RE in main organs, i.e., less burden on organs. The novel concept in this study focuses on the simplification of Mg-RE based alloys for biomedical purpose, and other biodegradable metals with single-phased microstructures are expected to be explored.

3.
Lancet Haematol ; 9(12): e930-e941, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36455608

RESUMO

Chimeric antigen receptor (CAR) T-cell therapies have achieved remarkable success in the treatment of haematological malignancies. Over the past 9 years, the use of CAR T-cell therapies has expanded throughout China, from the first clinical trials of CAR T cells conducted in 2013, to the world's largest number of CAR T-cell-related clinical trials in 2017, to a cumulative US$2·37 billion in funding for cell therapy companies in 2021, and a significant growth in the number of CAR T-cell-related clinical trials and basic research. This strong increase in activity is the result of a culmination of factors in China: strong government support, capital inflow, large patient demand, a unique health-care system, and the efforts of Chinese physicians and scientists. This Series paper provides an overview of the scope of CAR T-cell clinical trials in China (especially in the field of haematological malignancies), analyses the relevant policies, summarises the characteristics of corporate and capital support, and explores the achievements and challenges of CAR T-cell therapy in China to provide a better understanding for further promoting the development of cellular therapy and its clinical application.

4.
Chemosphere ; : 137431, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36455656

RESUMO

Despite the longstanding evidence on the effect of air pollutants on preterm birth (PTB), few studies have focused on its subtypes, including spontaneous preterm birth (sPTB) and medically indicated preterm birth (miPTB). Most studies evaluated only the short-term or long-term effects of particulate matter (PM) on PTB. Thus, we designed this study, based on a cohort of 179,385 women, to evaluate both short- and long-term effects of PM with diameter <2.5 µm and <10 µm (PM2.5 and PM10) on PTB, sPTB and miPTB in Shanghai. Generalized additive models (GAMs) were applied to evaluate short-term effects. Lagged effects were identified using different lag structures. Exposure-response correlation curves were plotted using GAMs after adjustment for confounders. ORs and 95% CIs were calculated using logistic regression to estimate the long-term effect after adjustment for confounders. There was 5.67%, 3.70% and 1.98% daily incidence of PTB, sPTB, and miPTB on average. Every 10 µg/m3 increase in PM2.5 and PM10 was positively associated with PTB and sPTB at lag 2 day. The exposure-response curves (lag 2 day) indicated a rapid increase in sPTB for PM2.5 and a linear increase for PM10, in PTB for PM2.5 and PM10 at concentrations over 100 µg/m3. Regarding long-term exposure, positive associations were found between 10 µg/m3 increases in PM2.5 and PM10 in 3rd trimester and greater odds of sPTB (aOR: 1.042, 95% CI: 1.018-1.065, and 1.018, 95% CI:1.002-1.034), and during the 3 months before conception and miPTB (aOR: 1.023, 95% CI: 1.003-1.042, and 1.017, 95% CI: 1.000-1.036). Acute exposure to PM2.5 and PM10 at lag 2 day and chronic exposure in 3rd trimester was significantly associated with sPTB, while miPTB was related to chronic exposure during the 3 months before pregnancy. These findings indicate that susceptibility windows of PM exposure can be influenced by different underlying etiologies of PTB.

