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1.
J Am Coll Health ; : 1-10, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35549991

RESUMO

Objective: To examine mental health status, COVID-19 vaccine intention and barriers among college students in the U.S. Participants: Students (n = 337) registered at a large public university in 2021. Methods: Cross-sectional survey data were collected online and analyzed using independent samples t test, chi-square test, and one-way ANOVA. Results: Compared to male students, females reported greater anxiety (p < .05) and fear (p < .01). Hispanic participants reported increased anxiety level and the least positive pandemic coping strategies (both p < .05) across the ethnic groups. Black students were the racial group with the lowest trust in the safety and effectiveness of COVID-19 vaccine (p < .05). Vaccine intention was positively correlated with factors such as vaccine safety measures, and perceptions toward vaccination (both p < .001). Conclusions: These gender- and ethnicity- based mental health struggles should be addressed immediately for better health and vaccine promotion outcomes amid the COVID-19 pandemic.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35551041

RESUMO

Liposome encapsulating cytarabine (CYT) and daunorubicin (DNR) is applied for treating Acute Myeloid Leukemia (AML) patients. To evaluate and compare relationship between the pharmacokinetics of free drug (drug which is not entrapped in liposomes) and liposome-encapsulated drug and the toxicity/efficacy, it is crucial to have trustworthy methods for separating the free and the encapsulated of the drug. In this study, methods were developed and validated to isolate and measure the free DNR/CYT (F-DNR/CYT), the encapsulated DNR/CYT (E-DNR/CYT) and the total DNR/CYT (T-DNR/CYT) in rat plasma. The methods involved solid-phase extraction (SPE) using reverse adsorbents for separating the F-DNR and E-DNR, SPE using cation exchange adsorbents for separating the E-CYT, ultrafiltration for isolating the F-CYT and protein precipitation (PPT) for releasing the T-DNR and T-CYT totally from the liposomal forms. The analytes were subsequently quantified on ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) individually with multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). The calibration curves showed good linear relationships over the concentration range of 0.22-44 µg/mL for E-DNR and T-DNR, 2-1000 ng/mL for F-DNR, 0.5-100 µg/mL for E-CYT and T-CYT, 4-2000 ng/mL for F-CYT respectively. For all the analytes, the within-and between-run precisions were less than13.6% and the accuracies (in terms of RE%) were within -12.5%. Besides, extraction recovery, matrix effect, dilution integrity and stability were also assessed. The methods were successfully applied to investigate the pharmacokinetics in Sprague-Dawley rats following i.v. administration liposomal formulation.

3.
Bioorg Chem ; 125: 105843, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35561529

RESUMO

Clostridioides difficile infection is one of the leading causes of antibiotic-associated infectious diarrhea, and is associated with increased incidence and severity worldwide. While antibiotics have traditionally been used for prophylaxis and treatment of C. difficile infection, elevated antibiotic resistance has promoted the development and spread of C. difficile infection. Since the current standard-of-care antibiotics are ineffective for treating infections, there is an urgent need for novel antibacterial drugs or strategies to target C. difficile infection. C. difficile virulence and vital physiological functions are considered to be ideal targets. Thus, several promising lead compounds have been identified through screening both synthetic and natural product libraries. The goal of this review is to provide an update of the current scientific knowledge of C. difficile infection, focusing on small molecule inhibitors, which can effectively inhibit C. difficile by suppressing virulence or destroying vital physiological structures.

