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1.
Cells ; 10(3)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33801396

RESUMO

This study investigated the effects of dietary C. butyricum ZJU-F1 on the apparent digestibility of nutrients, intestinal barrier function, immune response, and microflora of weaned piglets, with the aim of providing a theoretical basis for the application of Clostridium butyricum as an alternative to antibiotics in weaned piglets. A total of 120 weanling piglets were randomly divided into four treatment groups, in which piglets were fed a basal diet supplemented with antibiotics (CON), Bacillus licheniformis (BL), Clostridium butyricum ZJU-F1 (CB), or Clostridium butyricum and Bacillus licheniformis (CB-BL), respectively. The results showed that CB and CB-BL treatment increased the intestinal digestibility of nutrients, decreased intestinal permeability, and increased intestinal tight junction protein and mucin expression, thus maintaining the integrity of the intestinal epithelial barrier. CB and CB-BL, as exogenous probiotics, were also found to stimulate the immune response of weaned piglets and improve the expression of antimicrobial peptides in the ileum. In addition, dietary CB and CB-BL increased the proportion of Lactobacillus. The levels of butyric acid, propionic acid, acetic acid, and total acid were significantly increased in the ceca of piglets fed CB and CB-BL. Furthermore, we validated the effects of C. butyricum ZJU-F1 on the intestinal barrier function and immune response in vitro and found C. butyricum ZJU-F1 improved intestinal function and enhanced the TLR-2-MyD88-NF-κB signaling.

2.
Sensors (Basel) ; 21(5)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800173

RESUMO

A blur detection problem which aims to separate the blurred and clear regions of an image is widely used in many important computer vision tasks such object detection, semantic segmentation, and face recognition, attracting increasing attention from researchers and industry in recent years. To improve the quality of the image separation, many researchers have spent enormous efforts on extracting features from various scales of images. However, the matter of how to extract blur features and fuse these features synchronously is still a big challenge. In this paper, we regard blur detection as an image segmentation problem. Inspired by the success of the U-net architecture for image segmentation, we propose a multi-scale dilated convolutional neural network called MSDU-net. In this model, we design a group of multi-scale feature extractors with dilated convolutions to extract textual information at different scales at the same time. The U-shape architecture of the MSDU-net can fuse the different-scale texture features and generated semantic features to support the image segmentation task. We conduct extensive experiments on two classic public benchmark datasets and show that the MSDU-net outperforms other state-of-the-art blur detection approaches.

3.
BMC Cancer ; 21(1): 355, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823834

RESUMO

BACKGROUND: The long non-coding (lnc) RNA activated by small nucleolar RNA host gene 16 (SNHG16), which has been reported to play a vital role in a number of different types of cancer, is a novel lncRNA. However, following an osteosarcoma (OS) study, the expression pattern, biological roles, clinical values and potential molecular mechanism of SNHG16 remain unclear. In the current study, we aimed to examine its expression and possible function in osteosarcoma (OS). METHOD: Cell proliferation was measured by colony formation assay and Cell Counting Kit-8 (CCK-8) in vitro, and xenograft transplantation assay in vivo. Meanwhile, we used transwell chambers to test cell migration and invasion was evaluated. Cell cycle and apoptosis was evaluated by flow cytometry assay. Immunoblotting and qPCR analysis was carried out to detect protein and gene expression, respectively. Luciferase reporter assay was used to predict the potential downstream genes. RESULTS: The present study demonstrated that SNHG16 is highly expressed in both the tissues of patients with OS, as well as OS cell lines, and its expression level was positively correlated with clinical stage and poor overall survival. Functional assays revealed that the depletion of SNHG16 inhibits OS growth, OS cell progression and promotes apoptosis both in vivo and in vitro. In addition, the present study revealed that microRNA-1285-3p expression levels can be decreased by SNHG16 acting as a 'sponge', and that this pathway takes part in OS tumor growth in vivo, and OS cell proliferation, invasion, migration and apoptosis in vitro. CONCLUSIONS: The results from the present study demonstrate the role of lncRNA SNHG16 in OS progression, which is SNHG16 might exert oncogenic role in osteosarcoma (OS) by acting as a ceRNA of miR-1285-3p, and it may become a novel target in OS therapy.