6.
Tob Induc Dis ; 20: 97, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407938

RESUMO

INTRODUCTION: Smoking cessation is an efficient approach to reducing disease burden. Traditional Chinese Medicine (TCM) therapies such as acupuncture, acupressure, and herbal drugs are often used to help quit smoking. However, there is a lack of overarching bibliometric analysis of the clinical research on smoking cessation focusing on TCM. The aim of our study is to explore the current patterns and trends of TCM therapy for smoking cessation through bibliometric methods with visual presentation. METHODS: This study is an assessment of academic publications retrieved from the Scopus database on smoking cessation using TCM therapy published in the period 2005-2021. Sankey diagram, word-cloud, network analysis, thematic maps, tree-maps, and the collaborative work of authors, institutions and countries, were used to identify research trends on TCM therapy for smoking cessation. The total cited index and H-index (for journals, authors, countries, organizations) were used to identify the trends of worldwide development by R Package and Excel 2016. RESULTS: There was an upward trend, with some fluctuations, of 1908 articles from 2005 to 2021. The most productive country was China. The top institution in this field was Beijing University. The dominant author that contributed to TCM therapy for smoking cessation was Wang Y, who has the highest H-Index. The most productive cited journals were Evidence-Based Complementary and Alternative Medicines and the Chinese Journal of Clinical Rehabilitation. Liu L, (2011, STROKE) had the highest centrality. The keywords 'acupuncture', 'traditional Chinese medicine', 'colitis', 'hypertension', 'chronic obstructive pulmonary disease', 'risk factors' and 'alternative medicine' ranked highest in frequency. The diseases of healthy people concerned mainly cardiovascular, cancer, diabetes, hypertension and pregnancy. The diseases of the patients concerned mainly cancer, diabetes, hematopathy, stroke, cardiovascular, diabetes, lung disease, and hypertension. Treatment methods were mainly traditional Chinese medicine and acupuncture. The research methods mainly included randomized controlled trials that were multi-center and double-blind. CONCLUSIONS: A substantial number of articles on TCM therapy for smoking cessation, mainly focusing on TCM and acupuncture were identified. It is worth noting that research that focused on TCM therapy for smoking cessation also was related to COVID-19.

7.
J Cardiothorac Surg ; 17(1): 287, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36384539

RESUMO

BACKGROUND: Tracheoesophageal fistula (TEF) is a rare but life-threatening complication after esophagectomy. A new gastrointestinal occluder device provides treatment for TEF patients. However, TEF-related pneumonia and respiratory failure increase the difficulty of anesthesia management, especially in airway management. CASE PRESENTATION: A 64-year-old man with thoracic esophageal cancer underwent esophagectomy and gastric tube reconstruction one year ago. The patient presented with recurrent cough and sputum after surgery. Gastroscopy revealed a fistula between the esophagogastric anastomotic site and membrane of the trachea. Therefore, the patient received implantation of a new gastrointestinal occluder device under gastroscopy combined with tracheoscopy. Airway management under general anesthesia was discussed with an interdisciplinary decision, and cuffed endotracheal tube with an inner diameter of 5.5 mm was chosen. This airway management ensured adequate oxygenation during the operation and provided sufficient space for the operation of the tracheoscope in the trachea. Finally, the TEF disappeared after the operation, and the patient was administered an oral diet on the first postoperative day. CONCLUSIONS: The implantation of a new gastrointestinal occluder device under gastroscopy combined with tracheoscopy provides a new treatment for TEF patients. This case report suggests that it is important to select an endotracheal tube with an appropriate inner diameter that can not only meet the requirements of ventilation but also does not affect the operation of tracheoscopy in the trachea.


Assuntos
Anestesia , Fístula Traqueoesofágica , Masculino , Humanos , Pessoa de Meia-Idade , Fístula Traqueoesofágica/cirurgia , Fístula Traqueoesofágica/etiologia , Traqueia , Intubação Intratraqueal/efeitos adversos , Esofagectomia/efeitos adversos
8.
Transplant Cell Ther ; 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36402457

RESUMO

Between 2020 and 2021, 31,525 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) throughout mainland China. In this report, we describe the activity and current trends for HSCT in China during the SARS-CoV-2 pandemic. In 2020, a total of 13,415 cases of HSCT were reported from 166 transplant teams, and 75% (10,042 cases) were allogeneic HSCTs. In 2021, a total of 18,110 cases of HSCT were reported from 174 transplant teams, and 70% (12,744 cases) were allogeneic HSCTs. Haploidentical donor (HID) transplantation accounted for 63% (7977 cases) of allogeneic HSCTs in 2021. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (AML) (37%) and acute lymphoblastic leukemia (ALL) (23%), and the largest proportion of nonmalignant disease comprised aplastic anemia (AA) (13%). The PB stem cell source accounted for 41% of HIDs and 75% of MSDs. The BuCy-based regimen (57%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu-based regimen (28%) and TBI-based regimen (11%). This survey provides comprehensive information about the current activities and might benefit clinical physicians' decision planning for HSCT.

