Publications by authors named "Jing Nan"

53 Publications

Regulation of Formation, Stemness and Therapeutic Resistance of Cancer Stem Cells.

Front Cell Dev Biol 2021 7;9:641498. Epub 2021 Apr 7.

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Over the past 20 years cancer stem cells (CSCs) have been proposed as key players in the tumorigenesis and progression, which are closely related to the initiation, metastasis and therapeutic resistance of cancer. Evidences have been provided that both genetic and epigenetic factors contribute to the regulation of the formation and stemness maintenance as well as the therapeutic resistance of CSCs via affecting various signal pathways. In addition, the interaction between CSCs and tumor microenvironment has also been revealed to be involved in the above-described processes. With the aim of targeting CSCs to improve treatment outcome, we herein discuss the mechanisms that orchestrate the characteristic of CSCs by the three elements and potential therapeutic strategies. We also summarize how several key regulatory factors function in the regulation of not only the formation and stemness maintenance, but also the therapeutic resistance of CSCs. Thus, future studies focusing on these key factors would be helpful for the development of novel drugs targeting CSCs.
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http://dx.doi.org/10.3389/fcell.2021.641498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058412PMC
April 2021

Regulation of Anion Channel LRRC8 Volume-Regulated Anion Channels in Transport of 2'3'-Cyclic GMP-AMP and Cisplatin under Steady State and Inflammation.

J Immunol 2021 May 7;206(9):2061-2074. Epub 2021 Apr 7.

The Center for Microbes, Development and Health, Chinese Academy of Sciences Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China;

The recently identified anion channel LRRC8 volume-regulated anion channels (VRACs) are heteromeric hexamers constituted with the obligate LRRC8A subunit paired with at least one of the accessory LRRC8B to LRRC8E subunits. In addition to transport chloride, taurine, and glutamate, LRRC8 VRACs also transport the anticancer agent cisplatin and STING agonists 2'3'-cyclic GMP-AMP (cGAMP) and cyclic dinucleotides; hence, they are implicated in a variety of physiological and pathological processes, such as cell swelling, stroke, cancer, and viral infection. Although the subunit composition largely determines VRAC substrate specificity, the opening of various VRAC pores under physiological and pathological settings remains enigmatic. In this study, we demonstrated that VRACs comprising LRRC8A and LRRC8E (LRRC8A/E-containing VRACs), specialized in cGAMP transport, can be opened by a protein component present in serum under resting condition. Serum depletion ablated the tonic activity of LRRC8A/E-containing VRACs, decreasing cGAMP transport in various human and murine cells. Also, heating or proteinase K treatment abolished the ability of serum to activate VRAC. Genetic analyses revealed a crucial role for cGAMP synthase (cGAS) in serum/TNF-promoted VRAC activation. Notably, the presence of cGAS on the plasma membrane, rather than its DNA-binding or enzymatic activity, enabled VRAC activation. Moreover, phospholipid PIP2 seemed to be instrumental in the membrane localization of cGAS and its association with VRACs. Corroborating a role for LRRC8A/D-containing VRACs in cisplatin transport, serum and TNF markedly potentiated cisplatin uptake and killing of cancer cells derived from human or mouse. Together, these observations provide new insights into the complex regulation of VRAC activation and suggest a novel approach to enhance the efficacy of cGAMP and cisplatin in treating infection and cancer.
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http://dx.doi.org/10.4049/jimmunol.2000989DOI Listing
May 2021

Severe Acute Respiratory Syndrome Coronavirus 2 Viral RNA Load Status and Antibody Distribution Among Patients and Asymptomatic Carriers in Central China.

Front Cell Infect Microbiol 2021 19;11:559447. Epub 2021 Mar 19.

Department of Research Management, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, and People's Hospital of Henan University, Zhengzhou, China.

This study aimed to monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral loads and specific serum-antibodies (immunoglobulin [Ig] G and M) among confirmed patients and asymptomatic carriers from returning healthy travelers. The throat swabs, sputum, and stool samples from 57 hospitalized coronavirus disease (COVID-19) patients and 8 asymptomatic carriers, among 170 returning healthy travelers were tested using reverse-transcription real-time polymerase chain reaction. SARS-CoV-2 IgM/IgG antibodies were detected serum chemiluminescence assay. Sequential results showed higher viral RNA loads in the throat, sputum, and stool samples at 3-12 and 6-21 days after symptom onset among severely ill COVID-19 patients. Shorter viral habitation time (1-8 days) was observed in the oropharyngeal site and intestinal tract of asymptomatic carriers. The IgG and IgM response rates were 19/37 (51.4%) and 23/37 (62.6%) among the 29 confirmed patients and 8 asymptomatic carriers, respectively, within 66 days from symptom or detection onset. The median duration between symptom onset and positive IgG and IgM results was 30 (n=23; interquartile range [IQR]=20-66) and 23 (n=19; IQR=12-28) days, respectively. Of 170 returning healthy-travelers to China, 4.7% were asymptomatic carriers (8/170) within 2 weeks, and the IgG and IgM positivity rate was 12.8% (12/94). IgM/IgG-positivity confirmed 3 suspected SARS-CoV-2 cases, despite negative results for SARS-CoV-2 RNA. Compared with other respiratory viral infectious diseases, COVID-19 has fewer asymptomatic carriers, lower antibody response rates, and a longer antibody production duration in recovered patients and the contacted healthy population. This is an indication of the complexity of COVID-19 transmission.
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http://dx.doi.org/10.3389/fcimb.2021.559447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017178PMC
April 2021

Impact of the 2019 Novel Coronavirus Disease Pandemic on the Performance of a Cardiovascular Department in a Non-epidemic Center in Beijing, China.

Front Cardiovasc Med 2021 18;8:630816. Epub 2021 Feb 18.

Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Knowledge of the impact of the 2019 novel coronavirus disease (COVID-19) pandemic on the performance of a cardiovascular department in a medical referral hub center from a non-epidemic area of China is limited. The data on the total number of non-emergency medical cares (including the number of out-patient clinic attendances, the number of patients who were hospitalized in non-intensive care wards, and patients who underwent elective cardiac intervention procedures) and emergency medical cares [including the number of emergency department (ED attendances) and chest pain center (CPC attendances), as well as the number of patients who were hospitalized in coronary care unit (CCU) and the number of patients who underwent emergency cardiac intervention procedures] before and during the pandemic (time before the pandemic: 20th January 2019 to 31st March 2019 and time during the pandemic: 20th January 2020 to 31st March 2020) in the Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University were collected and compared. Both the non-emergency medical and emergency medical cares were affected by the pandemic. The total number of out-patient clinic attendance decreased by 44.8% and the total number of patients who were hospitalized in non-intensive care wards decreased by 56.4%. Pearson correlation analysis showed that the number of out-patient clinic attendance per day was not associated with the number of new confirmed COVID-19 cases and the cumulative number of confirmed COVID-19 patients in Beijing ( = -0.080, = 0.506 and = -0.071, = 0.552, respectively). The total number of patients who underwent non-emergency cardiac intervention procedures decreased during the pandemic, although there were no statistically significant differences except for patent foramen ovale (PFO) occlusion (1.7 ± 2.9 vs. 8.3 ± 2.3, = 0.035). As for the emergency medical cares, the ED attendances decreased by 22.4%, the total number of CPC attendances increased by 10.3%, and the number of patients who were hospitalized in CCU increased by 8.9%: these differences were not statistically significant. During the pandemic, the proportion of hospitalized patients with ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI) significantly increased (19.0 vs. 8.7%, < 0.001; 28.8 vs. 18.0%, < 0.001, respectively); also, the number of primary percutaneous coronary intervention (PCI) increased by 10.3%. There was no significant difference between patients before and during the pandemic regarding the age, gender, baseline and discharge medication therapy, as well as length of stay and in-hospital mortality. Our preliminary results demonstrate that both the non-emergency and emergency medical cares were affected by the COVID-19 pandemic even in a referral medical center with low cross-infection risk. The number of the out-patient clinic attendances not associated with the number of confirmed COVID-19 cases could be due to different factors, such as the local government contamination measures. The proportion of hospitalized patients with acute myocardial infarction increased in our center during the pandemic since other hospitals stopped performing primary angioplasty. A hub-and-spoke model could be effective in limiting the collateral damage for patients affected by cardiovascular diseases when the medical system is stressed by disasters, such as COVID-19 pandemic.
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http://dx.doi.org/10.3389/fcvm.2021.630816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929980PMC
February 2021

Molecular characterization of carbapenem-resistant and emergence of tigecycline non-susceptible strains in the Henan province in China: a multicentrer study.

J Med Microbiol 2021 Mar 15;70(3). Epub 2021 Feb 15.

Department of Clinical Microbiology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, 450003, PR China.

Carbapenem-resistant (CRE) have been responsible for nosocomial outbreaks worldwide and have become endemic in several countries. To better understand the epidemiological trends and characteristics of CRE in the Henan province. We assessed the molecular epidemiological characteristics of 305 CRE strains isolated from patients in 19 secondary or tertiary hospitals in ten areas of the Henan province in China. A total of 305 CRE isolates were subjected to multiple tests, including antimicrobial susceptibility testing, PCR for carbapenemase genes , , , , -. Tigecycline-resistant genes , , , A, , X, M, L were analysed in five tigecycline non-susceptible carbapenem-resistant isolates (TNSCRKP). Additionally, multilocus sequence typing (MLST) was performed for carbapenem-resistant (CRKP). The most common CRE species were (234, 77 %), (36, 12 %) and (13, 4 %). All strains exhibited multi-drug resistance. Overall, 97 % (295/305) and 97 % (297/305) of the isolates were susceptible to polymyxin B and tigecycline, respectively. A total of 89 % (271/305) of the CRE isolates were carbapenemase gene-positive, including 70 % , 13 % , 6 % , and 1 % combined / genes. carbapenemase (KPC) was the predominant carbapenemase in (87 %), whereas NDM and IMP were frequent in (53 %) and (69 %), respectively. Mutations in the , and genes were detected in five TNSCRKP. Moreover, 15 unique sequence types were detected, with ST11 (74 %), ST15 (9 %) and ST2237 (5 %) being dominant among strains. A high proportion of CRE strains were carbapenemase-positive, and five carbapenem-resistant isolates were tigecycline non-susceptible, indicating a need for the ongoing surveillance of CRE and effective measures for the prevention of CRE infections.
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http://dx.doi.org/10.1099/jmm.0.001325DOI Listing
March 2021

Antibacterial Potential of GJ1 against Citrus Huanglongbing.

Plants (Basel) 2021 Jan 29;10(2). Epub 2021 Jan 29.

College of Horticulture and Forestry, Ministry of Education Key Laboratory of Plant Biology, Huazhong Agricultural University, Wuhan 430070, China.

Citrus huanglongbing (HLB) is a destructive disease caused by Liberibacter species and is a serious global concern for the citrus industry. To date, there is no established strategy for control of this disease. Previously, GJ1 was screened as the biocontrol agent against HLB. In this study, two-year-old citrus infected by L. asiaticus were treated with GJ1 solution via root irrigation. In these plants, after seven irrigation treatments, the results indicated that the photosynthetic parameters, chlorophyll content, resistance-associated enzyme content and the expression of defense-related genes were significantly higher than for the plants treated with the same volume water. The content of starch and soluble sugar were significantly lower, compared to the control treatment. The parallel reaction monitoring (PRM) results revealed that treatment with GJ1 solution, the expression levels of 3 proteins with photosynthetic function were upregulated in citrus leaves. The accumulation of reactive oxygen species (ROS) in citrus leaves treated with GJ1 flag22 was significantly higher than untreated plants and induced the defense-related gene expression in citrus. Finally, surfactin was identified from the fermentation broth of GJ1 by high-performance liquid chromatography. These results indicate that GJ1 may improve the immunity of citrus by increasing the photosynthesis and enhancing the expression of the resistance-related genes.
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http://dx.doi.org/10.3390/plants10020261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910844PMC
January 2021

The stress hyperglycaemia ratio is associated with left ventricular remodelling after first acute ST-segment elevation myocardial infarction.

