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Analysis of the DNA-binding properties of Alx1, an evolutionarily conserved regulator of skeletogenesis in echinoderms.

J Biol Chem 2021 Jun 19:100901. Epub 2021 Jun 19.

Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania USA. Electronic address:

Alx1, a homeodomain (HD)-containing transcription factor, is a highly conserved regulator of skeletogenesis in echinoderms. In sea urchins, Alx1 plays a central role in the differentiation of embryonic primary mesenchyme cells (PMCs) and positively regulates the transcription of most biomineralization genes expressed by these cells. The alx1 gene arose via duplication and acquired a skeletogenic function distinct from its paralog (alx4) through the exonization of a 41-amino acid motif (the D2 domain). Read More

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Histone Deacetylase Inhibitor SAHA Induces Expression of Fatty Acid-Binding Protein 4 and Inhibits Replication of Human Cytomegalovirus.

Virol Sin 2021 Jun 22. Epub 2021 Jun 22.

CAS Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, 200031, China.

Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase inhibitor that shows marked efficacy against many types of cancers and is approved to treat severe metastatic cutaneous T-cell lymphomas. In addition to its anticancer activity, SAHA has significant effects on the growth of many viruses. The effect of SAHA on replication of human cytomegalovirus (HCMV) has not, however, been investigated. Read More

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MiR-99b-5p suppressed proliferation of human osteoblasts by targeting FGFR3 in osteoporosis.

Hum Cell 2021 Jun 22. Epub 2021 Jun 22.

Department of Emergency Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410001, Hunan, China.

Osteoporosis is a common skeletal disease characterized by reduced bone mass partially caused by an imbalance between bone resorption and formation. Considering the potential role of microRNAs (miRNAs) in osteoporosis, we attempted to identify deregulated miRNA that participates in the pathogenesis of osteoporosis. We analyzed online datasets for differentially expressed miRNAs and predicted deregulated miRNA target genes, applied these genes for signaling pathway enrichment annotation, and selected the possible miR-99b-5p/FGFR3 axis. Read More

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Rictor is a novel regulator of TRAF6/TRAF3 in osteoclasts.

J Bone Miner Res 2021 Jun 22. Epub 2021 Jun 22.

Department of Cell Biology, School of Basic Medical Science, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Southern Medical University, Guangzhou, 510515, China.

Tumor necrosis factor receptor-associated factors (TRAFs) are crucial for receptor activator of nuclear factor-κB (RANK) activation in osteoclasts. However, the upstream mechanisms of TRAF members in the osteoclastic lineage remain largely unknown. Here, we demonstrated that Rictor, a key component of mechanistic target of rapamycin complex 2 (mTORC2), was crucial for TRAF6/TRAF3 expression in osteoclasts. Read More

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Cornuside I promoted osteogenic differentiation of bone mesenchymal stem cells through PI3K/Akt signaling pathway.

J Orthop Surg Res 2021 Jun 21;16(1):397. Epub 2021 Jun 21.

Department of Orthopedics, Shanghai Fifth People's Hospital Affiliated to Fudan University, No. 801, Heqing Road, Minhang District, Shanghai, 200240, China.

Background: Osteoporosis is a common disease closely associated with aging. In this study, we aimed to investigate the role of Cornuside I in promoting osteogenic differentiation of bone mesenchymal stem cells (BMSCs) and the potential mechanism.

Methods: BMSCs were isolated and treated with different concentrations of Cornuside I (0, 10, 30, 60 μM). Read More

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Allosteric Activation of SARS-CoV-2 RNA-Dependent RNA Polymerase by Remdesivir Triphosphate and Other Phosphorylated Nucleotides.

mBio 2021 Jun 22:e0142321. Epub 2021 Jun 22.

Department of Microbiology, The Ohio State Universitygrid.261331.4, Columbus, Ohio, USA.

The catalytic subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) Nsp12 has a unique nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain that transfers nucleoside monophosphates to the Nsp9 protein and the nascent RNA. The NiRAN and RdRp modules form a dynamic interface distant from their catalytic sites, and both activities are essential for viral replication. We report that codon-optimized (for the pause-free translation in bacterial cells) Nsp12 exists in an inactive state in which NiRAN-RdRp interactions are broken, whereas translation by slow ribosomes and incubation with accessory Nsp7/8 subunits or nucleoside triphosphates (NTPs) partially rescue RdRp activity. Read More

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A karyopherin constrains nuclear activity of the NLR protein SNC1 and is essential to prevent autoimmunity in Arabidopsis.

