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1.
Front Aging Neurosci ; 13: 742176, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34819847

RESUMO

The detailed characteristics of neuronal cell populations in Alzheimer's disease (AD) using single-cell RNA sequencing have not been fully elucidated. To explore the characterization of neuronal cell populations in AD, this study utilized the publicly available single-nucleus RNA-sequencing datasets in the transgenic model of 5X familial Alzheimer's disease (5XFAD) and wild-type mice to reveal an AD-associated excitatory neuron population (C3:Ex.Neuron). The relative abundance of C3:Ex.Neuron increased at 1.5 months and peaked at 4.7 months in AD mice. Functional pathways analyses showed that the pathways positively related to neurodegenerative disease progression were downregulated in the C3:Ex.Neuron at 1.5 months in AD mice. Based on the differentially expressed genes among the C3:Ex.Neuron, four subtypes (C3.1-4) were identified, which exhibited distinct abundance regulatory patterns during the development of AD. Among these subtypes, the C3.1 neurons [marked by netrin G1 (Ntng1)] exhibited a similar regulatory pattern as the C3:Ex.Neuron in abundance during the development of AD. In addition, our gene set variation analysis (GSEA) showed that the C3.1 neurons, instead of other subtypes of the C3:Ex.Neuron, possessed downregulated AD pathways at an early stage (1.5 months) of AD mice. Collectively, our results identified a previously unidentified subset of excitatory neurons and provide a potential application of these neurons to modulate the disease susceptibility.

3.
Adv Mater ; : e2108114, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34813680

RESUMO

Metallic magnesium batteries are promising candidates beyond lithium-ion batteries; however, a passive interfacial layer because of the electro-reduction of solvents on Mg surfaces usually leads to ultra-high overpotential for the reversible Mg chemistry. Inspired by the excellent separation effect of permselective metal-organic framework (MOF) at angstrom scale, we here construct a large-area and defect-free MOF membrane directly on Mg surfaces. In this process, the electrochemical deprotonation of ligand can be facilitated to afford the self-healing of intercrystalline voids until a seamless membrane formed, which can eliminate nonselective intercrystalline diffusion of electrolyte and realize selective Mg2+ transport but precisely separate the solvent molecules from the MOF channels. Compared with the continuous solvent reduction on bare Mg anode, the as-constructed MOF membrane is demonstrated to significantly stabilize the Mg electrode via suppressing the permeation of solvents, hence contributing to a low-overpotential plating/stripping in conventional electrolytes. We demonstrate the concept that membrane separation can serve as solid-electrolyte interphase, which would be widely applicable to other energy-storage systems. This article is protected by copyright. All rights reserved.

4.
Sci Rep ; 11(1): 21430, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728708

RESUMO

Artificial neural network (ANN) is the main tool to dig data and was inspired by the human brain and nervous system. Several studies clarified its application in medicine. However, none has applied ANN to predict the efficacy of folic acid treatment to Hyperhomocysteinemia (HHcy). The efficacy has been proved to associate with both genetic and environmental factors while previous studies just focused on the latter one. The explained variance genetic risk score (EV-GRS) had better power and could represent the effect of genetic architectures. Our aim was to add EV-GRS into environmental factors to establish ANN to predict the efficacy of folic acid therapy to HHcy. We performed the prospective cohort research enrolling 638 HHcy patients. The multilayer perception algorithm was applied to construct ANN. To evaluate the effect of ANN, we also established logistic regression (LR) model to compare with ANN. According to our results, EV-GRS was statistically associated with the efficacy no matter analyzed as a continuous variable (OR = 3.301, 95%CI 1.954-5.576, P < 0.001) or category variable (OR = 3.870, 95%CI 2.092-7.159, P < 0.001). In our ANN model, the accuracy was 84.78%, the Youden's index was 0.7073 and the AUC was 0.938. These indexes above indicated higher power. When compared with LR, the AUC, accuracy, and Youden's index of the ANN model (84.78%, 0.938, 0.7073) were all slightly higher than the LR model (83.33% 0.910, 0.6687). Therefore, clinical application of the ANN model may be able to better predict the folic acid efficacy to HHcy than the traditional LR model. When testing two models in the validation set, we got the same conclusion. This study appears to be the first one to establish the ANN model which added EV-GRS into environmental factors to predict the efficacy of folic acid to HHcy. This model would be able to offer clinicians a new method to make decisions and individual therapeutic plans.

