Publications by authors named "Jing Han"

1,000 Publications

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Discovery of Novel 2,4-Dianilinopyrimidine Derivatives Containing 4-(Morpholinomethyl)phenyl and -Substituted Benzamides as Potential FAK Inhibitors and Anticancer Agents.

Molecules 2021 Jul 9;26(14). Epub 2021 Jul 9.

Department of Chemistry, Changzhi University, Changzhi 046011, China.

Focal adhesion kinase (FAK) is responsible for the development and progression of various malignancies. With the aim to explore novel FAK inhibitors as anticancer agents, a series of 2,4-dianilinopyrimidine derivatives - and - containing 4-(morpholinomethyl)phenyl and -substituted benzamides have been designed and synthesized. Among them, compound displayed potent anti-FAK activity (IC = 0.047 ± 0.006 μM) and selective antiproliferative effects against H1975 (IC = 0.044 ± 0.011 μM) and A431 cells (IC = 0.119 ± 0.036 μM). Furthermore, compound also induced apoptosis in a dose-dependent manner, arresting the cells in S/G2 phase and inhibiting the migration of H1975 cells, all of which were superior to those of TAE226. The docking analysis of compound was performed to elucidate its possible binding modes with FAK. These results established as our lead compound to be further investigated as a potential FAK inhibitor and anticancer agent.
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http://dx.doi.org/10.3390/molecules26144187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304610PMC
July 2021

Consistency of recommendations for the diagnosis and treatment of non-small cell lung cancer: a systematic review.

Transl Lung Cancer Res 2021 Jun;10(6):2715-2732

Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

Background: To systematically assess the consistency of recommendations regarding diagnosis and treatment of non-small cell lung cancer (NSCLC) in clinical practice guidelines (CPGs).

Methods: We systematically searched relevant literature databases and websites to identify CPGs related to NSCLC. We extracted the general characteristics of the included guidelines and their recommendations and descriptively compared and analyzed the consistency of recommendations across the guidelines.

Results: A total of 28 NSCLC guidelines were retrieved. The recommendations covered mainly diagnosis and treatment. The recommendations in the guidelines differed substantially in various topics, such as the application of positron emission tomography (PET) and the classification of stage III. Fourteen guidelines divided stage III into two types: operable and inoperable; and the remaining 14 guidelines into three sub-stages IIIA, IIIB and IIIC. Recommendations regarding the treatment in stage III were relatively inconsistent. In driver gene (EGFR, ALK, ROS1) positive patients, targeted therapy was the most common recommendation for first-line treatment, but recommendations regarding second-line treatment varied according to the site of the mutation. In driver gene negative patients, immunotherapy was the most frequently recommended option as both first- and second-line treatment, followed by chemotherapy.

Discussion: A number of countries are devoting themselves to develop NSCLC guidelines and the process of updating guidelines is accelerating, yet recommendations between guidelines are not consistent. We adopted a systematic review method to systematically search and analyze the NSCLC guidelines worldwide. We objectively reviewed the differences in recommendations for NSCLC diagnosis and treatment between the guidelines. Inconsistency of recommendations across guidelines can result from multiple potential reasons. Such as, the guidelines developed time, different countries and regions and many more. Poor consistency across CPGs can confuse the guideline users, and we therefore advocate paying more attention to examining the controversies and updating guidelines timely to improve the consistency among CPGs. Our study had also several limitations, we limited the search to CPGs published in Chinese or English, the interpretation of recommendations is inherently subjective, we did not evaluate the details of the clinical content of the CPG recommendations. Our research presents the current status of NSCLC guidelines worldwide and give the opportunity to pay more attention to the existing gaps. Further investigations should determine the reasons for inconsistency, the implications for recommendation development, and the role of synthesis across recommendations for optimal guidance of clinical care treatment. With the continuous revision and update of the guidelines, we are confident that future guidelines will be formulated with higher quality to form clear, definite and consistent recommendations for NSCLC diagnosis and treatment.
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http://dx.doi.org/10.21037/tlcr-21-423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264323PMC
June 2021

Joint analysis of D-dimer, N-terminal pro b-type natriuretic peptide, and cardiac troponin I on predicting acute pulmonary embolism relapse and mortality.

Sci Rep 2021 Jul 21;11(1):14909. Epub 2021 Jul 21.

Department of Respiratory and Critical Care Medicine, Kailuan General Hospital, 57 East Xinhua Rd, Tangshan, Hebei, China.

Previous studies on the adverse events of acute pulmonary embolism (APE) were mostly limited to single marker, and short follow-up duration, from hospitalization to up to 30 days. We aimed to predict the long-term prognosis of patients with APE by joint assessment of D-dimer, N-Terminal Pro-Brain Natriuretic Peptide (NT-ProBNP), and troponin I (cTnI). Newly diagnosed patients of APE from January 2011 to December 2015 were recruited from three hospitals. Medical information of the patients was collected retrospectively by reviewing medical records. Adverse events (APE recurrence and all-cause mortality) of all enrolled patients were followed up via telephone. D-dimer > 0.50 mg/L, NT-ProBNP > 500 pg/mL, and cTnI > 0.40 ng/mL were defined as the abnormal. Kaplan-Meier curve was used to compare the cumulative survival rate between patients with different numbers of abnormal markers. Cox proportional hazard regression model was used to further test the association between numbers of abnormal markers and long-term prognosis of patients with APE after adjusting for potential confounding. During follow-up, APE recurrence and all-cause mortality happened in 78 (30.1%) patients. The proportion of APE recurrence and death in one abnormal marker, two abnormal markers, and three abnormal markers groups were 7.69%, 28.21%, and 64.10% respectively. Patients with three abnormal markers had the lowest survival rate than those with one or two abnormal markers (Log-rank test, P < 0.001). After adjustment, patients with two or three abnormal markers had a significantly higher risk of the total adverse event compared to those with one abnormal marker. The hazard ratios (95% confidence interval) were 6.27 (3.24, 12.12) and 10.7 (4.1, 28.0), respectively. Separate analyses for APE recurrence and all-cause death found similar results. A joint test of abnormal D-dimer, NT-ProBNP, and cTnI in APE patients could better predict the long-term risk of APE recurrence and all-cause mortality.
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http://dx.doi.org/10.1038/s41598-021-94346-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295248PMC
July 2021

Quality control of Semen Hoveniae by HPLC coupled to Fourier transform-ion cyclotron resonance mass spectrometry.

J Sep Sci 2021 Jul 20. Epub 2021 Jul 20.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, P. R. China.