BMC Cardiovasc Disord 2021 02 4;21(1):72. Epub 2021 Feb 4.

Department of Cardioloy, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.

Background: Left ventricular negative remodelling after ST-segment elevation myocardial infarction (STEMI) is considered as the major cause for the poor prognosis. But the predisposing factors and potential mechanisms of left ventricular negative remodelling after STEMI remain not fully understood. The present research mainly assessed the association between the stress hyperglycaemia ratio (SHR) and left ventricular negative remodelling.

Methods: We recruited 127 first-time, anterior, and acute STEMI patients in the present study. All enrolled patients were divided into 2 subgroups equally according to the median value of SHR level (1.191). Echocardiography was conducted within 24 h after admission and 6 months post-STEMI to measure left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD). Changes in echocardiography parameters (δLVEF, δLVEDD, δLVESD) were calculated as LVEF, LVEDD, and LVESD at 6 months after infarction minus baseline LVEF, LVEDD and LVESD, respectively.

Results: In the present study, the mean SHR was 1.22 ± 0.25 and there was significant difference in SHR between the 2 subgroups (1.05 (0.95, 1.11) vs 1.39 (1.28, 1.50), p < 0.0001). The global LVEF at 6 months post-STEMI was significantly higher in the low SHR group than the high SHR group (59.37 ± 7.33 vs 54.03 ± 9.64, p  = 0.001). Additionally, the global LVEDD (49.84 ± 5.10 vs 51.81 ± 5.60, p  = 0.040) and LVESD (33.27 ± 5.03 vs 35.38 ± 6.05, p  = 0.035) at 6 months after STEMI were lower in the low SHR group. Most importantly, after adjusting through multivariable linear regression analysis, SHR remained associated with δLVEF (beta = -9.825, 95% CI -15.168 to -4.481, p  < 0.0001), δLVEDD (beta = 4.879, 95% CI 1.725 to 8.069, p  = 0.003), and δLVESD (beta = 5.079, 95% CI 1.421 to 8.738, p  = 0.007).

Conclusions: In the present research, we demonstrated for the first time that SHR is significantly correlated with left ventricular negative remodelling after STEMI.
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http://dx.doi.org/10.1186/s12872-021-01889-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863236PMC
February 2021

Fibrinolysis Therapy Combined with Deferred PCI versus Primary Angioplasty for STEMI Patients During the COVID-19 Pandemic: Preliminary Results from a Single Center.

Int J Gen Med 2021 19;14:201-209. Epub 2021 Jan 19.

Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.

Introduction: The efficacy of fibrinolysis therapy with deferred percutaneous coronary angioplasty (FPCI) versus primary angioplasty (PPCI) during the coronavirus disease 2019 (COVID-19) pandemic is unclear when medical quarantine is needed.

Patients And Methods: Acute ST segment elevation myocardial infarction (STEMI) patients underwent PPCI after finishing the screening protocol from January 23, 2020 to June 10, 2020 while FPCI was applied when COVID-19-confirmed cases reoccurred in Beijing near our hospital from June 11, 2020 to July 20, 2020. The door-to-balloon time (DTB) or door-to-needle time (DTN) as well as in-hospital adverse clinical outcomes were compared between the two groups. A propensity score-matched (PSM) analysis was performed to diminish the potential influence of confounding factors on the clinical outcomes.

Results: A total of 126 STEMI patients underwent PPCI after finishing the screening protocol and 17 patients received FPCI before PSM. Patients who received FPCI were younger than patients who underwent PPCI (50.8±14.0 versus 64.1±14.2 years, p=0.001), and chronic kidney disease (CKD) was less common in FPCI patients than in patients who underwent PPCI (0% versus 24.6%, p=0.024). The DTN was significantly shorter than DTB (25.8±4.2 versus 61.1±10.7, p=0.000) before PSM. The DTN was significantly shorter than DTB (26.9±4.2 versus 64.9±23.6, p=0.000); however, the incidence rate of in-hospital ischemia and bleeding adverse clinical outcomes were comparable between the two groups after PSM.

Conclusion: Fibrinolysis therapy combined with deferred PCI can reduce the ischemia time and has a similar in-hospital adverse clinical outcome rate compared with patients who underwent primary PCI during the COVID-19 pandemic.
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http://dx.doi.org/10.2147/IJGM.S292901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838526PMC
January 2021

The Impact of the COVID-19 Pandemic and the Importance of Telemedicine in Managing Acute ST Segment Elevation Myocardial Infarction Patients: Preliminary Experience and Literature Review.

J Med Syst 2021 Jan 3;45(1). Epub 2021 Jan 3.

Department of cardiology and macrovascular disease, Beijing Tiantan Hospital, Capital Medical University, No.119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People's Republic of China.

The coronavirus disease 2019 (COVID-19), which is caused by a novel coronavirus (SARS-COV-2), has compromised health care systems and normal management of patients with cardiovascular diseases [1-3]. Patients with non-communicable diseases, including acute myocardial infarction (AMI) are vulnerable to this stress [4, 5]. Acute ST segment elevation myocardial infarction (STEMI), the most critical type of AMI, is associated with high mortality even with modern medicine [6-8]. Timely reperfusion therapy is critical for STEMI patients because a short ischemia time is associated with better clinical outcomes and lower acute and long -term mortality [9-12]. The COVID-19 pandemic placed the management of STEMI patients in a difficult situation due to the need to balance timely reperfusion therapy and maintaining strict infection control practices [13, 14]. Telemedicine, which is used to deliver health care services using information or communication technology, provides an opportunity to carry out the evaluation, diagnosis, and even monitor the patients after discharge when social distancing is needed [15]. In this article, we reported our preliminary experience with the usefulness of telemedicine in managing STEMI patients during the COVID-19 pandemic. We also provided a review of this topic.
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http://dx.doi.org/10.1007/s10916-020-01703-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785918PMC
January 2021

The Predictive Value of Monocyte Count to High-Density Lipoprotein Cholesterol Ratio in Restenosis After Drug-Eluting Stent Implantation.

