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Integrative-omics for discovery of network-level disease biomarkers: a case study in Alzheimer's disease.

Brief Bioinform 2021 May 10. Epub 2021 May 10.

Department of BioHealth Informatics, Indiana University Purdue University Indianapolis, 420 University Blvd, Indianapolis, IN 46204, USA.

A large number of genetic variations have been identified to be associated with Alzheimer's disease (AD) and related quantitative traits. However, majority of existing studies focused on single types of omics data, lacking the power of generating a community including multi-omic markers and their functional connections. Because of this, the immense value of multi-omics data on AD has attracted much attention. Read More

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Targeting Poison Exons to Treat Developmental and Epileptic Encephalopathy.

Dev Neurosci 2021 May 10:1-6. Epub 2021 May 10.

Ken and Ruth Davee Department of Neurology, Northwestern University School of Medicine, Chicago, Illinois, USA.

Developmental and epileptic encephalopathies (DEEs) describe a subset of neurodevelopmental disorders categorized by refractory epilepsy that is often associated with intellectual disability and autism spectrum disorder. The majority of DEEs are now known to have a genetic basis with de novo coding variants accounting for the majority of cases. More recently, a small number of individuals have been identified with intronic SCN1A variants that result in alternative splicing events that lead to ectopic inclusion of poison exons (PEs). Read More

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Comparison of Cytokines in Skin Biopsies and Tape Strips from Adults with Atopic Dermatitis.

Dermatology 2021 May 10:1-6. Epub 2021 May 10.

Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.

Skin biomarkers for disease severity and treatment response in atopic dermatitis (AD) are needed. Biopsies cause scarring and tape stripping represents an alternative minimally invasive method for stratum corneum sampling. In this study, we examined the gene expression of cytokines in skin biopsies and cytokines in stratum corneum tape strips collected from adults with AD. Read More

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The expression of mimecan in adrenal tissue plays a role in an organism's responses to stress.

Aging (Albany NY) 2021 May 10;13. Epub 2021 May 10.

The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostic and Endocrinology, Shanghai Ninth People’s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao tong University School of Medicine, Shanghai 200011, China.

Mimecan encodes a secretory protein that is secreted into the human serum as two mature proteins with molecular masses of 25 and 12 kDa. We found 12-kDa mimecan to be a novel satiety hormone mediated by the upregulation of the expression of interleukin (IL)-1β and IL-6 in the hypothalamus. Mimecan was found to be expressed in human pituitary corticotroph cells and was up-regulated by glucocorticoids, while the secretion of adrenocorticotropic hormone (ACTH) in pituitary corticotroph AtT-20 cells was induced by mimecan. Read More

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Gene expression signatures differentiating major depressive disorder from subsyndromal symptomatic depression.

Aging (Albany NY) 2021 May 8;13. Epub 2021 May 8.

Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.

Subsyndromal symptomatic depression (SSD) and major depressive disorder (MDD) have been classified as distinct diseases, due to their dissimilar gene expression profiles and responses to venlafaxine. To identify specific biomarkers of these two diseases, we conducted a secondary analysis of the gene expression signatures of SSD patients, MDD patients and healthy controls (n=8/group) from the study of Yi et al. Global, individual, specific, enrichment and co-expression analyses were used to compare the transcriptomic profiles of peripheral blood lymphocytes from the three groups. Read More

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Effect of plasma glucose at admission on COVID-19 mortality: experience from a tertiary hospital.

Endocr Connect 2021 May 1. Epub 2021 May 1.

S Misra, Director and Chief Executive Officer, All India Institute of Medical Sciences Jodphur, Jodhpur, India.

Objective: Plasma glucose has been correlated with in-hospital mortality among many diseases including infections. We aimed to study plasma glucose at admission of hospitalized patients with COVID-19 at a tertiary care referral hospital at Jodhpur, India and its relation with mortality.

Design: A hospital-based clinical study of plasma glucose of COVID-19 patients conducted from May 15th to June 30th, 2020 after ethical approval. Read More

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Dietary protein source contributes to the risk of developing maternal syndrome in the Dahl salt-sensitive rat.

