Publications by authors named "Fei Gao"

1,770 Publications

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Monitoring the efficacy of tumor necrosis factor alpha antagonists in the treatment of Ankylosing spondylarthritis: a pilot study based on MR relaxometry technique.

BMC Med Imaging 2021 Jul 30;21(1):117. Epub 2021 Jul 30.

The Shengli Clinical Medical College, Fujian Medical University, Radiology Department of Fujian Provincial Hospital, 134 East Street, Gulou District, Fuzhou City, 350001, Fujian Province, China.

Background: SpA is a disease that seriously affects the quality of life and working ability of patients. At present, there is a lack of scientific and effective quantitative indicators to evaluate the activity of sacroilitis and the efficacy of tumor necrosis factor-α antagonists in the treatment of active sacroilitis. MRI STIR sequence is the most commonly used method for the diagnosis of sacroiliac joint inflammation, but its response to the disease still lags behind the pathological changes and cannot provide quantitative indicators. This study aimed to evaluate the feasibility of using MRI Relaxometry technique to monitor the efficacy of TNF-α antagonists in the treatment of SpA, so as to provide an effective quantitative index for monitoring the efficacy.

Methods: This is a prospective study, 114 patients with sacroiliac joint were enrolled, including 15 patients as a control group, 99 patients as the case group, and 20 patients in the case group as the treatment group. The differences of T1 mapping, T2 mapping, T2* mapping of subchondral bone marrow of sacroiliac joint were compared among different groups. The diagnostic efficacy was analyzed by ROC, and the best quantitative index of diagnostic efficiency was used to monitor curative effects of different treatment cycles in the treatment group.

Results: 1. Compared with the control group, values of three different relaxation times in the subchondral bone marrow region of the sacroiliac joint in the case group increased in varying degrees, and T1 mapping showed the best diagnostic efficacy. 2. The decreasing rate of T1 mapping in different treatment periods benefits the monitoring of curative effects.

Conclusion: This study indicates that T1 mapping technique is preferred in quantitative diagnosis. T1 mapping is superior to T2* mapping and T2 mapping in the diagnosis of subchondral BME of SpA. It can quantitatively monitor edema changes during treatment, benefiting clinical individualized treatment and timely adjustment of the treatment plan.
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http://dx.doi.org/10.1186/s12880-021-00646-9DOI Listing
July 2021

Identification of serum prognostic marker miRNAs and construction of microRNA-mRNA networks of esophageal cancer.

PLoS One 2021 30;16(7):e0255479. Epub 2021 Jul 30.

Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.

Esophageal cancer is a common tumor of the digestive system with poor prognosis. This study was to gain a better understanding of the mechanisms involved in esophageal cancer and to identify new prognostic markers. We downloaded the esophageal cancer miRNA expression profile microarray data (GSE113740, GSE112264, GSE122497, GSE113486, and GSE106817) from the GEO database, extracted the esophageal cancer miRNA sequencing data from The Cancer Genome Atlas (TCGA) database, and then used a bioinformatics approach to select common differentially expressed miRNAs (DEMs). Differentially expressed genes (DEGs) were selected by predicting DEM target genes using the miRWalk database and intersecting with differential genes obtained from TCGA database for esophageal cancer. The STRING database was used to obtain protein-protein interaction (PPI) relationships to construct the DEM-DEG network. Furthermore, we selected core genes and core miRNAs associated with esophageal cancer prognosis by performing survival and univariate/multivariate COX analysis on DEMs and DEGs in the network and performed GSEA analysis on core genes alone, and finally the expression of the markers was verified by qPCR in esophageal cancer cell lines Eca109, SKGT-4 and normal esophageal epithelial cells HEEC. Nine DEMs were obtained, of which three were upregulated and six were downregulated, and 326 DEGs were obtained, of which 105 were upregulated and 221 were downregulated. Survival univariate/multivariate COX analysis revealed that five genes, ZBTB16, AQP4, ADCYAP1R1, PDGFD, and VIPR2, and two microRNAs, miR-99a-5p, and miR-508-5p, were related to esophageal cancer prognosis. GSEA analysis showed that the following genes may be involved in esophageal cancer prognosis: ZBTB16 may through the MTOR signaling pathway, AQP4 through the GNRH signaling pathway, ADCYAP1R1 through the PPAR signaling pathway, VIPR2 through the P53 signaling pathway and PDGFD through the PENTOSE-PHOSPHATE signaling pathway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255479PLOS
July 2021

Reconfigurable meta-radiator based on flexible mechanically controlled current distribution in three-dimensional space.

Opt Lett 2021 Aug;46(15):3633-3636

In this paper, we provide an experimental proof-of-concept of this dynamic three-dimensional (3D) current manipulation through a 3D-printed reconfigurable meta-radiator with periodically slotted current elements. By utilizing the working frequency and the mechanical configuration comprehensively, the radiation pattern can be switched among 12 states. Inspired by maximum likelihood method in digital communications, a robustness-analysis method is proposed to evaluate the potential error ratio between ideal cases and practice. Our work provides a previously unidentified model for next-generation information distribution and terahertz-infrared wireless communications.
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http://dx.doi.org/10.1364/OL.430318DOI Listing
August 2021

Clinical Outcomes and Prognostic Factors of Salvage Treatment for Local Lymph Node Recurrence After Radical Resection of Oesophageal Carcinoma.

Cancer Manag Res 2021 23;13:5845-5853. Epub 2021 Jul 23.

Department of Radiation Oncology, The Second Affiliated Hospital of Soochow University, Su Zhou, 215004, Jiang Su Province, People's Republic of China.

Background: There are no standard therapeutic strategies for local lymph node (LN) recurrence after radical resection of oesophageal squamous cell carcinoma (ESCC), and prognostic risk factors remain controversial. We assessed clinical outcomes and prognostic factors of chemoradiotherapy (CRT) or radiotherapy (RT) for LN recurrence of ESCC after curative resection.

Methods: A total of 117 ESCC patients with LN recurrence after radical resection receiving salvage treatment at our hospital were retrospectively reviewed from 2014 to 2017. Overall survival (OS) was estimated using the Kaplan-Meier method; clinical characteristics were assessed using the Log rank test in the univariate analysis. Multivariate prognostic analysis was performed using the Cox proportional hazard model.

