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1.
Neural Regen Res ; 17(4): 806-811, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34472479

RESUMO

Pain is one of the manifestations of hip disorder and has been proven to lead to the remodeling of somatotopic map plasticity in the cortex. However, most studies are volume-based which may lead to inaccurate anatomical positioning of functional data. The methods that work on the cortical surface may be more sensitive than those using the full brain volume and thus be more suitable for map plasticity study. In this prospective cross-sectional study performed in Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China, 20 patients with osteonecrosis of the femoral head (12 males and 8 females, aged 56.80 ± 13.60 years) and 20 healthy controls (9 males and 11 females, aged 54.56 ± 10.23 years) were included in this study. Data of resting-state functional magnetic resonance imaging were collected. The results revealed that compared with healthy controls, compared with the healthy controls, patients with osteonecrosis of the femoral head (ONFH) showed significantly increased surface-based regional homogeneity (ReHo) in areas distributed mainly in the left dorsolateral prefrontal cortex, frontal eye field, right frontal eye field, and the premotor cortex and decreased surface-based ReHo in the right primary motor cortex and primary sensory cortex. Regions showing significant differences in surface-based ReHo values between the healthy controls and patients with ONFH were defined as the regions of interests. Seed-based functional connectivity was performed to investigate interregional functional synchronization. When the areas with decreased surface-based ReHo in the frontal eye field and right premotor cortex were used as the regions of interest, compared with the healthy controls, the patients with ONFH displayed increased functional connectivity in the right middle frontal cortex and right inferior parietal cortex and decreased functional connectivity in the right precentral cortex and right middle occipital cortex. Compared with healthy controls, patients with ONFH showed significantly decreased cortical thickness in the para-insular area, posterior insular area, anterior superior temporal area, frontal eye field and supplementary motor cortex and reduced volume of subcortical gray matter nuclei in the right nucleus accumbens. These findings suggest that hip disorder patients showed cortical plasticity changes, mainly in sensorimotor- and pain-related regions. This study was approved by the Medical Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (approval No. 2018-041) on August 1, 2018.

2.
Front Behav Neurosci ; 15: 717008, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34720898

RESUMO

Cerebral ischemia triggers vascular dementia (VD), which is characterized by memory loss, cognitive deficits, and vascular injury in the brain. Puerarin (Pur) represents the major isoflavone glycoside of Radix Puerariae, with verified neuroprotective activity and cardiovascular protective effects. However, whether Pur ameliorates cognitive impairment and vascular injury in rats with permanent occlusion of bilateral common carotid arteries (BCCAO) remains unknown. This work aimed to assess Pur's effects on BCCAO-induced VD and to dissect the underlying mechanisms, especially examining the function of transient receptor potential melastatin-related 2 (TRPM2) in alleviating cognitive deficits and vascular injuries. Rats with BCCAO developed VD. Pur (50, 100, and 150 mg/kg) dose-dependently attenuated the pathological changes, increased synaptic structural plasticity in the dorsal CA1 hippocampal region and decreased oxidative stress, which eventually reduced cognitive impairment and vascular injury in BCCAO rats. Notably, Pur-improved neuronal cell loss, synaptic structural plasticity, and endothelial vasorelaxation function might be mediated by the reactive oxygen species (ROS)-dependent TRPM2/NMDAR pathway, evidenced by decreased levels of ROS, malondialdehyde (MDA), Bax, Bax/Bcl2, and TRPM2, and increased levels of superoxide dismutase (SOD), Bcl2, and NR2A. In conclusion, Pur has therapeutic potential for VD, alleviating neuronal cell apoptosis and vascular injury, which may be related to the ROS-dependent TRPM2/NMDAR pathway.