A method based on HPLC and Fourier transform-ion cyclotron resonance mass spectrometer was developed to control the quality of Semen Hoveniae. Firstly, the chromatographic fingerprint was established in combination with the chemometrics methods such as similarity analysis, cluster analysis, principal component analysis and orthogonal partial least squares discriminant analysis to discover the qualitative markers. Then, an HPLC-MS method was developed to identify the chemical constituents in Semen Hoveniae. Moreover, the content of dihydromyricetin and dihydroquercetin in Semen Hoveniae were determined by HPLC. As a result, 9 common peaks were assigned in the fingerprints and the similarity of the 13 batch samples varied from 0.425 to 0.993, indicating an obviously different quality. Dihydromyricetin and dihydroquercetin were the main qualitative markers to differ the quality of Semen Hoveniae. Meanwhile, a total of 21 chemical compounds were characterized by HPLC-MS and six of them were identified by comparing with information of reference standards. Finally, the content of dihydromyricetin and dihydroquercetin in 13 batch samples varied from 0.824 mg·g to 7.499 mg·g and from 0.05941 mg·g to 4.258 mg·g was determined, respectively. In conclusion, the methods developed here will provide sufficient qualitative and quantitative information for the quality control of Semen Hoveniae. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jssc.202100240DOI Listing
July 2021

confers enhanced the resistance to by increasing proanthocyanidin biosynthesis in cucumber.

Phytopathology 2021 Jul 20. Epub 2021 Jul 20.

College of Horticulture Science and Engineering, Shandong Agricultural UniversityTaian, China, 271018;

Root rot caused by Fusarium solani is one of the most common fungal diseases in cucumber (Cucumis sativus L.). Proanthocyanidins (PAs) are known to play important roles in inhibiting the growth of phytopathogens. In addition, CsMYB60 is a known positive regulator of flavonol and PA biosynthesis in cucumber. However, it remains unclear that whether PAs could inhibit the growth of F. solani and whether CsMYB60 serves as a target gene for enhancing resistance to phytopathogens in cucumber. In this study, we demonstrated that PAs (or their building block, catechin) could enhance the resistance of cucumber seedlings to F. solani both in vitro and in vivo. The addition of catechins, or crude leaf extracts treated with different concentrations of catechins in culture medium, could significantly inhibit the hyphal growth of F. solani. On the other hand, the cucumber seedlings treated with catechins showed higher resistance to F. solani than the seedlings in control group. Moreover, the transgenic cucumber seedlings overexpressing CsMYB60, with the observed accumulation of PAs, were more resistant to F. solani than the non-transgenic siblings. Therefore, our results suggest that PAs (or catechin) can serve as a biological control agent to protect cucumber plants from the infection of F. solani. More importantly, CsMYB60 holds great promise as a target gene to confer disease resistance during the molecular breeding in cucumber.
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http://dx.doi.org/10.1094/PHYTO-05-21-0223-RDOI Listing
July 2021

An evaluation of the reporting quality in clinical practice guidelines for hepatocellular carcinoma using the RIGHT checklist.

Ann Transl Med 2021 Jun;9(12):1004

Department of Internal Medicine, Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Clinical practice guidelines (CPGs) on the prevention, surveillance, diagnosis and management of HCC are essential to guide clinical practice. The objective of this study was to evaluate the reporting quality of the most recent CPGs for HCC published worldwide.

Methods: We systematically searched literature databases and websites of guideline development organizations and medical associations to extract CPGs on HCC published between January 2018 and December 2020. We evaluated the reporting quality using the Reporting Items for practice Guidelines in Healthcare (RIGHT) statement. We assessed for each of the 35 RIGHT checklist items whether the guidelines reported the corresponding information. We calculated the mean (± standard error of the mean, SEM) percentages of the guidelines' compliance with the items (reporting rate), both overall and for each of the seven domains of the RIGHT checklist.

Results: We identified 22 guidelines, of which three (14%) were written in Chinese and 19 (86%) in English. The mean ±SEM overall reporting rate in the twenty-two guidelines was 56%±4%. The reporting rates of the seven domains were the following: basic information 81%±3%, background 58%±6%, evidence 58%±6%, recommendations 59%±5%, review and quality assurance 34%±10%, funding and declaration and management of interests 39%±4%, and other information 23%±6%.

Conclusions: The reporting quality of the recently published guidelines for HCC was suboptimal. While there is no doubt about the great value of the CPGs' recommendations in clinical practice, the reporting in CPGs for HCC still needs improvement.
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http://dx.doi.org/10.21037/atm-21-2611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267298PMC
June 2021

Evaluation of the reporting quality of guidelines for gastric cancer using the RIGHT checklist.

Ann Transl Med 2021 Jun;9(12):1003

Department of Internal Medicine, Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China.

Background: Gastric cancer is the fifth most common type of cancer globally. We aimed to evaluate the reporting quality of clinical practice guidelines in the field of gastric cancer.

Methods: We searched Medline (via PubMed), China Biology Medicine, Chinese National Knowledge Infrastructure and WanFang databases and the websites of the main guideline development organizations from 2018 to 2020 for guidelines on gastric cancer. Data were extracted and the reporting quality evaluated by two researchers independently using the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist. We assessed the compliance of the guidelines to each of the 35 items of RIGHT and summarized the reporting proportions of the seven domains of RIGHT.

Results: Eighteen guidelines were included. The mean proportion of appropriately reported RIGHT items was 52.4%. Among the seven domains of the RIGHT checklist, Basic information had the highest reporting rate (78.7%), and Review and quality assurance domain the lowest rate (16.7%). The domains Evidence (40.0%), Funding and declaration and management of interests (43.1%), and Other information (31.5%) had also reporting rates below 50%. Two RIGHT items (17 and 19b) were not reported by any of the guidelines.

Conclusions: The reporting quality of gastric cancer guidelines published in the years 2018-2020 was suboptimal, especially regarding the reporting of review, quality assurance and evidence. Guideline developers should pay attention on rigorous reporting following international standard to improve the quality of guidelines.
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http://dx.doi.org/10.21037/atm-21-2491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267280PMC
June 2021

Azilsartan protects against hyperglycemia-induced hyperpermeability of the blood-brain barrier.

Bioengineered 2021 Dec;12(1):3621-3633

Department of Neurosurgery, the People's Hospital of China Three Gorges University, Yichang, Hubei, China.

