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1.
Artigo em Inglês | MEDLINE | ID: mdl-32243134

RESUMO

As a bridge between homogeneous and heterogeneous catalysis, single-atom catalysts (SACs), especially the noble metal atoms, have caught an extensive attention from both the fundamental and applied perspectives recently. High cost and difficulty in synthesis are considerable factors, however, limiting the development and practical applications of SACs. Thus, seeking for non-noble SACs for substituting the noble ones is not only of vital importance but also a long-standing challenge. Herein, a surface modification strategy by introducing an oppositely charged dopant and inducing the charge transfer between the SAC and the substrate was proposed to improve the stability and catalytic performance of the non-noble Cu SAC. By using first-principles density functional theory (DFT) calculations, it was demonstrated that the introduction of C in the MoS2 monolayer (C: MoS2, experimentally available) can assist in stabilizing Cu and make it more positively charged, which will facilitate the adsorption of the reactants and further enhance the activity for CO oxidation. Strikingly, our results show that CO oxidation over the Cu-C: MoS2 is more favorable than the Pt atom deposited on the pristine MoS2 (Pt-MoS2), exhibiting its potential in noble metal substitution and low-temperature CO oxidation. Additionally, Cu-C: MoS2 was observed to have response to the visible light, which manifests that it may be a promising photocatalyst. The strategy proposed here provides an efficient route to regulate the electronic structures of SACs through the charge transfer following by promoting the reactivity of the non-noble metal SAC. We hope this strategy can contribute to designing more SACs with low cost and high efficiency, which will be beneficial for their practical applications.

2.
Chin J Nat Med ; 18(3): 169-177, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32245586

RESUMO

The objective of this study was to verify the protective effect of Bifidobacterium longum (BL) and the synergistical effect of Selenium and BL on alcohol plus high fat diet (HFD) induced hepatic injury in mice. We also want to explore the mechanism of Selenium-enriched Bifidobacterium longum (SeBL). C57BL/6 mice were treated with alcohol plus HFD with or without different dosage of BL or SeBL for 4 weeks. Serum levels of ALT, AST, TC, TG, LDL-C, HDL-C, FFAs, TNF-α, IL-6 and IL-1ß, hepatic MDA level, SOD activity, the mRNA levels of AMPK, PPAR-α and SREBP1 were invested. SeBL inhibited lipid accumulation in hepatocytes; reduced serum AST and ALT levels; improved dyslipidemia; decreased serum FFAs, TC, TG and LDL-C levels. SeBL also inhibited alcohol plus HFD-induced hepatocyte oxidative stress through decrease in hepatic MDA levels and increase in SOD activity. SeBL also regulated lipid metabolism related genes such as AMPK, PPAR-α and SREBP1. Although BL had similar effect as SeBL, SeBL is more effective than BL. SeBL protected mice from alcohol plus HFD-induced hepatic injury in mice because of its inhibitory effect on hepatocellular oxidative stress, lipogenesis and inflammation. Selenium enhanced the protective effect of BL.

3.
Integr Cancer Ther ; 19: 1534735420906463, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32248718

RESUMO

Chemotherapy is an effective treatment for invasive breast cancer. Paradoxically, many recently published findings showed that the first-line chemotherapeutic agent paclitaxel (PTX) showed pro-metastatic effects in the progress of treating breast cancer. Xiao-Ai-Ping (XAP) injection, composed of a traditional herbal medicine, Marsdenia tenacissimae extract, is known to exert antitumor effects on various cancers. However, there are few experimental studies on breast cancer. The underlying mechanism of the antitumor effect of XAP combined with chemotherapy agents has not been fully understood. In the present study, we sought to find the antitumor effects of XAP combined with PTX in vitro and in vivo. The data demonstrated that the combination of XAP with PTX resulted in remarkable enhancement of the pro-apoptotic, migration-inhibiting, and anti-invasive effects of PTX in vitro. Significantly, further study showed the overexpression of ATF3 in PTX-treated cell, while XAP counteracted the change of ATF3 induced by PTX. Moreover, it showed that combination treatment could promote the inhibition of tumor growth in MDA-MB-231 cell xenograft mouse model. Compared with PTX treatment, the downregulation of ATF3 indicated that ATF3 played a pivotal role in the combination of XAP with PTX to exert a synergistic effect. Overall, it is expected that PTX combined with XAP may serve as an effective agent for antitumor treatment, and dampening ATF3 maybe a potential strategy to improve the efficacy of PTX.