3.
Psychol Rep ; : 332941211054775, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787510

RESUMO

Since listening and speaking are two integral skills for effective second language (L2) communication, enhancing learners' motivation to listen to and speak in the target language will engage them in the learning process, eventually leading to improvements in these two skills. Yet despite its importance, L2 listening and speaking motivation is underexplored in the current literature. Drawing on self-determination theory, this study adapted, validated, and administered one L2 listening motivation scale and one L2 speaking motivation scale to 863 undergraduate students from different regions of China. Correlation analysis, confirmatory factor analysis, and inferential statistical analyses (e.g., ANOVA) were used to compute the data. The results revealed that the learners were both intrinsically and extrinsically motivated to listen to and speak in English. A strong association between L2 listening motivation and speaking motivation was observed. Furthermore, gender, geographical, and disciplinary differences were found in the two kinds of motivation, and overseas experience also affected the learners' motivation. The results provide insights into L2 learner motivation in specific linguistic domains and yield pedagogical implications for L2 teaching and learning.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34787947

RESUMO

The monoatomic zero-valent tin complex (stannylone) {[Si II (Xant)Si II ]Sn 0 } 5 stabilized by a bis(silylene)xanthene ligand, [Si II (Xant)Si II = PhC(N t Bu) 2 Si(Xant)Si(N t Bu) 2 CPh], and its bis-tetracarbonyliron complex {[Si II (Xant)Si II ]Sn 0 [Fe(CO) 4 ] 2 } 4 are reported. The stannylone 5 bearing a two-coordinate zero-valent tin atom is synthesized by reduction of the precursor 4 with potassium graphite. Compound 4 results from the Sn II halide precursor {[Si II (Xant)Si II ]Sn II Cl}Cl 2 or {[Si II (Xant)Si II ]SnBr 2 } 3 through reductive salt-metathesis reaction with K 2 Fe(CO) 4 . According to density functional theory (DFT) calculations, the highest occupied molecular orbital (HOMO) and HOMO-1 of 5 correspond to a π-type lone pair with delocalization into both adjacent vacant orbitals of the Si II atoms and a σ-type lone pair at the Sn 0 center, respectively, indicating genuine stannylone character.

6.
BMC Cancer ; 21(1): 1264, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34814869

RESUMO

BACKGROUND: Emerging evidence has indicated the critical role of TRPV4 in diverse human cancers. However, the underlying molecular mechanism of TRPV4 in colon cancer invasiveness is still unknown. METHODS: Immunohistochemistry staining was used to analyze the expression of TRPV4 and ZEB1 in clinical tissues; Wound healing and transwell assays were applied to determine the cell invasiveness; Western blot was used to explore the relation between TRPV4 and ZEB1. RESULTS: Colon cancer cells were transfected with siRNA against TRPV4 or HC067047 (a selective TRPV4 antagonist), TRPV4 full-length plasmid or siRNA against ZEB1, or both, in order to measure cell migration and invasion. And we found that TRPV4 silencing or inhibition exhibited an inhibitory role in colon cancer cell migration and invasion, coupled with compromised EMT process, and suppressed AKT activity. TRPV4 stimulated expression of ZEB1 and consequently contributed to EMT process and invasiveness. It was also revealed that overexpression of TRPV4 and ZEB1 in clinical patients with local metastasis, and positive correlation between TRPV4 and ZEB1. CONCLUSIONS: Our results uncovered the role of TRPV4 in tumor metastasis and highlighted the potential mechanism of TRPV4-ZEB1 axis in indicating EMT.

7.
Theranostics ; 11(20): 10064-10073, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815804

RESUMO

Rationale: Renal cysts in patients with autosomal dominant polycystic kidney disease (ADPKD) can originate from any nephron segments, including proximal tubules (PT), the loop of Henle (LOH), distal tubules (DT), and collecting ducts (CD). Previous studies mostly used limited cell markers and failed to identify cells negative for these markers. Therefore, the cell composition and origin of ADPKD cyst are still unclear, and mechanisms of cystogenesis of different origins await further exploration. Methods: We performed single-cell RNA sequencing for the normal kidney tissue and seven cysts derived from superficial or deep layers of the polycystic kidney from an ADPKD patient. Results: Twelve cell types were identified and analyzed. We found that a renal cyst could be derived either from CD or both PT and LOH. Gene set variation analysis (GSVA) showed that epithelial mesenchymal transition (EMT), TNFA signaling via the NFKB pathways, and xenobiotic metabolism were significantly activated in PT-derived cyst epithelial cells while robust expression of genes involved in G2M Checkpoint, mTORC1 signaling, E2F Targets, MYC Targets V1, MYC Targets V2 were observed in CD-derived cells. Conclusion: Our results revealed that a single cyst could originate from CD or both PT and LOH, suggesting heterogeneity of polycystic composition and origin. Furthermore, cyst epithelial cells with different origins have different gene set activation.

