Publications by authors named "Ming Xia"

206 Publications

BaZn(BO)F: a new beryllium-free zincoborate with a KBBF-type structure.

Dalton Trans 2021 Sep 15. Epub 2021 Sep 15.

CAS Key Laboratory of Functional Materials and Devices for Special Environments, Xinjiang Technical Institute of Physics & Chemistry, CAS, and Xinjiang Key Laboratory of Electronic Information Materials and Devices, 40-1 South Beijing Road, Urumqi 830011, China.

A new beryllium-free zincoborate, BaZn(BO)F, with a KBBF-type structure has been synthesized for the first time. The electrostatic force of interaction in BaZn(BO)F provides better linkage in neighboring [ZnBOF] single layers. BaZn(BO)F is the first case of borates with both [ZnOF] tetrahedra and [ZnO] octahedra, enriching the structural chemistry of borate system. All the coplanar [BO] triangles align in the same direction with a high density, which endows BaZn(BO)F with a large birefringence of cal. 0.076 at 1064 nm. This work is of great significance to design beryllium-free borates with a KBBF-type structure.
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http://dx.doi.org/10.1039/d1dt02356jDOI Listing
September 2021

Downregulation of miR‑214-3p attenuates mesangial hypercellularity by targeting PTEN‑mediated JNK/c-Jun signaling in IgA nephropathy.

Int J Biol Sci 2021 31;17(13):3343-3355. Epub 2021 Jul 31.

Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan, China.

Mesangial cell (MC) proliferation and matrix expansion are basic pathological characteristics of IgA nephropathy (IgAN). However, the stepwise mechanism of MC proliferation and the exact set of related signaling molecules remain largely unclear. In this study, we found a significant upregulation of miR-214-3p in the renal cortex of IgAN mice by miRNA sequencing. hybridization analysis showed that miR-214-3p expression was obviously elevated in MCs in the renal cortex in IgAN. Functionally, knockdown of miR-214-3p alleviated mesangial hypercellularity and renal lesions in IgAN mice. , the inhibition of miR-214-3p suppressed MC proliferation and arrested G1-S cell cycle pSrogression in IgAN. Mechanistically, a luciferase reporter assay verified PTEN as a direct target of miR-214-3p. Downregulation of miR-214-3p increased PTEN expression and reduced p-JNK and p-c-Jun levels, thereby inhibiting MC proliferation and ameliorating renal lesions in IgAN. Moreover, these changes could be attenuated by co-transfection with PTEN siRNA. Collectively, these results illustrated that miR-214-3p accelerated MC proliferation in IgAN by directly targeting PTEN to modulate JNK/c-Jun signaling. Therefore, miR-214-3p may represent a novel therapeutic target for IgAN.
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http://dx.doi.org/10.7150/ijbs.61274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416718PMC
July 2021

Identification of the Immune-Related Genes in Tumor Microenvironment That Associated With the Recurrence of Head and Neck Squamous Cell Carcinoma.

Front Cell Dev Biol 2021 20;9:723721. Epub 2021 Aug 20.

Department of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Head and neck squamous cell carcinomas (HNSCC) are still one of the most common malignant tumors in China, with a high metastasis rate and poor prognosis. The tumor immune microenvironment can affect the occurrence, development and prognosis of tumors, but the underlying mechanism is still unclear. In this study, we tried to describe the correlation between the recurrence of HNSCC and the tumor microenvironment (TME). The expression data [estimate the level of tumor stromal and immune infiltration, expression data (ESTIMATE)] algorithm was used to identify and estimate highly correlated stromal cells, immune cells, and prognostic scores in 116 samples of head and neck cancer patients from The Cancer Genome Atlas (TCGA) dataset. The functional enrichment analysis and protein-protein interaction (PPI) networks of differential expressed genes (DEGs) were constructed. Subsequently, the abundance of various infiltrating immune cells was estimated with the tumor immune estimation resource (TIMER) and the infiltration pattern of immune cells were explored in HNSCC. A total of 407 immune-related genes were identified to involve in the TME. We found that CCR5, CD3E, CD4, and HLA -DRB1 were the most obvious DEGs and the dendritic cells (DCs) showed the highest abundance in the TME of HNSCC. In addition, the unsupervised cluster analysis determined 10 clusters of immune infiltration patterns, and indicated that immune infiltrated CD4 + T and B cells may be related to the prognosis of HNSCC. In conclusion, our research determined the list of immune genes and immune infiltrating cells related to the prognosis of HNSCC, and provided a perspective for HNSCC evolution, anti-tumor drugs selection, and drug resistance research.
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http://dx.doi.org/10.3389/fcell.2021.723721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417745PMC
August 2021

Selenium-GPX4 axis protects follicular helper T cells from ferroptosis.

Nat Immunol 2021 09 19;22(9):1127-1139. Epub 2021 Aug 19.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Follicular helper T (T) cells are a specialized subset of CD4 T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of T cell survival remains unclear. Here we report that T cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for T cell survival. The deletion of GPX4 in T cells selectively abrogated T cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased T cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating T homeostasis, which can be targeted to enhance T cell function in infection and following vaccination.
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http://dx.doi.org/10.1038/s41590-021-00996-0DOI Listing
September 2021

BMI1 activates P-glycoprotein via transcription repression of and enhances chemoresistance of bladder cancer cell.

Aging (Albany NY) 2021 07 16;13(14):18310-18330. Epub 2021 Jul 16.

Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.

Chemoresistance is the most significant reason for the failure of cancer treatment following radical cystectomy. The response rate to the first-line chemotherapy of cisplatin and gemcitabine does not exceed 50%. In our previous research, elevated BMI1 (B-cell specific Moloney murine leukemia virus integration region 1) expression in bladder cancer conferred poor survival and was associated with chemoresistance. Herein, via analysis of The Cancer Genome Atlas database and validation of clinical samples, BMI1 was elevated in patients with bladder cancer resistant to cisplatin and gemcitabine, which conferred tumor relapse and progression. Consistently, BMI1 was markedly increased in the established cisplatin- and gemcitabine-resistant T24 cells (T24/DDP&GEM). Functionally, BMI1 overexpression dramatically promoted drug efflux, enhanced viability and decreased apoptosis of bladder cancer cells upon treatment with cisplatin or gemcitabine, whereas BMI1 downregulation reversed this effect. Mechanically, upon interaction with p53, BMI1 was recruited on the promoter of gene concomitant with an increase in the mono-ubiquitination of histone H2A lysine 119, leading to transcription repression of gene followed by derepression of (ATP binding cassette subfamily B member 1) gene. Moreover, suppression of P-glycoprotein by miR-3682-3p mimics or its inhibitor XR-9576, could significantly reverse chemoresistance of T24/DDP&GEM cells. These results provided a novel insight into a portion of the mechanism underlying BMI1-mediated chemoresistance in bladder cancer.
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http://dx.doi.org/10.18632/aging.203277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351696PMC
July 2021

Comprehensive signature analysis of drug metabolism differences in the White, Black and Asian prostate cancer patients.