Diabetes mellitus (DM) is a complex metabolic disease with significant neurological complications and is reported to be closely related to the blood-brain barrier (BBB) disruption. Azilsartan is an antagonist of the Angiotensin II receptor developed for the treatment of hypertension, and it has been recently reported to have neuroprotective effects. The present study aims to investigate the protective effect of Azilsartan against hyperglycemia-induced BBB disruption and its underlying mechanism. Male db/db mice were treated with Azilsartan (20 μg/day) for 10 consecutive days. Compared to the control group, increased BBB permeability, suppressed occludin expression, excessive release of inflammatory factors, and downregulation of krüppel-like factor 2 (KLF2) were observed in diabetic mice, all of which were dramatically reversed by Azilsartan treatment. In the experiments, elevated endothelial permeability and decreased expression of occludin and KLF2 were observed in high glucose-challenged endothelial cells, which were significantly alleviated by Azilsartan. Lastly, the silencing of KLF2 abolished the protective effects of Azilsartan against the high glucose-induced expression of occludin and endothelial monolayer permeability in bEnd.3 brain endothelial cells. Based on these observations, we concluded that Azilsartan protected against hyperglycemia-induced hyperpermeability of BBB via the KLF2/occludin axis.
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http://dx.doi.org/10.1080/21655979.2021.1948950DOI Listing
December 2021

Screening and diagnosis of colorectal cancer and advanced adenoma by Bionic Glycome method and machine learning.

Am J Cancer Res 2021 15;11(6):3002-3020. Epub 2021 Jun 15.

NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University Shanghai 200032, P. R. China.

Colorectal cancer (CRC), one of the major health problems worldwide, mostly develops from colorectal adenomas. Advanced adenomas are generally considered as precancerous lesions and patients are recommended to remove the adenomas. Screening for colorectal cancer is usually performed by fecal tests (FOBT or FIT) and colonoscopy, however, their benefits are limited by uptake and adherence. Most CRC develops from colorectal advanced adenomas, but there is currently a lack of effective noninvasive screening method for advanced adenomas. N-glycans in human serum hold the great potentials as biomarker for diagnosis of human cancers. Our aim was to discover blood-based markers for screening and diagnosis of advanced adenomas and CRC, and to ascertain their efficiency in classifying healthy controls, patients with advanced adenomas and CRC by incorporating machine learning techniques with reliable and simple quantitative method with "Bionic Glycome" as internal standard based on the high-throughput Matrix-assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS). The quantitative results showed that there is a positive correlation between multi-antennary, sialylated N-glycans and CRC progress, while bi-antennary core-fucosylated N-glycans are negatively correlated with CRC progress. Machine learning is a powerful classification tool, suitable for mining big data, especially the large amount of data generated by high-throughput technologies. Using the predictive model constructed by machine learning, we obtained the classification accuracy of 75% for classification of 189 samples including CRC, advanced adenomas and healthy controls, and the accuracy of 87% for detection of the disease group that required treatment, including CRC and advanced adenomas. To our delight, the model successfully applied to the prediction of 176 samples collected a few months later, and five samples were wrongly predicted in the disease group. Overall, this diagnostic model we constructed here has valuable potential in the clinical application of detecting advanced adenomas and colorectal cancer and could compensate for the limitations of the current screening methods for detection of CRC and advanced adenomas.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263652PMC
June 2021

Stapled, Long-Acting Xenopus GLP-1-Based Dual GLP-1/Glucagon Receptor Agonists with Potent Therapeutic Efficacy for Metabolic Disease.

Mol Pharm 2021 Jul 9. Epub 2021 Jul 9.

School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China.

Novel peptidic glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP-1R) dual agonists are reported to have increased efficacy over GLP-1R monoagonists for the treatment of diabetes and obesity. We identified a novel GLP-1-based dual GLP-1R/GCGR agonist (xGLP/GCG-13) designed with a proper activity ratio favoring the GLP-1R versus the GCGR. However, the clinical utility of xGLP/GCG-13 is limited by its short half-life. Starting from xGLP/GCG-13, dual Cys mutation was performed, followed by covalent side-chain stapling and serum albumin binder incorporation, resulting in a stabilized secondary structure, enhanced agonist potency at GLP-1R and GCGR, and improved stability. The lead peptide (stapled xGLP/GCG-13 analogue with a palmitic acid albumin binder) exhibits balanced GLP-1R and GCGR activations and potent, long-lasting effects on glucose control. was further explored pharmacologically in diet-induced obesity and rodent models. Chronic administration of potently induced body weight loss and hypoglycemic effects, improved glucose tolerance, increased energy expenditure, and normalized lipid metabolism and adiposity in relevant animal models. These results indicated that has potential for development as a novel antidiabetic and/or antiobesity drug. Furthermore, we propose that the incorporation of a proper serum protein-binding motif into a di-Cys staple is an effective method for improving the stabilities and bioactivities of peptides. This approach is likely applicable to other therapeutic peptides, such as glucose-dependent insulin-tropic peptide receptor (GIPR) and GLP-1R dual agonists or GLP-1R/GCGR/GIPR triagonists.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00995DOI Listing
July 2021

Impact of the COVID-19 Pandemic on the Management of Acute Myocardial Infarction.

Int J Gen Med 2021 2;14:3119-3124. Epub 2021 Jul 2.

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

Aim: The coronavirus (COVID-19) outbreak in 2019 has negatively impacted the care of patients with other life-threatening diseases, including acute myocardial infarction (AMI). However, there is little published information concerning the depth of the impact on the clinical management and outcome following AMI.

Methods: We enrolled patients with AMI who received urgent primary percutaneous coronary intervention at the Beijing Tiantan Hospital (Beijing, China) between December 1, 2019 and April 10, 2020. Patients were divided into 2 cohorts, the pre-COVID-19 group (from December 1, 2019 to January 31, 2020) and during-COVID-19 group (from February 1, 2020 to April 10, 2020) for analysis. The door-to-balloon (D to B) time, total hospitalization stay (days) and coronary care unit (CCU) hospitalization days were calculated. New York Heart Association heart functional class (NYHA class), re-hospitalization and death ratio in patients were assessed between the two cohorts.

Results: A total of 148 AMI patients were enrolled in this study comprising 53 patients pre-COVID-19 group and 95 patients during-COVID-19 group. Patients with AMI during-COVID-19 group had longer symptom onset to hospital time (4.5 [2.0-9.3] vs 3.0 [2.0-5.0] hours, p = 0.013) and D to B time (96 [74-119] vs 67 [52-81] minutes, p <0.001); the D to B time shortened during the study period. The two cohorts did not have significantly different number of hospitalization days, re-hospitalization rates, peak cTnI, BNP or death rates. For the one-year follow-up, the patients in the during-COVID-19 group were classified as NYHA class III-IV more frequently (9 [9.7%] vs 0 [0%], p=0.004).

