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1.
J Colloid Interface Sci ; 606(Pt 2): 1554-1562, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34500158

RESUMO

HYPOTHESIS: Janus nanosheets, which have two surfaces of different functionalities, exhibit unique interfacial properties. In this work, we propose a facile and scalable technique for preparation of silica-based Janus nanosheets, which is based on formation of high internal phase water-in-oil emulsions stabilized solely by alkyl-substituted polyethoxysiloxanes due to their hydrolysis-induced interfacial activity. EXPERIMENTS: Janus nanosheets are then obtained by crushing the silica foams converted from such emulsions. The morphology of Janus nanosheets is investigated by field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The chemical structure of functional silica materials is characterized by Fourier transform infrared spectroscopy (FT-IR). The asymmetric structure of silica nanosheets is observed by confocal laser scanning microscopy. FINDINGS: The resulting nanosheets have a rough hydrophobic surface and a smooth hydrophilic one, and are capable of stabilizing Pickering oil-in-water emulsions. Remarkably, pH-responsiveness of emulsions can be attained using the nanosheets whose hydrophilic surface is substituted with amino groups. Fast oil-water separation is achieved by the Janus nanosheets, which has been demonstrated by the nanosheets with a polystyrene-coated hydrophobic surface. This work paves a new avenue for large-scale production of functional silica-based Janus nanosheets suitable for numerous promising applications.


Assuntos
Dióxido de Silício , Tensoativos , Emulsões , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Infravermelho com Transformada de Fourier
2.
Magn Reson Med ; 87(2): 764-780, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34601751

RESUMO

PURPOSE: To develop a scan-specific model that estimates and corrects k-space errors made when reconstructing accelerated MRI data. METHODS: Scan-specific artifact reduction in k-space (SPARK) trains a convolutional-neural-network to estimate and correct k-space errors made by an input reconstruction technique by back-propagating from the mean-squared-error loss between an auto-calibration signal (ACS) and the input technique's reconstructed ACS. First, SPARK is applied to generalized autocalibrating partially parallel acquisitions (GRAPPA) and demonstrates improved robustness over other scan-specific models, such as robust artificial-neural-networks for k-space interpolation (RAKI) and residual-RAKI. Subsequent experiments demonstrate that SPARK synergizes with residual-RAKI to improve reconstruction performance. SPARK also improves reconstruction quality when applied to advanced acquisition and reconstruction techniques like 2D virtual coil (VC-) GRAPPA, 2D LORAKS, 3D GRAPPA without an integrated ACS region, and 2D/3D wave-encoded imaging. RESULTS: SPARK yields SSIM improvement and 1.5 - 2× root mean squared error (RMSE) reduction when applied to GRAPPA and improves robustness to ACS size for various acceleration rates in comparison to other scan-specific techniques. When applied to advanced reconstruction techniques such as residual-RAKI, 2D VC-GRAPPA and LORAKS, SPARK achieves up to 20% RMSE improvement. SPARK with 3D GRAPPA also improves RMSE performance by ~2×, SSIM performance, and perceived image quality without a fully sampled ACS region. Finally, SPARK synergizes with non-Cartesian, 2D and 3D wave-encoding imaging by reducing RMSE between 20% and 25% and providing qualitative improvements. CONCLUSION: SPARK synergizes with physics-based acquisition and reconstruction techniques to improve accelerated MRI by training scan-specific models to estimate and correct reconstruction errors in k-space.

