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1.
iScience ; 26(1): 105885, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36654858

RESUMO

The limited intrinsic regrowth capacity of corticospinal axons impedes functional recovery after cortical stroke. Although the mammalian target of rapamycin (mTOR) and p53 pathways have been identified as the key intrinsic pathways regulating CNS axon regrowth, little is known about the key upstream regulatory mechanism by which these two major pathways control CNS axon regrowth. By screening genes that regulate ubiquitin-mediated degradation of the p53 proteins in mice, we found that ubiquitination factor E4B (UBE4B) represses axonal regrowth in retinal ganglion cells and corticospinal neurons. We found that axonal regrowth induced by UBE4B depletion depended on the cooperative activation of p53 and mTOR. Importantly, overexpression of UbV.E4B, a competitive inhibitor of UBE4B, in corticospinal neurons promoted corticospinal axon sprouting and facilitated the recovery of corticospinal axon-dependent function in a cortical stroke model. Thus, our findings provide a translatable strategy for restoring corticospinal tract-dependent functions after cortical stroke.

2.
Brief Bioinform ; 2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36682005

RESUMO

Due to the lack of a method to efficiently represent the multimodal information of a protein, including its structure and sequence information, predicting compound-protein binding affinity (CPA) still suffers from low accuracy when applying machine-learning methods. To overcome this limitation, in a novel end-to-end architecture (named FeatNN), we develop a coevolutionary strategy to jointly represent the structure and sequence features of proteins and ultimately optimize the mathematical models for predicting CPA. Furthermore, from the perspective of data-driven approach, we proposed a rational method that can utilize both high- and low-quality databases to optimize the accuracy and generalization ability of FeatNN in CPA prediction tasks. Notably, we visually interpret the feature interaction process between sequence and structure in the rationally designed architecture. As a result, FeatNN considerably outperforms the state-of-the-art (SOTA) baseline in virtual drug evaluation tasks, indicating the feasibility of this approach for practical use. FeatNN provides an outstanding method for higher CPA prediction accuracy and better generalization ability by efficiently representing multimodal information of proteins via a coevolutionary strategy.

3.
Theriogenology ; 197: 198-208, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36525859

RESUMO

Activin/inhibin is an important factor for the fecundity of Hu sheep, and it is involved in follicular development in ovaries. Inhibin subunit beta A (INHBA) participates in the synthesis of activin A and inhibin A. In this study, we also noted a positive correlation between INHBA level and the secretion of both activin A and inhibin A in culture medium. Nevertheless, both knockdown and overexpression of INHBA downregulated the expression of Inhibin Subunit Alpha (INHA). Based on RNA-Sequencing, we further examined the effect and molecular mechanism of INHBA knockdown in GCs on mRNA expression. A total of 1,687 differentially expressed genes (DEGs) were identified (Fold change ≥ 2; False-discovory-rates (FDR) ≤ 0.01), of which 602 genes were upregulated and 1,087 genes were downregulated in the INHBA interference group compared with the control groups. Gene Ontology (GO) enrichment indicated that these DEGs were mainly involved in the regulation of cell cycle, protein serine/threonine kinase activity, and actin cytoskeleton reorganization. Moreover, DEGs were significantly enriched in 40 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including P53, progesterone-mediated oocyte maturation, and PI3K-AKT signaling pathways. We also noted a positive correlation between INHBA level and many PI3K/Akt/mTOR pathway-related genes at the gene or/and protein expression. Overall, this study may contribute to a better understanding of the roles of INHBA on GCs of prolific sheep, as well as the molecular effect of low INHBA expression on GCs, clarifying some reproductive failures.


