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1.
J Neuroimmunol ; 358: 577652, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34217885

RESUMO

BACKGROUND: Recent data reveal that interleukin-34 (IL-34) can drive inflammatory response, thereby participating in the pathogenesis of inflammatory diseases. However, the potential effect of IL-34 in acute ischemic stroke (AIS) remains unknown. The purpose of this study was to explore whether the levels of serum IL-34 were correlated with clinical severity or prognosis in AIS patients. METHODS: In this prospective cohort study, serum IL-34 levels were detected in 150 healthy controls and 155 AIS patients. Univariate and multivariate logistic regression analysis were conducted to investigate the effect of IL-34 on the diagnosis and prognosis of AIS. ROC curve was utilized to evaluate predictive values for IL-34. RESULTS: Serum IL-34 levels at admission were significantly higher in AIS patients than those in the healthy controls. Univariate and multivariate logistics regression analysis showed that IL-34 was an independent predictor of occurrence and functional outcome of AIS. The ROC curve demonstrated that IL-34 had a good predictive effect on the diagnosis and prognosis of AIS. CONCLUSIONS: IL-34 can be used as a novel and independent diagnostic and predicting prognostic biomarker in AIS.

2.
Nat Commun ; 12(1): 4144, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230476

RESUMO

To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.

3.
Adv Mater ; : e2008267, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34240474

RESUMO

Recently, sensors that can imitate human skin have received extensive attention. Capacitive sensors have a simple structure, low loss, no temperature drift, and other excellent properties, and can be applied in the fields of robotics, human-machine interactions, medical care, and health monitoring. Polymer matrices are commonly employed in flexible capacitive sensors because of their high flexibility. However, their volume is almost unchanged when pressure is applied, and they are inherently viscoelastic. These shortcomings severely lead to high hysteresis and limit the improvement in sensitivity. Therefore, considerable efforts have been applied to improve the sensing performance by designing different microstructures of materials. Herein, two types of sensors based on the applied forces are discussed, including pressure sensors and strain sensors. Currently, five types of microstructures are commonly used in pressure sensors, while four are used in strain sensors. The advantages, disadvantages, and practical values of the different structures are systematically elaborated. Finally, future perspectives of microstructures for capacitive sensors are discussed, with the aim of providing a guide for designing advanced flexible and stretchable capacitive sensors via ingenious human-made microstructures.

4.
Insect Sci ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34231971

RESUMO

U1 small nuclear ribonucleoproteins (U1 snRNP) associates with 5' splice sites in the form of ribonucleoprotein particles, is highly conserved among species. The physiological functions of U1 snRNP in a lepidopteran model insect Bombyx mori is mostly unknown. Here we showed that U1 snRNP plays an important role in the development of silkworm. Knockout of U1 snRNP in silkworm showed either delayed or stationary 1st-instar larva development compared with the wild type group. U1 snRNP deletion mutants exhibited abnormal cellular phenotypes with enlarged cell nucleus, scanty cytoplasm, and enlarged nuclei. RNA-seq analysis revealed that genes involved in metabolic pathway, biosynthesis of secondary metabolites and steroid hormone biosynthesis were significantly affected by U1 snRNP depletion. Taken together, our study suggests that U1 snRNP homeostasis plays an important role in silkworm development. This article is protected by copyright. All rights reserved.

5.
J Asian Nat Prod Res ; : 1-7, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236260

RESUMO

A new pair of enantiomeric isoprenylated chromone derivatives, (±)-pestaloficiol X [(±)-1], along with a known compound pestaloficiol J (2), were isolated from the plant endophytic fungus Pestalotiopsis sp. The racemic mixture 1 was separated through chiral HPLC. The structures of new compounds (±)-1 were elucidated on the basis of extensive spectroscopic data and their absolute configurations were further configured through computational analysis of their electronic circular dichroism (ECD) spectra. Compound (+)-1 showed significant inhibitory potency against HL-60 and HEP-3B cell lines, with IC50 values of 1.35 ± 0.15 and 3.70 ± 0.33 µM, respectively, while compound (-)-1 showed significant inhibitory potency against HL-60 and HEP-3B cell lines, with IC50 values of 2.39 ± 0.26 and 2.99 ± 0.35 µM, respectively.

