Publications by authors named "Hongbin Zhang"

292 Publications

Effects of Doping Ni on the Microstructures and Thermoelectric Properties of Co-Excessive NbCoSn Half-Heusler Compounds.

ACS Appl Mater Interfaces 2021 Jul 19. Epub 2021 Jul 19.

Department of Materials Science, Technical University of Darmstadt, Darmstadt 64287, Germany.

The half-Heusler (HH) compound NbCoSn with 18 valence electrons is a promising thermoelectric (TE) material due to its appropriate electrical properties as well as its suitable thermal and chemical stability. Nowadays, doping/substitution and tailoring of microstructures are common experimental approaches to enhance the TE performance of HH compounds. However, detailed theoretical insights into the effects of doping on the microstructures and TE properties are still missing. In this work, the microstructure of NbCoSn was tailored through precipitating the full-Heusler phases in the matrix by changing the nominal ratio of Co and Ni on the Co sites, focusing on the resulting TE properties. Further, first-principles calculations were employed to understand the relationship between the microstructure and the TE properties from the thermodynamic point of view. Detailed analysis of the electronic structure reveals that the presence of excess Co/Ni contributes to the increasing carrier concentration. Through an increase in the electrical conductivity and a reduction in the thermal conductivity, the TE performance is improved. Therefore, the present work offers a new pathway and insights to enhance the TE properties by modifying the microstructure of HH compounds via tailoring the chemical compositions.
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http://dx.doi.org/10.1021/acsami.1c08127DOI Listing
July 2021

MRI Features of Hepatic Sarcomatoid Carcinoma Different From Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

Front Oncol 2021 17;11:611738. Epub 2021 Jun 17.

Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Introduction: Hepatic sarcomatoid carcinoma (HSC) is a rare type of liver cancer with a high malignant grade and poor prognosis. This study compared the clinical characteristics and magnetic resonance imaging (MRI) features of HSCs with those of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), aiming to identify valuable features for HSC diagnosis.

Methods: In total, 17 pathologically confirmed HSC cases, 50 HCC cases and 50 common ICC cases were enrolled from two hospitals. The clinical characteristics and MRI features of all cases were summarized and statistically analyzed.

Results: On the one hand, the incidence rates of elevated carbohydrate antigen (CA) 19-9 and elevated carcinoembryonic antigen (CEA) were significantly higher in the HSC cases than in the HCC cases (29.4% 0%; 17.6% 0%). The HSC enhancement patterns, primarily including progressive enhancement, were also significantly different from HCC cases. The incidence rates of heterogeneous signals on T2-weighted imaging and during the arterial phase were significantly higher in the HSC cases than in the HCC cases (94.1% 66.0%; 100.0% 72.0%). The diameter of HSCs was significantly larger than that in the HCC cases (6.12 cm 4.21 cm), and the incidence rates of adjacent cholangiectasis, intrahepatic metastasis and lymph node enlargement were considerably higher in the HSC cases than in the HCC cases (52.9% 6.0%; 47.1% 12.0%; 41.2% 2.0%). On the other hand, the incidence rate of elevated CA199 was significantly lower in the HSC cases than in the ICC cases (29.4% 60.0%). The incidence rates of intratumoral necrosis and pseudocapsules were significantly higher in the HSC cases than in the HCC cases (35.3% 8.0%; 47.1% 12.0%). However, the incidence rates of target signs were significantly lower in the HSC cases than in the HCC cases (11.8% 42.0%). In addition, there was no significant difference in the enhancement patterns between HSC cases and ICC cases.

Conclusions: HSCs were frequently seen in elderly men with clinical symptoms and elevated CA199 levels. The MRI features, including large size, obvious heterogeneity, hemorrhage, progressive enhancement, pseudocapsule and lymph node enlargement, contributed to the diagnosis of HSC.
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http://dx.doi.org/10.3389/fonc.2021.611738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247642PMC
June 2021

Epitaxy Induced Highly Ordered SmCo-SmCo Nanoscale Thin-Film Magnets.

ACS Appl Mater Interfaces 2021 Jul 29;13(27):32415-32423. Epub 2021 Jun 29.

Institute of Materials Science, Technische Universität Darmstadt, 64287 Darmstadt, Germany.

Utilizing the molecular beam epitaxy technique, a nanoscale thin-film magnet of -axis-oriented SmCo and SmCo phases is stabilized. While typically in the prototype Sm(Co, Fe, Cu, Zr) pinning-type magnets, an ordered nanocomposite is formed by complex thermal treatments, here, a one-step approach to induce controlled phase separation in a binary Sm-Co system is shown. A detailed analysis of the extended X-ray absorption fine structure confirmed the coexistence of SmCo and SmCo phases with 65% SmCo and 35% SmCo. The SmCo phase is stabilized directly on an AlO substrate up to a thickness of 4 nm followed by a matrix of SmCo intermixed with SmCo. This structural transition takes place through coherent atomic layers, as revealed by scanning transmission electron microscopy. Highly crystalline growth of well-aligned SmCo and SmCo phases with coherent interfaces result in strong exchange interaction, leading to enhanced magnetization and magnetic coupling. The arrangement of SmCo and SmCo phases at the nanoscale is reflected in the observed magnetocrystalline anisotropy and coercivity. As next-generation permanent magnets require designing of materials at an atomic level, this work enhances our understanding of self-assembling and functioning of nanophased magnets and contributes to establishing new concepts to engineer the microstructure for beyond state-of-the-art magnets.
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http://dx.doi.org/10.1021/acsami.1c04780DOI Listing
July 2021

Transition-metal-free allylation of 2-azaallyls with allyl ethers through polar and radical mechanisms.