3.
MAbs ; 13(1): 2003281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34818120

RESUMO

The V-domain Ig Suppressor of T-cell Activation (VISTA) is an immune checkpoint regulator that suppresses immune responses and is readily expressed on human and murine myeloid cells and T cells. This immunosuppressive pathway can be activated using VISTA agonists. Here, we report the development of murine anti-human VISTA (anti-hVISTA) monoclonal antibodies (mAbs), anti-hVISTA nanobodies (Nbs), and cross-reactive rat anti-murine/human VISTA (anti-hmVISTA) mAbs. All mAbs and Nbs generated bound to VISTA (human and/or murine) with dissociation constants in the sub-nanomolar or low nanomolar range. Competition analysis revealed that the selected Nbs bound the same or a nearby epitope(s) as the human VISTA-specific mAbs. However, the cross-reactive mAbs only partially competed with Nbs for binding to hVISTA. All mAbs and one Nb (hVISTANb7) were able to strongly detect VISTA expression on primary human monocytes. Importantly, the murine anti-hVISTA mAbs 7E12 and 7G5 displayed strong agonistic activity in human peripheral blood mononuclear cell cultures, while Nb7 and rat anti-hmVISTA mAbs 3C3, 7C6, 7C7, and 7G1 also behaved as hVISTA agonists, albeit to a lesser extent. Cross-reactive mAbs 7C7 and 7G1 further displayed agonistic potential in murine splenocyte assays. Importantly, mAb 7G1 significantly reduced inflammation associated with the murine model of imiquimod-induced psoriasis. These agonistic VISTA mAbs may represent therapeutic leads to treat inflammatory disorders.

4.
Chin Med J (Engl) ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34802024

RESUMO

BACKGROUND: The past decade has witnessed an ever-increasing momentum of transcatheter aortic valve replacement (TAVR) and a subsequent paradigm shift in the contemporary management of severe aortic stenosis (AS). We conducted a multi-centric TAVR registry based on Chinese patients (the China Aortic valve tRanscatheter Replacement registrY [CARRY]) to delineate the clinical characteristics and outcomes of Chinese patients who underwent TAVR and compare the results between different valve types in different Chinese regions. METHODS: CARRY is an all-comer registry of aortic valve disease patients undergoing TAVR across China and was designed as an observational study that retrospectively included all TAVR patients at each participating site. Seven hospitals in China participated in the CARRY, and 1204 patients from April 2012 to November 2020 were included. Categorical variables were compared using the chi-squared test, and continuous variables were analyzed using a t test or analysis of variance (ANOVA) test. The Kaplan-Meier curve was used to estimate the risk of adverse events during follow-up. RESULTS: The mean age of the patients was 73.8 ±â€Š6.5 years and 57.2% were male. The median Society of Thoracic Surgeon-Predicted Risk of Mortality score was 6.0 (3.7-8.9). Regarding the aortic valve, the proportion of bicuspid aortic valve (BAV) was 48.5%. During the hospital stay, the stroke rate was 0.7%, and the incidence of high-degree atrioventricular block indicating permanent pacemaker implantation was 11.0%. The in-hospital all-cause mortality rate was 2.2%. After 1 year, the overall mortality rate was 4.5%. Compared to patients with tricuspid aortic valve (TAV), those with BAV had similar in-hospital complication rates, but a lower incidence of in-hospital mortality (1.4% vs. 3.3%) and 1 year mortality (2.3% vs. 5.8%). CONCLUSIONS: TAVR candidates in China were younger, higher proportion of BAV, and had lower rates of post-procedural complications and mortality than other international all-comer registries. Given the use of early generation valves in the majority of the population, patients with BAV had similar rates of complications, but lower mortality than those with TAV. These findings further propel the extension of TAVR in low-risk patients. TRIAL REGISTRATION: https://www.chictr.org.cn/ (No. ChiCTR2000038526).

6.
Elife ; 102021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787078

RESUMO

Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infection or tumorigenesis. HD is traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesions of a single wake-promoting nucleus, or even two simultaneously, did not exert serious HD. Therefore, the specific nucleus and neural circuitry for HD remain unknown. Here, we observed that the paraventricular nucleus of the hypothalamus (PVH) exhibited higher c-fos expression during the active period (23:00) than during the inactive period (11:00) in mice. Therefore, we speculated that the PVH, in which most neurons are glutamatergic, may represent one of the key arousal-controlling centers. By using vesicular glutamate transporter 2 (vglut2Cre) mice together with fiber photometry, multichannel electrophysiological recordings, and genetic approaches, we found that PVHvglut2 neurons were most active during wakefulness. Chemogenetic activation of PVHvglut2 neurons induced wakefulness for 9 h, and photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from sleep to wakefulness. Moreover, lesioning or chemogenetic inhibition of PVHvglut2 neurons dramatically decreased wakefulness. These results indicate that the PVH is critical for arousal promotion and maintenance.

