Publications by authors named "Min Liu"

3,178 Publications

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Integrated Analyses Reveal the Multi-Omics and Prognostic Characteristics of ATP5B in Breast Cancer.

Front Genet 2021 28;12:652474. Epub 2021 May 28.

Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

The beta subunit of F1Fo-ATP synthase (ATP5B) has been demonstrated to play an essential role in tumor progression and metastasis. However, there has been no comprehensive pan-cancer multi-omics analysis of ATP5B, while the clinical relevance of ATP5B and its potential mechanism in regulating breast cancer are still poorly understood. In this study, we demonstrated that ATP5B has a higher frequency of amplification than deletion in most cancer types, and the copy number variation (CNV) of ATP5B was significantly positively correlated with its mRNA expression level. DNA methylation analysis across pan-cancer also revealed a strong correlation between ATP5B expression and epigenetic changes. We identified 6 significant methylation sites involved in the regulation of ATP5B expression. Tissue microarrays (TMA) from 129 breast cancer samples, integrated with multiple additional breast cancer dataset, were used to evaluate the ATP5B expression and its correlation with prognosis. Higher levels of ATP5B expression were consistently associated with a worse OS in all datasets, and Cox regression analysis suggested that ATP5B expression was an independent prognostic factor. Gene enrichment analysis indicated that the gene signatures of DNA damage recognition, the E-cadherin nascent pathway and the PLK1 pathway were enriched in ATP5B-high patients. Moreover, somatic mutation analysis showed that a significant different mutation frequency of CDH1 and ADAMTSL3 could be observed between the ATP5B-high and ATP5B-low groups. In conclusion, this study reveals novel significance regarding the genetic characteristics and clinical value of ATP5B highlighted in predicting the outcome of breast cancer patients.
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http://dx.doi.org/10.3389/fgene.2021.652474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194306PMC
May 2021

A novel nomogram for predicting locoregional recurrence risk in breast cancer patients treated with neoadjuvant chemotherapy and mastectomy.

Radiother Oncol 2021 Jun 10. Epub 2021 Jun 10.

Department of Radiation Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China. Electronic address:

Background: This study aimed to establish a nomogram for predicting locoregional recurrence (LRR) in breast cancer patients treated with neoadjuvant chemotherapy (NAC) and mastectomy.

Methods: A total of 2368 patients who received NAC and mastectomy between 2000 and 2014 from 12 grade A tertiary hospitals in China were analyzed retrospectively. The nomogram was developed based on the patients treated in three cancer hospitals (training set, n=1629) and validated based on patients from the other nine general hospitals (validation set, n=739). Factors identified from Fine and Gray's competing risk analysis were used to establish the nomogram. The predictive performance of the nomogram model was compared with the cTNM stage, ypTNM stage, and the Neo-Bioscore model by using the area under the time dependent receiver operating characteristic curves (tAUC), calibration curve, and decision curve analysis (DCA).

Results: The nomogram incorporated six risk factors derived from multivariable analysis of the training set including age, ypT stage, ypN stage, lymph node ratio, postmastectomy radiotherapy, and endocrine therapy. In the training set, the AUC of the nomogram was 0.792, which was higher than the values of the cTNM stage (0.582), ypTNM stage (0.737), and the Neo-Bioscore prognosis model (0.658). In the validation set, the AUC of the cTNM (0.619); ypTNM (0.636); and Neo-Bioscore staging system (0.584) were also significantly lower than the AUC of the nomogram (0.705). Both in the training and validation sets, the calibration curve showed good agreement between the nomogram-based predictions and the actual observations CONCLUSION: The novel nomogram provides a more accurate evaluation of LRR for breast cancer patients treated with NAC and mastectomy.
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http://dx.doi.org/10.1016/j.radonc.2021.06.015DOI Listing
June 2021

Genomic insights into molecular adaptation to intertidal environments in the mangrove Aegiceras corniculatum.

New Phytol 2021 Jun 11. Epub 2021 Jun 11.

State Key Laboratory of Biocontrol, Guangdong Key Lab of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.

Mangroves have colonized extreme intertidal environments characterized by high salinity, hypoxia, and other abiotic stresses. Aegiceras corniculatum, a pioneer mangrove species that evolved two specialized adaptive traits (salt secretion and crypto-vivipary), is an attractive ecological model to investigate molecular mechanisms underlying adaptation to intertidal environments. We de novo assembled a high-quality reference genome of A. corniculatum and performed comparative genomic and transcriptomic analyses to investigate molecular mechanisms underlying adaptation to intertidal environments. We provide evidence that A. corniculatum experienced a whole-genome duplication (WGD) event around 35 million years ago. We inferred that maintenance of cellular environmental homeostasis is an important adaptive process in A. corniculatum. The 14-3-3 and H -ATPase protein-coding genes, essential for the salt homeostasis, were preferentially retained after the recent WGD event. Using comparative transcriptomics, we showed that genes up-regulated under high-salt conditions were involved in salt transport and ROS scavenging. We also found that all homologs of DELAY OF GERMINATION1 (DOG1) lost their heme-binding ability in A. corniculatum, which may contribute to crypto-vivipary. Our study provides insights into the genomic correlates of phenotypic adaptation to intertidal environments. It could contribute not only within the genomics community, but also to the field of plant evolution.
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http://dx.doi.org/10.1111/nph.17551DOI Listing
June 2021

Dual Inorganic Sacrificial Template Synthesis of Hierarchically Porous Carbon with Specific N Sites for Efficient Oxygen Reduction.

ACS Appl Mater Interfaces 2021 Jun 11. Epub 2021 Jun 11.

School of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan, China.

