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Molecular basis for diaryldiamine selectivity and competition with tRNA in a type-2 methionyl-tRNA synthetase from a Gram-negative bacterium.

J Biol Chem 2021 Apr 12:100658. Epub 2021 Apr 12.

Brazilian Biosciences National Laboratory (LNBio), Brazilian Centre for Research in Energy and Materials (CNPEM), CEP 13083-100, Campinas, SP, Brazil. Electronic address:

Gram-negative bacteria are responsible for a variety of human, animal and plant diseases. The spread of multidrug-resistant Gram-negative bacteria poses a challenge to disease control and highlights the need for novel antimicrobials. Due to their critical role in protein synthesis, aminoacyl-tRNA synthetases (AaRS), including the methionyl-tRNA synthetases MetRS1 and MetRS2, are attractive drug targets. Read More

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The dystonia gene THAP1 controls DNA double-strand break repair choice.

Mol Cell 2021 Apr 6. Epub 2021 Apr 6.

Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA. Electronic address:

The Shieldin complex shields double-strand DNA breaks (DSBs) from nucleolytic resection. Curiously, the penultimate Shieldin component, SHLD1, is one of the least abundant mammalian proteins. Here, we report that the transcription factors THAP1, YY1, and HCF1 bind directly to the SHLD1 promoter, where they cooperatively maintain the low basal expression of SHLD1, thereby ensuring a proper balance between end protection and resection during DSB repair. Read More

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Imeglimin preserves islet β-cell mass in Type 2 diabetic ZDF rats.

Endocrinol Diabetes Metab 2021 Apr 7;4(2):e00193. Epub 2020 Nov 7.

Poxel SA Lyon France.

Objectives: Type 2 diabetes (T2D) is driven by progressive dysfunction and loss of pancreatic β-cell mass. Imeglimin is a first-in-class novel drug candidate that improves glycaemia and glucose-stimulated insulin secretion in preclinical models and patients. Given evidence that imeglimin can attenuate β-cell dysfunction and protect β cells , we postulated that imeglimin could also exert longer term effects to prevent pancreatic β-cell death and preserve functional β-cell mass . Read More

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High Expression of PIGC Predicts Unfavorable Survival in Hepatocellular Carcinoma.

J Hepatocell Carcinoma 2021 6;8:211-222. Epub 2021 Apr 6.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.

Purpose: The effects of phosphatidylinositol glycan anchor biosynthesis, class C (PIGC), in the progression of liver cancer are unknown. In this study, we attempted to clarify the clinical significance and mechanism of PIGC in hepatocellular carcinoma (HCC).

Patients And Methods: To explore the expression profiles, DNA methylation, mutation status, clinical relevance, and prognostic value of PIGC in patients with HCC, a series of bioinformatic databases and websites were searched. Read More

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Sodium-glucose cotransporter-2 inhibitors and risk for genitourinary infections in older adults with type 2 diabetes.

Ther Adv Drug Saf 2021 29;12:2042098621997703. Epub 2021 Mar 29.

University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, 12850 E. Montview Blvd., Campus Box C238, Room V20-1127A, Aurora, CO 80045, USA.

Background And Aims: Although landmark clinical trials have demonstrated an increased risk for genitourinary infection (GUI) after initiation of sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy that led to an FDA label warning, real world findings have been inconsistent and evidence specifically in older adults is lacking. The objective of the study was to examine the incidence of GUI in patients aged 65 years or older initiated on SGLT2i compared with glucagon-like peptide-1 receptor agonist (GLP1-RA) therapy at a large academic health system.

Methods: A retrospective population-based cohort study was conducted using electronic health records of patients aged 65 years and older with a diagnosis of type 2 diabetes mellitus. Read More

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Making Insulin and Staying Out of Autoimmune Trouble: The Beta-Cell Conundrum.

Front Immunol 2021 29;12:639682. Epub 2021 Mar 29.

Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France.

Autoimmune type 1 diabetes (T1D) results from the intricate crosstalk of various immune cell types. CD8+ T cells dominate the pro-inflammatory milieu of islet infiltration (insulitis), and are considered as key effectors of beta-cell destruction, through the recognition of MHC Class I-peptide complexes. The pathways generating MHC Class I-restricted antigens in beta cells are poorly documented. Read More

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Nucleolin promotes IRES-driven translation of foot-and-mouth disease virus by supporting the assembly of translation initiation complexes.