7.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(10): 1002-1007, 2021 Oct 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34719414

RESUMO

OBJECTIVES: To explore the characteristics of immune function of healthy full-term infants at the age of 3 months, and to analyze the relationship of immune function with feeding pattern and sex. METHODS: A total of 84 healthy full-term infants born in four hospitals in Beijing and Hohhot, China were prospectively recruited. Their feeding patterns remained unchanged within 4 months after birth. They were divided into a breast-feeding group and a milk powder feeding group according to their feeding patterns. At the age of 3 months after birth, peripheral venous blood samples of the two groups were collected to evaluate cellular immunity and humoral immunity and perform routine blood test. The laboratory indices were compared between infants with different feeding patterns and sexes. RESULTS: Compared with the milk powder feeding group, the breast-feeding group had significantly lower proportion of T cell second signal receptor CD28, immunoglobulin M, and proportion and absolute count of neutrophils (P<0.05) and significantly higher expression and proportion of HLA-DR, a surface activation marker of CD8+ T cells, and proportion of lymphocytes (P<0.05). The male infants had a significantly lower white blood cell count and a significantly higher proportion of eosinophils compared with the female infants (P<0.05). CONCLUSIONS: Sex has no significant effect on the proportion of lymphocyte subsets in 3-month-old full-term infants, but feeding patterns are associated with the proportion of CD28+ T cells (lymphocyte functional subset) and HLA-DR+ T cells (lymphocyte activation subset), suggesting that feeding patterns have a certain effect on the development of immune function in 3-month-old full-term infants.


Assuntos
Linfócitos T CD8-Positivos , Antígenos HLA-DR , Aleitamento Materno , Feminino , Humanos , Lactente , Ativação Linfocitária , Masculino , Estudos Prospectivos
8.
J Diabetes Sci Technol ; : 19322968211056917, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34727783

RESUMO

BACKGROUND: With the rising prevalence of diabetes, machine learning (ML) models have been increasingly used for prediction of diabetes and its complications, due to their ability to handle large complex data sets. This study aims to evaluate the quality and performance of ML models developed to predict microvascular and macrovascular diabetes complications in an adult Type 2 diabetes population. METHODS: A systematic review was conducted in MEDLINE®, Embase®, the Cochrane® Library, Web of Science®, and DBLP Computer Science Bibliography databases according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. Studies that developed or validated ML prediction models for microvascular or macrovascular complications in people with Type 2 diabetes were included. Prediction performance was evaluated using area under the receiver operating characteristic curve (AUC). An AUC >0.75 indicates clearly useful discrimination performance, while a positive mean relative AUC difference indicates better comparative model performance. RESULTS: Of 13 606 articles screened, 32 studies comprising 87 ML models were included. Neural networks (n = 15) were the most frequently utilized. Age, duration of diabetes, and body mass index were common predictors in ML models. Across predicted outcomes, 36% of the models demonstrated clearly useful discrimination. Most ML models reported positive mean relative AUC compared with non-ML methods, with random forest showing the best overall performance for microvascular and macrovascular outcomes. Majority (n = 31) of studies had high risk of bias. CONCLUSIONS: Random forest was found to have the overall best prediction performance. Current ML prediction models remain largely exploratory, and external validation studies are required before their clinical implementation. PROTOCOL REGISTRATION: Open Science Framework (registration number: 10.17605/OSF.IO/UP49X).

9.
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.

