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1.
Int J Biol Macromol ; 192: 250-257, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34627844

RESUMO

The bioconversion of chitin into N-acetyl-d-glucosamine (GlcNAc) using chitinolytic enzymes is one of the important avenues for chitin valorization. However, industrial applications of chitinolytic enzymes have been limited by their poor thermostability. Therefore, it is necessary to discover thermostable chitinolytic enzymes for GlcNAc production from chitin. In this study, two chitinolytic enzyme-encoding genes CaChiT and CaHex from Caldicellulosiruptor acetigenus were identified and heterologously expressed in Escherichia coli. The purified recombinant CaChiT and CaHex showed optimal activities at 70 °C and 90 °C respectively, and exhibited good thermostability over a range of temperature below 70 °C and broad pH stability at pH range of 3.0-8.0. CaChiT and CaHex were active on colloidal chitin, pNP-(GlcNAc)2, pNP-(GlcNAc)3, and pNP-GlcNAc, pNP-(GlcNAc)2, pNP-(GlcNAc)3, pNP-Glc respectively. Besides, the chitin oligosaccharides and colloidal chitin hydrolysis profiles revealed that CaChiT degraded chitin chains through exo-mode of action. Furthermore, CaChiT and CaHex exhibited a synergistic effect in the degradation of colloidal chitin, reaching 0.60 mg/mL of GlcNAc production after 1 h incubation. These results suggested that a combination of CaChiT and CaHex have great potential for industrial applications in the enzymatic production of GlcNAc from chitin-containing biowastes.

2.
Toxins (Basel) ; 13(9)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34564606

RESUMO

Ligninolytic enzymes, including laccase, manganese peroxidase, and dye-decolorizing peroxidase (DyP), have attracted much attention in the degradation of mycotoxins. Among these enzymes, the possible degradation pathway of mycotoxins catalyzed by DyP is not yet clear. Herein, a DyP-encoding gene, StDyP, from Streptomyces thermocarboxydus 41291 was identified, cloned, and expressed in Escherichia coli BL21/pG-Tf2. The recombinant StDyP was capable of catalyzing the oxidation of the peroxidase substrate 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), phenolic lignin compounds 2,6-dimethylphenol, and guaiacol, non-phenolic lignin compound veratryl alcohol, Mn2+, as well as anthraquinone dye reactive blue 19. Moreover, StDyP was able to slightly degrade zearalenone (ZEN). Most importantly, we found that StDyP combined the catalytic properties of manganese peroxidase and laccase, and could significantly accelerate the enzymatic degradation of ZEN in the presence of their corresponding substrates Mn2+ and 1-hydroxybenzotriazole. Furthermore, the biological toxicities of the main degradation products 15-OH-ZEN and 13-OH-ZEN-quinone might be remarkably removed. These findings suggested that DyP might be a promising candidate for the efficient degradation of mycotoxins in food and feed.

3.
Nat Commun ; 12(1): 5243, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475406

RESUMO

Peroxisome, a special cytoplasmic organelle, possesses one or more kinds of oxidases for hydrogen peroxide (H2O2) production and catalase for H2O2 degradation, which serves as an intracellular H2O2 regulator to degrade toxic peroxides to water. Inspired by this biochemical pathway, we demonstrate the reactive oxygen species (ROS) induced tumor therapy by integrating lactate oxidase (LOx) and catalase (CAT) into Fe3O4 nanoparticle/indocyanine green (ICG) co-loaded hybrid nanogels (designated as FIGs-LC). Based on the O2 redistribution and H2O2 activation by cascading LOx and CAT catalytic metabolic regulation, hydroxyl radical (·OH) and singlet oxygen (1O2) production can be modulated for glutathione (GSH)-activated chemodynamic therapy (CDT) and NIR-triggered photodynamic therapy (PDT), by manipulating the ratio of LOx and CAT to catalyze endogenous lactate to produce H2O2 and further cascade decomposing H2O2 into O2. The regulation reactions of FIGs-LC significantly elevate the intracellular ROS level and cause fatal damage to cancer cells inducing the effective inhibition of tumor growth. Such enzyme complex loaded hybrid nanogel present potential for biomedical ROS regulation, especially for the tumors with different redox state, size, and subcutaneous depth.