Results: With a median follow-up of 19 months, the 1-, 2- and 3-year OS rates were 75.2%, 40.2% and 27.4%, respectively. The median survival time (MST) was 19.0 months. On univariate analysis for OS, pathological TNM stage, number of LN metastasis, LN maximum (Max) diameter, salvage treatment mode and tumor response were significantly associated with OS (P = 0.0074, P = 0.015, P = 0.0011, P = 0.028, P < 0.000, respectively). On multivariate analysis, tumor response [Response vs No-response hazard ratio (HR), 2.43; 95% confidence interval (CI), 1.53-3.90, P < 0.000] and LN Max diameter (≤28 mm vs >28 mm HR, 2.07; 95% CI, 1.33-3.32, P = 0.012) were independent prognostic factors.

Conclusion: Salvage CRT or RT was safe and effective for treating LN recurrence after radical resection in ESCC. Patients with the small LN Max diameter (≤28 mm) and obtained response after salvage therapy appeared to achieve long-term OS.
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http://dx.doi.org/10.2147/CMAR.S315127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315777PMC
July 2021

An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single-base resolution methylome and hydroxymethylome.

Clin Transl Med 2021 Jul;11(7):e498

Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Centre for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Cervical cancer (CC) is the second leading cause of cancer death among women worldwide. Epigenetic regulation of gene expression through DNA methylation and hydroxymethylation plays a pivotal role during tumorigenesis. In this study, to analyze the epigenomic landscape and identify potential biomarkers for CCs, we selected a series of samples from normal to cervical intra-epithelial neoplasia (CINs) to CCs and performed an integrative analysis of whole-genome bisulfite sequencing (WGBS-seq), oxidative WGBS, RNA-seq, and external histone modifications profiling data.

Results: In the development and progression of CC, there were genome-wide hypo-methylation and hypo-hydroxymethylation, accompanied by local hyper-methylation and hyper-hydroxymethylation. Hydroxymethylation prefers to distribute in the CpG islands and CpG shores, as displayed a trend of gradual decline from health to CIN2, while a trend of increase from CIN3 to CC. The differentially methylated and hydroxymethylated region-associated genes both enriched in Hippo and other cancer-related signaling pathways that drive cervical carcinogenesis. Furthermore, we identified eight novel differentially methylated/hydroxymethylated-associated genes (DES, MAL, MTIF2, PIP5K1A, RPS6KA6, ANGEL2, MPP, and PAPSS2) significantly correlated with the overall survival of CC. In addition, no any correlation was observed between methylation or hydroxymethylation levels and somatic copy number variations in CINs and CCs.

Conclusion: Our current study systematically delineates the map of methylome and hydroxymethylome from CINs to CC, and some differentially methylated/hydroxymethylated-associated genes can be used as the potential epigenetic biomarkers in CC prognosis.
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http://dx.doi.org/10.1002/ctm2.498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288011PMC
July 2021

Effect of transjugular intrahepatic portosystemic shunt on transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis.

Diagn Interv Radiol 2021 Jul 28. Epub 2021 Jul 28.

Department of Minimally Invasive - Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China;Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University State Key Laboratory of Oncology in South China, Guangzhou, China.

Purpose: Hepatocellular carcinoma (HCC) usually occurs accompanied by portal hypertension. Transcatheter arterial chemoembolization (TACE) is recommended as an effective treatment in HCC. Recent studies had conflicting results regarding the effectiveness and safety of TACE for HCC in patients with transjugular intrahepatic portosystemic shunt (TIPS). This meta-analysis aimed to evaluate the influence of TIPS on the effectiveness and safety of TACE for patients with HCC.

Methods: A comprehensive search of studies among PubMed, Web of Science and Cochrane Library was conducted, from the earliest publishing date to January 27th, 2020. Statistical analyses were all performed using the Stata 13.0 software. I2 index statistic was used to assess heterogeneity.

Results: Six studies with a total of 536 patients with HCC were included in the analysis. The pooled response rate was 51% (95% CI: 25% to 77%) with a significant heterogeneity (I2=93.3%, p < 0.001). The TACE + TIPS group had an inferior response rate than the non-TIPS group, but the difference had no statistical significance (p = 0.171) and heterogeneity was low (I2=0.00%, p = 0.490). Pooled hepatic failure rate was 8.8% (95% CI: 5.2% to 12.4%) with low heterogeneity (I2=0.0%, p = 0.747). But the pooled hepatic failure rate increased to 12.7% (95% CI: 5.7% to 19.7%) with low heterogeneity (I2=11.5%, p = 0.323) if the patients who received TIPS after TACE were excluded.

Conclusion: TIPS does not influence the effectiveness of TACE, but attention should be paid to the risk of hepatic failure.
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http://dx.doi.org/10.5152/dir.2021.20358DOI Listing
July 2021

Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis.

Nat Commun 2021 07 27;12(1):4560. Epub 2021 Jul 27.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.

Alcoholic hepatitis (AH) is associated with liver neutrophil infiltration through activated cytokine pathways leading to elevated chemokine expression. Super-enhancers are expansive regulatory elements driving augmented gene expression. Here, we explore the mechanistic role of super-enhancers linking cytokine TNFα with chemokine amplification in AH. RNA-seq and histone modification ChIP-seq of human liver explants show upregulation of multiple CXCL chemokines in AH. Liver sinusoidal endothelial cells (LSEC) are identified as an important source of CXCL expression in human liver, regulated by TNFα/NF-κB signaling. A super-enhancer is identified for multiple CXCL genes by multiple approaches. dCas9-KRAB-mediated epigenome editing or pharmacologic inhibition of Bromodomain and Extraterminal (BET) proteins, transcriptional regulators vital to super-enhancer function, decreases chemokine expression in vitro and decreases neutrophil infiltration in murine models of AH. Our findings highlight the role of super-enhancer in propagating inflammatory signaling by inducing chemokine expression and the therapeutic potential of BET inhibition in AH treatment.
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http://dx.doi.org/10.1038/s41467-021-24843-wDOI Listing
July 2021

Oral delivery of natural active small molecules by polymeric nanoparticles for the treatment of inflammatory bowel diseases.