4.
BMC Geriatr ; 22(1): 414, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35546663

RESUMO

BACKGROUND: Metabolic Syndrome (MetS) is a common health problem among older adults. Previous studies have revealed the relationship between sleep duration as well as global sleep status and MetS. OBJECTIVES: This study aims to examine the association between the specific sleep characteristic and MetS as well as MetS components among community-dwelling old adults. METHODS: This cross-sectional study included 1499 community residents aged ≥ 60 years. Sleep characteristics were assessed using the Pittsburgh Sleep Quality Index (PSQI) and bed/rise time of the residents. Logistic regression analysis and multiple linear regression analysis were used to examine the associations between sleep characteristics and MetS as well as MetS components. A generalized additive model was built to assess the smooth relationship between triglyceride (TG) levels and sleep duration. RESULTS: Of the 1499 participants, 449 (30.0%) had MetS, and 443 (29.6%) had poor sleep quality. The rise time was found to be associated with MetS (> 6:00 vs. 5:00 ~ 6:00: adjusted OR (95%) = 1.77 (1.17-2.69), P = 0.007). For the MetS components, a U-shaped relationship was first revealed for sleep duration and TG levels (EDF = 1.85, P < 0.001). Furthermore, significant associations also included the associations of subjective sleep quality and daytime dysfunction with hypertension, the associations of sleep efficiency and rise time with hyperglycemia, the associations of rise time with TG levels, and the association of bedtime with waist circumference. CONCLUSIONS: The different sleep characteristics were associated with different MetS components.

5.
Front Microbiol ; 13: 874354, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547130

RESUMO

The superbug Pseudomonas aeruginosa is among the most formidable antibiotic-resistant pathogens. With declining options for antibiotic-resistant infections, new medicines are of utmost importance to combat with P. aeruginosa. In our previous study, we demonstrated that Epigallocatechin-3-gallate (EGCG) can inhibit the production of quorum sensing (QS)-regulated virulence factors in vitro. Accordingly, the protective effect and molecular mechanisms of EGCG against P. aeruginosa-induced pneumonia were studied in a mouse model. The results indicated that EGCG significantly lessened histopathological changes and increased the survival rates of mice infected with P. aeruginosa. EGCG effectively alleviated lung injury by reducing the expression of virulence factors and bacterial burden. In addition, EGCG downregulated the production of pro-inflammatory cytokines, such as TNF-α, IL-1, IL-6, and IL-17, and increased the expression of anti-inflammatory cytokines IL-4 and IL-10. Thus, the experimental results supported for the first time that EGCG improved lung damage in P. aeruginosa infection by inhibiting the production of QS-related virulence factors in vivo.

6.
Am J Transl Res ; 14(4): 2637-2646, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559381

RESUMO

OBJECTIVE: To analyze the clinical efficacy and possible mechanism of butylphthalide in treatment of acute ischemic stroke. METHODS: In this retrospective study, 127 patients with ischemic stroke, hospitalized during Jan. 2019 to Jan. 2021, were enrolled and as assigned to observation group (n=65) and control group (n=62) according to treatment methods. The control group received routine treatment, and the observation group was treated with butylphthalide injection in addition to conventional cure. The treatments lasted for 2 weeks in both groups. Subsequently, the recovery of neurological deficits (NIHSS) and Barthel index (BI) of the two groups of patients, cerebrovascular vascular reserve function (CVR) values and pulsation index (PI) before and after treatment, and the levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and recombinant basic fibroblast growth factor (bFGF) were detected. The expression of Keap1-Nrf2/ARE signaling pathway related molecules was detected by ELISA. RESULTS: The overall response rate (ORR) of observation group was remarkably superior to that of control group (P<0.05). NIHSS score obviously decreased while BI remarkably increased in both groups after treatment (all P<0.05); and the observation group showed an significantly higher BI score but significantly lower NIHSS score compared with the control group (all P<0.05). The CVR of the two groups of patients after treatment was significantly higher than that before treatment (P<0.05), while PI was significantly lower than before treatment (P<0.05); The CVR of observation-group after treatment was substantially higher than that of control-group (P<0.05), while PI was lower than control-group (P<0.05). Serum Keap1 levels of the two groups of patients after treatment were significantly higher than that before treatment (P<0.05), while serum levels of NQO1, Nrf2, and ARE were significantly lower than that before treatment (P<0.05). The serum level of Keap1 in the observation group was remarkably higher than that of the control group (P<0.05), while the serum levels of NQO1, Nrf2 and ARE were evidently lower than those in the control group (P<0.05). The two groups had insignificant difference in incidence of adverse reactions (P>0.05). CONCLUSION: The butylphthalide can effectively improve the clinical efficacy of acute ischemic stroke, and promote patients' neurological function and activities of daily living. The mechanism may be that butylphthalide improves the CVR of patients, enhances the establishment of collateral compensatory vessels, and changes the expression of the Keap1-Nrf2/ARE signaling pathway, thereby exerting the neuroprotective effect. Clinically, butylphthalide may have good safety in adjuvant therapy of acute ischemic stroke.