Assuntos
Antineoplásicos/farmacologia , Nanogéis/química , Peroxissomos/enzimologia , Fotoquimioterapia/métodos , Animais , Antineoplásicos/química , Catalase/química , Catalase/metabolismo , Catálise , Linhagem Celular Tumoral , Óxido Ferroso-Férrico/química , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Verde de Indocianina/química , Camundongos , Oxigenases de Função Mista/química , Oxigenases de Função Mista/metabolismo , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral/efeitos dos fármacos
4.
Zhongguo Zhong Yao Za Zhi ; 46(17): 4511-4521, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581057

RESUMO

This study aims to explore the active components and molecular mechanism of Shenmai Injection in the treatment of atrial fibrillation(AF) based on the application of network pharmacology and molecular docking technology. The chemical components of single herbs of Shenmai Injection were collected from TCMSP and TCMID, with the standard chemical name and PubChem CID(referred to as CID) obtained from PubChem database. The active components were screened using SwissADME, and their targets were predicted using SwissTargetPrediction. Targets related to AF treatment were identified using GeneCards, OMIM, and other databases. Venn diagram was constructed using Venny 2.1 to obtain the intersection targets. The single herb-active component-potential target network was constructed using Cytoscape, and the clusterProfiler R function package was used to perform the gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment. The protein-protein interaction(PPI) network of intersection targets was generated based on the STRING database. The hub target protein was identified by visualization using Cytoscape, and then docked to its reverse-selected active components. The analysis showed that there were 65 active components with 681 corresponding targets in Shenmai Injection, 2 798 targets related to AF treatment, and 235 intersection targets involving 2 549 GO functions and 153 KEGG pathways. Finally, hub target proteins, including RAC-alpha serine/threonine-protein kinase(AKT1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA), and estrogen receptor 1(ESR1), were screened out by PPI network visualization. The molecular docking was performed for 39 active components screened out in reverse, among which 30 active components de-monstrated high affinity. Among them, homoisoflavanoids CID 10871974, CID 5319742, and CID 10361149 had stronger affinity docking with AKT1. This study preliminarily indicates that Shenmai Injection treats AF through multiple components, multiple targets, and multiple pathways. Homoisoflavonoids of Ophiopogon japonicus are its important active components, which target AKT1 to regulate metabolism, inflammation, and apoptosis in AF treatment.


Assuntos
Fibrilação Atrial , Medicamentos de Ervas Chinesas , Fibrilação Atrial/tratamento farmacológico , Combinação de Medicamentos , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular
5.
Stat Med ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542187

RESUMO

Increasing evidence has shown that gene-gene interactions have important effects in biological processes of human diseases. Due to the high dimensionality of genetic measurements, interaction analysis usually suffers from a lack of sufficient information and has unsatisfactory results. Biological network information has been massively accumulated, allowing researchers to identify biomarkers while taking a system perspective, conducting network selection (of functionally related biomarkers), and accommodating network structures. In main-effect-only analysis, network information has been incorporated. However, effort has been limited in interaction analysis. Recently, link networks that describe the relationships between genetic interactions have been demonstrated as effective for revealing multiscale hierarchical organizations in networks and providing interesting findings beyond node networks. In this study, we develop a novel structured Bayesian interaction analysis approach to effectively incorporate network information. This study is among the first to identify gene-gene interactions with the assistance of network selection, while simultaneously accommodating the underlying network structures of both main effects and interactions. It innovatively respects multiple hierarchies among main effects, interactions, and networks. The Bayesian technique is adopted, which may be more informative for estimation and prediction over some other techniques. An efficient variational Bayesian expectation-maximization algorithm is developed to explore the posterior distribution. Extensive simulation studies demonstrate the practical superiority of the proposed approach. The analysis of TCGA data on melanoma and lung cancer leads to biologically sensible findings with satisfactory prediction accuracy and selection stability.