Aging (Albany NY) 2021 06 18;13(12):16316-16340. Epub 2021 Jun 18.

Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.

The drug response sensitivity and related prognosis of prostate cancer varied from races, while the original mechanism remains rarely understood. In this study, the comprehensive signature including transcriptomics, epigenome and single nucleotide polymorphisms (SNPs) of 485 PCa cases- including 415 Whites, 58 Blacks and 12 Asians from the TCGA database were analyzed to investigate the drug metabolism differences between races. We found that Blacks and Whites had a more prominent drug metabolism, cytotoxic therapy resistance, and endocrine therapy resistance than Asians, while Whites were more prominent in drug metabolism, cytotoxic therapy resistance and endocrine therapy resistance than Blacks. Subsequently, the targeted regulation analysis indicated that the racial differences in cytotoxic therapy resistance, endocrine therapy resistance, might originate from drug metabolisms, and 19 drug metabolism-related core genes were confirmed in the multi-omics network for subsequent analysis. Furthermore, we verified that significantly affected antineoplastic drugs sensitivities in PCa cell lines, and these genes also showed good predictive efficiency of drug response and treatment outcomes for PCa in this cohort of patients. These findings revealed a comprehensive signature of drug metabolism differences for the Whites, Blacks and Asians, and it may provide some evidence for making individualized treatment strategies.
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http://dx.doi.org/10.18632/aging.203158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266326PMC
June 2021

Generation of neoantigen-specific T cells for adoptive cell transfer for treating head and neck squamous cell carcinoma.

Oncoimmunology 2021 05 25;10(1):1929726. Epub 2021 May 25.

Cytotherapy Laboratory, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen Guangdong, China.

Adoptive cell therapy using TCR-engineered T cells (TCR-T cells) represents a promising strategy for treating relapsed and metastatic cancers. We previously established methods to identify neoantigen-specific TCRs based on patients' PBMCs. However, in clinical practice isolation of PBMCs from advanced-stage cancer patients proves to be difficult. In this study, we substituted blood-derived T cells for tumor-infiltrating lymphocytes (TILs) and used an HLA-matched cell line of antigen-presenting cells (APCs) to replace autologous dendritic cells. Somatic mutations were determined in head and neck squamous cell carcinoma resected from two patients. HLA-A*02:01-restricted neoantigen libraries were constructed and transferred into HLA-matched APCs for stimulation of patient TILs. TCRs were isolated from reactive TIL cultures and functionality was tested using TCR- T cells and . To exemplify the screening approach, we identified the targeted neoantigen leading to recognition of the minigene construct that stimulated the strongest TIL response. Neoantigen peptides were used to load MHC-tetramers for T cell isolation and a TCR was identified targeting the KIAA1429 mutation. TCR-T cells were activated, exhibited cytotoxicity, and secreted cytokines in a dose-dependent manner, and only when stimulated with the mutant peptide. Furthermore, comparable to a neoantigen-specific TCR that was isolated from the patient's PBMCs, KIAA1429-specific TCR T cells destroyed human tumors in mice. The established protocol provides the required flexibility to methods striving to identify neoantigen-specific TCRs. By using an MHC-matched APC cell line and neoantigen-encoding minigene libraries, autologous TILs can be stimulated and screened when patient PBMCs and/or tumor material are not available anymore. Abbreviations: Head and neck squamous cell carcinoma (HNSCC); adoptive T cell therapy (ACT); T cell receptor (TCR); tumor-infiltrating lymphocytes (TIL); cytotoxic T lymphocyte (CTL); peripheral blood mononuclear cell (PBMC); dendritic cell (DC); antigen-presenting cells (APC).
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http://dx.doi.org/10.1080/2162402X.2021.1929726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158031PMC
May 2021

Individual and combined effects of BPA, BPS and BPAF on the cardiomyocyte differentiation of embryonic stem cells.

Ecotoxicol Environ Saf 2021 Sep 28;220:112366. Epub 2021 May 28.

The Ninth People's Hospital of Shanghai, Jiao Tong University School of Medicine, Shanghai 200011, PR China. Electronic address:

Exposure to many kinds of bisphenols (BPs) is common, and the effects of BP mixtures may differ from those of individual BPs. Therefore, evaluating combined exposure effects is necessary. Our study evaluated the individual and combined exposure effects of bisphenol A (BPA), bisphenol S (BPS) and bisphenol AF (BPAF) on embryonic development using an embryonic stem cell test (EST) and a concentration additive (CA) model at relatively high doses to uncover the interaction model of the three BPs. Environmentally relevant concentrations were then used to evaluate the possible effects of the individual and combined BPs at actual human exposure levels. Exposure to relatively high-dose BPA, BPS and BPAF inhibited embryonic stem cell differentiation into cardiomyocytes and exhibited weak embryo toxicity. Individually, BPA, BPS and BPAF inhibited endoderm, mesoderm and ectoderm marker expression but enhanced pluripotency marker expression. Combined exposure to BPs had an additive effect on cardiomyocyte differentiation and embryonic stem cell proliferation based on the CA model. Environmentally relevant individual or combined BP doses (10 ng/ml individual BPA, BPS and BPAF doses or 1 ng/ml and 10 ng/ml BP mixture doses) failed to cause oxidative stress, DNA damage or apoptosis changes in stem cell differentiation. The cardiomyocyte differentiation ratio also did not change significantly. Individual and combined exposure to environmentally relevant BP doses led to a significant increase in collagen expression. BPAF and the combination of BPs increased the type 1 collagen level, while the combination also increased the type 3 collagen level, which may be related to p38 pathway activation. The p38 pathway inhibitor SB203580 inhibited the increase in collagen during cardiomyocyte differentiation caused by low-dose BPs. These results suggest that relatively high-dose BPs in combination have an additive effect on cardiomyocyte differentiation. Low-dose BPs individually and in combination may affect cardiomyocyte collagen through the p38 pathway.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112366DOI Listing
September 2021

Intra-species sialic acid polymorphism in humans: a common niche for influenza and coronavirus pandemics?