Nat Commun 2021 06 23;12(1):3860. Epub 2021 Jun 23.

Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, Department of Chemistry, University of Pennsylvania, Philadelphia, PA, USA.

Allylation of nucleophiles with highly reactive electrophiles like allyl halides can be conducted without metal catalysts. Less reactive electrophiles, such as allyl esters and carbonates, usually require a transition metal catalyst to facilitate the allylation. Herein, we report a unique transition-metal-free allylation strategy with allyl ether electrophiles. Reaction of a host of allyl ethers with 2-azaallyl anions delivers valuable homoallylic amine derivatives (up to 92%), which are significant in the pharmaceutical industry. Interestingly, no deprotonative isomerization or cyclization of the products were observed. The potential synthetic utility and ease of operation is demonstrated by a gram scale telescoped preparation of a homoallylic amine. In addition, mechanistic studies provide insight into these C(sp)-C(sp) bond-forming reactions.
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http://dx.doi.org/10.1038/s41467-021-24027-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222226PMC
June 2021

Nickel-catalyzed enantioselective vinylation of aryl 2-azaallyl anions.

Chem Sci 2021 Mar 26;12(18):6406-6412. Epub 2021 Mar 26.

Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, Department of Chemistry, University of Pennsylvania 231 South 34th Street Philadelphia PA USA

A unique enantioselective nickel-catalyzed vinylation of 2-azaallyl anions is advanced for the first time. This method affords diverse vinyl aryl methyl amines with high enantioselectivities, which are frequently occurring scaffolds in natural products and medications. This C-H functionalization method can also be extended to the synthesis of enantioenriched 1,3-diamine derivatives by employing suitably elaborated vinyl bromides. Key to the success of this process is the identification of a Ni/chiraphos catalyst system and a less reducing 2-azaallyl anion, all of which favor an anionic vinylation route over a background radical reaction. A telescoped gram scale synthesis and a product derivatization study confirmed the scalability and synthetic potential of this method.
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http://dx.doi.org/10.1039/d1sc00972aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115067PMC
March 2021

Chemoprotective Effects of Geraniin against Azoxymethane Induced Colorectal Cancer by Reduction of Inflammatory Reaction.

J Oleo Sci 2021 ;70(6):817-825

Department of Oncology First Affiliated Hospital of Kunming Medical University.

The leading cause of cancer-related death is colorectal cancer, and inflammatory bowel disease is a risk factor for this disease. Azoxymethane (AOM) is a potent cancer inducer widely used in rats for colon cancer. The current study was scrutinizing the chemo-protective effect of geraniin against AOM induced colorectal cancer via alteration of oxidative stress and inflammatory cytokines. The rats were divided into different groups such as Group I: normal control, Group II geraniin (20 mg/kg), Group III: received AOM, Group IV-VI: AOM + geraniin (5, 10 and 20 mg/kg), respectively. All group of rats were received treatment for 16 weeks. At the end of the experimental study, the hepatic, biochemical, phase II antioxidant, antioxidant enzymes, cytokines, apoptosis and inflammatory mediators were estimated. Geraniin treatment significantly reduced tumor weight and enhanced body weight. Geraniin administration also altered the level of antioxidant parameters-superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR); phase I enzymes - cytochrome B, cytochrome P; phase II enzymes - Glutathione-S-Transferase (GST), UDP-Glucuronyl transferase (UDP-GT) respectively. Obtained results also demonstrate that geraniin treatment reduced the level of pro-inflammatory cytokines such as IL-2, IL-1α, IL-10, IL-1β, IL-4, IL-6, IL-12, IL-17A, IFN-γ, tumor necrosis factor-α, G-CSF, and GM-CSF. Geraniin also reduced the expression of IL-1α, IL-1β, IL-6, IFN-γ, G-CSF, and GM-CSF. On the basis of result we can conclude that geraniin reduced the colorectal cancer via inflammatory pathway.
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http://dx.doi.org/10.5650/jos.ess21034DOI Listing
January 2021

Identification of a Novel TAR RNA-Binding Protein 2 Modulator with Potential Therapeutic Activity against Hepatocellular Carcinoma.

J Med Chem 2021 06 26;64(11):7404-7421. Epub 2021 May 26.

Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.

Imbalance miRNAs contribute to tumor formation; therefore, the development of small-molecule compounds that regulate miRNA biogenesis is an important strategy in oncotherapy. Here, (-)-Gomisin M1 (GM) was found to modulate miRNA biogenesis to inhibit the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells. GM modulated expression profiles of miRNA and protein in HCC cells and suppressed tumor growth in a mouse model. Mechanistically, GM affected miRNA maturation by targeting TAR RNA-binding protein 2 (TRBP), with an efficacy higher than that of enoxacin, and promoted the binding of TRBP with Dicer. Structural simplification and a preliminary structure-activity relationship study via the synthesis of 20 GM derivatives showed that compound exhibited more potent inhibitory activity in HCC cell proliferation and affinity for TRBP than did GM. These results suggest that TRBP may be a novel potential therapeutic target in HCC and compound may be a potential drug candidate for the treatment of HCC.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00018DOI Listing
June 2021

IQGAP2 acts as an independent prognostic factor and is related to immunosuppression in DLBCL.