6.
Pain Ther ; 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34363598

RESUMO

INTRODUCTION: This aim of this study was to delineate current clinical scenarios of painful diabetic peripheral neuropathy (PDN) and associated anxiety and depression among patients in Mainland China, and to report current therapy and clinical practices. METHODS: A total of 1547 participants were enrolled in the study between 14 June 2018 and 11 November 2019. Recruitment was conducted using a multilevel sampling method. Participants' demographics, medical histories, glucose parameters, Douleur Neuropathique 4 Questionnaire (DN4) scores, visual analogue scale (VAS) pain scores, Patient Health Questionnaire 9 (PHQ-9) scores, Generalised Anxiety Disorder 7 (GAD-7) scores and therapies were recorded. RESULTS: The male-to-female ratio was 1.09:1 (807:740), and the mean age at onset was 61.28 ± 11.23 years. The mean DN4 score (± standard deviation) was 4.91 ± 1.88. The frequencies of DN4 sub-item phenotypes were: numbness, 81%; tingling, 68.71%; pins and needles, 62.90%; burning, 53.59%; hypoaesthesia to touch, 50.16%; electronic shocks, 43.31%; hypoaesthesia to pinprick, 37.94%; brushing, 37.82%; painful cold, 29.61%; and itching, 25.86%. Age, diabetic duration, depression history, PHQ-9 score and GAD-7 score were identified as risk factors for VAS pain score. Peripheral artery disease (PAD) was a protective factor for VAS pain score. For all participants currently diagnosed with PDN and for those previously diagnosed PDN, fasting blood glucose (FBG) was a risk factor for VAS; there was no association between FBG and VAS pain score for PDN diagnosed within 3 months prior to recruitment. Utilisation rate of opium therapies among enrolled participants was 0.71% , contradiction of first-line guideline recommendation for pain relief accounted for 9.43% (33/350) and contradiction of second-line guideline recommendation for opium dosage form was 0.57% (2/350). CONCLUSION: Moderate to severe neuropathic pain in PDN was identified in 73.11% of participants. Age, diabetic duration, depression history, PHQ-9 score, GAD-7 score and FBG were risk factors for VAS pain scores. PAD was protective factor. The majority of pain relief therapies prescribed were in accordance with guidelines. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03520608, retrospectively registered, 2018-05-11.

8.
Immunol Invest ; : 1-8, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236279

RESUMO

BACKGROUND: the aim of this study was to investigate the relationship between the risk of asthma and multiple single nucleotide polymorphisms (SNPs) in interleukin 7 receptor (IL7R) and IL6 genes, as well as the gene- environment interactions. METHODS: This is a hospital- based case- control study. A total of 430 patients with asthma were continuously recruited. Four SNPs within IL7R and IL6 gene were genotyped by PCR based restriction fragment length polymorphism. The Hardy- Weinberg balance of all participants was tested by SNPstats. The best interaction combination of four SNPs in IL7R and IL6 genes and smoking was screened by generalized multifactor dimensionality reduction (GMDR). Logistic regression was used to test the association between four SNPs and asthma, and stratified analysis for rs1800795 gene-smoking interaction, synergy index (SI) was calculated. RESULTS: The rs1494558-G and rs1800795-C were associated with an increased risk of asthma, adjusted ORs (95% CI) was 1.81 (1.29-2.42) and 1.75 (1.20-2.28), respectively. GMDR indicated that the test accuracy for two-locus model involving rs1800795 and smoking was 0.5721, and the p = .011, the results providing evidence for rs1800795 gene-smoking interaction. The asthma risk was higher in smokers with GC or CC genotype than the sum of risks in subjects with smoking or GC or CC genotype alone, compared to the never smokers with GG genotype, the OR (95%CI) was 4.97 (3.01-7.24), and the synergy index (SI) was 1.68 (1.08-2.60). CONCLUSIONS: The rs1494558-G and rs1800795-C alleles, gene- environment interaction between rs1800795 and smoking were all associated with increased asthma risk.