Emerg Microbes Infect 2021 Dec;10(1):1191-1199

Department of Chemistry and Biochemistry, Miami University, Oxford, OH, USA.

The ongoing COVID-19 pandemic has led to more than 159 million confirmed cases with over 3.3 million deaths worldwide, but it remains mystery why most infected individuals (∼98%) were asymptomatic or only experienced mild illness. The same mystery applies to the deadly 1918 H1N1 influenza pandemic, which has puzzled the field for a century. Here we discuss dual potential properties of the 1918 H1N1 pandemic viruses that led to the high fatality rate in the small portion of severe cases, while about 98% infected persons in the United States were self-limited with mild symptoms, or even asymptomatic. These variations now have been postulated to be impacted by polymorphisms of the sialic acid receptors in the general population. Since coronaviruses (CoVs) also recognize sialic acid receptors and cause severe acute respiratory syndrome epidemics and pandemics, similar principles of influenza virus evolution and pandemicity may also apply to CoVs. A potential common principle of pathogen/host co-evolution of influenza and CoVs under selection of host sialic acids in parallel with different epidemic and pandemic influenza and coronaviruses is discussed.
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http://dx.doi.org/10.1080/22221751.2021.1935329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208123PMC
December 2021

M2 subtype tumor associated macrophages (M2-TAMs) infiltration predicts poor response rate of immune checkpoint inhibitors treatment for prostate cancer.

Ann Med 2021 12;53(1):730-740

Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.

Background: Prostate cancer (PCa) is poor response to the immunotherapy for its high heterogeneity of immune microenvironment. In this study, we aim to introduce a new immune subtype for PCa involving M2 tumour associated macrophages M2-TAMs).

Methods: Three hundred and sixty-two PCa patients and matched normal prostate tissues were selected from the Cancer Genome Atlas and Gene Expression Omnibus databases. Patients' immune infiltration characters were then analyzed based on the gene expressions. The immune subtypes were identified by the method of unsupervised hierarchical clustering. Finally, the relationship between the M2-TAMs infiltration and anti-programmed death-ligand-1 (PD-L1) therapy was investigated in the IMvigor210 cohort.

Results: PCa expressed lower immune-related genes levels compared with the adjacent normal tissues. Based on the proved immunosuppressive mechanisms in PCa, tumour patients were classified into three independent subclasses with high infiltrated cytolytic activity (CYT), M2-TAMs and regulatory T cell (Tregs), respectively. Among these subtypes, M2-TAMs infiltration subtype showed the worst clinicopathological features and prognosis compared with the other two subtypes. The results of the IMvigor210 cohort demonstrated poor response of anti-PD-L1 therapy for patients with high M2-TAMs infiltration.

Conclusion: Prostate tumours involved in significant immunosuppression, and high infiltration of M2-TAMs can be applied to predict the effect of anti-PD-L1 therapy.Key MessagesPCa patients can be classified into three immunotypes of high infiltrated CYT, M2-TAMS, and Tregs according to the immunosuppressive mechanisms.High M2-TAMs infiltration subtype reflected the worst clinical characters, immune infiltration, and lowest expression of immune checkpoint inhibitors among the three subclasses in PCa.High M2-TAMs infiltration predicts the low response rate of anti-PD-L1 therapy.
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http://dx.doi.org/10.1080/07853890.2021.1924396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158194PMC
December 2021

Cs B O F : First Fluorooxoborate with [BF ] Involving Heteroanionic Units and Extremely Low Melting Point.

Chemistry 2021 Jul 21;27(38):9753-9757. Epub 2021 May 21.

CAS Key Laboratory of Functional Materials and Devices for Special Environments, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Xinjiang Key Laboratory of Electronic Information Materials and Devices, 40-1 South Beijing Road, Urumqi, 830011, P.R. China.

Herein, a new congruently melting mixed-anion compound Cs B O F has been characterized as the first fluorooxoborate with [BF ] involving heteroanionic units. Compound Cs B O F possesses two highly fluorinated anionic clusters and therefore its formula can be expressed as Cs (B O F ) ⋅ Cs(BF ). The influence of [BF ] units on micro-symmetry and structural evolution was discussed based on the parent compound. More importantly, Cs B O F shows the lowest melting point among all the available borates and thus sets a new record for such system. This work is of great significance to enrich and tailor the structure of borates using perfluorinated [BF ] units.
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http://dx.doi.org/10.1002/chem.202101321DOI Listing
July 2021

Fine particles in surgical smoke affect embryonic cardiomyocyte differentiation through oxidative stress and mitophagy.

Ecotoxicol Environ Saf 2021 Jul 25;217:112259. Epub 2021 Apr 25.

The Ninth People's Hospital of Shanghai, Jiao Tong University School of Medicine, Shanghai 200011, PR China. Electronic address:

Surgical smoke is widespread in operating rooms, and fine particles are the main toxic components. However, the effect of fine particles in surgical smoke on embryonic development has not yet been studied. This study evaluated the effect of fine particles in surgical smoke on embryonic development and compared it with that of atmospheric fine particles. Afterwards, differentiated cardiomyocytes were purified, and the effect of exposure to fine particles in surgical smoke on cardiomyocyte differentiation was evaluated. Fine particles in surgical smoke exhibited weak embryotoxicity toward an embryonic stem cell test model, and their inhibitory effect on cardiomyocyte differentiation was slightly stronger than that of atmospheric fine particles. Fine particles in surgical smoke specifically inhibited the differentiation of the mesoderm lineage and promoted the differentiation of the ectoderm lineage. Furthermore, fine particles in surgical smoke reduced the beating rate of purified cardiomyocytes, promoted mitophagy, reduced ATP production and increased the reactive oxygen species (ROS) content. Antioxidants attenuated the inhibition of cardiomyocyte differentiation and the reduction in the cardiomyocyte beating rate caused by fine particles in surgical smoke and simultaneously restored mitophagy and other processes to the control levels. However, mitophagy inhibitors treatment blocked only the inhibition of cardiomyocyte differentiation caused by fine particles in surgical smoke; it had little effect on other changes caused by fine particles. Based on the results described above, we propose that fine particles in surgical smoke and atmospheric fine particles exhibit similar levels of toxicity toward embryonic development. Fine particles in surgical smoke potentially affect the beating of cardiomyocytes by damaging mitochondria and increasing oxidative stress.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112259DOI Listing
July 2021

Discovery of First Magnesium Fluorooxoborate with Stable Fluorine Terminated Framework for Deep-UV Nonlinear Optical Application.