Adv Drug Deliv Rev 2021 Jul 24:113887. Epub 2021 Jul 24.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Beibei, Chongqing 400715, China. Electronic address:

The incidence of inflammatory bowel disease (IBD) is rapidly rising throughout the world. Although tremendous efforts have been made, limited therapeutics are available for IBD management. Natural active small molecules (NASMs), which are a gift of nature to humanity, have been widely used in the prevention and alleviation of IBD; they have numerous advantageous features, including excellent biocompatibility, pharmacological activity, and mass production potential. Oral route is the most common and acceptable approach for drug administration, but the clinical application of NASMs in IBD treatment via oral route has been seriously restricted by their inherent limitations such as their high hydrophobicity, instability, and poor bioavailability. With the development of nanotechnology, polymeric nanoparticles (NPs) have provided a promising platform that can efficiently encapsulate versatile NASMs, overcome multiple drug delivery barriers, and orally deliver the loaded NASMs to targeted tissues or cells while enhancing their stability and bioavailability. Thus, NPs can enhance the preventive and therapeutic effects of NASMs against IBD. Herein, we summarize the recent knowledge about polymeric matrix-based carriers, targeting ligands for drug delivery, and NASMs. We also discuss the current challenges and future developmental directions.
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http://dx.doi.org/10.1016/j.addr.2021.113887DOI Listing
July 2021

Targeted Therapies for Leigh Syndrome: Systematic Review and Steps Towards a 'Treatabolome'.

J Neuromuscul Dis 2021 Jul 20. Epub 2021 Jul 20.

Department of Clinical Neurosciences, School of Clinical Medicine, John Van Geest Centre for Brain Repair, University of Cambridge, UK.

Background: Leigh syndrome (LS) is the most frequent paediatric clinical presentation of mitochondrial disease. The clinical phenotype of LS is highly heterogeneous. Though historically the treatment for LS is largely supportive, new treatments are on the horizon. Due to the rarity of LS, large-scale interventional studies are scarce, limiting dissemination of information of therapeutic options to the wider scientific and clinical community.

Objective: We conducted a systematic review of pharmacological therapies of LS following the guidelines for FAIR-compliant datasets.

Methods: We searched for interventional studies within Clincialtrials.gov and European Clinical trials databases. Randomised controlled trials, observational studies, case reports and case series formed part of a wider MEDLINE search.

Results: Of the 1,193 studies initially identified, 157 met our inclusion criteria, of which 104 were carried over into our final analysis.Treatments for LS included very few interventional trials using EPI-743 and cysteamine bitartrate. Wider literature searches identified case series and reports of treatments repleting glutathione stores, reduction of oxidative stress and restoration of oxidative phosphorylation.

Conclusions: Though interventional randomised controlled trials have begun for LS, the majority of evidence remains in case reports and case series for a number of treatable genes, encoding cofactors or transporter proteins of the mitochondria. Our findings will form part of the international expert-led Solve-RD efforts to assist clinicians initiating treatments in patients with treatable variants of LS.
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http://dx.doi.org/10.3233/JND-210715DOI Listing
July 2021

Metformin inhibits MAPK signaling and rescues pancreatic Aquaporin 7 expression to induce insulin secretion in type 2 diabetes mellitus.

J Biol Chem 2021 Jul 22:101002. Epub 2021 Jul 22.

Department of Anatomy, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, People's Republic of China. Electronic address:

Metformin is the first-line anti-diabetic agent for type 2 diabetes mellitus (T2DM) treatment. Although accumulated evidence has shed light on the consequences of metformin action, the precise mechanisms of its action, especially in the pancreas, are not fully understood. Aquaporin 7 (AQP7) acts as a critical regulator of intra-islet glycerol content, which is necessary for insulin production and secretion. The aim of this study was to investigate the effects of different doses of metformin on AQP7 expression and explore the possible mechanism of its protective effects in the pancreatic islets. We used an in vivo model of high-fat diet in STZ-induced diabetic rats, and an in vitro model of rat pancreatic β-cells (INS-1 cells) damaged by hyperglycemia and hyperlipidemia. Our data showed that AQP7 expression levels were decreased, whereas p38 and JNK mitogen-activated protein kinases (MAPKs) were activated in vivo and in vitro in response to hyperglycemia and hyperlipidemia. T2DM rats treated with metformin demonstrated a reduction in blood glucose levels and increased regeneration of pancreatic β-cells. In addition, metformin upregulated AQP7 expression as well as inhibited activation of p38 and JNK MAPKs both in vivo and in vitro. Overexpression of AQP7 increased glycerol influx into INS-1 cells, whereas inhibition of AQP7 reduced glycerol influx, thereby decreasing subsequent insulin secretion. Our findings demonstrate a new mechanism by which metformin suppresses the p38 and JNK pathways, thereby upregulating pancreatic AQP7 expression, and promoting glycerol influx into pancreatic β-cells and subsequent insulin secretion in T2DM.
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http://dx.doi.org/10.1016/j.jbc.2021.101002DOI Listing
July 2021

Relationship between osteonecrosis and antiphospholipid antibodies in patients with systemic lupus erythematosus: a systematic review protocol.

BMJ Open 2021 Jul 22;11(7):e046163. Epub 2021 Jul 22.

Rheumatology, Fujian Medical University Provincial Clinical Medical College, Fuzhou, Fujian, China

Introduction: Osteonecrosis (ON) is characterised by the destruction of the normal blood supply to the bone tissue. ON is the main cause of disability in patients with systemic lupus erythematosus (SLE). Studies have reported the existence of many risk factors for SLE complicated by ON, including the use of high-dose glucocorticoids and high disease activity. The correlation between antiphospholipid antibodies (aPLs) and ON in SLE has been controversial. We aim to conduct a systematic review of the literature related to SLE, aseptic ON and aPLs, to provide a reference for the clinical screening of high-risk patients and for early prevention.

Methods And Analysis: The following six databases will be searched: MEDLINE/PubMed, Embase, Web of Science, Chinese Biomedical Literature Database, Wan-Fang Database and China National Knowledge Infrastructure. The database searches will not be restricted by date. Case-control studies, cohort studies or observational studies that compare aPLs between SLE patients with and without ON will be considered eligible. Articles published in English and Chinese will be included. Two researchers will independently perform the processes of study selection, data extraction and study quality assessment. The Newcastle-Ottawa Quality Assessment Scale will be used to assess the quality of the retrieved studies. A meta-analysis will be performed after screening the studies. Data will be analysed using ORs for dichotomous data.

Ethics And Dissemination: Ethical approval is not required because this systematic review will use published data. The systematic review will be electronically disseminated through a peer-reviewed publication or conference presentations.

Prospero Registration Number: CRD42020209637.
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http://dx.doi.org/10.1136/bmjopen-2020-046163DOI Listing
July 2021

Image analysis techniques to map pyramids, pyramid structure, glomerular distribution, and pathology in the intact human kidney from 3D MRI.

Am J Physiol Renal Physiol 2021 07 20. Epub 2021 Jul 20.

Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, United States.