5.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33809823

RESUMO

Dehydrins (DHNs) play an important role in abiotic stress tolerance in a large number of plants, but very little is known about the function of DHNs in pepper plants. Here, we isolated a Y1SK2-type DHN gene "CaDHN3" from pepper. To authenticate the function of CaDHN3 in salt and drought stresses, it was overexpressed in Arabidopsis and silenced in pepper through virus-induced gene silencing (VIGS). Sub-cellular localization showed that CaDHN3 was located in the nucleus and cell membrane. It was found that CaDHN3-overexpressed (OE) in Arabidopsis plants showed salt and drought tolerance phenotypic characteristics, i.e., increased the initial rooting length and germination rate, enhanced chlorophyll content, lowered the relative electrolyte leakage (REL) and malondialdehyde (MDA) content than the wild-type (WT) plants. Moreover, a substantial increase in the activities of antioxidant enzymes; including the superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), and lower hydrogen peroxide (H2O2) contents and higher O2•- contents in the transgenic Arabidopsis plants. Silencing of CaDHN3 in pepper decreased the salt- and drought-stress tolerance, through a higher REL and MDA content, and there was more accumulation of reactive oxygen species (ROS) in the CaDHN3-silenced pepper plants than the control plants. Based on the yeast two-hybrid (Y2H) screening and Bimolecular Fluorescence Complementation (BiFC) results, we found that CaDHN3 interacts with CaHIRD11 protein in the plasma membrane. Correspondingly, the expressions of four osmotic-related genes were significantly up-regulated in the CaDHN3-overexpressed lines. In brief, our results manifested that CaDHN3 may play an important role in regulating the relative osmotic stress responses in plants through the ROS signaling pathway. The results of this study will provide a basis for further analyses of the function of DHN genes in pepper.

6.
Environ Res ; : 111085, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33812874

RESUMO

BACKGROUND: To evaluate the impact of ambient air pollutant exposures on semen quality parameters during COVID-19 outbreak in China, and to identify susceptible windows for associations between air pollution and semen quality. METHODS: A case study was carried out, including 781 sperm donor candidates (1991 semen samples) collected between November 23, 2019 and July 23, 2020 (a period covering COVID-19 lock-down in China) in University-affiliated Sichuan provincial Human Sperm Bank. RESULT(S): Our results suggested that sperm motility is susceptible to ambient pollution exposure. Exposure to particulate matters (PM2.5 and PM10), O3 and NO2 during late stage of spermatogenesis appeared to have weak but positive association with semen quality. Exposure to CO late in sperm development appeared to have inverse relationship with sperm movement parameters. Exposure to SO2 appeared to influence semen quality throughout spermatogenesis. Collinearity did not appear to be a major issue in our analysis based on correlationship analysis; we conducted robustness test of the regression results with additional analysis on a subset of our study population to affirm our results. CONCLUSION(S): Male exposure to different air pollutants have different correlations with semen quality parameters during different exposure windows of spermatogenesis. Findings from current study help to further elucidate the importance of sensitive periods during spermatogenesis and could provide evidence for future intervention in male fertility.

7.
J Integr Med ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33814325

RESUMO

Cancer immunotherapy has led to a new era of cancer treatment strategies, and transforming healthcare for cancer patients. Meanwhile, reports of immune-related adverse events have been increasing, greatly hindering the use of cancer immunotherapy. Traditional Chinese medicine (TCM), which has been widely used in Asian countries for thousands of years, is known to play a complementary role in the treatment of cancer. Taken in combined with conventional modern therapies, such as resection, ablation and radiotherapy, TCM exerts its main anti-cancer effects in two ways: health-strengthening (Fu-Zheng) and pathogen-eliminating (Qu-Xie). Theoretically, pathogen-eliminating TCM can promote the release of tumor-related antigens and should be able to increase the effect of immunotherapy, while health-strengthening TCM may have immune-enhancing mechanisms that overlap with immunotherapy. In the era of cancer immunotherapy, it is important to balance the use of TCM and immunotherapy, with the goal of enhancing immune efficacy and antagonizing immune toxicity. In this article, we discuss this issue by considering the mechanism of tumor immunotherapy, alongside the theoretical basis of TCM treatment of tumors, with the aim of bringing new insights to future research in this field.