7.
Molecules ; 27(9)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35566138

RESUMO

Plastic-bonded explosives (PBXs) consisting of explosive grains and a polymer binder are commonly synthesized to improve mechanical properties and reduce sensitivity, but their intrinsic chemical behaviors while subjected to stress are not sufficiently understood yet. Here, we construct three composites of ß-HMX bonded with the HTPB binder to investigate the reaction characteristics under shock loading using the quantum-based molecular dynamics method. Six typical interactions between HMX and HTPB molecules are detected when the system is subjected to pressure. Although the initial electron structure is modified by the impurity states from HTPB, the metallization process for HMX does not significantly change. The shock decompositions of HMX/HTPB along the (100) and (010) surface are initiated by molecular ring dissociation and hydrogen transfer. The initial oxidations of C and H within HTPB possess advantages. As for the (001) surface, the dissociation is started with alkyl dehydrogenation oxidation, and a stronger hydrogen transfer from HTPB to HMX is detected during the following process. Furthermore, considerable fragment aggregation is observed, which mainly derives from the formation of new C-C and C-N bonds under high pressure. The effect of cluster evolution on the progression of the following reaction is further studied by analyzing the bonded structure and displacement rate.

8.
Polymers (Basel) ; 14(9)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35566875

RESUMO

In this study, we reported PVA nanocomposite films enhanced by polyethyleneimine (PEI)-lignin contained cellulose nanofibers (LCNFs) via the solvent casting method. An easy and available method was preformed to prepare LCNFs using a supermasscolloider from unbleached bamboo waste after a mild alkaline pretreatment. The results demonstrate that LCNF-PEI can greatly improve mechanical, hydrophobic, anti-UV shielding and antibacterial properties of the composite films. The tensile strength of LPP1 film was improved to 54.56 MPa, which was higher than 39.37 MPa of PVA film. The water contact angle of films increased from 35° to 104° with an increase in LCNF content from 0 to 6 wt%. Meanwhile, the nanocomposite film demonstrated the effect of full shielding against ultraviolet light when the amount of LCNF-PEI reached 6 wt%. The addition of LCNF-PEI endowed excellent antibacterial activity (against S. aureus and E. coli), which indicated potential applications in the packaging field.

9.
J Med Chem ; 65(9): 6573-6592, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35500243

RESUMO

EZH2 inhibitors that prevent trimethylation of histone lysine 27 (H3K27) are often limited to the treatment of a subset of hematological malignancies. In most solid tumors, EZH2 inhibitors induce reciprocal H3K27 acetylation that subsequently results in acquired drug resistance. The combination of EZH2 and BRD4 inhibitors to resensitize solid cancer cells to EZH2 inhibitors has proven to be effective, underlying the significance of developing dual inhibitors. Herein, we present the design, synthesis, and biological evaluation of first-in-class dual EZH2/BRD4 inhibitors. Our most promising compound, YM458, displays potent inhibitory activity against EZH2 and BRD4 and remarkable antiproliferative capacity against 11 solid cancer cell lines. Its in vivo therapeutic potential is validated in both lung cancer and pancreatic cancer xenograft tumor mice models, highlighting the potential of EZH2/BRD4 dual inhibitors to target a broad scope of EZH2 inhibitor-resistant solid tumors.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35560074