J Virol 2021 Apr 14. Epub 2021 Apr 14.

State Key Laboratory of Veterinary Etiological Biology, OIE/China National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, Gansu, P. R. China

Nucleolin (NCL), a stress-responsive RNA-binding protein, has been implicated in the translation of internal ribosome entry site (IRES)-containing mRNAs, which encode proteins involved in cell proliferation, carcinogenesis, and viral infection (Type I IRESs). However, the details of the mechanisms by which NCL participates in IRES-driven translation have not hitherto been described. Here, we identified NCL as a protein that interacts with the IRES of foot-and-mouth disease virus (FMDV), which is a Type II IRES. Read More

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Slovak Tokaj wines classification with respect to geographical origin by means of one class approaches.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Apr 1;257:119770. Epub 2021 Apr 1.

Institute of Analytical Chemistry, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, 812 37 Bratislava, Slovakia. Electronic address:

Tokaj wines could be produced only in so called Tokaj/Tokay wine region that falls within two countries Slovakia and Hungary. Thus, wines bearing Tokaj appellation must be produced only in Hungary and Slovakia by traditional process. Unfortunately, some counterfeit wines from neighbour region in Ukraine could be found in market. Read More

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Tetracoordinate Boron Intermediates Enable Unconventional Transformations.

Acc Chem Res 2021 Apr 14. Epub 2021 Apr 14.

Key Laboratory of Molecule Synthesis and Function Discovery, Fujian Province University, College of Chemistry at Fuzhou University, Fuzhou, Fujian 350108, China.

ConspectusOrganoboron compounds are a class of multifunctional reagents for the construction of carbon-carbon and carbon-heteroatom bonds in modern synthetic chemistry. The transformations of organoboron compounds are usually carried out through tetracoordinate boron intermediates and mainly include additions to unsaturated bonds, rearrangement reactions, transmetalation reactions, and so on. Although great progress has been achieved in improving tetracoordinate boron intermediates, there are still shortcomings, such as sparse activation modes, a paucity of reaction strategies and difficulties in stereoselective control. Read More

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Multivalent Tryptophan- and Tyrosine-Containing [60]Fullerene Hexa-Adducts as Dual HIV and Enterovirus A71 Entry Inhibitors.

Chemistry 2021 Apr 14. Epub 2021 Apr 14.

Universidad Complutense de Madrid, Organic Chemistry, SPAIN.

Unprecedented 3D hexa-adducts of [60]fullerene peripherally decorated with twelve tryptophan (Trp) or tyrosine (Tyr) residues have been synthesized. Studies on the antiviral activity of these novel compounds against HIV and EV71 reveal that they are much more potent against HIV and equally active against EV71 than the previously described dendrimer prototypes AL-385 and AL-463 , which possess the same number of Trp/Tyr residues on the periphery but attached to a smaller and more flexible pentaerythritol core. These results demonstrate the relevance of the globular 3D presentation of the peripheral groups (Trp/Tyr) as well as the length of the spacer connecting them to the central core to interact with the viral envelopes, particularly in the case of HIV, and support the hypothesis that [60]fullerene can be an alternative and attractive biocompatible carbon-based scaffold for this type of highly symmetrical dendrimers. Read More

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Glucose-Lowering Medication Use in CKD: Analysis of US Medicare Beneficiaries Between 2007 and 2016.

Kidney Med 2021 Mar-Apr;3(2):173-182.e1. Epub 2020 Dec 30.

Department of Pharmaceutical Care & Health Systems, University of Minnesota, College of Pharmacy, Minneapolis, MN.

Background: Information regarding the use of glucose-lowering medications in patients with chronic kidney disease (CKD) is limited.

Study Design: Retrospective cohort study.

Setting & Participants: Medicare 5% random sample of patients with CKD with type 2 diabetes, 2007 to 2016. Read More

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December 2020

Euglycemic Diabetic Ketoacidosis Caused by SGLT2 Inhibitors and a Ketogenic Diet: A Case Series and Review of Literature.

AACE Clin Case Rep 2021 Jan-Feb;7(1):17-19. Epub 2020 Dec 28.

Stony Brook Medicine Department of Endocrinology, Stony Brook University Hospital, Stony Brook, New York.

