Publications by authors named "Jian Zhou"

2,660 Publications

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CircRNA UBAP2 serves as a sponge of miR-1294 to increase tumorigenesis in hepatocellular carcinoma through regulating c-Myc expression.

Carcinogenesis 2021 Jul 27. Epub 2021 Jul 27.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.

Circular RNAs (circRNAs) are a class of regulatory RNAs with complex roles in healthy and diseased tissues. However, the oncogenic role of circRNAs in hepatocellular carcinoma (HCC) remains poorly understood, including the mechanisms by which the circular ubiquitin binding associated protein 2 (circUBAP2) contributes to tumorigenesis. We analyzed the expression of circUBAP2 in 20 paired samples of HCC and healthy tissue as well as in seven HCC cell lines via quantitative real-time polymerase chain reaction (qRT-PCR). Functional experiments, such as CCK8 viability assays, colony formation assays, wound healing, transwell assays, and flow cytometry, were conducted to assess the effects of circUBAP2 in vitro. To further elucidate the mechanisms by which circUBAP2 acts, we conducted dual-luciferase assays, western blots, RNA pull-down assays, and rescue experiments. CircUBAP2 was highly upregulated in most HCC tissues and was associated with poor prognosis. HCC patients with high circUBAP2 expression had greater vascular invasion and worse differentiation. Functionally, circUBAP2 overexpression enhanced HCC cell proliferation, migration, and invasion and inhibited apoptosis. Furthermore, we found that circUBAP2 upregulated c-Myc expression by sponging miR-1294, thus contributing to hepatocarcinogenesis. Inhibiting circUBAP2 expression in HCC attenuated the oncogenic effects of c-Myc. These findings suggest that circUBAP2 promotes HCC growth and metastasis. CircUBAP2 may have value as an independent prognostic biomarker or as a new target for the treatment of HCC.
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http://dx.doi.org/10.1093/carcin/bgab068DOI Listing
July 2021

Immunogenicity and safety of a recombinant fusion protein vaccine (V-01) against coronavirus disease 2019 in healthy adults: a randomized, double-blind, placebo-controlled, phase II trial.

Chin Med J (Engl) 2021 Jul 22. Epub 2021 Jul 22.

Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou, Guangdong 510440, China Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, Guangdong 511430, China Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China National Institutes for Food and Drug Control, Beijing 100050, China Gaozhou Center for Disease Control and Prevention, Maoming, Guangdong 525000, China Livzon Bio Inc., Zhuhai, Guangdong 519045, China Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112, China.

Background: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.

Methods: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.

Results: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.

Conclusions: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.

Trial Registration: http://www.chictr.org.cn/index.aspx(No.ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
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http://dx.doi.org/10.1097/CM9.0000000000001702DOI Listing
July 2021

miR-451 on Myocardial Ischemia-Reperfusion in Rats by Regulating AMPK Signaling Pathway.

Biomed Res Int 2021 6;2021:9933998. Epub 2021 Jul 6.

Department of Cardiac Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.

Myocardial infarction is the main cause of death in patients with coronary heart disease. At present, the main method to treat cardiovascular disease is perfusion therapy. Myocardial ischemia-reperfusion will inevitably lead to reperfusion injury, which is also a major problem in the treatment of cardiovascular diseases. It has been reported that mir-451 in microRNA family participates in the protection of myocardial ischemia-reperfusion by regulating AMPK. The aim of this study was to investigate the effect of mir-451 on myocardial ischemia-reperfusion in rats by regulating AMPK signaling pathway. Sixty adult male rats were selected to establish myocardial ischemia-reperfusion animal model by ligating and loosening coronary artery. The expression level of mir-451 was regulated by injection of mir-451 virus vector and antibody, and the effect of increased or decreased mir-451 expression level on the activity of AMPK signaling pathway was detected. The myocardial infarct area and apoptosis rate of myocardial tissue were detected after 75 min ischemia-reperfusion. The results showed that when the expression level of mir-451 decreased by 15.7%, the activity index of AMPK signaling pathway was increased by 18.3%, the infarct area was reduced by 22.4%, and the apoptosis rate of myocardial cells was decreased by 25.2%. At the same time, the pathological structure of myocardial tissue was improved. Therefore, mir-451 is an inhibitor gene of AMPK signaling pathway. Reducing the expression of mir-451 can enhance the activity of AMPK signal pathway, and the increase of AMPK signal pathway activity is beneficial to reduce myocardial ischemia-reperfusion injury.
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http://dx.doi.org/10.1155/2021/9933998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279856PMC
July 2021

COVID-19 and gastroenteric manifestations.

World J Clin Cases 2021 Jul;9(19):4990-4997

Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang 330100, Jiangxi Province, China.

Coronavirus disease 2019 (COVID-19), caused by the infection of a novel coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)], has become a pandemic. The infection has resulted in about one hundred million COVID-19 cases and millions of deaths. Although SARS-CoV-2 mainly spreads through the air and impairs the function of the respiratory system, it also attacks the gastrointestinal epithelial cells through the same receptor, angiotensin converting enzyme 2 receptor, which results in gastroenteric symptoms and potential fecal-oral transmission. Besides the infection of SARS-CoV-2, the treatments of COVID-19 also contribute to the gastroenteric manifestations due to the adverse drug reactions of anti-COVID-19 drugs. In this review, we update the clinical features, basic studies, and clinical practices of COVID-19-associated gastroenteric manifestations.
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http://dx.doi.org/10.12998/wjcc.v9.i19.4990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283602PMC
July 2021

Preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma.

NPJ Precis Oncol 2021 Jul 21;5(1):70. Epub 2021 Jul 21.

Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

While next-generation sequencing (NGS) is used to guide therapy in patients with metastatic lung adenocarcinoma (LUAD), use of NGS to determine pathologic LN metastasis prior to surgery has not been assessed. To bridge this knowledge gap, we performed NGS using MSK-IMPACT in 426 treatment-naive patients with clinical N2-negative LUAD. A multivariable logistic regression model that considered preoperative clinical and genomic variables was constructed. Most patients had cN0 disease (85%) with pN0, pN1, and pN2 rates of 80%, 11%, and 9%, respectively. Genes altered at higher rates in pN-positive than in pN-negative tumors were STK11 (p = 0.024), SMARCA4 (p = 0.006), and SMAD4 (p = 0.011). Fraction of genome altered (p = 0.037), copy number amplifications (p = 0.001), and whole-genome doubling (p = 0.028) were higher in pN-positive tumors. Multivariable analysis revealed solid tumor morphology, tumor SUVmax, clinical stage, SMARCA4 and SMAD4 alterations were independently associated with pathologic LN metastasis. Incorporation of clinical and tumor genomic features can identify patients at risk of pathologic LN metastasis; this may guide therapy decisions before surgical resection.
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http://dx.doi.org/10.1038/s41698-021-00210-2DOI Listing
July 2021

Association of HbA1c with all-cause mortality across varying degrees of glycemic variability in type 2 diabetes.

J Clin Endocrinol Metab 2021 Jul 19. Epub 2021 Jul 19.

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.

Context: The interaction of glycated hemoglobin A1c (HbA1c) and glycemic variability in relation to diabetes-related outcomes remains unknown.

Objective: To evaluate the relationship between HbA1c and all-cause mortality across varying degrees of glycemic variability in patients with type 2 diabetes.

Design, Setting, And Patients: This was a prospective study conducted in a single referral center. Data of 6090 hospitalized patients with type 2 diabetes was analyzed. Glucose coefficient of variation (CV) was obtained as the measure of glycemic variability by using continuous glucose monitoring (CGM) for 3 days. Cox proportional hazards regression models were used to estimate hazard ratios and 95% CIs for all-cause mortality.

Results: During a median follow-up of 6.8 years, 815 patients died. In patients with the lowest and middle tertiles of glucose CV, HbA1c ≥8.0% was associated with 136% (95%CI 1.46-3.81) and 92% (95%CI 1.22-3.03) higher risks of all-cause mortality as compared with HbA1c 6.0-6.9%, respectively, after adjusting for confounders. However, a null association of HbA1c with mortality was found in patients with the highest tertile of glucose CV.

Conclusions: HbA1c may not be a robust marker of all-cause mortality in patients with high degree of glycemic variability. New metrics of glycemic control may be needed in these individuals to achieve better diabetes management.
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http://dx.doi.org/10.1210/clinem/dgab532DOI Listing
July 2021

Uncovering the Subtype-Specific Molecular Characteristics of Breast Cancer by Multiomics Analysis of Prognosis-Associated Genes, Driver Genes, Signaling Pathways, and Immune Activity.

Front Cell Dev Biol 2021 1;9:689028. Epub 2021 Jul 1.

Department of Pathology, Harbin Medical University, Harbin, China.

Breast cancer is a heterogeneous malignant disease with different prognoses and has been divided into four molecular subtypes. It is believed that molecular events occurring in breast stem/progenitor cells contribute to the carcinogenesis and development of different breast cancer subtypes. However, these subtype-specific molecular characteristics are largely unknown. In this study, we employed 1217 breast cancer samples from The Cancer Genome Atlas (TCGA) database for a multiomics analysis of the molecular characteristics of different breast cancer subtypes based on PAM50 algorithms. We detected the expression changes of subtype-specific genes and revealed that the expression of particular subtype-specific genes significantly affected prognosis. We also investigated the mutations and copy number variations (CNVs) of breast cancer driver genes and the representative genes of ten signaling pathways in different subtypes and revealed several subtype-specifically altered genes. Moreover, we detected the infiltration of various immune cells in different subtypes of breast cancer and showed that the infiltration levels of major immune cell types are different among these subtypes. Additionally, we investigated the factors affecting the immune infiltration level and the immune cytolytic activity in different breast cancer subtypes, namely, the mutation burden, genome instability and cancer-associated fibroblast (CAF) infiltration. This study may shed light on the molecular events contributing to carcinogenesis and development and provide potential markers and targets for the clinical diagnosis and treatment of different breast cancer subtypes.
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http://dx.doi.org/10.3389/fcell.2021.689028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280810PMC
July 2021

Current Molecular Biology and Therapeutic Strategy Status and Prospects for circRNAs in HBV-Associated Hepatocellular Carcinoma.

Front Oncol 2021 2;11:697747. Epub 2021 Jul 2.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Circular RNAs (circRNAs) are newly classified noncoding RNA (ncRNA) members with a covalently closed continuous loop structure that are involved in immune responses against hepatitis B virus (HBV) infections and play important biological roles in the occurrence and pathogenesis of HCC progression. The roles of circRNAs in HBV-associated HCC (HBV-HCC) have gained increasing attention. Substantial evidence has revealed that both tissue and circulating circRNAs may serve as potential biomarkers for diagnostic, prognostic and therapeutic purposes. So far, at least four circRNA/miRNA regulatory axes such as circRNA_101764/miR-181, circRNA_100338/miR-141-3p, circ-ARL3/miR-1305, circ-ATP5H/miR-138-5p, and several circulating circRNAs were reported to be associated with HBV-HCC development. Notably, TGF/SMAD, JAK/STAT, Notch and Wnt/β-catenin signaling pathways may play pivotal roles in this HBV-driven HCC several circRNAs. Moreover, in non-HBV HCC patients or HCC patients partially infected by HBV, numerous circRNAs have been identified to be important regulators impacting the malignant biological behavior of HCC. Furthermore, the role of circRNAs in HCC drug resistance has become a focus of research with the aim of reversing chemoresistance and immune resistance. Herein, we review the molecular biology of circRNAs in HBV-HCC and their potential in therapeutic strategies.
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http://dx.doi.org/10.3389/fonc.2021.697747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284075PMC
July 2021

Cigarette smoke extract combined with LPS down-regulates the expression of MRP2 in chronic pulmonary inflammation may be related to FXR.

Mol Immunol 2021 Jul 14;137:174-186. Epub 2021 Jul 14.