BMC Cancer 2021 May 25;21(1):603. Epub 2021 May 25.

Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, No 1, Youyi Road, Yuzhong District, Chongqing, 400016, China.

Background: Almost one-third of patients with diffuse large B-cell lymphoma (DLBCL) cannot be cured with initial therapy and will eventually succumb to the disease. Further elaboration of prognostic markers of DLBCL will provide therapeutic targets. IQ motif-containing GTPase activating protein 2 (IQGAP2) acts as a tumour suppressor in hepatocellular, prostate, and gastric cancers. However, the role of IQGAP2 in DLBCL remains unclear.

Methods: We collected mRNA expression data from 614 samples and the corresponding clinical information. The survival time of patients was compared between groups according to the mRNA expression level of IQGAP2. Survival analyses were performed in different subgroups when considering the effect of age, tumour stage, serum lactate dehydrogenase (LDH) concentration, performance status, and the number of extra nodal disease sites. The biological processes associated with IQGAP2-associated mRNAs were analysed to predict the function of IQGAP2. The correlation of IQGAP2 mRNA with immunosuppressive genes and leukocyte infiltration were analysed.

Results: The overall survival of patients with increased IQGAP2 mRNA levels was reduced even after aggressive treatment independent of age, tumour stage, serum LDH concentration, performance status, and the number of extra nodal disease sites. Furthermore, the biological processes of IQGAP2-associated mRNAs were mainly immune processes. IQGAP2 mRNA expression was correlated with the expression of immunosuppressive genes and leukocyte infiltration.

Conclusion: IQGAP2 mRNA is an independent prognostic factor and is related to immunosuppression in DLBCL. This discovery may provide a promising target for further development of therapy.
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http://dx.doi.org/10.1186/s12885-021-08086-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152057PMC
May 2021

Accelerating biological insight for understudied genes.

Integr Comp Biol 2021 May 10. Epub 2021 May 10.

Bioengineering Branch, NASA Ames Research Center, Moffett Field, CA USA.

The rapid expansion of genome sequence data is increasing the discovery of protein-coding genes across all domains of life. Annotating these genes with reliable functional information is necessary to understand evolution, to define the full biochemical space accessed by nature, and to identify target genes for biotechnology improvements. The vast majority of proteins are annotated based on sequence conservation with no specific biological, biochemical, genetic, or cellular function identified. Recent technical advances throughout the biological sciences enable experimental research on these understudied protein-coding genes in a broader collection of species. However, scientists have incentives and biases to continue focusing on well documented genes within their preferred model organism. This perspective suggests a research model that seeks to break historic silos of research bias by enabling interdisciplinary teams to accelerate biological functional annotation. We propose an initiative to develop coordinated projects of collaborating evolutionary biologists, cell biologists, geneticists, and biochemists that will focus on subsets of target genes in multiple model organisms. Concurrent analysis in multiple organisms takes advantage of evolutionary divergence and selection, which causes individual species to be better suited as experimental models for specific genes. Most importantly, multisystem approaches would encourage transdisciplinary critical thinking and hypothesis testing that is inherently slow in current biological research.
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http://dx.doi.org/10.1093/icb/icab029DOI Listing
May 2021

The association between XRCC3 rs1799794 polymorphism and cancer risk: a meta-analysis of 34 case-control studies.

BMC Med Genomics 2021 Apr 30;14(1):117. Epub 2021 Apr 30.

Department of Oncology, the First Affiliated Hospital of Kunming Medical University, Yunnan Province, No. 295 Xichang Road, Kunming, 650032, People's Republic of China.

Background: Studies on the XRCC3 rs1799794 polymorphism show that this polymorphism is involved in a variety of cancers, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between rs1799794 polymorphism and susceptibility to cancer.

Methods: PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies through June 11, 2019. All analyses were performed with Stata 14.0. Subgroup analyses were performed by cancer type, ethnicity, source of control, and detection method. A total of 37 studies with 23,537 cases and 30,649 controls were included in this meta-analysis.

Results: XRCC3 rs1799794 increased cancer risk in the dominant model and heterozygous model (GG + AG vs. AA: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00-1.08, P = 0.051; AG vs. AA: OR = 1.05, 95% CI = 1.00-1.01, P = 0.015). The existence of rs1799794 increased the risk of breast cancer and thyroid cancer, but reduced the risk of ovarian cancer. In addition, rs1799794 increased the risk of cancer in the Caucasian population.

Conclusion: This meta-analysis confirms that XRCC3 rs1799794 is related to cancer risk, especially increased risk for breast cancer and thyroid cancer and reduced risk for ovarian cancer. However, well-designed large-scale studies are required to further evaluate the results.
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http://dx.doi.org/10.1186/s12920-021-00965-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086287PMC
April 2021

Lewis acid mediated cyclization: synthesis of 2 spirocyclohexylindolines.