10.
Front Oncol ; 11: 753330, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646782

RESUMO

The extracellular matrix (ECM) plays a central role in the formation of the tumor microenvironment. The deposition of the ECM is associated with poor prognosis in a variety of tumors. Aberrant ECM deposition could undermine the effect of chemotherapy and immunotherapy. However, there is no systematic analysis on the relationship between the ECM and prognosis or chemotherapy effect. In the present study, we applied the gene set variation analysis (GSVA) algorithm to score 2199 canonical pathways in 2125 cases of probe or sequencing data and identified the core matrisome as the driving factor in gastric cancer progression. We classified gastric cancer samples into three clusters according to the composition of the ECM and evaluated clinical and multi-omics characterization of ECM phenotypes. The ECM score was evaluated by GSVA score of core matrisome and a higher ECM score predicted poor prognosis of gastric cancer [Hazard Ratio (HR), 2.084; p-value < 2 × 10-16]. In The Cancer Genome Atlas (TCGA) cohort and KUGH, YUSH, and KUCM cohorts, we verified that patients with a low ECM score could benefit from chemotherapy. By contrast, patients with a high ECM score did not achieve satisfactory response from chemotherapy. Determining the characteristics of the ECM microenvironment might help to predict the prognosis and chemotherapy response of patients with gastric cancer, and help to resolve the enigma of chemoresistance acquisition, as well as providing inspiration to develop combination therapy.

11.
J Med Internet Res ; 23(10): e26486, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665149

RESUMO

BACKGROUND: Prior literature suggests that psychosocial factors adversely impact health and health care utilization outcomes. However, psychosocial factors are typically not captured by the structured data in electronic medical records (EMRs) but are rather recorded as free text in different types of clinical notes. OBJECTIVE: We here propose a text-mining approach to analyze EMRs to identify older adults with key psychosocial factors that predict adverse health care utilization outcomes, measured by 30-day readmission. The psychological factors were appended to the LACE (Length of stay, Acuity of the admission, Comorbidity of the patient, and Emergency department use) Index for Readmission to improve the prediction of readmission risk. METHODS: We performed a retrospective analysis using EMR notes of 43,216 hospitalization encounters in a hospital from January 1, 2017 to February 28, 2019. The mean age of the cohort was 67.51 years (SD 15.87), the mean length of stay was 5.57 days (SD 10.41), and the mean intensive care unit stay was 5% (SD 22%). We employed text-mining techniques to extract psychosocial topics that are representative of these patients and tested the utility of these topics in predicting 30-day hospital readmission beyond the predictive value of the LACE Index for Readmission. RESULTS: The added text-mined factors improved the area under the receiver operating characteristic curve of the readmission prediction by 8.46% for geriatric patients, 6.99% for the general hospital population, and 6.64% for frequent admitters. Medical social workers and case managers captured more of the psychosocial text topics than physicians. CONCLUSIONS: The results of this study demonstrate the feasibility of extracting psychosocial factors from EMR clinical notes and the value of these notes in improving readmission risk prediction. Psychosocial profiles of patients can be curated and quantified from text mining clinical notes and these profiles can be successfully applied to artificial intelligence models to improve readmission risk prediction.


Assuntos
Inteligência Artificial , Readmissão do Paciente , Idoso , Mineração de Dados , Humanos , Tempo de Internação , Estudos Retrospectivos , Fatores de Risco
12.
Antiviral Res ; 195: 105184, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34627935