Mol Plant 2021 Jun 18. Epub 2021 Jun 18.

Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720; Innovative Genomics Institute, University of California, Berkeley, CA 94720. Electronic address:

The nucleotide-binding and leucine-rich repeat (NLR) proteins comprise a major class of intracellular immune receptors that are capable of detecting pathogen-derived molecules and activating immunity and cell death in plants. The activity of some NLRs, particularly TIR type, is highly correlated with their nucleocytoplasmic distribution. However, whether and how the nucleocytoplasmic homeostasis of NLRs is coordinated through a bi-directional nuclear shuttling mechanism remains unclear. Read More

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Coronaviruses, cholesterol and statins: Involvement and application for Covid-19.

Biochimie 2021 Jun 18. Epub 2021 Jun 18.

Department of Endocrinology and Prevention of Cardiovascular Diseases, Institute of Cardiometabolism and Nutrition (ICAN), La Pitié-Salpêtrière Hospital, AP-HP, Paris, France. Electronic address:

The infectious power of coronaviruses is dependent on cholesterol present in the membranes of their target cells. Indeed, the virus enters the infected cell either by fusion or by endocytosis, in both cases involving cholesterol-enriched membrane microdomains. These membrane domains can be disorganized in-vitro by various cholesterol-altering agents, including statins that inhibit cell cholesterol biosynthesis. Read More

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Ca/calmodulin kinase II-dependent regulation of β-spectrin modulates cardiac fibroblast gene expression, proliferation, and contractility.

J Biol Chem 2021 Jun 18:100893. Epub 2021 Jun 18.

The Frick Center for Heart Failure and Arrhythmia, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH, USA; Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA. Electronic address:

Fibrosis is a pronounced feature of heart disease and the result of dysregulated activation of resident cardiac fibroblasts (CFs). Recent work identified stress-induced degradation of the cytoskeletal protein β-spectrin as an important step in CF activation and cardiac fibrosis. Further, loss of β-spectrin was found to depend on Ca/calmodulin-dependent kinase II (CaMKII). Read More

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Redistribution of metabolic fluxes in by variation of media nitrogen concentration.

Metab Eng Commun 2015 Dec 3;2:124-131. Epub 2015 Oct 3.

Johns Hopkins University, Department of Chemical and Biomolecular Engineering, 3400 N. Charles St., Maryland Hall 221, Baltimore, MD 21218, USA.

In this study, the Elementary Metabolite Unit (EMU) algorithm was employed to calculate intracellular fluxes for using previously generated growth and mass spec data. While the flux through glycolysis remained relatively constant, the pentose phosphate pathway (PPP) flux increased from 3% to 20% of the glucose uptake during nitrogen-limited growth. The TCA cycle flux decreased from 94% to 38% during nitrogen-limited growth while the flux of acetyl-CoA into lipids increased from 58% to 109% of the glucose uptake, increasing total lipid accumulation. Read More

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December 2015

Celecoxib ameliorates diabetic neuropathy by decreasing apoptosis and oxidative stress in dorsal root ganglion neurons via the miR-155/COX-2 axis.

Exp Ther Med 2021 Aug 2;22(2):825. Epub 2021 Jun 2.

Department of Neurology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.

Celecoxib (CXB) is the only clinical cyclooxygenase-2 (COX-2) inhibitor. Oral administration of CXB in experimental diabetic mice effectively relieved the symptoms of diabetic neuropathy (DN); however, the molecular mechanism remains unclear. The present study aimed to investigate the potential molecular mechanisms of CXB in the treatment of DN. Read More

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Analysis of Two SusE-Like Enzymes From Reveals a Potential Degradative Capacity for This Protein Family.

Front Microbiol 2021 4;12:645765. Epub 2021 Jun 4.

Department of Chemistry and Biochemistry, Wilfrid Laurier University, Waterloo, ON, Canada.

is a major constituent of the human gut microbiome and recognized as a prolific degrader of diverse and complex carbohydrates. This capacity is due to the large number of glycan-depolymerization and acquisition systems that are encoded by gene clusters known as polysaccharide utilization loci (PUL), with the starch utilization system (Sus) serving as the established model. Sharing features with the Sus are Sus-like systems, that require the presence of a specific membrane transporter and surface lipoprotein to be classified as Sus-like. Read More

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Mechanical role of intraluminal thrombus in aneurysm growth: A computational study.

Biomech Model Mechanobiol 2021 Jun 20. Epub 2021 Jun 20.