8.
J Pediatr ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33794217

RESUMO

OBJECTIVE: To compare the risk of liver-related adverse drug reactions (ADRs) in children and adults. STUDY DESIGN: A case/non-case analysis on spontaneous reports based on the China National Adverse Drug Reactions Monitoring System database were conducted, focusing on events of liver-related ADRs in children under 14 years of age. Both, the relative risk of liver-related ADRs in children versus entire population and the risk stratification in children were expressed as a measure of disproportionality using the reporting odds ratio (ROR). RESULTS: There were 1,206 cases of pediatric liver-related ADRs identified from 2012 to 2016, accounting for 2.82% of the entire population. The highest ROR values in children from 0-14 years versus the entire population were observed for analgesics (3.97, 95% CI 3.27-4.81), respiratory (2.60, 95% CI 1.04-6.43), antineoplastic (2.29, 95% CI 2.02-2.58), immunomodulatory (1.91, 95% CI 1.44-2.53), and antimicrobial agents (1.47, 95% CI 1.33-1.63). Notably, infants from 0 to 1 year old showed significantly higher risk (3.14, 95% CI 2.85-3.48) of liver-related ADRs than the other age groups of children. For infants, analgesics (3.21, 95% CI 2.20-4.66) and antimicrobials (3.15, 95% CI 2.50-3.97) agents were found to have the highest adjusted RORs than other drug categories. The highest RORs were found for meropenem, amoxicillin, fluconazole, vancomycin, cefaclor, and ceftazidime in the antimicrobial agents for infants. CONCLUSIONS: Children are sensitive to liver-related ADRs caused by several specific drug categories, and infants are the most sensitive.

9.
Adv Mater ; : e2100333, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792083

RESUMO

The development of highly efficient, multifunctional, and biocompatible sonosensitizer is still a priority for current sonodynamic therapy (SDT). Herein, a defect-rich Ti-based metal-organic framework (MOF) (D-MOF(Ti)) with greatly improved sonosensitizing effect is simply constructed and used for enhanced SDT. Compared with the commonly used sonosensitizer TiO2 , D-MOF(Ti) results in a superior reactive oxygen species (ROS) yield under ultrasound (US) irradiation due to its narrow bandgap, which principally improves the US-triggered electron-hole separation. Meanwhile, due to the existence of Ti3+ ions, D-MOF(Ti) also exhibits a high level of Fenton-like activity to enable chemodynamic therapy. Particularly, US as the excitation source of SDT can simultaneously enhance the Fenton-like reaction to achieve remarkably synergistic outcomes for oncotherapy. More importantly, D-MOF(Ti) can be degraded and metabolized out of the body after completion of its therapeutic functions without off-target toxicity. Overall, this work identifies a novel Ti-familial sonosensitizer harboring great potential for synergistic sonodynamic and chemodynamic cancer therapy.

10.
Medicine (Baltimore) ; 100(13): e25258, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787609

RESUMO

RATIONALE: Hereditary hemochromatosis (HH) is a hereditary disorder of iron metabolism. It is classified into 4 main types depending on the underlying genetic mutation: human hemochromatosis protein (HFE) (type 1), hemojuvelin (HJV) (type 2A), HAMP (type 2B), transferrin receptor-2 (TFER2) (type 3), and ferroportin (type 4). Type 4 HH is divided into 2 subtypes according to different mutations: type 4A (classical ferroportin disease) and type 4B (non-classical ferroportin disease). Type 4B HH is a rare autosomal dominant disease that results from mutations in the Solute Carrier Family 40 member 1 (SLC40A1) gene, which encodes the iron transport protein ferroportin. PATIENT CONCERNS: Here we report 2 elderly Chinese Han men, who were brothers, presented with liver cirrhosis, diabetes mellitus, skin hyperpigmentation, hyperferritinaemia as well as high transferrin saturation. DIAGNOSIS: Subsequent genetic analyses identified a heterozygous mutation (p. Cys326Tyr) in the SLC40A1 gene in both patients. INTERVENTIONS: We treated the patient with iron chelator and followed up for 3 years. OUTCOMES: Iron chelator helped to reduce the serum ferritin and improve the condition of target organs, including skin, pancreas, liver as well as pituitary. LESSONS: Type 4B HH is rare but usually tends to cause multiple organ dysfunction and even death. For those patients who have difficulty tolerating phlebotomy, iron chelator might be a good alternative.