It is still a challenge to achieve efficiently controlled preparation of functional oxygen reduction reaction (ORR) carbon electrocatalysts with multi-preferred structures (hierarchically porous networks and specific carbon-nitrogen bonds) from carbohydrate-containing small molecules via simple one-step pyrolysis. Based on the step-by-step spontaneous gas-foaming strategy, we successfully prepare 3D hierarchically porous networks with tunable N sites (N/N ≈ 1:1) by pyrolyzing diverse carbohydrates (glucose, maltose, and cyclodextrin) using nonmetal-metal dual inorganic sacrificial templates. In situ evaporation templates can simplify the procedure of the experiments and avoid the active site loss compared with traditional hard templates. Crucially, dual inorganic sacrificial templates can induce abundant defects and microscopic pore structures (the specific surface area increased from 922.403 to 1898.792 m·g) and tunable N sites compared with single nonmetal sacrificial templates. The regulatory mechanism of dual inorganic templates on N sites (N/N ≈ 1:1) is independent of the polymeric state of carbohydrate precursors or even the carbonization condition of the pyrolysis process. A series of carbon materials prepared by this strategy all have ORR-preferred structures and exhibit low ORR overpotentials compared with Pt/C. For instance, the Zn-air battery with βCD-DSC-950-1 exhibits an open-circuit potential of 1.51 V and a peak power density of 180.89 mW·cm, higher than those of Pt/C (1.47 V, 174.94 mW·cm). In general, the conversion of carbohydrate-containing small molecules to functional carbon materials provides a new strategy for the development of carbonaceous electrocatalysts.
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http://dx.doi.org/10.1021/acsami.1c04942DOI Listing
June 2021

Phosphorylation of TRIP13 at Y56 induces Radiation Resistance but Sensitizes Head and Neck Cancer to Cetuximab.

Mol Ther 2021 Jun 7. Epub 2021 Jun 7.

Department of Periodontics and Oral Medicine, School of Dentistry; Pathology, Medical School. Electronic address:

Radiation therapy, a mainstay of treatment for head and neck cancer, is not always curative due to the development of treatment resistance; additionally, multi-institutional trials have questioned the efficacy of concurrent radiation with cetuximab, the EGFR inhibitor. We unraveled a mechanism for radiation resistance; radiation induces EGFR, which phosphorylates TRIP13 on tyrosine 56. Phospho-TRIP13 promotes non-homologous end joining (NHEJ) repair to induce radiation resistance. NHEJ is the main repair pathway for radiation-induced DNA damage. Tumors expressing high TRIP13 do not respond to radiation but are sensitive to cetuximab or cetuximab combined with radiation. Suppression of phosphorylation of TRIP13 at Y56 abrogates these effects. These findings show that EGFR-mediated phosphorylation of TRIP13 at Y56 is a vital mechanism of radiation resistance. Notably, TRIP13-pY56 could be used to predict response to radiation or cetuximab and could be explored as an actionable target.
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http://dx.doi.org/10.1016/j.ymthe.2021.06.009DOI Listing
June 2021

CLEC14A protects against podocyte injury in mice with adriamycin nephropathy.

FASEB J 2021 Jul;35(7):e21711

Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China.

Podocyte injury is a major determinant of focal segmental glomerular sclerosis (FSGS) and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance for the treatment of FSGS. CLEC14A is a single-pass transmembrane glycoprotein belonging to the vascular expressed C-type lectin family. CLEC14A is found to be expressed in vascular endothelial cells during embryogenesis and is also implicated in tumor angiogenesis. However, the current understanding of the biological functions of CLEC14A in podocyte is very limited. In this study, we found that CLEC14A was expressed in podocyte and protected against podocyte injury in mice with Adriamycin (ADR)-induced FSGS. First, we observed that CLEC14A was downregulated in mice with ADR nephropathy and renal biopsies from individuals with FSGS and other forms of podocytopathies. Moreover, CLEC14A deficiency exacerbated podocyte injury and proteinuria in mice with ADR nephropathy accompanied by enhanced inflammatory cell infiltration and inflammatory responses. In vitro, overexpression of CLEC14A in podocyte had pleiotropic protective actions, including anti-inflammatory and anti-apoptosis effects. Mechanistically, CLEC14A inhibited high-mobility group box 1 protein (HMGB1) release, at least in part by directly binding HMGB1, and suppressed HMGB1-mediated signaling, including NF-κB signaling and early growth response protein 1 (EGR1) signaling. Taken together, our findings provide new insights into the pivotal role of CLEC14A in maintaining podocyte function, indicating that CLEC14A may be an innovative therapeutic target in FSGS.
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http://dx.doi.org/10.1096/fj.202100283RDOI Listing
July 2021

Enhanced Recovery After Surgery Impact on the Systemic Inflammatory Response of Patients Following Gynecological Oncology Surgery: A Prospective Randomized Study.

Cancer Manag Res 2021 1;13:4383-4392. Epub 2021 Jun 1.

Department of Obstetrics and Gynecology, Qilu hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.

Objective: Enhanced recovery after surgery (ERAS) protocol has widely gained acceptance in gynecological surgery. Its safety and efficacy should be evaluated fully via well-designed, randomized, control trials. The main objective of our study is to compare the ERAS protocol with the conventional perioperative care program after gynecological oncology. Furthermore, the secondary objectives of our study are the identification of markers that allow us to evaluate the effectiveness of the application of ERAS elements in the modulation of the body's response to surgical stress.

Methods: Patients with gynecological tumors indicated for surgery were randomly assigned to either the ERAS group or the conventional group. The ERAS protocol included short fasting time, fluid restriction, early oral feeding, reduced opioid consumption and immediate mobilization after surgery. The primary endpoint was the reduction of hospital stay in the ERAS group. The day of first flatus, postoperative nausea and vomiting (PONV), maximum pain score by the visual analogue scale (VAS) and complication, readmission rate, reoperation rate, postoperative mortality, total hospital cost and systemic inflammatory response (SIR) were secondary endpoints.

Results: A total of 130 patients in gynecological tumor surgery were enrolled (ERAS = 65, conventional = 65). The ERAS group had faster bowel function recovery, significantly less pain, less PONV, shorter hospital stay, and less total hospital costs. SIR markers were estimated and screened out that postoperative platelet, neutrophil-lymphocyte-ratio (NLR) and platelet-lymphocyte-ratio (PLR) were significantly lower in ERAS groups compared to conventional groups.

Conclusion: The implementation of ERAS protocol is safe and enhances postoperative recovery after gynecological oncology surgery. We firstly reveal the beneficial effect of ERAS protocols on the alleviation of postoperative SIR, which is a reflection of the magnitude of surgical trauma. Postoperative platelet, NLR or PLR could be the novel and inexpensive markers to assess how ERAS protocols modulate gynecological oncology surgery.