Institute for Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China; Institute for the Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, China. Electronic address:

The transporter multidrug resistance protein 2 (MRP2) plays an important role in chronic pulmonary inflammation by transporting cigarette smoke and other related inflammatory mediators. However, it is not completely clear whether pulmonary inflammation caused by cigarette smoke extract (CSE) and lipopolysaccharide (LPS) is related to MRP2 and its signal factors. In this study, CSE combined with LPS was used to establish an inflammation model in vivo and in vitro. We found that compared with the control group, after CSE combined with LPS treatment, the expression of MRP2 in rat lung tissue in vivo and human alveolar cell line in vitro was down-regulated, while the expression of inflammatory factors was up-regulated. Through silencing and overexpression of FXR, it was found that silent FXR could down-regulate MRP2 and up-regulate the expression of inflammatory factors. On the contrary, overexpression of FXR could up-regulate MRP2 and down-regulate the expression of inflammatory factors. Our results show that CSE combined with LPS can down-regulate the expression of MRP2 under inflammatory conditions, and the down-regulation of MRP2 expression may be achieved partly through the FXR signal pathway.
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http://dx.doi.org/10.1016/j.molimm.2021.06.019DOI Listing
July 2021

A novel preoperative predictive model of 90-day mortality after liver resection for huge hepatocellular carcinoma.

Ann Transl Med 2021 May;9(9):774

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education; Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Hepatectomy for huge hepatocellular carcinoma (HCC) (diameter ≥10 cm) is characterized by high mortality. This study aimed to establish a preoperative model to evaluate the risk of postoperative 90-day mortality for huge HCC patients.

Methods: We retrospectively enrolled 1,127 consecutive patients and prospectively enrolled 93 patients with huge HCC who underwent hepatectomy (training cohort, n=798; validation cohort, n=329; prospective cohort, n=93) in our institute. Based on independent preoperative predictors of 90-day mortality, we established a logistic regression model and visualized the model by nomogram.

Results: The 90-day mortality rates were 9.6%, 9.2%, and 10.9% in the training, validation, and prospective cohort. The α-fetoprotein (AFP) level, the prealbumin levels, and the presence of portal vein tumor thrombosis (PVTT) were preoperative independent predictors of 90-day mortality. A logistic regression model, AFP-prealbumin-PVTT score (APP score), was subsequently established and showed good performance in predicting 90-day mortality (training cohort, AUC =0.87; validation cohort, AUC =0.91; prospective cohort, AUC =0.93). Using a cut-off of -1.96, the model could stratify patients into low risk (≤-1.96) and high risk (>-1.96) with different 90-day mortality rates (~30% ~2%). Furthermore, the predictive performance for 90-day mortality and overall survival was significantly superior to the Child-Pugh score, the model of end-stage liver disease (MELD) score, and the albumin-bilirubin (ALBI) score.

Conclusions: The APP score can precisely predict postoperative 90-day mortality as well as long-term survival for patients with huge HCC, assisting physician selection of suitable candidates for liver resection and improving the safety and efficacy of surgical treatment.
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http://dx.doi.org/10.21037/atm-20-7842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246173PMC
May 2021

Simulation of portal/hepatic vein associated remnant liver ischemia/congestion by three-dimensional visualization technology based on preoperative CT scan.

Ann Transl Med 2021 May;9(9):756

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Remnant liver hypoperfusion is frequently observed after hepatectomy, and associated with a higher risk of postoperative complications and poorer survival. However, the development of remnant liver hypoperfusion was not fully understood.

Methods: We retrospectively analyzed patients who received hepatectomy and took contrast-enhanced computed tomography (CT) scans before, 1-week (POW1) and 4-week (POW4) after resection in our department from June 2017 to July 2019. We simulated and estimated the occurrence of portal-vein-related remnant liver ischemia (RLI) and hepatic-vein-related remnant liver congestion (RLC) after hepatectomy via three-dimensional visualization technology (3DVT) according to blood vessels ligated in the resection; then we analyzed association between the estimated RLI, RLC, and postoperative clinical outcomes.

Results: A total of 102 eligible patients were analyzed. Remnant liver hypoperfusion was observed in 47 (46%) patients in the POW1 CT scans and shrunk in the POW4 CT scans. RLC had better diagnostic significance than RLI in predicting remnant liver hypoperfusion [area under receiver operating characteristic (ROC) curve: 0.745 0.569, P=0.026]. Multivariate analysis showed that larger RLI [odds ratio (OR), 1.154; 95% confidence interval (CI), 1.075-1.240; P<0.001] was independent risk factor for post-hepatectomy liver failure (PHLF). Besides, larger RLC (OR, 1.114; 95% CI, 1.032-1.204; P=0.006) was independent risk factor for major postoperative complications.

Conclusions: Remnant liver hypoperfusion can be predicted during the preoperative surgical plan by 3DVT. Portal vein related RLI was associated with PHLF, and hepatic vein related RLC was associated with major postoperative complications. Preservation of the hepatic vein and complete removal of the perfusion territory of ligated vessels are essential procedures to reduce RLI/RLC and the risk of PHLF or other surgical complications.
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http://dx.doi.org/10.21037/atm-20-7920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246180PMC
May 2021

Pure spin photocurrent in non-centrosymmetric crystals: bulk spin photovoltaic effect.

Nat Commun 2021 Jul 15;12(1):4330. Epub 2021 Jul 15.

Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Spin current generators are critical components for spintronics-based information processing. In this work, we theoretically and computationally investigate the bulk spin photovoltaic (BSPV) effect for creating DC spin current under light illumination. The only requirement for BSPV is inversion symmetry breaking, thus it applies to a broad range of materials and can be readily integrated with existing semiconductor technologies. The BSPV effect is a cousin of the bulk photovoltaic (BPV) effect, whereby a DC charge current is generated under light. Thanks to the different selection rules on spin and charge currents, a pure spin current can be realized if the system possesses mirror symmetry or inversion-mirror symmetry. The mechanism of BSPV and the role of the electronic relaxation time [Formula: see text] are also elucidated. We apply our theory to several distinct materials, including monolayer transition metal dichalcogenides, anti-ferromagnetic bilayer MnBiTe, and the surface of topological crystalline insulator cubic SnTe.
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http://dx.doi.org/10.1038/s41467-021-24541-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282873PMC
July 2021

Atorvastatin Pretreatment Ameliorates Mesenchymal Stem Cell Migration through miR-146a/CXCR4 Signaling.

