Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.895
Filtrar
1.
Front Immunol ; 13: 970588, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36148233

RESUMO

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor of the digestive system. Its grim prognosis is mainly attributed to the lack of means for early diagnosis and poor response to treatments. Genomic instability is shown to be an important cancer feature and prognostic factor, and its pattern and extent may be associated with poor treatment outcomes in PDAC. Recently, it has been reported that long non-coding RNAs (lncRNAs) play a key role in maintaining genomic instability. However, the identification and clinical significance of genomic instability-related lncRNAs in PDAC have not been fully elucidated. Methods: Genomic instability-derived lncRNA signature (GILncSig) was constructed based on the results of multiple regression analysis combined with genomic instability-associated lncRNAs and its predictive power was verified by the Kaplan-Meier method. And real-time quantitative polymerase chain reaction (qRT-PCR) was used for simple validation in human cancers and their adjacent non-cancerous tissues. In addition, the correlation between GILncSig and tumor microenvironment (TME) and epithelial-mesenchymal transition (EMT) was investigated by Pearson correlation analysis. Results: The computational framework identified 206 lncRNAs associated with genomic instability in PDAC and was subsequently used to construct a genome instability-derived five lncRNA-based gene signature. Afterwards, we successfully validated its prognostic capacity in The Cancer Genome Atlas (TCGA) cohort. In addition, via careful examination of the transcriptome expression profile of PDAC patients, we discovered that GILncSig is associated with EMT and an adaptive immunity deficient immune profile within TME. Conclusions: Our study established a genomic instability-associated lncRNAs-derived model (GILncSig) for prognosis prediction in patients with PDAC, and revealed the potential functional regulatory role of GILncSig.

2.
Ecotoxicol Environ Saf ; 245: 114097, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36150305

RESUMO

Binary metallic organic frameworks can always play excellent functions for pollutants removal. One binary MOFs, UiO-66(Fe/Zr)), was newly synthesized and applied to remove aquatic selenite (SeIV) and selenate (SeVI). The adsorption behaviors and mechanisms were investigated using batch experiments, spectroscopic analyses, and theoretical calculations (DFT). The characterization results showed that the material inherited the topological structure of UiO-66 and excellent thermal stability. The large specific surface area (467.52 m2/g) and uniform mesoporous structures of the synthesized MOFs resulted in fast adsorption efficiency and high adsorption capacity for selenium species. The adsorbent kept high adsorption efficiency in a wide pH range from 2 to 11 with good anti-interference ability. The maximum adsorption capacity for Se(IV) and Se(VI) reached as high as 196 mg/g at pH 3 and 258 mg/g at pH 5, respectively. The process was conformed to fit pseudo-second-order kinetics and Langmuir isotherm, and could be explained by the formation of Fe/Zr-O-Se bond on the material surface, which was interpreted by the results of XPS, FTIR and DFT calculation. The regeneration and TCLP experiments demonstrated that UiO-66(Fe/Zr) could be regenerated for five cycles without obvious decrease of efficiencies, and the leaching rate of the adsorbed Se(IV) and Se(VI) in the spent adsorbent were only 4.8% and 2.3%. More than 99% of original Se(IV) and Se(VI) in the lake and tap water samples (1.0 mg/L of Se) could be removed in 2.0 h.