6.
iScience ; 24(11): 103296, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34755101

RESUMO

Autophagy is a conserved biological process that maintains cell homeostasis by targeting macromolecules for lysosome-mediated degradation. The levels of autophagy are relatively lower under normal conditions than under stress conditions (e.g., starvation), as autophagy is usually stimulated after multiple stresses. However, many autophagy-related regulators are still expressed under normal conditions. Although these regulators have been studied deeply in autophagy regulation, the nonautophagic roles of these regulators under normal conditions remain incompletely understood. Here, we found that autophagy-related 5 (ATG5), which is a key regulator of autophagy, regulates c-Myc protein degradation under normal conditions through the ubiquitin-proteasome pathway. We also found that ATG5 binds c-Myc and recruits the E3 ubiquitin-protein ligase FBW7 to promote c-Myc degradation. Moreover, ATG5-mediated degradation of c-Myc limits cell growth under normal conditions and is essential for embryonic stem cell differentiation. Therefore, this study reveals a nonautophagic role of ATG5 in regulating of c-Myc protein degradation.

7.
Int J Infect Dis ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34800687

RESUMO

OBJECTIVES: To estimate the COVID-19 vaccine effectiveness (VE) against concerned outcomes in real-world settings. METHODS: We included studies reported the COVID-19 VE from August 6, 2020, to October 6, 2021. We estimated the summary VE with 95% confidence intervals (95% CIs) against disease related to COVID-19. The results were presented in forest plots. Predefined subgroup analysis and sensitivity analysis was also performed. RESULTS: 51 records were included in this meta-analysis. In the full vaccination, the VE against SARS-CoV-2 infection, COVID-19 related hospitalization, admission to ICU, and death were 89.1% (95% CI, 85.6 to 92.6), 97.2% (95% CI, 96.1 to 98.3), 97.4% (95% CI, 96.0 to 98.8) and 99.0% (95% CI, 98.5 to 99.6), respectively. It showed that the VE against infection for general population aged 16 years or older, the elderly and health care workers (HCWs) were 86.1% (95% CI, 77.8 to 94.4), 83.8% (95% CI, 77.1 to 90.6) and 95.3% (95% CI, 92.0 to 98.6), respectively. For full vaccination against infection, 91.2% effectiveness of the Pfizer-BioNTech vaccine and the 98.1% effectiveness of Moderna vaccine were observed, while 65.7% effectiveness of the CoronaVac were reported. CONCLUSIONS: The COVID-19 vaccines are highly protective against SARS-CoV-2 related diseases in the real-world settings.

8.
BMC Microbiol ; 21(1): 299, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715786

RESUMO

BACKGROUND: Peanut (Arachis hypogaea L.) is an important oil and economic crop. Calcium modulates plants in response to abiotic stresses and improves plant resistance to pathogens. Enrichment of beneficial microorganisms in the rhizosphere is associated with plant disease resistance and soil development. The purpose of this study was to analyze the differences in peanut rhizosphere microbial community structure between the calcium treatment and the control during two growth stages and to explain why calcium application could improve the resistance of peanuts to soil-borne pathogens. RESULTS: The 16S rDNA amplicon sequencing of rhizosphere microbiome showed that calcium application significantly enriched Serratia marcescens and other three dominant strains at the seedling stage. At the pod filling stage, ten dominant stains such as Sphingomonas changbaiensis and Novosphingobium panipatense were enriched by calcium. Serratia marcescens aseptic fermentation filtrate was mixed with PDA medium and inoculated with the main soil-borne pathogens in the seedling stage, which could inhibit the growth of Fusarium solani and Aspergillus flavus. The aseptic fermentation filtrate of Novosphingobium panipatense was mixed with PDA medium and inoculated with the main soil-borne pathogens in the pod filling stage, which could inhibit the growth of Sclerotium rolfsii and Leptosphaerulina arachidicola. CONCLUSIONS: Calcium application increases the resistance of peanuts to soil-borne pathogens by enriching them with specific dominant bacteria.

9.
Appl Opt ; 60(26): 7888-7893, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34613047

RESUMO

A dual-output filter-free microwave photonic single sideband (SSB) up-converter with the mixing spurs highly suppressed is proposed and experimentally demonstrated. By introducing the balanced Hartley structure using a 90° optical hybrid, the lower sideband (LSB) and upper sideband (USB) up-converted RF signals can be generated simultaneously and output separately, with no need of either optical or electrical filtering. The structure avoids the special requirement with the optical modulation format of the local oscillator (LO) signal. The intermediate frequency signal is modulated with the optical carrier suppressed -SSB modulation format. The undesired optical components are highly suppressed. In this way, the high sideband and LO leakage suppression ratios of the SSB up-converter are guaranteed. The dual-output SSB up-conversion is experimentally achieved within the working frequency range of 10-30 GHz. The undesired sideband and LO leakage suppression ratios are larger than 67 dB for the whole frequency range. The spurious-free dynamic range of larger than 95.6dBc⋅Hz2/3 has also been achieved experimentally for both the LSB and USB up-conversion conditions.