Objective: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a relatively novel class of oral medications for the treatment of type 2 diabetes mellitus (T2DM). Their use has increased recently due to their beneficial renal and cardiovascular outcomes, but they come with the rare risk of diabetic ketoacidosis (DKA) at normal or slightly elevated glucose values, termed euglycemic DKA (euDKA). Recently, carbohydrate-deprived, ketogenic diets have gained popularity due to benefits of weight loss and improved control of T2DM. Read More

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December 2020

An algorithm for the robust estimation of the COVID-19 pandemic's population by considering undetected individuals.

Appl Math Comput 2021 Apr 8:126273. Epub 2021 Apr 8.

Departamento de Control Automático, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional. Av Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Gustavo A. Madero, Mexico City 07360, Mexico.

Due to the current COVID-19 pandemic, much effort has been put on studying the spread of infectious diseases to propose more adequate health politics. The most effective surveillance system consists of doing massive tests. Nonetheless, many countries cannot afford this class of health campaigns due to limited resources. Read More

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Exploring the Coordination Chemistry of N with Technetium PNP Pincer-Type Complexes.

Inorg Chem 2021 Apr 13. Epub 2021 Apr 13.

Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.

Dinitrogen (N) complexes of technetium (Tc) are rare, and only two examples have been reported. To complement this important class of complexes also for Tc, two different pincer-type complexes of Tc were studied to assess their abilities for coordinating dinitrogen. The reactions of the Tc complex [TcCl(PPh)(NCCH)] with the pincer ligands PNP and PNP respectively gave [Tc(PNP)Cl] and [Tc(PNP)Cl], the first structurally characterized Tc complexes with -coordinated pincer ligands. Read More

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OUTCOMES OF CHIMNEY/SNORKEL ENDOVASCULAR REPAIR FOR SYMPTOMATIC AND RUPTURED ABDOMINAL AORTIC ANEURYSMS.

J Vasc Surg 2021 Apr 10. Epub 2021 Apr 10.

Department of Surgery, Lenox Hill Hospital, Northwell Health, New York, NY.

Objectives: Symptomatic and ruptured abdominal aortic aneurysms (AAA) are increasingly managed with endovascular aneurysm repair (EVAR). We aimed to identify the outcomes of symptomatic and ruptured AAAs that underwent EVAR with chimney or snorkel techniques (ChEVAR).

Methods: A retrospective cohort study was performed using the Vascular Quality Initiative registry from March 2013 to July 2019. Read More

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Production of petaloid phenotype in the reproductive organs of compound flowerheads by the co-suppression of class-C genes in hexaploid Chrysanthemum morifolium.

Planta 2021 Apr 13;253(5):100. Epub 2021 Apr 13.

Institute of Vegetable and Floriculture Science, National Agriculture and Food Research Organization (NARO), Fujimoto 2-1, Tsukuba, Ibaraki, 305-0852, Japan.

Main Conclusion: Functional suppression of two types of class-C genes caused transformation of pistils and stamens into petaloid organs that exhibit novel phenotypes, which gives a distinct gorgeous impression in the florets of chrysanthemum. The multiple-petal trait is a breeding objective for many horticultural plants. The loss of function of class-C genes causes the multiple-petal trait in several plant species. Read More

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Synthesis, α-glucosidase and α-amylase inhibitory activities, acute toxicity and molecular docking studies of thiazolidine-2,4-diones derivatives.

J Biomol Struct Dyn 2021 Apr 13:1-12. Epub 2021 Apr 13.

Laboratory of Pharmacology and Toxicology, Biopharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco.

In the present study, a series of thiazolidine-2,4-diones derivatives () and () were synthesized and characterized by H NMR, C NMR and ESI-MS spectrometry. All compounds were screened for their α-glucosidase and α-amylase inhibitory activities. biological investigations revealed that most of compounds were active against α-glucosidase with IC values in the range of 43. Read More

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Multiple retrospective analysis of survival and evaluation of cardiac death predictors in a population of dogs affected by degenerative mitral valve disease in ACVIM class C treated with different therapeutic protocols.

Pol J Vet Sci 2021 Mar;24(1):109-118

University of Milan, University Veterinary Teaching Hospital, Via dell'Università n. 6, 26900 Lodi (LO), Italy.