Org Biomol Chem 2021 May;19(18):4043-4047

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research and Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan 650091, P. R. China.

Herein, we report the synthesis of 2-spirocyclohexylindolines based on a Lewis acid mediated cyclization. This diastereoselective procedure provides the target structures in a straightforward way via dual activation.
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http://dx.doi.org/10.1039/d1ob00293gDOI Listing
May 2021

Osteocalcin and Abdominal Aortic Calcification in Hemodialysis Patients: An Observational Cross-Sectional Study.

Front Endocrinol (Lausanne) 2021 19;12:620350. Epub 2021 Mar 19.

Department of Medical Imaging, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China.

Objectives: To investigate the serum level of osteocalcin (OC), also known as bone Gla protein, in maintenance hemodialysis (MHD) patients and its correlation with abdominal aortic calcification (AAC).

Methods: From July 2017 to February 2020, we enrolled 108 adult MHD patients. Routine fasting blood laboratory tests were performed before the start of the second hemodialysis in a week. Abdominal aortic calcification score (AACs) was assessed within 1 month. Pearson correlation and Logistic regression were used to analyze the data.

Results: The OC level was 231.56 (25.92,361.33) ng/ml, elevating significantly in this group of MHD patients. It had a positive correlation with serum phosphorus (r = 0.511, P = 0.001), intact parathyroid hormone(iPTH) (r = 0.594, P = 0.0001), fibroblast growth factor 23(FGF23) (r = 0.485, P = 0.003) and a negative correlation with age(r = -0.356, P = 0.039). Based on the AACs, patients were divided into two groups. Serum OC level were higher in patients with AACs≥5 (p=0.032). A multiple logistics regression analysis revealed that age (odds ratio [OR]1.14, P=0.005) and OC(OR=1.10, P=0.008)were risk factors for high AACs(≥5).

Conclusion: The study implicated that OC elevated significantly in this group of MHD patients.OC is positively correlated with phosphorus, iPTH, FGF23, and a negative correlation with age. OC was a risk factor for vascular calcification in this study, but this study did not classify osteocalcin as c-OC and unOC. Whether unOC is associated more directly with vascular calcification requires further study.
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http://dx.doi.org/10.3389/fendo.2021.620350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018234PMC
March 2021

Long non-coding RNA XIST promotes the proliferation of cardiac fibroblasts and the accumulation of extracellular matrix by sponging microRNA-155-5p.

Exp Ther Med 2021 May 12;21(5):477. Epub 2021 Mar 12.

Department of Cardiology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China.

Acute myocardial infarction (AMI) is characterized by cardiomyocyte death followed by myocardial fibrosis, eventually leading to heart failure. Long non-coding (lnc)RNA X-inactive specific transcript (XIST) serves a vital role in the regulation of fibrosis. The aim of the present study was to determine whether myocardial fibrosis may be regulated by XIST and to elucidate the underlying mechanism. The relative mRNA expression levels of the target genes were evaluated using reverse transcription-quantitative polymerase chain reaction. Cell viability and apoptosis were determined using a Cell Counting Kit-8 assay and flow cytometry, respectively. The apoptosis and fibrosis-related protein expression levels were detected using western blot analysis. Finally, the interaction between XIST and microRNA (miR)-155-5p was analyzed using a luciferase reporter assay. XIST-overexpression increased proliferation and the expression level of the fibrosis-related proteins in the human cardiac fibroblast cells (HCFs). XIST directly targeted miR-155-5p and downregulated its expression, while miR-155-5p downregulation abolished the effect of XIST-silencing on cell viability and the expression level of the fibrosis-related proteins in the HCFs. XIST promoted cell proliferation and the expression level of fibrosis-related proteins by sponging miR-155-5p. Therefore, XIST may represent a novel effective target for AMI treatment.
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http://dx.doi.org/10.3892/etm.2021.9908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976373PMC
May 2021

Clinicopathological and molecular characteristics of patients with hypermutant lung cancer: A retrospective cohort study.

Oncol Lett 2021 Apr 25;21(4):329. Epub 2021 Feb 25.

Department of Oncology, Hebei Chest Hospital, Research Center of Hebei Lung Cancer Prevention and Treatment, Shijiazhuang, Hebei 050041, P.R. China.

