Publications by authors named "Xiaobo Lu"

141 Publications

Baseline Neutrophil-to-Lymphocyte Ratio Is Independently Associated With 90-Day Transplant-Free Mortality in Patients With Cirrhosis.

Front Med (Lausanne) 2021 31;8:726950. Epub 2021 Aug 31.

Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Patients with cirrhosis have an increased risk of short-term mortality, however, few studies quantify the association between neutrophil-to-lymphocyte ratio (NLR) and 90-day transplant-free mortality in cirrhotic patients. We prospectively analyzed 3,970 patients with chronic liver diseases from two multicenter cohorts in China (January 2015 to December 2016 and July 2018 to January 2019). Restricted cubic splines (RCS) were used to analyze the relation of NLR and all-causes 90-day transplant-free mortality in cirrhosis. A total of 2,583 cirrhotic patients were enrolled in our study. Restricted cubic splines showed that the odds ratio (OR) of all causes 90-day transplant-free mortality started to increase rapidly until around NLR 6.5, and then was relatively flat ( for non-linearity <0.001). The risk of 90-day transplant-free mortality in cirrhotic patients with NLR < 6.5 increased with an increment of 23% for every unit increase in NLR ( < 0.001). The patients with NLR < 4.5 had the highest risk (OR: 2.34, 95% CI 1.66-3.28). In multivariable-adjusted stratified analyses, the increase in the incidence of 90-day transplant-free mortality with NLR increasing was consistent (OR >1.0) across all major prespecified subgroups, including infection group (OR: 1.04, 95% CI 1.00-1.09) and non-infection (OR: 1.06, 95% CI 1.02-1.11) group. The trends for NLR and numbers of patients with organ failure varied synchronously and were significantly increased with time from day 7 to day 28. We found a non-linear association between baseline NLR and the adjusted probability of 90-day transplant-free mortality. A certain range of NLR is closely associated with poor short-term prognosis in patients with cirrhosis.
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http://dx.doi.org/10.3389/fmed.2021.726950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438214PMC
August 2021

Invasive Pulmonary Aspergillosis in Acute-on-Chronic Liver Failure Patients: Short-Term Outcomes and Antifungal Options.

Infect Dis Ther 2021 Sep 1. Epub 2021 Sep 1.

Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No 1838, Guangzhou Dadao Bei, Guangzhou, 510515, People's Republic of China.

Introduction: Acute-on-chronic liver failure (ACLF) patients are susceptible to invasive fungal infections. We evaluated the prognosis and antifungal options in ACLF patients with invasive pulmonary aspergillosis (IPA).

Methods: ACLF patients with IPA from 15 hospitals were retrospectively screened from 2011 to 2018, and 383 ACLF patients without lung infections were included from a prospective cohort (NCT02457637). Demographic, laboratory, clinical data, and 28-day outcomes were documented in the two cohorts.

Results: ACLF patients with probable IPA (n = 145) had greater 28-day mortality (33.6% vs. 15.7%, p < 0.001) than those without (n = 383). The respiratory failure-associated 28-day mortality was greater in ACLF patients with IPA than in those without before (17.1% vs. 0.3%, p < 0.001) and after (16.0% vs. 0.0%, p < 0.001) propensity score matching in 116 pairs. IPA patients with lung injury had greater 28-day all-cause mortality (66.5% vs. 24.2%, p < 0.001) and IPA-associated mortality (45.8% vs. 8.1%, p < 0.001) than patients without lung injury (PaO2/FiO2 ≥ 400 mmHg). Antifungal therapy was prescribed to 139 of 145 patients, and 102 patients were treated with voriconazole alone (n = 59) or sequential/combined therapy (n = 43) with varying loading doses (100-800 mg) and daily maintenance doses (0-800 mg). A proposed optimal voriconazole regimen (loading dose, 200 mg twice daily; daily maintenance dose, 100 mg) achieved comparable short-term survival and optimal trough drug concentrations (1-5 μg/mL) on therapeutic drug monitoring in 26 patients.

Conclusion: Presence of IPA increases the short-term mortality of ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients.
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http://dx.doi.org/10.1007/s40121-021-00524-5DOI Listing
September 2021

Lower platelet counts were associated with 90-day adverse outcomes in acute-on-chronic liver disease patients.

Ann Palliat Med 2021 Aug 13. Epub 2021 Aug 13.

Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; Hepatology Unit, Zengcheng Branch, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Chronic liver diseases (CLD), including cirrhosis and non-cirrhotic liver diseases, are globally widespread and create a serious disease burden. Platelet count is a clinically accessible and affordable prognostic indicator of liver disease. We investigated the relationship between platelet count and 90-day prognosis in patients with acute-on-chronic liver diseases (AoCLD).

Methods: A total of 3,970 patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study, which included two prospective multi-center cohorts, were included in the study. We grouped the patients according to the platelet count and analyzed the 90-day adverse outcome (death or liver transplantation).

Results: In the final analysis, 3,939 patients with AoCLD were included, of whom 2,802 had definite liver cirrhosis. The cumulative incidence of 90-day adverse outcomes in patients increased with the change of platelet group (log-rank P<0.001). From univariate and multivariate analyses, platelet count was inversely associated with the incidence of 90-day adverse outcomes in patients (P for trend <0.001). The group with platelet count <20×109 /L had the highest risk (odds ratio, 3.15; 95% confidence interval, 1.59-6.25), with 21 (36.8%) of these patients having adverse outcomes within 90 days. The risk of a 90-day adverse outcome in patients increased by 5% for every 10×109 /L decrease in platelet count below 210×109 /L.

Conclusions: Lower platelet count was associated with a higher incidence of 90-day adverse outcomes in patients with AoCLD. Even within the normal platelet count range, the risk of a 90-day adverse outcome in patients increased with decreases in platelet count. Clinical trial number: NCT02457637, NCT03641872.
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http://dx.doi.org/10.21037/apm-21-1019DOI Listing
August 2021

Impact of Hepatic Encephalopathy on Clinical Characteristics and Adverse Outcomes in Prospective and Multicenter Cohorts of Patients With Acute-on-Chronic Liver Diseases.

Front Med (Lausanne) 2021 2;8:709884. Epub 2021 Aug 2.

Department of Gastroenterology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China.