RESUMO

Hepatitis B virus (HBV) infection leads to severe liver diseases, including cirrhosis and hepatocellular carcinoma (HCC). More than 257 million individuals are chronically infected, particularly in the Western Pacific region and Africa. Although nucleotide and nucleoside analogues (NUCs) and interferons (IFNs) are the standard therapeutics for HBV infection, none eradicates HBV covalently closed circular DNA (cccDNA) from the infected hepatocytes. In addition, long-term treatment with NUCs increases the risk of developing drug resistance and IFNs may cause severe side effects in patients. Thus, a novel HBV therapy that can achieve a functional cure, or even complete elimination of the virus, is highly desirable. Regarding the HBV life cycle, agents targeting the entry step of HBV infection reduce the intrahepatic cccDNA pool preemptively. The initial entry step in HBV infection involves interaction between the pre-S1 domain of the large hepatitis B surface protein (LHBsAg) and the sodium taurocholate cotransporting polypeptide (NTCP), which is a receptor for HBV. In this study, ergosterol peroxide (EP) was identified as a new inhibitor of HBV entry. EP inhibits an early step of HBV entry into DMSO-differentiated immortalized primary human hepatocytes HuS-E/2 cells, which were overexpressed NTCP. Also, EP interfered directly with the NTCP-LHBsAg interaction by acting on the NTCP. In addition, EP had no effect on HBV genome replication, virion integrity or virion secretion. Finally, the activity of EP against infection with HBV genotypes A-D highlights the therapeutic potential of EP for fighting HBV infection.

13.
Biomolecules ; 11(10)2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34680109

RESUMO

Cardiac arrhythmia has been defined as one of the abnormal heart rhythm symptoms, which is a common problem dealt with by cardiologists. Zebrafish were established as a powerful animal model with a transparent body that enables optical observation to analyze cardiac morphology and cardiac rhythm regularity. Currently, research has observed heart-related parameters in zebrafish, which used different approaches, such as starting from the use of fluorescent transgenic zebrafish, different software, and different observation methods. In this study, we developed an innovative approach by using the OpenCV library to measure zebrafish larvae heart rate and rhythm. The program is designed in Python, with the feature of multiprocessing for simultaneous region-of-interest (ROI) detection, covering both the atrium and ventricle regions in the video, and was designed to be simple and user-friendly, having utility even for users who are unfamiliar with Python. Results were validated with our previously published method using ImageJ, which observes pixel changes. In summary, the results showed good consistency in heart rate-related parameters. In addition, the established method in this study also can be widely applied to other invertebrates (like Daphnia) for cardiac rhythm measurement.

14.
ACS Synth Biol ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34591448

RESUMO

Metabolic pathways are commonly organized by sequestration into discrete cellular compartments. Compartments prevent unfavorable interactions with other pathways and provide local environments conducive to the activity of encapsulated enzymes. Such compartments are also useful synthetic biology tools for examining enzyme/pathway behavior and for metabolic engineering. Here, we expand the intracellular compartmentalization toolbox for budding yeast (Saccharomyces cerevisiae) with Murine polyomavirus virus-like particles (MPyV VLPs). The MPyV system has two components: VP1 which self-assembles into the compartment shell and a short anchor, VP2C, which mediates cargo protein encapsulation via binding to the inner surface of the VP1 shell. Destabilized green fluorescent protein (GFP) fused to VP2C was specifically sorted into VLPs and thereby protected from host-mediated degradation. An engineered VP1 variant displayed improved cargo capture properties and differential subcellular localization compared to wild-type VP1. To demonstrate their ability to function as a metabolic compartment, MPyV VLPs were used to encapsulate myo-inositol oxygenase (MIOX), an unstable and rate-limiting enzyme in d-glucaric acid biosynthesis. Strains with encapsulated MIOX produced ∼20% more d-glucaric acid compared to controls expressing "free" MIOX-despite accumulating dramatically less expressed protein-and also grew to higher cell densities. This is the first demonstration in yeast of an artificial biocatalytic compartment that can participate in a metabolic pathway and establishes the MPyV platform as a promising synthetic biology tool for yeast engineering.