Kidney pathologies are often highly heterogenous. To comprehensively understand kidney structure and pathology, it is critical to develop tool to map tissue microstructure in the context of the whole, intact organ. Magnetic resonance imaging (MRI) can provide a unique, three-dimensional (3D) view of the kidney and allows for measurement of multiple pathologic features. Here, we develop a platform to systematically render and map gross and microstructural features of the human kidney based on 3D MRI. These features include pyramid number and morphology, and associated medulla and cortex. in a subset of these kidneys, we also map individual glomeruli and glomerular volumes using cationic ferritin enhance-MRI to report intra-renal heterogeneity in glomerular density and size. Finally, we render and measure regions of nephron loss due to pathology and individual glomerular volumes in each pyramidal unit. This work provides new tools to comprehensively evaluate the kidney across scales, with potential applications in anatomical and physiological research, transplant allograft evaluation, biomarker development, biopsy guidance, and therapeutic monitoring. These image rendering and analysis tools could eventually impact the field of transplantation medicine to improve longevity matching of donor allografts and recipients and reduce discard rates through the direct assessment of donor kidneys.
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http://dx.doi.org/10.1152/ajprenal.00130.2021DOI Listing
July 2021

Collective energy-spectrum broadening of a proton beam in a gas-discharge plasma.

Phys Rev E 2021 Jun;103(6-1):063216

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

An accurate understanding of ion-beam transport in plasmas is crucial for applications in inertial fusion energy and high-energy-density physics. We present an experimental measurement on the energy spectrum of a proton beam at 270 keV propagating through a gas-discharge hydrogen plasma. We observe the energies of the beam protons changing as a function of the plasma density and spectrum broadening due to a collective beam-plasma interaction. Supported by linear theory and three-dimensional particle-in-cell simulations, we attribute this energy modulation to a two-stream instability excitation and further saturation by beam ion trapping in the wave. The widths of the energy spectrum from both experiment and simulation agree with the theory.
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http://dx.doi.org/10.1103/PhysRevE.103.063216DOI Listing
June 2021

Tumorigenic risk of Angelica sinensis on ER-positive breast cancer growth through ER-induced stemness in vitro and in vivo.

J Ethnopharmacol 2021 Jul 13:114415. Epub 2021 Jul 13.

School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong; Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen Virtual University Park, Nanshan, Shenzhen, China; Guangzhou University of Chinese Medicine, Daxuecheng Hongmian Road, Panyu District, Guangzhou, Guangdong Province, China. Electronic address:

Ethnopharmacological Relevance: The root of Angelica sinensis is widely used in traditional Chinese Medicine for relieving gynecological discomforts among the women population. However, its hormone-like effects have raised great attention on whether it is appropriate to use in breast cancer (BC) patients. Hence, this study aimed to investigate the tumorigenic effect of aqueous root extract of Angelica sinensis (AS) on estrogen receptor (ER)-positive BC growth through ER-induced stemness in-vitro and in-vivo.

Materials And Methods: The chemical composition of the AS was characterized by HPLC. Cell viability was detected by MTS assay. The in-vivo effect of AS was investigated by xenograft model, immunohistochemistry, histology, western blot, and self-renewal ability assay. Target verification was used by shRNA construction and transfection. Mammosphere formation assay was performed by flow cytometry.

Results: AS significantly promoted the proliferation of MCF-7 cells and inhibited the growth of MDA-MB-231 cells. AS significantly induced tumor growth (2.5 mg/kg) in xenograft models and however tamoxifen treatment significantly suppressed the AS-induced tumor growth. AS induced ERα expression in both in-vivo and in-vitro and promoted cancer stem cell activity in ER-positive BC.

Conclusion: AS shows the tumorigenic potential on ER-positive BC growth through ERα induced stemness, suggesting that the usage of AS is not recommended for BC in terms of safety measures.
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http://dx.doi.org/10.1016/j.jep.2021.114415DOI Listing
July 2021

MicroRNA-203-3p inhibits the proliferation, invasion and migration of pancreatic cancer cells by downregulating fibroblast growth factor 2.

Oncol Lett 2021 Aug 30;22(2):626. Epub 2021 Jun 30.

Department of Biliary and Pancreatic Surgery, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, Shanxi 030032, P.R. China.

Aberrant expression of fibroblast growth factor 2 (FGF2) is a major cause of poor prognosis in patients with pancreatic cancer. MicroRNA (miRNA/miR) miR-203-3p is a newly identified miRNA that can affect the biological behavior of tumors. The present study investigated the function of miR-203-3p on the regulation of FGF2 expression, and its role in pancreatic cancer cell proliferation, apoptosis, invasion and migration. Reverse transcription-quantitative PCR was used to determine the mRNA expression levels of miR-203-3p and FGF2 . Cell Counting Kit-8, Annexin V-APC/7-AAD double-staining Apoptosis Detection kit, wound healing and Transwell assays were used to determine the proliferation, apoptosis, migration and invasion of pancreatic cancer cells. The binding of miR-203-3p to FGF2 was assessed by a luciferase reporter assay. The results demonstrated that miR-203-3p expression was downregulated in pancreatic cancer cells. Gain- and loss-of-function experiments indicated that miR-203-3p inhibited the proliferation, migration and invasion, and promoted the apoptosis of pancreatic cancer cells . In addition, it was found that alteration of miR-203-3p abolished the promoting effects of FGF2 on pancreatic cancer cells. The present study demonstrated that FGF2 significantly promoted the proliferation, invasion and migration of pancreatic cancer cells. The mechanism involved the binding of miR-203-3p to the 3'-untranslated region of FGF2 mRNA, resulting in the downregulation of FGF2. In conclusion, miR-203-3p inhibited FGF2 expression, regulated the proliferation and inhibited the invasion and migration of pancreatic cancer cells.
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http://dx.doi.org/10.3892/ol.2021.12887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258624PMC
August 2021

Systems vaccinology of the BNT162b2 mRNA vaccine in humans.

Nature 2021 Jul 12. Epub 2021 Jul 12.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

The emergency use authorization of two mRNA vaccines in less than a year since the emergence of SARS-CoV-2 represents a landmark in vaccinology. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers vaccinated with the Pfizer-BioNTech mRNA vaccine. Vaccination resulted in robust production of neutralizing antibodies (nAbs) against the parent Wuhan strain and, to a lesser extent, the B.1.351 strain, and significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Booster vaccination stimulated a strikingly enhanced innate immune response compared to primary vaccination, evidenced by a greater: (i) frequency of CD14CD16 inflammatory monocytes; (ii) concentration of plasma IFN-g; (iii) transcriptional signature of innate antiviral immunity. Consistent with these observations, single-cell transcriptomics analysis demonstrated a ~100-fold increase in the frequency of a myeloid cell cluster, enriched in interferon-response transcription factors (TFs) and reduced in AP-1 TFs, following secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and nAb responses, and show that a monocyte-related signature correlates with the nAb response against the B.1.351 variant strain. Collectively, these data provide insights into immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response following booster immunization.
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http://dx.doi.org/10.1038/s41586-021-03791-xDOI Listing
July 2021

Aptamer-PROTAC Conjugates (APCs) for Tumor-specific Targeting in Breast Cancer.