Angew Chem Int Ed Engl 2021 Jun 20;60(26):14650-14656. Epub 2021 May 20.

CAS Key Laboratory of Functional Materials and Devices for Special Environments, Xinjiang Technical Institute of Physics & Chemistry, CAS, Xinjiang Key Laboratory of Electronic Information Materials and Devices, 40-1 South Beijing Road, Urumqi, 830011, China.

The generated light can be tuned to cover almost the entire spectral range from deep-ultraviolet to terahertz wavelengths by utilizing the nonlinear optical crystals with a simple frequency doubling process. Among them, the discovery of novel candidates for the production of deep-ultraviolet light is by extension a great challenge toward realizing the vast potential. Actually, the availability for this process mainly depends on whether the critical performance can be well coexisted in one practical crystal. Herein, the first magnesium fluorooxoborate MgB O F was synthesized as a new competitive candidate for deep-ultraviolet nonlinear optical application. It has a sufficiently large nonlinearity and a deep-ultraviolet phase matching wavelength, indicating that it holds great potential for the production of coherent light below 200 nm. The critical performance enhancement of MgB O F when compared with its isomorphic phases was demonstrated and discussed. More importantly, we proposed that fluorooxoborate system with the general formula of MB O F (M=divalent metal) possesses stable fluorine terminated framework, which makes them tend to retain their crystallized space groups unchanged.
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http://dx.doi.org/10.1002/anie.202103657DOI Listing
June 2021

Sequential receptor-mediated mixed-charge nanomedicine to target pancreatic cancer, inducing immunogenic cell death and reshaping the tumor microenvironment.

Int J Pharm 2021 May 29;601:120553. Epub 2021 Mar 29.

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, Qingdao, China. Electronic address:

Pancreatic cancer (PC) is an aggressive form of cancer with dense stroma and immune-suppressive microenvironment, which are the major barriers for treatment. To address such barriers, this study aimed to develop a sequential receptor-mediated mixed-charge targeted delivery system for PC based on 2-(3-((S)-5-amino-1-carboxypentyl)-ureido) pentanedioate (ACUPA) and triphenylphosphonium (TPP) modified nanomicelles containing ingenol-3-mebutate (I3A), which was named ACUPA/TPP-I3A or ACUPA/TPP-I3A. ACUPA/TPP-I3A induced immunogenic cell death (ICD), which significantly increased the number of tumor-infiltrating T lymphocytes, activated adaptive immunity, and achieved superior survival time. I3A, a novel anticancer drug, could induce PC cell necrosis to release damage-associated molecular patterns, thereby activating adaptive immunity. With certain ratios of negatively (ACUPA) and positively (TPP) charged ligands, ACUPA/TPP-I3A acquired a negative charge in plasma (pH 7.4, to inhibit aggregation and uptake in the circulation) and was neutral in the acidic tumor microenvironment (pH 5.0-6.0, to overcome electrostatic hindrances and facilitate transcytosis). Furthermore, neovascular endothelium-specific ACUPA enabled rapid transcytosis of ACUPA/TPP-I3A across tumor vessel walls, entering into endosome/lysosomes (pH 4.5-5.0, its charge became positive and exhibited lysosome escape). Then, ACUPA/TPP-I3A selectively targeted mitochondria, which correlated with TPP-mediated effect. Finally, I3A was released to induce ICD that activated adaptive immunity and achieved superior survival time. Therefore, reshaping of the tumor microenvironment and potentiating antitumor immunity using ACUPA/TPP-I3A constituted a novel strategy to prolong the survival time.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120553DOI Listing
May 2021

Ultrasensitive amyloid β-protein quantification with high dynamic range using a hybrid graphene-gold surface-enhanced Raman spectroscopy platform.

J Raman Spectrosc 2020 Mar 17;51(3):432-441. Epub 2019 Dec 17.

Department of Materials Science and Engineering, University of California, Los Angeles California, 90095, United States.

Surface enhanced Raman spectroscopy (SERS) holds great promise in biosensing because of its single-molecule, label-free sensitivity. We describe here the use of a graphene-gold hybrid plasmonic platform that enables quantitative SERS measurement. Quantification is enabled by normalizing analyte peak intensities to that of the graphene G peak. We show that two complementary quantification modes are intrinsic features of the platform, and that through their combined use, the platform enables accurate determination of analyte concentration over a concentration range spanning seven orders of magnitude. We demonstrate, using a biologically relevant test analyte, the amyloid β-protein (Aβ), a seminal pathologic agent of Alzheimer's disease (AD), that linear relationships exist between (a) peak intensity and concentration at a single plasmonic hot spot smaller than 100 nm, and (b) frequency of hot spots with observable protein signals, i.e. the co-location of an Aβ protein and a hot spot. We demonstrate the detection of Aβ at a concentration as low as 10 M after a single 20 μl aliquot of the analyte onto the hybrid platform. This detection sensitivity can be improved further through multiple applications of analyte to the platform and by rastering the laser beam with smaller step sizes.
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http://dx.doi.org/10.1002/jrs.5785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938713PMC
March 2020

Protective effect of bone marrow mesenchymal stem cell-derived exosomes against the reproductive toxicity of cyclophosphamide is associated with the p38MAPK/ERK and AKT signaling pathways.

Asian J Androl 2021 Jul-Aug;23(4):386-391

Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.