RESUMO

In a regression setup, we study in this brief the performance of Gaussian empirical gain maximization (EGM), which includes a broad variety of well-established robust estimation approaches. In particular, we conduct a refined learning theory analysis for Gaussian EGM, investigate its regression calibration properties, and develop improved convergence rates in the presence of heavy-tailed noise. To achieve these purposes, we first introduce a new weak moment condition that could accommodate the cases where the noise distribution may be heavy-tailed. Based on the moment condition, we then develop a novel comparison theorem that can be used to characterize the regression calibration properties of Gaussian EGM. It also plays an essential role in deriving improved convergence rates. Therefore, the present study broadens our theoretical understanding of Gaussian EGM.

11.
Methods Mol Biol ; 2504: 91-100, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35467281

RESUMO

Extracellular vesicles (EVs) secreted by human pluripotent stem cells-derived cardiovascular progenitor cells (hPSC-CVPCs) can improve repair of infarcted hearts in mouse and nonhuman primate myocardial infarction models. To fully achieve their values, it is essential to establish an efficient method for the isolation of EVs from hPSC-CVPCs. Here we describe the protocols for efficient isolation and characterization of EVs from the conditioned medium of hPSC-CVPCs.


Assuntos
Vesículas Extracelulares , Infarto do Miocárdio , Células-Tronco Pluripotentes , Animais , Meios de Cultivo Condicionados , Coração , Humanos , Camundongos , Infarto do Miocárdio/terapia
12.
ACS Omega ; 7(12): 10137-10143, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35382286

RESUMO

With the demand for carbon dioxide emission reduction, the sustainable conversion of useless biomass into high-value energy storage devices has received excellent scientific and technological attention. The high synthesis cost and low specific capacitance limited the supercapacitor application. Therefore, biomass-derived sulfur-doping porous carbon (SPC) has been synthesized from ulothrix using simple pyrolysis and chemical activation methods. The unique activated carbon material exhibits a high specific surface area (2490 m2 g-1), and the effect of the activator addition ratio was systematically investigated. The optimized SPC-2 displayed a high specific capacitance (324 F g-1 at 1 A g-1) and excellent cycling stability (90.6% retention after 50 000 cycles). Furthermore, a symmetric supercapacitor (SSC) based on SPC-2 demonstrated a high energy density (12.9 Wh kg-1) at an 800 W kg-1 power density. This work offers a simple, economical, and ecofriendly synthetic strategy of converting widespread, useless biomass waste into high-performance supercapacitor applications.

13.
Health Phys ; 122(5): 594-606, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35383636

RESUMO

ABSTRACT: A quasi-dynamic food chain model (Chi-FDMT) was developed to predict the consequences of nuclear accidents on the food chain through the ingestion pathway in Chinese agricultural conditions. The Chi-FDMT structure is based on ECOSYS-87, with some revised calculation processes and the adoption of new parameters; herein, it was applied to two regions in China. The model was used to estimate the spatial and temporal patterns of crop plant activity and ingestion dose in the Chinese agricultural environment at the scale of the Fukushima nuclear disaster. A comparative study between Chi-FDMT and an equilibrium model demonstrated good agreement for depositions occurring during the growth season. The parameter sensitivity analysis of Chi-FDMT indicated that the parameters of food intake and processing factor are sensitive, and the sensitivity of the transfer factors within plant and soil-plant systems are dependent on the deposition scenario.


Assuntos
Cadeia Alimentar , Acidente Nuclear de Fukushima , Agricultura , China , Solo/química
14.
Front Plant Sci ; 13: 839044, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386679

