Publications by authors named "Jiaxin Zhao"

51 Publications

Pressure-Induced Variation of the Crystal Stacking Order in the Hydrogen-Bonded Quasi-Two-Dimensional Layered Material Cu(OH)Cl.

Materials (Basel) 2021 Sep 2;14(17). Epub 2021 Sep 2.

State Key Laboratory of Superhard Materials, College of Physics, Jilin University, Changchun 130012, China.

The crystal stacking order plays a crucial role in determining the structure and physical properties of 2D layered materials. A variation in the stacking sequence of adjacent 2D building blocks causes drastic changes in their functionalities. In this work, the structural variation of belloite (Cu(OH)Cl), as a function of pressure, is presented. Through in situ synchrotron X-ray diffraction and Raman scattering studies, in combination with first-principles theoretical simulations, a structural transformation from the initial monoclinic phase into an orthorhombic one has been established at 18.7 GPa, featuring variations in the stacking sequence of the tectonic monolayers. In the monoclinic phase, they are arranged in an AAAA sequence. While in the orthorhombic phase, the monolayers are stacked in an ABAB sequence. Such phenomena are similar to those observed in van der Waals 2D materials, with pressure-induced changes in the stacking order between layers. In addition, an isostructural phase transition within the initial monoclinic phase is also observed to occur at 12.9-16 GPa, which is associated with layer-sliding and a change in hydrogen bond configuration. These results show that Cu(OH)Cl, as well as other hydrogen-bonded 2D layered materials, can provide a convenient platform for studying the effects of the crystal stacking order.
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http://dx.doi.org/10.3390/ma14175019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434516PMC
September 2021

Efficacy and safety profile of avelumab monotherapy.

Crit Rev Oncol Hematol 2021 Aug 28;166:103464. Epub 2021 Aug 28.

The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, 325027, China. Electronic address:

Avelumab can kill cancer cells through immune checkpoint inhibition and antibody-dependent cell-mediated cytotoxicity (ADCC). Here, we analyzed the clinical efficacy and adverse events (AEs) in 3935 cancer patients from 21 trials. Compared with conventional treatment, avelumab monotherapy was associated with more tumor responses and less AEs. The pooled objective response rate was 14.18 % (95 % CI, 10.68 %-18.08 %). More PD-L1 positive patients responded to avelumab monotherapy compared to PD-L1 negative patients. The overall incidence was 73.78 % for all-grade treatment-related AE (TRAE), 14.44 % for high-grade TRAE, 6.07 % for serious adverse event, 0.44 % for fatal adverse event, 17.86 % for all-grade immune-related AE (irAE), and 3.22 % for high-grade irAE. In summary, avelumab monotherapy presents an active anti-tumor activity, shows no sign of increased toxicity due to the ADCC. These characteristics provide rational for further application of avelumab in cancer treatment.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103464DOI Listing
August 2021

Correction to: Immunological significance of prognostic alternative splicing signature in hepatocellular carcinoma.

Cancer Cell Int 2021 Aug 24;21(1):448. Epub 2021 Aug 24.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No 109. Xueyuan West Road, Wenzhou, 325000, Zhejiang, China.

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http://dx.doi.org/10.1186/s12935-021-02139-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383396PMC
August 2021

The association of arsenic exposure with hypertension and blood pressure: A systematic review and dose-response meta-analysis.

Environ Pollut 2021 Aug 4;289:117914. Epub 2021 Aug 4.

Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China. Electronic address:

Chronic arsenic exposure can induce cardiovascular diseases through oxidative stress injury, inflammation and endothelial dysfunction. However, evidence for hypertension related to chronic arsenic exposure remains limited and inconclusive. To investigate the association of arsenic exposure with hypertension, we reviewed cross-sectional, case-control and longitudinal studies among general population (only excluded pregnant woman and children). Compared with non-exposure (or low exposure) group, we assessed relationship between the exposure (or high exposure) of arsenic and hypertension or blood pressure. We also examined the dose-response relationship to provide a theoretical basis for precision interventions in the population by conducting a two-stage random-effects dose-response meta-analysis. The weighted mean difference (WMD) was calculated to compare the blood pressure of exposed and reference arsenic exposure groups. Twenty-seven studies comprising 117,769 participants were included. The pooled OR and RR for hypertension compared the highest with lowest arsenic exposure categories were 1.14 [95 % confidence interval (CI): 1.06-1.23] and 1.30 [95 % CI: 0.91-1.84], respectively. A dose-response assessment of six studies with the necessary data available demonstrated that the OR of hypertension increased with an increasement of arsenic exposure. The differences in systolic blood pressure levels between the exposed and reference groups were 4.03 mmHg (95 % CI: 1.24-6.82). The meta-analysis further revealed the significant association of chronic arsenic exposure with hypertension among cross-sectional studies and the marginal significance in cohort studies. Besides, arsenic was mainly associated with increasing systolic blood pressure but not significantly related to diastolic blood pressure. We also demonstrated statistical evidence of a nonlinear dose-response association. Details on mechanisms and cohort studies are required to elucidate population-wide health influence of chronic arsenic exposure.
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http://dx.doi.org/10.1016/j.envpol.2021.117914DOI Listing
August 2021

Landscape of Prognostic m6A RNA Methylation Regulators in Hepatocellular Carcinoma to Aid Immunotherapy.

Front Cell Dev Biol 2021 5;9:669145. Epub 2021 Aug 5.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Hepatocellular carcinoma (HCC) is the sixth most common malignancy with a high mortality worldwide. N6-methyladenosine (m6A) may participate extensively in tumor progression. To reveal the landscape of tumor immune microenvironment (TIME), ESTIMATE analysis, ssGSEA algorithm, and the CIBERSORT method were used. Taking advantage of consensus clustering, two different HCC categories were screened. We analyzed the correlation of clustering results with TIME and immunotherapy. Then, we yielded a risk signature by systematical bioinformatics analyses. Immunophenoscore (IPS) was implemented to estimate the immunotherapeutic significance of risk signature. The m6A-based clusters were significantly correlated with overall survival (OS), immune score, immunological signature, immune infiltrating, and ICB-associated genes. Risk signature possessed robust prognostic validity and significantly correlated with TIME context. IPS was employed as a surrogate of immunotherapeutic outcome, and patients with low-risk scores showed significantly higher immunophenoscores. Collectively, m6A-based clustering subtype and signature was a robust prognostic indicator and correlated with TIME and immunotherapy, providing novel insight into antitumor management and prognostic prediction in HCC.
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http://dx.doi.org/10.3389/fcell.2021.669145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375309PMC
August 2021

Roxadustat Does Not Affect Platelet Production, Activation, and Thrombosis Formation.