Tumor mutation burden (TMB) is an independent indicator used to select patients sensitive to immunotherapy. The present study aimed to investigate the clinicopathological and molecular characteristics of patients with hypermutant lung cancer to identify an economical, simple and complementary method for predicting TMB and immunotherapy responses. In total, 1,000 patients with lung cancer were randomly selected, and their samples were submitted to next-generation sequencing, with their TMB status reviewed. The threshold of hypermutation was set to 17.24 mutations (muts)/Mb. The proportion of smokers was higher in the hypermutant cohort (n=67) compared with in the non-hypermutant cohort (n=933; 85.1 vs. 46.6%; P<0.0001). Compared with in the non-hypermutant cohort, the proportion of squamous cell carcinoma cases and small cell lung cancer cases was higher in the hypermutant cohort (22.4 vs. 13.1% and 6.0 vs. 2.6%, respectively). In addition, compared with in the non-hypermutant cohort, mutations in the low-density lipoprotein receptor-related protein 1B were more frequently observed in the hypermutant cohort (67.2 vs. 14.3%; P<0.0001). A similar trend was obtained for all genes tested, except for the EGFR gene. Furthermore, in the hypermutant cohort, the prevalence of microsatellite instability was extremely high (9.0%). The mutation frequency in DNA damage response (DDR) genes was notably higher in the hypermutant cohort, where several DDR-associated genes were enriched, compared with in the non-hypermutant cohort. The enrichment analysis revealed a strong association between mutations in Notch signaling and high TMB. To the best of our knowledge, the present study is the first to comprehensively investigate the clinical and genetic characteristics of patients with hypermutant lung cancer in a Chinese population. The results of the current study suggested that hypermutant lung cancer exerted distinctive clinical and genetic features, which may be used as complementary indicators for screening patients sensitive to immunotherapy.
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http://dx.doi.org/10.3892/ol.2021.12590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933761PMC
April 2021

Oligosaccharides from fucosylated glycosaminoglycan prevent breast cancer metastasis in mice by inhibiting heparanase activity and angiogenesis.

Pharmacol Res 2021 Apr 2;166:105527. Epub 2021 Mar 2.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China. Electronic address:

The invasion and metastasis of tumor cells are the hallmarks of malignant diseases and the greatest obstacle to overcome. Heparanase-mediated degradation of heparan sulfate (HS) is the critical process for tumor angiogenesis and metastasis, therefore, heparanase become an attractive target for cancer research. Herein, we reported a native fucosylated glycosaminoglycan (nHG) extracted from sea cucumber Holothuria fuscopunctata and a depolymerized nHG (dHG) and its contained oligosaccharides (hs17, hs14, hs11, hs8 and hs5), acting as heparanase inhibitors. nHG and its derivatives have the ability to bind with heparanase directly, leading to significant inhibition of heparanase activity. Moreover, their apparent binding affinity to heparanase was comparable to their inhibitory effect, which was elevated along with the increase of chain length, similar to the effect of heparins. In addition, oligosaccharides inhibited the migration and invasion of 4T1 mammary carcinoma cells and human umbilical vein endothelial cells (HUVECs) and also suppressed tube formation in Matrigel matrix and angiogenesis in the chick chorioallantoic membrane (CAM) assay. In the metastatic mouse model, oligosaccharides exhibited practical antimetastatic effects on 4T1 mammary carcinoma cells. According to the reported anticoagulant activity and the low bleeding tendency of dHG and its oligosaccharides, the use of the oligosaccharides may lead to better effects on tumor patients with thrombosis tendency.
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http://dx.doi.org/10.1016/j.phrs.2021.105527DOI Listing
April 2021

Immune Microenvironment: New Insight for Familial Adenomatous Polyposis.

Front Oncol 2021 8;11:570241. Epub 2021 Feb 8.

The Medical Department, 3D Medicines Inc., Shanghai, China.

Currently, the main treatment for familial adenomatous polyposis (FAP) is surgery, however, surgery is far from ideal as there are many complications such as uncontrollable bowel movements, pouch inflammation, anastomotic stricture, and secondary fibroids. Therefore, it is necessary to further expand the understanding of FAP and develop new treatments for FAP. The immune microenvironment including immune cells and cytokines, plays an important role in FAP and the progression of FAP to adenocarcinoma, thus it may be a promising treatment for FAP. In the current review, we summarized the recent progress in the immune microenvironment of FAP.
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http://dx.doi.org/10.3389/fonc.2021.570241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897671PMC
February 2021

Adverse Cardiovascular Effects of Phenylephrine Eye Drops Combined With Intravenous Atropine.

Front Pharmacol 2020 27;11:596539. Epub 2021 Jan 27.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Phenylephrine and atropine can cause serious adverse effects when applied in combination. We investigated the effect of phenylephrine eye drops combined with intravenous atropine on the cardiovascular system in patients under general anesthesia undergoing intraocular surgery. The effects of the drugs were observed through clinical study. Thirteen patients undergoing intraocular surgery under general anesthesia were observed in this study; all were injected intravenously with atropine due to the oculocardiac reflex during surgery. To study the combination of drugs, an study was performed on rats. Seventy-two standard deviation rats that received phenylephrine eye drops and intravenous atropine treatment under general anesthesia were assessed, of which 18 treated with these drugs simultaneously were administered normal saline, neostigmine or esmolol. Blood pressure and heart rate were recorded and analyzed. The age of the patients ranged from seven to 14 years old with an average age of 10.7 years old, and 11 patients were male. In patients, 5% phenylephrine eye drops combined with intravenous atropine led to a significant heart rate increase and the increase lasted 20 min. The significant increase in diastolic blood pressure and systolic blood pressure lasted for 15 and 25 min, respectively. From five to 25 min after intravenous atropine treatment, the systolic blood pressure and diastolic blood pressure were both more than 20% higher than that at baseline. In rats, the changes in blood pressure and heart rate were independent of the phenylephrine and atropine administration sequence but were related to the administration time interval. The neostigmine group showed a significant decrease in blood pressure after the increase from the administration of phenylephrine and atropine. Phenylephrine eye drops combined with intravenous atropine have obvious cardiovascular effects that can be reversed by neostigmine. This drug combination should be used carefully for ophthalmic surgery, especially in patients with cardio-cerebrovascular diseases.
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http://dx.doi.org/10.3389/fphar.2020.596539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873643PMC
January 2021

Β-Cyclodextrin-graft-poly(amidoamine) dendrons as the nitric oxide deliver system for the chronic rhinosinusitis therapy.