Trial Registration: The trial was registered in ClinicalTrials.gov (NCT03629626).
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http://dx.doi.org/10.2147/CMAR.S294718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179735PMC
June 2021

A phase I study of the safety and activity of K-001 in patients with advanced pancreatic ductal adenocarcinoma.

BMC Cancer 2021 Jun 7;21(1):672. Epub 2021 Jun 7.

Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that lack of effective therapeutic drugs. K-001 is an oral antitumor drug made from active ingredients of marine microorganisms. The current study aimed to evaluate safety and antitumor activity of K-001 in patients with advanced PDAC.

Methods: In this phase I, open-label trial, patients with advanced PDAC were recruited to a dose-escalation study in a standard 3 + 3 design. K-001 was administered twice daily in four-week cycles, and dose escalation from 1350 mg to 2160 mg was evaluated twice daily. Physical examination and laboratory tests were done at screening and then weekly. The safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of K-001 were assessed while tumor response was estimated by Response Evaluation Criteria in Solid Tumor (RECIST).

Results: Eighteen patients with advanced PDAC were screened, and twelve eligible patients were analyzed in the study. No DLT was observed. Totally, 47 adverse events (AEs) presented, and 14 drug-related AEs were reported in 7 patients, including 8 grade 1 events (57.1%) and 6 grade 2 events (42.9%). There was no grade 3 or 4 drug-related AE. In these 14 drug-related AEs, the most frequent ones were dyspepsia (21.4%), followed by flatulence, constipation, and hemorrhoid bleeding (above 10% of each). Among all 12 patients, 10 patients (83.3%) maintained stable disease (SD), and 2 patients (16.7%) had progressive disease (PD). The objective response rate (ORR) was 0% and the disease control rate (DCR) was 83.3%.

Conclusions: K-001 manifests satisfactory safety and tolerability, as well as meaningful antitumor activity in advanced PDAC patients. Further evaluation of K-001 in phase II/III appears warranted.

Trial Registration: NCT02720666 . Registered 28 Match 2016 - Retrospectively registered.
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http://dx.doi.org/10.1186/s12885-021-08375-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183060PMC
June 2021

Gene polymorphism-related differences in the outcomes of abiraterone for prostate cancer: a systematic overview.

Am J Cancer Res 2021 15;11(5):1873-1894. Epub 2021 May 15.

Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021, China.

Numerous prostate cancer (PC) associated genes have been reported in previous genome-wide association studies. Elucidation of prostate cancer pharmacogenomics have enhanced studies into the impact of germline genetic changes on treatment, in addition to evaluating related genomic alterations and biomarkers in prostate tumor tissues. Currently, Abiraterone (Abi) is used as one of the therapeutic options for PC. In this article, germline variants that have been associated with responses to Abi in patients with advanced PC are summarized. These include biomarker genes such as and that are involved in homologous recombination, as well as in gene expression mutations in important signaling pathways, such as WNT and Abi metabolic pathways.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167691PMC
May 2021

LuxQ-LuxU-LuxO pathway regulates biofilm formation by Vibrio parahaemolyticus.

Microbiol Res 2021 May 27;250:126791. Epub 2021 May 27.

Department of Marine Biology, College of Oceanography, Hohai University, Nanjing, Jiangsu, China. Electronic address:

Vibrio parahaemolyticus, a common foodborne pathogen, can form biofilms for survival in various environments and for bacterial transmission. Lux systems in Vibrio species are the typical two-component signal transduction systems, which have been demonstrated to contribute to various phenotypes; however, the functions of each homolog of the Lux system in V. parahaemolyticus in the regulation of biofilm formation remain largely unknown. In this study, we first showed that LuxQ, LuxU, and LuxO are essential for controlling biofilm formation by V. parahaemolyticus, through gene knockout studies. We also found that they acted in the same signaling pathway and their deletion mutants exhibited a similar level of biofilm formation. Furthermore, site-directed mutagenesis revealed that the conserved residues for phosphorylation in LuxQ (D784), LuxU (H56) and LuxO (D47) were critical for their regulatory functions on biofilm formation. Phos-tag™ sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the phosphorylation of LuxU and LuxQ in vivo. Finally, qPCR analysis displayed that the three mutants had a significant decrease in the transcription level of cps loci and cpsQ compared with the wild type strain, which is consistent with the observed phenotype of biofilm formation. Therefore, we propose that LuxQ and its downstream factors LuxU and LuxO function in the same signaling cascade to control biofilm formation by regulating the expression of cpsQ and cps loci. The results of this study provide new data regarding the role of the LuxQ-LuxU-LuxO pathway in biofilm formation by V. parahaemolyticus and help further understand the complex regulatory functions of Lux pathways.
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http://dx.doi.org/10.1016/j.micres.2021.126791DOI Listing
May 2021

Generation and characterization of three induced pluripotent stem cell lines (NUIGi047-A, NUIGi047-B, NUIGi047-C) from a 7-year-old healthy Caucasian male.

Stem Cell Res 2021 May 12;53:102389. Epub 2021 May 12.

Regenerative Medicine Institute, School of Medicine, National University of Ireland (NUI) Galway, Ireland; National Children's Research Centre, Children's Health Ireland at Crumlin, Dublin 12, Ireland. Electronic address:

We report the generation of three human induced pluripotent stem cell (hiPSC) lines (NUIGi047-A, NUIGi047-B, NUIGi047-C) from a healthy 7-year-old boy using non-integrational Sendai re-programming method expressing OCT4, SOX2, KLF4 and C-MYC. Stem cell characterization was confirmed through morphology, immunofluorescence staining and RT-qPCR. Differentiation potential in vitro was demonstrated to all three germ layers with STR lineage verification and normal molecular karyotyping through the process of re-programming.
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http://dx.doi.org/10.1016/j.scr.2021.102389DOI Listing
May 2021

Upregulation of LINC00659 expression predicts a poor prognosis and promotes migration and invasion of gastric cancer cells.

Oncol Lett 2021 Jul 24;22(1):557. Epub 2021 May 24.

Department of Medical Genetics and Developmental Biology, Medical School of Southeast University, Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing, Jiangsu 210009, P.R. China.