Conclusion: The COVID-19 pandemic significantly affected one measure of critical care of patients with AMI, NYHA classification, which may have resulted in increased medical expenses.
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http://dx.doi.org/10.2147/IJGM.S313165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260045PMC
July 2021

CsMYB60 directly and indirectly activates structural genes to promote the biosynthesis of flavonols and proanthocyanidins in cucumber.

Hortic Res 2020 Jul 1;7(1):103. Epub 2020 Jul 1.

State Key Laboratory of Crop Biology, Shandong Collaborative Innovation Center of Fruit & Vegetable Quality and Efficient Production, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops in Huang-Huai Region, Ministry of Agriculture, College of Horticultural Science and Engineering, Shandong Agricultural University, Tai'an, 271018, Shandong, China.

Flavonols and proanthocyanidins (PAs) are the main pigments in the black spines of cucumber (Cucumis sativus) fruit, and CsMYB60 is a key regulator of the biosynthesis of flavonols and PAs. However, in cucumber, the tissue distribution pattern of flavonols and PAs and the mechanism of their biosynthesis regulated by CsMYB60 remain unclear. In this study, we clarified the tissue-specific distribution of flavonoids and the unique transcriptional regulation of flavonoid biosynthesis in cucumber. CsMYB60 activated CsFLS and CsLAR by binding to their promoters and directly or indirectly promoted the expression of CsbHLH42, CsMYC1, CsWD40, and CsTATA-box binding protein, resulting in the formation of complexes of these four proteins to increase the expression of Cs4CL and interact with CsTATA-box binding protein to regulate the expression of CsCHS, thereby regulating the biosynthesis of flavonols and PAs in cucumber. Our data provide new insights into the molecular mechanism of flavonoid biosynthesis, which will facilitate molecular breeding to improve fruit quality in cucumber.
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http://dx.doi.org/10.1038/s41438-020-0327-zDOI Listing
July 2020

TERT Gene rs2736100 and rs2736098 Polymorphisms are Associated with Increased Cancer Risk: A Meta-Analysis.

Biochem Genet 2021 Jun 28. Epub 2021 Jun 28.

Department of The Sixth Dental Division, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, People's Republic of China.

Abnormal telomerase activity plays a key role in the development of carcinogenesis. The variants rs2736100 and rs2736098 of the telomerase reverse transcriptase (TERT) gene, which encodes the telomerase catalytic subunit, are associated with the risk of different types of cancers. However, the results remain controversy. We conducted a meta-analysis to more precisely assess this association. We comprehensively searched the PubMed and Web of Science databases up to June 1, 2020, and retrieved a total of 103 studies in 82 articles, including 89,320 cases and 121,654 controls. Among these studies, 69 published studies including 75,274 cases and 10,3248 controls were focused on rs2736100, and 34 published studies including 14,046 cases and 18,362 controls were focused on rs2736098. The results showed a strong association between variant rs2736100 and cancer risk in all populations. (G vs. T: OR 1.18, 95% CI 1.12-1.24; TG+GG vs. TT: OR 1.23, 95% CI 1.15-1.31; GG vs. TG+TT: OR 1.25, 95% CI 1.16-1.36); the variant rs2736098 was associated with cancer risk in all populations as well (A vs. G: OR 1.13, 95% CI 1.05-1.22; GA+AA vs. GG: OR 1.15, 95% CI 1.04-1.27; AA vs. GA+GG: OR 1.22, 95% CI 1.10-1.38). Stratified analysis based on the cancer type indicated that rs2736100 was associated with an increased risk of thyroid cancer, bladder cancer, lung cancer, glioma, and myeloproliferative neoplasms. rs2736098 only increased the risk of bladder cancer and lung cancer. Moreover, the TERT variants rs2736100 and rs2736098 were associated with a decreased risk of breast cancer and colorectal cancer. The variants rs2736098 and rs2736100 located in 5p15.33 around TERT were associated with increased cancer risk in all populations. These two variants had bidirectional effects in different tumors.
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http://dx.doi.org/10.1007/s10528-021-10097-0DOI Listing
June 2021

Bromodomain Inhibition Attenuates the Progression and Sensitizes the Chemosensitivity of Osteosarcoma by Repressing GP130/STAT3 Signaling.

Front Oncol 2021 8;11:642134. Epub 2021 Jun 8.

Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Osteosarcoma is the most common primary malignant bone tumor, and there are few ideal clinically available drugs. The bromodomain and extraterminal domain (BET) protein is an emerging target for aggressive cancer, but therapies targeting the BET in osteosarcoma have been unsuccessful in clinical trials to date, and further exploration of specific BET inhibitors is of great significance. In our study, we demonstrated that NHWD-870, a potent BET inhibitor in a phase I clinical trial, significantly inhibited tumor proliferation and promoted cell apoptosis by reversing the oncogenic signature in osteosarcoma. More importantly, we identified NHWD-870 impeded binding of BRD4 to the promoter of GP130 leading to diminished activation of JAK/STAT3 signaling pathway. Furthermore, GP130 knockdown significantly sensitizes the chemosensitivity . In OS cell-derived xenografts, NHWD-870 effectively inhibited the growth of osteosarcoma. Beyond that, NHWD-870 effectively inhibited the differentiation and maturation of precursor osteoclasts and attenuated osteoclast-mediated bone loss . Finally, we confirmed the efficacy of synthetic lethal effects of NHWD-870 and cisplatin in antagonizing osteosarcoma in a preclinical PDX model. Taken together, these findings demonstrate that NHWD-870, as an effective BET inhibitor, may be a potential candidate for osteosarcoma intervention linked to its STAT3 signaling inhibitory activity. In addition, NHWD-870 appears to be a promising therapeutic strategy for bone-associated tumors, as it interferes with the vicious cycle of tumor progression and bone destruction.
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http://dx.doi.org/10.3389/fonc.2021.642134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219214PMC
June 2021

Development and Molecular Cytogenetic Identification of a New Wheat- Keng Translocation Line Resistant to Powdery Mildew.

Front Plant Sci 2021 7;12:689502. Epub 2021 Jun 7.

College of Agronomy, Northwest A&F University, Yangling, China.