Hepatic encephalopathy is a severe complication, and its contribution to clinical adverse outcomes in patients with acute-on-chronic liver diseases from the East is unclear. We aimed to investigate the impact of hepatic encephalopathy on clinical characteristics and adverse outcomes in prospective and multicenter cohorts of patients with acute-on-chronic liver diseases. We conducted a cohort study of two multicenter prospective cohorts. China. Acute-on-chronic liver disease patients with various etiologies. The diagnosis and severity of hepatic encephalopathy were assessed using the West Haven scale. The correlation between clinical adverse outcomes and varying hepatic encephalopathy grades was analyzed in the target patients. A total of 3,949 patients were included, and 340 of them had hepatic encephalopathy. The incidence of hepatic encephalopathy was higher in patients with alcohol consumption (9.90%) than in those with hepatitis B virus infection (6.17%). The incidence of 28- and 90-day adverse outcomes increased progressively from hepatic encephalopathy grades 1-4. Logistic regression analysis revealed that hepatic encephalopathy grades 3 and 4 were independent risk factors for the 28- and 90-day adverse outcome in the fully adjusted model IV. Stratified analyses showed similar results in the different subgroups. Compared to grades 1-2 and patients without hepatic encephalopathy, those with grade 3 hepatic encephalopathy had a significant increase in clinical adverse outcomes, independent of other organ failures. Hepatic encephalopathy grades 3-4 were independent risk factors for 28- and 90-day adverse outcomes. Hepatic encephalopathy grade 3 could be used as an indicator of brain failure in patients with acute-on-chronic liver disease.
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http://dx.doi.org/10.3389/fmed.2021.709884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365160PMC
August 2021

Benzo[a]pyrene diol epoxide-induced transformed cells identify the significance of hsa_circ_0051488, a ERCC1-derived circular RNA in pulmonary squamous cell carcinoma.

Mol Carcinog 2021 10 28;60(10):684-701. Epub 2021 Jul 28.

Department of Toxicology, School of Public Health, China Medical University, Shenyang, Liaoning, China.

ERCC1 is a gene for repairing DNA damage whose function is related to carcinogenic-induced tumorigenesis and the effectiveness of platinum therapies. Circular RNAs (circRNAs) are products of posttranscriptional regulation with pleiotropic effects on the pathogenesis of lung cancer. We aim to identify that specific circRNAs derived from ERCC1 can regulate key biological processes involved in the development of lung cancer. We performed bioinformatics analysis, in vitro experiments, and analyzed clinical samples, to determine the biological features of a certain ERCC1-derived circRNA termed as hsa_circ_0051488 in benzo[a]pyrene diol epoxide-induced malignant transformed cell and lung cancer cell. The well-established model of transformed cells provided an ideal platform for analyzing the molecular characteristics of this circRNA in the malignant transformation of lung epithelial cell, which supports that hsa_circ_0051488 functions in the onset and growth of lung squamous cell carcinoma (LUSC). Further analysis indicates that the absence of hsa_circ_0051488 promoted the proliferation of cells with the malignant phenotype. Extensive experiments confirm that hsa_circ_0051488 is present in the cytoplasm and functioned as a competing endogenous RNA. In particular, hsa_circ_0051488 binds to mir-6717-5p, thereby modulating the expression of SATB2 gene, a lung cancer suppressor. Furthermore, our in silico experiments indicate that SATB2 can inhibit multiple tumor pathways and its expression positively correlated with the tumor suppressor gene CRMP1. These findings suggest a possible regulatory mechanism of hsa_circ_0051488 in LUSC, and that the newly discovered hsa_circ_0051488/miR-6717-5p/SATB2 axis may be a potential route for therapeutic intervention of LUSC.
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http://dx.doi.org/10.1002/mc.23335DOI Listing
October 2021

Multiple flat bands and topological Hofstadter butterfly in twisted bilayer graphene close to the second magic angle.

Proc Natl Acad Sci U S A 2021 Jul;118(30)

Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona 08860, Spain;

Moiré superlattices in two-dimensional van der Waals heterostructures provide an efficient way to engineer electron band properties. The recent discovery of exotic quantum phases and their interplay in twisted bilayer graphene (tBLG) has made this moiré system one of the most renowned condensed matter platforms. So far studies of tBLG have been mostly focused on the lowest two flat moiré bands at the first magic angle θ ∼ 1.1°, leaving high-order moiré bands and magic angles largely unexplored. Here we report an observation of multiple well-isolated flat moiré bands in tBLG close to the second magic angle θ ∼ 0.5°, which cannot be explained without considering electron-election interactions. With high magnetic field magnetotransport measurements we further reveal an energetically unbound Hofstadter butterfly spectrum in which continuously extended quantized Landau level gaps cross all trivial band gaps. The connected Hofstadter butterfly strongly evidences the topologically nontrivial textures of the multiple moiré bands. Overall, our work provides a perspective for understanding the quantum phases in tBLG and the fractal Hofstadter spectra of multiple topological bands.
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http://dx.doi.org/10.1073/pnas.2100006118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325360PMC
July 2021

CircFADS2 is downregulated in osteoarthritis and suppresses LPS-induced apoptosis of chondrocytes by regulating miR-195-5p methylation.

Arch Gerontol Geriatr 2021 Sep-Oct;96:104477. Epub 2021 Jul 10.

Department of Orthopaedics, The Affiliated Hospital of Southwest Medical University, Luzhou City, Sichuan Province, 646000, PR. China.. Electronic address:

Background: CircRNA circFADS2 has been reported to protect cells from LPS (Lipopolysaccharide)-induced cell injury, which contributes to osteoarthritis (OA). This study was carried out to study the role of circFADS2 in OA.

Methods: The expression of circFADS2 and miR-195-5p in synovial fluid samples from 63 OA patients and 63 healthy controls were detected by RT-qPCRs. The effects of overexpression of circFADS2 on the expression of miR-195-5p and the methylation of miR-195-5p gene in chondrocytes were evaluated by RT-qPCRs and MSPs, respectively. The roles of circFADS2 and miR-195-5p in regulating the LPS-induced apoptosis of chondrocytes were explored by cell apoptosis assay.

Results: CircFADS2 was downregulated in OA and inversely correlated with miR-195-5p. In chondrocytes, overexpression of circFADS2 and downregulation of miR-195-5p were observed after LPS treatment. In chondrocytes, overexpression of circFADS2 decreased the expression levels of miR-195-5p, and increased the methylation of miR-195-5p gene. Cell apoptosis assay showed that overexpression of circFADS2 reduced the apoptosis of chondrocytes under LPS treatment. Overexpression of miR-195-5p increased cell apoptosis and attenuated the effects of overexpression of circFADS2 on cell apoptosis.