9.
Toxins (Basel) ; 13(6)2021 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205294

RESUMO

The co-occurrence of multiple mycotoxins, including aflatoxin B1 (AFB1), zearalenone (ZEN) and deoxynivalenol (DON), widely exists in cereal-based animal feed and food. At present, most reported mycotoxins degrading enzymes target only a certain type of mycotoxins. Therefore, it is of great significance for mining enzymes involved in the simultaneous degradation of different types of mycotoxins. In this study, a dye-decolorizing peroxidase-encoding gene BsDyP from Bacillus subtilis SCK6 was cloned and expressed in Escherichia coli BL21/pG-Tf2. The purified recombinant BsDyP was capable of oxidizing various substrates, including lignin phenolic model compounds 2,6-dimethylphenol and guaiacol, the substrate 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), anthraquinone dye reactive blue 19 and azo dye reactive black 5, as well as Mn2+. In addition, BsDyP could efficiently degrade different types of mycotoxins, including AFB1, ZEN and DON, in presence of Mn2+. More important, the toxicities of their corresponding enzymatic degradation products AFB1-diol, 15-OH-ZEN and C15H18O8 were significantly lower than AFB1, ZEN and DON. In summary, these results proved that BsDyP was a promising candidate for the simultaneous degradation of multiple mycotoxins in animal feed and food.

10.
Mol Ther ; 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34111560

RESUMO

Cisplatin resistance is a major therapeutic challenge in advanced head and neck squamous cell carcinoma (HNSCC). Here, we aimed to investigate the key signaling pathway for cisplatin resistance in HNSCC cells. Vomeronasal type-1 receptor 5 (VN1R5) was identified as a cisplatin resistance-related protein and was highly expressed in cisplatin-resistant HNSCC cells and tissues. The long noncoding RNA (lncRNA) lnc-POP1-1 was confirmed to be a downstream target induced by VN1R5. VN1R5 transcriptionally regulated lnc-POP1-1 expression by activating the specificity protein 1 (Sp1) transcription factor via the cyclic AMP (cAMP)/protein kinase A (PKA) pathway. VN1R5 promoted cisplatin resistance in HNSCC cells in a lnc-POP1-1-dependent manner. Mechanistically, lnc-POP1-1 bound to the minichromosome maintenance deficient 5 (MCM5) protein directly and decelerated MCM5 degradation by inhibiting ubiquitination of the MCM5 protein, which facilitated the repair of DNA damage caused by cisplatin. In summary, we identified the cisplatin resistance-related protein VN1R5 and its downstream target lnc-POP1-1. Upon upregulation by VN1R5, lnc-POP1-1 promotes DNA repair in HNSCC cells through interaction with MCM5 and deceleration of its degradation.

11.
Appl Microbiol Biotechnol ; 105(10): 4167-4175, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33939024

RESUMO

Somatostatin (SS) is one of the peptide hormones that regulate the endocrine system in animals. When SS is used to immunize animals, the correspondingly generated anti-SS antibody neutralizes the SS and, therefore, alleviates its growth inhibiting effects. This is of great value to the livestock industry; however, previously developed methods fail to obtain enough recombinant SS in an economical way. Herein, we describe the employment of a commonly used feed enzyme, i.e., xylanase, as a carrier protein for recombinant expression of SS in large quantity. The SS gene was fused to one of the two xylanase genes (XynCDBFV and BsXynC) and recombinantly expressed in Pichia pastoris. The purified xylanase-SS fusion proteins displayed excellent antigenicity and immunogenicity. In addition, they retained the enzymatic activities and thermostability of the xylanases, indicating that they can catalyze hydrolysis of xylan in plant cell wall of the animal feeds and stand the high temperature in feed pelleting. Thus, the xylanase-SS fusion proteins serve as an excellent candidate chimeric bifunctional vaccine-feed enzyme protein retaining both SS immunogenicity and xylanase activity. KEY POINTS: • Somatostatin is expressed in P. pastoris as fusion proteins with two xylanases. • The chimeric proteins retain both immunogenicity and xylanase activity. • The xylanase-SS proteins may serve as bifunctional proteins in livestock industry.