7.
Nucleic Acids Res ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259319

RESUMO

Recent studies demonstrate that histones are subjected to a series of short-chain fatty acid modifications that is known as histone acylations. However, the enzymes responsible for histone acylations in vivo are not well characterized. Here, we report that HBO1 is a versatile histone acyltransferase that catalyzes not only histone acetylation but also propionylation, butyrylation and crotonylation both in vivo and in vitro and does so in a JADE or BRPF family scaffold protein-dependent manner. We show that the minimal HBO1/BRPF2 complex can accommodate acetyl-CoA, propionyl-CoA, butyryl-CoA and crotonyl-CoA. Comparison of CBP and HBO1 reveals that they catalyze histone acylations at overlapping as well as distinct sites, with HBO1 being the key enzyme for H3K14 acylations. Genome-wide chromatin immunoprecipitation assay demonstrates that HBO1 is highly enriched at and contributes to bulk histone acylations on the transcriptional start sites of active transcribed genes. HBO1 promoter intensity highly correlates with the level of promoter histone acylation, but has no significant correlation with level of transcription. We also show that HBO1 is associated with a subset of DNA replication origins. Collectively our study establishes HBO1 as a versatile histone acyltransferase that links histone acylations to promoter acylations and selection of DNA replication origins.

8.
Mol Brain ; 14(1): 113, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261484

RESUMO

Clock genes not only regulate the circadian rhythm of physiological activities but also participate in the pathogenesis of many diseases. Previous studies have documented the abnormal expression of clock genes in epilepsy. However, the molecular mechanism of brain and muscle Arnt-like protein 1 (Bmal1), one of the core clock genes, in the epileptogenesis and seizures of temporal lobe epilepsy (TLE) remain unclear. We first investigated the levels of Bmal1 and other clock proteins in the hippocampus of subjects with epilepsy to define the function of Bmal1. The levels of Bmal1 were decreased during the latent and chronic phases in the experimental group compared with those in the control group. Knockout of Bmal1 in hippocampal dentate gyrus (DG) neurons of Bmal1flox/flox mice by Synapsin 1 (Syn1) promoter AAV (adeno-associated virus) lowered the threshold of seizures induced by pilocarpine administration. High-throughput sequencing analysis showed that PCDH19 (protocadherin 19), a gene associated with epilepsy, was regulated by Bmal1. PCDH19 expression was also decreased in the hippocampus of epileptic mice. Furthermore, the higher levels of Bmal1 and PCDH19 were detected in patients with no hippocampal sclerosis (no HS) than in patients with HS International League Against Epilepsy (ILAE) type I and III. Altogether, these data suggest that decreased expression of clock gene Bmal1 may participate in epileptogenesis and seizures via PCDH19 in TLE.

9.
J Craniofac Surg ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34260459

RESUMO

ABSTRACT: Surgical navigation has greatly improved the accuracy of craniomaxillofacial bone surgery and is widely used in the clinic. However, during surgery, craniomaxillofacial soft tissue is always deformed due to traction and compression, which leads to intraoperative image drift. This, in turn, impacts navigation accuracy. In order to improve navigation accuracy, this technical note presents a preliminary proposal for fusion imaging technology, which combines ultrasound and computed tomography to address navigational image drift in craniomaxillofacial soft tissue surgery.

10.
Pharm Biol ; 59(1): 884-892, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34219593

RESUMO

CONTEXT: Laurolitsine is an aporphine alkaloid and exhibits potent antihyperglycemic and antihyperlipidemic effects in ob/ob mice. OBJECTIVE: To investigate the pharmacokinetics, tissue distribution and excretion of laurolitsine. MATERIALS AND METHODS: A LC-MS/MS method was established and validated to determine laurolitsine concentrations in the biological matrix of rats (plasma, tissue homogenate, urine and faeces). 10 Sprague-Dawley (SD) rats were used for plasma exposure study: 5 rats were injected with 2.0 mg/kg of laurolitsine via the tail vein, and the other 5 rats were administered laurolitsine (10.0 mg/kg) by gavage. 25 SD rats used for tissue distribution study and 5 SD rats for urine and faeces excretion study: rats administered laurolitsine (10.0 mg/kg) by gavage. After administered, serial blood, tissue, urine and faeces were collected. Analytical quantification was performed by a previous LC-MS/MS method. The pharmacokinetics, bioavailability, tissue distribution and excretion of laurolitsine were described. RESULTS: The pharmacokinetic parameters of oral and intravenous administration with Tmax were 0.47 and 0.083 h, t1/2 were 3.73 and 1.67 h, respectively. Oral bioavailability was as low as 18.17%. Laurolitsine was found at a high concentration in the gastrointestinal tract, liver, lungs and kidneys (26 015.33, 905.12, 442.32 and 214.99 ng/g at 0.5 h, respectively) and low excretion to parent laurolitsine in urine and faeces (0.03 and 1.20% in 36 h, respectively). CONCLUSIONS: This study established a simple, rapid and accurate LC-MS/MS method to determine laurolitsine in different rat samples and successful application in a pharmacokinetic study.