3.
J Clin Lab Anal ; : e24692, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098904

RESUMO

OBJECTIVE: The sensitivity and specificity of current biomarkers for gastric cancer were insufficient. The aim of the present study was to screen novel biomarkers and determine the diagnostic values of ornithine aminotransferase (OAT) and carbamoyl phosphate synthetase 1 (CPS1) for detecting gastric cancer. METHODS: With stable isotope tags, we labelled an initial discovery group of four paired gastric cancer tissue samples and identified with LC-ESI-MS/MS. A validation group of 159 gastric cancer samples and 30 healthy controls were used to validate the candidate targets. GSEA was used to explore the pathways activated in gastric cancer. RESULTS: Four hundred and thirty one proteins were found differentially expressed in gastric cancer tissues. Of these proteins, OAT and CPS1 were found over-expressed in gastric cancer patients, with sensitivity of 70.4% (95% CI: 63.3%-77.6%) and specificity of 80.5% (95% CI: 74.3%-86.7%) for ornithine aminotransferase, and with sensitivity of 68.6% (95% CI: 61.3%-75.8%) and specificity of 73% (95% CI: 66%-79.9%) for carbamoyl phosphate synthetase 1. The co-expression of OAT and CPS1 in gastric cancer tissues has a sensitivity of 81% (95% CI: 73.2%-88.8%) and specificity of 89% (95% CI: 83%-95%). Furthermore, both OAT and CPS1 were overexpressed in patients with local invasion T3 and T4 stages than those in patients with T1 and T2 stages. The co-expression of OAT and CPS1 was strongly correlated with histological grade I 68% (95% CI: 58.7%-77.3%) and TNM stage I/II 52% (95% CI: 42%-62%). The areas under ROC curves were up to 0.758 for the co-expression of OAT and CPS1 in gastric cancer. GSEA results showed that two gene sets and 30 gene sets were activated in OAT high- and CPS1 high-expression patients with gastric cancer, respectively. CONCLUSIONS: The present findings indicated a tight correlation between the co-expression of OAT and CPS1 and the histological grade, local invasion, and TNM stages of gastric cancer. Therefore, OAT and CPS1 might be predictors for gastric cancer invasion and potential targets for anticancer drug design for gastric cancer.

4.
J Am Chem Soc ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048164

RESUMO

The enantioconvergent cross-coupling of racemic alkyl halides represents a powerful tool for the synthesis of enantioenriched molecules. In this regard, the first-row transition metal catalysis provides a suitable mechanism for stereoconvergence by converting racemic alkyl halides to prochiral radical intermediates owing to their good single-electron transfer ability. In contrast to the noble development of chiral nickel catalyst, copper-catalyzed enantioconvergent radical cross-coupling of alkyl halides is less studied. Besides the enantiocontrol issue, the major challenge arises from the weak reducing capability of copper that slows the reaction initiation. Recently, significant efforts have been dedicated to basic research aimed at developing chiral ligands for copper-catalyzed enantioconvergent radical cross-coupling of racemic alkyl halides. This perspective will discuss the advances in this burgeoning area with particular emphasis on the strategic chiral anionic ligand design to tune the reducing capability of copper for the reaction initiation under thermal conditions from our research group.

5.
Environ Int ; 169: 107511, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36095929

RESUMO

BACKGROUND: Metals in the human body represent both environmental exposure and nutritional status. Little is known about the miRNA signature in relation to circulating metals in humans. OBJECTIVES: To characterize metal-associated miRNAs in leukocytes, individually and collectively as networks. METHODS: In a panel of 160 Chinese adults, we measured 23 metals/metalloids in plasma, and sequenced miRNAs and mRNAs in leukocytes. We used linear regression to model the associations between ln-transformed metal concentrations and normalized miRNA levels adjusting for potential confounders. We inferred the enriched leukocyte subtypes for the identified miRNAs using an association approach. We utilized mRNA sequencing data to explore miRNA functions. We also constructed modules to identify metal-associated miRNA networks. RESULTS: We identified 55 metal-associated miRNAs at false discovery rate-adjusted P < 0.05. In particular, we found that lead, nickel, and vanadium were positively associated with potentially lymphocyte-enriched miR-142-3p, miR-150-3p, miR-28-5p, miR-361-3p, and miR-769-5p, and were inversely associated with potentially granulocyte-enriched let-7a/c/d-5p and miR-1294. Interestingly, the five lymphocyte-enriched miRNAs inhibited, whereas miR-1294 activated, ROS and DNA repair pathways. We further confirmed the findings using oxidative damage biomarkers. Next, we clustered co-expressed miRNAs into modules, and identified four miRNA modules that were associated with different metals. The identified modules represented miRNAs enriched in different leukocyte subtypes, and were involved in biological processes including hematopoiesis and immune response, mitochondrial functions, and response to the stimulus. CONCLUSIONS: At commonly exposed low levels, circulating metals were associated with distinct miRNA signatures in leukocytes. The identified miRNAs, individually or as regulatory networks, may provide a mechanistic link between metal exposure and pathophysiological changes in the immune system.