Tissue Eng Regen Med 2021 Jul 14. Epub 2021 Jul 14.

Department of Radiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.

Background: We previously found that atorvastatin (ATV) enhanced mesenchymal stem cells (MSCs) migration, by a yet unknown mechanism. CXC chemokine receptor 4 (CXCR4) is critical to cell migration and regulated by microRNA-146a (miR-146a). Therefore, this study aimed to assess whether ATV ameliorates MSCs migration through miR-146a/CXCR4 signaling.

Methods: Expression of CXCR4 was evaluated by flow cytometry. Expression of miR-146a was examined by reverse transcription-quantitative polymerase chain reaction. A transwell system was used to assess the migration ability of MSCs. Recruitment of systematically delivered MSCs to the infarcted heart was evaluated in Sprague-Dawley rats with acute myocardial infarction (AMI). Mimics of miR-146a were used in vitro, and miR-146a overexpression lentivirus was used in vivo, to assess the role of miR-146a in the migration ability of MSCs.

Results: The results showed that ATV pretreatment in vitro upregulated CXCR4 and induced MSCs migration. In addition, flow cytometry demonstrated that miR-146a mimics suppressed CXCR4, and ATV pretreatment no longer ameliorated MSCs migration because of decreased CXCR4. In the AMI model, miR-146a-overexpressing MSCs increased infarct size and fibrosis.

Conclusion: The miR-146a/CXCR4 signaling pathway contributes to MSCs migration and homing induced by ATV pretreatment. miR-146a may be a novel therapeutic target for stimulating MSCs migration to the ischemic tissue for improved repair.
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http://dx.doi.org/10.1007/s13770-021-00362-zDOI Listing
July 2021

MiR-27a-3p/Hoxa10 Axis Regulates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting Kv4.3 Expression.

Front Pharmacol 2021 24;12:680349. Epub 2021 Jun 24.

Department of Basic Medicine, Chengde Medical College, Chengde, China.

Cardiac hypertrophy is a common pathological process of various cardiovascular diseases, which is often accompanied with structural and electrical remodeling, and can even lead to sudden cardiac death. However, its molecular mechanism still remains largely unknown. Here, we induced cardiomyocyte hypertrophy by angiotensin II (Ang II), and found that miR-27a-3p and hypertrophy-related genes were up-regulated. Further studies showed that miR-27a-3p-inhibitor can alleviate myocardial hypertrophy and electrical remodeling. Moreover, luciferase assay confirmed that miR-27a-3p could regulate the expression of downstream at the transcriptional level by targeting at its 3'UTR. At the same time, the protein expression of Hoxa10 was significantly reduced in Ang II-treated cardiomyocytes. Furthermore, overexpression of can reverse myocardial hypertrophy and electrical remodeling induced by Ang II in cardiomyocytes. Finally, we found that Hoxa10 positively regulated the expression of potassium channel protein Kv4.3 which was down-regulated in hypertrophic cardiomyocytes. Taken together, our results revealed miR-27a-3p/Hoxa10/Kv4.3 axis as a new mechanism of Ang II-induced cardiomyocyte hypertrophy, which provided a new target for clinical prevention and treatment of cardiac hypertrophy and heart failure.
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http://dx.doi.org/10.3389/fphar.2021.680349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263894PMC
June 2021

Phosphorus Deficiency Promoted Hydrolysis of Organophosphate Esters in Plants: Mechanisms and Transformation Pathways.

Environ Sci Technol 2021 Jul 12;55(14):9895-9904. Epub 2021 Jul 12.

Key Laboratory of Pollution Processes and Environmental Criteria, Ministry of Education, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, P. R. China.

The biotransformation of organophosphate esters (OPEs) in white lupin () and wheat ( L.) was investigated in hydroponic experiments with different phosphorus (P)-containing conditions. The hydrolysis rates of OPEs followed the order of triphenyl phosphate (TPHP) > tri--butyl phosphate (TnBP) > tris(1,3-dichloro-2-propyl) phosphate (TDCPP). Hydrolysis of OPEs was accelerated at P-deficient conditions, and faster hydrolysis took place in white lupin than in wheat. Coincidingly, the production of acid phosphatase (ACP) in both plants was promoted, and much higher intracellular and extracellular ACPs were observed in white lupin under P-deficient conditions. experiments revealed that ACP was a key enzyme to hydrolyze OPEs. The hydrolysis rates of OPEs were significantly correlated with the Hirshfeld charges, calculated by density functional theory, of the oxygen atom in the single P-O bond. Using ultra-high-performance liquid chromatography coupled with Orbitrap Fusion mass spectrometer, 30 metabolites were successfully identified. Some of these metabolites, such as sulfate-conjugated products, hydration of cysteine-conjugated products of TPHP, and reductively dechlorinated metabolites of TDCPP, were observed for the first time in plants. It is noteworthy that OPEs may transform into many hydroxylated metabolites, and special attention should be paid to their potential environmental effects.
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http://dx.doi.org/10.1021/acs.est.1c02396DOI Listing
July 2021

Expression and Prognostic Value of MCM Family Genes in Osteosarcoma.

Front Mol Biosci 2021 22;8:668402. Epub 2021 Jun 22.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, China.

We performed a detailed cancer VS normal analysis to explore the expression and prognostic value of minichromosome maintenance (MCM) proteinsin human sarcoma. The mRNA expression levels of the MCM family genes in sarcoma were analyzed using data from ONCOMINE, GEPIA and CCLE databases. KEGG database was used to analyze the function of MCM2-7 complex in DNA replication and cell cycle. QRT-PCR and western blot were used to confirm the differential expression of key MCMs in osteosarcoma cell lines. Cell Counting Kit-8 and flow cytometry method were used to detect the cell proliferation and apoptosis of hFOB1.19 cells. The results showed that MCM1-7 and MCM10 were all upregulated in sarcoma in ONCOMINE database. MCM2, and MCM4-7 were highly expressed in sarcoma in GEPIA database. Moreover, all these ten factors were highly expressed in sarcoma cell lines. Furthermore, we analyzed the prognostic value of MCMs for sarcoma in GEPIA and found that MCM2, MCM3, MCM4, and MCM10 are prognostic biomarkers for human sarcoma. Analysis results using KEGG datasets showed that MCM4 and MCM6-7 constituted a core structure of MCM2-7 hexamers. We found that AzadC treatment and overexpression of MCM4 significantly promoted hFOB1.19 cell proliferation and inhibited apoptosis. The present study implied that MCM2-4 and 10 are potential biomarkers for the prognosis of sarcoma. The prognostic role of MCM4 may be attributable to the change in its DNA methylation patterns.
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http://dx.doi.org/10.3389/fmolb.2021.668402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257954PMC
June 2021

A Semi-Automatic Step-by-Step Expert-Guided LI-RADS Grading System Based on Gadoxetic Acid-Enhanced MRI.