11.
Zhen Ci Yan Jiu ; 46(2): 87-94, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33788427

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Baihui" (GV20), "Shuigou" (GV26), etc. on the expressions of vascular endothelial growth factor (VEGF), collagen fibrillary acidic protein (GFAP), neuronal nucleus antigen(NeuN), ß-catenin and Axin2 protein and mRNA in rats with cerebral ischemia (CI), so as to explore its mechanism underlying improvement of ischemic stroke. METHODS: A total of 108 male SD rats were randomly divided into control, model and EA groups, which were further divided into 7 d, 14 d and 21 d subgroups, with 12 rats in each group. The CI model was established by occlusion of the middle cerebral artery. EA (2 Hz/100 Hz, 2-4 V) was applied to GV20, GV26, bilateral "Sanyinjiao" (SP6) and bilateral "Neiguan" (PC6) for 30 min, once daily (except Sundays) for 21 days at most. The neurological deficit score was evaluated according to Longa's methods. The cerebral infarction state was assessed by using a magnetic resonance T2 imaging system. The expression levels of neurovascular markers as VEGF,GFAP and NeuN, and ß-catenin and Axin2 protein and mRNA in the ischemic brain tissue were detected by using immunohistochemistry and quantitative real-time PCR, respectively. RESULTS: After modeling, the neurological deficit score and cerebral infarction size were significantly increased (P<0.01), and the expression of NeuN and Axin2 proteins and mRNAs were significantly and gradually decreased with time (day 7, 14 and 21) (P<0.01), whereas the expression levels of VEGF, GFAP, ß-catenin proteins and mRNAs were significantly increased on day 7, 14 and 21 in the model group relevant to the control group (P<0.01). Compared with the model group, the neurological deficit score, cerebral infarction size and the expressions of Axin2 protein and mRNA were significantly decreased on day 7, 14 and 21 (P<0.01), whereas the expression levels of VEGF, GFAP and NeuN and ß-catenin proteins and mRNAs were considerably up-regulated in the EA group on day 7, 14 and 21 (P<0.01). CONCLUSION: EA can protect the neurovascular units from injury, reduce the volume of cerebral infarction and improve the symptoms of neurological deficit in cerebral ischemic rats, which may be related to its effects in up-regulating ß-catenin expression and in down-regulating Axin2 expression to further activate classical Wnt/ ß-catenin signal pathway.


Assuntos
Isquemia Encefálica , Eletroacupuntura , Animais , Isquemia Encefálica/genética , Isquemia Encefálica/terapia , Infarto Cerebral , Masculino , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/genética , beta Catenina/genética
12.
Free Radic Biol Med ; 168: 6-15, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33781892

RESUMO

Autism spectrum disorders (ASDs) are highly associated with oxidative stress. We have recently shown that Disconnected-interacting protein homolog 2 A (DIP2A) functions in ASD pathophysiology by regulating cortactin acetylation for spine development and synaptic transmission. However, its role is not fully understood in the context of its abundant expression in mitochondria. In this paper, we found that DIP2A was involved in superoxide dismutase (SOD)-mediated antioxidative reactions. In mice, DIP2A knockout inhibited SOD activity and increased reactive oxygen species (ROS) levels in the cerebral cortex. In vitro gain-of-function experiments further confirmed the positive role of DIP2A in scavenging ROS upon oxidative stress. Moreover, DIP2A knockout caused irregular mitochondrial morphology in the cerebral cortex and impaired mitochondrial metabolism with an over consumption of lipids for energy supply. Taken together, these results revealed unrecognized functions of DIP2A in antioxidative protection, providing another possible explanation for DIP2A-mediated ASD pathophysiology.

