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1.
Phys Chem Chem Phys ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33449065

RESUMO

We comprehensively investigated the hydrogen evolution reaction (HER) activity of a series of transition metal phosphides (MPs) (M = Cr, Mn, Fe, Co, and Ni) using first-principles calculations. The free energy difference was calculated for possible sites on the surface to pinpoint the reactive sites and the associated catalytic activities. We found that the chemical properties of these considered MPs are different from those of WP, including CrP which has the same electronic configuration as WP but was shown not to be a good electrocatalyst. Different reactive sites other than WP were predicted, and notably, unlike WP, phosphorus can participate/catalyze the HER on the considered MP. Among these MPs, there are more active sites on FeP, CoP, and NiP than CrP and MnP. Our electronic structure analysis suggests that the spin polarization is critical in determining the hydrogen adsorption and hence the HER performance. We further explored the HER of metal- or phosphorus-deficit MPs, as samples can be grown under different conditions. In particular, phosphorus-deficit FeP, CoP, and NiP were found to have enhanced HER performance, with either better catalytic activities or more active sites. Therefore, we proposed that controlling of these defects can be an effective approach to tune the HER catalytic ability of these MPs. It can serve as the design principle to synthesize new MP based electrocatalysts.

2.
Theranostics ; 11(4): 1901-1917, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33408788

RESUMO

Rationale: Fc engineering has become the focus of antibody drug development. The current mutagenesis and in silico protein design methods are confined by the limited throughput and high cost, while the high-throughput phage display and yeast display technologies are not suitable for screening glycosylated Fc variants. Here we developed a mammalian cell display-based Fc engineering platform. Methods: By using mammalian cell display and next generation sequencing, we screened millions of Fc variants for optimized affinity and specificity for FcγRIIIa or FcγRIIb. The identified Fc variants with improved binding to FcγRIIIa were substituted into trastuzumab and rituximab and the effector function of antibodies were examined in the PBMC-based assay. On the other hand, the identified Fc variants with selectively enhanced FcγRIIb binding were applied to CD40 agonist antibody and the activities of the antibodies were measured on different cell assays. The immunostimulatory activity of CD40 antibodies was also evaluated by OVA-specific CD8+ T cell response model in FcγR/CD40-humanized mice. Results: Using this approach, we screened millions of Fc variant and successfully identified several novel Fc variants with enhanced FcγRIIIa or FcγRIIb binding. These identified Fc variants displayed a dramatic increase in antibody-dependent cellular cytotoxicity in PBMC-based assay. Novel variants with selectively enhanced FcγRIIb binding were also identified. CD40 agonist antibodies substituted with these Fc variants displayed activity more potent than the parental antibody in the in vitro and in vivo models. Conclusions: This approach increased the throughput of Fc variant screening from thousands to millions magnitude, enabled screening variants containing multiple mutations and could be integrated with glycoengineering technology, represents an ideal platform for Fc engineering. The initial efforts demonstrated the capability of the platform and the novel Fc variants could be substituted into nearly any antibody for the next generation of antibody therapeutics.

3.
Cell Res ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33390587

RESUMO

Glioblastoma (GBM) is an incurable and highly heterogeneous brain tumor, originating from human neural stem/progenitor cells (hNSCs/hNPCs) years ahead of diagnosis. Despite extensive efforts to characterize hNSCs and end-stage GBM at bulk and single-cell levels, the de novo gliomagenic path from hNSCs is largely unknown due to technical difficulties in early-stage sampling and preclinical modeling. Here, we established two highly penetrant hNSC-derived malignant glioma models, which resemble the histopathology and transcriptional heterogeneity of human GBM. Integrating time-series analyses of whole-exome sequencing, bulk and single-cell RNA-seq, we reconstructed gliomagenic trajectories, and identified a persistent NSC-like population at all stages of tumorigenesis. Through trajectory analyses and lineage tracing, we showed that tumor progression is primarily driven by multi-step transcriptional reprogramming and fate-switches in the NSC-like cells, which sequentially generate malignant heterogeneity and induce tumor phenotype transitions. We further uncovered stage-specific oncogenic cascades, and among the candidate genes we functionally validated C1QL1 as a new glioma-promoting factor. Importantly, the neurogenic-to-gliogenic switch in NSC-like cells marks an early stage characterized by a burst of oncogenic alterations, during which transient AP-1 inhibition is sufficient to inhibit gliomagenesis. Together, our results reveal previously undercharacterized molecular dynamics and fate choices driving de novo gliomagenesis from hNSCs, and provide a blueprint for potential early-stage treatment/diagnosis for GBM.