8.
Financ Res Lett ; 43: 102012, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34803532

RESUMO

The impacts of crises are never gender-neutral, and the COVID-19 pandemic is no exception. Using a brand-new dataset covering 24 countries, we document that women-led businesses are subject to a higher likelihood of closure and a longer closure duration than men-led businesses during the pandemic. Women business leaders are also more pessimistic about the future than men business leaders. The disadvantages suffered by women-led businesses widen in high gender inequality economies and developing economies. Our results further indicate that finance and labor factors are likely to be the major contributors to these disadvantages. We suggest that COVID-19's policy response should not be gender-neutral.

9.
Front Psychol ; 12: 758757, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803839

RESUMO

This study aims to investigate different types of English listening instruction, listening self-efficacy, and listening strategy use, particularly the mediating role of self-efficacy between listening instruction and strategy use. We first examined the types of L2 instruction being employed in English as a Foreign Language (EFL) listening classrooms and then we looked into the relationships between L2 listening instruction, listening self-efficacy, and listening strategy use. The results of exploratory factor analysis demonstrated four types of English listening instruction: process-based instruction, comprehension-based instruction, self-regulation-based instruction, and strategy-based instruction. The results of structural equation modeling showed that listening self-efficacy mediated the relationship between strategy-based instruction and listening strategy use, and self-regulation-based instruction and listening strategy use. This study has implications for understanding the effectiveness of different listening teaching practices in enhancing self-efficacy and strategy use.

10.
Gland Surg ; 10(10): 2935-2944, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34804881

RESUMO

Background: Papillary thyroid cancer (PTC) is a common endocrine malignancy, and its incidence rate has been increasing in recent years. Long noncoding RNAs (lncRNAs) participate in cell biological processes through a variety of regulatory ways, and play an essential role in tumor development. Methods: This study explored the expression of lncRNA small nucleolar RNA host gene 6 (SNHG6) in PTC by bioinformatics analysis, and quantitative real-time PCR (qRT-PCR). Cell counting kit-8 (CCK-8) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to study the effect of SNHG6 on the proliferation of PTC cells. Luciferase reporter gene assay and western blot were used to study the mechanism. Results: SNHG6 was highly expressed in PTC tissue samples and cell lines. In vitro, overexpression of SNHG6 promoted the proliferation of PTC cells, while silencing SNHG6 inhibited the proliferation of PTC cells. miR-186 is the downstream target of SNHG6. SNHG6 regulates the proliferation of PTC cells through miR-186. In addition, CDK6 is the target gene of miR-186, which can inhibit the expression of CDK6 protein. SNHG6 can promote the expression of CDK6 by regulating miR-186. Conclusions: SNHG6 is highly expressed in PTC and can promote the proliferation of PTC cells by regulating the miR-186/CDK6 axis, which is expected to become a potential therapeutic target for PTC.

11.
Front Endocrinol (Lausanne) ; 12: 722253, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733238

RESUMO

Objective: This prospective randomized controlled trial compared the reproductive outcomes of frozen embryo transfer (FET) with hormone replacement treatment (HRT) with or without gonadotropin-releasing hormone agonist (GnRHa) pretreatment. Methods: A total of 133 patients scheduled for HRT-FET mainly because of tubal and/or male factors who received two high-quality cleavage-stage embryos were enrolled at two participating centers. The GnRHa group (n = 65) received GnRHa pretreatment, while the control group (n = 68) did not. Analysis was based on the intention-to-treat (ITT) principle. Results: Among the 133 participants, 130 (97.7%) underwent embryo transfer and 127 (95.5%) completed the protocol. The clinical pregnancy rate according to ITT did not differ between the GnRHa and control groups [39/65 (60.0%) vs. 41/68 (60.3%), p = 0.887]. The implantation rate (47.6% vs. 45.3%, p = 0.713), early pregnancy loss rate (5.1% vs. 19.5%, p = 0.09), and live birth rate (49.2% vs. 50.0%, p = 0.920) were also comparable between groups. Conclusion: Pretreatment with GnRHa does not improve the reproductive outcomes for women receiving HRT-FET. Clinical Trial Registration: The study was registered with the Chinese Clinical Trial Registry (ChiCTR-IOR-17014170; http://www.chictr.org.cn).