Drug Deliv 2021 Dec;28(1):306-318

Department of Biomedical Engineering, Jinan University, Guangzhou, China.

Chronic rhinosinusitis (CRS) is a rather prevalent condition with a chronic inflammatory process, which is hard to cure. Herein, a new antibacterial drug, nitric oxide (NO), was used for the attempt on CRS therapy. To achieve this, a star copolymer (β-CD-PAMAM) consisting of the β-cyclodextrin (β-CD) core and seven PAMAM-G3 arms, which was designed as a low-cytotoxicity and high NO loading carrier, were synthesized and characterizied. The obtained β-CD-PAMAM/NONOate showed the effect in inhibiting and dispersing the biofilm of , as well as the effective antibacterial performance, implying the promising application in CRS treatment. The assay confirmed that β-CD-PAMAM/NONOate displayed excellent therapy effect on CRS and significantly improved the symptoms of the experimental rats, which was no significant different in therapy effect with the clinical Rhinocort. Incorporated with its little toxicity and , the β-CD-PAMAM/NONOate was suggested a promising application in CRS therapy.
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http://dx.doi.org/10.1080/10717544.2021.1876183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850337PMC
December 2021

Outcomes of juvenile myasthenia gravis: a comparison of robotic thymectomy with medication treatment.

Ann Thorac Surg 2021 Jan 19. Epub 2021 Jan 19.

Department of Surgery, Competence Center of Thoracic Surgery, Charité University Hospital Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address:

Background: The study aims to compare the clinical outcomes of patients with juvenile myasthenia gravis (JMG) who underwent robotic thymectomy with that of those who only received medication therapy.

Methods: We retrospectively reviewed patients who visited our institution for the diagnosis or treatment of MG with an age at onset younger than 18 years. Patients who underwent thymectomy comprised the surgical group and those who received only medication therapy comprised the nonsurgical group. The clinical outcomes were assessed according to the Myasthenia Gravis Foundation of America Post Intervention Status.

Results: Forty-seven patients (35 female: 12 male) were included as the surgical group and 20 patients (15 female: 5 male) comprised the nonsurgical group. Significant differences were observed between the surgical and nonsurgical groups in antibody against acetylcholinesterase receptor (91.5% versus 65%, p=0.012), disease duration (16 [7-25] months versus 96 [42-480] months, p<0.001) and corticosteroids requirement (53.2% versus 15%, p=0.004) at baseline. Kaplan-Meier analysis showed a higher cumulative probability of complete stable remission (CSR) in the surgical group (p=0.002), compared with that in the nonsurgical group. Moreover, thymectomy (HR 3.842, 95%CI: 1.116-13.230, p=0.033) and age at onset (HR 0.89, 95%CI: 0.80-0.99, p=0.037) were still associated with the achievement of CSR in the multivariable analysis. Furthermore, a significant steroid-sparing effect was only observed in the surgical group, but not in the nonsurgical group.

Conclusions: Robotic thymectomy seems to be more effective than medication therapy on JMG in terms of inducing remission and reducing the use of corticosteroids.
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http://dx.doi.org/10.1016/j.athoracsur.2020.12.045DOI Listing
January 2021

Stability analysis of switched systems with all subsystems unstable: A matrix polynomial approach.

ISA Trans 2021 Aug 6;114:99-105. Epub 2021 Jan 6.

School of Information and Communication Engineering, University of Electronic Science and Technology of China, Chengdu, PR China. Electronic address:

This paper concentrates on the problem of continuous-time switched linear systems with all subsystems unstable under average dwell time (ADT) criteria. Inspired by the matrix polynomial approach, a new method is proposed to further lessen conservativeness and improve system performance. The new method is based on a matrix polynomial and the discretized Lyapunov function (DLF) technique. Using the matrix polynomial, the DLF is successfully established and applied to switched systems. Based on this function, convex sufficient conditions are derived, thereby ensuring the global uniform exponential stability of the system. In addition, the method can be expanded to uncertain systems. Finally, a numerical example is presented to illustrate the potential of the proposed approach.
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http://dx.doi.org/10.1016/j.isatra.2020.12.031DOI Listing
August 2021

[IEAC versus CEAC high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation for lymphoma: analysis of efficacy and safety in 106 cases].