Spermatogenic dysfunction caused by cyclophosphamide (CP) chemotherapy has seriously influenced the life quality of patients. Unfortunately, treatments for CP-induced testicular spermatogenic dysfunction are limited, and the molecular mechanisms are not fully understood. For the first time, here, we explored the effects of bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) on CP-induced testicular spermatogenic dysfunction in vitro and in vivo. BMSC-exos could be taken up by spermatogonia (GC1-spg cells). CP-injured GC1-spg cells and BMSC-exos were cocultured at various doses, and then, cell proliferation was measured using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. In addition, photophosphorylation of extracellular-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), and protein kinase B (AKT) proteins was evaluated by western blotting as well as apoptosis in GC1-spg cells measured using flow cytometry. Treatment with BMSC-exos enhanced cell proliferation and reduced apoptosis of CP-injured GCI-spg cells. Phosphorylated levels of ERK, AKT, and p38MAPK proteins were reduced in CP-injured spermatogonia when co-treated with BMSC-exos, indicating that BMSC-exos acted against the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways. In experiments in vivo, CP-treated rats received BMSC-exos by injection into the tail vein, and testis morphology was compared between treated and control groups. Histology showed that transfusion of BMSC-exos inhibited the pathological changes in CP-injured testes. Thus, BMSC-exos could counteract the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways. The findings provide a potential treatment for CP-induced male spermatogenic dysfunction using BMSC-exos.
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http://dx.doi.org/10.4103/aja.aja_98_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269825PMC
February 2021

Aitongxiao improves pain symptoms of rats with cancer pain by reducing IL-1, TNF-α, and PGE2.

Int J Clin Exp Pathol 2021 1;14(1):133-139. Epub 2021 Jan 1.

Department of Oncology, Zibo Hospital of Traditional Chinese Medicine Zibo 255300, Shandong Province, China.

Objective: To explore the mechanism of Aitongxiao in improving pain symptoms of rats with cancer pain.

Methods: Walker 256 breast cancer cells were injected into the right tibial bone marrow cavity of normal female rats to establish a rat model of tibial cancer pain. The rats with successful model replication were randomly divided into normal group (NG), Hank solution group (HSG), cancer pain model group (CPMG), and Aitongxiao+cancer pain model group (ATX+CPMG). The pain response score, mechanical pain hindpaw withdrawal threshold, and latent heat pain of rats were evaluated, and the changes of serum IL-1β, TNF-α, PGE2 and blood cell counts of rats were detected.

Results: Compared with the NG, the pain response score was increased, the mechanical pain hindpaw withdrawal threshold and latent heat pain were decreased, and IL-1β, TNF-α, and PGE2 were increased in CPMG. Compared with the CPMG, the pain response score was decreased, the mechanical pain hindpaw withdrawal threshold and latent heat pain were increased, and IL-1β, TNF-α, and PGE2 were decreased in ATX+CPMG. There was no significant change in blood cell count in each group.

Conclusion: Aitongxiao can improve the pain symptoms of rats with tibial cancer pain. Its mechanism may be related to the reduction of IL-1β, TNF-α, and PGE2 levels.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847492PMC
January 2021

Immunofluorescence deposits in the mesangial area and glomerular capillary loops did not affect the prognosis of immunoglobulin a nephropathy except C1q:a single-center retrospective study.

BMC Nephrol 2021 01 29;22(1):43. Epub 2021 Jan 29.

Department of Nephrology, The Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, 410011, Hunan, China.

Background: Immunoglobulin A nephropathy (IgAN) is identified as mesangial IgA deposition and is usually accompanied by other immunofluorescence deposits. The impact of immunofluorescent features in IgAN patients, however, remains unclear.

Methods: Baseline clinicopathologic parameters and renal outcomes of 337 patients diagnosed with IgAN between January 2009 and December 2015 were analyzed. We then categorized these patients into four groups: without immunofluorescence deposits, mesangial-only, mesangial and glomerular capillary loops (GCLs), and GCLs-only. The study endpoint was end-stage kidney disease (ESKD) or a ≥ 50% decline in the estimated glomerular filtration rate (eGFR). Kaplan-Meier and Cox regression analyses were performed to calculate renal survival.

Results: Of the 337 IgAN patients, women comprised 57.0%. Compared to patients with IgA deposition in the mesangial-only group, patients with IgA deposition in the mesangial +GCLs group were much heavier, and exhibited higher systolic blood pressure, lower serum IgG levels, and heavier proteinuria (all P < 0.05). Patients with IgG deposition in the mesangial +GCLs group presented with higher levels of cholesterol, heavier proteinuria than IgG deposition in the mesangial-only group (both P < 0.05). Compared with the mesangial-only group exhibiting C3 deposits, patients in the mesangial +GCLs group with C3 deposition had a higher systolic blood pressure (P = 0.028). A total of 38 patients (11.3%) continued to the study endpoint after a median follow-up time of 63.5 months (range,49.8-81.4). Kaplan-Meier analysis and Cox regression analysis showed that C1q deposition in the mesangial +GCLs group predicted a poor renal prognosis.

Conclusions: IgA and IgG deposits in the mesangial region and GCLs were associated with more unfavorable clinical and histopathologic findings in IgAN patients. C1q deposition in the mesangial region and GCLs predicted a poor renal prognosis. However, the impact of the pattern of immunofluorescence deposits on renal outcomes remains to be proven by further investigation.
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http://dx.doi.org/10.1186/s12882-021-02237-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845044PMC
January 2021

Metal-organic frameworks/alginate composite beads as effective adsorbents for the removal of hexavalent chromium from aqueous solution.

Chemosphere 2021 May 31;270:129487. Epub 2020 Dec 31.

Department of Chemical Engineering (BK21 FOUR Integrated Engineering Program), Kyung Hee University, Yongin, 17104, South Korea. Electronic address:

Industrial waste discharge comprising heavy metals into potable water bodies induces many health hazards. This study investigates the role of metal-organic frameworks (MOFs) doped alginate beads ([email protected]) as potential adsorbents for Cr(VI). Effects of pH, stirring rate, temperature, initial chrome concentration, and particles dosage on Cr(VI) adsorption are studied to evaluate adsorption ability of [email protected] for Cr(VI) removal from aqueous solution. The adsorption kinetics follows pseudo second order and the equilibrium isotherm is consistent with Langmuir isotherm model. The maximum adsorption capacity of [email protected] calculated from the model conforms to the experimental results. The desorption experiment of Cr(VI) adsorbed [email protected] (82%) demonstrates satisfactory regeneration efficiency. Based on our findings and comparative controlled experiments, the superiority of [email protected] promises their potential application in Cr(VI) removal from wastewater.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129487DOI Listing
May 2021

A Nanoparticle-Based Trivalent Vaccine Targeting the Glycan Binding VP8* Domains of Rotaviruses.

Viruses 2021 Jan 6;13(1). Epub 2021 Jan 6.

Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Rotavirus causes severe gastroenteritis in children. Although vaccines are implemented, rotavirus-related diarrhea still claims ~200,000 lives annually worldwide, mainly in low-income settings, pointing to a need for improved vaccine tactics. To meet such a public health need, a P-VP8* nanoparticle displaying the glycan-binding VP8* domains, the major neutralizing antigens of rotavirus, was generated as a new type of rotavirus vaccine. We reported here our development of a P-VP8* nanoparticle-based trivalent vaccine. First, we established a method to produce tag-free P-VP8* nanoparticles presenting the VP8*s of P[8], P[4], and P[6] rotaviruses, respectively, which are the three predominantly circulating rotavirus P types globally. This approach consists of a chemical-based protein precipitation and an ion exchange purification, which may be scaled up for large vaccine production. All three P-VP8* nanoparticle types self-assembled efficiently with authentic VP8*-glycan receptor binding function. After they were mixed as a trivalent vaccine, we showed that intramuscular immunization of the vaccine elicited high IgG titers specific to the three homologous VP8* types in mice. The resulted mouse sera strongly neutralized replication of all three rotavirus P types in cell culture. Thus, the trivalent P-VP8* nanoparticles are a promising vaccine candidate for parenteral use against multiple P types of predominant rotaviruses.
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http://dx.doi.org/10.3390/v13010072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825513PMC
January 2021

Comprehensive analysis of circRNA expression profiles and circRNA-associated competing endogenous RNA networks in IgA nephropathy.

PeerJ 2020 3;8:e10395. Epub 2020 Dec 3.

Department of Nephrology, The Second Xiangya Hospital of Central University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan, China.

Background: Immunoglobulin A nephropathy (IgAN) is immune-mediated primary glomerulonephritis, which is the most common reason leading to renal failure worldwide. The exact pathogenesis of IgAN is not well defined. Accumulating evidence indicates that circular RNAs (circRNAs) play crucial roles in the immune disease by involving in the competing endogenous RNA (ceRNA) network mechanism. At present, the studies of the circRNA profiles and circRNA-associated ceRNA networks in the IgAN are still scarce. This study aimed to elucidate the potential roles of circRNA-associated ceRNA networks of peripheral blood mononuclear cells (PBMCs) in IgAN patients.

Method: CircRNA sequencing was used to identify the differential expressed circRNAs (DEcircRNAs) of PBMCs in IgAN and healthy controls; limma packages from data sets GSE25590 and GSE73953 in the Gene Expression Omnibus (GEO) database, were used to identify differentially expressed micro RNAs (miRNAs) and message RNAs (mRNAs). A circRNA-miRNA-mRNA ceRNA network was constructed to further investigate the mechanisms of IgAN. Then, GO analysis and KEGG enrichment analyses were used to annotate the genes involved in the circRNA-associated ceRNA network. Further, Protein-protein interaction (PPI) networks were established to screen potential hub genes, by using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Last, a quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify the hub genes in the ceRNA network.

Result: A total of 145 circRNAs, 22 miRNAs, and 1,117 mRNAs were differentially expressed in IgAN compared with controls ( < 0.05). A ceRNA network was constructed which contained 16 DEcircRNAs, 72 differential expressed mRNAs (DEmRNAs) and 11 differential expressed miRNAs (DEmiRNAs). KEGG pathway enrichment analysis illustrated the underlying biological functions of the ceRNA-associated genes, such as Nitrogen compound metabolic process, COPII-coated ER to Golgi transport vesicle, CAMP response element protein binding process ( < 0.01); meanwhile, Hepatitis B, GnRH signaling, and Prion disease were the most significant enrichment GO terms ( < 0.01). PPI network based on STRING analysis identified 4 potentially hub genes. Finally, Ankyrin repeat and SOCS box containing 16 (ASB16), SEC24 homolog C, COPII coat complex component (SEC24C) were confirmed by qRT-PCR ( < 0.05) and were identified as the hub genes of the ceRNA network in our study.

Conclusion: Our study identified a novel circRNA-mediated ceRNA regulatory network mechanisms in the pathogenesis of IgAN.
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http://dx.doi.org/10.7717/peerj.10395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719294PMC
December 2020

Cascaded residual U-net for fully automatic segmentation of 3D carotid artery in high-resolution multi-contrast MR images.

Phys Med Biol 2021 02 12;66(4):045033. Epub 2021 Feb 12.

College of Computer Science and Technology, Zhejiang University of Technology, Hangzhou, Zhejiang 310023 People's Republic of China.

Accurate and automatic carotid artery segmentation for magnetic resonance (MR) images is eagerly expected, which can greatly assist a comprehensive study of atherosclerosis and accelerate the translation. Although many efforts have been made, identification of the inner lumen and outer wall in diseased vessels is still a challenging task due to complex vascular deformation, blurred wall boundary, and confusing componential expression. In this paper, we introduce a novel fully automatic 3D framework for simultaneously segmenting the carotid artery from high-resolution multi-contrast MR sequences based on deep learning. First, an optimal channel fitting structure is designed for identity mapping, and a novel 3D residual U-net is used as a basic network. Second, high-resolution MR images are trained using both patch-level and global-level strategies, and the two pre-segmentation results are optimized based on structural characteristics. Third, the optimized pre-segmentation results are cascaded with the patch-cropped MR volume data and trained to segment the carotid lumen and wall. Extensive experiments demonstrate the proposed method outperforms the state-of-the-art 3D Unet-based segmentation models.
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http://dx.doi.org/10.1088/1361-6560/abd4bbDOI Listing
February 2021

Effects of rotavirus NSP4 protein on the immune response and protection of the S-VP8* nanoparticle rotavirus vaccine.

Vaccine 2021 01 11;39(2):263-271. Epub 2020 Dec 11.

Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address:

Rotavirus causes severe diarrhea and dehydration in young children. Even with the implementation of the current live vaccines, rotavirus infections still cause significant mortality and morbidity, indicating a need for new rotavirus vaccines with improved efficacy. To this end, we have developed an S-VP8*/S-VP8* nanoparticle rotavirus vaccine candidate that will be delivered parenterally with Alum adjuvant. In this study, as parts of our further development of this nanoparticle vaccine, we evaluated 1) roles of rotavirus nonstructural protein 4 (NSP4) that is the rotavirus enterotoxin, a possible vaccine target, and an immune stimulator, and 2) effects of CpG adjuvant that is a toll-like receptor 9 (TLR9) ligand and agonist on the immune response and protection of our S-VP8*/S-VP8* nanoparticle vaccine. The resulted vaccine candidates were examined for their IgG responses in mice. In addition, the resulted mouse sera were assessed for i) blocking titers against interactions of rotavirus VP8* proteins with their glycan ligands, ii) neutralization titers against rotavirus replication in cell culture, and iii) passive protection against rotavirus challenge with diarrhea in suckling mice. Our data showed that the Alum adjuvant appeared to work better with the S-VP8*/S-VP8* nanoparticles than the CpG adjuvant, while an addition of the NSP4 antigen to the S-VP8*/S-VP8* vaccine may not help to further increase the immune response and protection of the resulted vaccine.
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http://dx.doi.org/10.1016/j.vaccine.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822095PMC
January 2021

Au-Pd nanoparticles immobilized on TiO nanosheet as an active and durable catalyst for solvent-free selective oxidation of benzyl alcohol.

J Colloid Interface Sci 2021 Apr 30;588:787-794. Epub 2020 Nov 30.

State Key Laboratory Breeding Base of Coal Science and Technology Co-founded by Shanxi Province and the Ministry of Science and Technology, Taiyuan University of Technology, Taiyuan 030024, Shanxi, PR China. Electronic address:

TiOnanocrystals with controlled facets have been extensively investigated due to their excellent photocatalytic performance in sustainable and green energy field. However, the applications in thermal catalysis without applying UV irradiation are comparably less and the identification of their intrinsic roles, especially the different catalytic behaviors of each crystal facet, remains not fully recognized. In this study, bimetallic AuPd nanoparticles supported on anatase TiO nanosheets exposing {001} facets or TiO nanospindles exposing {101} as a catalyst were prepared by sol-immobilization method and used for solvent-free benzyl alcohol oxidation. The experimental results indicated that the exposed facet of the support has a significant effect on the catalytic performance. AuPd/TiO-001 catalyst exhibited a higher benzyl alcohol conversion than that of the AuPd/TiO-101. Meanwhile, all the prepared AuPd/TiO catalysts were characterized by XRD, ICP-AES, XPS, BET, TEM, and HRTEM. The results revealed that the higher number of oxygen vacancies in TiO-sheets with the exposed {001} facets of higher surface energy could be responsible for the observed enhancement in the catalytic performance of benzyl alcohol oxidation. The present study displays that it is plausible to enhance the catalytic performance for the benzyl alcohol oxidation by tailoring the exposed facet of the TiO as a catalyst support.
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http://dx.doi.org/10.1016/j.jcis.2020.11.112DOI Listing
April 2021

Deep eutectic solvent-based liquid-phase microextraction coupled with reversed-phase high-performance liquid chromatography for determination of α-, β-, γ-, and δ-tocopherol in edible oils.

Anal Bioanal Chem 2021 Jan 18;413(2):577-584. Epub 2020 Nov 18.

State Key Laboratory of Coal Conversion, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan, 030001, Shanxi, China.

For simultaneous analysis of four fat-soluble tocopherols (α-, β-, γ-, and δ-) in edible oils, an efficient and green method using deep eutectic solvent-based liquid-phase microextraction (DES-LPME) coupled with reversed-phase high-performance liquid chromatography (RP-HPLC) was developed. The DESs formed by different quaternary ammonium salts and ethanol were used as the extractants. Tetrabutylammonium chloride (TBAC)-ethanol DES at a molar ratio of 1:2 achieved the best extraction efficiency. Under the optimized conditions, the detection limits were in the range of 2.1-3.0 ng mL. The intra-day and inter-day repeatability were in the ranges of 3.9-5.3% and 4.8-7.1%, respectively, and the recoveries for the real samples varied from 80.7% to 105.4%. The developed method was successfully employed for the determination of all four tocopherol homologues with an RP-HPLC system containing a COSMOSIL π-NAP column in five edible oils collected locally. Graphical abstract.
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http://dx.doi.org/10.1007/s00216-020-03029-1DOI Listing
January 2021

Coagulation parameters are associated with the prognosis of immunoglobulin a nephropathy: a retrospective study.

BMC Nephrol 2020 10 27;21(1):447. Epub 2020 Oct 27.

Department of Nephrology, The Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, 410011, Hunan, China.

Background: Interstitial fibrosis/tubular atrophy (T) score is a known determinant of the progression of immunoglobulin A nephropathy (IgAN). Strong evidence indicates that the components of the coagulation system closely linked with fibrotic events have been highlighted in the kidney. However, whether the coagulation system can affect the renal outcome of IgAN remains unclear. Herein, we investigated the association of coagulation parameters and pathological phenotype of IgAN and their combined effects on the deterioration of renal function.

Methods: This retrospective study included N = 291 patients with biopsy-proven IgAN from May 2009 to April 2013 in the Second Xiangya Hospital. Clinical data, pathological features were collected, and the associations of coagulation parameters at biopsy, T score, and renal outcome were evaluated. T score indicated the degree of tubular atrophy or interstitial fibrosis. The renal outcome was defined as an end-stage renal disease (ESRD) or an irreversible 50% estimated glomerular filtration rate (eGFR) reduction.

Results: Shorter prothrombin time (PT) and the activated partial thromboplastin time (APTT) were significantly associated with T (both p < 0.001). PT (< 11.15 s) or APTT (< 29.65 s) had worse cumulative survival rate (p = 0.008, p = 0.027 respectively) and were significantly but not independently associated with a higher risk of renal outcome (p = 0.012, p = 0.032 respectively). In the combined analyses of PT, APTT, and T lesions, the odd ratios for the outcome were significantly higher in the presence of T with PT (< 11.15 s) or APTT (< 29.65 s).

Conclusion: Shorter PT and APTT are associated with an increased incidence of the T lesion and are additional factors that portend a poorer prognosis in IgAN. Monitoring coagulation function might be important when assessing the risk of progression. Additional studies exploring the molecular mechanism between coagulation and IgAN pathology are needed.
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http://dx.doi.org/10.1186/s12882-020-02111-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590710PMC
October 2020

Association between Serum Calcium and First Incident Acute Myocardial Infarction: A Cross-Sectional Study.

Iran J Public Health 2020 Jul;49(7):1278-1288

Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.