4.
Schizophr Bull ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32133506

RESUMO

Creativity represents one of the most important and partially heritable human characteristics, yet little is known about its genetic basis. Epidemiological studies reveal associations between creativity and psychiatric disorders as well as multiple personality and behavioral traits. To test whether creativity and these disorders or traits share genetic basis, we performed genome-wide association studies (GWAS) followed by polygenic risk score (PRS) analyses. Two cohorts of Han Chinese subjects (4,834 individuals in total) aged 18-45 were recruited for creativity measurement using typical performance test. After exclusion of the outliers with significantly deviated creativity scores and low-quality genotyping results, 4,664 participants were proceeded for GWAS. We conducted PRS analyses using both the classical pruning and thresholding (P+T) method and the LDpred method. The extent of polygenic risk was estimated through linear regression adjusting for the top 3 genotyping principal components. R2 was used as a measurement of the explained variance. PRS analyses demonstrated significantly positive genetic overlap, respectively, between creativity with schizophrenia ((P+T) method: R2(max) ~ .196%, P = .00245; LDpred method: R2(max) ~ .226%, P = .00114), depression ((P+T) method: R2(max) ~ .178%, P = .00389; LDpred method: R2(max) ~ .093%, P = .03675), general risk tolerance ((P+T) method: R2(max) ~ .177%, P = .00399; LDpred method: R2(max) ~ .305%, P = .00016), and risky behaviors ((P+T) method: R2(max) ~ .187%, P = .00307; LDpred method: R2(max) ~ .155%, P = .00715). Our results suggest that human creativity is probably a polygenic trait affected by numerous variations with tiny effects. Genetic variations that predispose to psychiatric disorders and risky behaviors may underlie part of the genetic basis of creativity, confirming the epidemiological associations between creativity and these traits.

5.
Int J Med Sci ; 17(5): 599-608, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210709

RESUMO

Background: Ulcerative colitis (UC) is a chronically remittent and progressive inflammatory disorder. LRCH1 is reported to be involved in the immune-regulation of several diseases. However, the exact roles of LRCH1 in UC are still obscure. Materials and Methods: LRCH1 expression was analyzed in the inflamed mucosa and peripheral blood mononuclear cells (PBMCs) from patients with UC by quantitative RT-PCR and immunohistochemistry. Peripheral blood CD4+ T cells were transfected with lentivirus-expressing LRCH1 (LV-LRCH1) or LV-sh-LRCH1, and cytokine expression was determined by using flow cytometry, quantitative RT-PCR and ELISA. Transfected CD4+ T cells were harvested to examine the capacity of chemotaxis using Transwell plate. Results: LRCH1 expression was highly decreased in colonic mucosa and PBMCs from patients with A-UC, and negatively correlated with disease activity. Up or down regulation of LRCH1 did not affect the differentiation of CD4+ T cells, and the related cytokines expression. Moreover, LRCH1 inhibited migratory capacity of CD4+ T cells toward CXCL12 by PKCα. Conclusion: LRCH1 plays an important role in the pathogenesis of UC, possibly through modulating the migration of CD4+ T cells. Therefore, targeting LRCH1 might serve as a novel therapeutic approach in the management of UC.