J Hepatocell Carcinoma 2021 29;8:671-683. Epub 2021 Jun 29.

Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Purpose: Liver imaging reporting and data system (LI-RADS) classification, especially the identification of LR-3 to 5 lesions with hepatocellular carcinoma (HCC) probability, is of great significance to treatment strategy determination. We aimed to develop a semi-automatic LI-RADS grading system on multiphase gadoxetic acid-enhanced MRI using deep convolutional neural networks (CNN).

Patients And Methods: An internal data set of 439 patients and external data set of 71 patients with suspected HCC were included and underwent gadoxetic acid-enhanced MRI. The expert-guided LI-RADS grading system consisted of four deep 3D CNN models including a tumor segmentation model for automatic diameter estimation and three classification models of LI-RADS major features including arterial phase hyper-enhancement (APHE), washout and enhancing capsule. An end-to-end learning system comprising single deep CNN model that directly classified the LI-RADS grade was developed for comparison.

Results: On internal testing set, the segmentation model reached a mean dice of 0.84, with the accuracy of mapped diameter intervals as 82.7% (95% CI: 74.4%, 91.7%). The area under the curves (AUCs) were 0.941 (95% CI: 0.914, 0.961), 0.859 (95% CI: 0.823, 0.890) and 0.712 (95% CI: 0.668, 0.754) for APHE, washout and capsule, respectively. The expert-guided system significantly outperformed the end-to-end system with a LI-RADS grading accuracy of 68.3% (95% CI: 60.8%, 76.5%) vs 55.6% (95% CI: 48.8%, 63.0%) (<0.0001). On external testing set, the accuracy of mapped diameter intervals was 91.5% (95% CI: 81.9%, 100.0%). The AUCs were 0.792 (95% CI: 0.745, 0.833), 0.654 (95% CI: 0.602, 0.703) and 0.658 (95% CI: 0.606, 0.707) for APHE, washout and capsule, respectively. The expert-guided system achieved an overall grading accuracy of 66.2% (95% CI: 58.0%, 75.2%), significantly higher than the end-to-end system of 50.1% (95% CI: 43.1%, 58.1%) (<0.0001).

Conclusion: We developed a semi-automatic step-by-step expert-guided LI-RADS grading system (LR-3 to 5), superior to the conventional end-to-end learning system. This deep learning-based system may improve workflow efficiency for HCC diagnosis in clinical practice.
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http://dx.doi.org/10.2147/JHC.S316385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255313PMC
June 2021

Burden of Sleep Disturbance During COVID-19 Pandemic: A Systematic Review.

Nat Sci Sleep 2021 28;13:933-966. Epub 2021 Jun 28.

Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.

Coronavirus disease 2019 (COVID-19) pandemic may exert adverse impacts on sleep among populations, which may raise awareness of the burden of sleep disturbance, and the demand of intervention strategies for different populations. We aimed to summarize the current evidence for the impacts of COVID-19 on sleep in patients with COVID-19, healthcare workers (HWs), and the general population. We searched PubMed and Embase for studies on the prevalence of sleep disturbance. Totally, 86 studies were included in the review, including 16 studies for COVID-19 patients, 34 studies for HWs, and 36 studies for the general population. The prevalence of sleep disturbance was 33.3%-84.7%, and 29.5-40% in hospitalized COVID-19 patients and discharged COVID-19 survivors, respectively. Physiologic and psychological traumatic effects of the infection may interact with environmental factors to increase the risk of sleep disturbance in COVID-19 patients. The prevalence of sleep disturbance was 18.4-84.7% in HWs, and the contributors mainly included high workloads and shift work, occupation-related factors, and psychological factors. The prevalence of sleep disturbance was 17.65-81% in the general population. Physiologic and social-psychological factors contributed to sleep disturbance of the general population during COVID-19 pandemic. In summary, the sleep disturbance was highly prevalent during COVID-19 pandemic. Specific health strategies should be implemented to tackle sleep disturbance.
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http://dx.doi.org/10.2147/NSS.S312037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253893PMC
June 2021

Compatibility of Photoluminescence Properties in ScPO₄:Eu, Tb Phosphor for White Light Emitting Diodes.

J Nanosci Nanotechnol 2021 12;21(12):5890-5895

School of Resources Environment and Jewelry, Jiangxi College of Applied Technology, Ganzhou 341000, China.

ScPO₄:Eu, Tb phosphors with tuned emission color were prepared through high temperature solid-state reaction. The structure, morphology and photoluminescence properties of the title samples were collected by XRD, SEM and fluorescence spectrophotometer, respectively. Co-doping Eu and Tb in ScPO₄ does not change the body-centered tetragonal structure of the host. And the morphology remains essentially unchanged except for slight agglomeration. Changing the ratio of Tb/Eu, the tuned emission can be achieved, the color could be adjusted from green through yellow to orange-red. The ScPO₄:0.03Tb, 0.03Eu phosphor with high thermal stability as the single matrix phosphor can be suitable for the NUV-pumped white LED. The white LED with a color rendering index of 86.5 and a correlated color temperature of 3470 K has been generated by packaging BAM:Eu with ScPO₄:0.03Tb, 0.03Eu on an NUV-InGaN chip.
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http://dx.doi.org/10.1166/jnn.2021.19507DOI Listing
December 2021

Highly Efficient and Thermally Stable Eu-Doped CaNd(PO₄) Phosphor for Near-Ultraviolet White-Emission LED Applications.