Background: The role of serum calcium in coronary artery disease (CAD) patients with or without first incident acute myocardial infarction has not been studied previously. This study aimed to assess the relationship between serum calcium and first incident acute myocardial infarction.

Methods: This cross-sectional study was conducted from Jan 2014 to Dec 2016. All the participants were from our database, described in detail elsewhere including 1609 cases and 3252 controls. Multiple logistic regression was carried out to explore the effect of serum calcium on first incident acute myocardial infarction. Interaction between serum calcium and risk factors were evaluated.

Results: Patients with first incident acute myocardial infarction have significantly lower serum calcium concentrations than those without acute myocardial infarction (2.18 (0.21) vs 2.24 (0.19) mmol/L, <0.0001). After adjusting for sex and age, logistic regression showed that serum calcium was significantly associated with first incident acute myocardial infarction (odds ratio (OR): 1.50, 95% confidence interval (CI): 1.41-1.60). Further adjusted for potential confounders, serum calcium was associated with first incident acute myocardial infarction (OR: 1.32, 95% CI: 1.22-1.42). Moreover, the association still existed when patients were divided into subgroups according to gender and age. A significant interaction was found between serum calcium and diabetes mellitus (DM), lipoprotein (a) (Lp (a)), and serum albumin.

Conclusion: Serum calcium was associated with first incident acute myocardial infarction among CAD patients in both sexes and in age categories. This study provides further evidence showing the value of serum calcium levels in clinical practice.
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http://dx.doi.org/10.18502/ijph.v49i7.3581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548486PMC
July 2020

Long noncoding RNA DLEU2 predicts a poor prognosis and enhances malignant properties in laryngeal squamous cell carcinoma through the miR-30c-5p/PIK3CD/Akt axis.

Cell Death Dis 2020 06 18;11(6):472. Epub 2020 Jun 18.

Department of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwuweiqi Road, 250021, Jinan, Shandong Province, China.

Long noncoding RNAs (lncRNAs) have been identified as potential prognostic tools and therapeutic biomarkers for a variety of human cancers. However, the functional roles and underlying mechanisms of key lncRNAs affecting laryngeal squamous cell carcinomas (LSCCs) are largely unknown. Here, we adopted a novel subpathway strategy based on the lncRNA-mRNA profiles from the Cancer Genome Atlas (TCGA) database and identified the lncRNA deleted in lymphocytic leukemia 2 (DLEU2) as an oncogene in the pathogenesis of LSCCs. We found that DLEU2 was significantly upregulated and predicted poor clinical outcomes in LSCC patients. In addition, ectopic overexpression of DLEU2 promoted the proliferation and migration of LSCC cells both in vivo and in vitro. Mechanistically, DLEU2 served as a competing endogenous RNA to regulate PIK3CD expression by sponging miR-30c-5p and subsequently activated the Akt signaling pathway. As a target gene of DLEU2, PIK3CD was also upregulated and could predict a poor prognosis in LSCC patients. In conclusion, we found that the novel LSCC-related gene DLEU2 enhances the malignant properties of LSCCs via the miR-30c-5p/PIK3CD/Akt axis. DLEU2 and its targeted miR-30c-5p/PIK3CD/Akt axis may represent valuable prognostic biomarkers and therapeutic targets for LSCCs.
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http://dx.doi.org/10.1038/s41419-020-2581-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303144PMC
June 2020

Histo-blood group antigens as divergent factors of groups A and C rotaviruses circulating in humans and different animal species.

Emerg Microbes Infect 2020 Dec;9(1):1609-1617

Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Histo-blood group antigens (HBGAs) have been found to be important host susceptibility factors or receptors for human rotavirus (RVs) with genotype-specific host ranges, impacting the disease patterns, epidemiology, and strategy development against RV diseases in humans. However, how the glycan factors contribute to RV diversity and host ranges to different animal species remains unclear. In this study using recombinant VP8* proteins as probes to perform glycan array analyses of RVs, we observed a wide range of glycan-binding profiles, including those binding to sialic acid-containing glycans, among group A (RVA) and group C (RVC) RVs that mainly infect different animal species. A tri-saccharide glycan Galα1-3Galβ1-4Glc containing a terminal α-Gal was recognised by multiple RVA/RVC genotypes, providing valuable information on RV evolution under selection of the step-wisely synthesised HBGAs in many animals before they were introduced to humans to be human pathogens. Saliva binding studies of VP8* also revealed strain-specific host ranges or species barriers between humans and these animal RV genotypes, further improved our understanding on RV host ranges, disease burdens, epidemiology, and vaccine strategy against RVs.
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http://dx.doi.org/10.1080/22221751.2020.1782270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473324PMC
December 2020

MYB41, MYB107, and MYC2 promote ABA-mediated primary fatty alcohol accumulation via activation of in wound suberization in kiwifruit.

Hortic Res 2020 1;7(1):86. Epub 2020 Jun 1.

Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, Zhejiang University, 310058 Hangzhou, China.

Wound damage triggers the accumulation of abscisic acid (ABA), which induces the expression of a large number of genes involved in wound suberization in plants. Fatty acyl-CoA reductase (FAR) catalyzes the generation of primary fatty alcohols by the reduction of fatty acids in suberin biosynthesis. However, the regulatory effects of transcription factors (TFs) on in response to ABA are unexplored. In this study, kiwifruit displayed a biological function analogous to that of FAR in transiently overexpressed tobacco () leaves. The positive role of TFs, including AchnMYB41, AchnMYB107, and AchnMYC2, in the regulation of was identified. The three TFs could individually bind to the promoter to activate gene transcription in yeast one-hybrid and dual-luciferase assays. Transient overexpression of TFs in tobacco leaves resulted in the upregulation of aliphatic synthesis genes (including ) and the increase in aliphatics, including primary alcohols, α,ω-diacids, ω-hydroxyacids, and fatty acids. Moreover, exogenous ABA treatment elevated TF-mediated expression and the accumulation of primary alcohols. Conversely, fluridone, an inhibitor of ABA biosynthesis, suppressed the expression of and TF genes and reduced the formation of primary alcohols. The results indicate that AchnMYB41, AchnMYB107, and AchnMYC2 activate transcription to promote ABA-mediated primary alcohol formation in wound suberization in kiwifruit.
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http://dx.doi.org/10.1038/s41438-020-0309-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261769PMC
June 2020
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