Assuntos
Endo-1,4-beta-Xilanases , Pichia , Endo-1,4-beta-Xilanases/genética , Endo-1,4-beta-Xilanases/metabolismo , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Pichia/genética , Pichia/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes/genética , Saccharomycetales , Somatostatina/genética
12.
Bioinformatics ; 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33961050

RESUMO

SUMMARY: For understanding complex diseases, gene-environment (G-E) interactions have important implications beyond main G and E effects. Most of the existing analysis approaches and software packages cannot accommodate data contamination/long-tailed distribution. We develop GEInter, a comprehensive R package tailored to robust G-E interaction analysis. For both marginal and joint analysis, for data without and with missingness, for continuous and censored survival responses, it comprehensively conducts identification, estimation, visualization, and prediction. It can fill an important gap in the existing literature and enjoy broad applicability. AVAILABILITY AND IMPLEMENTATION: https://cran.r-project.org/web/packages/GEInter/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

13.
Biotechnol Bioeng ; 118(7): 2448-2459, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33719068

RESUMO

Clostridium butyricum has been widely used as a probiotic for humans and food animals. However, the mechanisms of beneficial effects of C. butyricum on the host remain poorly understood, largely due to the lack of high-throughput genome engineering tools. Here, we report the exploitation of heterologous Type II CRISPR-Cas9 system and endogenous Type I-B CRISPR-Cas system in probiotic C. butyricum for seamless genome engineering. Although successful genome editing was achieved in C. butyricum when CRISPR-Cas9 system was employed, the expression of toxic cas9 gene result in really poor transformation, spurring us to develop an easy-applicable and high-efficient genome editing tool. Therefore, the endogenous Type I-B CRISPR-Cas machinery located on the megaplasmid of C. butyricum was co-opted for genome editing. In vivo plasmid interference assays identified that ACA and TAA were functional protospacer adjacent motif sequences needed for site-specific CRISPR attacking. Using the customized endogenous CRISPR-Cas system, we successfully deleted spo0A and aldh genes in C. butyricum, yielding an efficiency of up to 100%. Moreover, the conjugation efficiency of endogenous CRISPR-Cas system was dramatically enhanced due to the precluding expression of cas9. Altogether, the two approaches developed herein remarkably expand the existing genetic toolbox available for investigation of C. butyricum.

14.
Acta Pharmacol Sin ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767380

RESUMO

Alzheimer's disease (AD) is associated with high incidence of cardiovascular events but the mechanism remains elusive. Our previous study reveals a tight correlation between cardiac dysfunction and low mitochondrial aldehyde dehydrogenase (ALDH2) activity in elderly AD patients. In the present study we investigated the effect of ALDH2 overexpression on cardiac function in APP/PS1 mouse model of AD. Global ALDH2 transgenic mice were crossed with APP/PS1 mutant mice to generate the ALDH2-APP/PS1 mutant mice. Cognitive function, cardiac contractile, and morphological properties were assessed. We showed that APP/PS1 mice displayed significant cognitive deficit in Morris water maze test, myocardial ultrastructural, geometric (cardiac atrophy, interstitial fibrosis) and functional (reduced fractional shortening and cardiomyocyte contraction) anomalies along with oxidative stress, apoptosis, and inflammation in myocardium. ALDH2 transgene significantly attenuated or mitigated these anomalies. We also noted the markedly elevated levels of lipid peroxidation, the essential lipid peroxidation enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4), the transcriptional regulator for ACLS4 special protein 1 (SP1) and ferroptosis, evidenced by elevated NCOA4, decreased GPx4, and SLC7A11 in myocardium of APP/PS1 mutant mice; these effects were nullified by ALDH2 transgene. In cardiomyocytes isolated from WT mice and in H9C2 myoblasts in vitro, application of Aß (20 µM) decreased cell survival, compromised cardiomyocyte contractile function, and induced lipid peroxidation; ALDH2 transgene or activator Alda-1 rescued Aß-induced deteriorating effects. ALDH2-induced protection against Aß-induced lipid peroxidation was mimicked by the SP1 inhibitor tolfenamic acid (TA) or the ACSL4 inhibitor triacsin C (TC), and mitigated by the lipid peroxidation inducer 5-hydroxyeicosatetraenoic acid (5-HETE) or the ferroptosis inducer erastin. These results demonstrate an essential role for ALDH2 in AD-induced cardiac anomalies through regulation of lipid peroxidation and ferroptosis.