Arterioscler Thromb Vasc Biol 2021 Oct 5;41(10):2523-2537. Epub 2021 Aug 5.

Department of Cardiology, Ruijin Hospital (J.Z., R.Z., X.Y.), Shanghai Jiao Tong University School of Medicine, China.

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.121.316495DOI Listing
October 2021

Keratoconus detection of changes using deep learning of colour-coded maps.

BMJ Open Ophthalmol 2021 13;6(1):e000824. Epub 2021 Jul 13.

Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

Objective: To evaluate the accuracy of convolutional neural networks technique (CNN) in detecting keratoconus using colour-coded corneal maps obtained by a Scheimpflug camera.

Design: Multicentre retrospective study.

Methods And Analysis: We included the images of keratoconic and healthy volunteers' eyes provided by three centres: Royal Liverpool University Hospital (Liverpool, UK), Sedaghat Eye Clinic (Mashhad, Iran) and The New Zealand National Eye Center (New Zealand). Corneal tomography scans were used to train and test CNN models, which included healthy controls. Keratoconic scans were classified according to the Amsler-Krumeich classification. Keratoconic scans from Iran were used as an independent testing set. Four maps were considered for each scan: axial map, anterior and posterior elevation map, and pachymetry map.

Results: A CNN model detected keratoconus versus health eyes with an accuracy of 0.9785 on the testing set, considering all four maps concatenated. Considering each map independently, the accuracy was 0.9283 for axial map, 0.9642 for thickness map, 0.9642 for the front elevation map and 0.9749 for the back elevation map. The accuracy of models in recognising between healthy controls and stage 1 was 0.90, between stages 1 and 2 was 0.9032, and between stages 2 and 3 was 0.8537 using the concatenated map.

Conclusion: CNN provides excellent detection performance for keratoconus and accurately grades different severities of disease using the colour-coded maps obtained by the Scheimpflug camera. CNN has the potential to be further developed, validated and adopted for screening and management of keratoconus.
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http://dx.doi.org/10.1136/bmjophth-2021-000824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278890PMC
July 2021

Biochemical and Phylogenetic Characterization of a Novel NADP-Specific Isocitrate Dehydrogenase From the Marine Microalga .

Front Mol Biosci 2021 5;8:702083. Epub 2021 Jul 5.

Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases, Key Laboratory of Biomedicine in Gene Diseases and Health of Anhui Higher Education Institutes, College of Life Sciences, Anhui Normal University, Wuhu, China.

Isocitrate dehydrogenase (IDH) family of proteins is classified into three subfamilies, namely, types I, II, and III. Although IDHs are widely distributed in bacteria, archaea, and eukaryotes, all type III IDHs reported to date are found only in prokaryotes. Herein, a novel type III IDH subfamily member from the marine microalga (PtIDH2) was overexpressed, purified, and characterized in detail for the first time. Relatively few eukaryotic genomes encode this type of IDH and PtIDH2 shares the highest homology with marine bacterial monomeric IDHs, suggesting that PtIDH2 originated through a horizontal gene transfer event between a marine alga and a bacterium. Size-exclusion chromatography revealed that the native PtIDH2 is a homotetramer (∼320 kDa) in solution, comprising four monomeric IDH-like subunits (80 kDa each). Enzymatic characterization showed that PtIDH2 is a bivalent metal ion-dependent enzyme and Mn is the optimal activator. The recombinant PtIDH2 protein exhibited maximal activity at 35°C and pH 8.0 in the presence of Mn. Heat-inactivation analysis revealed that PtIDH2 is a cold-adapted enzyme. Kinetic analysis demonstrated that PtIDH2 is a completely NADP-specific IDH with no detectable NAD-associated catalytic activity. The three putative key NADP-binding residues (His604, Arg615, and Arg664) in PtIDH2 were also evaluated by site-directed mutagenesis. The HL/RD/RS triple mutant showed a 3.25-fold preference for NAD over NADP, implying that the coenzyme specificity of PtIDH2 can be converted from NADP to NAD through rational engineering approaches. Additionally, the roles of the conserved residues Ala718 and Leu742 in the thermostability of PtIDH2 were also explored by site-directed mutagenesis. We found that the LF mutant displayed higher thermostability than wild-type PtIDH2. This study expands the phylogeny of the IDH family and provides new insights into the evolution of IDHs.
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http://dx.doi.org/10.3389/fmolb.2021.702083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287583PMC
July 2021

Multi-omics analysis reveals prognostic value of tumor mutation burden in hepatocellular carcinoma.

Cancer Cell Int 2021 Jul 3;21(1):342. Epub 2021 Jul 3.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No 109. Xueyuan West Road, Wenzhou, 325000, Zhejiang, China.

Background: Hepatocellular carcinoma (HCC) was the sixth common malignancies characteristic with highly aggressive in the world. It was well established that tumor mutation burden (TMB) act as indicator of immunotherapeutic responsiveness in various tumors. However, the role of TMB in tumor immune microenvironment (TIME) is still obscure.

Method: The mutation data was analyzed by employing "maftools" package. Weighted gene co-expression network analysis (WGCNA) was implemented to determine candidate module and significant genes correlated with TMB value. Differential analysis was performed between different level of TMB subgroups employing R package "limma". Gene ontology (GO) enrichment analysis was implemented with "clusterProfiler", "enrichplot" and "ggplot2" packages. Then risk score signature was developed by systematical bioinformatics analyses. K-M survival curves and receiver operating characteristic (ROC) plot were further analyzed for prognostic validity. To depict comprehensive context of TIME, XCELL, TIMER, QUANTISEQ, MCPcounter, EPIC, CIBERSORT, and CIBERSORT-ABS algorithm were employed. Additionally, the potential role of risk score on immune checkpoint blockade (ICB) immunotherapy was further explored. The quantitative real-time polymerase chain reaction was performed to detect expression of HTRA3.