4.
BMC Complement Med Ther ; 21(1): 36, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446182

RESUMO

BACKGROUND: During the fresh cycles of in vitro fertilization and embryo transfer, a disturbance in the reproductive endocrine environment following controlled ovarian hyperstimulation (COH) is closely related to compromised endometrial receptivity. This is a major disadvantage for women during pregnancy. Based on the theory of traditional Chinese medicine, Bushen Huoxue recipe (BSHXR) has been indicated to facilitate embryo implantation. METHODS: The COH model (Kunming breed) was induced by injecting mice with pregnant mare serum gonadotrophin (0.4 IU/g) and human chorionic gonadotropin (1 IU/g), followed by treatment with BSHXR at three different concentrations (5.7, 11.4, and 22.8 g/kg), Bushen recipe (BSR) (5.7 g/kg), and Huoxue recipe (HXR) (5.7 g/kg). After successful mating, the pregnancy rate and implantation sites were examined on embryo day 8 (ED8), and the weight ratio of endometrium was calculated on ED4 midnight. Serum estrogen, progesterone, and endometrial PGE2 levels were measured using enzyme-linked immunosorbent assay. The endometrial microvasculature was evaluated using CD31 immunostaining. The protein and mRNA levels of the angiogenic factors in the endometrium were evaluated using western blot, immunohistochemistry, and polymerase chain reaction. RESULTS: In the COH group, the pregnancy rate and implantation sites were significantly decreased, and abnormal serum hormone levels and impaired endometrial vascular development were observed. After BSHXR treatment, the supraphysiological serum progesterone level in COH mice was restored to normalcy. Moreover, the abnormal expression of the endometrial pro-angiogenic factors, including HIF1α, COX2-PGE2 pathway, and the down-stream factors, namely, MMP2, MMP9, TIMP2, and FGF2 after subjecting mice to COH was significantly improved after BSHXR treatment. CONCLUSION: BSHXR could improve embryo implantation by regulating hormonal balance and modulating endometrial angiogenesis in mice, without inducing any side effects in normal pregnancy.

5.
Cell Death Dis ; 12(1): 32, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33414476

RESUMO

Histone deacetylase 5 (HDAC5) belongs to class II HDAC subfamily and is reported to be increased in the kidneys of diabetic patients and animals. However, little is known about its function and the exact mechanism in diabetic kidney disease (DKD). Here, we found that HDAC5 was located in renal glomeruli and tubular cells, and significantly upregulated in diabetic mice and UUO mice, especially in renal tubular cells and interstitium. Knockdown of HDAC5 ameliorated high glucose-induced epithelial-mesenchymal transition (EMT) of HK2 cells, indicated in the increased E-cadherin and decreased α-SMA, via the downregulation of TGF-ß1. Furthermore, HDAC5 expression was regulated by PI3K/Akt signaling pathway and inhibition of PI3K/Akt pathway by LY294002 treatment or Akt phosphorylation mutation reduced HDAC5 and TGF-ß1 expression in vitro high glucose-cultured HK2 cells. Again, high glucose stimulation downregulated total m6A RNA methylation level of HK2 cells. Then, m6A demethylase inhibitor MA2 treatment decreased Akt phosphorylation, HDAC5, and TGF-ß1 expression in high glucose-cultured HK2 cells. In addition, m6A modification-associated methylase METTL3 and METTL14 were decreased by high glucose at the levels of mRNA and protein. METTL14 not METTL3 overexpression led to PI3K/Akt pathway inactivation in high glucose-treated HK2 cells by enhancing PTEN, followed by HDAC5 and TGF-ß1 expression downregulation. Finally, in vivo HDACs inhibitor TSA treatment alleviated extracellular matrix accumulation in kidneys of diabetic mice, accompanied with HDAC5, TGF-ß1, and α-SMA expression downregulation. These above data suggest that METTL14-regulated PI3K/Akt signaling pathway via PTEN affected HDAC5-mediated EMT of renal tubular cells in diabetic kidney disease.