15.
Biomark Med ; 15(1): 15-28, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33427498

RESUMO

Background: TP53 is ranked as the most common mutated gene in head and neck squamous cell carcinoma (HNSCC). Results: The status of TP53 mutation was investigated on International Cancer Genome Consortium and The Cancer Genome Atlas database and TP53-related differentially expressed genes were screened out from transcriptome data and mutation information. A TP53-related prognostic gene signature (TIMP4, ONECUT2, CGNL1, DMRTA2 and NKX2.3) was constructed based on Cox regression analysis and LASSO algorithm. Univariate and multivariate analyses were carried out to identify promising prognosticators for HNSCC. Conclusion: Our findings provide a well-rounded landscape of TP53 mutation in HNSCC and pave the groundwork for developing innovative and effective cancer treatment methods for HNSCC.

16.
Nanoscale Res Lett ; 16(1): 14, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33475910

RESUMO

In recent years, multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise in nanomedicine. In this study, we report the environmentally friendly synthesis of fluorescent carbon nano-dots such as carbon quantum dots (CQDs) by microplasma using o-phenylenediamine. The produced CQDs exhibited a wide absorption peaks at 380-500 nm and emitted bright yellow fluorescence with a peak at 550 nm. The CQDs were rapidly taken up by HeLa cancer cells. When excited under blue light, a bright yellow fluorescence signal and intense reactive oxygen species (ROS) were efficiently produced, enabling simultaneous fluorescent cancer cell imaging and photodynamic inactivation, with a 40% decrease in relative cell viability. Furthermore, about 98% cells were active after the incubation with 400 µg mL-1 CQDs in the dark, which revealed the excellent biocompatibility of CQDs. Hence, the newly prepared CQDs are thus demonstrated to be materials which might be effective and safe to use for in vivo bioimaging and imaging-guided cancer therapy.

17.
Neuroreport ; 32(1): 23-28, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33252476

RESUMO

OBJECTIVE: The aim of this study was to explore the upper motor neurons (UMN) and lower motor neurons (LMN) degeneration in amyotrophic lateral sclerosis (ALS) from the perspective of the clinical neurological examination and MRI-electromyography manifold detection, respectively. METHODS: The clinical data, cortical thickness of corresponding areas in different body regions in MRI and electromyography data were collected from 108 classical ALS patients. RESULTS: The kappa value of UMN and LMN involvement signs in the bulbar region (0.31) was higher than that of the left upper limb (-0.13), right upper limb (-0.27), left lower limb (-0.05) and right lower limb (-0.08). The cortical thickness in the positive LMN damage group was thinner than that of the negative LMN damage group in the left head-face area (P < 0.05; Cohen's d = 0.84); however, cortical thickness showed no significant differences in the right head-face, bilateral tongue-larynx, upper-limb, trunk and lower-limb areas between LMN-damage-positive and LMN-damage-negative groups. CONCLUSION: The degeneration of motor neuron could be independent through UMN and LMN levels. The degenerative process was not only confined to UMN and LMN levels but can also expand to white matter fiber tracts. Thus, the degeneration of UMN and LMN might be independent of the motor system's three-dimensional anatomy.

18.
ACS Appl Mater Interfaces ; 12(46): 51555-51562, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33156604

RESUMO

The reasonable construction of heterojunction photocatalysts with clear nanostructures and a good interface contact especially the one-dimensional/two-dimensional (1D/2D) composite heterojunction with unique morphology is considered one of the most effective strategies for designing highly efficient photocatalysts. Herein, a series of the 1D ß-keto-enamine-based covalent organic framework (COF)/2D g-C3N4 composite materials COF-CN (1:x; where 1:x represents the mass ratio of COF and g-C3N4, x = 2.5, 5, 10, 15, 20) is prepared through the in situ reaction of 2,4,6-triformylphloroglucinol (Tp) and benzidine (BD) in stripped g-C3N4 suspension. A series of characterizations, such as X-ray diffraction (XRD), Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), have verified their 1D/2D heterojunction structure. With the introduction of 1D COF nanobelts, the absorption of the composite is largely extended to 560 nm. Photocatalytic experiments reveal that the composite COF/CN shows evidently superior photocatalytic performance than individual COF and g-C3N4. The optimized COF-CN (1:10) exhibits a H2 production rate of 12.8 mmol g-1·h-1 under visible-light (λ ≥ 420 nm) irradiation, which is about 62 and 284 times higher than those of COF and g-C3N4, respectively. The apparent quantum efficiency (AQE) of COF-CN (1:10) is about 15.09% under 500 nm light irradiation, which is one of the highest among previous COF- or g-C3N4-based materials. This work provides important strategies for designing and constructing high-efficiency heterojunction photocatalysts with multidimensional features.