Results: TMB value was positively correlated with older age, male gender and early T status. A total of 75 intersection genes between TMB-related genes and differentially expressed genes (DEGs) were screened and enriched in extracellular matrix-relevant pathways. Risk score based on three hub genes significantly affected overall survival (OS) time, infiltration of immune cells, and ICB-related hub targets. The prognostic performance of risks score was validated in the external testing group. Risk-clinical nomogram was constructed for clinical application. HTRA3 was demonstrated to be a prognostic factor in HCC in further exploration. Finally, mutation of TP53 was correlated with risk score and do not interfere with risk score-based prognostic prediction.

Conclusion: Collectively, a comprehensive analysis of TMB might provide novel insights into mutation-driven mechanism of tumorigenesis further contribute to tailored immunotherapy and prognosis prediction of HCC.
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http://dx.doi.org/10.1186/s12935-021-02049-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254981PMC
July 2021

Investigation of the Multi-Target Mechanism of Guanxin-Shutong Capsule in Cerebrovascular Diseases: A Systems Pharmacology and Experimental Assessment.

Front Pharmacol 2021 13;12:650770. Epub 2021 May 13.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Guanxin-Shutong capsule (GXSTC), a combination of Mongolian medicines and traditional herbs, has been clinically proven to be effective in treating cerebrovascular diseases (CBVDs). However, the underlying pharmacological mechanisms of GXSTC in CBVDs remain largely unknown. In this study, a combination of systems pharmacology and experimental assessment approach was used to investigate the bioactive components, core targets, and possible mechanisms of GXSTC in the treatment of CBVDs. A total of 15 main components within GXSTC were identified using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD) and a literature research. Fifty-five common genes were obtained by matching 252 potential genes of GXSTC with 462 CBVD-related genes. Seven core components in GXSTC and 12 core genes of GXSTC on CBVDs were further determined using the protein-protein interaction (PPI) and component-target-pathway (C-T-P) network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results predicted that the molecular mechanisms of GXSTC on CBVDs were mainly associated with the regulation of the vascular endothelial function, inflammatory response, and neuronal apoptosis. Molecular docking results suggested that almost all of core component-targets have an excellent binding activity (affinity < -5 kcal/mol). More importantly, in middle cerebral artery occlusion (MCAO) -injured rats, GXSTC significantly improved the neurological function, reduced the infarct volume, and decreased the percentage of impaired neurons in a dose-dependent manner. Western blotting results indicated that GXSTC markedly upregulated the expression of vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS), while downregulating the expression of cyclooxygenase-2 (COX-2) and transcription factor AP-1 (c-Jun) in MCAO-injured rats. These findings confirmed our prediction that GXSTC exerts a multi-target synergetic mechanism in CBVDs by maintaining vascular endothelial function, inhibiting neuronal apoptosis and inflammatory processes. The results of this study may provide a theoretical basis for GXSTC research and the clinical application of GXSTC in CBVDs.
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http://dx.doi.org/10.3389/fphar.2021.650770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155632PMC
May 2021

Evidence for Moiré Trions in Twisted MoSe Homobilayers.

Nano Lett 2021 May 10;21(10):4461-4468. Epub 2021 May 10.

State Key Laboratory of Low-Dimensional Quantum Physics and Department of Physics, Tsinghua University, Beijing 100084, P.R. China.

Moiré superlattices of van der Waals structures offer a powerful platform for engineering band structure and quantum states. For instance, Moiré superlattices in magic-angle twisted bilayer graphene, ABC trilayer graphene have been shown to harbor correlated insulating and superconducting states, while in transition metal dichalcogenide (TMD) twisted bilayers, Moiré excitons have been identified. Here we show that the effects of a Moiré superlattice on the band structure are general: In TMD twisted bilayers, excitons and exciton complexes can be trapped in the superlattice in a manner analogous to ultracold bosonic or Fermionic atoms in optical lattices. Using twisted MoSe homobilayers as a model system, we present evidence for Moiré trions. Our results thus open possibilities for designer van der Waals structures hosting arrays of Fermionic or bosonic quasiparticles, which can be used to realize tunable many-body states crucial for quantum simulation and quantum information processing.
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http://dx.doi.org/10.1021/acs.nanolett.1c01207DOI Listing
May 2021

Ultralow Threshold Polariton Condensate in a Monolayer Semiconductor Microcavity at Room Temperature.

Nano Lett 2021 Apr 2;21(7):3331-3339. Epub 2021 Apr 2.

Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.

Exciton-polaritons, hybrid light-matter bosonic quasiparticles, can condense into a single quantum state, i.e., forming a polariton Bose-Einstein condensate (BEC), which represents a crucial step for the development of nanophotonic technology. Recently, atomically thin transition-metal dichalcogenides (TMDs) emerged as promising candidates for novel polaritonic devices. Although the formation of robust valley-polaritons has been realized up to room temperature, the demonstration of polariton lasing remains elusive. Herein, we report for the first time the realization of this important milestone in a TMD microcavity at room temperature. Continuous wave pumped polariton lasing is evidenced by the macroscopic occupation of the ground state, which undergoes a nonlinear increase of the emission along with the emergence of temporal coherence, the presence of an exciton fraction-controlled threshold and the buildup of linear polarization. Our work presents a critically important step toward exploiting nonlinear polariton-polariton interactions, as well as offering a new platform for thresholdless lasing.
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http://dx.doi.org/10.1021/acs.nanolett.1c01162DOI Listing
April 2021

Immunological significance of prognostic alternative splicing signature in hepatocellular carcinoma.

Cancer Cell Int 2021 Apr 1;21(1):190. Epub 2021 Apr 1.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No 109. Xueyuan West Road, Wenzhou, 325000, Zhejiang, China.

Background: Hepatocellular carcinoma (HCC) ranks the sixth prevalent tumors with high mortality globally. Alternative splicing (AS) drives protein diversity, the imbalance of which might act an important factor in tumorigenesis. This study aimed to construct of AS-based prognostic signature and elucidate the role in tumor immune microenvironment (TIME) and immunotherapy in HCC.