Keng, a wild relative of common wheat with many desirable traits, is an invaluable source of genetic material for wheat improvement. Few wheat- translocation lines resistant to powdery mildew have been reported. In this study, a wheat- line, E24-3-1-6-2-1, was generated distant hybridization, ethyl methanesulfonate (EMS) mutagenesis, and backcross breeding. A chromosome karyotype of 2 = 44 was observed at the mitotic stage in E24-3-1-6-2-1. Genomic hybridization (GISH) analysis revealed four translocated chromosomes in E24-3-1-6-2-1, and chromosome-specific marker analysis showed that the alien chromosome fragment was from the 4Ns chromosome. Moreover, fluorescence hybridization (FISH) analysis demonstrated that reciprocal translocation had occurred between the 4Ns chromosome and the wheat 3D chromosome; thus, E24-3-1-6-2-1 carried two translocations: T3DS·3DL-4NsL and T3DL-4NsS. Translocation also occurred between wheat chromosomes 2A and 4A. At the adult stage, E24-3-1-6-2-1 was highly resistant to powdery mildew, caused by prevalent pathotypes in China. Further, the spike length, numbers of fertile spikelets, kernels per spike, thousand-kernel weight, and grain yield of E24-3-1-6-2-1 were significantly higher than those of its wheat parent 7182 and addition line 24-6-3-1. Thus, this translocation line that is highly resistant to powdery mildew and has excellent agronomic traits can be used as a novel promising germplasm for breeding resistant and high-yielding cultivars.
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http://dx.doi.org/10.3389/fpls.2021.689502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215663PMC
June 2021

High Th2 cytokine levels and upper airway inflammation in human inherited T-bet deficiency.

J Exp Med 2021 Aug 23;218(8). Epub 2021 Jun 23.

Institute of Microbiology, Eidgenössische Technische Hochschule Zurich, Zurich, Switzerland.

We have described a child suffering from Mendelian susceptibility to mycobacterial disease (MSMD) due to autosomal recessive, complete T-bet deficiency, which impairs IFN-γ production by innate and innate-like adaptive, but not mycobacterial-reactive purely adaptive, lymphocytes. Here, we explore the persistent upper airway inflammation (UAI) and blood eosinophilia of this patient. Unlike wild-type (WT) T-bet, the mutant form of T-bet from this patient did not inhibit the production of Th2 cytokines, including IL-4, IL-5, IL-9, and IL-13, when overexpressed in T helper 2 (Th2) cells. Moreover, Herpesvirus saimiri-immortalized T cells from the patient produced abnormally large amounts of Th2 cytokines, and the patient had markedly high plasma IL-5 and IL-13 concentrations. Finally, the patient's CD4+ αβ T cells produced most of the Th2 cytokines in response to chronic stimulation, regardless of their antigen specificities, a phenotype reversed by the expression of WT T-bet. T-bet deficiency thus underlies the excessive production of Th2 cytokines, particularly IL-5 and IL-13, by CD4+ αβ T cells, causing blood eosinophilia and UAI. The MSMD of this patient results from defective IFN-γ production by innate and innate-like adaptive lymphocytes, whereas the UAI and eosinophilia result from excessive Th2 cytokine production by adaptive CD4+ αβ T lymphocytes.
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http://dx.doi.org/10.1084/jem.20202726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225679PMC
August 2021

The Mediating Effect of Positive Illness Cognitions on Experiential Avoidance and Quality of Life in Breast Cancer Patients.

Asia Pac J Oncol Nurs 2021 Jul-Aug;8(4):427-432. Epub 2021 Apr 24.

School of Nursing, Xuzhou Medical University, Department of Nursing Administration, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Objective: Illness cognition plays an essential role during physical, psychological, and social adjustment among patients with cancer. The present study aims to explore the mediating effects of positive illness cognition on experiential avoidance and quality of life (QOL) in this population.

Methods: Between August 2017 and June 2019, we recruited 312 patients with breast cancer in the treatment period from a general tertiary hospital's breast department using convenience sampling. We used the Illness Cognition Questionnaire, the Acceptance and Action Questionnaire II, and the Functional Assessment of Cancer Therapy-Breast Scale.

Results: The mean score of QOL was 93.39 (SD: 18.60) for patients with breast cancer. Positive illness cognition was closely related to the QOL and experiential avoidance. Experiential avoidance significantly negatively correlated with QOL ( = -0.59, < 0.01) and positive illness cognition ( = -0.60, < 0.01), while positive illness cognition significantly positively correlated with QOL ( = 0.82, < 0.01). Positive illness cognition had a mediating effect between experiential avoidance and QOL (effect size: -0.56), accounting for 87.14% of the total effect.

Conclusions: The QOL was low in Chinese patients with breast cancer. Positive illness cognition had a mediating effect between experiential avoidance and QOL. Caregivers should indirectly improve patients' QOL with breast cancer by improving their positive illness cognition levels.
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http://dx.doi.org/10.4103/apjon.apjon-20102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186393PMC
April 2021

Effect of Low Nutrition and T-2 Toxin on C28/I2 Chondrocytes Cell Line and Chondroitin Sulfate-Modifying Sulfotransferases.

Cartilage 2021 Jun 19:19476035211023555. Epub 2021 Jun 19.

School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.

Objective: To investigate the effects of low nutrition and trichothecenes-2 toxin (T-2) on human chondrocytes cell line C28/I2 and the gene expression levels of some chondroitin sulfate (CS)-modifying sulfotransferases.

Methods: The chondrocytes were divided into 4 intervention groups: (a) control group (Dulbecco's modified Eagle's medium/Nutrient Mixture F-12 [DMEM/F-12] with fetal bovine serum [FBS]), (b) low-nutrition group (DMEM/F-12 without FBS), (c) T-2 group (DMEM/F-12 with FBS plus 20 ng/mL T-2), and (d) combined group (DMEM/F-12 without FBS plus 20 ng/mL T-2). Twenty-four hours postintervention, ultrastructural changes in the chondrocytes were observed by transmission electron microscopy (TEM). Live cell staining and methyl thiazolyl tetrazolium (MTT) assay were performed to observe cell viability. The expression of CS-modifying sulfotransferases, including carbohydrate sulfotransferase 3, 12, 13, 15 (CHST-3, CHST-12, CHST-13, and CHST-15, respectively), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction (RT-qPCR) analysis.

Results: The cells in the T-2 group and combined group had significantly lower live cell counts and relative survival rates than the control group. TEM pictures revealed decreased electron density of mitochondria in the low-nutrition group. The T-2 group and combined group both caused mitochondrial swelling, damage, and reduction in mitochondrial number. RT-qPCR showed a trend of altered expression of CHST and increased expression of UST genes under low-nutrition, T-2 toxin and combined interventions.