RESUMO

Genomic copy number variations (CNVs) are among the most important structural variations of genes found to be related to the risk of individual cancer and therefore they can be utilized to provide a clue to the research on the formation and progression of cancer. In this paper, an improved computational gene selection algorithm called CRIA (correlation-redundancy and interaction analysis based on gene selection algorithm) is introduced to screen genes that are closely related to cancer from the whole genome based on the value of gene CNVs. The CRIA algorithm mainly consists of two parts. Firstly, the main effect feature is selected out from the original feature set that has the largest correlation with the class label. Secondly, after the analysis involving correlation, redundancy and interaction for each feature in the candidate feature set, we choose the feature that maximizes the value of the custom selection criterion and add it into the selected feature set and then remove it from the candidate feature set in each selection round. Based on the real datasets, CRIA selects the top 200 genes to predict the type of cancer. The experiments' results of our research show that, compared with the state-of-the-art related methods, the CRIA algorithm can extract the key features of CNVs and a better classification performance can be achieved based on them. In addition, the interpretable genes highly related to cancer can be known, which may provide new clues at the genetic level for the treatment of the cancer.

15.
Sci China Life Sci ; 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35391626

RESUMO

Centromere identity is defined by nucleosomes containing CENP-A, a histone H3 variant. The deposition of CENP-A at centromeres is tightly regulated in a cell-cycle-dependent manner. We previously reported that the spatiotemporal control of centromeric CENP-A incorporation is mediated by the phosphorylation of CENP-A Ser68. However, a recent report argued that Ser68 phosphoregulation is dispensable for accurate CENP-A loading. Here, we report that the substitution of Ser68 of endogenous CENP-A with either Gln68 or Glu68 severely impairs CENP-A deposition and cell viability. We also find that mice harboring the corresponding mutations are lethal. Together, these results indicate that the dynamic phosphorylation of Ser68 ensures cell-cycle-dependent CENP-A deposition and cell viability.

16.
Front Plant Sci ; 13: 818909, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422824

RESUMO

Polygonum cuspidatum Sieb. et Zucc is an important industrial crop because it contains a large amount of medicinal secondary metabolites (such as polydatin, resveratrol, chrysophanol, and emodin). However, it is unclear whether root endophytic fungi increase the content of secondary metabolites in the plant. This study aimed to analyze the effects of Funneliformis mosseae (Fm) and Piriformospora indica (Pi) alone or in combination on plant growth, root morphology, thirteen sugars concentrations, and six secondary metabolites (physcion, chrysophanol, emodin, aloe-emodin, polydatin, and resveratrol) concentrations of P. cuspidatum. After 11 weeks of the fungal inoculation, the roots could be colonized by Fm and Pi single or in combination, along with the higher root colonization frequency of Fm > Pi > Fm + Pi in the descending order. In addition, Fm and Pi improved plant growth performance (plant height, stem diameter, leaf number, and shoot and root biomass) and root morphology (average diameter, maximum diameter, total length, area, and volume) to varying degrees, depending on fungal inoculations, in which Pi displayed a relatively better effect on plant growth. Single Fm and Pi inoculation significantly increased three disaccharides (sucrose, maltose, and trehalose) accumulation, while dual inoculum (Fm + Pi) only elevated sucrose concentrations. Most monosaccharides concentrations, such as D-arabinose, D-galactose, D-sorbitol, D-fructose, glucose, and L-rhamnose were not altered or inhibited by the endophytic fungi, except the increase in L-fucose and inositol. All fungal treatments significantly increased root chrysophanol and resveratrol concentrations, while decreased aloe-emodin concentrations. In addition, single Pi and dual Fm + Pi increased emodin concentrations, and single Fm and dual Fm + Pi elevated physcion and polydatin concentrations. It was concluded that Fm and Pi promoted the growth of P. cuspidatum, and the combination of Fm and Pi was more conducive to the production of some secondary metabolites than single inoculation.