Conclusion: CircFADS2 may downregulate miR-19-5p through methylation to suppress LPS-induced apoptosis of chondrocytes, thereby suppressing OA.
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http://dx.doi.org/10.1016/j.archger.2021.104477DOI Listing
September 2021

Different Effects of Total Bilirubin on 90-Day Mortality in Hospitalized Patients With Cirrhosis and Advanced Fibrosis: A Quantitative Analysis.

Front Med (Lausanne) 2021 23;8:704452. Epub 2021 Jun 23.

Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China.

Total bilirubin (TB) is a major prognosis predictor representing liver failure in patients with acute on chronic liver failure (ACLF). However, the cutoff value of TB for liver failure and whether the same cutoff could be applied in both cirrhotic and non-cirrhotic patients remain controversial. There is a need to obtain the quantitative correlation between TB and short-term mortality evidence-based methods, which is critical in establishing solid ACLF diagnostic criteria. Patients hospitalized with cirrhosis or advanced fibrosis (FIB-4 > 1.45) were studied. TB and other variables were measured at baseline. The primary outcome was 90-day transplantation-free mortality. Multi-variable Cox proportional hazard model was used to present the independent risk of mortality due to TB. Generalized additive model and second derivate (acceleration) were used to plot the "TB-mortality correlation curves." The mathematical (maximum acceleration) and clinical (adjusted 28-day transplantation-free mortality rate reaching 15%) TB cutoffs for liver failure were both calculated. Among the 3,532 included patients, the number of patients with cirrhosis and advanced fibrosis were 2,592 and 940, respectively, of which cumulative 90-day mortality were 16.6% (430/2592) and 7.4% (70/940), respectively. Any increase of TB was found the independent risk factor of mortality in cirrhotic patients, while only TB >12 mg/dL independently increased the risk of mortality in patients with advanced fibrosis. In cirrhotic patients, the mathematical TB cutoff for liver failure is 14.2 mg/dL, with 23.3% (605/2592) patients exceeding it, corresponding to 13.3 and 25.0% adjusted 28- and 90-day mortality rate, respectively. The clinical TB cutoff for is 18.1 mg/dL, with 18.2% (471/2592) patients exceeding it. In patients with advanced fibrosis, the mathematical TB cutoff is 12.1 mg/dL, 33.1% (311/940) patients exceeding it, corresponding to 2.9 and 8.0% adjusted 28- and 90-day mortality rate, respectively; the clinical TB cutoff was 36.0 mg/dL, 1.3% (12/940) patients above it. This study clearly demonstrated the significantly different impact of TB on 90-day mortality in patients with cirrhosis and advanced fibrosis, proving that liver failure can be determined by TB alone in cirrhosis but not in advanced fibrosis. The proposed TB cutoffs for liver failure provides solid support for the establishment of ACLF diagnostic criteria.
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http://dx.doi.org/10.3389/fmed.2021.704452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260970PMC
June 2021

Signatures of Wigner crystal of electrons in a monolayer semiconductor.

Nature 2021 07 30;595(7865):53-57. Epub 2021 Jun 30.

Institute for Quantum Electronics, ETH Zürich, Zürich, Switzerland.

When the Coulomb repulsion between electrons dominates over their kinetic energy, electrons in two-dimensional systems are predicted to spontaneously break continuous-translation symmetry and form a quantum crystal. Efforts to observe this elusive state of matter, termed a Wigner crystal, in two-dimensional extended systems have primarily focused on conductivity measurements on electrons confined to a single Landau level at high magnetic fields. Here we use optical spectroscopy to demonstrate that electrons in a monolayer semiconductor with density lower than 3 × 10 per centimetre squared form a Wigner crystal. The combination of a high electron effective mass and reduced dielectric screening enables us to observe electronic charge order even in the absence of a moiré potential or an external magnetic field. The interactions between a resonantly injected exciton and electrons arranged in a periodic lattice modify the exciton bandstructure so that an umklapp resonance arises in the optical reflection spectrum, heralding the presence of charge order. Our findings demonstrate that charge-tunable transition metal dichalcogenide monolayers enable the investigation of previously uncharted territory for many-body physics where interaction energy dominates over kinetic energy.
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http://dx.doi.org/10.1038/s41586-021-03590-4DOI Listing
July 2021

Co-exposure to BPA and DEHP enhances susceptibility of mammary tumors via up-regulating Esr1/HDAC6 pathway in female rats.

Ecotoxicol Environ Saf 2021 Sep 26;221:112453. Epub 2021 Jun 26.

Department of Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New District, Shenyang 110122, Liaoning Province, PR China. Electronic address:

Breast cancer (BrCa) as one of the major malignancies threatening women's health worldwide occurs due to the genetic and environmental interactions. Epidemiological studies have suggested that exposure to endocrine disrupting chemicals (EDCs) can elevate the risk of breast cancer. Di-(2-ethylhexyl)-phthalate (DEHP) and bisphenol A (BPA) are known as two typical EDCs. Although several studies have implied that there appear to have adverse effects of exposure to BPA or DEHP alone on breast development, no study to date has demonstrated the exact toxic effect of combined exposure to DEHP and BPA on breast tumorigenesis. In the present study, we performed an in vivo experiment including 160 female Sprague-Dawley (SD) rats, in which 80 rats were randomly allocated to 4 groups including control group given to normal diet, DEHP (150 mg/kg body weight/day), BPA (20 mg/kg body weight/day), and DEHP (150 mg/kg body weight/day) combined with BPA (20 mg/kg body weight/day) by gavage for 30 weeks. Additionally, a DEN/MNU/DHPN (DMD)-induced carcinogenesis animal model was also established to assess their effect on tumor promotion. Namely, the other 80 SD rats were separated into another 4 groups: in addition to DMD initiation each group treated with vehicle, DEHP, BPA and the combination of BPA and DEHP respectively. Our data demonstrated that BPA alone or in combination with DEHP may induce hyperplasia of mammary glands, including the proliferation of ductal epithelial cells and an increase in the number of lobules and acinus after a 30-week exposure. Notably, co-exposure to DEHP and BPA increased the incidence and reduced the latency of mammary tumor, which seemed to enhance the susceptibility of carcinogens-induced tumor. Mechanistically, our results supported the hypothesis that exposure to BPA and DEHP might promote breast cancer dependent on Esr1 and HDAC6 as pivotal factors, and further lead to the activation of oncogene c-Myc. Our study suggested that BPA combined with DEHP facilitate the occurrence of mammary tumors, which contributed to advance our understanding in the complex effects of compound exposure to endocrine disrupting chemicals.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112453DOI Listing
September 2021

Ultrasensitive Calorimetric Measurements of the Electronic Heat Capacity of Graphene.