Methods: Univariate Cox regression analysis was performed to determine the prognosis-related AS events and gene set enrichment analysis (GSEA) was employed for functional annotation, followed by the development of prognostic signatures using univariate Cox, LASSO and multivariate Cox regression. K-M survival analysis, proportional hazards model, and ROC curves were conducted to validate prognostic value. ESTIMATE R package, ssGSEA algorithm and CIBERSORT method and TIMER database exploration were performed to uncover the context of TIME in HCC. Quantitative real-time polymerase chain reaction was implemented to detect ZDHHC16 mRNA expression. Cytoscape software 3.8.0 were employed to visualize AS-splicing factors (SFs) regulatory networks.

Results: A total of 3294 AS events associated with survival of HCC patients were screened. Based on splicing subtypes, eight AS prognostic signature with robust prognostic predictive accuracy were constructed. Furthermore, quantitative prognostic nomogram was developed and exhibited robust validity in prognostic prediction. Besides, the consolidated signature was significantly correlated with TIME diversity and ICB-related genes. ZDHHC16 presented promising prospect as prognostic factor in HCC. Finally, the splicing regulatory network uncovered the potential functions of splicing factors (SFs).

Conclusion: Herein, exploration of AS patterns may provide novel and robust indicators (i.e., risk signature, prognostic nomogram, etc.,) for prognostic prediction of HCC. The AS-SF networks could open up new approach for investigation of potential regulatory mechanisms. And pivotal players of AS events in context of TIME and immunotherapy efficiency were revealed, contributing to clinical decision-making and personalized prognosis monitoring of HCC.
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http://dx.doi.org/10.1186/s12935-021-01894-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017877PMC
April 2021

Associations between air pollutant exposure and renal function: A prospective study of older adults without chronic kidney disease.

Environ Pollut 2021 May 16;277:116750. Epub 2021 Feb 16.

Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China. Electronic address:

We used real-world exposure scenarios to evaluate the effect of six ambient air pollutant (PM, PM, NO, SO, CO, and O) exposure on renal function among older adults without chronic kidney disease (CKD). We recruited 169 older adults without CKD in Beijing, China, for a longitudinal study from 2016 to 2018. The Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (EPI) equations were employed to derive the estimated glomerular filtration rate (eGFR). A linear mixed-effects model with random intercepts for participants was employed to determine the effects of air pollutants on renal function evaluated on the basis of eGFR and urinary albumin/creatinine ratio at different exposure windows (1-, 2-, 3-, 5-, 7-, 14-, 28-, 45-, and 60-days moving averages). An interquartile range (IQR) increase in NO for was associated with significant decreases of in eGFR (MDRD equation) [percentage changes: -4.49 (95% confidence interval: -8.44, -0.37), -5.51 (-10.43, -0.33), -2.26 (-4.38, -0.08), -3.71 (-6.67, -0.65), -5.44 (-9.58, -1.11), -5.50 (-10.24, -0.51), -6.15 (-10.73, -1.33), and -6.34 (-11.17, -1.25) for 1-, 2-, 5-, 7-, 14-, 28-, 45-, and 60-days moving averages, respectively] and in eGFR (EPI equation) [percentage changes: -5.04 (-7.09, -2.94), -6.25 (-8.81, -3.62), -5.16 (-7.34, -2.92), -5.10 (-7.85, -2.28), -5.83 (-8.23, -3.36), -6.04 (-8.55, -3.47) for 1-, 2-, 14-, 28-, 45-, and 60-days moving averages, respectively]. In two-pollutant model, only the association of NO exposure with eGFR remained robust after adjustment for any other pollutant. This association was stronger for individuals with hypertension for the EPI equation or BMI <25 kg/m for the MDRD equation at lags 1 and 1-2. Our findings suggest that NO exposure is associated with eGFR reduction among older adults without CKD for short (1-, 2-days) and medium (14-, 28-, 45-, 60-days) term exposure periods; thus, NO exposure may contribute to renal impairment.
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http://dx.doi.org/10.1016/j.envpol.2021.116750DOI Listing
May 2021

Review on Development and Dental Applications of Polyetheretherketone-Based Biomaterials and Restorations.

Materials (Basel) 2021 Jan 15;14(2). Epub 2021 Jan 15.

Department of Advanced Oral Sciences and Therapeutics, School of Dentistry, University of Maryland, Baltimore, MD 21021, USA.

Polyetheretherketone (PEEK) is an important high-performance thermoplastic. Its excellent strength, stiffness, toughness, fatigue resistance, biocompatibility, chemical stability and radiolucency have made PEEK attractive in dental and orthopedic applications. However, PEEK has an inherently hydrophobic and chemically inert surface, which has restricted its widespread use in clinical applications, especially in bonding with dental resin composites. Cutting edge research on novel methods to improve PEEK applications in dentistry, including oral implant, prosthodontics and orthodontics, is reviewed in this article. In addition, this article also discusses innovative surface modifications of PEEK, which are a focus area of active investigations. Furthermore, this article also discusses the necessary future studies and clinical trials for the use of PEEK in the human oral environment to investigate its feasibility and long-term performance.
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http://dx.doi.org/10.3390/ma14020408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830426PMC
January 2021

A Modified Quasisteady Aerodynamic Model for a Sub-100 mg Insect-Inspired Flapping-Wing Robot.

Appl Bionics Biomech 2020 22;2020:8850036. Epub 2020 Dec 22.

National Key Laboratory of Science and Technology on Micro/Nano Fabrication, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

This study proposes a modified quasisteady aerodynamic model for the sub-100-milligram insect-inspired flapping-wing robot presented by the authors in a previous paper. The model, which is based on blade-element theory, considers the aerodynamic mechanisms of circulation, dissipation, and added-mass, as well as the inertial effect. The aerodynamic force and moment acting on the wing are calculated based on the two-degree-of-freedom (2-DOF) wing kinematics of flapping and rotating. In order to validate the model, we used a binocular high-speed photography system and a customized lift measurement system to perform simultaneous measurements of the wing kinematics and the lift of the robot under different input voltages. The results of these measurements were all in close agreement with the estimates generated by the proposed model. In addition, based on the model, this study analyzes the 2-DOF flapping-wing dynamics of the robot and provides an estimate of the passive rotation-the main factor in generating lift-from the measured flapping kinematics. The analysis also reveals that the calculated rotating kinematics of the wing under different input voltages accord well with the measured rotating kinematics. We expect that the model presented here will be useful in developing a control strategy for our sub-100 mg insect-inspired flapping-wing robot.
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http://dx.doi.org/10.1155/2020/8850036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772018PMC
December 2020

Serum MG53/TRIM72 Is Associated With the Presence and Severity of Coronary Artery Disease and Acute Myocardial Infarction.