13.
Ying Yong Sheng Tai Xue Bao ; 32(3): 921-930, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33754558

RESUMO

Fertilization is an effective way to improve soil quality, increase soil fertility and soil microbial diversity in paddy soil. To explore the changes of soil labile organic carbon (C) fractions and hydrolytic enzyme activity after 34 years fertilization treatments in a field experiment in double-cropping rice system of southern China. There were four treatments, including chemical fertilizer alone (MF), rice residue and chemical fertilizer (RF), 30% organic matter and 70% chemical fertilizer (OM), and the control without fertilizer input (CK). We measured soil organic carbon (SOC) content, soil labile organic C fractions, SOC related hydrolytic enzyme activity, correlation coefficients of soil enzyme activity with SOC content and its labile organic C fractions. The results showed that MF, RF and OM increased SOC content by 4.5%, 22.4% and 53.5%, respectively. Compared with MF and CK, RF and OM increased soil labile organic C fractions [cumulative C mineralization (Cmin), permanganate oxidizable C (KMnO4-C), particulate organic C (POC), dissolved organic C (DOC), light fraction organic C (LFOC), microbial biomass C (MBC)] and the proportion of each labile organic C fractions to total organic C. The contents of Cmin, KMnO4-C, POC, DOC, LFOC and MBC under OM treatment were 3.5, 3.1, 3.7, 1.9, 1.2 and 1.9 times higher than CK treatment, respectively. The proportion of labile organic C fractions to total organic C of RF and OM treatments was significantly higher than that in CK. The order of soil hydrolytic enzyme activity [α-glucosidase (αG), ß-glucosidase (ßG), ß-xylosidase (ßX), cellobiohydrolase (GBH), and N-acetyl-ß-glucosaminidase (NAG)] was OM>RF>MF>CK. The soil hydrolytic enzyme activity under OM treatment increased by 111.8%, 14.1%, 127.3%, 285.6% and 91.4% compared with CK, respectively. Furthermore, RF and OM treatments were beneficial to soil peroxidase (POD) activity. MF treatment was beneficial to soil polyphenol oxidase (PPO) activity. There was a significant positive correlation between soil hydrolytic enzyme activity and SOC content and its labile organic C fractions. In conclusion, the combined application of organic manure, rice straw returning and chemical fertilizer is an effective method to improve soil labile organic C fractions and hydrolytic enzyme activity in a double-cropping rice paddy field of southern China.


Assuntos
Fertilizantes , Oryza , Agricultura , Carbono/análise , China , Fertilizantes/análise , Solo
14.
Nano Lett ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33769812

RESUMO

The controllable synthesis of metal-based nanoclusters for heterogeneous catalytic reactions has received considerable attention. Nevertheless, manufacturing these architectures, while avoiding aggregation and retaining surface activity, remains challenging. Herein, for the first time we designed NiCoFe-Prussian blue analogue (PBA) nanocages as a support for in situ dispersion and anchoring of polymetallic phosphide nanoparticles (pMP-NPs). Benefiting from the porous surfaces and the synergistic effects between pMP-NPs and the cyano groups in PBA, the NiCoFe-P-NP@NiCoFe-PBA nanocages exhibit a significantly enhanced catalytic activity for oxygen evolution reaction (OER) with an overpotential of 223 mV at 10 mA cm-2 and a Tafel slope of 78 mV dec-1, outperforming the NiCoFe-PBA nanocubes, NiCoFe-P nanocages, NiFe-P-NP@NiFe-PBA nanocubes, and CoFe-P-NP@CoFe-PBA nanoboxes. This work not only offers the synthesis strategy of in situ anchoring pMP-NPs on PBA nanocages but also provides a new insight into optimized Gibbs free energy of OER by regulating electron transfer from metallic phosphides to PBA substrate.