6.
Front Oncol ; 12: 959322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091173

RESUMO

Cancer is one of the most serious diseases threatening human health, so it is particularly important to develop effective tumor-targeting drugs. As the first CDK4/6 inhibitor, palbociclib effectively inhibits tumor proliferation by blocking the cell cycle to the G1 phase. 10-HCPT is a Topo I inhibitor; however, its clinical application has been greatly limited due to its high toxicity. Based on the successful development of double target inhibitors, three novel palbociclib derivatives (HP-1, HP-2, and HP-3) were designed and synthesized from Palbociclib and 10-HCPT, and their biological activities were investigated. At first, the possible binding sites of the three compounds to Topo I and CDK4/6 were predicted by molecular docking. Then, we evaluated the anti-proliferative effects of the three palbociclib derivatives. In general, human lung cancer cells were more sensitive to HP-1, HP-2, and HP-3, especially NCI-H460. In addition, cell cycle arrest and apoptosis induction were investigated by flow cytometry. The three palbociclib derivatives, especially HP-1, had obvious cell cycle arrest phenomenon on NCI-H460 cells and induced apoptosis of NCI-H460 cells significantly. In the end, it was proved that these three drugs had obvious cyclin-dependent kinase inhibitory activities. In short, all the data showed that HP-1, HP-2, and HP-3 could play anti-cancer roles by acting on dual targets and had the characteristics of high efficiencies and low toxicities, which opened up a new idea for the study of palbociclib derivatives.

7.
Front Plant Sci ; 13: 962246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092412

RESUMO

Zinc is an essential minor element for rice growth and human health, which can also change the structure of the microorganisms. However, it remains unclear for the effects of zinc fertilizer on microbiome function in agricultural soils and crops. To solve this research gap, we investigated the relationship between improving rice (Oryza sativa L.) yield, Zn concentration, soil microbial community diversity, and function by the application of Zn fertilizer. The field trials included three rice varieties (Huanghuazhan, Nanjing9108, and Nuodao-9925) and two soil Zn levels (0 and 30 kg ha-1) in Jiangsu province, China. As a test, we studied the variety of soil bacterial composition, diversity, and function using 16S rRNA gene sequencing. The results showed that soil Zn application reduced the diversity of microbial community, but the bacterial network was more closely linked, and the metabolic function of bacterial community was improved, which increased the grain yield (17.34-19.52%) and enriched the Zn content of polished rice (1.40-20.05%). Specifically, redundancy analysis (RDA) and Mantel's test results revealed soil total nitrogen (TN) was the primary driver that led to a community shift in the rice rhizosphere bacterial community, and soil organic carbon (SOC) was considered to have a strong influence on dominant phyla. Furthermore, network analysis indicated the most critical bacterial taxa were identified as Actinobacteria, Bacteroidetes, Proteobacteria, and Chloroflexi based on their topological roles of microorganisms. KEGG metabolic pathway prediction demonstrated that soil Zn application significantly (p < 0.05) improved lipid metabolism, amino acid metabolism, carbohydrate metabolism, and xenobiotic biodegradation. Overall, their positive effects were different among rice varieties, of which Nanjing-9108 (NJ9108) performed better. This study opens new avenues to deeply understand the plant and soil-microbe interactions by the application of fertilizer and further navigates the development of Zn-rich rice cultivation strategies.