Front Physiol 2020 17;11:617845. Epub 2020 Dec 17.

Department of Vascular and Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Mitsugumin 53 or Tripartite motif 72 (MG53/TRIM72), a myokine/cardiokine belonging to the tripartite motif family, can protect the heart from ischemic injury and regulate lipid metabolism in rodents. However, its biological function in humans remains unclear. This study sought to investigate the relationship between circulating MG53 levels and coronary artery disease (CAD). The concentration of MG53 was measured by enzyme-linked immunosorbent assay (ELISA) in serum samples from 639 patients who underwent angiography, including 205 controls, 222 patients with stable CAD, and 212 patients with acute myocardial infarction (AMI). Logistic and linear regression analyses were used to analyze the relationship between MG53 and CAD. MG53 levels were increased in patients with stable CAD and were highest in patients with AMI. Additionally, patients with comorbidities, such as chronic kidney disease (CKD) and diabetes also had a higher concentration of MG53. We found that MG53 is a significant diagnostic marker of CAD and AMI, as analyzed by logistic regression models. Multivariate linear regression models revealed that serum MG53 was significantly corelated positively with SYNTAX scores. Global Registry of Acute Coronary Events (GRACE) scores also correlated with serum MG53 levels, indicating that MG53 levels were associated with the severity of CAD and AMI after adjusting for multiple risk factors and clinical biomarkers. MG53 is a valuable diagnostic marker whose serum levels correlate with the presence and severity of stable CAD and AMI, and may represent a novel biomarker for diagnosing CAD and indicating the severity of CAD.
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http://dx.doi.org/10.3389/fphys.2020.617845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773634PMC
December 2020

The effect of ambient ozone on glucose-homoeostasis: A prospective study of non-diabetic older adults in Beijing.

Sci Total Environ 2021 Mar 4;761:143308. Epub 2020 Nov 4.

Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China. Electronic address:

Objective: To investigate potential effects of short- and medium-term exposure to low levels of ozone (O3) on glucose-homeostasis in non-diabetic older adults.

Methods: 166 non-diabetic, older participants in Beijing were deemed eligible to partake in this longitudinal population-based study. Observations were recorded on three separate occasions from November 2016 up until January 2018. Concentrations of outdoor O3 were monitored throughout the study period. Biomarkers indicative of glucose-homeostasis, including fasting blood glucose, insulin, HbAlc, glycated albumin percentage (glycated albumin/albumin), HOMA-IR and HOMA-B were measured at 3 sessions. A linear mixed effects model with random effects was adopted to quantify the effect of O3 across a comprehensive set of glucose-homeostasis markers.

Results: Short-term O3 exposure positively associated with increased fasting blood glucose, insulin, HOMA-IR and HOMA-B. The effect on glucose occurred at 3-, 5-, 6- and 7-days, although the largest effect manifested on 6-days (5.6%, 95% CI: 1.4, 9.9). Significant associations with both insulin and HOMA-IR were observed on the 3- and 4-days. For HOMA-B, positive associations were identified from 3- to 7-days with estimates ranging from 40.0% (95% CI: 2.3, 91.5) to 83.1% (95% CI: 25.3, 167.5). Stratification suggests that women may be more susceptible to short-term O3 exposure. There does not appear to be a significant association between O3 and glucose-homeostasis in medium-term exposures.

Conclusions: In this study, we found that O3 exposure is at least partially associated with type II diabetes in older adults with no prior history of this condition. O3 therefore appears to be a potential risk factor, which is a particular concern when we consider the rise in global concentrations. Evidence also suggests that women may be more susceptible to short-term O3 exposure although we are not quite sure why. Future research may look to investigate this phenomenon further.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143308DOI Listing
March 2021

Prognostic Value of Circulating MG53 Levels in Acute Myocardial Infarction.

Front Cardiovasc Med 2020 28;7:596107. Epub 2020 Oct 28.

Department of Vascular & Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Mitsugumin 53 (MG53), a muscle-specific protein belonging to the TRIM family, has been demonstrated to protect the heart against oxidative injury. Although previous studies indicated that ischemic hearts released MG53 into circulation in mice, its effects in humans remains unknown. We aimed to evaluate the prognostic value of MG53 in patients with ST-segment elevation myocardial infarction (STEMI). Serum levels of MG53 were measured in 300 patients with STEMI, all patients were followed for 3 years. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular (CV) death, heart failure causing-rehospitalization, recurrent myocardial infarction (MI), and stroke. Patients with a higher concentration of serum MG53 tended to be older, with a history of diabetes. MG53 levels were also highly associated with indicators reflecting heart function, such as left ventricular ejection fraction (LVEF), N terminal pro B type natriuretic peptide (NT-pro-BNP), and cardiac troponin I (cTnI) at baseline. Kaplan-Meier survival curves demonstrated that patients with MG53 levels above the cutoff value (132.17 pg/ml) were more likely to have MACEs. Moreover, it was found to be a significant predictor of CV death (HR: 6.12; 95% CI: 2.10-17.86; = 0.001). Furthermore, the C-statistic and Integrated Discrimination Improvement (IDI) values for MACEs were improved with MG53 as an independent risk factor or when combined with cTnI. MG53 is a valuable prognostic marker of MACE in patients with AMI, independent of established conventional risk factors, highlighting the significance of MG53 in risk stratification post-MI.
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http://dx.doi.org/10.3389/fcvm.2020.596107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655532PMC
October 2020

Resource allocation strategies among vegetative growth, sexual reproduction, asexual reproduction and defense during growing season of Aconitum kusnezoffii Reichb.

Plant J 2021 02 21;105(4):957-977. Epub 2020 Dec 21.