Pregnancy Hypertens 2021 May 5;24:126-134. Epub 2021 May 5.

Department of Physiology, Augusta University, United States.

Preeclampsia (PE) is a disorder of pregnancy, which is categorized by hypertension and proteinuria or signs of end-organ damage. Though PE is the leading cause of maternal and fetal morbidity and mortality, the mechanisms leading to PE remain unclear. The present study examined the contribution of dietary protein source (casein versus wheat gluten) to the risk of developing maternal syndrome utilizing two colonies of Dahl salt-sensitive (SS/JrHsdMcwi) rats. Read More

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Agronomic performance of polyethylene and biodegradable plastic film mulches in a maize cropping system in a humid continental climate.

Sci Total Environ 2021 Apr 30;786:147460. Epub 2021 Apr 30.

College of Land and Environment, Shenyang Agricultural University, Shenyang 110086, China.

Plastic polyethylene mulch has been widely used in crop production, but also causes environmental pollution if plastic residues accumulate in soil. Biodegradable plastic mulches (BDM) are a potential solution to problems caused by polyethylene mulches, as BDMs are designed be tilled into the soil after the growing season and then biodegrade. However, the agronomic performance of BDMs still needs to be tested for comparison to polyethylene mulch. Read More

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Effective utilisation of influence maximization technique for the identification of significant nodes in breast cancer gene networks.

Comput Biol Med 2021 Apr 18;133:104378. Epub 2021 Apr 18.

School of Computer Science and Engineering, Vellore Institute of Technology, Vellore, India. Electronic address:

Background: Identifying the most important genes in a cancer gene network is a crucial step in understanding the disease's functional characteristics and finding an effective drug.

Method: In this study, a popular influence maximization technique was applied on a large breast cancer gene network to identify the most influential genes computationally. The novel approach involved incorporating gene expression data and protein to protein interaction network to create a customized pruned and weighted gene network. Read More

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An autoantigen profile of human A549 lung cells reveals viral and host etiologic molecular attributes of autoimmunity in COVID-19.

J Autoimmun 2021 Apr 27;120:102644. Epub 2021 Apr 27.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, USA. Electronic address:

We aim to establish a comprehensive COVID-19 autoantigen atlas in order to understand autoimmune diseases caused by SARS-CoV-2 infection. Based on the unique affinity between dermatan sulfate and autoantigens, we identified 348 proteins from human lung A549 cells, of which 198 are known targets of autoantibodies. Comparison with current COVID data identified 291 proteins that are altered at protein or transcript level in SARS-CoV-2 infection, with 191 being known autoantigens. Read More

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SARS-CoV-2 rapid antigen test: High sensitivity to detect infectious virus.

J Clin Virol 2021 Apr 24;140:104846. Epub 2021 Apr 24.

Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Linköping University, 581 85 Linköping, Sweden. Electronic address:

Background: The COVID-19 pandemic has highlighted the need for rapid, cost effective and easy-to-use diagnostic tools for SARS-CoV-2 infections that can be used in point of care settings to limit disease transmission.

Objective: We evaluated two rapid antigen immunochromatographic tests, Abbott Panbio™ COVID-19 Ag Rapid Test (Panbio) and Zhejiang Orient Gene/Healgen Biotech Coronavirus Ag rapid test cassette (Orient gene) for detection of infectious SARS-CoV-2.

Results: The tests were evaluated on nasopharyngeal samples taken from individuals having respiratory and/or COVID-19 related symptoms, which had been analyzed for SARS-CoV-2 RNA using real-time PCR. Read More

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VDAC1 as a target in cisplatin anti-tumor activity through promoting mitochondria fusion.

Biochem Biophys Res Commun 2021 May 7;560:52-58. Epub 2021 May 7.

Key Laboratory of Molecular Epidemiology of Hunan Province, School of Medicine, Hunan Normal University, Changsha, 410081, PR China. Electronic address:

Cisplatin is one of the most effective anti-cancer drugs, but its efficacy is limited by the development of resistance. Previous studies have shown that mitochondria play critical roles in cisplatin cytotoxicity, however, the exact mechanism of mitochondria involved in cisplatin sensitivity has not been clarified. In this study, cisplatin triggered mitochondrial oxidative stress and the decrease of mitochondria membrane potential in human cervical cancer cells. Read More

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1,2,3-Triazole tethered 1,2,4‑trioxane trimer induces apoptosis in metastatic cancer cells and inhibits their proliferation, migration and invasion.