6.
Brain Imaging Behav ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398778

RESUMO

Hippocampal atrophy is often considered as one of the important biomarkers for early diagnosis of Alzheimer's disease (AD), which is an irreversible neurodegenerative disorder. Traditional methods for hippocampus analysis usually computed the shape and volume features from structural Magnetic Resonance Image (sMRI) for the computer-aided diagnosis of AD as well as its prodromal stage, i.e., mild cognitive impairment (MCI). Motivated by the success of deep learning, this paper proposes a deep learning method with the multi-channel cascaded convolutional neural networks (CNNs) to gradually learn the combined hierarchical representations of hippocampal shapes and asymmetries from the binary hippocampal masks for AD classification. First, image segmentation is performed to generate the bilateral hippocampus binary masks for each subject and the mask difference is obtained by subtracting them. Second, multi-channel 3D CNNs are individually constructed on the hippocampus masks and mask differences to extract features of hippocampal shapes and asymmetries for classification. Third, a 2D CNN is cascaded on the 3D CNNs to learn high-level correlation features. Finally, the features learned by multi-channel and cascaded CNNs are combined with a fully connected layer followed by a softmax classifier for disease classification. The proposed method can gradually learn the combined hierarchical features of hippocampal shapes and asymmetries to enhance the classification. Our method is verified on the baseline sMRIs from 807 subjects including 194 AD patients, 397 MCI (164 progressive MCI (pMCI) + 233 stable MCI (sMCI)), and 216 normal controls (NC) from Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Experimental results demonstrate that the proposed method achieves an AUC (Area Under the ROC Curve) of 88.4%, 74.6% and 71.9% for AD vs. NC, MCI vs. NC and pMCI vs. sMCI classifications, respectively. It proves the promising classification performance and also shows that both hippocampal shape and asymmetry are helpful for AD diagnosis.

7.
Biol Trace Elem Res ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33415583

RESUMO

Copper is often used as a growth promoter, at the same time copper is one of the most important essential trace elements for fur animals, especially Rex rabbits. However, too much copper added to the diet may harm animal health, and copper excreted in feces can pollute the environment. In this study, 3-month-old Rex rabbits were randomly divided into four groups and fed a basal diet containing 0, 30, 60, or 120 mg/kg Cu for 5 weeks. The diet supplemented with 30 mg/kg Cu significantly increased (P < 0.05) the average daily feed intake (ADFI) and the average daily gain (ADG) and also the activity of serum Cu-Zn (zinc) superoxide dismutase and the digestibility of ether extract. Supplemental Cu up to 120 mg/kg did not significantly adversely affect the Zn metabolism of growing Rex rabbits. Overall, the data in this study indicate that 30 mg/kg is the optimal level of Cu supplementation in the diet of growing Rex rabbits. The results will provide a reference to improve the breeding of Rex rabbits and possibly other animals. In follow-up studies, the amount of copper in the diet should be reduced as much as possible from the baseline of 30 mg/kg copper.

8.
Food Microbiol ; 94: 103643, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33279069

RESUMO

Our purpose was to investigate the main bacterial microbiota and volatile profiles in the Chinese traditional dry-cured product-Jinhua ham during different processing stages and to analyze the role of the main microbiota in the formation of characteristic flavor. We determined the microbiota of Jinhua ham by using 16 S high throughput sequencing, and found that Staphylococcus constituted the predominant microbiota throughout the flavor formation process. Based on the volatile profiles of Jinhua dry-cured products from 11 different processing via SPME-GC-MS analysis, Aldehydes were the main groups of volatiles, with the most abundant ones being hexanal (13.89%) and nonanal (3.96%). To further investigate the relationship between predominant microbiota and the major volatile compounds in Jinhua ham, we screened and isolated genus Staphylococcus with high protease and lipase activities. The main Staphylococcus isolates, S. saprophyticus (53.4%) and S. equorum (31.0%) are related to the yields of aldehydes by producing hexanal, nonanal, benzaldehyde, and phenylacetaldehyde, indicating their contributions on the formation of characteristic flavor substances in Jinhua ham.