8.
Ultrasonics ; 127: 106837, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36075161

RESUMO

In this article, a novel ultrasound computed tomography (USCT) reconstruction algorithm for breast imaging is proposed. This algorithm is based on an ultrasound propagation model, the refract-ray model (RRM). In this model, the field of imaging is assumed as piecewise homogenous and is divided into several regions. The ultrasound propagation paths are considered polylines that only refract at the borders of the regions. The edge information is provided by B-mode imaging. Both simulations and experiments are implemented to validate the proposed algorithm. Compared with the traditional bent-ray model (BRM), the time of reconstructions using RRM decreases by over 90 %. In simulations, the imaging qualities for RRM and BRM are comparable, in terms of the root mean square error, the Tenengrad value, and the deformation of digital phantom. In the experiments, a cylindrical agar phantom is imaged using a customized imaging system. When imaging using RRM, the estimate of the phantom radius is about 0.1 mm in error, while it is about 0.3 mm in error using BRM. Moreover, the Tenengrad value of the result using RRM is much higher than that using BRM (9.76 compared to 0.79). The results show that the proposed algorithm can better delineate the phantom within a water bath. In future work, further experimental work is required to validate the method for improving imaging quality under breast-mimicking imaging conditions.

9.
Huan Jing Ke Xue ; 43(9): 4413-4424, 2022 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-36096582

RESUMO

Owing to the significant impact of heavy metals in atmospheric deposition on soil, clear knowledge on the present situation and temporal and spatial variation in fluxes of heavy metals in atmospheric deposition all around China is urgently needed. In this study, we collected 99 published papers on deposition fluxes of heavy metals from 2001 to 2021 based on the CNKI and Web of Science database and extracted 718 to 1672 monitoring points from these papers. The Meta-analysis method was used to calculate the weighted average of deposition fluxes of heavy metals, and the spatial-temporal characteristics in different periods from 2000 to 2018 were studied by subgroup analysis, which compared the differences between different types of areas, such as agricultural and rural areas and urban and industrial areas. The results showed that the annual fluxes of heavy metals in atmospheric deposition[mg·(m2·a)-1] in China were as follows:Zn (96.75)>Pb (23.37)>Cu (12.77)>Cr (11.04)>Ni (6.61)>As (2.97)>Cd (0.48)>Hg (0.05). Overall, the estimated value of deposition fluxes in China from 2000 to 2018 was higher than that of rural areas in England from 1995 to 1998. The deposition fluxes in industrial areas and urban areas were much higher than those in the agricultural and rural areas, especially the industrial areas where the heavy metal pollution was more serious. The deposition fluxes of As and Cd in the Changsha-Zhuzhou-Xiangtan area were relatively high, whereas the atmospheric deposition of heavy metals in Northeast China, the Pearl River Delta, and North China Plain was more serious than that in the other areas. In the past 20 years, the annual deposition fluxes of Cd fluctuated around the overall average, without an obviously declining trend, whereas the deposition fluxes of Cd in the urban, agricultural, and rural areas showed a trend of growth. These results suggested that precise and risk control measures of atmospheric emissions should be established based on the characteristics of regional industrial structure, which should cover all levels, all types, and all regions. In addition, more restrictive measures should be taken to solve the current problem caused by the higher deposition flux of Cd in atmospheric deposition.


Assuntos
Monitoramento Ambiental , Metais Pesados , Cádmio/análise , China , Monitoramento Ambiental/métodos , Metais Pesados/análise , Rios/química
10.
Org Lett ; 24(37): 6800-6804, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36074729

RESUMO

Four emestrin hybrid polymers, asperemestrins A-D (1-4, respectively), were isolated from the fungus Aspergillus nidulans. Asperemestrins A-C are the first examples of emestrin-sterigmatocystin heterodimers bearing a 7/5/6/6/5/5/6/6/6 nonacyclic system with a 2,5-diazabicyclo[2.2.2]octane-3,6-dione core, while asperemestrin D features an unprecedented 2,15-dithia-17,19-diazabicyclo[14.2.2]icosa-4,8-diene-12,18,20-trione core skeleton. Their structures were determined by extensive spectroscopic data, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Asperemestrin B showed moderate cytotoxicity against cancer cell lines, including SU-DHL-2, HEPG2, and HL-60.