6.
J Trace Elem Med Biol ; 60: 126475, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32142957

RESUMO

Protection of Resveratrol (RSV) against the neurotoxicity induced by high level of fluoride was investigated. Sprague-Dawley (SD) rats and their offspring, as well as cultures of primary neurons were divided randomly into four groups: untreated (control); treated with 50 mg RSV/kg/ (once daily by gavage) or (20 M in the cultured medium); exposed to 50 ppm F- in drinking water or 4 mmol/l in the cultured medium; and exposed to fluoride then RSV as above. The adult rats were treated for 7 months and the offspring sacrificed at 28 days of age; the cultured neurons for 48 h. For general characterization, dental fluorosis was assessed and the fluoride content of the urine measured (by fluoride-electrode) in the rates and the survival of cultured neurons monitored with the CCK-8 test. The spatial learning and memory of rats were assessed with the Morris water maze test. The levels of α7 and α4 nicotinic acetylcholine receptors (nAChRs) were quantified by Western blotting; and the activities of superoxide dismutase (SOD) and catalase (CAT), and the levels of malondialdehyde (MDA) and H2O2 assayed biochemically. The results showed that chronic fluorosis resulted in the impaired learning and memory in rats and their offspring, and more oxidative stress in both rat brains and cultured neurons, which may be associated the lower levels of α7 and α4 nAChR subunits. Interestingly, RSV attenuated all of these toxic effects by fluorosis, indicating that protection against the neurotoxicity of fluoride by RSV might be in mechanism involved enhancing the expressions of these nAChRs.

7.
Women Birth ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32222355

RESUMO

BACKGROUND: Labour pain is an individual experience embedded in a socio-cultural context. In childbirth, the father's involvement provides important support to the mother during labour. However, few published studies have evaluated couples' experiences of paternal involvement and labour pain management in the Chinese context. AIM: This study aimed to understand the experience of labour pain management and the father's involvement in childbirth from the perspectives of women and their partners in Hong Kong. METHODS: An exploratory qualitative design was adopted. A purposive sample of 45 Chinese parents was recruited at the postnatal unit of a regional hospital. Data were collected through semi-structured face-to-face interviews within 1 month after birth. The data were subjected to content analysis. FINDINGS: The findings revealed six major themes: the mothers' experience of labour pain, effectiveness of pain relief measures, mothers' perceptions of support from their partners, mothers' perceptions of support from healthcare professionals, fathers' experience of involvement in childbirth and suggested improvements to maternity services. DISCUSSION: Chinese mothers experienced intense labour pain and used various pain relief measures. Both parents considered the involvement of fathers and support from healthcare professionals to be highly significant during childbirth. CONCLUSIONS: This study highlights the need for a family-centred model of care during childbirth that involves both parents in the decision-making process. Chinese maternity services should implement individualised birth plans that acknowledge both parents' expectations and preferences, thus promoting a positive childbirth experience for the parents.

8.
J Proteomics ; 219: 103737, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32198072

RESUMO

The gut microbiota is the largest and most complex microbial community in the human body. Host-gut microbiota interactions have significant implications on health and disease. The development of genome-sequencing technologies, especially the application of next-generation sequencing (NGS), has accelerated the study of the gut microbiota. Most gut microbiota studies rely on 16S rRNA sequencing, metagenomics, and metatranscriptomics, but metaproteomics, based on mass spectrometry (MS), provides functional information on the signaling and metabolic pathways in the gut microbiota. This review is intended to introduce different research methods to study the gut microbiota, with a specific focus on the current progress and application of metaproteomics. SIGNIFICANCE: The gut microbiota plays a key role in human health and disease. In this review, different research methods are described and compared in the field of the gut microbiota. Among these research methods, metaproteomics reveals the taxonomy and functionality of the gut microbiota, especially the functional pathways associated with diseases. Thus, the current progress and application of metaproteomics are summarized, in order to enhance a comprehensive depiction of metaproteomics.

9.
Fitoterapia ; 143: 104559, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32199958

RESUMO

Four undescribed oxylipin vanillyl acetals with four stereogenic carbons were isolated from the herbs of Solanum lyratum. A comprehensive set of spectroscopic methods were used to elucidate the structures and relative configurations of 1-4. The absolute configurations of the naturally occurring compounds are assigned as 7S, 9'S, 10'S, 11'R at the site of six-membered cyclic acetal attachment by electronic circular dichroism (ECD) calculations and the modified Mosher's method. Compounds 1 and 3 displayed moderate selective inhibition against Hep3B and HepG2 cells, respectively. Further Annexin V-FITC/PI staining assay revealed that 1 and 3 might have inhibitory effects on hepatoma cells through induction of apoptosis.