10.
Stat Med ; 40(4): 842-858, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33174296

RESUMO

Chance imbalance in baseline characteristics is common in randomized clinical trials. Regression adjustment such as the analysis of covariance (ANCOVA) is often used to account for imbalance and increase precision of the treatment effect estimate. An objective alternative is through inverse probability weighting (IPW) of the propensity scores. Although IPW and ANCOVA are asymptotically equivalent, the former may demonstrate inferior performance in finite samples. In this article, we point out that IPW is a special case of the general class of balancing weights, and advocate to use overlap weighting (OW) for covariate adjustment. The OW method has a unique advantage of completely removing chance imbalance when the propensity score is estimated by logistic regression. We show that the OW estimator attains the same semiparametric variance lower bound as the most efficient ANCOVA estimator and the IPW estimator for a continuous outcome, and derive closed-form variance estimators for OW when estimating additive and ratio estimands. Through extensive simulations, we demonstrate OW consistently outperforms IPW in finite samples and improves the efficiency over ANCOVA and augmented IPW when the degree of treatment effect heterogeneity is moderate or when the outcome model is incorrectly specified. We apply the proposed OW estimator to the Best Apnea Interventions for Research (BestAIR) randomized trial to evaluate the effect of continuous positive airway pressure on patient health outcomes. All the discussed propensity score weighting methods are implemented in the R package PSweight.

11.
J Am Soc Echocardiogr ; 34(1): 72-82, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33121857

RESUMO

BACKGROUND: No study has examined intima thickness of the carotid artery and peripheral arteries in subjects with acute ischemic stroke due to large-artery atherosclerosis (LAAS). The aim of this study was to test whether carotid intima thickness (CIT), radial intima thickness (RIT), and dorsalis pedis intima thickness (PIT) are closely associated to atherosclerotic risk factors and whether they possess independent and additive value for differentiating LAAS stroke. METHODS: One hundred and two patients with LAAS stroke and 104 age- and gender-matched control subjects were enrolled. CIT, RIT, and PIT were measured using a 24-MHz, high-resolution ultrasound system. Multivariate linear regression was performed to determine associations between ultrasonic parameters and risk factors. Binary logistic regression was used to evaluate the diagnostic value of different parameters. Receiver operating characteristic curves were plotted to compare the performance of several diagnostic models. RESULTS: CIT ([36.97 ± 11.27] × 10-2 vs [23.68 ± 5.12] × 10-2 mm, P < .001) and RIT ([15.40 ± 3.62] × 10-2 vs [11.06 ± 2.22] × 10-2 mm, P < .001) were significantly thicker in patients with LAAS stroke than in control subjects. CIT and RIT were associated with traditional risk factors for atherosclerosis, including age, systolic blood pressure, and serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, homocysteine, and glucose. CIT had incremental diagnostic value to traditional risk factors for LAAS stroke (area under the curve, 0.945 vs 0.860; P = .006). The addition of CIT and RIT to traditional risk factors had the best diagnostic performance (area under the curve, 0.961). CONCLUSIONS: Measurement of CIT, RIT, and PIT is feasible and reliable using newly developed ultrasound techniques. CIT and RIT were associated with traditional risk factors for atherosclerosis and exhibited incremental value to traditional risk factors for differentiating patients with LAAS stroke from control subjects.

12.
Angew Chem Int Ed Engl ; 60(4): 2155-2159, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33022829

RESUMO

Here we report a general approach to make unnatural amino acids from readily available cysteine derivatives. This method capitalizes on an intramolecular radical substitution process that generates alkyl radicals through C-S cleavage. The resulting alkyl radicals partook in diverse C-C bond forming events. These reactions proceed under mild, photocatalytic conditions at room temperature, and can be performed open to air. The utility of these transformations is further demonstrated in the straightforward synthesis of various unnatural amino acids and peptides that are difficult to access previously.