15.
Reproduction ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33730690

RESUMO

Long non-coding RNAs (lncRNAs) regulate a complex array of fundamental biological processes, while its molecular regulatory mechanism in Leydig cells (LCs) remains unclear. In the present study, we established the lncRNA LOC102176306/miR-1197-3p/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) regulatory network by bioinformatic prediction, and investigated its roles in goat LCs. We found that lncRNA LOC102176306 could efficiently bind to miR-1197-3p and regulate PPARGC1A expression in goat LCs. Downregulation of lncRNA LOC102176306 significantly repressed testosterone (T) synthesis and adenosine triphosphate (ATP) production, decreased the activities of antioxidant enzymes and mitochondrial complex I and complex III, caused the loss of mitochondrial membrane potential, and inhibited the proliferation of goat LCs by decreasing PPARGC1A expression, while these effects could be restored by miR-1197-3p inhibitor treatment. In addition, miR-1197-3p mimics treatment significantly alleviated the positive effects of lncRNA LOC102176306 overexpression on T and ATP production, antioxidant capacity and proliferation of goat LCs. Taken together, lncRNA LOC102176306 functioned as a sponge for miR-1197-3p to maintain PPARGC1A expression, thereby affecting the steroidogenesis, cell proliferation and oxidative stress of goat LCs. These findings extend our understanding of the molecular mechanisms of T synthesis, cell proliferation and oxidative stress of LCs.

16.
Health Qual Life Outcomes ; 19(1): 103, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33752686

RESUMO

BACKGROUND: More than 210,000 medical workers have fought against the outbreak of Coronavirus Disease 2019 (COVID-19) in Hubei in China since December 2019. However, the prevalence of mental health problems in frontline medical staff after fighting COVID-19 is still unknown. METHODS: Medical workers in Wuhan and other cities in Hubei Province were invited to participate a cross-sectional and convenience sampling online survey, which assessed the prevalence of anxiety, insomnia, depression, and post-traumatic stress disorder (PTSD). RESULTS: A total of 1,091 responses (33% male and 67% female) were valid for statistical analysis. The prevalence was anxiety 53%, insomnia 79%, depression 56%, and PTSD 11%. Healthcare workers in Wuhan were more likely to face risks of anxiety (56% vs. 52%, P = 0.03) and PTSD (15% vs. 9%, P = 0.03) than those in other cities of Hubei. In terms of educational attainment, those with doctoral and masters' (D/M) degrees may experience more anxiety (median of 7.0, [interquartile range (IQR) 2.0-8.5] vs. median 5.0 [IQR 5.0-8.0], P = 0.02) and PTSD (median 26.0 [IQR 19.5-33.0] vs. median 23.0 [IQR 19.0-31.0], P = 0.04) than those with lower educational degrees. CONCLUSIONS: The mental problems were an important issue for the healthcare workers after COVID-19. Thus, an early intervention on such mental problems is necessary for healthcare workers.

17.
Schizophr Bull ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33768244

RESUMO

Recent large-scale integrative analyses (including Transcriptome-Wide Association Study [TWAS] and Summary-data-based Mendelian Randomization [SMR]) have identified multiple genes whose cis-regulated expression changes may confer risk of schizophrenia. Nevertheless, expression quantitative trait loci (eQTL) data and genome-wide associations used for integrative analyses were mainly from populations of European ancestry, resulting in potential missing of pivotal biological insights in other continental populations due to population heterogeneity. Here we conducted TWAS and SMR integrative analyses using blood eQTL (from 162 subjects) and GWAS data (22 778 cases and 35 362 controls) of schizophrenia in East Asian (EAS) populations. Both TWAS (P = 2.89 × 10-14) and SMR (P = 6.04 × 10-5) analyses showed that decreased TMEM180 mRNA expression was significantly associated with risk of schizophrenia. We further found that TMEM180 was significantly down-regulated in the peripheral blood of schizophrenia cases compared with controls (P = 8.63 × 10-4 in EAS sample), and its expression was also significantly lower in the brain tissues of schizophrenia cases compared with controls (P = 1.87 × 10-5 in European sample from PsychENCODE). Functional explorations suggested that Tmem180 knockdown affected neurodevelopment, ie, proliferation and differentiation of neural stem cells. RNA sequencing showed that pathways regulated by Tmem180 were significantly enriched in brain development and synaptic transmission. In conclusion, our study provides convergent lines of evidence for the involvement of TMEM180 in schizophrenia, and highlights the potential and importance of resource integration and sharing at this big data era in bio-medical research.