Faculty of Mechanical Engineering and Naval Architecture, University of Zagreb, Ivana Lučića 5, 10000, Zagreb, Croatia.

Models that seek to improve our current understanding of biochemical processes and predict disease progression have been increasingly in use over the last decades. Recently, we proposed a finite element implementation of arterial wall growth and remodeling with application to abdominal aortic aneurysms (AAAs). The study focused on changes within the aortic wall and did not include the complex role of intraluminal thrombus (ILT) during the AAA evolution. Read More

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Pien-Tze-Huang, a Chinese patent formula, attenuates NLRP3 inflammasome-related neuroinflammation by enhancing autophagy via the AMPK/mTOR/ULK1 signaling pathway.

Biomed Pharmacother 2021 Jun 17;141:111814. Epub 2021 Jun 17.

College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China. Electronic address:

NLRP3 inflammasome is a key mediator in ischemic stroke-induced neuroinflammation and subsequent brain injury. Our previous study demonstrated the potent activity of Pien-Tze-Huang (PTH), a well-known Chinese patent formula, in reducing mitochondria-mediated neuronal apoptosis in cerebral ischemia/reperfusion impaired rats. This study aims to elucidate the mechanistic action of PTH related to neuroinflammation in LPS-induced BV2 microglial cells and cerebral ischemia/reperfusion impaired rats. Read More

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Anti-inflammatory role and mechanism of microRNA-92b-3p in the progression of hypoxic pulmonary hypertension.

Life Sci 2021 Jun 16:119725. Epub 2021 Jun 16.

Department of Respiratory, Linyi People's Hospital, Linyi 276000, PR China. Electronic address:

Aims: Pulmonary hypertension (PH) is a serious lung disease that caused by cellular proliferation, vascular wall inflammation and fibrosis. MicroRNAs (miRNAs) have been known to participate in the pathogenesis of PH and could be used to treat PH. In this study, we investigated the molecular mechanism of a miRNA candidate and its roles in the process of hypoxic PH. Read More

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Roles of the ubiquitin ligase CUL4B and ADP-ribosyltransferase TiPARP in TCDD-induced nuclear export and proteasomal degradation of the transcription factor AHR.

J Biol Chem 2021 Jun 16:100886. Epub 2021 Jun 16.

Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA.

The aryl hydrocarbon receptor (AHR) is a transcription factor activated by exogenous halogenated polycyclic aromatic hydrocarbon compounds, including the environmental toxin TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and naturally occurring dietary and endogenous compounds. Activated AHR enhances transcription of specific genes including phase I and phase II metabolism enzymes and other targets genes like the TCDD-inducible poly ADP-ribose Polymerase (TiPARP). The regulation of AHR activation is a dynamic process: immediately following transcriptional activation of the AHR by TCDD, AHR is exported from the nucleus to the cytoplasm where it is subjected to proteasomal degradation. Read More

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Tanshinol alleviates ulcerative colitis by promoting the expression of VLDLR.

Drug Dev Res 2021 Jun 18. Epub 2021 Jun 18.

Department of Anorectal Surgery, Wuxi Traditional Chinese Medicine Hospital, Wuxi, PR China.

Tanshinol (TAN) is a widely used Chinese medicine ingredient with anti-inflammatory activity. The therapeutic effect of TAN in ulcerative colitis (UC) deserves further investigation. DSS induced UC model for mice, and TAN of different concentrations was used for in vivo therapy. Read More

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Cortisol activity partially accounts for a relationship between community socioeconomic position and atherosclerosis.

Psychoneuroendocrinology 2021 Jun 2;131:105292. Epub 2021 Jun 2.

Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address:

Compared to others, individuals living in communities of socioeconomic disadvantage experience more atherosclerotic cardiovascular disease (CVD) and a greater extent of preclinical atherosclerosis. Although the mechanisms underlying these associations remain unclear, it is widely hypothesized that alterations in normative cortisol release from the Hypothalamic Pituitary Adrenal (HPA) axis may play a role in linking lower community socioeconomic position (C-SEP) to CVD risk. The current study examined this hypothesis in relation to a marker of preclinical atherosclerosis among 488 healthy midlife adults (30-54 years, Mean age= 43, 52% Female, 81% White). Read More

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Yoga in women with abdominal obesity - Do lifestyle factors mediate the effect? Secondary analysis of a RCT.

Complement Ther Med 2021 Jun 15:102741. Epub 2021 Jun 15.

Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany; National Centre for Naturopathic Medicine, Southern Cross University, Lismore, Australia; Australian Research Center in Complementary and Integrative Medicine, Faculty of Health, University of Technology-Sydney, Sydney, Australia.

Introduction: The reduction of obesity is an important challenge for health policy. Although dietary interventions are widely available, patient adherence is usually low. A promising alternative is yoga. Read More

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Editing Light Emission with Stable Crystalline Covalent Organic Frameworks via Wall Surface Perturbation.

Angew Chem Int Ed Engl 2021 Jun 18. Epub 2021 Jun 18.

Japan Advanced Institute of Science and Technology: Hokuriku Sentan Kagaku Gijutsu Daigakuin Daigaku, Materials Chemistry, JAPAN.

The ordered π skeletons of covalent organic frameworks make them viable light-emitting materials but their limited tunability has precluded further implementation. Here we report the synthesis of hydrazone-linked frameworks which are stable in water, acid, and base, and demonstrate their utility as a platform for light emission. The polygonal backbone is designed to be luminescent and partially π conjugated while the pore wall is docked with single atom or unit to induce resonance, hyperconjugation, and tautomerization effects. Read More

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Therapeutic candidates for keloid scars identified by qualitative review of scratch assay research for wound healing.

PLoS One 2021 18;16(6):e0253669. Epub 2021 Jun 18.

Epithelial Therapeutics Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, North Bethesda, Maryland, United States of America.

The scratch assay is an in vitro technique used to analyze cell migration, proliferation, and cell-to-cell interaction. In the assay, cells are grown to confluence and then 'scratched' with a sterile instrument. For the cells in the leading edge, the resulting polarity induces migration and proliferation in attempt to 'heal' the modeled wound. Read More

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Stability of human salivary extracellular vesicles containing dipeptidyl peptidase IV under simulated gastrointestinal tract conditions.

Biochem Biophys Rep 2021 Sep 3;27:101034. Epub 2021 Jun 3.

Faculty of Pharmaceutical Sciences, Teikyo Heisei University, 4-21-2 Nakano, Nakano-ku, Tokyo, 164-8530, Japan.

Background: Extracellular vesicles (EVs) have been isolated from various sources, including primary and cultured cell lines and body fluids. Previous studies, including those conducted in our laboratory, have reported the stability of EVs under various storage conditions.

Methods: EVs from human whole saliva were separated via size-exclusion chromatography. Read More

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September 2021

Galangin attenuates oxidative stress-mediated apoptosis in high glucose-induced renal tubular epithelial cells through modulating renin-angiotensin system and PI3K/AKT/mTOR pathway.

Toxicol Res (Camb) 2021 May 17;10(3):551-560. Epub 2021 May 17.

Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China.

This study was to evaluate the regulatory network among Galangin (Gal), oxidative stress, and renin-angiotensin system (RAS) in diabetic nephropathy (DN) . A cell model of DN was set up by exposing HK-2 cells to high glucose (HG, 30 mM) for 48 h and Gal was applied at 10 μM when needed. mRNA expression was analyzed by qPCR and protein level was detected by western blot. Read More

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Management of Asthma Exacerbations in Southeast Asian Tertiary Care.

J Asthma Allergy 2021 10;14:629-640. Epub 2021 Jun 10.

The Lung Centre, Pantai Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.

Background: There have been limited reports looking into the care of patients with asthma exacerbations admitted to tertiary hospitals in Southeast Asia. This study aims to determine the extent in which the 2019 Global Initiative for Asthma (GINA) guidelines were being met.

Methods: A retrospective study of patients with asthma exacerbations admitted to the University of Malaya Medical Centre (UMMC) and Pantai Hospital Kuala Lumpur (PHKL), Malaysia from 1 July 2019 to 31 December 2019. Read More

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[γδ1 T cells derived from breast cancer tissue induce immunosenescence of naive CD4 T cells by producing IL-17D].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Jul;37(7):623-632

Key Laboratory of Birth Defects Prevention and Treatment, Linyi Maternal and Child Health Care Hospital, Linyi 276000; Department of Experimental Center of Molecular Biology, Shandong Medical College, Linyi 276000, China. *Corresponding author, E-mail:

Objective To investigate the mechanism underlying the immunosuppressive effect and its reverse of γδ1 T cells derived from breast cancer tissues by inducing immunosenescence. Methods After γδ1 T cells isolated from breast cancer tissues were co-cultured with peripheral blood-derived naive CD4 T cells, the proliferation of treated CD4 T cells was detected by CCK-8 assay, and the activity of senescence-associated β-galactosidase (SA-β-Gal) in treated CD4 T cells was detected by SA-β-Gal staining. After the induced senescent CD4 T cells were co-cultured with the naive CD4 T cells, the proliferation, apoptosis, activity of the treated CD4 T cells were examined by CCK-8 assay, flow cytometry and SA-β-Gal staining, respectively; the expression of cell cycle-associated proteins P53, P21 and P16 in the treated CD4 T cells was detected by Western blot analysis in order to verify the immunosuppressive effect of the senescent CD4 T cells. Read More

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Behavioral Factors Mediating the Impact of Educational Attainment on Incident Heart Failure - A Mediation Analysis.