Assuntos
Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Feminino , Animais , Ovinos/genética , RNA-Seq/veterinária , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Inibinas/metabolismo , Células da Granulosa/fisiologia
4.
Biomed Pharmacother ; 158: 114094, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36502755

RESUMO

As an emerging tumor therapy, ideal oncolytic viruses preferentially replicate in malignant cells, reverse the immunosuppressive tumor microenvironment, and eventually can be eliminated by the patient. It is of great significance for cancer treatment to discover new excellent oncolytic viruses. Here, we found that WNV live attenuated vaccine WNV-poly(A) could be developed as a novel ideal oncolytic agent against several types of cancers. Mechanistically, due to its high sensitivity to type Ι interferon (IFN-Ι), WNV-poly(A) could specifically kill tumor cells rather than normal cells. At the same time, WNV-poly(A) could activate Dendritic cells (DCs) and trigger tumor antigen specific response mediated by CD8 + T cell, which contributed to inhibit the propagation of original and distal tumor cells. Like intratumoral injection, intravenous injection with WNV-poly(A) also markedly delays Huh7 hepatic carcinoma (HCC) transplanted tumor progression. Most importantly, in addition to an array of mouse xenograft tumor models, WNV-poly(A) also has a significant inhibitory effect on many different types of patient-derived tumor tissues and HCC patient-derived xenograft (PDX) tumor models. Our studies reveal that WNV-poly(A) is a potent and excellent oncolytic agent against many types of tumors and may have a role in metastatic and recurrent tumors.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Vírus Oncolíticos , Animais , Camundongos , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Imunidade , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia , Vírus Oncolíticos/metabolismo , Microambiente Tumoral , Replicação Viral
5.
Antiviral Res ; 209: 105507, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36565755

RESUMO

The Omicron variant is sweeping the world, which displays striking immune escape potential through mutations at key antigenic sites on the spike protein, making broad-spectrum SARS-CoV-2 prevention or therapeutical strategies urgently needed. Previously, we have reported a hACE2-targeting neutralizing antibody 3E8, which could efficiently block both prototype SARS-CoV-2 and Delta variant infections in prophylactic mouse models, having the potential of broad-spectrum to prevent SARS-CoV-2. However, preparation of monoclonal neutralizing antibodies is severely limited by the time-consuming process and the relative high cost. Here, we utilized a modified VEEV replicon with two subgenomic (sg) promoters engineered to express the light and heavy chains of the 3E8 mAb. The feasibility and protective efficacy of replicating mRNA encoding 3E8 against Omicron infection in the hamster were demonstrated through the lung targeting delivery with the help of VEEV-VRP. Overall, we developed a safe and cost-effective platform of broad-spectrum to prevent SARS-CoV-2 infection.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Cricetinae , Camundongos , SARS-CoV-2/genética , COVID-19/prevenção & controle , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes , RNA Mensageiro , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos Antivirais
6.
Front Pediatr ; 10: 972809, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36545666

RESUMO

Background: To explore the geographical pattern and temporal trend of autism spectrum disorders (ASD) epidemiology from 1990 to 2019, and perform a bibliometric analysis of risk factors for ASD. Methods: In this study, ASD epidemiology was estimated with prevalence, incidence, and disability-adjusted life-years (DALYs) of 204 countries and territories by sex, location, and sociodemographic index (SDI). Age-standardized rate (ASR) and estimated annual percentage change (EAPC) were used to quantify ASD temporal trends. Besides, the study performed a bibliometric analysis of ASD risk factors since 1990. Publications published were downloaded from the Web of Science Core Collection database, and were analyzed using CiteSpace. Results: Globally, there were estimated 28.3 million ASD prevalent cases (ASR, 369.4 per 100,000 populations), 603,790 incident cases (ASR, 9.3 per 100,000 populations) and 4.3 million DALYs (ASR, 56.3 per 100,000 populations) in 2019. Increases of autism spectrum disorders were noted in prevalent cases (39.3%), incidence (0.1%), and DALYs (38.7%) from 1990 to 2019. Age-standardized rates and EAPC showed stable trend worldwide over time. A total of 3,991 articles were retrieved from Web of Science, of which 3,590 were obtained for analysis after removing duplicate literatures. "Rehabilitation", "Genetics & Heredity", "Nanoscience & Nanotechnology", "Biochemistry & Molecular biology", "Psychology", "Neurosciences", and "Environmental Sciences" were the hotspots and frontier disciplines of ASD risk factors. Conclusions: Disease burden and risk factors of autism spectrum disorders remain global public health challenge since 1990 according to the GBD epidemiological estimates and bibliometric analysis. The findings help policy makers formulate public health policies concerning prevention targeted for risk factors, early diagnosis and life-long healthcare service of ASD. Increasing knowledge concerning the public awareness of risk factors is also warranted to address global ASD problem.