Angew Chem Int Ed Engl 2021 Jul 9. Epub 2021 Jul 9.

Second Military Medical University, School of Pharmacy, 325 Guohe Road, 200433, Shanghai, CHINA.

Development of proteolysis targeting chimeras (PROTACs) is emerging as a promising strategy for targeted protein degradation. However, the drug development using the heterobifunctional PROTAC molecules is generally limited by poor membrane permeability, low in vivo efficacy and indiscriminate distribution. Herein an aptamer-PROTAC conjugation approach was developed as a novel strategy to improve the tumor-specific targeting ability and in vivo antitumor potency of conventional PROTACs. As proof of concept, the first aptamer-PROTAC conjugate (APC) was designed by conjugating a BET-targeting PROTAC to the nucleic acid aptamer AS1411 (AS) via a cleavable linker. Compared with the unmodified BET PROTAC, the designed molecule (APR) showed improved tumor targeting ability in a MCF-7 xenograft model, leading to enhanced in vivo BET degradation and antitumor potency and decreased toxicity. Thus, the APC strategy may pave the way for the design of tumor-specific targeting PROTACs and have broad applications in the development of PROTAC-based drugs.
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http://dx.doi.org/10.1002/anie.202107347DOI Listing
July 2021

Regulation of IFN-Is by MEF2D Promotes Inflammatory Homeostasis in Microglia.

J Inflamm Res 2021 29;14:2851-2863. Epub 2021 Jun 29.

Department of Experimental Surgery, Tangdu Hospital, Airforce Medical University of PLA, Xi'an, Shaanxi, 710038, People's Republic of China.

Background: Microglia play an essential role in the central nervous system immune response. The transcription factor myocyte enhancer factor-2 D (MEF2D) is known to participate in stress regulation in various cell types and is easily activated in microglia. MEF2D has been shown to transcriptionally regulate several cytokine genes in immune cells and directly regulates the inflammatory response, suggesting that MEF2D may act as a key stimulus response regulator of microglia and is involved in the regulation of brain microhomeostasis. To uncover the molecular mechanism of MEF2D in the inflammatory system, in the present study, we investigated the global effect of MEF2D in activated microglia and explored its potential regulatory network.

Methods: Experiments with a recombinant lentiviral vector containing either shRNA or overexpressing MEF2D were performed in the murine microglial BV2 cell line. Transcriptome sequencing and global gene expression patterns were analysed in lipopolysaccharide-stimulated shMEF2D BV2 cells. Pro- and anti-inflammatory factors were assessed by Western blot, qPCR or ELISA, and microglial activity was assessed by phagocytosis and morphologic analysis. The direct binding of MEF2D to the promoter region of interferon regulatory factor 7 (IRF7) was tested by ChIP-qPCR. The interferon-stimulated genes (ISGs) were tested by qPCR.

Results: MEF2D actively participated in the inflammatory response of BV2 microglial cells. Stably expressed RNAi-induced silencing of MEF2D disrupted the microglial immune balance in two ways: (1) the expression of proinflammatory factors, such as NLRP3, IL-1β, and iNOS was promoted; and (2) the type-I interferon signalling pathway was markedly inhibited by directly modulating IRF7 transcription. In contrast, overexpression of MEF2D significantly reduced the expression of NLRP3 and iNOS under LPS stimulation and alleviated the level of immune stress in microglia.

Conclusion: These findings demonstrate that MEF2D plays an important role in regulating inflammatory homeostasis partly through transcriptional regulation of the type-I interferon signalling pathway.
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http://dx.doi.org/10.2147/JIR.S307624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254549PMC
June 2021

Defect capturing and charging dynamics and their effects on magneto-transport of electrons in quantum wells.

J Phys Condens Matter 2021 Jul 27;33(39). Epub 2021 Jul 27.

Department of Nuclear Engineering and Radiological Sciences, University of Michigan, Ann Arbor, MI 48109, United States of America.

The calculated defect corrections to the polarization and dielectric functions for Bloch electrons in quantum wells are presented. These results were employed to derive the first two moment equations from the Boltzmann transport theory and then applied to explore the role played by defects on the magneto-transport of Bloch electrons. Additionally, we have derived analytically the inverse momentum-relaxation time and mobility tensor for Bloch electrons by making use of the screened defect-corrected polarization function. Based on quantum-statistical theory, we have investigated the defect capture and charging dynamics by employing a parameterized physics-based model for defects to obtain defect wave functions. Both capture and relaxation rates, as well as the density for captured Bloch electrons, were calculated self-consistently as functions of temperature, doping density and chosen defect parameters. By applying the energy-balance equation, the number of occupied energy levels and the chemical potential of defects were determined, with which the transition rate for defect capturing was obtained. By applying these results, the defect energy-relaxation, capture and escape rates, and Bloch-electron chemical potential were calculated self-consistently for a non-canonical subsystem of Bloch electrons. At the same time, the energy- and momentum-relaxation rates of Bloch electrons, as well as the current suppression factor, were also investigated quantitatively. By combining all these results, the temperature dependence of the Hall and longitudinal mobilities was presented for Bloch electrons in either single- or multi-quantum wells.
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http://dx.doi.org/10.1088/1361-648X/ac1239DOI Listing
July 2021

CCND1 copy number increase and cyclin D1 expression in acral melanoma: a comparative study of fluorescence in situ hybridization and immunohistochemistry in a Chinese cohort.

Diagn Pathol 2021 Jul 5;16(1):60. Epub 2021 Jul 5.

Department of Pathology, School of Basic Medical Sciences, Third Hospital, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.

Background: CCND1 copy number increase is characteristic of acral melanoma and is useful in distinguishing benign and malignant acral melanocytic lesions. Increase of the gene copy number may result in protein overexpression. This raises the possibility that detection of high expression of cyclin D1 by immunohistochemistry (IHC) may be used as a surrogate for direct evaluation of increase in the CCND1 gene copy number.