12.
Chemosphere ; 285: 131411, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34246936

RESUMO

Dissolved organic matter (DOM) is one of the most significant parameters to affect the remediation efficiency of Pb(II) by apatites. Numerous studies chose humic substances as a surrogate of DOM to investigate its influence on Pb(II) immobilization. However, the effect of low-molecular-weight organic acids such as oxalic acid (OA), which is ubiquitous in the environment and a primary component of DOM, in immobilizing Pb(II) was still not fully understood. Herein, humic acid (HA) and OA were examined to distinguish their influence on Pb(II) immobilization by a green synthesized nanocrystalline hydroxyapatite (nHAP). Various parameters were considered to evaluate the removal performance of nHAP towards Pb(II) as affected by HA/OA. Results indicated that Pb(II) immobilization was significantly promoted in the coexistence of OA owing to the precipitation of hydroxypyromorphite (HPY) as well as PbC2O4, but was independent on the addition sequence and slightly hindered by HA, disclosing that Pb(II) preferred to bind directly with nHAP instead of via HA. Characterization of the Pb(II) loaded solids by multiple technologies revealed that HPY was the predominant precipitate both in the absence and presence of HA, while the formation of PbC2O4 was preferred over that of HPY in the existence of OA. X-ray photoelectron spectroscopy indicated that PbC2O4 was the prevalent solid phase with the ratio of 62.97% after Pb(II) immobilization by nHAP in the presence of OA. These findings implied that the transformation efficiency of Pb(II) to HPY by apatites can be overestimated in the presence of OA due to the precipitation of PbC2O4.

13.
Virus Res ; 303: 198501, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34252491

RESUMO

Posa-like viruses have been detected in the fecal samples of several host species and are considered unclassified members of Picornavirales. Here, we identified genomic fragments of novel posa-like viruses (monsaviruses) in monkey specimens through next generation sequencing and obtained 11 full-length genomes. This monsavirus shared 88.5-89.2% nucleotide similarity with the Tottori-HG1 strain (GenBank accession LC123275). In total, 713 nucleotide polymorphism sites were identified, indicating their persistent evolution during circulation. The genomic organization and phylogenetic relationship of monsavirus were determined. Subsequent phylogenetic analysis of the conserved replication block of Hel-Pro-RdRp and core RNA-dependent RNA polymerase domain-based analysis of posa-like viruses showed significant separation compared with other known families. Further, posa-like virus genomes possessed the classical replication block of picornavirus in the 5' part of genome and picorna-like capsid domains at the structural coding region of 3' part of genome. Based on these results, we proposed the new family Posaliviridae, within Picornavirales. Four genera, which showed 68.6-75.5% amino acid distances but similar genomic organization including the conserved replication block of Hel-Pro-RdRp, the same order of the genomic coding region, and picorna-like capsid domains, were identified. The flexible genomic organization strategy and a large evolutionary scale of Posaliviridae was explicit. This study provides novel information on monsaviruses and important taxonomic data for the family Posaliviridae.