10.
Schizophr Bull ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32219399

RESUMO

Catatonia is a psychomotor syndrome defined by a constellation of predominantly motor symptoms. The aim of the present study was to determine whether recently admitted psychiatric patients with catatonia exhibited higher serum C-reactive protein (hs-CRP) levels compared to non-catatonic psychiatric patients and healthy controls (HCs). Recently admitted psychiatric patients were screened and evaluated for the catatonia syndrome using the Bush-Francis Catatonia Rating Scale and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The study sample was formed by 150 individuals (39 male and 111 female), including 51 catatonic patients, 55 non-catatonic patients, and 44 HCs. Serum hs-CRP levels were processed with the enzyme-linked immunosorbent assay. Serum levels of creatine kinase (CK), adrenocorticotropic hormone (ACTH), immunoglobulin G (IgG), complement component 3 (C3), and complement component 4 (C4) were also determined. There was a significantly higher percentage of patients with high inflammatory levels (hs-CRP > 3000ng/ml) in the catatonic (43.1%) than in the non-catatonic (14.5%) or HCs group (9.1%) (χ 2 =18.9, P < .001). Logistic regression showed that catatonic patients had significantly higher hs-CRP levels compared to non-catatonic patients even after controlling for other clinical and laboratory variables (OR = 3.52, P = .015, 95% CI 1.28-9.79). Multiple linear regression analysis revealed that log-transformed hs-CRP was independently predicted by body mass index and log-transformed C4, ACTH, and Cortisol in catatonic patients. Findings of the present study suggest that catatonia is specifically linked to a higher level of systemic inflammation, not merely attributable to the overall psychopathology, or alterations in the stress level and complement system.

11.
Biotechnol Lett ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32219689

RESUMO

OBJECTIVES: To screening of bacteria with cyclic amino alcohol deamination activity for enantioselective synthesis of chiral cyclic ß-amino alcohols. RESULTS: A new strain named Arthrobacter sp. TYUT010-15 with the (R)-selective deamination activity of cyclic ß-amino alcohol has been isolated from nature via a high throughput solid-phase screening method. The reaction conditions of TYUT010-15 were optimized. Using the resting cell of TYUT010-15 as the catalyst, kinetic resolution of trans-2-aminocyclopentanol, trans-2-aminocyclohexanol and cis-1-amino-2-indanol was carried out to afford (1S, 2S)-trans-2-aminocyclopentanol, (1S, 2S)-trans-2-aminocyclohexanol and (1R, 2S)-cis-1-amino-2-indanol in > 99% ee and 49.6-50% conversion. Four aromatic ß-amino alcohols and two amines were also resolved, (S)-ß-amino alcohols and (R)-amines were obtained in > 99% ee. Preparation experiment was conducted with 200 mM (23.2 g L-1) racemic trans-2-aminocyclohexanol, yielding the desired (1S, 2S)-trans-2-aminocyclohexanol in 40% isolated yield, > 99% ee and 5.8 g L-1 d-1 space time yields. CONCLUSIONS: This study provides a high throughput solid-phase method for screening of bacteria with cyclic amino alcohol deamination activity and a first example for practical preparation of chiral cyclic ß-amino alcohol by Arthrobacter sp. TYUT010-15.