Long non-coding RNAs (lncRNAs) serve an important role in the progression of cancer. LINC00659 was recently identified as a novel oncogenic lncRNA involved in colon cancer cell proliferation via modulating the cell cycle. However, the function of LINC00659 in other types of cancer, especially in gastric cancer (GC), remains unknown. In the present study, bioinformatics analysis combined with cell experiments were performed to explore the function of LINC00659 in GC. It was revealed that LINC00659 expression was significantly upregulated in GC tissues and cell lines. Increased levels of LINC00659 were associated with advanced tumor stage and unfavorable prognosis of patients with GC. Additionally, upregulated LINC00659 expression promoted the migration and invasion of GC cells. Further analysis using a bioinformatics method revealed that matrix metalloproteinase 15 and IQ motif-containing GTPase activating protein 3 were potential downstream targets of LINC00659 involved in tumor metastasis, although the precise underlying mechanism requires further exploration.
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http://dx.doi.org/10.3892/ol.2021.12818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161466PMC
July 2021

Exosomal circ-BRWD1 contributes to osteoarthritis development through the modulation of miR-1277/TRAF6 axis.

Arthritis Res Ther 2021 Jun 3;23(1):159. Epub 2021 Jun 3.

Department of Orthopaedics, Second Hospital of Shanxi Medical University, No.2 Hospital, Shanxi Medical University, 382 Wuyi Road, Xinghualing District, Taiyuan City, Shanxi Province, China.

Background: Circular RNAs (circRNAs) can act as vital players in osteoarthritis (OA). However, the roles of circRNAs in OA remain obscure. Herein, we explored the roles of exosomal circRNA bromodomain and WD repeat domain containing 1(circ-BRWD1) in OA pathology.

Methods: In vitro model of OA was constructed by treating CHON-001 cells with interleukin-1β (IL-1β). Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used for circ-BRWD1, BRWD, miR-1277, and TNF receptor-associated factor 6 (TRAF6) levels. RNase R assay was conducted for the feature of circ-BRWD1. Transmission electron microscopy (TEM) was employed to analyze the morphology of exosomes. Western blot assay was performed for protein levels. Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis, and 5-Ethynyl-2'-deoxyuridine (EDU) assay were adopted for cell viability, apoptosis, and proliferation, respectively. Enzyme-linked immunosorbent assay (ELISA) was carried out for the concentrations of interleukin-6 (IL-6) and interleukin-8 (IL-8). Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to analyze the interaction between miR-1277 and circ-BRWD1 or TRAF6.

Results: Circ-BRWD1 was increased in OA cartilage tissues, IL-1β-treated CHON-001 cells, and the exosomes derived from IL-1β-treated CHON-001 cells. Exosome treatment elevated circ-BRWD1 level, while exosome blocker reduced circ-BRWD1 level in IL-1β-treated CHON-001 cells. Silencing of circ-BRWD1 promoted cell viability and proliferation and repressed apoptosis, inflammation, and extracellular matrix (ECM) degradation in IL-1β-stimulated CHON-001 cells. For mechanism analysis, circ-BRWD1 could serve as the sponge for miR-1277 to positively regulate TRAF6 expression. Moreover, miR-1277 inhibition ameliorated the effects of circ-BRWD1 knockdown on IL-1β-mediated CHON-001 cell damage. Additionally, miR-1277 overexpression relieved IL-1β-induced CHON-001 cell injury, while TRAF6 elevation restored the impact.

Conclusion: Exosomal circ-BRWD1 promoted IL-1β-induced CHON-001 cell progression by regulating miR-1277/TRAF6 axis.
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http://dx.doi.org/10.1186/s13075-021-02541-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173917PMC
June 2021

Correlation between lncRNA H19 rs2839698 polymorphism and susceptibility to NK / T cell lymphoma in Chinese population.

J BUON 2021 Mar-Apr;26(2):587-591

Department of Hematology, Jingzhou Central Hospital, Institute of Hematology, Yangtze University, Jingzhou, China.

Purpose: Gene polymorphism has a potential influence cancer susceptibility. This study aimed to explore the role of lncRNA H19 rs2839698 polymorphism and its genotypes in influencing NK/T cell lymphoma (NKTCL) in Chinese population.

Methods: NKTCL patients (n=573) and healthy participants (n=688) were recruited. Their blood samples were collected for detecting H19 rs2839698 polymorphism and its genotypes using PCR-RFLP. The correlations of H19 rs2839698 polymorphism with NKTCL susceptibility and pathological indexes were analyzed by logistic regression analysis.

Results: No significant differences in age, body mass index (BMI), smoking, drinking and family history of cancer were detected between NKTCL patients and healthy participants. Hypertension and diabetes were statistically significant between groups. H19 rs2839698 polymorphism and its genotypes were correlated with NKTCL susceptibility. Moreover, compared with NKTCL patients carrying GG allele, patients carrying AG, AA and AG+AA alleles had more advanced tumor stage and higher incidence of EBV(+) and original involvement of non-paranasal structure.

Conclusions: LncRNA H19 rs2839698 polymorphism and its genotypes are correlated with NKTCL susceptibility.
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June 2021

Efficacy of postoperative radiotherapy combined with taxol+carboplatin chemotherapy regimens in the treatment of high-risk early-stage endometrial cancer.

J BUON 2021 Mar-Apr;26(2):561-568

Department of Oncology, Yanan University Affiliated Hospital, Yanan, China.

Purpose: To compare the efficacy and safety of postoperative extrapelvic irradiation intensity-modulated radiotherapy (IMRT)+concurrent chemotherapy and vaginal brachytherapy (VBT)+concurrent chemotherapy in the treatment of patients with high-risk early-stage endometrial cancer, and analyze the influencing factors for the prognosis of patients.

Methods: A total of 126 patients with high-risk stage Ic-IIa endometrial cancer were divided into extrapelvic irradiation IMRT + concurrent taxol+carboplatin (TC) chemotherapy group (IMRT group, n=63) and VBT + concurrent TC chemotherapy group (VBT group, n=63). Then, the efficacy and the incidence rate of adverse reactions were compared between the two groups of patients. Additionally, the possible influencing factors for the prognosis of patients were analyzed.