National & Local United Engineering Laboratory for Chinese Herbal Medicine Breeding and Cultivation, School of Life Sciences, Jilin University, Changchun, Jilin Province, 130012, China.

Natural plants must actively allocate their limited resources for survival and reproduction. Although vegetative growth, sexual reproduction, asexual reproduction and defense are all basic processes in the life cycle of plants, the strategies used to allocate resources between these processes are poorly understood. These processes are conspicuous in naturally grown Aconitum kusnezoffii Reichb., which makes it a suitable study subject. Here, the morphology, dry matter, total organic carbon, total nitrogen and aconitum alkaloid levels of shoot, principal root (PR) and lateral roots were measured throughout the growing season. Then, transcriptome and metabolite content analyses were performed. We found that vegetative growth began first. After vegetative growth ceased, sexual development began. Flower organ development was accompanied by increased photosynthesis and the PR consumed temporarily stored resources after flower formation. Asexual propagule development initiated earlier than sexual reproduction and kept accumulating resources after that. Development was slow before flower formation, mainly manifesting as increasing length; then, after flower formation it accelerated via enhanced material transport and accumulation. Defense compounds were maintained at low levels before flowering. In particular, the turnover of defense compounds was enhanced before and after flower bud emergence, providing resources for other processes. After flower formation, defense compounds were accumulated. The pattern found herein provides a vivid example for further studies on resource allocation strategies. The exciting finding that the PR, as a more direct storage site for photosynthate, is a buffer unit for resources, and that defense compounds can be reused for other processes, suggests a need to explore potential mechanisms.
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http://dx.doi.org/10.1111/tpj.15080DOI Listing
February 2021

Risk factors for myocardial injury in patients with coronavirus disease 2019 in China.

ESC Heart Fail 2020 Oct 2. Epub 2020 Oct 2.

Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui Jin Road II, Shanghai, 200025, China.

Aims: In patients with coronavirus disease 2019 (COVID-19), the involvement of the cardiovascular system significantly relates to poor prognosis. However, the risk factors for acute myocardial injury have not been sufficiently studied. Thus, we aimed to determine the characteristics of myocardial injury and define the association between routine blood markers and cardiac troponin I, in order to perform a predictive model.

Methods And Results: This retrospective cohort study included patients with confirmed COVID-19 from Wuhan Tongji Hospital (Wuhan, China). Data were compared between those with and without myocardial injury. Kaplan-Meier analysis and Cox regression models were used to describe the association between myocardial injury and poor prognosis. Simple correlation analyses were used to find factors associated with high-sensitivity cardiac troponin I levels. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with myocardial injury. The area under the receiver operating characteristic curve was used to determine the predictive value of the model. Of 353 patients included in the study, 79 presented myocardial injury. Patients with myocardial injury had higher levels of inflammation markers, poorer liver and kidney function, and more complications compared with patients without myocardial injury. High-sensitivity cardiac troponin I levels were significantly associated with neutrophil/lymphocyte ratio, creatinine, d-dimer, lactate dehydrogenase, and inflammatory cytokines and negatively associated with oxygen saturation. It was significantly associated with poor prognosis after adjusting for age, sex, and complications. Multivariate regression showed that myocardial injury was associated with a high neutrophil/lymphocyte ratio (odds ratio 2.30, 95% CI 1.11-4.75, per standard deviation increase, P = 0.02), creatinine (3.58, 1.35-8.06, P = 0.01), and lactate dehydrogenase (3.39, 1.42-8.06, P = 0.01) levels. Using a predictive model, the area under the receiver operating characteristic curve was 0.92 (0.88-0.96).

Conclusions: In patients with COVID-19, neutrophil/lymphocyte ratio, creatinine, and lactate dehydrogenase are blood markers that could help identify patients with a high risk of myocardial injury at an early stage.
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http://dx.doi.org/10.1002/ehf2.13022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537185PMC
October 2020

Effects of air-abrasion pressure on mechanical and bonding properties of translucent zirconia.

Clin Oral Investig 2021 Apr 11;25(4):1979-1988. Epub 2020 Aug 11.

Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, 250012, China.

Objectives: The purpose of this in vitro study was to investigate the effects of different air-abrasion pressures on flexural strength and shear bond strength of a translucent zirconia.

Materials And Methods: The translucent zirconia surface was treated with 50 μm abrasive alumina particles at different pressure: 0.1 MPa; 0.2 MPa; 0.3 MPa; 0.4 MPa; 0.5 MPa; untreated specimens were used as control group (n = 33). For each group, three-point bending test was used to evaluate the flexural strength, and surface characterizations were analyzed. Following adhesive bonding and water storage for 24 h, specimens were subdivided into groups baseline and aged (5000 thermocycles). Then, shear bond strength was measured and failure mode was recorded. Statistical analysis was performed with one-way ANOVA and Tukey test (α = 0.05).

Results: Increasing air-abrasion pressure (0.3 MPa, 0.4 MPa, and 0.5 MPa) decreased the flexural strength. Higher air-abrasion pressure resulted in rougher zirconia surfaces and caused more microcracks. The highest shear bond strength was obtained for zirconia surfaces abraded at 0.2 MPa (15.88 ± 2.70 MPa) and 0.3 MPa (14.32 ± 1.12 MPa). Aging did not decrease the strength for all groups except control group (p < 0.001).

Conclusions: Air-abrasion with 50 μm abrasive alumina particles at 0.2 MPa could achieve good strength for translucent zirconia ceramics while maintaining adequate and durable bonding with resin cement.

Clinical Relevance: A total of 0.2 MPa is recommended for air-abrasion procedure applied before a dental restoration fabricated with translucent zirconia is bonded to resin cement.
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http://dx.doi.org/10.1007/s00784-020-03506-yDOI Listing
April 2021

Efficacy of PD-1/PD-L1 blockade monotherapy in clinical trials.

Ther Adv Med Oncol 2020 16;12:1758835920937612. Epub 2020 Jul 16.

The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.

Background: Inhibitors targeting programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have unprecedented effects in cancer treatment. However, the objective response rates (ORRs), progression-free survival (PFS), and overall survival (OS) of PD-1/PD-L1 blockade monotherapy have not been systematically evaluated.