12.
Anim Reprod Sci ; 215: 106328, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32216937

RESUMO

Yes-associated protein 1 (YAP1) transcription regulator of the Hippo protein kinase pathway, serves as a key regulator of tissue growth and organ size by regulating cell proliferation and apoptosis. Effects of YAP1 on proliferation and apoptosis of sheep endometrial epithelial cells (EEC) as a result of estradiol-17ß (E2) treatment, however, remain unclear. In the present study, the abundance of YAP1 protein in the uterine horn was greater than that in the uterine body or cervix. The YAP1 protein was primarily localized in the endometrial luminal and glandular epithelial cells of the uterine horn of ewes on day 2 of the estrous cycle. Compared with control samples, there was a lesser abundance of YAP1 mRNA transcript that was associated with a lesser proliferation and greater apoptosis of EEC. There were also lesser concentrations of epidermal growth factor and insulin-like growth factor 1 in the spent culture medium when there was a lesser abundance of YAP1 mRNA in EEC compared with those in the control group. When there was a greater abundance of YAP1 mRNA transcript, there were greater concentrations of epidermal growth factor and insulin-like growth factor 1 in the spent media. Furthermore, with estradiol-17ß treatment the abundance of YAP1 mRNA transcript was similar to that of the control samples. Taken together, estradiol-17ß may function as an essential regulator of EEC proliferation and apoptosis by modulation of concentrations of YAP1 protein in the sheep uterus. These results indicate there are molecular mechanisms of estradiol-17ß and YAP1 in EEC proliferation and apoptosis of ewes.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32193514

RESUMO

Genome-wide association studies (GWAS) have reported substantial single-nucleotide polymorphisms (SNPs) associated with major depressive disorder (MDD), but the underlying functional variations in the GWAS risk loci are unclear. Here we show that the European MDD genome-wide risk-associated allele of rs12129573 at 1p31.1 is associated with MDD in Han Chinese, and this SNP is in strong linkage disequilibrium (LD) with a human-unique Alu insertion polymorphism (rs70959274) in the 5' flanking region of a long non-coding RNA (lncRNA) LINC01360 (Long Intergenic Non-Protein Coding RNA 1360), which is preferably expressed in human testis in the currently available expression datasets. The risk allele at rs12129573 is almost completely linked with the absence of this Alu insertion. The Alu insertion polymorphism (rs70959274) is significantly associated with a lower RNA level of LINC01360 and acts as a transcription silencer likely through modulating the methylation of its internal CpG sites. Luciferase assays confirm that the presence of Alu insertion at rs70959274 suppresses transcriptional activities in human cells, and deletion of the Alu insertion through CRISPR/Cas9-directed genome editing increases RNA expression of LINC01360. Deletion of the Alu insertion in human cells also leads to dysregulation of gene expression, biological processes and pathways relevant to MDD, such as the alterations of mRNA levels of DRD2 and FLOT1, transcription of genes involved in synaptic transmission, neurogenesis, learning or memory, and the PI3K-Akt signaling pathway. In summary, we identify a human-unique DNA repetitive polymorphism in robust LD with the MDD risk-associated SNP at the prominent 1p31.1 GWAS loci, and offer insights into the molecular basis of the illness.

14.
Phytochemistry ; 174: 112348, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32213358

RESUMO

Six undescribed sesquiterpenoids, including three acorane-type sesquiterpenoids (daphneaines A-C), three guaiane-type sesquiterpenoids (daphneaines E-G) and three known analogues were isolated from the roots of Daphne genkwa Siebold et Zucc. Their gross structures were elucidated by comprehensive spectroscopic analyses. The relative configurations of daphneaines A-C were determined by NOESY experiments. In addition, the relative configuration of daphneaine G was elucidated by performing a quantum chemical calculation of the NMR chemical shifts coupled with an advanced statistical procedure DP4+. The comparison of experimental and calculated electronic circular dichroism (ECD) data led to the establishment of the absolute configurations of daphneaines A-G. All isolates were tested for their inhibitory activity towards the LPS-induced NO production in RAW 264.7 macrophages, and daphneaine F showed inhibitory effect on NO production with an IC50 value of 35.68 ± 3.18 µM.

15.
J Cell Mol Med ; 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32174013

RESUMO

Leptin is well acknowledged as an anorexigenic hormone that plays an important role in feeding control. Hypothalamic GABA system plays a significant role in leptin regulation on feeding and metabolism control. However, the pharmacological relationship of leptin and GABA receptor is still obscure. Therefore, we investigated the effect of leptin or combined with baclofen on the food intake in fasted mice. We detected the changes in hypothalamic c-Fos expression, hypothalamic TH, POMC and GAD67 expression, plasma insulin, POMC and GABA levels to demonstrate the mechanisms. We found that leptin inhibit fasting-induced increased food intake and activated hypothalamic neurons. The inhibitory effect on food intake induced by leptin in fasted mice can be reversed by pretreatment with baclofen. Baclofen reversed leptin's inhibition on c-Fos expression of PAMM in fasted mice. Therefore, these results indicate that leptin might inhibit fasting-triggered activation of PVN neurons via presynaptic GABA synaptic functions which might be partially blocked by pharmacological activating GABA-B. Our findings identify the role of leptin in the regulation of food intake.