12.
Hum Mol Genet ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36130215

RESUMO

Hereditary hearing loss is a highly genetically heterogeneous disorder. More than 150 genes have been identified to link to human nonsyndromic hearing impairment. To identify genetic mutations and underlying molecular mechanisms in affected individuals and families with congenital hearing loss, we recruited a cohort of 389 affected individuals in 354 families for whole-exome sequencing analysis. In the present study, we report a novel homozygous missense variant (c.233A > G, p.Lys78Arg) in the OXR1 gene, which was identified in a 4-year-old girl with sensorineural hearing loss (SNHL). OXR1 encodes Oxidation Resistance 1 and is evolutionarily conserved from zebrafish to human. We found that the ortholog oxr1b gene is expressed in the statoacoustic ganglion (SAG, a sensory ganglion of ear) and posterior lateral line ganglion (pLL) in zebrafish. Knockdown of oxr1b in zebrafish resulted in a significant developmental defect of SAG and pLL. This phenotype can be rescued by co-injection of wild-type human OXR1 mRNAs, but not mutant OXR1 (c.233A > G) mRNAs. OXR1-associated pathway analysis revealed that mutations of TBC1D24, a TLDc-domain-containing homolog gene of OXR1, have previously been identified in patients with hearing loss. Interestingly, mutations or knockout of OXR1 interacting molecules such as ATP6V1B1 and ESR1 are also associated with hearing loss in patients or animal models, hinting an important role of OXR1 and associated partners in cochlear development and hearing function.

13.
Ann Transl Med ; 10(16): 878, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36110990

RESUMO

Background: Henan province is an area with a serious disease burden of colorectal cancer (CRC) in China. Understanding the current incidence and mortality and the time-trend is critical to formulate and optimize prevention and control strategies for CRC. However, the current incidence and mortality and time-trend of CRC in Henan province, China have not been reported. Methods: CRC data was got from the Henan Provincial Central Cancer Registry of China in which the data was submitted from local cancer registries. Combined with the census data, the incidence, mortality, proportion, age-standardized rate by Chinese population (ASRC), age-standardized rate by world population (ASRW), and cumulative incidence and mortality (0-74 years old) of CRC by urban and rural population, gender, and age groups were estimated. The average annual percentage change (AAPC) and its 95% confidence interval (CI) of ASRC from 2010 to 2017 were analyzed. Results: In 2017, it was estimated that there were 20,275 new cases and 10,046 deaths of CRC in Henan province. The crude incidence was 18.73/100,000, with an age-standardized incidence rate by Chinese population (ASIRC) of 13.97/100,000 and age-standardized mortality rate by world population (ASIRW) of 13.78/100,000. The cumulative incidence was 1.66%. The mortality rate was 9.28/100,000, with an age-standardized mortality rate by Chinese population (ASMRC) of 6.49/100,000 and an age-standardized mortality rate by world population (ASMRW) of 6.45/100,000. The cumulative mortality rate was 0.69%. The ASIRC and ASMRC were higher in urban areas (15.89/100,000, 7.19/100,000) than in rural areas (13.13/100,000, 6.20/100,000), and higher in males (15.53/100,000, 7.44/100,000) than in females (12.48/100,000, 5.66/100,000). The age-specific incidence reached the peak at age of 80-84, and the age-specific mortality reached the peak at age 85. From 2010 to 2017, the overall ASIRC and ASMRC showed a steady trend (P>0.05), while an upward trend was observed in the mortality rate in urban males (AAPC =3.4, 95% CI: 0.2-6.7, P=0.040). Conclusions: The incidence and mortality of CRC were high in Henan province, and higher in urban areas and males. It is critical to strengthen the prevention and control of CRC, carry out targeted intervention, and promote screening and early diagnosis and treatment, particularly among urban areas and males.