Circ J 2021 Jun 15. Epub 2021 Jun 15.

Cardiology Department, First Affiliated Hospital of Sun Yat-Sen University.

Background: To examine the association of low educational attainment with incident heart failure (HF) and explore potential behavioral mediators of the causal pathway.Methods and Results:A total of 12,109 participants in the Atherosclerosis Risk in Communities Study (ARIC) were included. Educational attainment was measured at baseline, and the risk of HF across educational attainment groups was assessed by Cox proportional hazards models. Read More

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Mechanisms underlying divergent responses of genetically distinct macrophages to IL-4.

Sci Adv 2021 Jun 16;7(25). Epub 2021 Jun 16.

Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.

Mechanisms by which noncoding genetic variation influences gene expression remain only partially understood but are considered to be major determinants of phenotypic diversity and disease risk. Here, we evaluated effects of >50 million single-nucleotide polymorphisms and short insertions/deletions provided by five inbred strains of mice on the responses of macrophages to interleukin-4 (IL-4), a cytokine that plays pleiotropic roles in immunity and tissue homeostasis. Of >600 genes induced >2-fold by IL-4 across the five strains, only 26 genes reached this threshold in all strains. Read More

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Phytotoxicity of the chiral herbicide dichlorprop: Cross-talk between nitric oxide, reactive oxygen species and phytohormones.

Sci Total Environ 2021 Sep 20;788:147866. Epub 2021 May 20.

MOE Key Laboratory of Environmental Remediation & Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

Nitric oxide (NO), reactive oxygen species (ROS), and phytohormones in plants often initiate responses to sources of abiotic stress. However, we have a poor understanding of the cross-talk between NO, ROS, and phytohormones during exogenous chiral auxin-induced phytotoxicity. In this study, the toxicity of the chiral synthetic auxin herbicide dichlorprop (DCPP) to Arabidopsis thaliana, as well as the mutual regulation of NO, hydrogen peroxide (HO), superoxide anion (O), and phytohormones at the enantiomeric level was investigated. Read More

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September 2021

Hierarchical CoFe LDH/MOF nanorods array with strong coupling effect grown on carbon cloth enables efficient oxidation of water and urea.

Nanotechnology 2021 Jun 15. Epub 2021 Jun 15.

School of Environmental and Chemical Engineering, Shanghai University, Shangda Road 99, Shanghai, 200444, CHINA.

The construction of bifunctional non-noble electrocatalyst for oxygen evolution reaction (OER) and urea oxidation reaction (UOR) is urgent for overall water and urea splitting. Herein, a facile one-step chemical etching- reconstruction strategy is presented for fabricating one-dimensional hierarchical nanorods array composed of CoFe layered double hydroxide (LDH)/MOF supported on carbon cloth as OER and UOR catalysts. By precisely controlling the etching rate, the ligands from Co-MOFs are partially removed, and corresponding metal centers coordinates with hydroxyl ions to generate ultrathin amorphous CoFe LDH nanosheets. Read More

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Ultrathin 2D Fe-Nanosheets Stabilized by 2D Mesoporous Silica: Synthesis and Application in Ammonia Synthesis.

ACS Appl Mater Interfaces 2021 Jun 15. Epub 2021 Jun 15.

Department of Heterogeneous Reactions, Max Planck Institute for Chemical Energy Conversion, 45470 Mülheim an der Ruhr, Germany.

Developing high-performance Fe-based ammonia catalysts through simple and cost-efficient methods has received an increased level of attention. Herein, we report for the first time, the synthesis of two-dimensional (2D) FeOOH nanoflakes encapsulated by mesoporous SiO (mSiO) via a simple solution-based method for ammonia synthesis. Due to the sticking of the mSiO coating layers and the limited spaces in between, the Fe after reduction retains the 2D morphology, showing high resistance against the sintering in the harsh Haber-Bosch process. Read More

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