18.
Mol Psychiatry ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686213

RESUMO

Alternative splicing of schizophrenia risk genes, such as DRD2, GRM3, and DISC1, has been extensively described. Nevertheless, the alternative splicing characteristics of the growing number of schizophrenia risk genes identified through genetic analyses remain relatively opaque. Recently, transcriptomic analyses in human brains based on short-read RNA-sequencing have discovered many "local splicing" events (e.g., exon skipping junctions) associated with genetic risk of schizophrenia, and further molecular characterizations have identified novel spliced isoforms, such as AS3MTd2d3 and ZNF804AE3E4. In addition, long-read sequencing analyses of schizophrenia risk genes (e.g., CACNA1C and NRXN1) have revealed multiple previously unannotated brain-abundant isoforms with therapeutic potentials, and functional analyses of KCNH2-3.1 and Ube3a1 have provided examples for investigating such spliced isoforms in vitro and in vivo. These findings suggest that alternative splicing may be an essential molecular mechanism underlying genetic risk of schizophrenia, however, the incomplete annotations of human brain transcriptomes might have limited our understanding of schizophrenia pathogenesis, and further efforts to elucidate these transcriptional characteristics are urgently needed to gain insights into the illness-correlated brain physiology and pathology as well as to translate genetic discoveries into novel therapeutic targets.

19.
BMC Cancer ; 21(1): 272, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33711965

RESUMO

BACKGROUND: Bile duct invasion is a relatively rare event and is not well characterised in hepatocellular carcinoma (HCC). It remains very difficult to diagnose HCC with bile duct tumour thrombus (BDTT) before surgery. Increasing evidence has revealed that inflammation plays a critical role in tumorigenesis. This study aimed to develop nomograms based on systemic and hepatic inflammation markers to predict microscopic BDTT (micro-BDTT) before surgery in HCC. METHODS: A total of 723 HCC patients who underwent hepatectomy as initial therapy between January 2012 and June 2020 were included in the study. Logistic regression analysis was used to identify independent risk factors for micro-BDTT. The nomograms were constructed using significant predictors, including α-fetoprotein (AFP), alkaline phosphatase (ALP), direct bilirubin (DB), prognostic nutritional index (PNI), and γ-glutamyl transferase (γ-GT)/alanine aminotransferase (ALT). The prediction accuracies of the nomograms were evaluated using the area under the receiver operating characteristic (ROC) curve. RESULTS: AFP, ALP, DB, PNI, and γ-GT/ALT were independent risk factors for predicting micro-BDTT (P = 0.036, P = 0.004, P = 0.013, P = 0.012, and P = 0.006, respectively), which were assembled into the nomograms. The area under the ROC curve of the nomograms combining PNI and γ-GT/ALT for predicting micro-BDTT was 0.804 (95% confidence interval [CI]: 0.730-0.878). The sensitivity and specificity values when used in predicting micro-BDTT before surgery were 0.739 (95% CI: 0.612-0.866) and 0.781 (95% CI: 0.750-0.813), respectively. CONCLUSIONS: The nomogram based on combining systemic and hepatic inflammation markers is suitable for predicting micro-BDTT before surgery in HCC patients, leading to a rational therapeutic choice for HCC.

20.
Nano Lett ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33728921

RESUMO

Graphene nanoribbons are predicted to support low-loss and tunable plasmonic waveguide modes with an ultrasmall mode area. Experimental observation of the plasmonic waveguide modes in graphene nanoribbons, however, is challenging because conventional wet lithography has difficulty creating a clean graphene nanoribbon with a low edge roughness. Here, we use a dry lithography method to fabricate ultraclean and low-roughness graphene nanoribbons, which are then encapsulated in hexagonal boron nitride (hBN). We demonstrate low-loss plasmon propagation with a quality factor up to 35 in the ultraclean nanoribbon waveguide using cryogenic infrared nanoscopy. In addition, we observe both the fundamental and the higher-order plasmonic waveguide modes for the first time. All the plasmon waveguide modes can be tuned through electrostatic gating. The observed tunable plasmon waveguide modes in ultraclean graphene nanoribbons agree well with the finite-difference time-domain (FDTD) simulation results. They are promising for reconfigurable photonic circuits and devices at a subwavelength scale.

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