8.
Eur Radiol ; 2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36571606

RESUMO

OBJECTIVES: To describe the dynamic changes in cardiac deformation and tissue characteristics using cardiac magnetic resonance (CMR) in asymptomatic patients during 12 months after heart transplantation (HT). METHODS: From April 2020 to January 2021, 21 consecutive HT patients without clinical symptoms were included in this prospective study. Multiparametric CMR was performed at 3, 6, and 12 months after HT. Twenty-five healthy volunteers served as controls. RESULTS: During follow-up, a decline in left ventricular (LV) global radial strain (GRS) (p = 0.020) and right ventricular (RV) global longitudinal strain (GLS) (p < 0.001) and an increase in post-contrast T1 (p = 0.024) and T2 (p < 0.001) in asymptomatic HT patients occurred at 3 months, which normalized at 6 months postoperatively, compared with those in healthy controls. A decline in LVGLS (p < 0.001) and LV global circumferential strain (GCS) (p < 0.001) and an increase in native T1 (p < 0.001), T2 (p < 0.001), and extracellular volume (ECV) (p < 0.001) occurred at 3 months. Although most parameters improved gradually, LVGLS, native T1, and ECV remained abnormal compared with those in healthy controls at 12 months; only T2 and LVGCS were normalized at 6 months and 12 months, respectively. ECV was significantly correlated with LVGLS, LVGCS, and LVGRS. CONCLUSION: Cardiac deformation and tissue characteristics were abnormal early after HT, although the patients were clinically asymptomatic. The dynamic changes in CMR characteristics demonstrate a gradual recovery of myocardial injury associated with transplantation during the first 12 months after HT. KEY POINTS: • Multiparametric CMR can detect the dynamic changes of transplantation-associated myocardial injury. • Post-contrast T1, T2, LVGRS, and RVGLS values are normalized at 6 months after HT. • Native T1, ECV, and LVGLS values remain abnormal compared with those in healthy controls at 12 months after HT.

9.
Eur Radiol ; 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36547672

RESUMO

OBJECTIVES: To develop a machine learning-based radiomics model based on multiparametric magnetic resonance imaging (MRI) for preoperative discrimination between central neurocytomas (CNs) and gliomas of lateral ventricles. METHODS: A total of 132 patients from two medical centers were enrolled in this retrospective study. Patients from the first medical center were divided into a training cohort (n = 74) and an internal validation cohort (n = 30). Patients from the second medical center were used as the external validation cohort (n = 28). Features were extracted from contrast-enhanced T1-weighted and T2-weighted images. A support vector machine was used for radiomics model investigation. Performance was evaluated using the sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). The model's performance was also compared with those of three radiologists. RESULTS: The radiomics model achieved an AUC of 0.986 in the training cohort, 0.933 in the internal validation cohort, and 0.903 in the external validation cohort. In the three cohorts, the AUC values were 0.657, 0.786, and 0.708 for radiologist 1; 0.838, 0.799, and 0.790 for radiologist 2; and 0.827, 0.871, and 0.862 for radiologist 3. When assisted by the radiomics model, two radiologists improved their performance in the training cohort (p < 0.05) but not in the internal or external validation cohorts. CONCLUSIONS: The machine learning radiomics model based on multiparametric MRI showed better performance for distinguishing CNs from lateral ventricular gliomas than did experienced radiologists, and it showed the potential to improve radiologist performance. KEY POINTS: • The machine learning radiomics model shows excellent performance in distinguishing CNs from gliomas. • The radiomics model outweighs two experienced radiologists (area under the receiver operating characteristic curve, 0.90 vs 0.79 and 0.86, respectively). • The radiomics model has the potential to enhance radiologist performance.