14.
J Virol ; : JVI0046121, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34287045

RESUMO

The emergence of the CRISPR-Cas system as a technology has transformed our ability to modify nucleic acids, and the CRISPR-Cas13 system has been used to target RNA. CasRx is a small sized type VI-D effector (Cas13d) with RNA knockdown efficiency that may have an interference effect on RNA viruses. However, the RNA virus-targeting activity of CasRx still needs to be verified in vivo in vertebrates. In this study, we successfully engineered a highly effective CasRx system for fish virus interference. We designed synthetic mRNA coding for CasRx and used CRISPR RNAs to guide it to target the grouper nervous necrosis virus (RGNNV). This technique resulted in significant interference with virus infections both in vitro and in vivo. These results indicate that CRISPR/CasRx can be used to engineer interference against RNA viruses in fish, which provides a potential novel mechanism for RNA-guided immunity against other RNA viruses in vertebrates. Importance RNA viruses are most important viral pathogens infecting vertebrates and mammals. RNA virus populations are highly dynamic due to short generation times, large population sizes, and high mutation frequencies. Therefore, it is difficult to find a widely effective ways to inhibit RNA viruses. Therefore, we urgently need to develop effective antiviral methods. CasRx is a small sized type VI-D effector (Cas13d) with RNA knockdown efficiency that can have an interference effect on RNA viruses. Nervous necrosis virus (NNV), a non-enveloped positive-strand RNA virus, is one of the most serious viral pathogens infecting more than 40 cultured fish species resulting in huge economic losses worldwide. Here, we establish a novel efective CasRx system for RNA virus interference using NNV and grouper (Epinephelus coioices) as model. Our data show that CasRx have the most robust for RNA virus interference applications in fish and demonstrate its suitability for studying key questions relating to virus biology.

15.
J Control Release ; 336: 433-442, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34197861

RESUMO

Random conjugations of chemotherapeutics to monoclonal antibodies result in heterogeneous antibody-drug conjugates (ADCs) with suboptimal pharmacological properties. We recently developed a new technology for facile generation of homogeneous ADCs by harnessing human CD38 catalytic domain and its dinucleotide-derived covalent inhibitor, termed ADP-ribosyl cyclase-enabled ADCs (ARC-ADCs). Herein we advance this technology by designing and synthesizing ARC-ADCs with customizable drug-to-antibody ratios (DARs). Through varying numbers and locations of CD38 fused to an antibody targeting human C-type lectin-like molecule-1 (hCLL-1), ARC-ADCs featuring DARs of 2 and 4 were rapidly generated via a single step with cytotoxic monomethyl auristatin F (MMAF) as payloads. In contrast to anti-hCLL-1 ARC-ADC carrying 2 drug molecules, anti-hCLL-1 ARC-ADC with a DAR of 4 shows highly potent activity in killing hCLL-1-positive acute myeloid leukemia (AML) cells both in vitro and in vivo. This work provides novel ADC candidates for combating AML and supports ARC-ADC as a general and versatile approach for producing site-specific ADCs with defined DARs.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34270432

RESUMO

Passenger-flow anomaly detection and prediction are essential tasks for intelligent operation of the metro system. Accurate passenger-flow representation is the foundation of them. However, spatiotemporal dependencies, complex dynamic changes, and anomalies of passenger-flow data bring great challenges to data representation. Taking advantage of the time-varying characteristics of data, we propose a novel passenger-flow representation model based on low-rank dynamic mode decomposition (DMD), which also integrates the global low-rank nature and sparsity to explore the spatiotemporal consistency of data and depict abrupt data, respectively. The model can detect anomalies and predict short-term passenger flow conveniently and flexibly. For anomaly detection, we further introduce a strong temporal Toeplitz regularization to characterize the temporal periodic change of data, so as to more accurately detect anomalies. We conduct experiments with smart card transaction data from the Beijing metro system to assess the performance of the model in two use cases. In terms of anomaly detection, the experimental results demonstrate that our method can detect anomalies efficiently, especially for time sequence anomalies. As for short-term prediction, our model is superior to other methods in most cases.

17.
Oncogene ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272474

RESUMO

Dexamethasone (Dex), as a pretreatment agent, is widely used to attenuate the side effects of chemotherapy in breast cancer treatment. However, whether and how Dex affects breast cancer metastasis remain to be furtherly understood. In this study, we established several mouse breast cancer metastatic models to study the effect of Dex in vitro and in vivo. Transwell, Western Blot and RNA interference were applied to study the molecular mechanism of Dex in promoting breast cancer cell migration. Meanwhile, the effect of Dex on lung metastasis of breast cancer in Dex combined with PTX chemotherapy was discussed. Our results confirmed that Dex could promote breast cancer cell metastasis both in vitro and in vivo. Mechanistic studies revealed that this pro-metastatic effect of Dex was mediated by the GR-PI3K-SGK1-CTGF pathway in tumor cells. Ligation of Dex and glucocorticoid receptor (GR) on tumor cells activated the PI3K signaling pathway and upregulated serum glucocorticoid-inducible kinase 1 (SGK1) expression, and then increased the expression of connective tissue growth factor (CTGF) through Nedd4l-Smad2. Moreover, Dex was the leading factor for lung metastasis in a standard regimen for breast cancer treatment with paclitaxel and Dex. Importantly, targeting SGK1 with the inhibitor GSK650394 remarkably reduced lung metastasis in this regimen. Our present data provide new insights into Dex-induced breast cancer metastasis and indicate that SGK1 could be a candidate target for the treatment of breast cancer metastasis.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34273077