Methods: We examined increases in CCND1 copy number with fluorescence in situ hybridization (FISH), and examined cyclin D1 protein expression with IHC in 61 acral melanomas.

Results: Using FISH, 29 acral melanomas (29/61, 47.5%) showed increase in the CCND1 copy number, including 8 (8/61, 13.1%) which showed low-level increase in the CCND1 copy number and 21 (21/61, 34.4%) with high-level increase in the CCND1 copy number. By analysis of IHC, the median IHC score was 15% (range: 1-80%) in acral melanomas with no CCND1 copy number alteration. In acral melanomas with low-level CCND1 copy number increase, the median IHC score was 25% (range: 3-90%). In acral melanomas with high-level CCND1 copy number increase, the median IHC score was 60% (range: 1-95%). Comparing FISH and IHC, cyclin D1 protein expression level has no corelation with the CCND1 copy number in acral melanomas which have no CCND1 copy number alteration and low-level CCND1 copy number increase (P = 0.108). Cyclin D1 protein expression level correlated positively with CCND1 copy number in acral melanomas with high-level CCND1 copy number increase (P = 0.038). The sensitivity, specificity and positive predictive value of using cyclin D1 IHC to predict CCND1 FISH result was 72.4, 62.5 and 63.6%. Increase in CCND1 copy number was associated with Breslow thickness in invasive acral melanoma.

Conclusion: High-level increase in the CCND1 copy number can induce high cyclin D1 protein expression in acral melanomas. However low-level increase and normal CCND1 copy number have no obvious correlation with protein expression. Cyclin D1 IHC cannot serve as a surrogate for CCND1 FISH in acral melanomas.
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http://dx.doi.org/10.1186/s13000-021-01116-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259423PMC
July 2021

Synergy-based knee angle estimation using kinematics of thigh.

Gait Posture 2021 Jun 23;89:25-30. Epub 2021 Jun 23.

Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Shatin, Hong Kong, China. Electronic address:

Background: Lower limb assistive devices have been developed to help amputees or stroke patients. To precisely mimic the required function, researchers focused on how to estimate/predict the required knee angle for knee devices.

Research Question: The objective is to estimate the motion of the human knee joint during walking using the kinematics of wearer's thigh measured by a single Inertial Measurement Unit (IMU). The hypotheses are that the proposed method can precisely estimate knee angle and have good universality on different subjects, speeds and strides.

Method: 8 healthy subjects walked on the level ground at three different speeds. An IMU mounted on the thigh was employed to collect the kinematic information of the thigh including angular velocities and accelerations. A long short-term memory (LSTM) neural network model was adopted to model intra-limb synergy between the motion of thigh and the knee joint. Such that with the trained LSTM model, the knee angle can be precisely predicted.

Results: Compared with the existing studies, the proposed approach based on an LSTM model has better estimation performance. The average RMSE for eight subjects can be limited to 3.89°. The proposed method has speed and stride adaptability.

Significance: The proposed method is promising to generate a desired and harmonious knee trajectory in line with thigh motion for assistive robotic devices.
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http://dx.doi.org/10.1016/j.gaitpost.2021.06.015DOI Listing
June 2021

Decrease of choriocapillary vascular density measured by optical coherence tomography angiography in Vogt-Koyanagi-Harada disease.

Graefes Arch Clin Exp Ophthalmol 2021 Jul 3. Epub 2021 Jul 3.

Department of Ophthalmology, Peking Union Medical College Hospital (Dongdan Campus), Chinese Academy of Medical Sciences, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.

Purpose: Changes of choroidal circulation throughout the disease course of Vogt-Koyanagi-Harada (VKH) disease and the clinical significance remain unclear. Choriocapillary vascular density (CC VD) measured by optical coherence tomography angiography (OCTA) were compared in different disease stages of VKH and its correlation with other parameters was analyzed, aiming to explore their clinical relevance.

Methods: This is a retrospective case series. One hundred and fourteen VKH patients and 47 normal controls (NCs) were included. Patients were grouped into the acute uveitic, convalescent, and chronic recurrent stages (only anterior recurrent cases included), and OCTA images were obtained from VKH patients in these stages. Best corrected visual acuity (BCVA), CC VD, and subfoveal choroidal thickness (SFCT) were recorded and compared.

Results: CC VD in acute (58.26% ± 0.84%), convalescent (64.85% ± 0.33%), and chronic recurrent (62.78% ± 0.70%) stage of VKH patients were all significantly lower than that in NCs (66.37% ± 0.41%) (p < 0.001, p = 0.017, and p < 0.001, respectively). CC VD increased by 6.59% ± 0.91% with resolution of acute inflammation (p < 0.001) and decreased by 2.07% ± 0.74% during anterior uveitis relapse (p = 0.009). Patients with a positive history of anterior recurrence had lower CC VD (- 2.43% ± 0.75%, p = 0.003) in the convalescent stage than those without. CC VD was negatively correlated with logMAR BCVA in VKH (r =  - 0.261, p < 0.001).

Conclusion: CC VD was decreased in every stage of VKH. CC VD has the potential to reflect the status of uveitis and might be promising in monitoring the disease activity. OCTA is a convenient and straightforward tool to evaluate choroidal vascularity, and CC VD provides supplemental quantitative information of the choriocapillaris. Further studies are needed to explore the values of OCTA quantitative parameters in monitoring VKH progression, predicting visual prognosis, and guiding clinical decisions.
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http://dx.doi.org/10.1007/s00417-021-05238-5DOI Listing
July 2021

Solvent-Mediated Shell Dimension Reconstruction of [email protected] [email protected] Nanocrystals for Robust C1 and C2 Alcohol Electrocatalysis.

Small 2021 Jul 2:e2101428. Epub 2021 Jul 2.

College of Chemistry Chemical Engineering and Materials Science Soochow University, Suzhou, 215123, China.