10.
Front Cardiovasc Med ; 9: 955780, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36440034

RESUMO

Introduction: Heart failure with preserved ejection fraction (HFpEF), which is a common co-morbidity in patients with maintenance hemodialysis (MHD), results in substantial mortality and morbidity. However, there are still no effective therapeutic drugs available for HFpEF currently. Sacubitril/valsartan has been shown to significantly improve clinical outcomes and reverse myocardial remodeling among patients with heart failure with reduced ejection fraction (HFrEF). The effect of sacubitril/valsartan in MHD patients with HFpEF remains unclear. Our study was designed to assess the efficacy and safety of sacubitril/valsartan in MHD patients with HFpEF. Methods: A total of 247 MHD patients with HFpEF treated with sacubitril/valsartan were included in this retrospective study. Patients were followed up regularly after medication treatment. The alterations in clinical, biochemical, and echocardiographic parameters before and after taking sacubitril/valsartan were collected. In addition, the safety of the sacubitril/valsartan treatment was also assessed. Among those 247 patients with MHD, 211 patients were already in treatment with angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs) before being treated with sacubitril/valsartan. We also performed an analysis to compare the differences between the 211 patients who had previously received ACEi/ARB treatment and the 36 patients who were sacubitril/valsartan naive. Results: Among those 247 patients with MHD, compared with baseline levels, systolic blood pressure (BP) (149.7 ± 23.6 vs. 137.2 ± 21.0 mmHg, P < 0.001), diastolic BP (90.2 ± 16.1 vs. 84.5 ± 14.1 mmHg, P < 0.001), heart rate (83.5 ± 12.5 vs. 80.0 ± 8.7 bpm, P < 0.001), N-terminal B-type natriuretic peptide precursor (NT-proBNP) [29125.0 (11474.5, 68532.0) vs. 12561.3 (4035.0, 37575.0) pg/ml, P < 0.001], and cardiac troponin I [0.044 (0.025, 0.078) vs. 0.0370 (0.020, 0.064) µg/L, P = 0.009] were markedly decreased after treatment with sacubitril/valsartan. New York Heart Association (NYHA) functional class showed a notable trend of improvement after 3-12 months of follow-up. Echocardiographic parameters including left ventricular posterior wall thickness (LVPWT) (11.8 ± 2.0 vs. 10.8 ± 1.9 mm, P < 0.001), intraventricular septal thickness in diastole (11.8 ± 2.0 vs. 11.2 ± 2.0 mm, P < 0.001), left ventricular end-diastolic diameter (53.8 ± 6.9 vs. 51.2 ± 7.1 mm, P < 0.001), left atrial diameter (LAD) (40.5 ± 6.2 vs. 37.2 ± 7.2 mm, P < 0.001), left ventricular end-diastolic volume (LVEDV) [143.0 (111.5, 174.0) vs. 130.0 (105.0, 163.0) ml, P < 0.001], left ventricular end-systolic volume (LVESV) [57.0 (43.0, 82.5) vs. 48.0 (38.0, 74.0) ml, P < 0.001], and pulmonary arterial systolic pressure [39.0 (30.5, 50.0) vs. 28.0 (21.0, 37.5) mmHg, P < 0.001] were significantly reduced after initiating the treatment of sacubitril/valsartan. The parameters of left ventricular diastolic function including E/A ratio [0.8 (0.7, 1.3) vs. 0.9 (0.8, 1.3), P = 0.008], maximal tricuspid regurgitation velocity [2.7 (2.5, 3.2) vs. 2.4 (2.0, 2.8) m/s, P < 0.001], septal e'wave velocity (8.0 ± 0.6 vs. 8.2 ± 0.5 cm/s, P = 0.001), lateral e' wave velocity (9.9 ± 0.8 vs. 10.2 ± 0.7 cm/s, P < 0.001), E/e' [8.3 (6.4, 11.8) vs. 7.2 (6.1, 8.9), P < 0.001], and left atrial volume index (37.9 ± 4.2 vs. 36.4 ± 4.1 ml/m2, P < 0.001) were significantly improved by sacubitril/valsartan. Among 211 patients who were already in treatment with ACEi/ARB and 36 patients who were sacubitril/valsartan naive, the improvement of cardiac function demonstrated by clinical outcomes and echocardiographic parameters were similar to the previous one of the 247 MHD patients with HFpEF. During the follow-up, none of the patients showed severe adverse drug reactions. Conclusion: Our study suggested that sacubitril/valsartan treatment in MHD patients with HFpEF was effective and safe.