Authors:
Jian Zhou Si-Li Ren

J Nanosci Nanotechnol 2021 Dec;21(12):5859-5866

School of Metallurgy and Chemistry Engineering, Jiangxi University of Science and Technology, Ganzhou 341000, China.

Various Eu-based CaNd(PO₄) (CNP:xEu, with different values) materials are prepared via facile solid-state reaction. Their crystal structures are investigated in detail by means of the Rietveld refinement. The structure of CNP:Eu with a trigonal lattice is analogous to that of -Ca₃(PO₄)₂. Therefore, Eu2+ ions tend to incorporate calcium sites in the host. All the obtained samples can be excited using near ultraviolet (nUV) light to present blue-green emission. An optimal dopant concentration is verified at = 0.8 with a large critical interaction radius (11.21 Å). The mechanism of the concentration quenching effect is assigned to the multipole-multipole interaction. CNP:xEu possesses a short decay lifetime of ∼60 s and can endure severe working conditions thanks to its great thermal stability. The relative photoluminescence (PL) intensity of CNP:0.8Eu can retain 84.75% of the pristine intensity measured at room temperature, and the relative intensity remains as high as 69.97% at 423 K. The CNP:Eu phosphors also show great performance in the WLED demonstration. The correlated color temperature (CCT) of the prototype device is 3404 K, with an extremely high Ra (97.6). Therefore, CNP:Eu could be regarded as a promising alternative to blue green phosphors in nUV chip-based WLED applications.
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http://dx.doi.org/10.1166/jnn.2021.19505DOI Listing
December 2021

Dietary Improves Serum Antioxidant Capacity and Intestinal Immunity and Alters Colonic Microbiota in Weaned Piglets.

Front Nutr 2021 17;8:679129. Epub 2021 Jun 17.

Key Laboratory of Plant Resources/Beijing Botanical Garden, Institute of Botany, Chinese Academy of Sciences, Beijing, China.

(MCR), as a common traditional Chinese medicine, has been widely used as an antipyretic, antiseptic, and anti-inflammatory agent in China. This study aimed to investigate the effects of dietary MCR supplementation on the antioxidant capacity and intestinal health of the pigs and to explore whether MCR exerts positive effects on intestinal health regulating nuclear factor kappa-B (NF-κB) signaling pathway and intestinal microbiota. MCR powder was identified by LC-MS analysis. Selected 32 weaned piglets (21 d of age, 6.37 ± 0.10 kg average BW) were assigned (8 pens/diet, 1 pig/pen) to 4 groups and fed with a corn-soybean basal diet supplemented with 0, 2,000, 4,000, and 8,000 mg/kg MCR for 21 d. After the piglets were sacrificed, antioxidant indices, histomorphology examination, and inflammatory signaling pathway expression were assessed. The 16s RNA sequencing was used to analyze the effects of MCR on the intestinal microbiota structure of piglets. Supplemental 4,000 mg/kg MCR significantly increased ( < 0.05) the average daily weight gain (ADG), average daily feed intake (ADFI), total antioxidative capability, colonic short-chain fatty acids (SCFA) concentrations, and the crypt depth in the jejunum but decreased ( < 0.05) the mRNA expression levels of interferon γ, tumor necrosis factor-α, interleukin-1β, inhibiting kappa-B kinase β (IKKβ), inhibiting nuclear factor kappa-B (IκBα), and NF-κB in the jejunum and ileum. Microbiota sequencing identified that MCR supplementation significantly increased the microbial richness indices (Chao1, ACE, and observed species, < 0.05) and the relative abundances of and ( < 0.05), decreased the relative abundances of , and ( < 0.05) and had no significant effects on the diversity indices (Shannon and Simpson, > 0.05). Microbial metabolic phenotypes analysis also showed that the richness of aerobic bacteria and facultative anaerobic bacteria, oxidative stress tolerance, and biofilm forming were significantly increased ( < 0.05), and the richness of anaerobic bacteria and pathogenic potential of gut microbiota were reduced ( < 0.05) by MCR treatment. Regression analysis showed that the optimal MCR supplemental level for growth performance, serum antioxidant capacity, and intestinal health of weaned piglets was 3,420 ~ 4,237 mg/kg. MCR supplementation improved growth performance and serum antioxidant capacity, and alleviated intestinal inflammation by inhibiting the IKKβ/IκBα/NF-κB signaling pathway and affecting intestinal microbiota in weaned piglets.
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http://dx.doi.org/10.3389/fnut.2021.679129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247480PMC
June 2021

Development and Validation of a Nomogram Based on Perioperative Factors to Predict Post-hepatectomy Liver Failure.

J Clin Transl Hepatol 2021 Jun 15;9(3):291-300. Epub 2021 Mar 15.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Background And Aims: Post-hepatectomy liver failure (PHLF) is a severe complication and main cause of death in patients undergoing hepatectomy. The aim of this study was to build a predictive model of PHLF in patients undergoing hepatectomy.

Methods: We retrospectively analyzed patients undergoing hepatectomy at Zhongshan Hospital, Fudan University from July 2015 to June 2018, and randomly divided them into development and internal validation cohorts. External validation was performed in an independent cohort. Least absolute shrinkage and selection operator (commonly referred to as LASSO) logistic regression was applied to identify predictors of PHLF, and multivariate binary logistic regression analysis was performed to establish the predictive model, which was visualized with a nomogram.

Results: A total of 492 eligible patients were analyzed. LASSO and multivariate analysis identified three preoperative variables, total bilirubin (=0.001), international normalized ratio (<0.001) and platelet count (=0.004), and two intraoperative variables, extent of resection (=0.002) and blood loss (=0.004), as independent predictors of PHLF. The area under receiver operating characteristic curve (referred to as AUROC) of the predictive model was 0.838 and outperformed the model for end-stage liver disease score, albumin-bilirubin score and platelet-albumin-bilirubin score (AUROCs: 0.723, 0.695 and 0.663, respectively; <0.001 for all). The optimal cut-off value of the predictive model was 14.7. External validation showed the model could predict PHLF accurately and distinguish high-risk patients.