9.
Adv Mater ; : e2207447, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36353895

RESUMO

Synthesis of large-area patterned MoS2 is considered the principle base for realizing high-performance MoS2 -based flexible electronic devices. Patterning and transferring MoS2 films to target flexible substrates, however, require conventional multi-step photolithography patterning and transferring process, despite tremendous progress in the facilitation of practical applications. Herein, we report an approach to directly synthesize large-scale MoS2 patterns that combines inkjet printing and thermal annealing. We prepare an optimal precursor ink that can deposit arbitrary patterns on polyimide films. By introducing a gas atmosphere of Ar/H2 , thermal treatment at 350°C enables an in-situ decomposition and crystallization in the patterned precursors and, consequently, results in the formation of MoS2 . Without complicated processes, patterned MoS2 is obtained directly on polymer substrate, exhibiting superior mechanical flexibility and durability (∼2% variation in resistance over 10,000 bending cycles) as well as excellent chemical stability, which we attribute to the generated continuous and thin microstructures as well as their strong adhesion with the substrate. As a step further, we employ this approach to manufacture various flexible sensing devices that are insensitive to body motions and moisture, including temperature sensors and biopotential sensing systems for real-time, continuously monitoring skin temperature, electrocardiography, and electromyography signals. This article is protected by copyright. All rights reserved.

10.
Ann Hematol ; 101(12): 2731-2741, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36318288

RESUMO

The use of Bcl-2 inhibitor Venetoclax (VEN) combined with hypomethylating agents or chemotherapy has shown efficacy in treating acute myeloid leukemia (AML) as frontline treatment and for relapse, allowing more patients to bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the influence of VEN-based therapy on the prognosis of subsequent allogeneic HSCT remains unknown. We retrospectively collected data from patients who proceeded to allo-HSCT between November 2018 and November 2020 after VEN-based therapy at five transplant centers in Zhejiang Province, China. A total of 39 patients were analyzed. Thirty-one patients were diagnosed with AML (28 de novo, 3 secondary to MDS), 6 with MDS, and 2 with CMML. The majority (74.4%) of patients received VEN-based therapy for the treatment of relapse (38.5%) or refractory disease (35.9%); 5 (12.8%) received it as an initial treatment, and 5 (12.8%) patients who were already in complete remission (CR) received VEN for further consolidation or deep remission before HSCT. Twenty-seven (69.2%) patients were in CR at the time of HSCT. Day + 100 cumulative incidences of grade I-IV acute graft-versus-host disease (aGVHD) and grade II-IV aGVHD were 43.6% and 15.4%, respectively. Of 34 evaluable patients, 6.4% and 25.6% developed chronic GVHD at 1 year and 2 years. The 100-day cytomegalovirus (CMV) reactivation occurred in 76.3% of patients and Epstein-Barr virus (EBV) reactivation occurred in 29.7% of patients. With a median follow-up of 14.7 months, overall survival, progression-free survival, relapse, and non-relapse mortality incidence at 1 year were 75.5%, 61.6%, 16.7%, and 21.7%, respectively. Both univariate and multivariate analysis revealed that relapsed/refractory (R/R) disease was associated with inferior PFS (HR 4.849, 95% CI 1.009-23.30; p = 0.049). Prior poor response to VEN was found to be a significant factor predicting higher risk of relapse (HR 4.37, 95% CI 1.130-16.9; p = 0.033). Our results showed that VEN-based regimen therapy followed by allo-HSCT in AML patients is feasible and does not increase the risk of transplant-related mortality and toxicity.


Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Estudos Retrospectivos , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/complicações , Doença Enxerto-Hospedeiro/etiologia , Recidiva
11.
iScience ; 25(11): 105443, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36388951

RESUMO

Lysine benzoylation (Kbz) is a newly discovered protein post-translational modification (PTM). This PTM can be stimulated by benzoate and contributes to gene expression. However, its regulatory enzymes and substrate proteins remain largely unknown, hindering further functional studies. Here we identified and validated the lysine acetyltransferase (KAT) HBO1 as a "writer" of Kbz in mammalian cells. In addition, we report the benzoylome in mammalian cells, identifying 1747 Kbz sites; among them at least 77 are the HBO1-targeted Kbz substrates. Bioinformatics analysis showed that HBO1-targeted Kbz sites were involved in multiple processes, including chromatin remodeling, transcription regulation, immune regulation, and tumor growth. Our results thus identify the regulatory elements of the Kbz pathway and reveal the non-canonical enzymatic activity and functions of HBO1 in cellular physiology.

12.
Eur J Pharmacol ; 936: 175357, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36330901

RESUMO

BACKGROUND: Ventricular arrhythmias (VAs) after myocardial infarction (MI) are an important cause of death in patients. Inhibition of sodium-glucose ligand transporter type 2 (SGLT-2) has been shown to reduce cardiovascular mortality in myocardial infarction independent of glycemic sham and prevent ventricular arrhythmias, and it is unclear whether these effects can be further enhanced by additional SGLT-1 inhibition. We investigated the effects of chronic treatment with the dual SGLT-1 and 2 inhibitor sotagliflozin (Sto) on VAs and their underlying mechanisms after MI. METHODS: MI was induced by ligation of the left anterior coronary artery in 6-8 weeks-old male mice, which were fed Sto at a dose of 30 mg/kg/day for 4 weeks after surgery. The effects were assessed by echocardiography, histopathology, Langendorff Heart Perfusion System, ambulatory electrocardiography, and Western blot. In vitro experiments were performed to assess the effect of Sto on cardiomyocytes subjected to hypoxic. RESULTS: Compared to the MI group, Sto treatment significantly improved cardiac function and reduced infarct size and fibrosis levels. Sto also decreased action potential duration (APD) and APD alternation thresholds. Ambulatory ECG and BURST stimulation showed that Sto reduced the incidence of VAs. In addition, Sto significantly improved the expression levels of ion channels and CX43 and ameliorated the abnormal expression of Ca2+ handling proteins after MI. Mechanistically, in vivo and in vitro experiments confirmed that TLR4/CaMKII activation was enhanced after MI, while Sto significantly inhibited the activation of the TLR4/CaMKII signaling pathway. CONCLUSION: Sto improved LV remodeling and reduced the incidence of VAs after MI, which was regulated by modulating the TLR4/CaMKII signaling pathway.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Infarto do Miocárdio , Masculino , Camundongos , Animais , Receptor 4 Toll-Like , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/etiologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Miócitos Cardíacos , Transportador 2 de Glucose-Sódio
13.
Neural Netw ; 157: 323-335, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36379102

RESUMO

Deep learning based facial landmark detection (FLD) has made rapid progress. However, the accuracy and robustness of FLD algorithms are degraded heavily when the face is subject to diverse expressions, posture deflection, partial occlusion and other uncertain circumstances. To learn more discriminative representations and reduce the negative effect caused by outliers, a stacked attention hourglass network (SAHN) is proposed for FLD, where new attention mechanism is introduced. Basically, in the design of SAHN, a spatial attention residual (SAR) unit is constructed such that relevant areas of facial landmarks are specially emphasized and essential features of different scales can be well extracted, and a channel attention branch (CAB) is introduced to better guide the next-level hourglass network for feature extraction. Due to the introduction of SAR and CAB, only two hourglass networks are stacked as the proposed SAHN with fewer parameters, which is different from traditional SHNs stacked by four hourglass networks. Furthermore, a variable robustness (VR) loss function is introduced for the training of SAHN. The robustness of the proposed model for FLD is guaranteed with the help of the VR loss by adaptively adjusting a continuous parameter. Extensive experimental results on three public datasets including 300W, WFLW and COFW confirm that our method is superior to some previous ones.