15.
Light Sci Appl ; 10(1): 176, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465726

RESUMO

Efforts to mitigate the COVID-19 crisis revealed that fast, accurate, and scalable testing is crucial for curbing the current impact and that of future pandemics. We propose an optical method for directly imaging unlabeled viral particles and using deep learning for detection and classification. An ultrasensitive interferometric method was used to image four virus types with nanoscale optical path-length sensitivity. Pairing these data with fluorescence images for ground truth, we trained semantic segmentation models based on U-Net, a particular type of convolutional neural network. The trained network was applied to classify the viruses from the interferometric images only, containing simultaneously SARS-CoV-2, H1N1 (influenza-A virus), HAdV (adenovirus), and ZIKV (Zika virus). Remarkably, due to the nanoscale sensitivity in the input data, the neural network was able to identify SARS-CoV-2 vs. the other viruses with 96% accuracy. The inference time for each image is 60 ms, on a common graphic-processing unit. This approach of directly imaging unlabeled viral particles may provide an extremely fast test, of less than a minute per patient. As the imaging instrument operates on regular glass slides, we envision this method as potentially testing on patient breath condensates. The necessary high throughput can be achieved by translating concepts from digital pathology, where a microscope can scan hundreds of slides automatically.

16.
Front Physiol ; 12: 703281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512379

RESUMO

Aims: Obstructive sleep apnea (OSA) is a risk factor for steroid-resistant (SR) asthma. However, the underlying mechanism is not well defined. This study aimed to investigate how chronic intermittent hypoxia (CIH), the main pathophysiology of OSA, influenced the effects of glucocorticoids (GCs) on asthma. Main Methods: The effects of dexamethasone (Dex) were determined using the ovalbumin (OVA)-challenged mouse model of asthma and transforming growth factor (TGF)-ß treated airway smooth muscle cells (ASMCs), with or without CIH. The p38 MAPK signaling pathway activity was then detected in the mouse (n = 6) and ASMCs models (n = 6), which were both treated with the p38 MAPK inhibitor SB239063. Key Findings: Under CIH, mouse pulmonary resistance value, inflammatory cells in bronchoalveolar lavage fluid (BALF), and inflammation scores increased in OVA-challenged combined with CIH exposure mice compared with OVA-challenged mice (p < 0.05). These indicators were similarly raised in the OVA + CIH + Dex group compared with the OVA + Dex group (P < 0.05). CIH exposure enhanced the activation of the p38 MAPK pathway, oxidative stress injury, and the expression of NF-κB both in lung tissue and ASMCs, which were reversed by treatment with Dex and SB239063. In the in vitro study, treatment with Dex and SB239063 decreased ASMCs proliferation induced by TGF-ß combined with CIH and suppressed activation of the p38 MAPK pathway, oxidative stress injury, and NF-κB nuclear transcription (p < 0.05). Significance: These results indicated that CIH decreased GC sensitivity by activating the p38 MAPK signaling pathway.

17.
Carbohydr Polym ; 273: 118546, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560958

RESUMO

This study investigated the effect of konjac glucomannan (KGM) of different molecular weight on fecal microflora against antibiotic disturbance. KGM (~1.8 × 107 Da) was partially hydrolysed with trifluoroacetic acid (TFA) for 10 and 60 min to KGM1 (~2.1 × 104 Da) and KGM2 (7413 Da), respectively. The acid treatment caused significant reduction of intrinsic viscosity, average molecular weight (MW) and particle size of KGM, but brought limited change to the molecular structure. Low-MW KGM2 showed the most significant effect on fecal microflora in the presence of two common antibiotics (ampicillin and clindamycin), by increasing the relative abundance of Bifidobacteriaceae while decreasing the proportion of Enterobacteriaceae. Additionally, both the native and acid-treated KGM counteracted the adverse influence of antibiotics on the production of short chain fatty acids. The results have demonstrated the effect of KGM on gut microbiota with antibiotic disturbance.