14.
Ann Transl Med ; 10(16): 899, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36111000

RESUMO

Background: It is great of significance to figure the time-trend of esophageal cancer (EC) and its current status for effective prevention and control, especially in EC high risk areas. As one of world-renowned high-risk areas, the epidemiology of EC in Henan has not been recently updated. Therefore, we aimed to depict the status quo of EC and analyze its time-trend in Henan. Methods: The EC data were extracted from the Henan Provincial Cancer registry database derived from the population based cancer registry system, which covered 30.51% of the whole population in Henan and were qualified according to national and international guidelines. The incidence and mortality of EC were estimated by area (rural/urban), gender, and age groups. The age-standardized rates (ASRs) were calculated according to the Segi's population. Joinpoint regression was used to calculate annual percentage change (APC) and average annual percentage change (AAPC) to evaluate the time-trend of EC. Results: As estimated, there were 29,913 new EC cases in Henan, 2018. The crude incidence and the age-standardized incidence rate by world standard population (ASIRW) was 27.43/105 and 19.96/105, respectively. The incidence in males and rural was 1.83 and 1.51 times higher than that in females and urban areas, respectively. Meanwhile, it was estimated that 22,688 deaths occurred in 2018. The crude mortality and the age-standardized mortality rate by world standard population (ASMRW) were 20.80/105 and 14.47/105, respectively. Similarly, males and rural areas had higher mortality compared with females and urban areas. The age-specific incidence and mortality of EC showed significant increasing after 60-64 years group. In general, the time-trend of incidence (APC: -8.9, P<0.001) and mortality (APC: -7.6, P<0.001) of EC showed a significant decreasing trend since 2014, and downward trend were also observed in rural areas for incidence (APC: -5.2, P<0.001) and mortality (APC: -3.9, P<0.001) from 2010 to 2018. Conclusions: The EC incidence and mortality in Henan has exhibited a significant declining trend in past years. Nonetheless, the disease burden remains high, especially in males and rural areas. Therefore, the ongoing prevention and control strategies of EC should be maintained alongside the establishment of more effective strategies.

15.
Artigo em Inglês | MEDLINE | ID: mdl-36131604

RESUMO

The tetracationic cyclophane, cyclobis(paraquat-p-phenylene), also known as the little blue box, constitutes a modular receptor that has facilitated the discovery of many host-gust complexes and mechanically interlocked molecules during the past 35 years. Its versatility in binding small π-donors in its tetracationic state, as well as forming trisradical tricationic complexes with viologen radical cations in its doubly reduced bisradical dicationic state, renders it valuable for the construction of various stimuli-responsive materials. Since the first reports in 1988, the little blue box has been featured in over 500 publications in the literature. All this research activity would not have been possible without the seminal contributions carried out by Siegfried Hünig, who, not only pioneered the syntheses of viologen-containing cyclophanes, but also revealed their rich redox chemistry in addition to their ability to undergo intramolecular π-dimerization. This review describes how his pioneering research led to the design and synthesis of the little blue box, and how this redox-active host evolved into the key component of molecular shuttles, switches and machines.

16.
Contrast Media Mol Imaging ; 2022: 9696403, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034197

RESUMO

With the changes of people's diet and lifestyle, the number of patients with abdominal malignant tumors is increasing year by year. In order to analyze the effectiveness of cone-beam CT (CBCT) enhancement technology in improving the accuracy of radiotherapy for clinical malignant tumors, 92 patients with abdominal malignant tumor are divided into the control group and the CBCT radiotherapy group. The experimental results show that precise radiotherapy technology can promote the recovery of the immune function of patients with abdominal malignant tumors, improve the effect of treatment, and decrease the incidence of complications.


Assuntos
Radioterapia Guiada por Imagem , Tomografia Computadorizada de Feixe Cônico , Humanos , Planejamento da Radioterapia Assistida por Computador
17.
Cerebellum ; 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36040660

RESUMO

The classical motor center cerebellum is one of the most consistent structures of abnormality in autism spectrum disorders (ASD), and neuropeptide oxytocin is increasingly explored as a potential pharmacotherapy for ASD. However, whether oxytocin targets the cerebellum for therapeutic effects remains unclear. Here, we report a localization of oxytocin receptor (OXTR) in Purkinje cells (PCs) of cerebellar lobule Crus I, which is functionally connected with ASD-implicated circuits. OXTR activation neither affects firing activities, intrinsic excitability, and synaptic transmission of normal PCs nor improves abnormal intrinsic excitability and synaptic transmission of PCs in maternal immune activation (MIA) mouse model of autism. Furthermore, blockage of OXTR in Crus I in wild-type mice does not induce autistic-like social, stereotypic, cognitive, and anxiety-like behaviors. These results suggest that oxytocin signaling in Crus I PCs seems to be uninvolved in ASD pathophysiology, and contribute to understanding of targets and mechanisms of oxytocin in ASD treatment.