Nano Lett 2021 Jun 8;21(12):5330-5337. Epub 2021 Jun 8.

ICFO, Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Castelldefels, Barcelona 08860, Spain.

Heat capacity is an invaluable quantity in condensed matter physics and yet has been completely inaccessible in two-dimensional (2D) van der Waals (vdW) materials, owing to their ultrafast thermal relaxation times and the lack of suitable nanoscale thermometers. Here, we demonstrate a novel thermal relaxation calorimetry scheme that allows the first measurements of the electronic heat capacity of graphene. It is enabled by combining a radio frequency Johnson noise thermometer, which can measure the electronic temperature with a sensitivity of ∼20 mK/Hz, and a photomixed optical heater that modulates with a frequency of up to Ω = 0.2 THz. This allows record sensitive measurements of the electronic heat capacity < 10 J/K and the fastest measurement of electronic thermal relaxation time < 10 s yet achieved by a calorimeter. These features advance heat capacity metrology into the realm of nanoscale and low-dimensional systems and provide an avenue for the investigation of their thermodynamic quantities.
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http://dx.doi.org/10.1021/acs.nanolett.1c01553DOI Listing
June 2021

3'-UTR Polymorphism rs15869 Alters Susceptibility to Papillary Thyroid Carcinoma via Binding hsa-mir-1178-3p.

Pharmgenomics Pers Med 2021 6;14:533-544. Epub 2021 May 6.

Department of Head and Neck Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, People's Republic of China.

Objective: To investigate the associations of polymorphisms in the following DNA double-strand break repair (DSBR) genes with papillary thyroid carcinoma (PTC) risk (including rs11852786, rs963917, rs12516 and rs8176318, rs15869, rs2035990 and rs2440).

Materials And Methods: A matched case-control study was implemented to examine associations between PTC risk and the above polymorphisms. Subsequently, we evaluated the effects of the potential PTC susceptibility-related variant rs15869 on BRCA2 mRNA secondary structure and BRCA2 expression through bioinformatics analysis and experiment validation. Additionally, luciferase assay was used to identify whether rs15869 polymorphism can substantially affect the binding of hsa-miR-1178-3p to mRNA. Finally, Pearson correlation analysis was performed to determine the correlation between the expression of hsa-miR-1178-3p and BRCA2 mRNA and protein in thyroid tissues harboring rs15869 different genotypes.

Results: rs15869 CC genotype was associated with a higher risk of PTC than its AA genotype. Subsequently, stratified analyses came to the same conclusion in the female or age<50 population. Furthermore, we confirmed that the A-to-C substitution of rs15869 changed BRCA2 mRNA secondary structure and contributed to a decreased BRCA2 expression. Mechanistically, a significantly decreased luciferase activity verified a greater binding between hsa-miR-1178-3p and rs15869 C allele, but not the A allele, which was evidenced by the significant negative correlation between hsa-miR-1178-3p with BRCA2 mRNA and protein levels in thyroid tissues with AC and CC genotype but not AA genotype at rs15869.

Conclusion: rs15869 is characterized as a potential biomarker associated with PTC risk, highlighting the contribution of the hsa-miR-1178-3p via functional exploration.
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http://dx.doi.org/10.2147/PGPM.S300783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112253PMC
May 2021

Recursive Copy and Paste GAN: Face Hallucination from Shaded Thumbnails.

IEEE Trans Pattern Anal Mach Intell 2021 Feb 23;PP. Epub 2021 Feb 23.

Existing face hallucination methods based on convolutional neural networks (CNNs) have achieved impressive performance on low-resolution (LR) faces in a normal illumination condition. However, their performance degrades dramatically when LR faces are captured in non-uniform illumination conditions. This paper proposes a Recursive Copy and Paste Generative Adversarial Network (Re-CPGAN) to recover authentic high-resolution (HR) face images while compensating for non-uniform illumination. To this end, we develop two key components in our Re-CPGAN: internal and recursive external Copy and Paste networks (CPnets). Our internal CPnet exploits facial self-similarity information residing in the input image to enhance facial details; while our recursive external CPnet leverages an external guided face for illumination compensation. Specifically, our recursive external CPnet stacks multiple external Copy and Paste (EX-CP) units in a compact model to learn normal illumination and enhance facial details recursively. By doing so, our method offsets illumination and upsamples facial details progressively in a coarse-to-fine fashion, thus alleviating the ambiguity of correspondences between LR inputs and external guided inputs. Furthermore, a new illumination compensation loss is developed to capture illumination from the external guided face image effectively. Extensive experiments demonstrate that our method achieves authentic HR images in a uniform illumination condition with a 16x magnification factor and outperforms state-of-the-art methods qualitatively and quantitatively.
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http://dx.doi.org/10.1109/TPAMI.2021.3061312DOI Listing
February 2021

Bisphenol A at a human exposed level can promote epithelial-mesenchymal transition in papillary thyroid carcinoma harbouring BRAF mutation.

J Cell Mol Med 2021 02 19;25(3):1739-1749. Epub 2021 Jan 19.

Department of Toxicology, School of Public health, China Medical University, Shenyang, China.

Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, alters the function of endocrine system and enhances the susceptibility to tumorigenesis in several hormone-dependent tumours as thyroid carcinoma. About 50% of papillary thyroid cancers (PTC), the most common type of thyroid malignancy, harbours the BRAF mutation. This study aimed to investigate a potential combined effect of BPA exposure and BRAF mutation on epithelial-mesenchymal transition (EMT) in PTC. Firstly, the level of BPA in plasma, the evaluation of BRAF mutation and the level of EMT-related proteins in PTC samples were individually determined. Additionally, the migration, invasion, colony formation capacity and the expression of EMT-related proteins after exposure to BPA were precisely analysed in vitro thyroid cells genetically modified by the introduction of BRAF mutation. Moreover, ERK-Cox2 signalling pathway was also introduced to explore the possible mechanism in PTC development. As expected, whether the clinical investigation or cultured thyroid cells demonstrated that BPA at a concentration compatible with human exposed levels (10  M) synergized with the BRAF mutation promoted EMT via the activation of ERK-Cox2 signalling pathway. Our findings offer some evidence that BPA as an environmental risk factor can facilitate the progression of PTC harbouring BRAF mutation.
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http://dx.doi.org/10.1111/jcmm.16279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875916PMC
February 2021

[Double internal fixations of clavicle and scapula and intraoperative reduction of glenopolar angle for treatment of floating shoulder injuries].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jan;35(1):76-81

Department of Bone & Joint Surgery, Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000, P.R.China;Sichuan Provincial Laboratory of Orthopaedic Engineering, Luzhou Sichuan, 646000, P.R.China.