13.
Food Funct ; 12(1): 241-251, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33295905

RESUMO

Long-term high-fat-diet (HFD)-induced obesity is associated with many comorbidities, such as cognitive impairment and anxiety, which are increasing public health burdens that have gained prevalence in adolescents. Although low-dose alcohol could attenuate the risk of cardiovascular disease, its mechanism on HFD-induced anxiety-related behavior remains not clear. The mice were divided into 4 groups, Control (Con), Alcohol (Alc), HFD and HFD + Alc groups. To verify the effects of low-dose alcohol on HFD-induced anxiety-related behavior, the mice were fed with HFD for 16 weeks. At the beginning of week 13, the HFD-fed mice were administered intragastrically with low-dose alcohol (0.8 g kg-1) for 4 weeks. After 4 weeks of oral administration, low-dose alcohol decreased body weight and Lee's index in HFD-induced obese mice. Moreover, low-dose alcohol alleviated the anxiety-related behaviors of obese mice in the open field test and the elevated plus maze test. The HFD-induced damage to the hippocampus was improved in hematoxylin-eosin staining assay in mice. In addition, low-dose alcohol also suppressed HFD-induced oxidative stress and increased HFD-suppressed adiponectin (APN) expression and nuclear factor erythroid 2-related factor 2 (Nrf2) activation in the hippocampus. Taken together, low-dose alcohol significantly ameliorates HFD-induced obesity, oxidative stress and anxiety-related behavior in mice, which might be related to APN upregulation, Nrf2 activation and related antioxidase expression including SOD1, HO-1, and catalase.

14.
Food Chem ; 340: 127953, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32916405

RESUMO

Large uptakes of nitrite have been proven to be detrimental to human health, therefore, the development of high-performance nitrite sensors is highly emergent. Herein, a carbon selenide nanofilms modified carbon fiber cloth (CSe2 NF/CC) electrode was obtained via in-situ synthesis to detect nitrite. The electrode integrates the collective merits of macroporous CC and pleated carbon selenide nanofilms, possessing a low overpotential of 0.83 V, a high electrochemical active surface area (EASA) of 5.39 cm2, great electrical conductivity, and fast charge transport as well as ion diffusion. The proposed electrode achieved a low limit of detection of 0.04 µmol L-1 (S/N = 3), a high sensitivity of 2048.56 µA mmol L-1 cm-2, excellent selectivity, and long-term stability. Additionally, the CSe2 NF/CC was successfully used for nitrite detection in different food samples such as pickled vegetables and sausage samples.


Assuntos
Fibra de Carbono/química , Eletroquímica/instrumentação , Engenharia , Limite de Detecção , Nitritos/análise , Compostos Organosselênicos/química , Eletrodos , Humanos , Propriedades de Superfície
15.
Neurochem Int ; 142: 104926, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33276022

RESUMO

Major depressive disorder (MDD) is a prevalent psychiatric disorder that brings great harm and burden to both patients and society. This study aimed to examine the effects of whole-body vibration (WBV) training on a chronic restraint stress (CRS) induced depression rat model and provide an initial understanding of related molecular mechanisms. Adult Sprague-Dawley male rats were randomly divided into the following three groups: a) control group, b) depressive disorder group, and c) depression with WBV training treatment group. Daily food intake, body weight, sucrose preference test, open field test, elevated plus maze, forced swimming test, and Barnes maze task tests were performed. Immunofluorescence staining and ELISA analysis were used to assess neuronal damage, synaptic proteins, glial cells, and trophic factors. The data of behavioral tests and related biochemical indicators were statistically analyzed and compared between groups. Rats undergoing CRS showed increased anxiety-like behavior and memory impairment, along with synaptic atrophy and neuronal degeneration. WBV could reverse behavioral dysfunction, inhibit the degeneration of neurons, alleviate the damage of neurons and the pathological changes of glial cells, enhance trophic factor expression, and ameliorate the downregulation of dendritic and synaptic proteins after CRS. The effect of WBV in rats may be mediated via the reduction of hippocampal neuronal degeneration and by improving expression of synaptic proteins. WBV training exerts multifactorial benefits on MDD that supports its use as a promising new therapeutic option for improving depression-like behaviors in the depressive and/or potentially depressive.