Conclusions: These results show early-stage Kashin-Beck disease chondrocyte pathophysiology, consisting of chondrocyte cell damage and compensatory upregulation of CHST and UST genes.
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http://dx.doi.org/10.1177/19476035211023555DOI Listing
June 2021

Personalized medicine modality based on patient-derived xenografts from a malignant transformed GCTB harboring H3F3A G34W mutation.

J Orthop Translat 2021 Jul 1;29:106-112. Epub 2021 Jun 1.

Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.

Background: The function of H3F3A G43W mutation, which has been observed in almost all GCTB, remains poorly characterized. Breakthrough in malignant GCTB has been trapped by the lack of clinical available drugs, limited canonical patient samples and paucity of fidelity preclinical models.

Methods: Tumor samples obtained from a malignant GCTB was implanted in immunodeficient mice for the generation of PDX. Histological examination and short tandem repeat (STR) were used for inherited features analyses. An epigenetic/transcriptional targeted compound library was selected for drug screening. The in vivo effects of selected drug were validated in PDX model.

Results: We established the PDX model with recurrent malignant GCTB specimens, histological examination and STR analyses revealed that PDX and their corresponding parental patients shared the same STRs and histologic features, suggesting common origins. ITF-2357 was the most significant compound with an IC50 lower than 0.1 uM. The results of the drug screening and in vivo PDX validation demonstrated that ITF-2357 might be a promising drug targeted H3F3A G34W mutation MGCTBs.

Conclusion: Our study demonstrates that PDX model maintained the same histologic and genetic features as those in the original patient. targeting HDAC through ITF-2357 effectively overcomes malignant GCTB progression in vitro and in vivo.

Translational Potential Statement: As PDX retain the principal histologic and genetic characteristics of the primary tumors, mad it a valuable research tool in predictive clinical efficacy. In this study, we first established a malignant GCTB PDX model, which might further accelerate the progress of drug development in malignant GCTB.
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http://dx.doi.org/10.1016/j.jot.2021.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173097PMC
July 2021

MicroRNA-135b/CAMK2D Axis Contribute to Malignant Progression of Gastric Cancer through EMT Process Remodeling.

Int J Biol Sci 2021 10;17(8):1940-1952. Epub 2021 May 10.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital, Fu-Cheng Road, Beijing, 100142, China.

There is a continued need for investigating the roles of microRNAs (miRNAs) and their targets on the progression of gastric cancer (GC), especially metastasis. Here, we performed an integrated study to identify dysregulated miRNAs critical for GC development and progression. miR-135b was determined as a promising biomarker for GC. The expression level of miR-135b was increased among GC cell lines, patient tumor tissues, serum samples, and correlation with aggravation of the GC patients. The functional assays demonstrated overexpression of miR-135b promoted cell proliferation, migration and invasion in GC, while miR-135b inhibition led to the opposite results. CAMK2D was found to be the direct target of miR-135b, serving as a tumor suppressor in GC cells. Based on our and public datasets, we confirmed the attenuation of CAMK2D expression in GC tissues. And, the expression levels of miR-135b and CAMK2D were closely associated with prognosis of GC patients. Ectopic expression of miR-135b resulted in the down-regulation of CAMK2D. Additionally, CAMK2D was a prerequisite for miR-135b to promote GC cells proliferation and migration by regulating the EMT process, which was confirmed by the experiments. Importantly, injection of miR-135b antagomir significantly repressed the tumor growth and metastasis of xenograft models, which suggested that the miR-135b antagomir were promising for clinical applications. Taken together, these results indicate that miR-135b/CAMK2D axis drives GC progression by EMT process remodeling, suggesting that miR-135b may be utilized as a new therapeutic target and prognostic marker for GC patients.
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http://dx.doi.org/10.7150/ijbs.58062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193265PMC
May 2021

Efficacy and safety of bloodletting for herpes zoster: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jun;100(22):e26169

Shandong University of Traditional Chinese Medicine.

Background: The study aims to evaluate the effectiveness and safety of bloodletting therapy for herpes zoster.

Methods: The following electronic databases will be searched from PubMed (1966 to March 2020), the Cochrane Central Register of Controlled Trials (update to March 2020), EMBASE (1980 to March 2020), China National Knowledge Infrastructure (1979 to March 2020), Wan Fang Data (1980 to March 2020), Chinese Scientific Journal Database (1989 to March 2020), Chinese Biomedical Database (1978 to March 2020) and traditional Chinese medicine Literature Analysis and Retrieval Database (1949 to March 2020). All randomized controlled trials without any limitation of blinding or publication language about this topic will be included, exclude cohort studies and case reports. Two independent researchers will operate article retrieval, duplication removing, screening, quality evaluation, and data analyses by Review Manager (V.5.3.5). Meta-analyses, subgroup analysis, and/or descriptive analysis will be performed based on the included data conditions.

Results: High-quality synthesis and/or descriptive analysis of current evidence will be provided from cure rate, converting to clinical diagnosis rate, and side effects of bloodletting.

Conclusion: This study will provide the evidence of whether bloodletting is an effective and safe intervention for herpes zoster.

Prospero Registration Number: CRD42020171976.
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http://dx.doi.org/10.1097/MD.0000000000026169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183816PMC
June 2021

Yinzhihuang Oral Liquid Ameliorates Hyperbilirubinemia Induced by δ-Aminolevulinic Acid and Novobiocin in Neonatal Rats.

Chem Biodivers 2021 Jun 3. Epub 2021 Jun 3.

School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin, 300072, P. R. China.

Yinzhihuang oral liquid (YZH) is a traditional Chinese medicine that has been widely used in Asia to prevent and treat neonatal hyperbilirubinemia, but the published preclinical studies on its anti-hyperbilirubinemia effect are conducted in adult animals, partly due to the lack of preclinical neonatal hyperbilirubinemia animal models. In the present study, we tested six reagents to induce hyperbilirubinemia in neonatal rats, and established two appropriate neonatal hyperbilirubinemia rat models by subcutaneous injection of δ-Aminolevulinic acid (ALA, 200 mg/kg) or novobiocin (NOVO, 200 mg/kg). Oral treatment of YZH (80, 160 and 320 mg/kg) significantly decreased serum conjugated bilirubin levels in ALA-treated neonatal rats and serum unconjugated bilirubin levels in NOVO-treated neonatal rats, respectively. Additionally, pre-treatment of YZH also prevented the increase of serum bilirubin levels in both ALA- and NOVO-treated rats. Mechanistically, YZH significantly up-regulated the mRNA expression of genes involved in hepatic bilirubin disposition (organic anion-transporting polypeptide 1b2, Oatp1b2; multidrug resistance-associated protein 2, Mrp2) and bilirubin conjugation (UDP-glucuronosyltransferase 1a1, Ugt1a1). Additionally, YZH up-regulated the mRNA expression of cytochrome P450 1A1 (Cyp1a1), the target gene of aryl hydrocarbon receptor (AhR), and increased the nuclear protein levels of AhR in livers of neonatal rats. YZH and its two active ingredients, namely baicalin (BCL) and 4'-hydroxyacetophenone (4-HT), up-regulated the mRNA expression of AhR target genes (CYP1A1 and UGT1A1) and increased nuclear protein levels of AhR in HepG2 cells. In conclusion, the present study provides two neonatal hyperbilirubinemia animal models and evaluates the anti-hyperbilirubinemia effect and mechanisms of YZH in neonatal animals.
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http://dx.doi.org/10.1002/cbdv.202100222DOI Listing
June 2021

Emotional State and Feedback-Related Negativity Induced by Positive, Negative, and Combined Reinforcement.