Objective: To investigate the effectiveness of double internal fixations of clavicle and scapula and intraoperative reduction of glenopolar angle in the treatment of floating shoulder injuries.

Methods: Between January 2010 and June 2019, 13 patients with floating shoulder injury were treated with double internal fixation of clavicle and scapula and intraoperative reduction of glenopolar angle. There were 11 males and 2 females with an average age of 48 years (range, 25-65 years). The causes of injury included falling from height in 2 cases, traffic accident injury in 3 cases, heavy object injury in 2 cases, and other injuries in 6 cases. There were 2 cases of Ⅰ-B-3 type, 1 case of Ⅰ-C-2 type, 1 case of Ⅰ-C-3 type, 3 cases of Ⅱ-B-2 type, 1 case of Ⅱ-B-3 type, 1 case of Ⅱ-B-4 type, 2 cases of Ⅱ-C-2 type, 1 case of Ⅱ-C-4 type, and 1 case of Ⅱ-D-3 type according to the classification of floating shoulder injury. All patients had unilateral clavicle fracture with scapular neck fracture, 1-4 superior shoulder suspensory complex (SSSC) injuries. The time from injury to operation was 7-17 days, with an average of 12 days. The glenopolar angle, subacromail space, anteroposterior inclination angle of scapular glenoid, scapular glenoid up and down angle were measured before and after operation; Constant-Murly score and Herscovici score were used to evaluate the recovery of shoulder joint function.

Results: All incisions healed by first intention, and there was no early postoperative complications such as infection. All 13 cases were followed up 12-48 months, with an average of 25.2 months. Both the clavicle and the scapula had bone union, and the average healing time was 6 months and 4 months respectively. There were no complications such as nonunion, shoulder deformity, plate fracture or failure of internal fixation, acromion impingement syndrome, and frozen shoulder. At last follow-up, the glenopolar angle, subacromail space, anteroposterior inclination angle of scapular glenoid, and scapular glenoid up and down angle were all corrected significantly ( <0.05). The pain, function, activity, muscle strength scores, and total score in Constant-Murly score were significantly improved when compared with preoperative scores ( <0.05). According to the Herscovici scoring standard, the shoulder joint function was evaluated as excellent in 8 cases, good in 3 cases, and fair in 2 cases. The excellent and good rate was 84.6%.

Conclusion: Double internal fixation of clavicle and scapula to stabilize SSSC and reduct glenopolar angle during operation is an effective method for treating the floating shoulder injury.
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http://dx.doi.org/10.7507/1002-1892.202007104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171606PMC
January 2021

Cohort profile: a multicentre prospective validation cohort of the Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study.

BMJ Open 2021 01 8;11(1):e037793. Epub 2021 Jan 8.

Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Purpose: Acute-on-chronic liver failure (ACLF) is a clinical syndrome with high short-term mortality, unclear mechanism and controversial diagnosis criteria. The Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study has been conducted in China to fill the gaps. In the first phase (the CATCH-LIFE investigation cohort), 2600 patients were continuously recruited from 14 national nationwide liver centres from 12 different provinces of China in 2015-2016, and a series of important results were obtained. To validate the preliminary results, we designed and conducted this multicentre prospective observational cohort (the CATCH-LIFE validation cohort).

Participants: Patients diagnosed with chronic liver disease and hospitalised for acute decompensation (AD) or acute liver injure were enrolled, received standard medical therapy. We collected the participants' demographics, medical history, laboratory data, and blood and urine samples during their hospitalisation.

Findings To Date: From September 2018 to March 2019, 1370 patients (73.4% men) aged from 15 to 79 years old were enrolled from 13 nationwide liver centres across China. Of these patients, 952 (69.5%) had chronic hepatitis B, 973 (71.1%) had cirrhosis and 1083 (79.1%) complicated with AD at admission. The numbers and proportions of enrolled patients from each participating centre and the patients' baseline characteristics are presented.

Future Plans: A total of 12 months is required for each participant to complete follow-up. Outcome information (survival, death or receiving liver transplantation) collection and data cleansing will be done before June 2020. The data in the CATCH-LIFE validation cohort will be used for comparison between the new ACLF diagnostic criteria derivated from the CATCH-LIFE investigation cohort with existing ones. Moreover, future proteomic and metabolic omics analyses will provide valuable insights into the mechanics of ACLF, which will promote the development of specific therapy that leads to decrease patients' mortality.

Registration: NCT03641872.
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http://dx.doi.org/10.1136/bmjopen-2020-037793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799133PMC
January 2021

Face Hallucination With Finishing Touches.

IEEE Trans Image Process 2021 14;30:1728-1743. Epub 2021 Jan 14.

Obtaining a high-quality frontal face image from a low-resolution (LR) non-frontal face image is primarily important for many facial analysis applications. However, mainstreams either focus on super-resolving near-frontal LR faces or frontalizing non-frontal high-resolution (HR) faces. It is desirable to perform both tasks seamlessly for daily-life unconstrained face images. In this paper, we present a novel Vivid Face Hallucination Generative Adversarial Network (VividGAN) for simultaneously super-resolving and frontalizing tiny non-frontal face images. VividGAN consists of coarse-level and fine-level Face Hallucination Networks (FHnet) and two discriminators, i.e., Coarse-D and Fine-D. The coarse-level FHnet generates a frontal coarse HR face and then the fine-level FHnet makes use of the facial component appearance prior, i.e., fine-grained facial components, to attain a frontal HR face image with authentic details. In the fine-level FHnet, we also design a facial component-aware module that adopts the facial geometry guidance as clues to accurately align and merge the frontal coarse HR face and prior information. Meanwhile, two-level discriminators are designed to capture both the global outline of a face image as well as detailed facial characteristics. The Coarse-D enforces the coarsely hallucinated faces to be upright and complete while the Fine-D focuses on the fine hallucinated ones for sharper details. Extensive experiments demonstrate that our VividGAN achieves photo-realistic frontal HR faces, reaching superior performance in downstream tasks, i.e., face recognition and expression classification, compared with other state-of-the-art methods.
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http://dx.doi.org/10.1109/TIP.2020.3046918DOI Listing
June 2021

Interlayer Exciton Transport in MoSe/WSe Heterostructures.

ACS Nano 2021 Jan 8;15(1):1539-1547. Epub 2021 Jan 8.

Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba 305-0044, Japan.