Results: In the Functional Assessment of Cancer Therapy-General Version 4 (FACT-G-V4) scale for the quality of life of patients, the scores of physiological status, social/family status, emotional status and functional status were dramatically higher in the VBT group than in the IMRT group at 3 months after treatment. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 87.3% and 73.0% in the IMRT group and 82.5% and 66.7% in the VBT group, respectively. Furthermore, advanced age, lower uterine segment involvement and anemia before treatment were independent risk factors for tumor progression in patients with endometrial cancer.

Conclusions: For patients with high-risk early-stage endometrial cancer, postoperative VBT + concurrent TC chemotherapy has similar efficacy to postoperative extrapelvic irradiation IMRT + concurrent TC chemotherapy, but patients receiving the former have fewer adverse reactions and high quality of life. Advanced age, lower uterine segment involvement and anemia before treatment are independent risk factors affecting tumor progression in such patients.
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June 2021

Investigation on Crystallization and Magnetic Properties of (Nd, Pr, Ce)FeB/α-Fe Nanocomposite Magnets by Microwave Annealing Treatment.

Materials (Basel) 2021 May 22;14(11). Epub 2021 May 22.

Department Key Laboratory for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083, China.

In the present work, the structures and magnetic properties of (Nd, Pr, Ce) FeB/α-Fe nanocomposite magnets were thoroughly investigated. The microwave annealing was applied to achieve a uniform heating effect and uniform grains. Microwave annealing is more favorable to obtain α-Fe phase than conventional annealing, which leads to the enhanced coercivity of hysteresis loops. The coercivity of nanocomposite magnets was 245 kA/m after annealing at 2000 W for 10 min.
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http://dx.doi.org/10.3390/ma14112739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196883PMC
May 2021

The Association between Influenza Vaccination and COVID-19 and Its Outcomes: A Systematic Review and Meta-Analysis of Observational Studies.

Vaccines (Basel) 2021 May 20;9(5). Epub 2021 May 20.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.

Influenza could circulate in parallel with COVID-19. In the context of COVID-19, some studies observed inverse associations between influenza vaccination and SARS-CoV-2 infection and clinical outcomes, while others did not. We conducted a meta-analysis to assess the association between influenza vaccination and SARS-CoV-2 infection and clinical outcomes, aiming to provide evidence for COVID-19 prevention and vaccination promotion. We searched four databases from inception to 10 March, 2021. Random effects and fixed effects models were used to pool odds ratios (ORs) and adjusted estimates with 95% confidence intervals (CIs). We used funnel plots to evaluate the publication bias, I2 statistics to evaluate the heterogeneity, and conducted subgroup analyses. Sixteen observational studies involving 290,327 participants were included. Influenza vaccination was associated with a lower risk of SARS-CoV-2 infection (pooled adjusted OR: 0.86, 95%CI: 0.81-0.91), while not significantly associated with adverse outcomes (intensive care: adjusted OR 0.63, 95%CI: 0.22-1.81; hospitalization: adjusted OR 0.74, 95%CI: 0.51-1.06; mortality: adjusted OR 0.89, 95%CI: 0.73-1.09). Our findings suggest that influenza vaccination is associated with a lower risk of SARS-CoV-2 infection. It is crucial for policy makers to implement strategies on influenza vaccination, for it may also have benefits for COVID-19 prevention.
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http://dx.doi.org/10.3390/vaccines9050529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161076PMC
May 2021

Ultrapermeable Composite Membranes Enhanced Via Doping with Amorphous MOF Nanosheets.

ACS Cent Sci 2021 Apr 25;7(4):671-680. Epub 2021 Mar 25.

Department of Chemical Engineering, The University of Melbourne, Parkville, VIC 3010, Australia.

Thin-film composite (TFC) polymeric membranes have attracted increasing interest to meet the demands of industrial gas separation. However, the development of high-performance TFC membranes within their current configuration faces two key challenges: (i) the thickness-dependent gas permeability of polymeric materials (mainly poly(dimethylsiloxane) (PDMS)) and (ii) the geometric restriction effect due to the limited pore accessibility of the underlying porous substrate. Here we demonstrate that the incorporation of trace amounts (∼1.8 wt %) of amorphous metal-organic framework (MOF) nanosheets into the gutter layer of TFC assemblies can simultaneously address these two limitations by the creation of rapid, transmembrane gas diffusion pathways. The resultant PDMS&MOF membrane displayed excellent CO permeance of 10450 GPU and CO/N selectivity of 9.1. Leveraging this strategy, we successfully fabricate a novel TFC membrane, consisting of a PDMS&MOF gutter and an ultrathin (∼54 nm) poly(ethylene glycol) top selective layer via surface-initiated atom transfer radical polymerization. The complete TFC membrane exhibits excellent processability and remarkable CO/N separation performance (1990 GPU with a CO/N ideal selectivity of 39). This study reveals a strategy for the design and fabrication of a new TFC membrane system with unprecedented gas-separation performance.
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http://dx.doi.org/10.1021/acscentsci.0c01711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155479PMC
April 2021

Loss of Setd2 associates with aberrant microRNA expression and contributes to inflammatory bowel disease progression in mice.

Genomics 2021 May 28;113(4):2441-2454. Epub 2021 May 28.

Shanghai Mental Health Center, School of Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai 200030, China. Electronic address:

Both SETD2-mediated H3K36me3 and miRNAs play critical epigenetic roles in inflammatory bowel disease (IBD) and involve in the dysfunctional intestinal barrier. However, little is known about cross-talk between these two types of regulators in IBD progression. We performed small RNA sequencing of Setd2 epithelium-specific knockout mice (Setd2) and wild-type controls, both with DSS-induced colitis, and designed a framework for integrative analysis. Firstly, we integrated the downloaded ChIP-seq data with miRNA expression profiles and identified a significant intersection of pre-miRNA expression and H3K36me3 modification. A significant inverse correlation was detected between changes of H3K36me3 modification and expression of the 171 peak-covered miRNAs. We further integrated RNA-seq data with predicted miRNA targets to screen negatively regulated miRNA-mRNA pairs and found the H3K36me3-associated differentially expressed microRNAs significantly enriched in cell-cell junction and signaling pathways. Using network analysis, we identified ten hub miRNAs, among which six are H3K36me3-associated, suggesting therapeutic targets for IBD patients with SETD2-deficiency.
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http://dx.doi.org/10.1016/j.ygeno.2021.05.034DOI Listing
May 2021

Integrated Strategy of Network Pharmacological Prediction and Experimental Validation Elucidate Possible Mechanism of Bu-Yang Herbs in Treating Postmenopausal Osteoporosis via ESR1.