Methods: We searched Embase, PubMed, and Cochrane database from inception to July 2019 for prospective clinical trials on single-agent PD-1/PD-L1 antibodies (avelumab, atezolizumab, durvalumab, cemiplimab, pembrolizumab, and nivolumab) with information regarding ORR, PFS, and OS.

Results: Totally, 28,304 patients from 160 perspective trials were included. Overall, 4747 responses occurred in 22,165 patients treated with PD-1/PD-L1 monotherapy [ORR, 20.21%; 95% confidence interval (CI), 18.34-22.15%]. Compared with conventional therapy, PD-1/PD-L1 blockade immunotherapy was associated with more tumor responses (odds ratio, 1.98; 95% CI, 1.52-2.57) and better OS [hazard ratio (HR), 0.75; 95% CI, 0.67-0.83]. The ORRs varied significantly across cancer types and PD-L1 expression status. Line of treatment, clinical phase and drug target also impacted the response rates in some tumors. A total of 2313 of 9494 PD-L1 positive patients (ORR, 24.39%; 95% CI, 22.29-26.54%) and 456 of 4215 PD-L1 negative patients (ORR, 10.34%; 95% CI, 8.67-12.14%) achieved responses. For PD-L1 negative patients, the ORR (odds ratio, 0.92; 95% CI, 0.70-1.20) and PFS (HR, 1.15; 95% CI, 0.87-1.51) associated with immunotherapy and conventional treatment were similar. However, PD-1/PD-L1 blockade monotherapy decreased the risk of death in both PD-L1 positive (HR, 0.66; 95% CI, 0.60-0.72) and PD-L1 negative (HR, 0.86; 95% CI, 0.74-0.99) patients compared with conventional therapy.

Conclusion: The efficacies associated with PD-1/PD-L1 monotherapy vary significantly across cancer types and PD-L1 expression. This comprehensive summary of clinical benefit from immunotherapy in cancer patients provides an important guide for clinicians.
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http://dx.doi.org/10.1177/1758835920937612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366397PMC
July 2020

Fatal adverse events associated with programmed cell death protein 1 or programmed cell death-ligand 1 monotherapy in cancer.

Ther Adv Med Oncol 2020 6;12:1758835919895753. Epub 2020 Feb 6.

Zhuhai People's Hospital, Zhuhai Hospital affiliated with Jinan University, Zhuhai, China.

Background: The introduction of antibodies targeting programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) into clinical practice has had a revolutionary effect on cancer treatment. However, the incidence and risk of fatal adverse events (FAEs) following PD-1/PD-L1 inhibitor administration are controversial.

Methods: We performed a systematic search for randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitors (atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab) in Embase, PubMed, the Cochrane database, and abstracts presented at American Society of Clinical Oncology and European Society of Medical Oncology from inception to July 2018. FAEs were extracted from each study and pooled to calculate overall incidence and odds ratios (ORs).

Results: In total, 20 RCTs involving 12,398 patients with solid tumors were included in this study. The overall incidence of FAEs with PD-1/PD-L1 inhibitors was 0.43% [95% confidence interval (CI), 0.25-0.66%]. However, the incidences of FAEs varied significantly by tumor type and median follow-up time. Compared with conventional agents, the application of PD-1/PD-L1 inhibitors significantly reduced the risk of FAEs (OR, 0.56; 95% CI, 0.35-0.89;  = 0.015). Moreover, trial sequential analysis confirmed that our results were solid and reliable; further studies were unlikely to alter this conclusion. FAEs occurred dispersed in major organ systems, with the most common mortalities appearing in the respiratory system (46.2%).

Conclusions: Compared with conventional treatment, PD-1/PD-L1 blockade monotherapy is associated with a significantly reduced risk of mortality in patients with solid tumors.
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http://dx.doi.org/10.1177/1758835919895753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005982PMC
February 2020

Molecular Insights into Sequence Distributions and Conformation-Dependent Properties of High-Phenyl Polysiloxanes.

Polymers (Basel) 2019 Dec 2;11(12). Epub 2019 Dec 2.

School of Materials Science and Engineering, Shandong University, Jinan 250061, China.

The excellent performance and wide applications of phenyl polysiloxanes are largely due to their phenyl units and monomer sequences. However, the relationship between molecular structure and material properties has not been explicitly elucidated. In this work, the sequence distribution and microstructure of random copolymers were quantitatively investigated by means of a molecular dynamics (MD) simulation combined with experimental verification. The results of Si NMR showed that the large number of phenyl units not only shortened the length of the dimethyl units, but also significantly increased the proportion of consecutive phenyl units. The simulation results indicated the attraction between adjacent phenyl groups that were effectively strengthened intra- and inter- molecular interactions, which determined the equilibrium population of conformations and the dynamics of conformational transitions. Furthermore, the evolution of bond angle distribution, torsion distribution, and mean-squared displacements (MSD) shed light on the conformational characteristics that induce the unique thermodynamics properties and photophysical behavior of high-phenyl polysiloxanes. Differential scanning calorimetry (DSC), dynamical mechanical analysis (DMA), spectrofluorimetry, and laser scanning confocal microscopy (LSCM) were performed to verify the conclusions drawn from the simulation. Overall, the complementary use of MD simulations and experiments provided a deep molecular insight into structure-property relationships, which will provide theoretical guidance for the rational design and preparation of high-performance siloxanes.
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http://dx.doi.org/10.3390/polym11121989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960887PMC
December 2019

Host-Induced Silencing of Genes Enhances the Resistance of to Head Blight.

Front Plant Sci 2019 30;10:1362. Epub 2019 Oct 30.

State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant Protection, Northwest A&F University, Yangling, China.

head blight (FHB) caused by pathogens are devastating diseases worldwide. Host-induced gene silencing (HIGS) which involves host expression of double-stranded RNA (dsRNA)-generating constructs directed against genes in the pathogen has been a potential strategy for the ecological sound control of FHB. In this study, we constructed transgenic lines carrying RNA interference (RNAi) cassettes to target two essential protein kinase genes and , and cytochrome P450 lanosterol C14-α-demethylase (CYP51) encoding genes (, , and ) of , respectively. Northern blotting confirmed the presence of short interfering RNAs (siRNA) derived from , , and in transgenic plants, and the transcript levels of the corresponding genes were down-regulated in the colonizing spikes. All the corresponding independent, -RNAi, -RNAi, and -RNAi transgenic T2 lines exhibited strong resistance to , suggesting that silencing molecules produced by transgenic plants inhibited the corresponding gene function by down-regulating its expression, thereby reducing pathogenicity. Our results indicate that and are effective targets for HIGS and can be applied to construct transgenic HIGS materials to enhance FHB resistance in wheat and other cereal crops.
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http://dx.doi.org/10.3389/fpls.2019.01362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831556PMC
October 2019

Factors influencing cultivated ginseng (Panax ginseng C. A. Meyer) bioactive compounds.