10.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(5): 612-615, 2021 Oct 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34636212

RESUMO

Parotid gland tumors are usually solitary tumors, and multiple tumors of the parotid gland are extremely rare. We present a highly unusual case of bilateral and simultaneous pleomorphic adenoma and basal cell adenoma of the parotid gland. We review the literature and discuss the clinical manifestations, diagnosis, and treatment of these two rare tumors.


Assuntos
Adenoma Pleomorfo , Neoplasias Parotídeas , Humanos , Glândula Parótida , Neoplasias Parotídeas/diagnóstico
11.
Polymers (Basel) ; 13(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34641093

RESUMO

Nanocomposite foam with a large expansion ratio and thin cell walls is promising for electromagnetic interference (EMI) shielding materials, due to the low electromagnetic (EM) reflection and high EM absorption. To overcome the dimensional limitation from two-dimension (2D) thin walls on the construction of conductive network, a strategy combining hybrid conductive nanofillers in semi-crystalline matrix together with supercritical CO2 (scCO2) foaming was applied: (1) one-dimension (1D) CNTs with moderate aspect ratio was used to minimize the dimensional confinement from 2D thin walls while constructing the main EM absorbing network; (2) zero-dimension (0D) carbon black (CB) with no dimensional confinement was used to connect the separated CNTs in thin walls and to expand the EM absorbing network; (3) scCO2 foaming was applied to obtain a cellular structure with multi-layer thin walls and a large amount of air cells to reduce the reflected EM; (4) semi-crystalline polymer was selected so that the rheological behavior could be adjusted by optimizing crystallization and filler content to regulate the cellular structure. Consequently, an advanced material featured as lightweight, high EM absorption and low EM reflection was obtained at 0.48 vol.% hybrid nanofillers and a density of 0.067 g/cm3, whose specific EMI shielding performance was 183 dB cm3/g.

12.
PLoS Pathog ; 17(10): e1009928, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34695164

RESUMO

Non-specific protective effects of certain vaccines have been reported, and long-term boosting of innate immunity, termed trained immunity, has been proposed as one of the mechanisms mediating these effects. Several epidemiological studies suggested cross-protection between influenza vaccination and COVID-19. In a large academic Dutch hospital, we found that SARS-CoV-2 infection was less common among employees who had received a previous influenza vaccination: relative risk reductions of 37% and 49% were observed following influenza vaccination during the first and second COVID-19 waves, respectively. The quadrivalent inactivated influenza vaccine induced a trained immunity program that boosted innate immune responses against various viral stimuli and fine-tuned the anti-SARS-CoV-2 response, which may result in better protection against COVID-19. Influenza vaccination led to transcriptional reprogramming of monocytes and reduced systemic inflammation. These epidemiological and immunological data argue for potential benefits of influenza vaccination against COVID-19, and future randomized trials are warranted to test this possibility.


Assuntos
COVID-19/imunologia , Proteção Cruzada/fisiologia , Imunidade Inata/fisiologia , Vacinas contra Influenza/administração & dosagem , COVID-19/epidemiologia , COVID-19/prevenção & controle , Citocinas/imunologia , Citocinas/metabolismo , Regulação para Baixo , Imidazóis/imunologia , Incidência , Vacinas contra Influenza/imunologia , Países Baixos/epidemiologia , Recursos Humanos em Hospital , Poli I-C/imunologia , Proteômica , Fatores de Risco , Análise de Sequência de RNA
13.
Stem Cell Res ; 57: 102581, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34688993

RESUMO

Serine hydroxymethyltransferase 2 (SHMT2), a catalytic enzyme playing an important role in aerobic cellular respiration and mitochondrial metabolism, might be pivotal in self-renewal and differentiation of human pluripotent stem cells. Herein, we used the CRISPR/Cas9 editing system to construct a homozygous SHMT2 knockout (SHMT2-KO) human embryonic stem cell (hESC) line, exhibiting a normal karyotype, colony morphology, and high expression levels of pluripotent proteins. Furthermore, SHMT2 knockout did not impact the self-renewal ability or differentiation potential into three germ layers of hESCs. Accordingly, this cell line provides a valuable model for further assessing SHMT2 functions in human embryonic development.