Bioorg Chem 2021 Apr 29;112:104952. Epub 2021 Apr 29.

Department of Chemistry, North-Eastern Hill University, Shillong 793022, India. Electronic address:

Artemisinin (ART) has been in use against different cancer cells and its derivatives and conjugates are more cytotoxic to iron-rich cancer cells. It is desirable to develop easily achievable synthetic 1,2,4-trioxanes having the same pharmacophore as that of ART. To explore more efficient compounds, a 1,2,3-triazole tethered 1,2,4‑trioxane trimer (4T) was synthesized and the anti-cancer effects of ART and 4T on MDA-MB-435 and MDA-MB-231 cells were investigated concerning regulation of osteopontin (OPN) expression, which is associated with cancer progression and malignancy. Read More

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Macrophage-preferable delivery of the leucine-rich repeat domain of NLRX1 ameliorates lethal sepsis by regulating NF-κB and inflammasome signaling activation.

Biomaterials 2021 May 4;274:120845. Epub 2021 May 4.

Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea; Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea; Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul, 04763, Republic of Korea. Electronic address:

Sepsis is an acute systemic inflammatory disease triggered by bacterial infection leading organ dysfunctions that macrophages are responsible for major triggering of systemic inflammation. Treatment options are limited to antibiotics and drugs to manage the symptoms of sepsis, but there are currently no molecular-targeted therapies. Here, we identified a novel macrophage-preferable delivery peptide, C10, which we conjugated to truncated domains of NLRX1 (leucine-rich repeat region (LRR), and nucleotide binding domain (NBD)) to obtain C10-LRR and C10-NBD. Read More

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miR-133b inhibits cell proliferation, migration, and invasion of lung adenocarcinoma by targeting CDCA8.

Pathol Res Pract 2021 Apr 28;223:153459. Epub 2021 Apr 28.

Department of Cancer Radiotherapy and Chemotherapy, Zhejiang Quhua Hospital, Quzhou, 324004, China. Electronic address:

Objective: Lung adenocarcinoma (LUAD) is the most common type of lung cancer. This study aims to explore the mechanism by which CDCA8 regulates cell proliferation, invasion, and migration of LUAD, and to generate novel insights into targeted therapy of LUAD.

Methods: Expression profiles of mature microRNAs (miRNAs) and mRNAs, along with clinical data of LUAD were downloaded from TCGA database for differential analysis and survival analysis to mine differentially expressed mRNAs. Read More

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Tumstatin attenuates the promotion effect of IL-17 secreted by Th17 cells on the stemness maintenance of glioma cells.

Pathol Res Pract 2021 May 5;223:153463. Epub 2021 May 5.

Department of Neurosurgery, Beilun District People's Hospital of Ningbo City, Ningbo, Zhejiang, 315800, China. Electronic address:

The presence and clinical significance of IL-17 and IL-17-expressing cells have been studied for several cancers, although their correlation with tumor development remains controversial. Peripheral blood was collected from healthy donors and glioma patients to isolate peripheral blood mononuclear cells (PBMCs). The percentage of IL-17-expressing cells and the production of inflammatory cytokines in PBMCs and tissues were measured. Read More

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Role and mechanism of action of circular RNA and laryngeal cancer.

Pathol Res Pract 2021 Apr 30;223:153460. Epub 2021 Apr 30.

Clinical Laboratory, Linyi Central Hospital, Linyi, 276400 Shandong, China. Electronic address:

Laryngeal squamous cell carcinoma (LSCC), is the second most common malignant cancer of the head and neck after oral cavity cancer. Laryngeal cancer is associated with huge socio-economic burden worldwide. Studies have widely explored the role of non-coding RNAs, especially microRNAs and long non-coding RNAs in pathogenesis of laryngeal cancer. Read More

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Destroying the structure of extracellular polymeric substance to improve the dewatering performance of waste activated sludge by ionic liquid.