Front Psychol 2021 10;12:647263. Epub 2021 May 10.

MOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an, China.

Reinforcement learning relies on the reward prediction error (RPE) signals conveyed by the midbrain dopamine system. Previous studies showed that dopamine plays an important role in both positive and negative reinforcement. However, whether various reinforcement processes will induce distinct learning signals is still unclear. In a probabilistic learning task, we examined RPE signals in different reinforcement types using an electrophysiology index, namely, the feedback-related negativity (FRN). Ninety-four participants were randomly assigned into four groups: base (no money incentive), positive reinforcement (presentation of money rewards), negative reinforcement (removal of money losses), and combined reinforcement (money rewards and removal of money losses) groups. In addition, in order to evaluate the engagement of emotional activity in the different reinforcement processes, Positive and Negative Affect Schedule-Expanded Form (PANAS-X) scales were applied before and after the experiment to detect the emotional changes. The results showed that there was no difference between groups in the dopamine-related learning bias. However, compared to the other three groups, negative reinforcement elicited smaller FRN (the difference-wave measure) during the learning, stronger positive affect and joviality, and less fatigue after the learning, in which the difference between the negative and positive reinforcement groups was smaller. The results indicated that pure avoidance motivation may induce distinct emotional fluctuations, which influence the feedback processing.
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http://dx.doi.org/10.3389/fpsyg.2021.647263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141566PMC
May 2021

Stress Controllability Modulates Basal Activity of Dopamine Neurons in the Substantia Nigra Compacta.

eNeuro 2021 May-Jun;8(3). Epub 2021 Jun 16.

MOE Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xi'an 710062, China

Prolonged stress induces neural maladaptations in the mesolimbic dopamine (DA) system and produces emotional and behavioral disorders. However, the effects of stress on activity of DA neurons are diverse and complex that hinge on the type, duration, intensity, and controllability of stressors. Here, controlling the duration, intensity, and type of the stressors to be identical, we observed the effects of stressor controllability on the activity of substantia nigra pars compacta (SNc) DA neurons in mice. We found that both lack and loss of control (LOC) over shock enhance the basal activity and intrinsic excitability of SNc DA neurons via modulation of I current, but not via corticosterone serum level. Moreover, LOC over shock produces more significant enhancement in the basal activity of SNc DA neurons than that produced by shock per se, and therefore attenuates the response to natural reward. This attenuation can be reversed by control over shock. These results indicate that although chronic stress per se tends to enhance the basal activity of SNc DA neurons, LOC over the stressor is able to induce a larger enhancement in the basal activity of SNc DA neurons and produce more severe behavioral deficits. However, control over stress ameliorates the deleterious effects of stress, highlighting the role of stress controllability.
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http://dx.doi.org/10.1523/ENEURO.0044-21.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211467PMC
July 2021

Analysis of dose monitoring for external exposure to radiology in hospital workers from 2010 to 2018.

Am J Transl Res 2021 15;13(4):3357-3362. Epub 2021 Apr 15.

Department of Infection Prevention and Control, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology Beijing, China.

Objective: To investigate the individual level of radiation exposure in hospital workers from 2010 to 2018.

Methods: Oral radiology workers in our hospital including medical imaging technicians and radiation therapists from 2010 to 2018 were selected as the subjects of investigation. The oral radiological workers were monitored quarterly according to the level of external exposure via individual dose monitoring standards. The monitoring data were aggregated, analyzed and evaluated.

Results: A total of 531 hospital radiology workers were monitored from 2010 to 2018. The rate of effective monitoring per year for medical imaging technicians and radiation therapists was 97.35% and 97.47%, respectively. The average collective effective dose was 8.511 mSv, and annual effective dose per capita was 0.148 mSv. The highest collective effective dose was in 2017, while the highest annual effective dose per capita was in 2010. The annual effective dose per capita for medical imaging technicians was lower than that for radiation therapists. The abnormal rate of personal doses of radiation therapists was higher than that for medical imaging technicians. The collective effective dose changes in the two types of radiation workers were monitored from 2010 to 2018, showing an increased trend. The fluctuations of annual effective dosing per capita monitored from 2010 to 2018 in radiation therapists was more significant than that in medical imaging technicians.

Conclusions: Oral radiation workers monitored were all far below the dose limit of 20 mSv, which indicated that the working environment of oral radiation workers in our hospital was safe with good radiation condition and protection.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129226PMC
April 2021

Characteristics of purified Anti-β2GPI IgG N-glycosylation associate with thrombotic, obstetric, and catastrophic antiphospholipid syndrome.

Rheumatology (Oxford) 2021 May 20. Epub 2021 May 20.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.

Objective: Anti-β-2 glycoprotein I (anti-β2GPI) antibodies, defined as primary pathogenic antibody in antiphospholipid syndrome (APS). It has been reported that IgG Fc N-glycosylation affects IgG effector, we aim to investigate the association of Fc glycosylation profiles of purified anti-β2GP1 IgG with clinical features of APS.

Methods: We purify anti-β2GPI IgG and total IgG from 82 APS patients including 9 catastrophic antiphospholipid syndrome (CAPS) patients, as well as total IgG from 103 healthy controls to quantitatively analyze all detectable Fc N-glycanforms of all IgG subclasses with Multiple Reaction Monitoring (MRM) method based on UPLC-ESI-QqQ mass spectrometry.