Conclusions: PHLF can be accurately predicted by this model in patients undergoing hepatectomy, which may significantly contribute to the postoperative care of these patients.
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http://dx.doi.org/10.14218/JCTH.2021.00013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237151PMC
June 2021

Light-Induced Quantum Anomalous Hall Effect on the 2D Surfaces of 3D Topological Insulators.

Adv Sci (Weinh) 2021 Jul 2:e2101508. Epub 2021 Jul 2.

Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Quantum anomalous Hall (QAH) effect generates quantized electric charge Hall conductance without external magnetic field. It requires both nontrivial band topology and time-reversal symmetry (TRS) breaking. In most cases, one can break the TRS of time-reversal invariant topological materials to yield QAH effect, which is essentially a topological phase transition. However, conventional topological phase transition induced by external field/stimulus usually needs a route along which the bandgap closes and reopens. Hence, the transition occurs only when the magnitude of field/stimulus is larger than a critical value. In this work the authors propose that using gapless systems, the transition can happen at an arbitrarily weak (but finite) external field strength. For such an unconventional topological phase transition, the bandgap closing is guaranteed by bulk-edge correspondence and symmetries, while the bandgap reopening is induced by external fields. This concept is demonstrated on the 2D surface states of 3D topological insulators like Bi Se , which become 2D QAH insulators once a circularly polarized light is turned on, according to the Floquet time crystal theory. The sign of quantized Chern number can be controlled via the chirality of the light. This provides a convenient and dynamic approach to trigger topological phase transitions and create QAH insulators.
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http://dx.doi.org/10.1002/advs.202101508DOI Listing
July 2021

Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma.

Nat Commun 2021 07 2;12(1):4091. Epub 2021 Jul 2.

Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People's Republic of China.

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.
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http://dx.doi.org/10.1038/s41467-021-24386-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253833PMC
July 2021

Safety and immunogenicity of a recombinant interferon-armed RBD dimer vaccine (V-01) for COVID-19 in healthy adults: A randomised, double-blind, placebo-controlled, phase I trial.

Emerg Microbes Infect 2021 Jul 1:1-48. Epub 2021 Jul 1.

Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou, China.

Safe and effective vaccines are still urgently needed to cope with the ongoing COVID-19 pandemic. Recently, we developed a recombinant COVID-19 vaccine (V-01) containing fusion protein (IFN-PADRE-RBD-Fc dimer) as antigen verified to induce protective immunity against SARS-CoV-2 challenge in pre-clinical study, which supported progression to Phase Ⅰ clinical trials in humans. A Randomized, double-blind, placebo-controlled phase I clinical trial was initiated at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China) in February, 2021. Healthy adults aged between 18 and 59 years and over 60 years were sequentially enrolled and randomly allocated into three subgroups (1:1:1) either to receive vaccine (10, 25, and 50μg) or placebo (V-01: Placebo=4:1) intramuscularly with a 21-day interval by a sentinel and dose escalation design. The data showed promising safety profile with approximately 25% vaccine related overall adverse events within 30 days and no grade 3 or worse adverse events. Besides, V-01 provoked rapid and strong immune responses, elicited substantially high-titre neutralizing antibodies and anti-RBD IgG peaked at day 35 or 49 after first dose, presented with encouraging immunogenicity at low dose (10μg) subgroup and elderly participants, which showed great promise to be used as all-aged (18 and above) vaccine against COVID-19. Taken together, our preliminary findings indicate that V-01 is safe and well tolerated, capable of inducing rapid and strong immune responses, and warrants further testing in phase Ⅱ/Ⅲ clinical trials.
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http://dx.doi.org/10.1080/22221751.2021.1951126DOI Listing
July 2021

Amplitude of low-frequency fluctuation may be an early predictor of delayed motor development due to neonatal hyperbilirubinemia: a fMRI study.

Transl Pediatr 2021 May;10(5):1271-1284

Department of Neonatology, Children' Hospital of Fudan University, Shanghai, China.

Background: Acute bilirubin encephalopathy or kernicterus is the worst consequence of brain damage caused by the elevation of total unbound serum bilirubin (TSB) in neonates. The present study aimed to visualize the characteristic brain regions of neonates with hyperbilirubinemia (HB) using functional magnetic resonance imaging (fMRI) and to measure the amplitude of low-frequency fluctuation (ALFF) values.

Methods: This was a prospective cohort study, which included newborns with HB who were hospitalized at the Children's Hospital of Fudan University. The control group included neonates admitted with neonatal simple wet lung or pneumonia without neurological disease or brain injury. Newborns were divided into a severe hyperbilirubinemia group (SHB), moderate HB group, and control group based on TSB levels. The newborns completed routine MRI combined with fMRI scans and brainstem auditory evoked potentials (BAEPs) during their hospitalization.

Results: A total of 251 newborns were included in this study. There were 45 patients in the SHB group, 65 in the HB group, and 141 in the control group. The average ALFF value in the basal ganglia region in the SHB group was the highest, which was greater than that in the HB and control groups (P<0.001). The ALFF increased with an increase in TSB concentration. Based on the results of the Bayley Scales of infant development assessment, we further found that the most significant difference in ALFF remained in the basal ganglia region between newborns with motor development scores above 70 (including 70) and below 70. Correlation analysis revealed a strong negative correlation between motor development scores and ALFF (r=-0.691, P<0.001). When ALFF alone was used to predict motor development, the sensitivity was 89%. When ALFF was combined with TSB and BEAP results, the area under the ROC curve was the largest (AUC =0.85). The sensitivity and specificity of the model were 67.86% and 90.77%, respectively.

Conclusions: The ALFF value may be able to serve as an early imaging biomarker and has a greater sensitivity than TSB or BAEP results in predicting long-term motor development (18 m) in HB.
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http://dx.doi.org/10.21037/tp-20-447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192981PMC
May 2021

Association between visit-to-visit variability of glycated albumin and diabetic retinopathy among patients with type 2 diabetes - A prospective cohort study.

J Diabetes Complications 2021 May 29:107971. Epub 2021 May 29.

Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, China. Electronic address:

Aim: There is a paucity of studies regarding the association between long-term glycemic variability with the risk of diabetic retinopathy (DR) in patients with type 2 diabetes. Therefore, the purpose of this study is to explore the association of glycated albumin (GA) variability and HbA1c variability with the risk of DR in patients with type 2 diabetes.