RESUMO

Severe haze frequently hits the North China Plain (NCP), especially in winter during recent years. Meteorological factors affect aerosol formation and its optical properties, and accurate meteorological fields are imperative for accurate aerosol simulations. The impacts of Global Positioning System Zenith Total Delay (GPS-ZTD) data assimilation on meteorology and aerosol simulations were evaluated in this study using the WRF-CMAQ (the Weather Research and Forecasting model and Community Multiscale Air Quality) modelling system over the NCP during 01-31 December 2019. After bias correction, GSP-ZTD data were assimilated into the WRF model using the 3DVAR technique. Two sensitivity tests (CTR and ZTD) were conducted. The WRF model had generally acceptable performance for surface and upper air meteorological variables, PM2.5 and visibility. From the aspect of BIAS, STDE, RMSE, and R, the assimilation of ZTD data improved the underestimation of ground relative humidity (RH). The improvement was more pronounced in the first 18 forecast hours. The mean RH BIAS decreased by 8%. Surface pressure was also improved in ZTD. The influence of ZTD data assimilation on ground temperature and wind tended to be neutral. The BIAS of ZTD decreased by 3% after data assimilation while STED or RMSE increased slightly. After ZTD data assimilation, the PM2.5 underestimation decreased by 3.4% over NCP. And station mean BIAS or RMSE of PM2.5 decreased at more than 70% stations. After ZTD data assimilation, the visibility overestimation was reduced by 2.5%. And more than 81% stations over had lower visibility BIAS or RMSE. Station mean PM2.5 mass concentration increased by 1.5% in ZTD. The primary aerosol species increased by approximately 1%, and most secondary aerosol species increased by greater than 2% affected by both aerosol physical and chemical process. Although the improvement of PM2.5 seems marginal from the perspective of regional or temporal average, the contribution of ZTD data assimilation on specific pollution episodes at specific stations can be great. The improvement of PM2.5 troughs was in the range of 1-5 µg/m3, while the overestimation of PM2.5 peaks was reduced by few up to dozens µg/m3. This will contribute to the extreme value prediction during pollution episode.

19.
Urol Int ; : 1-8, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34265766

RESUMO

PURPOSE: The aim of this study was to investigate the role of BIRC5 for early diagnosis and prognosis in clear-cell renal cell carcinoma (ccRCC) by studying the expression of BIRC5 and the correlation between BIRC5 expression and clinicopathological parameters and prognosis in ccRCC. METHODS: The BIRC5 expression in ccRCC tissues and normal kidney tissues was measured using the Cancer Genome Atlas database and the Human Protein Atlas database. The correlation between BIRC5 expression and clinicopathological parameters and prognosis in ccRCC was analyzed using UALCAN, the Kaplan-Meier plotter, GEPIA, and SurvExpress. Thirteen-paired ccRCC plasma samples were used to verify the BIRC5 early diagnosis value of ccRCC. RESULTS: The BIRC5 expression is significantly higher in ccRCC than in normal kidney tissues, and is correlated with the clinical stage and pathological grade of ccRCC (p < 0.05). The result of analyzing the relationship between BIRC5 expression and outcomes in ccRCC indicates that a high BIRC5 expression is an independent prognostic factor affecting the overall survival and disease-free survival of ccRCC (p < 0.05). Compared with normal kidney tissues, the immunohistochemical test shows that BIRC5 is significantly upregulated in ccRCC tissues. mRNA expression levels of BIRC5 were significantly higher in the ccRCC plasma than normal (p < 0.05). CONCLUSIONS: The high expression of BIRC5 is an important indicator for the prognosis of ccRCC, which makes BIRC5 an effective biomarker for predicting the prognosis of patients in ccRCC. BIRC5 may be a great potential biomarker for early diagnosis of ccRCC.

20.
Nat Commun ; 12(1): 4144, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: covidwho-1298839

RESUMO

To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.

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