14.
Environ Technol ; : 1-13, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36409524

RESUMO

ABSTRACTA parametric model of the second-layer influent distributor is proposed to increase the reaction efficiency of the up-flow anaerobic sludge blanket. The impacts on the flow efficiency of the main parameters, including the length of distribution pipe, that is, the cylinder radius r1, the eccentricity of the nozzle e, and the number of nozzles n1, are investigated. The optimal parameter combination of the second-layer influent distributoris obtained by single factor analysis and orthogonal analysis. Then the two-layer distributor combination model, including the bottom influent distributor and the second-layer influent distributor, is established and the simulations are conducted to study the effect of the two-layer distributor on flow inside the reactor. The simulation results show that the proposed two-layer distributor can achieve a higher mixture efficiency than the single distributor.

15.
J Genet Eng Biotechnol ; 20(1): 149, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36318347

RESUMO

BACKGROUND: COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rigorous detection and treatment strategies against SARS-CoV-2 have become very challenging due to continuous evolutions to the viral genome. Therefore, careful genomic analysis is sorely needed to understand transmission, the cellular mechanism of pathogenicity, and the development of vaccines or drugs. OBJECTIVE: In this study, we intended to identify SARS-CoV-2 genome variants that may help understand the cellular and molecular foundation of coronavirus infections required to develop effective intervention strategies. METHODS: SARS-CoV-2 genome sequences were downloaded from an open-source public database, processed, and analyzed for variants in target detection sites and genes. RESULTS: We have identified six unique variants, G---AAC, T---AAC---T, AAC---T, AAC--------T, C----------T, and C--------C, at the nucleocapsid region and eleven major hotspot mutant genes: nsp3, surface glycoprotein, nucleocapsid phosphoprotein, ORF8, nsp6, nsp2, nsp4, helicase, membrane glycoprotein, 3'-5' exonuclease, and 2'-O-ribose methyltransferases. In addition, we have identified eleven major mutant genes that may have a crucial role in SARS-CoV-2 pathogenesis. CONCLUSION: Studying haplotype variants and 11 major mutant genes to understand the mechanism of action of fatal pathogenicity and inter-individual variations in immune responses is inevitable for managing target patient groups with identified variants and developing effective anti-viral drugs and vaccines.

16.
J Oncol ; 2022: 9636790, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339648

RESUMO

Objectives: Primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is a common phenotype of extranodal non-Hodgkin's lymphoma (NHL). This research aims to identify a model for predicting overall survival (OS) and cancer-specific survival (CSS) in PG-DLBCL. Methods: A total of 1716 patients diagnosed with PG-DLBCL between 1975 and 2017 were obtained from the SEER database and further randomly divided into the training and validating cohorts at a ratio of 7 : 3. Univariate and multivariate cox analyses were conducted to determine significant variables for the construction of nomogram. The performance of the model was then assessed by the concordance index (C-index), the calibration plot, and the area under the receiver operating characteristic (ROC) curve (AUC). Results: Multivariate analysis revealed that age, race, insurance status, Ann Arbor stage, marital status, chemotherapy, and radiation therapy all showed a significant association with OS and CSS. These characteristics were applied to build a nomogram. In the training cohort, the discrimination of nomogram for OS and CSS prediction was excellent (C-index = 0.764, 95% CI, 0.744-0.784 and C-index = 0.756, 95% CI, 0.732-0.780). The AUC of the nomogram for predicting 3- and 5-year OS was 0.779 and 0.784 and CSS was 0.765 and 0.772. Similar results were also observed in the internal validation set. Conclusions: We have successfully established a novel nomogram for predicting OS and CSS in PG-DLBCL patients with good accuracy, which can help physicians to quickly and accurately complete the evaluation of survival probability, risk stratification, and therapeutic strategy at diagnosis.