Front Pharmacol 2021 11;12:654714. Epub 2021 May 11.

Graduated School, Jiangxi University of Chinese Medicine, Nanchang, China.

Postmenopausal osteoporosis (PMOP) is a type of bone metabolism disease-related to estrogen deficiency with an increasing incidence. Traditional Chinese (TCM) has always been used and showed effectiveness in treating PMOP. In the current study, Bu-Yang herbs were considered to be the most frequently used and efficient TCM herbs in PMOP treatment. However, chemical and pharmacological profiles were not elucidated. Network pharmacology was conducted on representative Bu-Yang herbs (Yin-Yang-Huo. Du-Zhong, Bu-Gu-Zhi, Tu-Si-Zi) to investigate the mechanism of Bu-Yang herbs on PMOP. Chemical compounds, potential targets, and disease related genes were available from the corresponding database. Results showed that Bu-Yang herbs could interact with ESR1 and estrogen signaling pathways. For further validation, the Bu-Yang decoction (BYD), formula consisted of the above-mentioned 4 Bu-Yang herbs was presented for experimental validation. , BYD significantly reversed ovariectomy (OVX)-induced osteoporosis progress in a dose-dependent manner by up-regulation of bone mineral density and amelioration of bone microarchitecture. , BYD dramatically improved the proliferation and mineral nodules formation of osteoblasts. Both and results illustrated that the phenotype change induced by BYD is correlated with up-regulated of ESR1 and activation of the β-catenin pathway. Meanwhile, inhibition of ESR1 by ICI182, 780 blocked the osteogenic phenotype and β-catenin pathway activation induced by BYD. In conclusion, the current study suggested that Bu-Yang herbs are the most useful TCM herbs in treating PMOP. Furthermore, the integrated strategy of network pharmacology prediction with experimental validation suggested that BYD exerted its anti-PMOP via ESR1 and the downstream mechanism might be activation of the β-catenin signaling pathway.
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http://dx.doi.org/10.3389/fphar.2021.654714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144472PMC
May 2021

Tourism experiences and the lower risk of mortality in the Chinese elderly: a national cohort study.

BMC Public Health 2021 05 27;21(1):996. Epub 2021 May 27.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No.38, Xueyuan Road, Haidian District, Beijing, 100191, China.

Background: Cohort studies about the effects of tourism experiences on the risk of death among Chinese older adults are still lacking. We aimed to examine the association between tourism experiences and mortality in Chinese aged 65 or above.

Methods: We included 9520 participants aged 65 years or above from the Chinese Longitudinal Healthy Longevity Survey at baseline in 23 provinces in 2011. They were followed up in 2014 and 2018. Cox proportional hazards models were used to assess the association between tourism experiences and the risk of death.

Results: Among 9520 participants, 7.85% had at least one tourism experience outside of their local city/county during the past 2 years. During 35,994.26 person-years of follow-up, in total 4635 deaths were observed. The crude rate of death was greater in participants who had no tourism experience than in older travelers (incidence rate: 13.70 versus 5.24 per 100 person-years). Elderly travelers had a significantly lower risk for all-cause mortality (crude hazard ratio: 0.38, 95% CI: 0.33-0.44) compared with non-travelers. After adjustment for all covariates, the risk of all-cause mortality was 27% lower among those with at least one tourism experience than among non-travelers (adjusted hazard ratio: 0.73, 95% CI: 0.62-0.85). Subgroup analysis showed that the associations between tourism and the decreased risk of mortality were stable.

Conclusions: Tourism decreases the risk of mortality in the Chinese elderly. Tourism should be considered as a modifiable lifestyle factor and an effective way to reduce mortality and promote longevity and healthy aging.
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http://dx.doi.org/10.1186/s12889-021-11099-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157616PMC
May 2021

Potential Predictors and Survival Analysis of the Relapse of HIV-Associated Cryptococcal Meningitis: A Retrospective Study.

Front Med (Lausanne) 2021 10;8:626266. Epub 2021 May 10.

Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China.

We intend to investigate the relapse of HIV-associated cryptococcal meningitis (CM), assess potential predictors and conduct survival analysis, with a view to establishing a valid reference for the management of the relapse of CM. This is a retrospective study in Chinese patients with HIV-associated CM and those who experience relapse of CM. Baseline demographic, laboratory and clinical characteristics of patients with HIV-associated CM were collected. Predictors for relapse of HIV-associated CM were analyzed using univariate and multivariate logistic regression. Survival probability in relapse cases was determined by Kaplan-Meier survival curves. During the study period, 87 of 348 (25.0%) HIV patients experienced the relapse of CM. CD4+ T-cell counts, antiretroviral therapy (ART) status and the time from symptom onset to presentation were all statistically associated with the relapse of CM ( = 0.013, 0.018 and 0.042, respectively). The overall survival among 46 HIV CM relapse patients whose survival information were obtained, was 78.3%. The proportion of patients who died after antifungal treatment for CM was greater in those whose interval from symptom onset to presentation ≥4 weeks, compared with those <4 weeks ( = 0.0331). In order to reduce the relapse of CM and increase the survival possibility of these patients, we can promote the importance of ART before CM occurs, emphasize timely consultation when any CM-associated clinical symptoms occurs, and individualized the timing of ART initiation according to indicators which can reflect the severity of CM.
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http://dx.doi.org/10.3389/fmed.2021.626266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141581PMC
May 2021

Lithium doped nickel oxide nanocrystals with a tuned electronic structure for oxygen evolution reaction.

Chem Commun (Camb) 2021 Jun;57(49):6070-6073

International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.