A moiré superlattice formed by stacking two lattice mismatched transition metal dichalcogenide monolayers, functions as a diffusion barrier that affects the energy transport and dynamics of interlayer excitons (electron and hole spatially concentrated in different monolayers). In this work, we experimentally quantify the diffusion barrier experienced by interlayer excitons in hexagonal boron nitride-encapsulated molybdenum diselenide/tungsten diselenide (MoSe/WSe) heterostructures with different twist angles. We observe the localization of interlayer excitons at low temperature and the temperature-activated diffusivity as a function of twist angle and hence attribute it to the deep periodic potentials arising from the moiré superlattice. We further support the observations with theoretical calculations, Monte Carlo simulations, and a three-level model that represents the exciton dynamics at various temperatures.
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http://dx.doi.org/10.1021/acsnano.0c08981DOI Listing
January 2021

Long non-coding RNA (LncRNA) MRPL23-AS1 promotes tumor progression and carcinogenesis in osteosarcoma by activating Wnt/β-catenin signaling via inhibiting microRNA miR-30b and upregulating myosin heavy chain 9 (MYH9).

Bioengineered 2021 12;12(1):162-171

Department of Orthopaedics, The Affiliated Hospital of Southwest Medical University , Luzhou City, P.R. China.

Long non-coding RNA (LncRNA) contributes to the occurrence and development of osteosarcoma (OS), although the underlying mechanism is not clear. In the present study, we showed that lncRNA MRPL23-AS1 was remarkably increased in OS tissues and cell lines. Stable knockdown of MRPL23-AS1 evidently attenuated cell viability and invasive ability, meanwhile inhibited tumor growth and dissemination. In terms of mechanism, luciferase reporter, RNA pull-down and fluorescence in situ hybridization (FISH) assays showed that MRPL23-AS1 competitively interacted with miR-30b, increasing myosin heavy chain 9 (MYH9) expression, a trans- activator of β-catenin, resulting in the activation of Wnt/β-catenin pathway, thereby promoting OS tumorigenesis and metastasis. Importantly, high MRPL23-AS1 was positively correlated with MYH9, while conversely correlated with miR-30b, suggesting that the regulatory axis of MRPL23-AS1/miR-30b/MYH9 does exist in OS. Clinically, OS patients with high MRPL23-AS1 had larger tumor size, higher stage and easier metastasis than those with low MRPL23-AS1, moreover, MRPL23-AS1 was identified as an adverse prognostic factor for OS survival. In conclusion, our results show that MRPL23-AS1 is a key oncogenic lncRNA in OS, targeting of MRPL23-AS1 may be a promising treatment for OS patients.
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http://dx.doi.org/10.1080/21655979.2020.1863014DOI Listing
December 2021

The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway.

J Clin Lab Anal 2021 Mar 12;35(3):e23655. Epub 2020 Dec 12.

Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Department of Surgical Oncology and General Surgery, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: N6-methyladenosine (m6A) modification may participate in the regulation of occurrence and development of tumors. However, the m6A level and the potential regulatory mechanism of m6A in gastric cancer (GC) remain uncertain.

Methods: RNA m6A quantification assay was conducted to detect the m6A level in GC tissues and cell lines. Methyltransferase-like 14 (METTL14) expression in GC tissues was explored by bioinformatics and immunohistochemistry. Then, the function of METTL14 in GC cells was examined by CCK-8, colony formation assay, wound healing assay, and Transwell assay. Besides, Western blotting was conducted to probe the PI3K/AKT/mTOR pathway and the epithelial-mesenchymal transformation (EMT) pathway-related gene expression.

Results: The m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 was downregulated in GC by analyzing both clinical samples and bioinformatics. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3K/AKT/mTOR pathway and the EMT pathway, respectively.

Conclusions: Our findings indicate that METTL14 partakes in the biological process of GC as a tumor suppressor and may be an emerging biomarker in GC.
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http://dx.doi.org/10.1002/jcla.23655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957981PMC
March 2021

Lanthanum chloride causes blood-brain barrier disruption through intracellular calcium-mediated RhoA/Rho kinase signaling and myosin light chain kinase.

Metallomics 2020 12;12(12):2075-2083

Department of Occupational and Environmental Health, School of Public Health, Jinzhou Medical University, #40 Section Three Songpo Road, Jinzhou 121001, P. R. China.

Rare earth elements (REEs) have caused bioaccumulation and adverse health effects attributed to extensive application. The penetrability of REEs across the blood-brain barrier (BBB) contributes to their neurotoxicity process, but potential mechanisms affecting BBB integrity are still obscure. The present study was designed to investigate the effects of lanthanum on BBB adheren junctions and the actin cytoskeleton in vitro using bEnd.3 cells. After lanthanum chloride (LaCl3, 0.125, 0.25 and 0.5 mM) treatment, cytotoxicity against bEnd.3 cells was observed accompanied by increased intracellular Ca2+. Higher paracellular permeability presented as decreased TEER (transendothelial electrical resistance) and increased HRP (horse radish peroxidase) permeation, and simultaneously reduced VE-cadherin expression and F-actin stress fiber formation caused by LaCl3 were reversed by inhibition of ROCK (Rho-kinase) and MLCK (myosin light chain kinase) using inhibitor Y27632 (10 μM) and ML-7 (10 μM). Moreover, chelating overloaded intracellular Ca2+ by BAPTA-AM (25 μM) remarkably abrogated RhoA/ROCK and MLCK activation and downstream phosphorylation of MYPT1 (myosin phosphatase target subunit 1) and MLC2 (myosin light chain 2), therefore alleviating LaCl3-induced BBB disruption and dysfunction. In conclusion, this study indicated that lanthanum caused endothelial barrier hyperpermeability accompanied by loss of VE-cadherin and rearrangement of the actin cytoskeleton though intracellular Ca2+-mediated RhoA/ROCK and MLCK pathways.
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http://dx.doi.org/10.1039/d0mt00187bDOI Listing
December 2020

Modulation Doping via a Two-Dimensional Atomic Crystalline Acceptor.

Nano Lett 2020 Dec 9;20(12):8446-8452. Epub 2020 Nov 9.

Department of Physics, Boston College, Chestnut Hill, Massachusetts 02467, United States.