Clinical records of dogs with spontaneous degenerative mitral valve disease (DMVD) with clinical signs related to congestive heart failure (CHF) recruited during routine clinical practice between 2001 and 2018 at the Cardiology Unit of the Veterinary Teaching Hospital (University of Milan) were included in this retrospective cohort study. Baseline echocardiographic data were evaluated. Median survival time (MST) was calculated. Read More

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A trigger phosphodiesterase modulates the global c-di-GMP pool, motility and biofilm formation in .

J Bacteriol 2021 Apr 12. Epub 2021 Apr 12.

Programa de Biología de Sistemas y Biología Sintética, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.

cells transit from free swimming to surface adapted lifestyles, such as swarming colonies and three-dimensional biofilms. These transitions are regulated by sensory modules and regulatory networks that involve the second messenger cyclic dimeric guanosine monophosphate (c-di-GMP). In this work, we show that a previously uncharacterized c-di-GMP phosphodiesterase (VP1881) from plays an important role in modulating the c-di-GMP pool. Read More

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Antibiotic prescriptions for children younger than 5 years with acute upper respiratory infections in China: a retrospective nationwide claims database study.

BMC Infect Dis 2021 Apr 12;21(1):339. Epub 2021 Apr 12.

National Clinical Research Center for Respiratory Diseases, Department of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.

Background: In China, there were few studies to estimate antibiotic use for children with upper respiratory infections at the national level. The aim of this study was to describe the antibiotic prescribing practice for children aged < 5 years old with upper respiratory infections (URIs) using a nationwide claims database.

Methods: This was a retrospective cross-sectional study using a sampled database from the China Health Insurance Research Association (CHIRA). Read More

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Removal of antibiotic resistance genes from secondary effluent by processes combining nano-iron, ultrasound-activated persulfate, and ultrafiltration.

Water Sci Technol 2021 Apr;83(7):1578-1590

Key Laboratory of Urban Stormwater System and Water Environment, Ministry of Education, Beijing University of Civil Engineering and Architecture, Beijing 100044, China E-mail:

Antibiotic resistance genes (ARGs), as a new type of environmental pollutant that threaten human health, have been detected in the effluent of sewage treatment systems. In this study, the removal from water of ARGs, 16S rRNA, class 1 integron (intI1), and dissolved organic carbon (DOC) were investigated using processes combining nano-iron (nFe), ultrasound (US), activated persulfate (PS) and ultrafiltration (UF). The oxidation mechanism was also studied. Read More

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Latent class derived patterns of musculoskeletal disorders in sedentary workers and chair ergonomic design.

Int J Occup Saf Ergon 2021 Apr 12:1-20. Epub 2021 Apr 12.

Isfahan Health Center, Isfahan University of Medical Sciences, Isfahan, Iran, Email:

The present study aimed to define specific patterns of multisite MSDs of office employees and to examine how derived patterns are related to the ergonomic chair design. in this cross-sectional study of 254 office employees, major patterns of MSDs were extracted using latent class analysis and investigated its association with the ergonomic chair design. Four major patterns of MSDs were extracted using latent class analysis. Read More

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The potential roles of different metacaspases in maize defense response.

Plant Signal Behav 2021 Apr 12:1906574. Epub 2021 Apr 12.

The Key Laboratory of Plant Development and Environmental Adaptation Biology, Ministry of Education, School of Life Sciences, Shandong University, Qingdao, Shandong, PR China.

Metacaspases (MCs), a class of cysteine-dependent proteases, act as important regulators in plant defense response. In maize genome, there are 11 which have been categorized into two types (type I and II) based on their structural differences. In this study, we investigated the different transcript patterns of 11 in maize defense response mediated by the nucleotide-binding, leucine-rich-repeat protein Rp1-D21. Read More

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Nomogram prediction of vulnerable periodontal condition before orthodontic treatment in the anterior teeth of Chinese patients with skeletal Class III malocclusion.

Acta Odontol Scand 2021 Apr 10:1-9. Epub 2021 Apr 10.

Department of Periodontology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, P. R. China.

Objective: To establish and verify models predictive of thin periodontal phenotype and alveolar fenestration/dehiscence in the anterior teeth of patients with skeletal Class III malocclusion.