Results: Both purified anti-β2GPI IgG and APS total IgG showed altered N-glycan profiles when compared with HC IgG. Anti-β2GPI IgG presented with lower galactosylation, increased bisection and core fucosylation compared with APS total IgG and HC IgG. We found higher galactosylation of aβ2GPI IgG2 in thrombotic APS compared with the obstetric APS, and lower galactosylation of aβ2GPI IgG2 associated with late pregnancy morbidity. Moreover, low galactosylation of all anti-β2GPI IgG subclasses, increased bisection and core fucosylation of anti-β2GPI IgG1/2 were strongly associated with CAPS and triple positivity of antiphospholipid antibodies (aPLs).

Conclusion: We comprehensively characterize the N-Glycans landscape of both anti-β2GP1 and total IgG in APS. Altered N-glycan profiles of anti-β2GPI IgG enables enabled the antibodies with proinflammatory properties. Furthermore, we associated levels of IgG Fc-glycosylation with clinical features antiphospholipid syndrome. These findings could increase our understanding of anti-β2GPI antibody mediated mechanisms in APS and be used to develop diagnostics and new target treatments.
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http://dx.doi.org/10.1093/rheumatology/keab416DOI Listing
May 2021

Sensing ATP: Zeolitic Imidazolate Framework-67 Is Superior to Aptamers for Target Recognition.

Anal Chem 2021 06 17;93(21):7707-7713. Epub 2021 May 17.

Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.

In a typical biosensor, a biomolecule such as an aptamer is used for target recognition, and a nanomaterial is used for signal generation. Herein, we communicate a reverse system using a nanomaterial for target recognition and a DNA for signaling. We discovered that a classic metal-organic framework material, zeolitic imidazolate framework (ZIF)-67, has ultrahigh selectivity for recognizing adenosine triphosphate (ATP), allowing a fluorescently labeled DNA oligonucleotide to be used for signal generation. This sensor showed up to a 24-fold increase in fluorescence upon adding 1 mM ATP, while the fluorescence increase after adding adenosine or guanosine triphosphate was less than twofold. Its selectivity is much better than that of the ATP aptamer, which binds adenosine even better. Using isothermal titration calorimetry, the selective binding of ATP was independently verified. This sensor has a detection limit of 29 nM ATP and it can even detect ATP in serum. By replacing Co with Zn to form ZIF-8 or by using CoO, the selectivity for ATP was lost. Therefore, by sophisticated material design, ultrahigh selectivity for molecular recognition can be achieved.
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http://dx.doi.org/10.1021/acs.analchem.1c00976DOI Listing
June 2021

Nonlinear super-resolution imaging via orientationally enhanced photorefractive effect in polymer.

Opt Lett 2021 May;46(10):2441-2444

Resulting from the attenuation of evanescent waves in imaging, conventional microscopy techniques always yield few subwavelength features. In this Letter, a nonlinear far-field super-resolution technique is investigated, which is theoretically beyond the linear diffraction limitation. Based on the orientationally enhanced photorefractive effect of polymer, an inherently phase-matched diffraction grating is established and generates daughter modes by wave mixture. Almost all of these modes can pass through a finite-aperture filter and be sensed for reconstruction. An improvement of resolution of about four times is obtained and expected to be increased further. This work may provide a potential strategy for various subwavelength-resolved imaging applications.
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http://dx.doi.org/10.1364/OL.424482DOI Listing
May 2021

Tunable dual-band mid-infrared absorber based on the coupling of a graphene surface plasmon polariton and Tamm phonon-polariton.

Opt Express 2021 May;29(10):15228-15238

We propose and demonstrate a tunable dual-band mid-infrared absorber structure based on the coupling effect of a surface plasmon polariton (SPP) and Tamm phonon-polariton (TPhP). The structure is composed of the distributed Bragg reflector (DBR), air layer, SiC and graphene ribbons. In the air layer, the graphene ribbons are embedded to realize the localized SPP (LSPP), which makes the structure support both the graphene LSPP (GLSPP) and TPhP. The absorption properties of the structure are investigated theoretically and numerically. It is found that strong coupling of the GLSPP and TPhP can be realized by choosing reasonable parameters, which causes a dual-frequency perfect absorption and makes the maximum Rabi splitting of the coupled mode reach 5.76 meV. Furthermore, the mode coupling and absorption intensity can be tuned by adjusting the thickness of the air layer and the Fermi level of the graphene ribbons. This work might provide new possibilities for the development of mid-infrared band sensors, filters and emitters based on the coupling of multiple modes.
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http://dx.doi.org/10.1364/OE.424101DOI Listing
May 2021

MYLK4 promotes tumor progression through the activation of epidermal growth factor receptor signaling in osteosarcoma.

J Exp Clin Cancer Res 2021 May 12;40(1):166. Epub 2021 May 12.

Department of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, P. R. China.

Background: Osteosarcoma (OS) is the most common primary bone cancer in adolescents and lung metastasis is the leading cause of death in patients with OS. However, the molecular mechanisms that promote OS growth and metastasis remain unknown.

Methods: We investigated the expression of myosin light chain kinase family members between metastasis and non-metastasis patients in the TARGET database and ensured that only myosin light chain kinase family member 4 (MYLK4) had higher expression in metastatic osteosarcoma patients. Then we confirmed the results by immunohistochemistry (IHC) and Western blotting (WB) of OS tissues. The effect of MYLK4 on the metastasis and proliferation of OS cells was investigated by wound healing, Transwell and colony-formation assays. Mass spectrum analysis was used to ensure the new binding protein of MYLK4. Tissue microarrays analysis was used to show the correlation between MYLK4 and pEGFR (Y1068). A series of in vivo experiments were conducted to reveal the mechanisms by which MYLK4 modulated the metastasis and proliferation of OS.

Results: Myosin Light Chain Kinase Family Member 4 (MYLK4) was significantly upregulated in metastatic human OS tissues. Growth and metastasis of OS could be accelerated by MYLK4 overexpression, whereas silencing MYLK4 expression resulted in decreased cell growth and metastasis. Mechanistically, mass spectrum analysis showed that MYLK4 interacted with the epidermal growth factor receptor (EGFR) in osteosarcoma cells and promoted growth and metastasis via the EGFR signaling pathway. Tissue microarrays analysis also showed that MYLK4 expression had a positive correlation with the expression of pEGFR (Y1068). Moreover, the EGFR inhibitor gefitinib could partially reverse the effect of cell proliferation and metastasis caused by MYLK4 overexpression. Importantly, the combination of MYLK4 and EGFR inhibitors had synergistic effects on growth and metastasis of OS in vitro and in vivo.

Conclusion: Our results indicate that MYLK4 promotes OS growth and metastasis by activating the EGFR signaling pathway and can be a novel therapeutic target for the treatment of OS patients.
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http://dx.doi.org/10.1186/s13046-021-01965-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114533PMC
May 2021
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