Two-dimensional nanoelectronics, plasmonics, and emergent phases require clean and local charge control, calling for layered, crystalline acceptors or donors. Our Raman, photovoltage, and electrical conductance measurements combined with calculations establish the large work function and narrow bands of α-RuCl enable modulation doping of exfoliated single and bilayer graphene, chemical vapor deposition grown graphene and WSe, and molecular beam epitaxy grown EuS. We further demonstrate proof of principle photovoltage devices, control via twist angle, and charge transfer through hexagonal boron nitride. Short-ranged lateral doping (≤65 nm) and high homogeneity are achieved in proximate materials with a single layer of α-RuCl. This leads to the best-reported monolayer graphene mobilities (4900 cm/(V s)) at these high hole densities (3 × 10 cm) and yields larger charge transfer to bilayer graphene (6 × 10 cm).
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http://dx.doi.org/10.1021/acs.nanolett.0c03493DOI Listing
December 2020

[Analysis of effectiveness of greater trochanteric osteotomy approach and K-L posterior approach in patients with type Pipkin fracture].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Oct;34(10):1258-1262

Department of Bone and Joint Surgery, Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000, P.R.China.

Objective: To investigate the effectiveness of two surgical approaches in the treatment of type Ⅳ Pipkin fracture.

Methods: The clinical data of 15 patients with type Ⅳ Pipkin fracture treated surgically between July 2013 and June 2018 were retrospectively analyzed. According to different surgical approaches, they were divided into group A (8 cases, using K-L posterior approach) and group B (7 cases, using greater trochanter osteotomy approach). There was no significant difference in gender, age, cause of injury, and interval from injury to operation between the two groups ( >0.05). The incision length, operation time, intraoperative blood loss, hospital stay, fracture healing time, and complications of the two groups were recorded. Hip joint function recovery was evaluated according to Thompson-Epstein functional evaluation system.

Results: All the 15 patients were followed up 1-5 years, with an average of 2.5 years. There was no significant difference in operation time between the two groups ( =14.681, =0.100); the incision length, intraoperative blood loss, and fracture healing time in group A were all greater than those in group B, and the hospital stay was shorter than that in group B, showing significant differences ( <0.05). In group A, 1 patient presented hip pain, clasthenia, and limited mobility after operation, 1 patient presented ossifying myositis, 1 patient presented osteonecrosis of the femoral head, 1 patient presented fat liquefaction of incision, and 1 patient presented sciatica, with a complication incidence of 62.5%. Postoperative hip pain occurred in 1 patient and ossifying myositis in 2 patients in group B, with a complication incidence of 42.9%. There was no significant difference in the incidence of complications between the two groups ( =-0.735, =0.462). At last follow-up, according to Thompson-Epstein functional evaluation system, the results in group A were excellent in 3 cases, good in 2 cases, fair in 2 cases, and poor in 1 case, with an excellent and good rate of 62.5%; in group B, the results were excellent in 4 cases, good in 2 cases, and fair in 1 case, and the excellent and good rate was 85.7%. There was no significant difference in good and fair rate between the two groups ( =-0.990, =0.322).

Conclusion: K-L posterior approach is more convenient in the fracture treatment during operation, but it has greater trauma, greater vascular damage, and more blood loss. The greater trochanter osteotomy approach can better protect the blood supply of femoral head, shorten the operation time, reduce intraoperative blood loss, and reduce postoperative complications. It is an ideal way in the surgical treatment of type Ⅳ Pipkin fracture.
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http://dx.doi.org/10.7507/1002-1892.202003059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171889PMC
October 2020

Potassium voltage-gated channel subfamily D member 2 induces an aggressive phenotype in lung adenocarcinoma.

Neoplasma 2021 Jan 24;68(1):135-143. Epub 2020 Sep 24.

Department of General Practice, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

The study aimed to investigate the roles of potassium voltage-gated channel subfamily D member 2 (KCND2) in lung adenocarcinoma (AD). RNA sequencing data from The Cancer Genome Atlas (TCGA) database showed that the expression of KCND2 was elevated in lung AD samples compared to the normal samples, and its upregulation was significantly associated with the unfavorable clinic outcome of lung AD patients. Cell proliferation and transwell assays revealed that the growth, migration, and invasion of lung AD cells, which was crucial to cancer aggressiveness, were markedly inhibited after the depletion of KCND2. Importantly, we demonstrated that the depletion of KCND2 suppressed the biological behaviors of lung AD cells via restraining the expression of four tumor-related genes including PCNA, CDH2, SNAI1, and MMP2. Overall, KCND2 promotes the aggressiveness of lung AD and can be considered as a potential predictor of the prognosis of lung AD patients. Downregulation of KCND2 may contribute to the therapy of lung AD.
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http://dx.doi.org/10.4149/neo_2020_200629N667DOI Listing
January 2021

Meron-like topological spin defects in monolayer CrCl.

Nat Commun 2020 Sep 18;11(1):4724. Epub 2020 Sep 18.

Department of Physics, Washington University in St. Louis, St. Louis, MO, 63130, USA.

Noncollinear spin textures in low-dimensional magnetic systems have been studied for decades because of their extraordinary properties and promising applications derived from the chirality and topological nature. However, material realizations of topological spin states are still limited. Employing first-principles and Monte Carlo simulations, we propose that monolayer chromium trichloride (CrCl) can be a promising candidate for observing the vortex/antivortex type of topological defects, so-called merons. The numbers of vortices and antivortices are found to be the same, maintaining an overall integer topological unit. By perturbing with external magnetic fields, we show the robustness of these meron pairs and reveal a rich phase space to tune the hybridization between the ferromagnetic order and meron-like defects. The signatures of topological excitations under external magnetic field also provide crucial information for experimental justifications. Our study predicts that two-dimensional magnets with weak spin-orbit coupling can be a promising family for realizing meron-like spin textures.
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http://dx.doi.org/10.1038/s41467-020-18573-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501285PMC
September 2020

Terahertz Photogalvanics in Twisted Bilayer Graphene Close to the Second Magic Angle.

Nano Lett 2020 Oct 30;20(10):7152-7158. Epub 2020 Sep 30.

Terahertz Center, University of Regensburg, 93040 Regensburg, Germany.

We report on the observation of photogalvanic effects in tBLG with a twist angle of 0.6°. We show that excitation of the tBLG bulk causes a photocurrent, whose sign and magnitude are controlled by the orientation of the radiation electric field and the photon helicity. The observed photocurrent provides evidence for the reduction of the point group symmetry in low twist-angle tBLG to the lowest possible one. The developed theory shows that the current is formed by asymmetric scattering in gyrotropic tBLG. We also detected the photogalvanic current formed in the vicinity of the edges. For both bulk and edge photocurrents, we demonstrate the emergence of pronounced oscillations upon variation of the gate voltage. The gate voltages associated with the oscillations correlate with peaks in resistance measurements. These are well explained by interband transitions between a multitude of isolated bands in tBLG.
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http://dx.doi.org/10.1021/acs.nanolett.0c02474DOI Listing
October 2020

Circular RNA hsa_Circ_101141 as a Competing Endogenous RNA Facilitates Tumorigenesis of Hepatocellular Carcinoma by Regulating miR-1297/ROCK1 Pathway.