Material And Methods: Retrospective data of 669 anterior teeth (305 in maxillae and 364 in mandibles) from 80 patients with skeletal Class III malocclusion before augmented corticotomy were collected. Distribution of thin periodontal phenotype and alveolar fenestration and dehiscence were evaluated and their associations with potential influencing factors were explored using univariate and multivariate analyses. Read More

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Disparities between US Hispanic and non-Hispanic women in obesity-related perinatal outcomes: a prospective cohort study.

J Matern Fetal Neonatal Med 2021 Apr 11:1-8. Epub 2021 Apr 11.

Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA.

Background: Mortality figures and national health surveillance data have demonstrated that Hispanics have a 24% lower risk of all-cause mortality compared to their non-Hispanic counterparts despite increased rates of obesity and related illnesses.

Objective: The aim of this study is to evaluate if this paradox exists for obesity-related perinatal outcomes in otherwise low-risk Hispanic women.

Materials And Methods: A prospective cohort study of low-risk women across all BMI classes with a singleton, non-anomalous term pregnancy admitted in active labor or undergoing induction of labor between May 2014 and April 2017. Read More

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Screening of postpartum diabetes in women with gestational diabetes: high-risk subgroups and areas for improvements-the STRONG observational study.

Acta Diabetol 2021 Apr 12. Epub 2021 Apr 12.

AMD-SID Diabetes and Pregnancy Study Group, Rome, Italy.

Aims: To assess the proportion of women with gestational diabetes (GDM) by performing postpartum Oral Glucose Tolerance Test (OGTT) and to identify GDM phenotypes at high-risk of postpartum dysglycemia (PPD).

Methods: Observational, retrospective, multicenter study involving consecutive GDM women. Recursive partitioning (RECPAM) analysis was used to identify distinct and homogeneous subgroups of women at different PPD risk. Read More

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Super-Enhancers and CTCF in Early Embryonic Cell Fate Decisions.

Front Cell Dev Biol 2021 25;9:653669. Epub 2021 Mar 25.

Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, United States.

Cell fate decisions are the backbone of many developmental and disease processes. In early mammalian development, precise gene expression changes underly the rapid division of a single cell that leads to the embryo and are critically dependent on autonomous cell changes in gene expression. To understand how these lineage specifications events are mediated, scientists have had to look past protein coding genes to the regulatory elements (CREs), including enhancers and insulators, that modulate gene expression. Read More

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3-Deoxysappanchalcone Inhibits Skin Cancer Proliferation by Regulating T-Lymphokine-Activated Killer Cell-Originated Protein Kinase and .

Front Cell Dev Biol 2021 25;9:638174. Epub 2021 Mar 25.

Department of Pathophysiology, School of Basic Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, China.

Background: Skin cancer is one of the most commonly diagnosed cancers worldwide. The 5-year survival rate of the most aggressive late-stage skin cancer ranges between 20 and 30%. Thus, the discovery and investigation of novel target therapeutic agents that can effectively treat skin cancer is of the utmost importance. Read More

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Transcriptional Responses of Blastospores Cultured Under Varying Glucose Concentrations.

Front Cell Infect Microbiol 2021 24;11:644372. Epub 2021 Mar 24.

Crop Bioprotection Research Unit, National Center for Agricultural Utilization Research, United States Department of Agriculture, Agriculture Research Service, Peoria, IL, United States.

Culturing the entomopathogenic fungus, , under high glucose concentrations coupled with high aeration results in a fungal developmental shift from hyphal growth to mostly blastospores (yeast-like cells). The underlying molecular mechanisms involved in this shift remain elusive. A systematic transcriptome analysis of the differential gene expression was preformed to uncover the fungal transcriptomic response to osmotic and oxidative stresses associated with the resulting high blastospore yield. Read More

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Effect of methylglyoxal on the alteration in structure and digestibility of α-lactalbumin, and the formation of advanced glycation end products under simulated thermal processing.

Food Sci Nutr 2021 Apr 28;9(4):2299-2307. Epub 2021 Feb 28.

Tianjin Key Laboratory of Food Science and Health School of Medicine Nankai University Tianjin China.

α-Dicarbonyl compounds (α-DCs) are a class of compounds generated during the thermal processing of food. Due to the high reactivity, α-DCs were endowed with the ability to react with food components thus lowering nutrition value and even leading to a potential risk for food safety. In this study, methylglyoxal (MG), the most abundant α-DCs, was selected to investigate the alteration effects on the structure and digestibility of α-lactalbumin (αLA) under thermal processing (60-100°C). Read More

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