Nan Fang Yi Ke Da Xue Xue Bao 2020 Dec;40(12):1760-1767

Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

To evaluate the efficacy and safety of IEAC (idarubici, etoposide, cytosine arabinoside, and cyclophosphamide) and CEAC (lomustine, etoposide, cytosine arabinoside, and cyclophosphamide) high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) in the treatment of lymphoma.We retrospectively analyzed the data of 106 lymphoma patients undergoing ASCT from 2013 to 2018 using IEAC (=43) or CEAC (=63) regimens. The time of hematopoietic reconstruction, adverse events and the patients' survival outcomes in the two groups were compared to evaluate the efficacy and safety of the two regimens. Univariate and multivariate analyses were performed to identify the factors potentially affecting the patients' survival.In the total of 106 patients, successful hematopoietic reconstruction was achieved in 104 patients and treatment-related deaths occurred in 2 patients. No significant differences were observed in the time to hematopoietic recovery, adverse events or survival outcomes between the patients receiving IEAC and CEAC regimens. In the 104 patients with successful hematopoietic reconstruction who were followed for a median of 27.4 months (range 4.3 to 74.3 months), the 5-year progress-free survival (PFS) and overall survival (OS) rates were 72.9% and 81.9%, respectively. The main adverse events (beyond grade 2 based on CTCAE v5.0) included infection, oral mucositis, nausea and vomiting, liver damage, cardiotoxicity, hypokalemia, and diarrhea. No significant difference was found in the survival outcomes or adverse events between the 2 regimens. T cell lymphoma and failure to achieve complete remission (CR) before ASCT were the risk factors of PFS (=0.015 and =0.007, respectively) and OS (=0.038 and 0.031, respectively). The patients who achieved CR 3 months after the transplantation had higher rates of PFS (=0.007) and OS (=0.003).IEAC and CEAC regimens prior to by ASCT are both safe and effective in the treatment of lymphoma and can be used as alternative conditioning regimens for lymphoma patients undergoing ASCT.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2020.12.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835682PMC
December 2020

Synthesis, physicochemical properties, and health aspects of structured lipids: A review.

Compr Rev Food Sci Food Saf 2020 03 4;19(2):759-800. Epub 2020 Feb 4.

Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.

Structured lipids (SLs) refer to a new type of functional lipids obtained by chemically, enzymatically, or genetically modifying the composition and/or distribution of fatty acids in the glycerol backbone. Due to the unique physicochemical characteristics and health benefits of SLs (for example, calorie reduction, immune function improvement, and reduction in serum triacylglycerols), there is increasing interest in the research and application of novel SLs in the food industry. The chemical structures and molecular architectures of SLs define mainly their physicochemical properties and nutritional values, which are also affected by the processing conditions. In this regard, this holistic review provides coverage of the latest developments and applications of SLs in terms of synthesis strategies, physicochemical properties, health aspects, and potential food applications. Enzymatic synthesis of SLs particularly with immobilized lipases is presented with a short introduction to the genetic engineering approach. Some physical features such as solid fat content, crystallization and melting behavior, rheology and interfacial properties, as well as oxidative stability are discussed as influenced by chemical structures and processing conditions. Health-related considerations of SLs including their metabolic characteristics, biopolymer-based lipid digestion modulation, and oleogelation of liquid oils are also explored. Finally, potential food applications of SLs are shortly introduced. Major challenges and future trends in the industrial production of SLs, physicochemical properties, and digestion behavior of SLs in complex food systems, as well as further exploration of SL-based oleogels and their food application are also discussed.
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http://dx.doi.org/10.1111/1541-4337.12537DOI Listing
March 2020

Thermal conductivity of h-BN monolayers using machine learning interatomic potential.

J Phys Condens Matter 2021 Mar;33(10):105903

Institute of Materials Science, Technical University of Darmstadt, Darmstadt 64287, Germany.

Thermal management materials are of critical importance for engineering miniaturized electronic devices, where theoretical design of such materials demands the evaluation of thermal conductivities which are numerically expensive. In this work, we applied the recently developed machine learning interatomic potential (MLIP) to evaluate the thermal conductivity of hexagonal boron nitride monolayers. The MLIP is obtained using the Gaussian approximation potential method, and the resulting lattice dynamical properties and thermal conductivity are compared with those obtained from explicit frozen phonon calculations. It is observed that accurate thermal conductivity can be obtained based on MLIP constructed with about 30% representative configurations, and the high-order force constants provide a more reliable benchmark on the quality of MLIP than the harmonic approximation.
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http://dx.doi.org/10.1088/1361-648X/abcf61DOI Listing
March 2021

Antimicrobial Carbohydrate-Based Macromolecules: Their Structures and Activities.

J Org Chem 2020 Nov 24. Epub 2020 Nov 24.

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.

Emerging drug resistance is creating an urgent demand for new antimicrobial therapeutics. Besides the development of conventional antibiotics, antimicrobial agents with novel mechanisms have attracted great attention, such as antimicrobial peptides and polymers. Interactions between carbohydrates and proteins on microbes are believed to be the first step of pathogenesis. Thus, considerable efforts have been made on the development of carbohydrate-containing molecules in antimicrobial research. Recent progress of glycosylated macromolecules for antimicrobial applications has been discussed with an emphasis on synthetic glycosylated materials.
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http://dx.doi.org/10.1021/acs.joc.0c01597DOI Listing
November 2020

Discovery of potentially biased agonists of mu-opioid receptor (MOR) through molecular docking, pharmacophore modeling, and MD simulation.