Int J Gen Med 2020 25;13:1255-1263. Epub 2020 Nov 25.

Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.

Background: The clinical value of monocyte count to high-density lipoprotein cholesterol ratio (MHR) in in-stent restenosis (ISR) of patients who have undergone bare metal stent implantation has been studied. However, the predictive value of MHR in ISR for patients who have undergone drug-eluting stent (DES) implantation has not been explored.

Methods: Non-ST segment elevation acute coronary syndrome (NSTE-ACS) patients who had undergone DES implantation and coronary angiography follow-up at the Beijing Shijitan Hospital, Capital Medical University, between January 1, 2008, and December 31, 2018, were retrospectively enrolled. Patients were divided into ISR and non-ISR groups depending on the follow-up coronary angiography results. Relative clinical information was recorded and analyzed. The receiver operating characteristic curve analysis was used to determine the optimum cut-off pre-procedural MHR to predict ISR.

Results: A total of 214 patients were enrolled in our study. The mean period between two coronary angiography procedures was 25.4±9.8 months. Percutaneous coronary intervention due to NSTE myocardial infarction, a bifurcation lesion, increased platelet count, and a high MHR were the independent risk factors in multivariate logistic regression analyses.

Conclusion: Our results indicated that elevated MHR is an independent and useful predictor of ISR in NSTE-ACS patients who have undergone DES implantation.
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http://dx.doi.org/10.2147/IJGM.S275202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701365PMC
November 2020

Arborinine, a potential LSD1 inhibitor, inhibits epithelial-mesenchymal transition of SGC-7901 cells and adriamycin-resistant gastric cancer SGC-7901/ADR cells.

Invest New Drugs 2021 Jun 19;39(3):627-635. Epub 2020 Nov 19.

Clinical Laboratory, Henan Provincial People's Hospital, Zhengzhou, 450003, China.

Arborinine is a natural product isolated from G. parva leaf extracts, which displays potentially antiproliferative activity against human cervical cancer cells. In contrast, its anticancer effects against gastric cancer cells and drug-resistant gastric cancer cells remain unknown. In this work, arborinine was evaluated as a broad-spectrum antiproliferative agent, and it exhibited potently inhibitory activity against NCI-N87 (IC = 5.67 μM), BGC-823 (IC = 7.26 μM), MGC803 (IC = 4.75 μM), SGC-7901 (IC = 1.96 μM), HGC-27 (IC = 5.70 μM), SGC-7901/ADR (IC = 0.24 μM), SGC-7901/VCR (IC = 1.09 μM), and MGC803/PTX (IC = 1.32 μM) cell lines. Subsequent target verification experiments demonstrated that arborinine selectively and reversibly inhibited LSD1 in a time-dependent manner. Furthermore, it was found that arborinine suppressed the epithelial-mesenchymal transition of gastric cancer cell line SGC-7901 and adriamycin-resistant gastric cancer cell line SGC-7901/ADR in a dose-dependent manner. The in vivo antitumor study further indicated that arborinine can significantly reduce the growth of tumors both in SGC-7901 and SGC-7901/ADR xenograft mouse models. Overall, we demonstrated the potential of arborinine as an effective treatment for gastric cancer and adriamycin-resistant gastric cancer.
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http://dx.doi.org/10.1007/s10637-020-01016-yDOI Listing
June 2021

Glycosylation of anthocyanins enhances the apoptosis of colon cancer cells by handicapping energy metabolism.

BMC Complement Med Ther 2020 Oct 15;20(1):312. Epub 2020 Oct 15.

Key Lab of Industrial Biocatalysis, Ministry of Education, Tsinghua University, Beijing, China.

Background: While anthocyanins are proven to be effective in inhibiting tumour cell proliferation, the underlying mechanisms remain unclear. This research aims to explore the glycosylation of anthocyanins in the tumour inhibitory effects and the potential mechanism.

Methods: The tumour inhibitory effect on mouse colon cancer cells (MC38) was examined by MTT and flow cytometric analyses. The inhibitory pathway of anthocyanin was explored by assessment of tumour cell mitochondrial membrane potential (MMP), the caspase-3 and caspase-9 activity, as well as the cell energy metabolism in terms of the glucose uptake, the NAD/NADH ratio and the ATP level.

Results: We found that 500 μM bilberry anthocyanins extract (BAE) induced 48.1% mitochondrial damage, activated the downstream caspase cascade to form apoptotic bodies (caspase-3 activity increased by 169%, caspase-9 activity increased by 186%), and inhibited cell proliferation (survival rate: 55.97%, 24 h). In contrast, the same concentration of anthocyanidin (cyanidin) led to marginal mitochondrial damage (only 9.85%) and resulted in little inhibition of MC38 cells (survival rate: 86.84%, 24 h). For cells incubated with 500 μM BAE, reactive oxygen species (ROS) decreased by 53.8%, but the ratio of NAD/NADH increased to 3.67, demonstrating that the mitochondrial damage was induced by blocking energy metabolism. Furthermore, cell energy metabolism is related to glucose uptake since the presence of 200 μM GLUT1 inhibitor substantially enhanced the inhibitory effects of cyanidin-3-O-glucoside (Cy-3-Glu) at 500 μM (survival rate: 51.08%, 24 h).