PLoS One 2019 16;14(10):e0223763. Epub 2019 Oct 16.

National & Local United Engineering Laboratory for Chinese Herbal Medicine Breeding and Cultivation, Jilin University, Changchun, Jilin, China.

We aimed to investigate the effects of genome, age, and soil factors on cultivated Panax ginseng C. A. Meyer (CPG) compounds under identical climate and agronomic practices. Eight populations of CPG from different years and rhizosphere soils were collected from garden and cropland in the city of Ji'an, China. Inter-simple sequence repeat (ISSR) primers were used to detect genetic diversity and identity, and soil microbial community diversity. Soil enzyme activities and nutrients were also measured. The contents of total ginsenosides (TG), Rg1, Re, Rf, Rd, and ginsenoside extractions of CPG were analyzed by spectrophotometry and HPLC. The relative importance of each factor was analyzed by mathematical methods such as correlation analysis, stepwise line regression, and path analysis. Regression equations of similarity values of HPLC fingerprint (SVHF), richness index of HPLC fingerprint (RIHF) and the TG, Rg1, Re, Rf, and Rd contents with their respective significant correlation factors were obtained. For SVHF, the relative importance is age>microbial community diversity>genetic diversity. For RIHF, the relative importance is age>genetic diversity>microbial community diversity. For TG, Rg1, and Rf contents, the relative importance is age>microbial community diversity. Ginseng age and genetic identity influenced Rd content, and age was more important. Total phosphorus was the only directly negative effect on Re. According to regression equations and path analysis, increasing age and decreasing Shannon (H') could improve the TG, Rg1, and Rf contents, with little effect on SVHF. Adding age, genetic diversity, and decreasing Shannon (H') increased RIHF. Adding age and genetic identity could also improve Rd content. Appropriate decreases in total phosphorus might increase Re content. These findings are significant for CPG scientific cultivation methods, through which CPG bioactive ingredients could be finely controlled via regulation of genotypes and cultural conditions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223763PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795439PMC
March 2020

Incidence and Risk of Fatal Adverse Events in Cancer Patients Treated With Vascular Endothelial Growth Factor Receptor 2-Targeted Agents: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials.

Front Med (Lausanne) 2019 7;6:176. Epub 2019 Aug 7.

The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

Agents targeting vascular endothelial growth factor (VEGF) pathway have dramatically improved the outlook of cancer treatment. Meanwhile, it is well-known that they are associated with increases in the risk of fatal adverse events (FAEs). Vascular endothelial growth factor receptor 2 (VEGFR2)-targeted drugs have been approved for the treatment of several malignancies. However, little is known regarding the FAEs induced by VEGFR2-targeted agents across different tumor types and treatment regimens. We searched PubMed and Embase database from January 1966 to April 2018 for randomized controlled trials (RCTs) to calculate the incidence and relative risks (RRs) of FAE. Seventeen RCTs involving 6,982 subjects with solid tumors were included in this study. The overall incidence of FAEs associated with VEGFR2-targeted agents was 1.7% (95% CI: 0.9-2.4%). Compared with controls, the administration of VEGFR2-targeted agents did not increase the risk of FAEs (RR, 1.29; 95% CI: 0.90-1.86). No significant association was found between FAE and VEGFR2-targeted agents in subgroup analyses based on tumor type, treatment strategy, clinical phase, masking method, median treatment duration, and approval status. Additionally, FAEs occurred in the major organ systems dispersedly. Trial sequential analysis revealed that our results are solid and further studies are unlikely to change this. VEGFR2-targeted agents were not associated with an increased risk of FAEs.
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http://dx.doi.org/10.3389/fmed.2019.00176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693387PMC
August 2019

Risk of fatal adverse events in cancer patients treated with sunitinib.

Crit Rev Oncol Hematol 2019 May 16;137:115-122. Epub 2019 Mar 16.

The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, 325027, China; The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China. Electronic address:

Sunitinib, a tyrosine kinase inhibitor, is widely used in several malignancies. However, the association between sunitinib administration and fatal adverse events (FAEs) is not completely clear. Here, to calculate the overall incidence and relative risks (RRs) of FAE induced by sunitinib, PubMed and Embase were searched from inception to September 2017 for phase III randomized controlled trials (RCTs). A total of 7470 patients with a variety of solid tumors from 12 trials were included in this study. The overall incidence of FAEs with sunitinib was 1.2% (95% CI: 0.7%-1.8%). Compared with control, the addition of sunitinib significantly increased the risk of FAEs (RR, 2.34; 95% CI, 1.34-4.09; P < 0.001). Trial sequential analysis demonstrated the cumulative z curve crossed the trial sequential monitoring boundary, established sufficient and conclusive evidence. Accordingly, further studies were unlikely to alter this conclusion. The association between sunitinib and FAEs varied significantly with treatment duration or treatment strategy, but not with tumor types or sunitinib dosage. The most common causes of FAEs was hemorrhage (26.9%). In conclusion, the use of sunitinib was associated with an increased risk of FAEs in patients with solid tumors.
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http://dx.doi.org/10.1016/j.critrevonc.2019.03.007DOI Listing
May 2019

Corrigendum to "Incidence and clinical parameters associated with eribulin mesylate-induced peripheral neuropathy" [Crit. Rev. Oncol./Hematol. 128 (August) (2018) 110-117].

Crit Rev Oncol Hematol 2019 Mar 24;135:20. Epub 2019 Jan 24.

The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China. Electronic address:

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http://dx.doi.org/10.1016/j.critrevonc.2019.01.007DOI Listing
March 2019
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