11.
J Environ Pathol Toxicol Oncol ; 41(4): 11-23, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36374959

RESUMO

Gestational diabetes mellitus (GDM), a common complication in pregnancy, could threaten the health of both pregnancies and their offspring. miR-210-3p has been reported that play a crucial role in many diseases. Nevertheless, the molecular mechanism and clinical significance of miR-210-3p in the GDM is still unclear. miR-210-3p was overexpressed in the pancreas of the GDM mouse model. Meanwhile, miR-210-3p weakens cell viability and promotes the apoptosis of pancreatic ß cells, impairing the function of pancreatic ß cells. Bioinformatics analysis showed that miR-210-3p directly targets the expression of Dtx1, and miR-210-3p negatively regulated dtx1. Down-expression of Dtx1 could increase the expression of insulin and boost the function of pancreatic ß cells through inhibiting expressions of p-Akt, p-mTOR, p-4E-BP1, and p-SGK1. Rescue experiments verified that miR-210-3p could regulate the function of pancreatic ß cells and adjust the content of TG, TC, and HDL in the blood of mice with GDM via regulating the expression of Dtx1. The study demonstrated that miR-210-3p is significantly overexpressed in the pancreas of the GDM mouse model, which could impair the function and cell viability of pancreatic ß cells via suppressing the expression of Dtx1 promotes the progression of GDM. These findings provide a novel strategy to treat GDM.


Assuntos
Diabetes Gestacional , Células Secretoras de Insulina , MicroRNAs , Ubiquitina-Proteína Ligases , Animais , Feminino , Humanos , Camundongos , Gravidez , Apoptose , Diabetes Gestacional/genética , Insulina , Células Secretoras de Insulina/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
12.
J Sleep Res ; : e13710, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36377256

RESUMO

Obstructive sleep apnea (OSA) is a common chronic sleep-related breathing disorder in children. Previous studies showed widespread alterations in white matter (WM) in children with OSA mainly by using diffusion tensor imaging (DTI), while diffusional kurtosis imaging (DKI) extended DTI and exhibited improved sensitivity in detecting developmental and pathological changes in neural tissues. Therefore, we conducted whole-brain DTI and DKI analyses and compared the differences in kurtosis and diffusion parameters within the skeleton between 41 children with OSA and 32 healthy children. Between-group differences were evaluated by tract-based spatial statistics (TBSS) analysis (p < 0.05, TFCE corrected), and partial correlations between DKI metrics and sleep parameters were assessed considering age and gender as covariates. Compared with the controls, children with OSA showed significantly decreased kurtosis fractional anisotropy (KFA) mainly in white matter regions with a complex fibre arrangement including the posterior corona radiate (PCR), superior longitudinal fasciculus (SLF), and inferior fronto-occipital fasciculus (IFOF), while decreased FA in white matter regions with a coherent fibre arrangement including the posterior limb of internal capsule (PLIC), anterior thalamic radiation (ATR), and corpus callosum (CC). Notably, the receiver operating characteristic (ROC) curve analysis demonstrated the KFA value in complex tissue regions significantly (p < 0.001) differentiated children with OSA from the controls. In addition, the KFA value in the left PCR, SLF, and IFOF showed significant partial correlations to the sleep parameters for children with OSA. Combining DKI derived kurtosis and diffusion parameters can provide complementary neuroimaging biomarkers for assessing white matter alterations, and reveal pathological changes and monitor disease progression in paediatric OSA.