The electronic structure of catalysts influences the electrocatalytic behavior. Herein, the electronic structure of NiO nanocrystals is modified by doping with a small amount of Li+. The Li+ doped NiO nanocrystals show much better OER activity than pristine NiO and LiNiO2, which is a result of tuned Fermi levels, stronger hybridization between Ni 3d and O 2p, and narrowed energy band gap. This work provides a facile strategy to regulate NiO electronic energy bands to promote OER performance.
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http://dx.doi.org/10.1039/d1cc01655eDOI Listing
June 2021

[Changes and Potential Sources of Atmospheric Black Carbon Concentration in Shanghai over the Past 40 Years Based on MERRA-2 Reanalysis Data].

Huan Jing Ke Xue 2021 Jun;42(6):2668-2678

Shanghai Key Laboratory for Urban Ecological Processes and Eco-restoration, School of Ecological and Environmental Sciences, East China Normal University, Shanghai 200241, China.

As an important component of atmospheric aerosols, black carbon (BC) has a great influence on the regional and global radiation balance, climate, and human health due to its small particle size, large specific surface area, and radiative forcing potential. Here, the spatio-temporal characteristics of atmospheric BC were investigated based on modern-era retrospective analysis for research and applications version 2 (MERRA-2) reanalysis data and ground observation data during 1980-2019 in Shanghai, a highly urbanized city in mainland China. The influences of local emissions and regional transmission on regional-scale BC concentrations were examined using the M-K trend test, backward trajectory analysis, and the potential source contribution function (PSCF). The results showed that:① MERRA-2 BC and ground observation datasets showed good consistency (∈[0.68, 0.72]), indicating that MERRA-2 reanalysis data can be used to reveal long-term changes in ground-level atmospheric BC concentrations; ② Atmospheric BC concentrations in Shanghai over the past 40 years can be divided into three stages:a "low value" stage of slow growth[1980-1986, (1.75±0.17) μg·m], a relatively stable "median value" stage[1987-1999, (2.18 ±0.07) μg·m], and a fluctuating "high value" stage[2000-2019, (3.07±0.31) μg·m]. Seasonally, Shanghai's BC concentrations generally show a "U" pattern with low concentrations in summer and high concentrations in winter. As a result of black carbon emissions from marine diesel engines and other engines used for water transportation, a small peak also occurs in July; ③ The diagnostic quality ratio of air pollutants and the bivariate correlation analysis[(BC-NO)(BC-CO)(BC-SO)] indicated that traffic emissions were the main sources of atmospheric BC in Shanghai, especially by heavy diesel vehicles; ④ The backward trajectory and PSCF analyses found that the air mass of Shanghai in summer was dominated by a clean sea breeze, accounting for 77.18%. In contrast, during the other seasons, more than 50% of the air mass came from the north. The potential source regions of atmospheric BC in Shanghai are mainly distributed in eastern China, expanding outwards and centering on the Yangtze River Delta, and the expansion direction is consistent with the directions of the backward trajectories.
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http://dx.doi.org/10.13227/j.hjkx.202009217DOI Listing
June 2021

Association between meteorological factors and daily new cases of COVID-19 in 188 countries: A time series analysis.

Sci Total Environ 2021 Aug 23;780:146538. Epub 2021 Mar 23.

Department of Epidemiology and Biostatics, School of Public Health, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing 100191, China. Electronic address:

By 31 December 2020, Coronavirus disease 2019 (COVID-19) had been prevalent worldwide for one year, and most countries had experienced a complete seasonal cycle. The role of the climate and environment are essential factors to consider in transmission. We explored the association between global meteorological conditions (including mean temperature, wind speed, relative humidity and diurnal temperature range) and new cases of COVID-19 in the whole past year. We assessed the relative risk of meteorological factors to the onset of COVID-19 by using generalized additive models (GAM) and further analyzed the hysteresis effects of meteorological factors using the Distributed Lag Nonlinear Model (DLNM). Our findings revealed that the mean temperature, wind speed and relative humidity were negatively correlated with daily new cases of COVID-19, and the diurnal temperature range was positively correlated with daily new cases of COVID-19. These relationships were more apparent when the temperature and relative humidity were lower than their average value (21.07°Cand 66.83%). The wind speed and diurnal temperature range were higher than the average value(3.07 m/s and 9.53 °C). The maximum RR of mean temperature was 1.30 under -23°C at lag ten days, the minimum RR of wind speed was 0.29 under 12m/s at lag 24 days, the maximum RR of range of temperature was 2.21 under 28 °C at lag 24 days, the maximum RR of relative humidity was 1.35 under 4% at lag 0 days. After a subgroup analysis of the countries included in the study, the results were still robust. As the Northern Hemisphere enters winter, the risk of global covid-19 remains high. Some countries have ushered in a new round of COVID-19 epidemic. Thus, active measures must be taken to control the source of infection, block transmission and prevent further spread of COVID-19 in winter.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986348PMC
August 2021

A Zwitterionic-Aromatic Motif-Based ionic skin for highly biocompatible and Glucose-Responsive sensor.

J Colloid Interface Sci 2021 May 6;600:561-571. Epub 2021 May 6.

Department of Biochemical Engineering, School of Chemical Engineering and Technology, Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (MOE), Tianjin University, Tianjin 300350, China; Frontier Technology Research Institute, Tianjin University, Tianjin 301700, China. Electronic address:

Electronic skins that can sense external stimuli have been of great significance in artificial intelligence and smart wearable devices in recent years. However, most of current skin materials are unable to achieve high biocompatibility and anti-bacterial activity, which are particularly critical to wearable sensors for neonatal/premature monitoring or tissue-interfaced biosensors (such as electronic wound dressing and smart contact lens). Herein, a zwitterionic-aromatic motif-based conductive hydrogel with electrostatic and π-π interactions is designed for the development of ionic skin sensors. The hydrogel possesses high biocompatibility, anti-bacterial activity, especially glucose-responsive property which has not been achieved by previous ionic skins. Due to its unique molecular design, the zwitterionic-aromatic skin sensor exhibits excellent mechanical properties (robust elasticity and large stretchability) and high-sensitive pressure detection (including a gentle finger touch, small water droplets, and vocal cord vibration). More importantly, aromatic motives in phenylboronic acid segments endow the skin with glucose-responsive property. This skin sensor not only shows great potential in wearable e-skins, but also possesses a promising property for the tissue-interfaced and implantable continuous-glucose-monitor biosensors such as smart wound dressing with a high demand of biocompatibility.
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http://dx.doi.org/10.1016/j.jcis.2021.05.012DOI Listing
May 2021

Efficient three-phase electrocatalytic CO reduction to formate on superhydrophobic Bi-C interfaces.