14.
J Hazard Mater ; 424(Pt B): 127508, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34688005

RESUMO

Nanoplastics can be ingested by organisms and penetrate biological barriers to affect multiple physiological functions. However, few studies have focused on the effects of nanoplastics on the mammalian immune system. We evaluated the effects and underlying mechanism of nanoplastics of varying particle sizes and surface charges on murine splenic lymphocytes. We found that nanoplastics penetrated into splenic lymphocytes and that nanoplastics of a diameter of 50 nm were absorbed more efficiently by the cells. The nanoplastics decreased cell viability, induce cell apoptosis, up-regulated apoptosis-related protein expression, elicited the production of reactive oxygen species, altered mitochondrial membrane potential, and impaired mitochondrial function. Positively charged nanoplastics exerted the strongest toxicity. Negatively charged and uncharged nanoplastics caused oxidative stress and mitochondrial structural damage in lymphocytes, while positively charged nanoplastics induced endogenous apoptosis directly. Moreover, nanoplastics inhibited the expression of activated T cell markers on the T cell surface, while inhibiting the differentiation of CD8+ T cells and the expression of helper T cell cytokines. In terms of the mechanism, a series of key signaling molecules in the pathways of T cell activation and function were markedly down-regulated after exposure to nanoplastics.

15.
J Sport Health Sci ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34547483

RESUMO

BACKGROUND: A goal of 10,000 steps per day is widely advocated, but there is little evidence to support that goal. Our purpose was to examine the dose-response relationships between step count and all-cause mortality and cardiovascular disease risk. METHODS: Cochrane Central Register of Controlled Trials, EMBASE, OVID, PubMed, Scopus, and Web of Science databases were systematically searched for studies published before July 9, 2021, that evaluated the association between daily steps and at least 1 outcome. RESULTS: Sixteen publications (12 related to all-cause mortality, 5 related to cardiovascular disease; and 1 article contained 2 outcomes: both all-cause death and cardiovascular events) were eligible for inclusion in the meta-analysis. There was evidence of a nonlinear dose-response relationship between step count and risk of all-cause mortality or cardiovascular disease (p = 0.002 and p = 0.014 for nonlinearity, respectively). When we restricted the analyses to accelerometer-based studies, the third quartile had a 40.36% lower risk of all-cause mortality and a 35.05% lower risk of cardiovascular event than the first quartile (all-cause mortality: Q1 = 4183 steps/day, Q3 = 8959 steps/day; cardiovascular event: Q1 = 3500 steps/day, Q3 = 9500 steps/day; respectively). CONCLUSION: Our meta-analysis suggests inverse associations between higher step count and risk of premature death and cardiovascular events in middle-aged and older adults, with nonlinear dose-response patterns.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34478371

RESUMO

We propose a partial point cloud completion approach for scenes that are composed of multiple objects. We focus on pairwise scenes where two objects are in close proximity and are contextually related to each other, such as a chair tucked in a desk, a fruit in a basket, a hat on a hook and a flower in a vase. Different from existing point cloud completion methods, which mainly focus on single objects, we design a network that encodes not only the geometry of the individual shapes, but also the spatial relations between different objects. More specifically, we complete the missing parts of the objects in a conditional manner, where the partial or completed point cloud of the other object is used as an additional input to help predict the missing parts. Based on the idea of conditional completion, we further propose a two-path network, which is guided by a consistency loss between different sequences of completion. Our method can handle difficult cases where the objects heavily occlude each other. Also, it only requires a small set of training data to reconstruct the interaction area compared to existing completion approaches. We evaluate our method qualitatively and quantitatively via ablation studies and in comparison to the state-of-the-art point cloud completion methods.

17.
Colloids Surf B Biointerfaces ; 208: 112087, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34500204

RESUMO

Herein, the Cu2O yolk-shell nanospheres, nanocubes and microcubes were successfully prepared by a simple seed-medium process. The formation of the Cu2O yolk-shell nanospheres can be attributed to the self-assembly process caused by the introduction of the seed medium. The formation mechanism of our obtained Cu2O yolk-shell nanospheres and the dependence of Cu2O morphology on different surfactants have been studied. The obtained samples were applied in the field of non-enzymatic glucose detection. The electrochemical response characteristics of the modified electrodes toward glucose were investigated by cyclic voltammetry (CV) and chronoamperometry (CA). The electrode modified with C-Cu2O (obtained by using CTAB as surfactant) shared the highest sensitivity of 3123 µAmM-1 cm-2, whereas, the electrode modified with S-Cu2O (obtained by using SDBS as surfactant) exhibited the lowest LOD of 0.87 µM and the widest linear range of 0.05-10.65 mM. All obtained sensors showed fast response to the addition of glucose. The obtained electrodes showed better responses to glucose than other coexisting interferences, indicating that the obtained electrodes had the acceptable selectivity to glucose. In addition, the stability for 5 consecutive weeks had also been studied and exhibited satisfactory results. The obtained electrode was also used to detect the glucose content in real serum. The acceptable selectivity, stability together with the excellent sensing ability in real serum make the obtained electrodes a potential for practical applications.