Conclusions: The study suggested that the glycosides of anthocyanins might handicap glucose transport and inhibit energy metabolism, which, in turn, led to mitochondrial damage and apoptosis of tumour cells.
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http://dx.doi.org/10.1186/s12906-020-03096-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566133PMC
October 2020

Comparing anticoagulation therapy alone versus anticoagulation plus single antiplatelet drug therapy after transcatheter aortic valve implantation in patients with an indication for anticoagulation: a systematic review and meta-analysis.

Cardiovasc Drugs Ther 2020 Oct 8. Epub 2020 Oct 8.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.

Purpose: This meta-analysis compared the efficacy and safety of oral anticoagulation (OAC) therapy alone versus OAC plus single antiplatelet therapy (SAPT) in patients with an indication for chronic OAC (mostly due to atrial fibrillation) after transcatheter aortic valve implantation (TAVI).

Methods: A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases to identify relevant studies. Data was extracted from the eligible studies and outcomes expressed as relative risks (RRs) with 95% confidence intervals (CIs).

Results: Five studies comprising 1344 patients with an indication for chronic OAC and undergoing TAVI were included. Of the 1344 patients, 480 patients received OAC therapy alone and 864 patients received OAC plus SAPT. There were no significant differences between OAC alone versus OAC plus SAPT in all-cause mortality (RR = 1.05, 95% CI 0.84-1.30, p = 0.69) and ischemic stroke (RR = 0.95, 95% CI 0.95-1.61, p = 0.86). However, OAC alone was associated with significantly lower risks of all bleeding events (RR = 0.62, 95% CI 0.49-0.69, p < 0.0001) and major and/ life-threatening bleeding events (RR = 0.57, 95% CI 0.42-0.76, p = 0.0002) compared to OAC plus SAPT.

Conclusion: In patients with an indication for chronic anticoagulation, post-TAVI antithrombotic therapy with OAC alone compared to OAC plus SAPT may be not significantly different in reducing all-cause mortality and ischemic stroke, but has an important benefit in a significantly lower risk of all bleeding and major and/life-threatening bleeding events.
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http://dx.doi.org/10.1007/s10557-020-07081-yDOI Listing
October 2020

Comparison of Clinical Outcomes in Patients with ST Elevation Myocardial Infarction with Percutaneous Coronary Intervention and the Use of a Telemedicine App Before and After the COVID-19 Pandemic at a Center in Beijing, China, from August 2019 to March 2020.

Med Sci Monit 2020 Sep 17;26:e927061. Epub 2020 Sep 17.

Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (mainland).

BACKGROUND The efficacy of telemedicine in reducing delay times and short-term adverse clinical outcomes in patients with ST segment elevation myocardial infarction (STEMI) during the coronavirus disease 2019 (COVID-19) pandemic is unclear. This study compared outcomes in patients with STEMI who had percutaneous coronary intervention (PCI) and the use of a telemedicine app from August 2019 to March 2020 at a single center in Beijing, China. MATERIAL AND METHODS A total of 243 patients with STEMI who underwent PCI were consecutively enrolled and divided into 2 groups according to the date, before or after the pandemic. The 2 groups were further divided into patients who used the app for consulting and those who did not. RESULTS The time from symptom onset to calling an ambulance (SCT), door to balloon time (DTB), and total ischemia time (TIT) were significantly prolonged in patients after the pandemic. Patients who used the app had shorter SCT, DTB, and TIT before and after the pandemic compared to those who did not. Adverse clinical outcomes were significantly higher after compared with before the pandemic, despite the incidence rate of stroke, any revascularization, and stent thrombosis. However, there was no significant difference in short-term adverse clinical outcomes between patients who used the app and those who did not before and after the pandemic. CONCLUSIONS Telemedicine reduced the delay time of STEMI patients during the COVID-19 pandemic. The difference in short-term adverse clinical outcomes was not statistically significant between patients who used the app and those who did not.
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http://dx.doi.org/10.12659/MSM.927061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521072PMC
September 2020

Modified subintimal plaque modification improving future recanalization of chronic total occlusion percutaneous coronary intervention.

J Geriatr Cardiol 2020 Jul;17(7):393-399

Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: Subintimal plaque modification (SPM) is often performed to restore antegrade flow and facilitate subsequent lesion recanalization. This study aimed to compare the safety and efficacy of modified SPM with traditional SPM.

Methods: A total of 1454 consecutive patients who failed a chronic total occlusion percutaneous coronary intervention (CTO PCI) attempt and underwent SPM from January 2015 to December 2019 at our hospital were reviewed retrospectively. Fifty-four patients who underwent SPM finally were included in this study. We analyzed the outcomes of all the patients, and the primary endpoint was recanalization rate, which was defined as Thrombolysis in Myocardial Infarction (TIMI) grades 2-3 flow on angiography 30 to 90 days post-procedure.

Results: The baseline characteristics were similar between the two groups. In the follow-up, the recanalization rate was noticeably higher in the modified SPM group compared with the traditional SPM group (90.9% 62.5%, < 0.05). The proposed strategy in the modified group was more aggressive, including a larger balloon size (1.83 ± 0.30 2.48 ± 0.26 mm, < 0.05) and longer subintimal angioplasty (0.59 ± 0.16 0.92 ± 0.12 mm, < 0.05). Also, the common use of a Stingray balloon and guide catheter extension resulted in improvement of patients in the modified SMP group (12.5% 100%, < 0.05).

Conclusion: Modified SPM, which is associated with a high likelihood of successful recanalization, is an effective and safe CTO PCI bail out strategy.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2020.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416063PMC
July 2020

A virus-induced conformational switch of STAT1-STAT2 dimers boosts antiviral defenses.

Cell Res 2021 Feb 5;31(2):206-218. Epub 2020 Aug 5.

Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.