18.
Front Bioeng Biotechnol ; 10: 973496, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992358

RESUMO

Myocardial infarction (MI) is a common cardiovascular disease caused by permanent loss of cardiomyocytes and the formation of scar tissue due to myocardial ischemia. Mammalian cardiomyocytes lose their ability to proliferate almost completely in adulthood and are unable to repair the damage caused by MI. Therefore, transplantation of exogenous cells into the injured area for treatment becomes a promising strategy. Pluripotent stem cells (PSCs) have the ability to proliferate and differentiate into various cellular populations indefinitely, and pluripotent stem cell-derived cardiomyocytes (PSC-CMs) transplanted into areas of injury can compensate for part of the injuries and are considered to be one of the most promising sources for cell replacement therapy. However, the low transplantation rate and survival rate of currently transplanted PSC-CMs limit their ability to treat MI. This article focuses on the strategies of current research for improving the therapeutic efficacy of PSC-CMs, aiming to provide some inspiration and ideas for subsequent researchers to further enhance the transplantation rate and survival rate of PSC-CMs and ultimately improve cardiac function.

19.
Neural Netw ; 154: 413-424, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35952539

RESUMO

Graph, as a powerful data structure, has shown superior capability on modeling complex systems. Since real-world objects and their interactions are often multi-modal and multi-typed, compared with traditional homogeneous graphs, heterogeneous graphs can represent real-world objects more effectively. Meanwhile, rich semantic information brings great challenges for learning heterogeneous graph representation (HGR). Most existing HGR methods are based on the concept of meta-path, which is constructed based on direct neighbors and define composite semantic relations in heterogeneous graph. However, when the direct neighbor information is inadequate, which always happens due to insufficient observation, the quality of meta-paths cannot be guaranteed. Therefore, we propose a novel HGR framework based on latent direct neighbors. Specifically, random walks are first utilized to discover the potential candidates from indirect neighbors. Then HodgeRank is introduced to determine the latent direct neighbors according to their importance to the target. After that, neighborhood relationships are augmented with the selected latent direct neighbors, and the adjacency tensor of the heterogeneous graph is refactored correspondingly. Finally, Graph Transformer Network is adopted to construct semantic meta-paths automatically and generate HGR. Numerical experiments on different real-world heterogeneous networks show that our new approach can produce more meta-path instances and introduce more complex and diverse semantic information, and consequently achieves more accurate predictions compared with several state-of-the-art baselines.

20.
Front Psychiatry ; 13: 929812, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935436

RESUMO

Major depressive disorder (MDD) is a common psychiatric condition associated with aberrant large-scale distributed brain networks. However, it is unclear how the network dysfunction in MDD patients is characterized by imbalance or derangement of network modular segregation. Fifty-one MDD patients and forty-three matched healthy controls (HC) were recruited in the present study. We analyzed intrinsic brain activity derived from resting-state functional magnetic resonance imaging (R-fMRI) and then examined brain network segregation by computing the participation coefficient (PC). Further intra- and inter-modular connections analysis were preformed to explain atypical PC. Besides, we explored the potential relationship between the above graph theory measures and symptom severity in MDD. Lower modular segregation of the frontal-parietal network (FPN) was found in MDD compared with the HC group. The MDD group exhibited increased inter-module connections between the FPN and cingulo-opercular network (CON), between the FPN and cerebellum (Cere), between the CON and Cere. At the nodal level, the PC of the anterior prefrontal cortex, anterior cingulate cortex, inferior parietal lobule (IPL), and intraparietal sulcus showed larger in MDD. Additionally, the inter-module connections between the FPN and CON and the PC values of the IPL were negatively correlated with depression symptom in the MDD group. These findings might give evidence about abnormal FPN in MDD from the perspective of modular segregation in brain networks.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...