12.
Plant Dis ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34735281

RESUMO

In July 2020, symptoms of crown and root rot were observed on about 10% of 4-month-old plants of industrial hemp Cannabis sativa cultivar Yunma-1 in Weifang City, Shandong Province in eastern China (Fig 1). During this month, the local temperature ranged from 19-32°C, and the total precipitation was 148mm. The disease symptoms included leaf chlorosis, crown and root rot, stunted growth, and wilting (Figs. 1 and 2). The diseased stem and root tissues were collected and cut into fragments of 0.5cm each. The fragments were surface-sterilized by dipping into 1% NaClO for 1 min, rinsed in sterile water and plated on potato dextrose agar (PDA) and on oomycetes-selective medium PARP (Jeffers and Martin 1986). The plates were incubated at 25°C in the dark for 3 days and 18 total single-hyphal purified isolates were obtained for further analyses with 8 from PDA and 10 from PARP. The colonies of all 18 isolates were white, had abundant aerial hyphae, and were cottony in appearance, resembling Pythium spp (Watanabe 2002). The grass-leaf method (Van Der Plaats-Niterink 1981) induced their sexual reproduction. The size and shape of hyphae, oogonia, antheridia, and oospores were all consistent with those of Pythium aphanidermatum (Fig 3). DNA was extracted from three isolates and their internal transcribed spacer (ITS) regions of rDNA were amplified and sequenced using the primers ITS1/ITS4 (White et al. 1990). The ITS sequences of all three isolates were identical to each other (GenBank accession OK091124.1) and showed a 100% query coverage and 99.88% nucleotide sequence identity with that of type strain of P. aphanidermatum (GenBank accession AY598622.2). Pathogenicity tests were performed with three isolates on hemp cultivar B1. Sterile substrates were prepared in 2L-pots containing peat soil and vermiculite in a 2:1 ratio, with test hemp plants grown from rooted stem cuttings. Plants were kept in a greenhouse at 22 to 27°C under 16 h photoperiod, watered every two days (about 200ml each time) and supplied commercial nutrient solution once a week. A month after transplanting to pots, a wound of 1 mm deep and 10 mm long (made by a sterilized needle) on the surface of the root crown area of the main stem was inoculated with an 8-mm-diameter agar disk of mycelia grown on PDA for 4 days. Six plants were tested for each isolate and three plants were inoculated with sterile agar medium without mycelia as negative controls. The experiment was repeated twice. After one month, plants inoculated with P. aphanidermatum isolates showed the same disease symptoms as observed on field plants while all negative control plants remained disease-free. P. aphanidermatum was reisolated from the diseased tissue and confirmed to be identical to those inoculated based on ITS sequencing and colony morphology. To our knowledge, this is the first report of P. aphanidermatum causing crown and root rot on hemp in China. With an estimated 66,700 hectares hemp cultivation in China producing over US$1 billion worth of hemp fiber (McGrath 2020), this pathogen represents a serious threat to the hemp industry. This pathogen has been reported on hemp in the US and Canada (Beckerman et al. 2017; Punja et al. 2018). The origin of P. aphanidermatum on hemp in China and its relationship to those in North America remain to be examined.

13.
Medicine (Baltimore) ; 100(45): e27557, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766560

RESUMO

BACKGROUND: Gastric cancer is considered to be the sixth prevalent cancer and the third widespread trigger of cancer-associated deaths globally. One of the major method of treating this harmful condition is completely resecting the entire tumor. Standard treatment procedures, including radiotherapy, surgery, and chemotherapy are ineffective for patients with advanced gastric cancer (AGC), mainly because the predictions are deficient. Many studies have recently sought to examine the effect of combining chemotherapy and molecular-targeted therapy, supposing that such developments could become effective for treating AGC. Still, the advantages of combining chemotherapy plus molecular-targeted therapy to treat advanced gastric cancer appear to be unconvincing. METHODS AND ANALYSIS: We intend to perform an electronic search using information obtained from PubMed, EMBASE, Cochrane Library, ScienceDirect, Web of Science, China National Knowledge Infrastructure, and WanFang databases. Specifically, we will consider all randomized controlled trials published in English or Chinese, and focus only on those assessing the effectiveness and safety of a MIC of chemotherapy and molecular-targeted therapy to treat AGC. Furthermore, two independent authors will conduct data extraction as well as explore the risk of bias. Furthermore, we intend to use the odds ratio for dichotomous data, mean differences or standardized mean differences for continuous data, along with hazard ratio for time-to-event data, with 95% confidence intervals (CIs). ETHICS AND DISSEMINATION: Because of the nature of this study, we will not require ethical approval. Instead, we will report the review reported in a peer-reviewed journal.