Type I interferons (IFN-I) protect us from viral infections. Signal transducer and activator of transcription 2 (STAT2) is a key component of interferon-stimulated gene factor 3 (ISGF3), which drives gene expression in response to IFN-I. Using electron microscopy, we found that, in naive cells, U-STAT2, lacking the activating tyrosine phosphorylation, forms a heterodimer with U-STAT1 in an inactive, anti-parallel conformation. A novel phosphorylation of STAT2 on T404 promotes IFN-I signaling by disrupting the U-STAT1-U-STAT2 dimer, facilitating the tyrosine phosphorylation of STATs 1 and 2 and enhancing the DNA-binding ability of ISGF3. IKK-ε, activated by virus infection, phosphorylates T404 directly. Mice with a T-A mutation at the corresponding residue (T403) are highly susceptible to virus infections. We conclude that T404 phosphorylation drives a critical conformational switch that, by boosting the response to IFN-I in infected cells, enables a swift and efficient antiviral defense.
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http://dx.doi.org/10.1038/s41422-020-0386-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405385PMC
February 2021

Three Patients with COVID-19 and Pulmonary Tuberculosis, Wuhan, China, January-February 2020.

Emerg Infect Dis 2020 11 15;26(11):2755-2758. Epub 2020 Jul 15.

During January-February 2020, coronavirus disease (COVID-19) and tuberculosis were diagnosed for 3 patients in Wuhan, China. All 3 patients had COVID-19 pneumonia. One severely ill patient died after acute respiratory distress syndrome developed. Clinicians and public health officials should be aware of underlying chronic infections such as tuberculosis in COVID-19 patients.
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http://dx.doi.org/10.3201/eid2611.201536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588523PMC
November 2020

Loss of ZIP facilitates JAK2-STAT3 activation in tamoxifen-resistant breast cancer.

Proc Natl Acad Sci U S A 2020 06 12;117(26):15047-15054. Epub 2020 Jun 12.

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong, People's Republic of China;

Tamoxifen, a widely used modulator of the estrogen receptor (ER), targets ER-positive breast cancer preferentially. We used a powerful validation-based insertion mutagenesis method to find that expression of a dominant-negative, truncated form of the histone deacetylase ZIP led to resistance to tamoxifen. Consistently, increased expression of full-length ZIP gives the opposite phenotype, inhibiting the expression of genes whose products mediate resistance. An important example is By binding to two specific sequences in the promoter, ZIP suppresses expression. Increased expression and activation of JAK2 when ZIP is inhibited lead to increased STAT3 phosphorylation and increased resistance to tamoxifen, both in cell culture experiments and in a mouse xenograft model. Furthermore, data from human tumors are consistent with the conclusion that decreased expression of ZIP leads to resistance to tamoxifen in ER-positive breast cancer.
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http://dx.doi.org/10.1073/pnas.1910278117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334450PMC
June 2020

Evaluation of Bronopol and Disulfiram as Potential Liberibacter asiaticus Inosine 5'-Monophosphate Dehydrogenase Inhibitors by Using Molecular Docking and Enzyme Kinetic.

Molecules 2020 May 14;25(10). Epub 2020 May 14.

College of Horticulture and Forestry, Key Laboratory of Horticultural Plant Biology of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China.

Citrus huanglongbing (HLB) is a destructive disease that causes significant damage to many citrus producing areas worldwide. To date, no strategy against this disease has been established. Inosine 5'-monophosphate dehydrogenase (IMPDH) plays crucial roles in the de novo synthesis of guanine nucleotides. This enzyme is used as a potential target to treat bacterial infection. In this study, the crystal structure of a deletion mutant of Las IMPDHΔ98-201 in the apo form was determined. Eight known bioactive compounds were used as ligands for molecular docking. The results showed that bronopol and disulfiram bound to Las IMPDHΔ98-201 with high affinity. These compounds were tested for their inhibition against Las IMPDHΔ98-201 activity. Bronopol and disulfiram showed high inhibition at nanomolar concentrations, and bronopol was found to be the most potent molecule (K = 234 nM). The K value of disulfiram was 616 nM. These results suggest that bronopol and disulfiram can be considered potential candidate agents for the development of Las inhibitors.
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http://dx.doi.org/10.3390/molecules25102313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287799PMC
May 2020

Hypoxia in acute cardiac injury of coronavirus disease 2019: lesson learned from pathological studies.

J Geriatr Cardiol 2020 Apr;17(4):221-223

Department of Rheumatology and Immunology, Beijing Haidian Hospital, Beijing Haidian Section of Peking University Third Hospital, Beijing, China.

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http://dx.doi.org/10.11909/j.issn.1671-5411.2020.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189261PMC
April 2020

Bilberry anthocyanin extracts enhance anti-PD-L1 efficiency by modulating gut microbiota.

Food Funct 2020 Apr;11(4):3180-3190

Department of Chemical Engineering, Tsinghua University, Beijing 100084, China. and Key Lab of Industrial Biocatalysis, Ministry of Education, Beijing 100084, China.

The undesirable low response rate is a major hurdle to garnering the maximum potential of immune checkpoint inhibitors in cancer treatments. Recent advances in exploring the effects of intestinal flora on the medical efficacy of immune checkpoint blockade have shed new light on the application of immune checkpoint inhibitors. Inspired by the prebiotic role of anthocyanin-rich extracts, we propose using bilberry anthocyanin extracts to modulate the composition of gut microbiota and eventually, promote the efficiency of immune checkpoint inhibitors. This study demonstrates the effectiveness of orally administered bilberry anthocyanin extracts in enhancing the anti-tumor efficiency of the PD-L1 antibody in the experimental mouse MC38 tumor model. We observed an increase in the fecal abundance of Clostridia and Lactobacillus johnsonii and improved effective community diversity. These findings reinforce the importance of intestinal flora composition and open up unprecedented opportunities in using natural compounds to enhance the efficacy of immune checkpoint inhibitors.
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http://dx.doi.org/10.1039/d0fo00255kDOI Listing
April 2020

Biostimulating Gut Microbiome with Bilberry Anthocyanin Combo to Enhance Anti-PD-L1 Efficiency against Murine Colon Cancer.