18.
Proc Natl Acad Sci U S A ; 118(37)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34493676

RESUMO

Body-centered cubic metals including steels and refractory metals suffer from an abrupt ductile-to-brittle transition (DBT) at a critical temperature, hampering their performance and applications. Temperature-dependent dislocation mobility and dislocation nucleation have been proposed as the potential factors responsible for the DBT. However, the origin of this sudden switch from toughness to brittleness still remains a mystery. Here, we discover that the ratio of screw dislocation velocity to edge dislocation velocity is a controlling factor responsible for the DBT. A physical model was conceived to correlate the efficiency of Frank-Read dislocation source with the relative mobility of screw versus edge dislocations. A sufficiently high relative mobility is a prerequisite for the coordinated movement of screw and edge segments to sustain dislocation multiplication. Nanoindentation experiments found that DBT in chromium requires a critical mobility ratio of 0.7, above which the dislocation sources transition from disposable to regeneratable ones. The proposed model is also supported by the experimental results of iron, tungsten, and aluminum.

19.
Ann Phys Rehabil Med ; 65(4): 101570, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34536570

RESUMO

BACKGROUND: Anterior cruciate ligament (ACL) reconstruction requires an extended period of postoperative rehabilitation. Psychological factors can affect recovery after surgery. Study of psychological factors is still limited to self-motivation, fear and pain. Study of personality traits associated with early rehabilitation outcome after ACL reconstruction is scarce. OBJECTIVE: We aimed to explore the effect of personality traits on early rehabilitation after ACL reconstruction and provide a reference for clinicians in designing a personalized rehabilitation plan. METHODS: This prospective analysis investigated 155 patients at 3 and 6 months after ACL reconstruction. Follow-up involved administration of a general data questionnaire, the Chinese Big Five Personality Inventory Brief Version, the Tegner activity score, the International Knee Documentation Committee Subjective Knee Score, the Knee injury and Osteoarthritis Outcome Score, the Lysholm Score and a balance test. RESULTS: Among the 155 patients included (124 males), Neuroticism was negatively correlated with subjective knee scores at 3 and 6 months after surgery (p<0.001). The odds of a poor balance test result was increased for each 1-point increase in Neuroticism score (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.28-2.36, p<0.001). We found a positive correlation between Conscientiousness score and subjective knee scores at 3 and 6 months after surgery (p<0.001). For every 1-point increase in Conscientiousness score, the odds of a poor balance test result were decreased (OR 0.29, 95% CI 0.16-0.54, p<0.001). Agreeableness and Openness to experience scores were positively correlated with subjective knee scores at 3 and 6 months after surgery (p<0.001). We found no correlation between Extraversion and subjective knee scores at 3 and 6 months after surgery (p>0.05) but a positive correlation with the Tegner activity score at 3 and 6 months after surgery (p<0.05). CONCLUSION: We found a significant correlation between the Big Five personality dimensions and the early rehabilitation effect after ACL reconstruction, which can provide a reference for clinicians in designing a personalized rehabilitation plan.

20.
J Med Chem ; 64(18): 13356-13372, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34473510

RESUMO

Based on the novel allosteric site of deoxyhypusine synthase (DHPS), two series of 30 novel 5-(2-methoxyphenoxy)-2-phenylpyrimidin-4-amine derivatives as DHPS inhibitors were designed and synthesized. Among them, compound 8m, with the best DHPS inhibitory potency (IC50 = 0.014 µM), exhibited excellent inhibition against melanoma cells, which was superior to that of GC7. Besides, molecular docking and molecular dynamics (MD) simulations further proved that compound 8m was tightly bound to the allosteric site of DHPS. Flow cytometric analysis and enzyme-linked immunosorbent assay (ELISA) showed that compound 8m could inhibit the intracellular reactive oxygen species (ROS) level. Furthermore, by western blot analysis, compound 8m effectively activated caspase 3 and decreased the expressions of GP-100, tyrosinase, eIF5A2, MMP2, and MMP9. Moreover, both Transwell analysis and wound healing analysis showed that compound 8m could inhibit the invasion and migration of melanoma cells. In the in vivo study, the tumor xenograft model showed that compound 8m effectively inhibited melanoma development with low toxicity.

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