Water Res 2021 Apr 17;199:117161. Epub 2021 Apr 17.

Sichuan Base of International Science and Technology Cooperation for Green Chemical Industry, School of Chemical Engineering, Sichuan University, Chengdu, 610065, China. Electronic address:

The disposal and resource utilization of waste activated sludge (WAS) is a big challenge for its high moisture content. Ionic liquid (IL), 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([EMIM][OTf]), was innovatively used as a conditioner to improve the dewatering performance of WAS. The WAS was characterized by flocs size, three-dimensional excitation-emission matrix (3D-EEM), zeta potential, Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM) for the investigation of intensification mechanism. Read More

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Robust prediction of mortality of COVID-19 patients based on quantitative, operator-independent, lung CT densitometry.

Phys Med 2021 Apr 30;85:63-71. Epub 2021 Apr 30.

Medical Physics, San Raffaele Scientific Institute, Milano, Italy. Electronic address:

Purpose: To train and validate a predictive model of mortality for hospitalized COVID-19 patients based on lung densitometry.

Methods: Two-hundred-fifty-one patients with respiratory symptoms underwent CT few days after hospitalization. "Aerated" (AV), "consolidated" (CV) and "intermediate" (IV) lung sub-volumes were quantified by an operator-independent method based on individual HU maximum gradient recognition. Read More

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Evaluation of immunogenicity and protection mediated by Lawsonia intracellularis subunit vaccines.

Vet Immunol Immunopathol 2021 May 7;237:110256. Epub 2021 May 7.

Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Saskatchewan, Canada. Electronic address:

Lawsonia intracellularis is an economically important bacterium that causes ileitis in pigs. Current vaccines for L. intracellularis do not allow for differentiation between infected and vaccinated animals (DIVA), which is beneficial for disease tracking and surveillance. Read More

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Application of lectin immobilized on polyHIPE monoliths for bioprocess monitoring of glycosylated proteins.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Apr 25;1174:122731. Epub 2021 Apr 25.

Faculty for Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia; COBIK, Tovarniška 26, 5270 Ajdovščina, Slovenia. Electronic address:

In-process monitoring of glycosylated protein concentration becomes very important with the introduction of perfusion bioprocesses. Affinity chromatography based on lectins allows selective monitoring when carbohydrates are accessible on the protein surface. In this work, we immobilized lectin on polyHIPE type of monoliths and implemented it for bioprocess monitoring. Read More

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Tatibody, a recombinant antibody with higher internalization potency.

Mol Immunol 2021 May 7;135:320-328. Epub 2021 May 7.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Using antibody drug conjugates (ADC) which can exclusively bind to their target cells and upon internalization release their toxic agent, is one of the most effective methods for killing tumor cells. Therefore, increasing the internalization rate is an important factor for tumor treatment in this case. The aim of the present study was to develop a new variant of pertuzumab (an anti-ErbB2 humanized antibody) with higher internalization rate that can be a good candidate for the production of ADC. Read More

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Whole transcriptome analysis of schinifoline treatment in Caenorhabditis elegans infected with Candida albicans.

Mol Immunol 2021 May 7;135:312-319. Epub 2021 May 7.

Nanjing Institute for Comprehensive Utilization of Wild Plants, Nanjing, 211100, China. Electronic address:

Candida albicans is an opportunistic fungal human pathogen that has been causing an increasing number of deaths each year. Due to the widespread use of broad-spectrum antibiotics and immunosuppressants, C. albicans resistance to these therapies has increased. Read More

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Kappa-carrageenan enhances the gelation and structural changes of egg yolk via electrostatic interactions with yolk protein.

Food Chem 2021 Apr 28;360:129972. Epub 2021 Apr 28.

Department of Food Science and Technology, National University of Singapore, 117542, Singapore; National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Suzhou, Jiangsu 215123, PR China. Electronic address:

The effect of κ-carrageenan (κ-C) on yolk over heat-induced gelation at natural yolk pH (6.2) and natural whole egg pH (7.5) was studied. Read More

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Synergistic cardioptotection by tilianin and syringin in diabetic cardiomyopathy involves interaction of TLR4/NF-κB/NLRP3 and PGC1a/SIRT3 pathways.