The [email protected] structure dimension of the Pd-based nanocrystals deeply impacts their catalytic properties for C1 and C2 alcohol oxidation reactions. However, the precise simultaneous control on the synthesis of [email protected] nanocrystals with different shell dimensions is difficult, and most synthesis on Pd-based [email protected] nanocatalysts involves the surfactants participation by multiple steps, thus leads to limited catalytic properties. Herein, for the first time, a facile one-step surfactant-free strategy is developed for shell dimension reconstruction of [email protected] [email protected] nanocrystals by altering volume ratios of mixed solvents. The Pd-based sunflower-like (SL) and coral grass-like (CGL) nanocrystals are obtained with different 2D hexagonal nanosheet assembles and 3D network shells, respectively. Benefitting from the clean surface shell of 2D ultrathin nanosheets structure, high atom utilization efficiency, and robust electronic effect. The [email protected] SL achieves the ascendant methanol/ethanol/ethylene glycol oxidation reaction (MOR/EOR/EGOR) activities, much higher than Pd/C catalysts, as well as the improved antipoisoning ability. Notably, this one-step construction shell dimension of [email protected] [email protected] catalysts not only provide a significant reference for the improvement of surfactant-free synthetic routes, but also shed light on the advanced engineering on shell dimensions in [email protected] nanostructures for electrocatalysis and so forth.
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http://dx.doi.org/10.1002/smll.202101428DOI Listing
July 2021

The use of the posterior interosseous artery flap and anterolateral thigh flap for post-traumatic soft tissue reconstruction of the hand.

Medicine (Baltimore) 2021 Jul;100(26):e26517

Department of Hand and Foot Surgery, The Affiliated Hospital of Qingdao University, No. 1677 Wutaishan Road, Qingdao, Shandong, China.

Abstract: The purpose of this study was to examine the differences between the use of a posterior interosseous artery (PIA) flap and an anterolateral thigh (ALT) flap for post-traumatic, medium-sized soft tissue reconstruction of the hand based on flap characteristics, postoperative complications, and aesthetic outcomes.From October, 2010 to March, 2016, 62 patients undergoing soft tissue reconstruction of the hand with 30 PIA flaps and 32 ALT flaps were included in this study. The 62 patients were divided into the PIA flap group and the ALT flap group. The differences between the 2 groups were analyzed.The 62 patients included 52 males and 10 females, and the mean age at the time of surgery was 41 years. The flap failure rate was 13.3% (4/30) in the PIA flap group and 9.4% (3/32) in the ALT flap group. No significant differences in flap failure rate, recipient site complication rate, or donor site complication rate were observed between the 2 groups. However, the operative time (136 min vs 229 min) and aesthetic outcomes (flap bulk swelling, 0 cases vs 31 cases) were statistically significantly different.Both the pedicled PIA flap and the free ALT flap were comparable for the reconstruction of post-traumatic, medium-sized soft tissue defects of the hand according to the evaluated outcomes of postoperative complications. Based on the surgical characteristics of the flap and the evaluation of aesthetic outcomes, the pedicled PIA flap was significantly superior to the free ALT flap.
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http://dx.doi.org/10.1097/MD.0000000000026517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257892PMC
July 2021

Comparative Epigenomics Reveals Host Diversity of the Epigenomes and Their Effects on Differential Parasitism.

Front Cell Dev Biol 2021 11;9:681839. Epub 2021 Jun 11.

Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis/College of Veterinary Medicine, Jilin University, Changchun, China.

Comparative epigenomics provides new insights on evolutionary biology in relation with complex interactions between species and their environments. In the present study, we focus on deciphering the conservation and divergence of DNA methylomes during evolution. Whole-genome bisulfite sequencing and RNA-seq were performed on the two clades of species, in addition to whole-genome sequencing. We demonstrate that methylation patterns of sing-copy orthologous genes (SCOs) of the 12 species are host-related and can mirror known phylogenetic relationships. Among these SCOs, we identify a panel of genes exhibiting hyper-/hypo-methylated features in gene-bodies or respective promoters that play pivotal roles in transcriptome regulation. These hyper-/hypo-methylated SCOs are also of functional significance across developmental stages, as they are highly enriched species-specific and stage-specific expressed genes both in Ad and ML stages. We further identify a set of parasitism-related functional genes that exhibit host-related differential methylation and expression among those SCOs, including p53-like transcription factor and Cdc37 that are of functional significance for elucidating differential parasitology between the two clades of . This comparative epigenome study can help to decipher the environmental effects on differential adaptation and parasitism of the genus .
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http://dx.doi.org/10.3389/fcell.2021.681839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226246PMC
June 2021

Resveratrol Pretreatment Improved Heart Recovery Ability of Hyperglycemic Bone Marrow Stem Cells Transplantation in Diabetic Myocardial Infarction by Down-Regulating MicroRNA-34a.

Front Pharmacol 2021 20;12:632375. Epub 2021 Apr 20.

Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

To examine the effect of resveratrol (RSV) on bone marrow mesenchymal stem cells (BMSCs) under hyperglycemic conditions and on BMSCs transplantation in diabetic rats with myocardial infarction (MI). , BMSCs were isolated from 3-week-old male Sprague Dawley (SD) rats and cultured under hyperglycemic conditions for up to 28 days. Cell viability was analyzed by cell counting kit-8 (CCK-8) assays. The expression of miR-34a was measured by RT-qPCR. Western blotting was used to examine the protein expression of SIRT1, P21, P16, VEGF and HIF-1α. A senescence-associated β-galactosidase assay was used to examine the senescence level of each group. , a diabetes model was established by feeding rats a high-sugar and high-fat diet for 8 weeks, injecting the animals with streptozotocin (STZ) and continuing high-sugar and high-fat feeding for 4 additional weeks. Then, left anterior descending coronary artery (LAD) cessation was used to established the myocardial infarction (MI) models. Each group of rats was transplanted with differentially preconditioned BMSCs after myocardial infarction. Ultrasound was used to analyze cardiac function 1 and 3 weeks after the operation, and frozen heart sections were used for immunohistochemical analysis, Masson staining and CD31 measurement. In addition, ELISA analysis of serum cytokine levels was performed. This study showed that the viability of BMSCs cultured under hyperglycemic conditions was decreased, the cells became senescent. Besides, an obviously increased in the expression of miR-34a was detected. Moreover, RSV preconditioning reduced the expression of miR-34a in BMSCs after high glucose stimulation and rejuvenated BMSCs under hyperglycemic conditions. Further analysis showed that the transplantation of RSV-BMSCs were benefit to heart recovery following infarction in diabetic rats, promoted proangiogenic factor release and increased arteriole and capillary densities. RSV rejuvenated BMSCs after chronic hyperglycemia-induced senescence by interacting with miR-34a and optimized the therapeutic effect of BMSCs on diabetes with myocardial infarction.
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http://dx.doi.org/10.3389/fphar.2021.632375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223511PMC
April 2021

Single cell imaging reveals cisplatin regulating interactions between transcription (co)factors and DNA.

Chem Sci 2021 Feb 25;12(15):5419-5429. Epub 2021 Feb 25.

Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, National Centre for Mass Spectrometry in Beijing, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences Beijing 100190 People's Republic of China

Cisplatin is an extremely successful anticancer drug, and is commonly thought to target DNA. However, the way in which cisplatin-induced DNA lesions regulate interactions between transcription factors/cofactors and genomic DNA remains unclear. Herein, we developed a dual-modal microscopy imaging strategy to investigate, , the formation of ternary binding complexes of the transcription cofactor HMGB1 and transcription factor Smad3 with cisplatin crosslinked DNA in single cells. We utilized confocal microscopy imaging to map EYFP-fused HMGB1 and fluorescent dye-stained DNA in single cells, followed by the visualization of cisplatin using high spatial resolution (200-350 nm) time of flight secondary ion mass spectrometry (ToF-SIMS) imaging of the same cells. The superposition of the fluorescence and the mass spectrometry (MS) signals indicate the formation of HMGB1-Pt-DNA ternary complexes in the cells. More significantly, for the first time, similar integrated imaging revealed that the cisplatin lesions at Smad-binding elements, for example GGC(GC)/(CG) and AGAC, disrupted the interactions of Smad3 with DNA, which was evidenced by the remarkable reduction in the expression of Smad-specific luciferase reporters subjected to cisplatin treatment. This finding suggests that Smad3 and its related signalling pathway are most likely involved in the intracellular response to cisplatin induced DNA damage.
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http://dx.doi.org/10.1039/d0sc06760aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179581PMC
February 2021

Epigallocatechin gallate regulates inflammatory responses and new bone formation through Wnt/β-Catenin/COX-2 pathway in spondyloarthritis.

Int Immunopharmacol 2021 Jun 18;98:107869. Epub 2021 Jun 18.

Department of Rheumatology, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, PR China; Department of Rheumatology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, Fujian Province, PR China.

Objective: Spondyloarthritis (SpA) is mainly characterized by bone erosion, new bone formation, inflammation and potential disability. Epigallocatechin gallate (EGCG) has been proved to be closely related with the regulation of inflammation and bone metabolism. However, whether EGCG could improve SpA remains unclear.

Methods: SpA animal model was established using proteoglycan. Cell proliferation were measured by CCK-8 assay. The mRNA expression levels of genes were detected using qRT-PCR, protein levels were assessed via western blotting and immunohistochemistry. ELISA assay was performed to examined the inflammatory cytokine release. Lesions in spine cartilage tissues were observed using hematoxylin-eosin (HE) and Safranin O staining. Alkaline phosphatase (ALP) assay and Alizarin Red S staining was used to investigate osteoblast mineralization.

Results: We found that EGCG could inhibit inflammation and new bone formation in SpA mice. Besides, inflammatory factor expression and osteogenic differentiation in osteoblasts isolated from SpA mice were also decreased by EGCG. Further, EGCG treatment suppressed the activation of Wnt/β-Catenin/COX-2 pathway and the activator of this pathway partially reversed the effects of EGCG on inflammation and osteoblast differentiation.

Conclusions: EGCG repressed inflammatory responses and new bone formation, and further improved SpA through Wnt/β-Catenin/COX-2 pathway. Our findings may provide a new thought for the prevention and treatment of SpA.
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http://dx.doi.org/10.1016/j.intimp.2021.107869DOI Listing
June 2021

The effects of comfort care on the recovery quality of oral and maxillofacial surgery patients undergoing general anesthesia.

Am J Transl Res 2021 15;13(5):5003-5010. Epub 2021 May 15.

Department of Surgery and Anesthesiology, Ji'nan Stomatological Hospital (Binzhou Medical University Hospital) Ji'nan, Shandong Province, China.

Objective: To explore the effects of comfort care on the recovery quality of oral and maxillofacial surgery patients undergoing general anesthesia.

Methods: Ninety-eight oral and maxillofacial surgery patients undergoing general anesthesia were recruited for this prospective study and were then randomly divided into two groups. The patients in the experimental group (49 cases) underwent comfort care, and the patients in the control group (49 cases) underwent routine care. Several indexes, including the hemodynamic indexes, the analgesic dosages, the recovery times, the extubation complications, the recovery room indwelling times, the related complications, and the final satisfaction scores were recorded and compared between the two groups.

Results: Compared with the control group, the analgesic dosages and the recovery times in the experimental group were largely decreased (P<0.05), the occurrences of cough reactions during extubation were strongly reduced (P<0.05), and the recovery room indwelling times were also effectively shortened (P<0.05). In addition, the patients' hemodynamics in the experimental group were more stable during the recovery period (P<0.05), and the other complications, except for incision dehiscence, were significantly reduced (P<0.05), and the patient satisfaction scores were also much higher in the experimental group than they were in the control group (P<0.05).

Conclusion: The recovery times of oral and maxillofacial surgery patients undergoing general anesthesia were largely shortened, and the complications during the recovery period were effectively reduced with the help of the comfort care, so it is worthy of further research and clinical promotion.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205744PMC
May 2021

Hybrid network with difference degree and attention mechanism combined with radiomics (H-DARnet) for MVI prediction in HCC.

Magn Reson Imaging 2021 Jun 17;83:27-40. Epub 2021 Jun 17.

Department of Radiology, Henan Provincial People's Hospital, ZhengZhou, China.

MVI is a risk assessment factor related to hepatocellular carcinoma (HCC) recurrence after hepatectomy or liver transplantation. The goal of this paper is to study the preoperative diagnosis of microvascular invasion (MVI) by using a deep learning algorithm in non-contrast T2 weighted magnetic resonance imaging (MRI) images instead of pathological images. Herein, an ensemble learning algorithm named H-DARnet-based on the difference degree and attention mechanism, combined with radiomics, for MVI prediction-is proposed. Our hybrid network combines the fine-grained, high-level semantic, and radiomics features and exhibits a rich multilevel-feature architecture composed of global-local-prior knowledge with suitable complementarity. The total loss function comprises two regularization items--the triplet and the cross-entropy loss function--which are selected for the triplet network and SE-DenseNet, respectively. The hard triplet sample selection strategy for a triplet network and data augmentation for small-scale liver image datasets in convolutional neural network (CNN) training is indispensable. For 200 patch level test samples (135 positive samples and 65 negative samples), our method can obtain the best prediction results, the AUC, sensitivity, and specificity were 0.826, 79.5% and 73.8%, respectively. The experiment results show that MVI can be predicted by using MRI images, and the proposed method is better than other deep learning algorithms and hand-crafted feature algorithms. The proposed ensemble learning algorithm is proved to be an effective method for MVI prediction.
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http://dx.doi.org/10.1016/j.mri.2021.06.018DOI Listing
June 2021
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