Microorganisms 2020 Jan 25;8(2). Epub 2020 Jan 25.

Key Lab of Industrial Biocatalysis, Ministry of Education, Dept of Chemical Engineering, Tsinghua University, Beijing 100084, China.

Recent advances have revealed the essential role of gut microbiomes in the therapeutic efficiency of immune checkpoint inhibitors (ICIs). Inspired by biostimulation, a method using nutrients to accelerate the growth of soil microorganisms and the recovery of soil microbial consortia, here we propose a bilberry anthocyanin combo containing chitosan and low molecular citrus pectin (LCP), in which LCP-chitosan is used to encapsulate anthocyanins so to enhance its digestive stability and, moreover, modulate the microbiome more favorable for the PD-L1 blockade treatment. Using murine MC38 colon cancer as a model system, we examined the effects of the combo on modulating the gut microbiome and therapeutic efficiency of PD-L1 blockade treatment. It was shown that bilberry anthocyanins enriched the subdominant species, increased both the concentration and the proportion of butyrate in feces and enhanced intratumoral CD8 T cell infiltrations. The application of the bilberry anthocyanin combo restored the species diversity of gut microbiome decreased by LCP-chitosan and achieved the best control of tumor growth. These preliminary results indicated unprecedented opportunities of probiotics combo in improving the therapeutic efficiency of immune checkpoint inhibitor through manipulating gut microbiome.
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http://dx.doi.org/10.3390/microorganisms8020175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074734PMC
January 2020

Embedded reservoir and constructed wetland for drinking water source protection: Effects on nutrient removal and phytoplankton succession.

J Environ Sci (China) 2020 Jan 22;87:260-271. Epub 2019 Jul 22.

College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China. Electronic address:

An embedded reservoir that provides an efficient nutrient removal system protects drinking water. However, embedded reservoirs are rarely used in eutrophic shallow lakes because of their undetermined nutrient retention efficiency and unknown effects by the phytoplankton community. In this study, we aim to investigate the nutrient retention and algae succession in an embedded reservoir and adjacent wetland from April 2017 to September 2018 in the eastern part of Lake Taihu, China. More than 40% of total phosphorus (TP) and 45% of particulate phosphorous entering the reservoir were retained semi-annually, and the highest TP removal efficiency was achieved in the reservoir during autumn with an average value of 53.3% ± 9.9%. The overall nitrogen retention efficiency (21.7% ± 37.8%) was lower than that of TP (41.8% ± 27.8%). Similar trends were obtained in the wetland area. An important pathway for phosphorus removal is through particulate matter retention. Our study revealed that nutrient retention mechanisms in the reservoir were primarily via macrophyte absorption, particulate substance sedimentation, and prolonged water residence time. Consequently, the phytoplankton biomass (Chl-a) in the reservoir decreased (from 48.0 to 25.2 μg/L) and water transparency improved, due to the decreased P level and transformation of the phytoplankton group into simple structures with good ecological status. Therefore, the combination of embedded reservoir and constructed wetland ecosystem can be used successfully to protect surface water. The results will be advantageous to groups seeking to preserve drinking water sources.
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http://dx.doi.org/10.1016/j.jes.2019.07.005DOI Listing
January 2020

Evaluation of an optimized method to directly identify bacteria from positive blood cultures using MALDI-TOF mass spectrometry.

J Clin Lab Anal 2020 Apr 13;34(4):e23119. Epub 2019 Nov 13.

Department of Clinical Microbiology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China.

Background: Although various methods have been developed to directly identify bacteria from positive blood cultures by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), the necessity of using commercial kits still leads to a high cost and long assay time. Moreover, few evaluations of these methods have been conducted. This study aimed to evaluate the feasibility of an optimized MALDI-TOF MS method for direct identification of bacteria in positive blood cultures.

Methods: A total of 829 non-repeated positive cultures were collected from July 2018 to August 2019, and direct identification was performed by an optimized MALDI-TOF MS method. The same positive blood cultures were sub-cultivated to obtain a single bacterial colony and identified by classical biochemical BD testing, which is the gold standard to compare the accuracy of direct identification of positive blood cultures by MALDI-TOF MS.

Results: After excluding 7 false-positive samples from the 829 positive blood cultures, the most accurate rate of direct identification by this optimized MALDI-TOF MS method was for gram-negative bacteria (91.5%), followed by gram-positive bacteria (88.3%), fungi (84.8%), anaerobic bacteria (80%), and other rare bacteria (66.67%).

Conclusion: Common bacteria in positive blood cultures can be identified directly within 1 hour by MALDI-TOF MS, and thus, this optimized method can be used as a primary identification method by clinicians. Routine implementation of this method may significantly increase the optimal utilization rate of antibiotics and decrease mortality in bacteremia patients.
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http://dx.doi.org/10.1002/jcla.23119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171327PMC
April 2020

Continuous synthesis of carbon dots with full spectrum fluorescence and the mechanism of their multiple color emission.

Lab Chip 2019 12 29;19(23):3974-3978. Epub 2019 Oct 29.

The State Key Lab of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.

Carbon dots with different emission fluorescence have a great number of potential applications for various areas from in vitro imaging and biotherapy, due to the good biosafety of red fluorescent CDs, to efficient ion detection and photocatalysis, due to the excellent photoluminescence properties of blue fluorescent carbon dots. Traditional methods for the synthesis of full-spectrum carbon dots require 24 h of synthesis and complex column chromatography. In this paper, a facile and efficient microfluidic method to continuously synthesize small and uniform carbon dots with full-spectrum emission fluorescence is developed for the first time. The synthesis process could be reduced to 20 minutes. Through XPS analysis and DFT calculations, it is quantitatively revealed that the number of primary amino groups determines the energy gap of the carbon dots and thus determines the fluorescence emission wavelength of the carbon dots. Applications for precise Fe detection and in vitro bio-imaging were successfully implemented, showing great potential application value of the carbon dots.
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http://dx.doi.org/10.1039/c9lc00683dDOI Listing
December 2019

Discovery and evaluation of Atopaxar hydrobromide, a novel JAK1 and JAK2 inhibitor, selectively induces apoptosis of cancer cells with constitutively activated STAT3.