Chem Commun (Camb) 2021 Jun;57(49):6011-6014

College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, P. R. China.

Bi-C catalysts with the three-phase interfaces of CO2 (gas), electrolyte (liquid) and catalyst (solid) exhibit a remarkable electrocatalytic CO2 reduction (ECR) to formate selectivity (above 95% faradaic efficiency) with a high current (100 mA cm-2) in a broad potential range.
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http://dx.doi.org/10.1039/d1cc01974kDOI Listing
June 2021

Sensitivity, specificity, and safety of a novel ESAT6-CFP10 skin test for tuberculosis infection in China: two randomized, self-controlled, parallel-group phase 2b trials.

Clin Infect Dis 2021 May 22. Epub 2021 May 22.

Center for Disease Control and Prevention of Jiangsu Province, Nanjing, Jiangsu Province, PR, China.

Background: Diagnostics to identify tuberculosis infection are limited. We aimed to assess the diagnostic accuracy and safety of the novel ESAT6-CFP10 (EC) skin test for tuberculosis infection in Chinese adults.

Methods: We conducted two randomized, parallel-group clinical trials in healthy participants and tuberculosis patients. All participants were tested with the T-SPOT.TB test, then received EC skin test and tuberculin skin test (TST). The diameter of skin indurations and/or redness at injection sites were measured at different time periods. A Bacillus Calmette Guerin (BCG) model was also established to assess the diagnosis of tuberculosis infection using EC skin test.

Results: In total, 777 healthy participants and 96 tuberculosis patients were allocated to receive the EC skin test at 1.0μg/0.1ml or 0.5μg/0.1ml. The area under the curve was 0.95 (95% CI, 0.91-0.97) from the EC skin test at a dose of 1.0μg/0.1ml at 24-72 hours. Compared to the T-SPOT.TB test, the EC skin test demonstrated similar sensitivity (87.5, 95% CI 77.8-97.2 versus 86.5, 95% CI 79.5-93.4) and specificity (98.9, 95% CI 96.0-99.9 versus 96.1, 95% CI 93.5-97.8). Among BCG vaccinated participants, the EC skin test had high consistency with the T-SPOT.TB test (96.3, 95% CI, 92.0-100.0). No serious adverse events related to the EC skin test were observed.

Conclusions: The EC skin test demonstrated both high specificity and sensitivity at a dose of 1.0μg/0.1ml, comparable to the T-SPOT.TB test. The diagnostic accuracy of the EC skin test was not impacted by BCG vaccination.
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http://dx.doi.org/10.1093/cid/ciab472DOI Listing
May 2021

Myeloid-derived growth factor inhibits inflammation and alleviates endothelial injury and atherosclerosis in mice.

Sci Adv 2021 May 21;7(21). Epub 2021 May 21.

Department of Endocrinology, General Hospital of Central Theater Command, Wuluo Road 627, Wuhan 430070, Hubei Province, China.

Whether bone marrow modulates systemic metabolism remains unknown. Here, we found that (i) myeloid cell-specific myeloid-derived growth factor (MYDGF) deficiency exacerbated vascular inflammation, adhesion responses, endothelial injury, and atherosclerosis in vivo. (ii) Myeloid cell-specific MYDGF restoration attenuated vascular inflammation, adhesion responses and leukocyte homing and alleviated endothelial injury and atherosclerosis in vivo. (iii) MYDGF attenuated endothelial inflammation, apoptosis, permeability, and adhesion responses induced by palmitic acid in vitro. (iv) MYDGF alleviated endothelial injury and atherosclerosis through mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4)/nuclear factor κB (NF-κB) signaling. Therefore, we concluded that MYDGF inhibits endothelial inflammation and adhesion responses, blunts leukocyte homing, protects against endothelial injury and atherosclerosis in a manner involving MAP4K4/NF-κB signaling, and serves as a cross-talk factor between bone marrow and arteries to regulate the pathophysiology of arteries. Bone marrow functions as an endocrine organ and serves as a potential therapeutic target for metabolic disorders.
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http://dx.doi.org/10.1126/sciadv.abe6903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139583PMC
May 2021

The histone methyltransferase SETD2 modulates oxidative stress to attenuate experimental colitis.

Redox Biol 2021 Jul 13;43:102004. Epub 2021 May 13.

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200127, China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Epigenetic regulation disorder is important in the onset and pathogenesis of inflammatory bowel disease (IBD). SETD2, a trimethyltransferase of histone H3K36, is frequently mutated in IBD samples with a high risk of developing colorectal cancer (CRC). However, functions of SETD2 in IBD and colitis-associated CRC remain largely undefined. Here, we found that SETD2 modulates oxidative stress to attenuate colonic inflammation and tumorigenesis in mice. SETD2 expression became decreased in IBD patients and dextran sodium sulfate (DSS)-induced colitic mice. Setd2 mice showed increased susceptibility to DSS-induced colitis, accompanied by more severe epithelial barrier disruption and markedly increased intestinal permeability that subsequently facilitated inflammation-associated CRC. Mechanistically, we found that Setd2 depletion resulted in excess reactive oxygen species (ROS) by directly down-regulating antioxidant genes, which led to defects in barrier integrity and subsequently inflammatory damage. Moreover, overexpression of antioxidant PRDX6 in Setd2 intestinal epithelial cells (IECs) largely alleviated the overproductions of ROS and improved the cellular survival. Together, our findings highlight an epigenetic mechanism by which SETD2 modulates oxidative stress to regulate intestinal epithelial homeostasis and attenuate colonic inflammation and tumorigenesis. SETD2 might therefore be a pivotal regulator that maintains the homeostasis of the intestinal mucosal barrier.
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http://dx.doi.org/10.1016/j.redox.2021.102004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141928PMC
July 2021