13.
Front Microbiol ; 13: 1031853, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338047

RESUMO

Pulp and paper mill effluent is rich in recalcitrant and toxic pollutants compounds and causes pollution. To find an efficient biocatalyst for the treatment of effluent, a dye-decolorizing peroxidase from Bacillus amyloliquefaciens MN-13, which is capable of degrading lignin, was used for the bioremediation of paper and pulp mill effluent. The dye-decolorizing peroxidase from Bacillus amyloliquefaciens (BaDyP) exhibited high-redox potential to 2, 2'-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) ammonium salt (ABTS), veratryl alcohol, Mn2+, reactive blue 19, reactive black 5 and lignin dimer guaiacylglycerol-beta-guaiacyl ether (GGE). When GGE was used as substrate, BaDyP broke ß-O-4 bond of GGE and then oxidize Cα to generate vanillin. The Km values for ABTS and veratryl alcohol were 2.19 mm and 0.07 mm, respectively. The Vmax for ABTS and veratryl alcohol were 1.8 mm/min and 14.12 mm/min, respectively. The BaDyP-mediated treatment of pulp and paper mill effluent led to significant reduction of chemical oxygen demand (COD) and color. When 5% (v/v) of effluent was treated with BaDyP for 12 h at 30°C and pH 2, the removal of COD, color, and lignin was achieved at 82.7, 80.2, and 78.20%, respectively. In detoxification assay, the seeds of Vigna unguiculata grown in treated effluent showed a significant increase in germination rate from 66.7% (untreated effluent) to 90%, and in radicle length from 0.68 cm (untreated effluent) to 1.26 cm, respectively. In the meanwhile, the inhibition of Escherichia coli and Bacillus subtilis by the treated effluent reduced significantly as compared to untreated effluent, indicating high detoxification performance of BaDyP for the treatment of pulp and paper mill effluent. The findings suggest that BaDyP is a potential catalyst for bioremediation of pulp and paper mill effluent, as it is effective in substantial lowering of pollutants load as well as reduces COD, color, and toxicity of effluent.

14.
BMC Med Educ ; 22(1): 766, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348392

RESUMO

BACKGROUND: The effectiveness of online classes is always a concern, and it can be overcome by opting for active learning strategies like team-based learning (TBL). This study was conducted to find out the effectiveness of online TBL as an active learning strategy. We also aimed to explore the satisfaction and perception of students toward TBL. METHODS: This is a mixed-method study conducted among 29 third-year Bachelor of Medicine and Bachelor of Surgery (MBBS) students of Gandaki Medical College using purposive sampling method in the duration of January to September 2021. Three two hours online TBL sessions were used for teaching introduction to medical ethics. The individual readiness assurance test (IRAT) scores were compared to the group readiness assurance test (GRAT) scores to evaluate the effect of TBL through cooperative learning. Learner reactions and satisfaction of students towards TBL were assessed using a validated questionnaire comprising of a five-point Likert scale. An open-ended question asking the participants to describe their overall experience of the TBL sessions was also included to explore their perceptions towards TBL. The data were collected using Google form and exported to Microsoft Excel and the quantitative data were then analyzed using Statistical Package for Social Sciences (SPSS) version 16.0. To check the normal distribution of the data, Kolmogorov Smirnov and Shapiro-Wilk test were used. Non-parametric tests were used for the non-normally distributed data. P value of < 0.05 was regarded as significant. Thematic analysis was conducted for the qualitative data. RESULTS: The median GRAT scores were significantly higher (p = 0.006 in TBL 1 and 0.001 in TBL 2) than IRAT scores. Learner reactions toward TBL sessions were positive as shown by the mean scores which were in the range of 3.59 to 4.66. Five themes were generated from the codes: "effective learning method", "positive experience", "gained knowledge", "expression of gratitude" and "the way of conduction of the sessions". CONCLUSION: Online TBL in medical ethics was effective as a teaching learning tool in our setting. The students were satisfied with the learning process and rated the learning strategy positively.