17.
ESC Heart Fail ; 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369767

RESUMO

AIMS: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have made considerable progress in the field of heart failure, but their application in arrhythmia remains to be in-depth. Right heart disease (RHD) often leads to right heart dysfunction and is associated with atrial fibrillation (AF). Here, we explored the possible electrophysiologic effect of dapagliflozin (a type of SGLT2is) in the development of AF in rats with RHD. METHODS AND RESULTS: Rats in the experimental group were intraperitoneally injected with a single dose of 60 mg/kg monocrotaline (MCT group, n = 32) on the first day of the experiment, whereas rats in the control group were injected with vehicle (CTL group, n = 32). Rats in the treatment subgroup were treated with dapagliflozin solution orally (MCT + DAPA and CTL + DAPA groups) for a total of 4 weeks, whereas rats in the rest of subgroups were given sterile drinking water. After 4 weeks, echocardiography demonstrated that MCT group rats developed obvious pulmonary arterial hypertension and right heart dysfunction. In addition, there were also obvious inflammatory infiltration, fibrosis, and muscularization in right atrial and pulmonary arteries. The P-wave duration (17.00 ± 0.53 ms, vs. 14.43 ± 0.57 ms in CTL; 14.00 ± 0.65 ms in CTL + DAPA; 14.57 ± 0.65 ms in MCT + DAPA; P < 0.05), RR interval (171.60 ± 1.48 ms, vs. 163.10 ± 1.10 ms in CTL; 163.30 ± 1.19 ms in CTL + DAPA; 163.10 ± 1.50 ms in MCT + DAPA; P < 0.05), Tpeak-Tend interval (65.93 ± 2.55 ms, vs. 49.55 ± 1.71 ms in CTL; 48.27 ± 3.08 ms in CTL + DAPA; P < 0.05), and corrected QT interval (200.90 ± 2.40 ms, vs. 160.00 ± 0.82 ms in CTL; 160.40 ± 1.36 ms in CTL + DAPA; 176.6 ± 1.57 ms in MCT + DAPA; P < 0.01) were significantly prolonged in the MCT group after 4 weeks, whereas P-wave amplitude (0.07 ± 0.0011 mV, vs. 0.14 ± 0.0009 mV in CTL; 0.14 ± 0.0011 mV in CTL + DAPA; 0.08 ± 0.0047 mV in MCT + DAPA; P < 0.05) and T-wave amplitude (0.04 ± 0.002 mV, vs. 0.13 ± 0.003 mV in CTL; 0.13 ± 0.003 mV in CTL + DAPA; P < 0.01) were decreased, and atrial 90% action potential duration (47.50 ± 0.93 ms, vs. 59.13 ± 2.1 ms in CTL; 59.75 ± 1.13 ms in CTL + DAPA; 60.63 ± 1.07 ms in MCT + DAPA; P < 0.01) and effective refractory periods (41.14 ± 0.88 ms, vs. 62.86 ± 0.99 ms in CTL; 63.14 ± 0.67 ms in CTL + DAPA; 54.86 ± 0.70 ms in MCT + DAPA; P < 0.01) were shortened. Importantly, the inducibility rate (80%, vs. 0% in CTL; 10% in CTL + DAPA; 40% in MCT + DAPA; P < 0.05) and duration of AF (30.85 ± 22.90 s, vs. 0 ± 0 s in CTL; 0.24 ± 0.76 s in CTL + DAPA; 5.08 ± 7.92 s in MCT + DAPA; P < 0.05) were significantly increased, whereas the expression levels of cardiac ion channels and calcium-handling proteins such as potassium/calcium channels and calmodulin were decreased. Mechanistically, 'NACHT, LRR, and PYD domain-containing protein 3' inflammasome-related pathway was significantly activated in the MCT group. Nevertheless, in the MCT + DAPA group, the above abnormalities were significantly improved. CONCLUSIONS: Dapagliflozin reduces pulmonary vascular damage and right heart dysfunction, as well as the susceptibility to AF in RHD rats.