Comput Biol Chem 2021 Feb 1;90:107405. Epub 2020 Nov 1.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, People's Republic of China. Electronic address:

Opioids are well known for their potent analgesic efficacy and severe side effects. Studies have shown that analgesic effects are mediated by the downstream G-protein-dependent pathway of the μ-opioid receptor (MOR), and another β-arrestin-dependent pathway mediates side effects such as respiratory depression, constipation and tolerance etc. TRV130 is a biased ligand for G-protein-dependent pathway, which has high analgesia and has fewer side effects than morphine. In this study, the structure similarity search was performed on the IBSSC database using Oliceridine (TRV130) and PZM21 as templates. The 3D structure-based pharmacophore model was built and combined molecular docking prediction mode was selected to filter out small molecules, Finally, based on affinity prediction, four candidate molecules were obtained. Molecular dynamics simulations explored the detailed interaction mechanism of proteins with small molecules under dynamics. These results suggest that these candidate molecules are potential MOR agonists.
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http://dx.doi.org/10.1016/j.compbiolchem.2020.107405DOI Listing
February 2021

Interfacial rheology, emulsifying property and emulsion stability of glyceryl monooleate-modified corn fiber gum.

Food Chem 2021 May 20;343:128416. Epub 2020 Oct 20.

Advanced Rheology Institute, Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

The present work aims to develop novel glyceryl monooleate (GMO)-modified corn fiber gum (CFG) emulsifiers (GMO-CFG) and investigate the role of the interfacial properties on emulsion stability. GMO-CFG with different degrees of substitution (DS) were prepared, and their interfacial rheology and emulsification were appraised for potential applications in stabilizing oil/water emulsions. Various oil/water interfacial properties (i.e., adsorption kinetics, viscoelasticity, and adsorbed amount) were determined as a function of DS by using interfacial shear rheology and quartz crystal microbalance with dissipation monitoring techniques. Hydrophobically modified CFG provides an increased capacity to produce fine droplets and stable emulsions. Esterification and its degree exert non-negligible effects on the critical micelle concentration, interfacial tension, interfacial adsorbed amount, and viscoelasticity of the interfacial layer. The rheological properties of the interfacial layers play an important role in macroscopic emulsion stability.
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http://dx.doi.org/10.1016/j.foodchem.2020.128416DOI Listing
May 2021

Total Synthesis of Dactylicapnosines A and B.

J Org Chem 2020 11 20;85(21):13772-13778. Epub 2020 Oct 20.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan 650091, P. R. China.

Dactylicapnosines A and B, two natural products from , exhibited potent anti-inflammatory and analgesic activities both in vitro and in vivo. In this paper, we report our second-generation synthesis of dactylicapnosine A and the first total synthesis of dactylicapnosine B. Our synthetic route features acid-induced isomerization of -quinone (), Co-mediated regioselective ring contraction of -quinone (), and oxidative methoxylation of enone (). This modified sequence provides dactylicapnosine A in 14 steps with an overall yield of 12% from a known compound () and also offers opportunities to synthesize dactylicapnosine-like analogues for biological investigations.
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http://dx.doi.org/10.1021/acs.joc.0c01900DOI Listing
November 2020

Targeted design for adaptive clinical trials via semiparametric model.

Int J Biostat 2020 Oct 6. Epub 2020 Oct 6.

Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University, Washington, DC 20057, USA.

Precision medicine approach that assigns treatment according to an individual's personal (including molecular) profile is revolutionizing health care. Existing statistical methods for clinical trial design typically assume a known model to estimate characteristics of treatment outcomes, which may yield biased results if the true model deviates far from the assumed one. This article aims to achieve model robustness in a phase II multi-stage adaptive clinical trial design. We propose and study a semiparametric regression mixture model in which the mixing proportions are specified according to the subjects' profiles, and each sub-group distribution is only assumed to be unimodal for robustness. The regression parameters and the error density functions are estimated by semiparametric maximum likelihood and isotonic regression estimators. The asymptotic properties of the estimates are studied. Simulation studies are conducted to evaluate the performance of the method after a real data analysis.
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http://dx.doi.org/10.1515/ijb-2018-0100DOI Listing
October 2020

Knockdown of circ_HIPK3 inhibits tumorigenesis of hepatocellular carcinoma via the miR-582-3p/DLX2 axis.

Biochem Biophys Res Commun 2020 12 22;533(3):501-509. Epub 2020 Sep 22.

Department of Emergency, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, China. Electronic address:

Hepatocellular carcinoma (HCC) is the most common type in the sub-classification of liver cancer. Circular RNAs (circRNAs) play a fundamental role in tumor occurrence and progression. This research aimed to investigate the role and molecular basis of circRNA homeodomain-interacting protein kinase 3 (circ_HIPK3) in HCC. Circ_HIPK3 and DLX2 levels were enhanced, and miR-582-3p level was reduced in HCC tissues and cells. Silencing of circ_HIPK3 impeded proliferation, migration and invasion and expedited apoptosis in HCC cells. Furthermore, circ_HIPK3 modulated HCC progression via sponging miR-582-3p, and miR-582-3p suppressed HCC progression via targeting DLX2. Moreover, circ_HIPK3 knockdown inhibited tumor growth in vivo. Circ_HIPK3 facilitated HCC progression by mediating miR-582-3p/DLX2 pathway, suggesting a new potential biomarker for HCC treatment.
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http://dx.doi.org/10.1016/j.bbrc.2020.09.050DOI Listing
December 2020