17.
CNS Neurosci Ther ; 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35429132

RESUMO

AIMS: This multicenter, open-label, randomized study (Registration No. ChiCTR-OCH-14004528) aimed to compare the efficacy and effects of oxcarbazepine (OXC) with levetiracetam (LEV) as monotherapies on patient quality of life and mental health for patients with newly diagnosed focal epilepsy from China. METHODS: Patients with newly diagnosed focal epilepsy who had experienced 2 or more unprovoked seizures at greater than a 24-h interval during the previous year were recruited. Participants were randomly assigned to the OXC group or LEV group. Efficacy, safety, quality of life, and mental health were evaluated over 12-week and 24-week periods. RESULTS: In total, we recruited 271 newly diagnosed patients from 23 centers. Forty-four patients were excluded before treatment for reasons. The rate of seizure freedom of OXC was significantly superior to that of LEV at 12 weeks and 24 weeks (p < 0.05). The quality of life (except for the seizure worry subsection) and anxiety scale scores also showed significant differences from before to after treatment in the OXC and LEV groups. CONCLUSIONS: OXC monotherapy may be more effective than LEV monotherapy in patients with newly diagnosed focal epilepsy. Both OXC and LEV could improve the quality of life and anxiety state in adult patients with focal epilepsy.

18.
Drug Discov Today ; 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35390545

RESUMO

Clostridioides difficile bacteria can cause life-threatening diarrhea and colitis owing to limited treatment options and unacceptably high recurrence rates among infected patients. This necessitates the development of alternative routes for C. difficile treatment. Drug repurposing with new indications represents a proven shortcut. Here, we present a refined focus on 16 FDA-approved drugs that would be suitable for further development as potential anti-C. difficile drugs. Of these drugs, clinical trials have been conducted on five currently used drugs; however, ursodeoxycholic acid is the only drug to enter Phase IV clinical trials to date. Thus, drug repurposing promotes the study of mechanistic and therapeutic strategies, providing new options for the development of next-generation anti-C. difficile agents.

19.
Artigo em Inglês | MEDLINE | ID: mdl-35471884

RESUMO

Attention Deficit Hyperactivity Disorder (ADHD) is a type of mental health disorder that can be seen from children to adults. Accurate diagnosis of ADHD as early as possible is very important for the treatment of patients in clinical applications. In this paper, we propose two novel deep learning approaches for ADHD classification based on functional magnetic resonance imaging (fMRI). The first method incorporates independent component analysis with convolutional neural network. It first extracts independent components from each subject. The independent components are then fed into a convolutional neural network as input features to classify the ADHD patients from typical controls. The second method, called the correlation autoencoder method, uses correlations between regions of interest of the brain as the input of an autoencoder to learn latent features, which are then used in the classification task by a new neural network. These two methods use different ways to extract the inter-voxel information from fMRI, but both use convolutional neural networks to further extract predictive features for the classification task. Empirical experiments show that both methods are able to outperform the classical methods such as logistic regression, support vector machines, and some other methods used in previous studies.

20.
Opt Express ; 30(9): 15037-15048, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35473235

RESUMO

High speed surface defects detection of mirrors is of great significance, for detecting the quality of the mirrors on-site, and ultimately for monitoring the operating states of laser systems. The speeds of conventional proposals are relatively low as they utilize mechanically scanning methods or two-dimensional charge-coupled devices. Here, we propose a high speed surface detection method based on ultrafast single-pixel imaging, which consists of a spatial Fourier optical module for frequency-space mapping and a dispersive Fourier transform module for frequency-time mapping. An optical grating is utilized to map the wideband spectrum of dissipative soliton into the spatial domain under far-field diffraction, where the mirror is inspected. Dispersive Fourier transform is used to map the surface-defects-coded spectral information into the temporal domain, then recorded by a high speed single-pixel detector. The detection system permits continuous single-shot spectra measurement with a frame rate equivalent to the pulse repetition rate (8.4 MHz). We extract amplitude defects by demodulating light intensity, and obtain phase defects by demodulating the interference spectrum with a Mach-Zehnder interferometer structure. Experimental results show that the damaged mirror with a two-dimensional width of 10 × 13 mm can be obtained with a spatial resolution of 90 µm. The obtained phase accuracy after Hilbert transformation is 0.00217 rad, corresponding to a depth resolution of 51 nm. This scheme can find promising applications for surface defects detection of large aperture mirrors, and real-time monitoring of laser systems with high energy.

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