Int Immunopharmacol 2021 May 7;96:107728. Epub 2021 May 7.

Department of Endocrinology and Metabolism, Changzhou No.2 People's Hospital, Changzhou, Jiangsu 213003, China. Electronic address:

Diabetic cardiomyopathy (DCM) is a chronic multifactorial complication of type-2 diabetes mellitus, leading to heart failure. A combination of multifaceted therapeutics for the management of DCM is needed. Here, we investigated the combined effect of syringin and tilianin on DCM by evaluating cardiac function, inflammation, oxidative stress, apoptosis and mitochondrial function, and explored the contribution of TLR4/NF-κB/NLRP3 and PGC1α/SIRT3 pathways in diabetic rats and hyperglycemic-H9c2 cells. Read More

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Natural antioxidants enhance the power of physical and mental activities versus risk factors inducing progression of Alzheimer's disease in rats.

Int Immunopharmacol 2021 May 7;96:107729. Epub 2021 May 7.

Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt. Electronic address:

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease that is exacerbated by social isolation (SI) and protein malnutrition (PM). Antioxidants, physical and mental activities (Ph&M) can maintain cognitive functions and protect against dementia.

Objective: To investigate the impact of Epigallocatechin-3-gallate (EGCG), Vitamin E (VE), Vitamin C (VC), and Selenium (Se), in enhancing the potential effect of Ph&M versus SI&PM as risk factors in the progression of AD in rats. Read More

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CircATRNL1 protects against osteoarthritis by targeting miR-153-3p and KLF5.

Int Immunopharmacol 2021 May 7;96:107704. Epub 2021 May 7.

Department of Orthopaedics, the 1st Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address:

Background: Osteoarthritis (OA) is characterized by chondrocyte injury. Circular RNAs (circRNAs) are involved in the pathogenesis of various diseases, including OA. The purpose of this study was to determine the potential role of circATRNL1 in OA pathology in vitro. Read More

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Design, synthesis and biological evaluation of imidazopyridazine derivatives containing isoquinoline group as potent MNK1/2 inhibitors.

Bioorg Med Chem 2021 May 2;40:116186. Epub 2021 May 2.

Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address:

Mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are located at the meeting-point of ERK and p38 MAPK signaling pathways, which can phosphorylate eukaryotic translation initiation factor 4E (eIF4E) at the conserved serine 209 exclusively. MNKs modulate the translation of mRNA involved in tumor-associated signaling pathways. Consequently, selective inhibitors of MNK1/2 could reduce the level of phosphorylated eIF4E. Read More

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Exploiting the HSP60/10 chaperonin system as a chemotherapeutic target for colorectal cancer.

Bioorg Med Chem 2021 Apr 19;40:116129. Epub 2021 Apr 19.

Indiana University School of Medicine, Department of Biochemistry and Molecular Biology, 635 Barnhill Dr., Indianapolis, IN 46202, United States. Electronic address:

Over the past few decades, an increasing variety of molecular chaperones have been investigated for their role in tumorigenesis and as potential chemotherapeutic targets; however, the 60 kDa Heat Shock Protein (HSP60), along with its HSP10 co-chaperone, have received little attention in this regard. In the present study, we investigated two series of our previously developed inhibitors of the bacterial homolog of HSP60/10, called GroEL/ES, for their selective cytotoxicity to cancerous over non-cancerous colorectal cells. We further developed a third "hybrid" series of analogs to identify new candidates with superior properties than the two parent scaffolds. Read More

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JTE-013 Alleviates Inflammatory Injury and Endothelial Dysfunction Induced by Sepsis In Vivo and Vitro.

J Surg Res 2021 May 7;265:323-332. Epub 2021 May 7.

Special Functions Section, The Fourth Sanatorium Area of Hangzhou Special Service Sanatorium Center of Air Force, Nanjing City, Jiangsu Province, China. Electronic address:

Background: Nowadays, there is no approved targeted agent for lung injury induced by sepsis. S1PR2 is confirmed to be a promising diagnosis and treatment target. JTE-013 as S1PR2 antagonists may be an agent of great potential. Read More

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