18.
Front Immunol ; 13: 947080, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420271

RESUMO

Both colorectal and gastric cancer are lethal solid-tumor malignancies, leading to the majority of cancer-associated deaths worldwide. Although colorectal cancer (CRC) and gastric cancer (GC) share many similarities, the prognosis and drug response of CRC and GC are different. However, determinants for such differences have not been elucidated. To avoid genetic background variance, we performed multi-omics analysis, including single-cell RNA sequencing, whole-exome sequencing, and microbiome sequencing, to dissect the tumor immune signature of synchronous primary tumors of GC and CRC. We found that cellular components of juxta-tumoral sites were quite similar, while tumoral cellular components were specific to the tumoral sites. In addition, the mutational landscape and microbiome contributed to the distinct TME cellular components. Overall, we found that different prognoses and drug responses of GC and CRC were mainly due to the distinct TME determined by mutational landscape and microbiome components.


Assuntos
Neoplasias Colorretais , Microbiota , Neoplasias Primárias Múltiplas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Mutação , Neoplasias Colorretais/genética
19.
IEEE Trans Biomed Eng ; PP2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36417736

RESUMO

Automatically personalizing complex control of robotic prostheses to improve gait performance, such as gait symmetry, is challenging. Recently, human-in-the-loop (HIL) optimization and reinforcement learning (RL) have shown promise in achieving optimized control for each individual user in the field of wearable robots. However, HIL optimization methods lack scalability for high-dimensional space, while RL has mostly focused on optimizing robot kinematic performance. Thus, we propose a novel hierarchical framework to personalize robotic knee prosthesis control and improve overall gait performance. Specifically, in this study the framework was implemented to simultaneously design target knee kinematics and tune 12 impedance control parameters for improved symmetry of propulsive impulse in walking. In our proposed framework, HIL optimization is used to identify an optimal target knee kinematics with respect to symmetry improvement, while RL is leveraged to yield an optimal policy for tuning impedance parameters in high-dimensional space to match the kinematics target. The proposed framework was validated on human subjects, walking with our robotic knee prosthesis. The results showed that our design successfully shaped the target knee kinematics as well as configured 12 impedance control parameters to improve propulsive impulse symmetry of the human users. The knee kinematics that yielded best propulsion symmetry did not preserve the normative knee kinematics profile observed in non-disabled individuals, suggesting that restoration of normative joint biomechanics in walking does not necessarily optimize the gait performance of human-prosthesis systems. This new framework for prosthesis control personalization may be extended to other wearable devices or different gait performance optimization goals in the future.

20.
Front Genet ; 13: 947758, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313460

RESUMO

The Mongolian population exceeds six million and is the largest population among the Mongolic speakers in China. However, the genetic structure and admixture history of the Mongolians are still unclear due to the limited number of samples and lower coverage of single-nucleotide polymorphism (SNP). In this study, we genotyped genome-wide data of over 700,000 SNPs in 38 Mongolian individuals from Fuxin in Liaoning Province to explore the genetic structure and population history based on typical and advanced population genetic analysis methods [principal component analysis (PCA), admixture, FST, f 3 -statistics, f 4 -statistics, qpAdm/qpWave, qpGraph, ALDER, and TreeMix]. We found that Fuxin Mongolians had a close genetic relationship with Han people, northern Mongolians, other Mongolic speakers, and Tungusic speakers in East Asia. Also, we found that Neolithic millet farmers in the Yellow River Basin and West Liao River Basin and Neolithic hunter-gatherers in the Mongolian Plateau and Amur River Basin were the dominant ancestral sources, and there were additional gene flows related to Eurasian Steppe pastoralists and Neolithic Iranian farmers in the gene pool of Fuxin Mongolians. These results shed light on dynamic demographic history, complex population admixture, and multiple sources of genetic diversity in Fuxin Mongolians.

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