16.
Inorg Chem ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32174112

RESUMO

Three classical Fe-MOFs, viz., MIL-100(Fe), MIL-101(Fe), and MIL-53(Fe), were synthesized to serve as platforms for the investigation of structure-activity relationship and catalytic mechanism in the selective conversion of H2S to sulfur. The physicochemical properties of the Fe-MOFs were characterized by various techniques. It was disclosed that the desulfurization performances of Fe-MOFs with well-defined microstructures are obviously different. Among these, MIL-100(Fe) exhibits the highest catalytic performance (ca. 100% H2S conversion and 100% S selectivity at 100-180 °C) that is superior to that of commercial Fe2O3. Furthermore, the results of systematic characterization and DFT calculation reveal that the difference in catalytic performance is mainly because of discrepancy in the amount of Lewis acid sites. A plausible catalytic mechanism has been proposed for H2S selective conversion over Fe-MOFs. This work provides critical insights that are helpful for rational design of desulfurization catalysts.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32155388

RESUMO

Background: Leptospira is the causative agent of leptospirosis, a zoonotic disease of global importance. To have a better understanding on the host species of Leptospira, we investigated the prevalence of Leptospira species in hedgehogs in Central China. Materials and Methods: Hedgehogs were captured in Hubei Province, China in May and October, 2018. Total DNA was extracted from the kidney tissues of hedgehogs for determining the Leptospira species by PCR amplification of the rrs2, secY, and flaB genes with genus-specific primers. Results: PCR amplification indicated that the positive rate of hedgehogs to the rrs2, secY, and flaB genes were 19.5% (8/41), 12.2% (5/41), and 9.8% (4/41), respectively. The homology of the partial sequence of rrs2, secY, and flaB genes were 99.0-100% among the Leptospira strains from hedgehogs. Phylogenetic analysis revealed that Leptospira species detected in this study clustered together with Leptospira interrogans. Conclusions: We detected L. interrogans from hedgehogs in Central China, suggesting hedgehogs are the hosts of L. interrogans.

18.
BMC Bioinformatics ; 21(Suppl 2): 82, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32164528

RESUMO

BACKGROUND: Genomic micro-satellites are the genomic regions that consist of short and repetitive DNA motifs. Estimating the length distribution and state of a micro-satellite region is an important computational step in cancer sequencing data pipelines, which is suggested to facilitate the downstream analysis and clinical decision supporting. Although several state-of-the-art approaches have been proposed to identify micro-satellite instability (MSI) events, they are limited in dealing with regions longer than one read length. Moreover, based on our best knowledge, all of these approaches imply a hypothesis that the tumor purity of the sequenced samples is sufficiently high, which is inconsistent with the reality, leading the inferred length distribution to dilute the data signal and introducing the false positive errors. RESULTS: In this article, we proposed a computational approach, named ELMSI, which detected MSI events based on the next generation sequencing technology. ELMSI can estimate the specific length distributions and states of micro-satellite regions from a mixed tumor sample paired with a control one. It first estimated the purity of the tumor sample based on the read counts of the filtered SNVs loci. Then, the algorithm identified the length distributions and the states of short micro-satellites by adding the Maximum Likelihood Estimation (MLE) step to the existing algorithm. After that, ELMSI continued to infer the length distributions of long micro-satellites by incorporating a simplified Expectation Maximization (EM) algorithm with central limit theorem, and then used statistical tests to output the states of these micro-satellites. Based on our experimental results, ELMSI was able to handle micro-satellites with lengths ranging from shorter than one read length to 10kbps. CONCLUSIONS: To verify the reliability of our algorithm, we first compared the ability of classifying the shorter micro-satellites from the mixed samples with the existing algorithm MSIsensor. Meanwhile, we varied the number of micro-satellite regions, the read length and the sequencing coverage to separately test the performance of ELMSI on estimating the longer ones from the mixed samples. ELMSI performed well on mixed samples, and thus ELMSI was of great value for improving the recognition effect of micro-satellite regions and supporting clinical decision supporting. The source codes have been uploaded and maintained at https://github.com/YixuanWang1120/ELMSI for academic use only.