Assuntos
Estudantes de Medicina , Humanos , Avaliação Educacional/métodos , Ética Médica/educação , Processos Grupais , Nepal , Projetos Piloto , Aprendizagem Baseada em Problemas/métodos
15.
J Mater Chem B ; 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36440610

RESUMO

Osteoporosis is a growing public health concern worldwide. To avoid extra surgeries, developing biodegradable bone cement is critical for the treatment of osteoporosis. Herein, we designed calcium phosphate/calcium sulfate cement reinforced with sodium carboxymethyl cellulose (CMC/OPC). It presents an appropriate physicochemical performance for clinical handling. Meanwhile, CMC/OPC bone cement promotes osteogenic differentiation in vitro. Results of the immune response in vitro and in vivo confirmed that increasing the cellulose content triggered macrophage switching into the M2 phenotype and CMC/OPC exhibited significant anti-inflammation. Furthermore, in vitro and in vivo degradation demonstrated that cellulose tailors the degradation rate of composite bone cement, which achieved a linear degradation process and could degrade by more than 90% for 12 weeks. In summary, the composite bone cement CMC/OPC is a promising candidate for bone repair applications.

16.
Emerg Med Int ; 2022: 6889237, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438861

RESUMO

Purpose: At present, not enough is known about the symptoms before cardiac arrest. The purpose of this study is to describe the precursor symptoms of cardiac arrest, focusing on the relationship between symptoms and cardiac arrest, and to establish a quick scoring model of symptoms for predicting cardiac arrest. Patients and Methods. A retrospective case-control study was carried out on cardiac arrest patients who visited the emergency department of Peking University Third Hospital from January 2018 to June 2019. Symptoms that occurred or were obviously aggravated within the 14 days before CA were defined as warning symptoms. Results: More than half the cardiac arrest patients experienced warning symptoms within 14 days before cardiac arrest. Dyspnea (p < 0.001) was found to be associated with cardiac arrest; syncope and cold sweat are other symptoms that may have particular clinical significance. Gender (p < 0.001), age (p < 0.001), history of heart failure (p=0.006), chronic kidney disease (p=0.011), and hyperlipidemia (p=0.004) were other factors contributing to our model. Conclusions: Warning symptoms during the 14 days prior to cardiac arrest are common for CA patients. The Quick Scoring Model for Cardiac Arrest (QSM-CA) was developed to help emergency physicians and emergency medical services (EMS) personnel quickly identify patients with a high risk of cardiac arrest.

17.
Foods ; 11(19)2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36230159

RESUMO

In the present study, maize starch (MS), potato starch (PS), high-amylose maize starch (HAMS), and wheat starch (WS) were deep-fried in soybean oil that was continuously heated for 40 h under 180 °C. The thermodynamic and pasting properties of deep-fried starch samples were determined. The results suggested that starch-lipid complexes formed with the extension of frying oils' usage; however, their number was not dependent on the frying oils' life cycle. Importantly, the results of pasting properties revealed the following strength of intermolecular force in deep-fried starch samples: PS > MS > HAMS > WS. The results of XRD and FTIR analysis confirmed the formation of starch-lipid complexes during the deep-frying process. Furthermore, the results of the in vitro digestibility of deep-fried starch revealed that the formation of starch-lipid complexes inhibited the swelling of starch granules and prevented the entrance of amylase into the interior. Additionally, the results of the oxidation stability of deep-frying oil indicated that the formation of starch-lipid complexes did not alter the trend of lipid oxidation as an effect of the limited number of starch-lipid complexes. These results could have critical implications for the development of healthier deep-fried foods.