19.
Int J Mol Med ; 46(6): 2115-2125, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33125101

RESUMO

Oral cancer (OC) is the most common type of head and neck malignant tumor. Tumor­derived exosomes induce a complex extracellular environment that affects tumor immunity. In the present study, exosomes were isolated from OC cell lines (WSU­HN4 and SCC­9) by ultrafiltration and the protein content of these oral cancer­derived exosomes (OCEXs) was analyzed by mass spectrometry, which revealed the enrichment of transforming growth factor (TGF)­ß1. Natural killer (NK) cells were examined by flow cytometry following co­culture with OCEXs. The expression of killer cell lectin like receptor K1 (KLRK1; also known as NKG2D, as used herein) and natural cytotoxicity triggering receptor 3 (NCR3; also known as NKp30, as used herein) in NK cells was found to be significantly upregulated following co­culture with the OCEXs for 1 day, whereas this expression decreased at 7 days. Killer cell lectin like receptor C1 (KLRC1; also known as NKG2A; as used herein) expression exhibited an opposite trend at 1 day. In addition, NK cell cytotoxicity against the OC cells was enhanced at 1 day, but was attenuated at 7 days. TGF­ß1 inhibited the function of NK cells at 7 days, whereas it had no obvious effects at 1 and 3 days. On the whole, the findings of the present study reveal changes in NK cell function and provide new insight into NK cell dysfunction.

20.
Metabolism ; 113: 154397, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33058849

RESUMO

OBJECTIVE: Cold exposure provokes cardiac remodeling and cardiac dysfunction. Autophagy participates in cold stress-induced cardiovascular dysfunction. This study was designed to examine the impact of Beclin1 haploinsufficiency (BECN+/-) in cold stress-induced cardiac geometric and contractile responses. METHODS AND MATERIALS: Wild-type (WT) and BECN+/- mice were assigned to normal or cold exposure (4 °C) environment for 4 weeks prior to evaluation of cardiac geometry, contractile and mitochondrial properties. Autophagy, apoptosis and ferroptosis were evaluated. RESULTS: Our data revealed that cold stress triggered cardiac remodeling, compromised myocardial contractile capacity including ejection fraction, fractional shortening, peak shortening and maximal velocity of shortening/relengthening, duration of shortening and relengthening, intracellular Ca2+ release, intracellular Ca2+ decay, mitochondrial ultrastructural disarray, superoxide production, unchecked autophagy, apoptosis and ferroptosis, the effects of which were negated by Beclin1 haploinsufficiency. Circulating levels of corticosterone were elevated in both WT and BECN+/- mice. Treatment of corticosterone synthesis inhibitor metyrapone or ferroptosis inhibitor liproxstatins-1 rescued cold stress-induced cardiac dysfunction and mitochondrial injury. In vitro study noted that corticosterone challenge compromised cardiomyocyte function, provoked lipid peroxidation and mitochondrial injury, the effects of which were nullified by Beclin1 haploinsufficiency, inhibitors of lipoxygenase, ferroptosis and autophagy. In addition, ferroptosis inducer erastin abrogated Beclin1 deficiency-offered cardioprotection. CONCLUSION: These data suggest that Beclin1 haploinsufficiency protects against cold exposure-induced cardiac dysfunction possibly through corticosterone- and ferroptosis-mediated mechanisms.


Assuntos
Proteína Beclina-1/genética , Temperatura Baixa , Ferroptose/genética , Haploinsuficiência , Mitocôndrias Cardíacas/patologia , Remodelação Ventricular , Animais , Autofagia , Cálcio/metabolismo , Camundongos , Camundongos Transgênicos , Miócitos Cardíacos/metabolismo , Estresse Fisiológico
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