Cell Transplant 2020 Jan-Dec;29:963689720948016

Department of Infectious Disease Center, 159427The First Affiliated Hospital of Xinjiang Medical University, Urumqi City, Xinjiang Uygur Autonomous Region, China.

As a novel class of noncoding RNAs, circular RNAs (circRNAs) have been recently reported to be involved in cell development and function. However, the functional role of circRNAs in hepatocellular carcinoma (HCC) remains unclear. In the present study, we found that the expression of human circ_101141 was upregulated in HCC tissues and cells. In addition, downregulation of circ_101141 dramatically inhibited cell proliferation, migration, and invasion in HCC cells. In addition, by using the bioinformatics tools, the potential target of circ_101141 was predicted. Mechanistic investigations indicated that circ_101141 acted as a miR-1297 "sponge"; meanwhile, Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) was a direct target of miR-1297. Further experiments demonstrated that circ_101141 contributed to the progression of HCC by acting as competing endogenous RNA (ceRNA) of miR-1297 to regulate ROCK1 expression. Furthermore, knockdown of circ_101141 attenuated HCC tumorigenesis in vivo. Taken together, these findings indicated that circRNA circ_101141 acted as a ceRNA to facilitate tumorigenesis of HCC by regulating miR-1297/ROCK1 pathway.
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http://dx.doi.org/10.1177/0963689720948016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563807PMC
July 2021

Combined effects of di (2-ethylhexyl) phthalate and bisphenol A on thyroid hormone homeostasis in adolescent female rats.

Environ Sci Pollut Res Int 2020 Nov 17;27(32):40882-40892. Epub 2020 Jul 17.

Department of Toxicology, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China.

Phthalates and bisphenols are two typical classes of endocrine-disrupting chemicals (EDCs) which cause endocrine disorder in humans and animals. Phthalates and bisphenols are suggested to be associated with thyroid dysfunction. However, the effects of combined exposure and the detailed mechanisms are yet poorly understood. We investigated the combined effects of di (2-ethylhexyl) phthalate (DEHP) and bisphenol A (BPA) on thyroid function during puberty. Female Sprague Dawley rats were gavaged from postnatal 28 to 70 days with a single or combined exposure of DEHP (0, 150, and 750 mg/kg/day) and BPA (0, 20, and 100 mg/kg/day) according to a 3 × 3 factorial design. The thyroid weights reduced after combined exposure to the highest dose of DEHP and BPA, which noted their adverse effects on thyroid. Additionally, DEHP could increase the number of follicular epithelial cells in thyroid. Both DEHP and in combination with BPA could disturb the levels of thyroid hormones in serum, such as TT3 and TT4. Meanwhile, the possible mechanism was also discussed in the present study. DEHP treatment induced a significant increase of phosphorylation of cAMP-response element binding protein (Creb) via estrogen receptor α (Esr1), while the upregulation was nullified by the concomitant presence of BPA. In conclusion, the complex action of DEHP/BPA mixture may disturb the thyroid hormone homeostasis, which ultimately would affect the development of thyroid during puberty.
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http://dx.doi.org/10.1007/s11356-020-09949-wDOI Listing
November 2020

Untying the insulating and superconducting orders in magic-angle graphene.

Nature 2020 07 6;583(7816):375-378. Epub 2020 Jul 6.

ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain.

The coexistence of superconducting and correlated insulating states in magic-angle twisted bilayer graphene prompts fascinating questions about their relationship. Independent control of the microscopic mechanisms that govern these phases could help uncover their individual roles and shed light on their intricate interplay. Here we report on direct tuning of electronic interactions in this system by changing the separation distance between the graphene and a metallic screening layer. We observe quenching of correlated insulators in devices with screening layer separations that are smaller than the typical Wannier orbital size of 15 nanometres and with twist angles that deviate slightly from the magic angle of 1.10 ± 0.05 degrees. Upon extinction of the insulating orders, the vacated phase space is taken over by superconducting domes that feature critical temperatures comparable to those in devices with strong insulators. In addition, we find that insulators at half-filling can reappear in small out-of-plane magnetic fields of 0.4 tesla, giving rise to quantized Hall states with a Chern number of 2. Our study suggests re-examination of the often-assumed 'parent-and-child' relation between the insulating and superconducting phases in moiré graphene, and suggests a way of directly probing the microscopic mechanisms of superconductivity in strongly correlated systems.
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http://dx.doi.org/10.1038/s41586-020-2459-6DOI Listing
July 2020

Glucocorticoid versus traditional therapy for hepatitis B virus-related acute-on-chronic liver failure: A systematic review and meta-analysis.

Medicine (Baltimore) 2020 Jun;99(25):e20604

Infectious Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.

Objective: This meta-analysis aimed to assess the efficacy and safety of glucocorticoid versus traditional therapy for hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).

Methods: PubMed, Cochrane Central Register of Clinical Trials, and EMBASE were searched. All clinical studies, including randomized controlled studies and cohort studies, comparing glucocorticoids with traditional treatments (until November 1, 2018), were included.

Results: A total of 3 randomized controlled trials and 5 cohort studies (including 3 retrospective cohort studies), involving 538 patients, were subjected to the meta-analysis. The total bilirubin levels before treatment were not significantly different (odds ratio [OR]: -0.97; 95% confidence interval [CI]: -2.56 to 0.62; P = .23), and, however, they were significantly reduced after treatment in the corticosteroid group compared with the traditional treatment group (OR: -8.83; 95% CI: -14.99 to 2.67; P = .005). Moreover, prothrombin time was significantly long before treatment in either group, with no significant differences (OR: 0.28; 95% CI: -0.79 to 1.34; P = 0.61). However, after treatment, prothrombin time was significantly shortened in the traditional treatment group (OR: 31.71; 95% CI: 3.62-59.81; P = .03). Furthermore, inpatient mortality (OR: 0.23; 95% CI: 0.08-0.67; P = .007) and ascites events (OR: 0.35; 95% CI: 0.18-0.67; P = .90) were significantly lower in the corticosteroid treatment group.

Conclusions: Glucocorticoid is more effective for reducing the T-bili level, significantly decreasing in-hospital mortality and ascites events in HBV-related ACLF patients. Moreover, bilirubin may play a pivotal role in the early stage of HBV-related ACLF progression to advanced liver failure.
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http://dx.doi.org/10.1097/MD.0000000000020604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310991PMC
June 2020
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