18.
Cancer Med ; 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36271485

RESUMO

AIM: To explore factors associated with decision regret after cystectomy among Chinese bladder cancer patients. METHODS: This cross-sectional study involved 112 patients, who had received radical bladder cancer resection. Participants were recruited from August 2021 until January 2022. The decision regret scale (DRS), decision conflict scale (DCS), and the Functional Assessment of Cancer Therapy-Bladder cancer (FACT-BL) form were used to measure decision regret, decision conflict, and quality of life. Investigator-designed items further explored perceptions involved in decision-making participation and outcomes. RESULTS: The average score for decision regret was 26.21 (SD 15.886), while decision conflict was 20.27 (SD 13.375) and quality of life was 94.74 (SD 20.873). 57.1% of our participants had a little knowledge about the quality of life of patients who chose an alternate urinary diversion method; however, only 13.4% reported having a clear understanding. In addition, 8.9%, 26.8%, and 36.6% thought that quality of life related to alternate decisions was poor, average, or good, respectively. Multiple regression analysis suggested that decision regret is associated with decision conflict, quality of life, and the perceptions that others (who took alternate urinary diversion decisions) had a better quality of life. CONCLUSION: Decision regret is common among Chinese bladder cancer patients, after cystectomy. The prevalence of regret appears to be much higher in Chinese bladder cancer patients compared to similar studies from other regions. Decisions in mainland China are often made by the treating physician or by family members which may cause more profound regret. However, education and economic status are positively related to higher levels of regret which creates questions around knowing, participation, and expectations, which must be explored.

19.
Front Plant Sci ; 13: 990929, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36247587

RESUMO

B-box (BBX) proteins are one of the zinc-finger transcription factor that plays a critical role in plant development, growth, and multiple stress responses. Although BBX genes have been reported in many model organisms, no comprehensive study has yet been conducted on the BBX genes in Melilotus albus, and the biological functions of this family remain unknown. In this study, a total of 20 BBX (MaBBX) genes were identified in M. albus and were phylogenetically divided into five clades. BBX members within the same clade showed similar conserved domain, suggesting similarity of potential biological function. Analysis of MaBBX conserved motifs showed that every subfamily contained two common motifs. Distribution mapping shows that BBX proteins are nonrandomly localized in eight chromosomes. The synteny showed that most homologous gene pairs of the MaBBX gene family were amplified by segmental replication, which meant segmental replication was the main way for the MaBBX gene family to evolve. Additionally, the cis-element analysis predicted light-responsive, various hormone and stress-related elements in the promoter regions of MaBBXs. Furthermore, the expression levels of all 20 MaBBX genes were detected by qRT-PCR under salt, cold, and dark stresses in M. albus. Moreover, it was observed that 16 genes had higher expression levels after 3 h of salt treatment, 10 genes were significantly upregulated after 3 h of cold treatment, and all genes were up regulated after 3 h of dark treatment, and then appeared to decline. In addition, it was also noticed that MaBBX13 may be an important candidate for improving tolerance to abiotic stress. The prediction of protein tertiary structure showed that the tertiary structures of members of the same subfamily of MaBBX proteins were highly similar. The hypothesis exhibited that most of the MaBBX proteins were predicted to be localized to the nucleus and cytoplasm and was validated by transient expression assays of MaBBX15 in tobacco leaf epidermal cells. This study provides useful information for further investigating and researching the regulatory mechanisms of BBX family genes in response to abiotic stresses in M. albus.

20.
IEEE Trans Image Process ; 31: 6487-6501, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36223353

RESUMO

Transferable adversarial attacks against Deep neural networks (DNNs) have received broad attention in recent years. An adversarial example can be crafted by a surrogate model and then attack the unknown target model successfully, which brings a severe threat to DNNs. The exact underlying reasons for the transferability are still not completely understood. Previous work mostly explores the causes from the model perspective, e.g., decision boundary, model architecture, and model capacity. Here, we investigate the transferability from the data distribution perspective and hypothesize that pushing the image away from its original distribution can enhance the adversarial transferability. To be specific, moving the image out of its original distribution makes different models hardly classify the image correctly, which benefits the untargeted attack, and dragging the image into the target distribution misleads the models to classify the image as the target class, which benefits the targeted attack. Towards this end, we propose a novel method that crafts adversarial examples by manipulating the distribution of the image. We conduct comprehensive transferable attacks against multiple DNNs to demonstrate the effectiveness of the proposed method. Our method can significantly improve the transferability of the crafted attacks and achieves state-of-the-art performance in both untargeted and targeted scenarios, surpassing the previous best method by up to 40% in some cases. In summary, our work provides new insight into studying adversarial transferability and provides a strong counterpart for future research on adversarial defense.


Assuntos
Redes Neurais de Computação
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