19.
Transl Psychiatry ; 10(1): 98, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32184385

RESUMO

Genome-wide association studies (GWAS) of major depression and its relevant biological phenotypes have been extensively conducted in large samples, and transcriptome-wide analyses in the tissues of brain regions relevant to pathogenesis of depression, e.g., dorsolateral prefrontal cortex (DLPFC), have also been widely performed recently. Integrating these multi-omics data will enable unveiling of depression risk genes and even underlying pathological mechanisms. Here, we employ summary data-based Mendelian randomization (SMR) and integrative risk gene selector (iRIGS) approaches to integrate multi-omics data from GWAS, DLPFC expression quantitative trait loci (eQTL) analyses and enhancer-promoter physical link studies to prioritize high-confidence risk genes for depression, followed by independent replications across distinct populations. These integrative analyses identify multiple high-confidence depression risk genes, and numerous lines of evidence supporting pivotal roles of the netrin 1 receptor (DCC) gene in this illness across different populations. Our subsequent explorative analyses further suggest that DCC significantly predicts neuroticism, well-being spectrum, cognitive function and putamen structure in general populations. Gene expression correlation and pathway analyses in DLPFC further show that DCC potentially participates in the biological processes and pathways underlying synaptic plasticity, axon guidance, circadian entrainment, as well as learning and long-term potentiation. These results are in agreement with the recent findings of this gene in neurodevelopment and psychiatric disorders, and we thus further confirm that DCC is an important susceptibility gene for depression, and might be a potential target for new antidepressants.

20.
Acta Biomater ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32147471

RESUMO

Various types of photodynamic agents have been explored for photodynamic therapy (PDT) to destroy cancers located in deep tissues. However, these agents are generally limited by low singlet oxygen (1O2) yields owing to weak absorption in the optical transparent window of biological tissues. Accordingly, in this work, we developed a nanocomposite through the assembly of gold nanobipyramids (GNBPs) on black phosphorus nanosheets (BPNSs). This nanocomposite could simultaneously enhance 1O2 generation and hyperthermia by localized surface plasmon resonance in cancer therapy. As two-dimensional inorganic photosensitizers, BPNSs were hybridized with GNBPs to form BPNS-GNBP hybrid nanosheets. The hybridization markedly increased 1O2 production by the BPNSs through plasmon-enhanced light absorption. The nanocomposite exhibited a higher photothermal conversion efficiency than the BPNSs alone. In vitro and in vivo assays indicated that the BPNS-GNBP hybrid nanocomposite exhibited good tumor inhibition efficacy owing to simultaneous dual-modality phototherapy. In vivo, the nanocomposite suppressed deep-seated tumor growth with minimal adverse effects in mice bearing orthotopic A549 human lung tumors. Taken together, these results demonstrated that our BPNS-GNBP nanocomposite could function as a promising dual-modality phototherapeutic agent for enhanced cancer therapy in future cancer treatments. STATEMENT OF SIGNIFICANCE: In this study, we established a new nanocomposite by assembly of gold nanobipyramids (GNBPs) on black phosphorus nanosheets (BPNSs). Characterization of this nanocomposite showed that BPNS-GNBP enhanced 1O2 generation and hyperthermia. BPNS-GNBP exhibited good tumor inhibition efficacy in vivo and in vitro owing to simultaneous dual-modal phototherapy functions. Moreover, BPNS-GNBP suppressed deep-seated tumor growth in vivo and did not show adverse effects in mice bearing orthotopic A549 human lung tumors. Overall, these results showed that BPNS-GNBP may be used as a promising dual-modal phototherapeutic agent for enhanced cancer therapy in future clinical applications.

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