Methods: This prospective cohort study included 315 inpatients with type 2 diabetes (191 males and 124 females) with at least 3 measurements of GA and HbA1c within 2years prior to the baseline investigation. Different GA and HbA1c variability markers were calculated, including CV, variability independent of the mean (VIM), and the average real variability (ARV). Cox proportional hazard regression models were used to explore the association between visit-to-visit variability of GA and HbA1c and the risk of DR.

Results: After an average follow-up of 3.42years, 81 patients developed incident DR. Multivariable-adjusted (diabetes duration, smoking status, systolic blood pressure, albumin to creatinine ratio, triglycerides, using fibrates, and mean HbA1c) hazard ratios of DR associated with each unit increase in GA-CV, GA-VIM, and GA-ARV were 1.05 (95% CI 1.02-1.09), 1.69 (95% CI 1.24-2.32), and 1.13 (95%CI 1.04-1.23), respectively. However, there was no significant association between visit-to-visit HbA1c variability and the risk of DR.

Conclusions: The present study indicated that visit-to-visit variability of GA can predict the risk of incident DR in patients with type 2 diabetes, and the prediction ability is independent of the average HbA1c levels.
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http://dx.doi.org/10.1016/j.jdiacomp.2021.107971DOI Listing
May 2021

Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized clinical trial.

Front Med 2021 Jun 29;15(3):460-471. Epub 2021 Jun 29.

Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Lifestyle interventions, including dietary adjustments and exercise, are important for obesity management. This study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet (LCD) or exercise is more effective in metabolism improvement. Forty-five eligible subjects were randomly divided into an LCD group (n = 22) and an exercise group (EX, n = 23). The subjects either adopted LCD (carbohydrate intake < 50 g/day) or performed moderate-to-vigorous exercise (⩾ 30 min/day) for 3 weeks. After the interventions, LCD led to a larger weight loss than EX ( - 3.56 ± 0.37 kg vs. - 1.24 ± 0.39 kg, P < 0.001), as well as a larger reduction in fat mass ( - 2.10 ± 0.18 kg vs. - 1.25 ± 0.24 kg, P = 0.007) and waist circumference ( - 5.25 ± 0.52 cm vs. - 3.45 ± 0.38 cm, P = 0.008). Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin resistance. Triglycerides decreased in both two groups, whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX group. Various glycemic parameters, including serum glycated albumin, mean sensor glucose, coefficient of variability (CV), and largest amplitude of glycemic excursions, substantially declined in the LCD group. Only CV slightly decreased after exercise. This pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin resistance. Compared with exercise, LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.
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http://dx.doi.org/10.1007/s11684-021-0861-6DOI Listing
June 2021

A novel anticaries agent, honokiol-loaded poly(amido amine) dendrimer, for simultaneous long-term antibacterial treatment and remineralization of demineralized enamel.

Dent Mater 2021 Jun 23. Epub 2021 Jun 23.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address:

Objective: Existing agents to induce enamel self-repair and inhibit the progression of dental caries in the early stage have been proven to be inadequate and far from satisfactory. In this study, a honokiol-loaded poly(amido amine) (PAMAM) dendrimer (PAMH) was constructed to combat early caries lesions in enamel.

Methods: PAMH was prepared via a codissolution method. Computational simulation analysis was used to explore the mechanism of honokiol release. The cytotoxicity of PAMH was tested. The antibacterial effects of PAMH were tested by planktonic growth assays and biofilm formation inhibition assays. The remineralization effect of PAMH was examined via transverse microradiography and scanning electron microscopy after a pH cycling model. The in vivo anti-caries effect of PAMH was carried out in a rat model.

Results: Honokiol released from PAMH was slower but more durable in a cariogenic pH environment than in a neutral pH environment, which could be explained through the computational simulation analysis results. Under electrostatic action, P3 beads with the same charge repelled each other and extended outwards, resulting in the rapid expansion of the PAMAM dendrimer and accelerating the release of the drug. At a low pH of 5.5, the protonated P3 beads were not charged and the protonated P1 beads were positively charged. However, the electrostatic repulsive interaction between protonated P1 beads was restricted by the P3 beads in the outermost layer of the PAMAM dendrimer, so the swelling rate was relatively slow, resulting in the slow release of drug molecules in the acidic environment. The cytotoxicity demonstration and the biocompatibility experiment in animal study showed that PAMH is biologically safe. PAMH showed excellent enamel remineralizing ability after pH cycling and showed a long-term antibacterial effect in vitro. Meanwhile, PAMH showed long-term anticaries efficacy in vivo.

Significance: Our findings indicated that PAMH had great potential to combat early caries lesions in enamel for future clinical application.
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http://dx.doi.org/10.1016/j.dental.2021.06.003DOI Listing
June 2021

Identification of a novel Sox5 transcript in mouse testis.

Gene Expr Patterns 2021 Jun 22;41:119197. Epub 2021 Jun 22.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China. Electronic address:

The transcription factor SOX5 is present in two distinct isoforms in both human and mouse, L-SOX5 and S-SOX5 (long and short isoforms of SOX5). Here, we identified and characterized a novel transcript of Sox5 (S-Sox5 variant) in mouse testis. eCLIP-based amplification of cDNA ends were performed to identify the potential Sox5 mRNA variant. This novel transcript shares a high similarity with the previously reported S-Sox5 in nucleotide sequence, but with a unique stretch of 5'UTR and an additional exon 9. Semi-quantitative PCR analysis revealed both S-Sox5 variant and S-Sox5 express specifically in mouse testis. Both transcripts increase significantly in mouse testis at postnatal day 21, when round spermatids appear. We further made a series of truncated Sox5 constructs and tagged them with eGFP in HeLa cells. In vitro transfection assay identified the N-terminus and the DNA-binding HMG domain are required for the nuclear localization of SOX5. Our results provides a basis for the future study to investigate the biological function of SOX5 in spermatogenesis.
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http://dx.doi.org/10.1016/j.gep.2021.119197DOI Listing
June 2021
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