Assuntos
Técnicas Biossensoriais , Cobre , Técnicas Eletroquímicas , Eletrodos , Glucose , Tensoativos
18.
J Hematol Oncol ; 14(1): 136, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479611

RESUMO

Extracellular vesicles (EVs) are cell-derived membrane structures enclosing proteins, lipids, RNAs, metabolites, growth factors, and cytokines. EVs have emerged as essential intercellular communication regulators in multiple physiological and pathological processes. Previous studies revealed that mesenchymal stem cells (MSCs) could either support or suppress tumor progression in different cancers by paracrine signaling via MSC-derived EVs. Evidence suggested that MSC-derived EVs could mimic their parental cells, possessing pro-tumor and anti-tumor effects, and inherent tumor tropism. Therefore, MSC-derived EVs can be a cell-free cancer treatment alternative. This review discusses different insights regarding MSC-derived EVs' roles in cancer treatment and summarizes bioengineered MSC-derived EVs' applications as safe and versatile anti-tumor agent delivery platforms. Meanwhile, current hurdles of moving MSC-derived EVs from bench to bedside are also discussed.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/citologia , Neoplasias/terapia , Animais , Antineoplásicos/uso terapêutico , Apoptose , Proliferação de Células , Vesículas Extracelulares/transplante , Humanos , Células-Tronco Mesenquimais/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia
19.
Cell Metab ; 33(10): 2076-2089.e9, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34343500

RESUMO

Ionizing radiation-induced DNA damages cause genome instability and are highly cytotoxic. Deoxyribonucleotide metabolism provides building blocks for DNA repair. Nevertheless, how deoxyribonucleotide metabolism is timely regulated to coordinate with DNA repair remains elusive. Here, we show that ionizing radiation results in TBK1-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2 at T228, thereby enhancing PRPS1/2 catalytic activity and promoting deoxyribonucleotide synthesis. DNA damage-elicited activation of cGAS/STING axis and ATM-mediated PRPS1/2 S16 phosphorylation are required for PRPS1/2 T228 phosphorylation under ionizing radiation. Furthermore, T228 phosphorylation overrides allosteric regulator-mediated effects and preserves PRPS1/2 with high activity. The expression of non-phosphorylatable PRPS1/2 mutants or inhibition of cGAS/STING axis counteracts ionizing radiation-induced PRPS1/2 activation, deoxyribonucleotide synthesis, and DNA repair, and further impairs cell viability. This study highlights a novel and important mechanism underlying an innate immune response-guided deoxyribonucleotide metabolism, which supports DNA repair.

20.
Front Cell Dev Biol ; 9: 662780, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268302

RESUMO

Non-syndromic cleft lip and palate (NSCLP) is one of the most common congenital malformations with multifactorial etiology. Although long non-coding RNAs (lncRNAs) have been implicated in the development of lip and palate, their roles in NSCLP are not fully elucidated. This study aimed to investigate how dysregulated lncRNAs contribute to NSCLP. Using lncRNA sequencing, bioinformatics analysis, and clinical tissue sample detection, we identified that lncRNA ZFAS1 was significantly upregulated in NSCLP. The upregulation of ZFAS1 mediated by SP1 transcription factor (SP1) inhibited expression levels of Wnt family member 4 (WNT4) through the binding with CCCTC-binding factor (CTCF), subsequently inactivating the WNT/ß-catenin signaling pathway, which has been reported to play a significant role on the development of lip and palate. Moreover, in vitro, the overexpression of ZFAS1 inhibited cell proliferation and migration in human oral keratinocytes and human umbilical cord mesenchymal stem cells (HUC-MSCs) and also repressed chondrogenic differentiation of HUC-MSCs. In vivo, ZFAS1 suppressed cell proliferation and numbers of chondrocyte in the zebrafish ethmoid plate. In summary, these results indicated that ZFAS1 may be involved in NSCLP by affecting cell proliferation, migration, and chondrogenic differentiation through inactivating the WNT/ß-catenin signaling pathway.

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