16.
Biomed Pharmacother ; 133: 111062, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378965

RESUMO

Diabetic peripheral neuropathy (DPN) is the common complication of diabetes mellitus. Histone deacetylase (HDAC) inhibitor trichostatin A (TSA) is reported to ameliorate the peripheral nerves degeneration of DPN. However, the exact mechanism is still not well elucidated. Here, we first revealed that TSA promoted nerve conduction and brain derived neurotrophic factor (BDNF) expression in the sciatic nerves of diabetic mice. In line, TSA also reversed high glucose-reduced mature BDNF expression in vitro cultured rat Schwann cells (RSC96). Then unexpectedly, the downstream targets of TSA HDAC1 and HDAC5 were not involved in TSA-improved BDNF expression. Furthermore, unfolded protein response (UPR) chaperone GRP78 was revealed to be downregulated with high glucose stimulation in RSC96 cells, which was avoided with TSA treatment. Also, GRP78 upregulation mediated TSA-improved mature BDNF expression in high glucose-cultured RSC96 cells by binding with BDNF. As well, TSA treatment enhanced the binding of GRP78 with BDNF in RSC96 cells. Again, UPR-associated transcription factors XBP-1s and ATF6 were involved in TSA-increased GRP78 expression in high glucose-stimulated RSC96 cells. Finally, conditioned medium from high glucose-cultured RSC96 cells delayed neuron SH-SY5Y differentiation and that from TSA-treated high glucose-cultured RSC96 cells promoted SH-SY5Y cell differentiation. Taken together, our findings suggested that TSA increased BDNF expression to ameliorate DPN by improving XBP-1s/ATF6/GRP78 axis in Schwann cells.

17.
Colloids Surf B Biointerfaces ; 197: 111370, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33049661

RESUMO

A facile methodology was explored by using glutaraldehyde as a cross-linking reagent for in situ modification of polyvinyl alcohol (PVA) electrospun nanofibers doped with monodisperse silver nanoparticles (AgNPs) via the one-pot reactions. The hydroxyl groups along the PVA molecule chains can serve as both the reactive sites and stabilizers for AgNPs. Meanwhile, the cross-linking degree can be easily tuned by controlling the charged amounts of glutaraldehyde to obtain either partial or cured cross-linked PVA nanofibrous mats doped with AgNPs. It was revealed that such different cross-linking degrees could effectively control the release contents and rates of the embedded Ag to the surrounding aqueous solution. Furthermore, such release behavior was also found to be pH-responsive and acid-labile due to the formation of acetal groups during the cross-linking reactions. Besides both the partial and cured cross-linked PVA doped with Ag nanoparticles can still bear good antibacterial efficacy against S. aureus while have low cytotoxicity against mouse embryo fibroblasts (NIH3T3), human embryonic kidney cells (293T) and human histiocytic lymphoma cells (U937).

18.
J Exp Med ; 218(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33125052

RESUMO

During thymocyte development, medullary thymic epithelial cells (mTECs) provide appropriate instructive cues in the thymic microenvironment for not only negative selection but also the generation of regulatory T (T reg) cells. Here, we identify that miR-155, a microRNA whose expression in T reg cells has previously been shown to be crucial for their development and homeostasis, also contributes to thymic T reg (tT reg) cell differentiation by promoting mTEC maturation. Mechanistically, we show that RANKL stimulation induces expression of miR-155 to safeguard the thymic medulla through targeting multiple known and previously uncharacterized molecules within the TGFß signaling pathway, which is recognized for its role in restricting the maturation and expansion of mTECs. Our work uncovers a miR-155-TGFß axis in the thymic medulla to determine mTEC maturity and, consequently, the quantity of tT reg cells and suggests that miR-155 ensures proper tT reg cell development in both cell-intrinsic and -extrinsic manners.

19.
Am J Epidemiol ; 190(1): 189-190, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33155637
20.
Hum Cell ; 34(1): 229-237, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33063235

RESUMO

Mounting evidence indicates that the long non-coding RNA (lncRNA) LINC00460 plays an oncogenic role in tumor progression; however, the role of LINC00460 in cervical cancer (CC) remains unknown. In this study, we found that LINC00460 was frequently upregulated in CC tissues and cell lines. Knockdown of LINC00460 repressed CC cell growth and invasion in vitro and attenuated tumorigenesis in vivo. Mechanistically, miR-361-3p was predicted as a direct target of LINC00460 by bioinformatics analysis, which was further confirmed by qRT-PCR, dual-luciferase reporter assays, and rescue experiments. Furthermore, miR-361-3p targeted the 3' untranslated region (UTR) of Gli1 mRNA and repressed its expression. Taken together, our study revealed that LINC00460 functions as an oncogenic lncRNA in CC, indicating the likely participation of the LINC00460/miR-361-3p/Gli1 pathway in the disease. Accordingly, our results provide new insight into CC tumorigenesis.

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