14.
Sensors (Basel) ; 21(21)2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34770329

RESUMO

Laser-induced graphene (LIG) has been widely used in flexible sensors due to its excellent mechanical properties and high conductivity. In this paper, a flexible pressure sensor prepared by bionic micro/nanostructure design and LIG mass fraction regulation is reported. First, prepared LIG and conductive carbon paste (CCP) solutions were mixed to obtain a conductive polymer. After the taro leaf structure was etched on the surface of the aluminum alloy plate by Nd:YAG laser processing, the conductive polymer was evenly coated on the template. Pressure sensors were packaged with a stencil transfer printing combined with an Ecoflex flexible substrate. Finally, the effects of different laser flux and the proportion of LIG in the composite on the sensitivity of the sensor are discussed. The results show that when the laser flux is 71.66 J·cm-2 and the mass fraction of LIG is 5%, the sensor has the best response characteristics, with a response time and a recovery time of 86 ms and 101 ms, respectively, with a sensitivity of 1.2 kPa-1 over a pressure range of 0-6 kPa, and stability of 650 cycle tests. The LIG/CCP sensor with a bionic structure demonstrates its potential in wearable devices.


Assuntos
Grafite , Nanoestruturas , Dispositivos Eletrônicos Vestíveis , Condutividade Elétrica , Lasers
15.
Signal Transduct Target Ther ; 6(1): 405, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795208

RESUMO

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

16.
Front Public Health ; 9: 675487, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722430

RESUMO

Background: The most recent international guidelines recommended support training of chest compression (CC) using feedback devices. This study aimed to compare the training efficacy of a simplified feedback trainer with the traditional cardiopulmonary resuscitation (CPR) simulator in CPR training. Methods: A total of 60 soldiers were randomly allocated into three groups equally, trained with a simplified external cardiac massage (ECM) trainer named Soul SheathTM (SS) (SS group), a Resusci Anne manikin (RA group), or traditional simulation training with instructor feedback, respectively. After 7 days of training, the CPR skills were tested blindly in a 2-min assessment session. The primary outcome was the proportion of effective CC, and the secondary outcome included CC rate, depth, compression position, and extent of the release. Results: The percentage of effective CC achieved in the SS group was comparable with the RA group (77.0 ± 15.52 vs. 77.5 ± 10.73%, p = 0.922), and significantly higher than that in the control group (77.0 ± 15.52 vs. 66.8 ± 16.87%, p = 0.037). Both the SS and RA groups showed better CC performance than the control group in terms of CC rate (SS group vs. control group, P = 0.032 and RA group vs. control group, P = 0.026), the proportion of shallow CC (SS group vs. control group, P = 0.011 and RA group vs. control group, P = 0.017). No difference between the SS group and RA group was found in all the CC parameters. Conclusions: The simplified ECM trainer (SS) provides a similar efficacy to the traditional manikin simulator with feedback in CC training to improve the quality of CPR skills.


Assuntos
Reanimação Cardiopulmonar , Massagem Cardíaca , Simulação por Computador , Retroalimentação , Manequins
17.
Anticancer Res ; 41(11): 5507-5515, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732421

RESUMO

BACKGROUND/AIM: The aim of the present study was to correlate the survival response to regional arterial-perfusion chemotherapy (RAPC) with Borrmann classification in patients with gastric cancer. PATIENTS AND METHODS: The survival response of 270 patients with advanced gastric cancer treated with RAPC was analyzed and Borrmann classification of the tumors was retrospectively correlated to survival. RESULTS: The median survival time of RAPC-treated patients with Borrmann type I/II was 53 months compared with 19 and 12 months for those with Borrmann type III and IV, respectively (p<0.001). CONCLUSION: Borrmann classification is a potential indicator to predict prognosis of patients with advanced gastric cancer treated with RAPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional , Terapia Neoadjuvante , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional/mortalidade , Feminino , Gastrectomia , Humanos , Excisão de Linfonodo , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do Tratamento
18.
Mol Cancer ; 20(1): 144, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753486