Invest New Drugs 2020 08 14;38(4):1003-1011. Epub 2019 Oct 14.

School of Life Sciences, Lanzhou University, Lanzhou, 730000, Gansu, China.

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway plays a vital role in immunity, cell division, cell death and tumor formation. Disrupted JAK-STAT signaling may lead to various diseases, especially cancer and immune disorders. Because of its importance, this signaling pathway has received significant attention from the pharmaceutical and biotechnology industries as a therapeutic target for drug design. However, few JAK or STATs inhibitors have been developed for cancer treatment. We used an in vitro STAT3 luciferase reporter assay to find novel inhibitors that could effectively block the JAK-STAT pathway. In our study, we screened 16,081 drug-like chemicals and found that atopaxar hydrobromide (AHB) is a specific inhibitor of JAK-STAT3 signaling. Our results suggest that AHB not only blocks constitutively activated and cytokine-induced STAT3 phosphorylation but also inhibits JAK1 and JAK2 phosphorylation. Moreover, AHB induces G1 phase cell cycle arrest, which stops cancer cell growth and induces apoptosis. AHB also inhibited tumor cell growth in vivo. In conclusion, AHB is a potential inhibitor that could be developed as a JAK-STAT pathway drug.
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http://dx.doi.org/10.1007/s10637-019-00853-wDOI Listing
August 2020

TGF-β2 antagonizes IL-6-promoted cell survival.

Mol Cell Biochem 2019 Nov 29;461(1-2):119-126. Epub 2019 Jul 29.

School of Life Science, Lanzhou University, Lanzhou, 73000, Gansu, People's Republic of China.

Transforming growth factor beta is a key cytokine involved in the pathogenesis of fibrosis in many organs, whereas interleukin-6 plays an important role in the regulation of inflammation. They are both potent angiogenesis inducers with opposite effects on cell survival and apoptosis. TGF-β2 induces apoptosis; in contrast, IL-6 protects cells from apoptosis. The possible interaction between these two cytokines is indicated in various disease states. In this study, we have assessed the effect of TGF-β2 on IL-6 signaling and found that TGF-β2 could strongly inhibit IL-6-induced STAT3 activation and synergy with IL-6 resulting in enhanced SOCS3 expression. Interestingly, IL-6 also slows down the decay of TGF-β2 mRNA. Consistent with this mechanism, we found that TGF-β2 could antagonize IL-6 effect on cell survival in both γ-irradiation and UV light-induced apoptosis. Taken together, the finding shows that TGF-β2 serves as a negative regulator of IL-6 signaling and antagonizes the anti-apoptosis effect of IL-6.
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http://dx.doi.org/10.1007/s11010-019-03595-8DOI Listing
November 2019

Effect of Microwave Sintering on the Properties of 0.95(CaSr)TiO₃⁻0.05(BiNa)TiO₃ Ceramics.

Materials (Basel) 2019 Mar 8;12(5). Epub 2019 Mar 8.

College of Materials Science and Engineering, Nanjing Tech University, Nanjing 210009, China.

Perovskite ceramics are a common microwave dielectric material, but the development and application of this material has been limited by the high, positive resonance frequency temperature coefficient and sintering temperature. Therefore, adjusting the temperature coefficient of the resonance frequency and reducing the sintering temperature have become important research directions. In this work, 0.95(CaSr)TiO₃⁻0.05(BiNa)TiO₃ ceramics (referred to as 0.95CST-0.05BNT) were prepared by standard solid-state reaction and microwave sintering. Microwave sintering greatly shortened the sintering period and holding time. Moreover, the 0.95CST⁻0.05BNT ceramics showed more uniform grain size distribution, and microwave sintering reduced energy consumption in the experiment. Therefore, the temperature coefficient of the resonance frequency of MWS ceramics was reduced by 119 × 10 /℃. All of the ceramics, which were sintered at 1300 °C for 40 minutes, showed optimal microwave dielectric properties: = 187.6, × = 8958 GHz, and = +520 × 10 /°C.
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http://dx.doi.org/10.3390/ma12050803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427490PMC
March 2019

E2F is required for STAT3-mediated upregulation of cyclin B1 and Cdc2 expressions and contributes to G2-M phase transition.

Acta Biochim Biophys Sin (Shanghai) 2019 Mar;51(3):313-322

School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.

Activation of transcription factor STAT3 is involved in cell proliferation, differentiation, and cell survival. Constitutive activation of STAT3 pathway has been associated with the oncogenesis of various types of cancers. It has been reported that STAT3 plays a key role in the G1 to S phase cell cycle transition induced by the cytokine receptor subunit gp130, through the upregulation of cyclins D1, D2, D3, A, and Cdc25A and the concomitant downregulation of p21 and p27. However, its role in mediating G2-M phase transition has not been studied. The cyclin B1/Cdc2 complex is widely accepted as the trigger of mitosis in all organisms and is believed to be necessary for progression through S phase and keep active during the G2-M transition and progression. In the present study, we found that activation of STAT3 stimulates cyclin B1 and Cdc2 expressions. Deletion and site-directed mutations on cyclin B1 and Cdc2 promoters indicated that E2F element mediates the upregulation of these two promoters in a STAT3-dependent manner. The findings reported here demonstrated that STAT3 participates in modulating G2-M phase checkpoint by regulating gene expressions of cyclin B1 and Cdc2 via E2F.
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http://dx.doi.org/10.1093/abbs/gmy174DOI Listing
March 2019