RESUMO

BACKGROUND: CD8+ T cells play a critical role in the innate antitumour immune response. Recently, CD8+ T cell dysfunction has been verified in various malignant cancers, including non-small cell lung cancer (NSCLC). However, the molecular biological mechanisms of CD8+ T cell dysfunction in human NSCLC are still unclear. METHODS: The expression of circular ubiquitin-specific protease-7 (circUSP7) in NSCLC tissues, exosomes, and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were isolated from the culture medium of NSCLC cells and the plasma of NSCLC patients using an ultracentrifugation method and the ExoQuick Exosome Precipitation Solution kit. The exosomes were then characterized by transmission electronic microscopy (TEM), NanoSight and western blotting. The role of circUSP7 in CD8+ T cell dysfunction was assessed by enzyme-linked immunosorbent assay (ELISA). In vivo circular RNA (circRNA) precipitation (circRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanisms of circUSP7 in CD8+ T cells. In a retrospective study, the clinical characteristics and prognostic significance of circUSP7 in NSCLC tissues were determined. RESULTS: The expression levels of circUSP7 were higher in human NSCLC tissues than in matched adjacent nontumour tissues. Increased levels of circUSP7 indicate poor clinical prognosis and CD8+ T cell dysfunction in patients with NSCLC. The circUSP7 found in NSCLC patient plasma is predominantly secreted by NSCLC cells in an exosomal manner, and circUSP7 inhibits IFN-γ, TNF-α, Granzyme-B and Perforin secretion by CD8+ T cells. Furthermore, circUSP7 inhibits CD8+ T cell function by upregulating the expression of Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) via sponging miR-934. Finally, we show that circUSP7 may promote resistance to anti-PD1 immunotherapy in NSCLC patients. CONCLUSIONS: Exosomal circUSP7 is predominantly secreted by NSCLC cells and contributes to immunosuppression by promoting CD8+ T cell dysfunction in NSCLC. CircUSP7 induces resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for NSCLC patients.

19.
Nat Commun ; 12(1): 6323, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732703

RESUMO

Cancers develop from the accumulation of somatic mutations, yet it remains unclear how oncogenic lesions cooperate to drive cancer progression. Using a mouse model harboring NRasG12D and EZH2 mutations that recapitulates leukemic progression, we employ single-cell transcriptomic profiling to map cellular composition and gene expression alterations in healthy or diseased bone marrows during leukemogenesis. At cellular level, NRasG12D induces myeloid lineage-biased differentiation and EZH2-deficiency impairs myeloid cell maturation, whereas they cooperate to promote myeloid neoplasms with dysregulated transcriptional programs. At gene level, NRasG12D and EZH2-deficiency independently and synergistically deregulate gene expression. We integrate results from histopathology, leukemia repopulation, and leukemia-initiating cell assays to validate transcriptome-based cellular profiles. We use this resource to relate developmental hierarchies to leukemia phenotypes, evaluate oncogenic cooperation at single-cell and single-gene levels, and identify GEM as a regulator of leukemia-initiating cells. Our studies establish an integrative approach to deconvolute cancer evolution at single-cell resolution in vivo.

20.
Nanotechnology ; 33(6)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34736234

RESUMO

Artificial synapses that integrate functions of sensing, memory and computing are highly desired for developing brain-inspired neuromorphic hardware. In this work, an optoelectronic synapse based on the ZnO nanowire (NW) transistor is achieved, which can be used to emulate both the short-term and long-term synaptic plasticity. Synaptic potentiation is present when the device is stimulated by light pulses, arising from the light-induced O2desorption and the persistent photoconductivity behavior of the ZnO NW. On the other hand, synaptic depression occurs when the device is stimulated by electrical pulses in dark, which is realized by introducing a charge trapping layer in the gate dielectric to trap carriers. Simulation of a neural network utilizing the ZnO NW synapses is carried out, demonstrating a high recognition accuracy over 90% after only 20 training epochs for recognizing the Modified National Institute of Standards and Technology digits. The present nanoscale optoelectronic synapse has great potential in the development of neuromorphic visual systems.

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