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viscoelastic properties estimation in subcutaneous adipose tissue by integration of poroviscoelastic-mass transport model (pve-MTM) into wearable electrical impedance tomography (w-EIT).

Biomed Phys Eng Express 2021 Apr 22. Epub 2021 Apr 22.

Department of Mechanical Engineering, Graduate School of Science and Engineering, Chiba University, 1-33 Yayoi-cho Inage-ku, Chiba-shi, Chiba-ken, 263-8522, JAPAN.

viscoelastic properties have been estimated in human subcutaneous adipose tissue (SAT) by integration of poroviscoelastic-mass transport model (-MTM) into wearable electrical impedance tomography (-EIT) under the influence of external compressive pressure -. The-MTM predicts the ion concentration distributionby coupling the poroviscoelastic and mass transport model to describe the hydrodynamics, rheology, and transport phenomena inside SAT. The-EIT measures the time-difference conductivity distributionin SAT resulted from the ion transport. Read More

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Metrics of pN-staging in oral squamous cell carcinoma: An analysis of 1,905 patients.

Eur J Cancer 2021 Apr 19;150:33-41. Epub 2021 Apr 19.

Department of Otorhinolaryngology, Region Hospital West Jutland, Holstebro, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark.

Background: We aimed to compare the predictive performance of pN-categories in oral squamous cell carcinoma (OSCC) encompassing the most recent 8th edition (TNM8), its predecessor (TNM7), and a newly proposed algorithm (pN-N), which classifies patients according to the number of positive lymph nodes and extranodal extension.

Methods: Consecutive, primary OSCC patients from seven previously published cohorts were included and classified according to the three pN-classifications: TNM7, TNM8 and pN-N. Overall survival probabilities were summarised with the Kaplan-Meier method. Read More

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Paeonol-Loaded PLGA Nanoparticles as an Oral Drug Delivery System: Design, Optimization and Evaluation.

Int J Pharm 2021 Apr 19:120617. Epub 2021 Apr 19.

Anhui University of Chinese Medicine, Hefei, China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, China; Engineering Technology Research Center of Modernized Pharmaceutics Anhui Education Department (AUCM); Anhui Province Key Laboratory of Pharmaceutical Technology and Application (Anhui University of Chinese Medicine), Hefei, China.

Herein, we report a novel type of NPs by loading paeonol (Pae) into PLGA NPs, to enhance drug stability and oral bioavailability. The paeonol (Pae)-loaded polylactic-co-Gly-colic acid (PLGA) nanoparticles (Pae-PLGA-NPs) were prepared by nanoprecipitation method. The resultant NPs were in spherical shape with an average particle size around 237. Read More

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Structural insights into the mechanisms and pharmacology of K potassium channels.

J Mol Biol 2021 Apr 19:166995. Epub 2021 Apr 19.

Cardiovascular Research Institute; Departments of Biochemistry and Biophysics, and Cellular and Molecular Pharmacology; California Institute for Quantitative Biomedical Research; Kavli Institute for Fundamental Neuroscience University of California, San Francisco, California 93858-2330 USA; Molecular Biophysics and Integrated Bio-imaging Division Lawrence Berkeley National Laboratory, Berkeley, CA 94720 USA. Electronic address:

Leak currents, defined as voltage and time independent flows of ions across cell membranes, are central to cellular electrical excitability control. The K (KCNK) potassium channel class comprises an ion channel family that produces potassium leak currents that oppose excitation and stabilize the resting membrane potential in cells in the brain, cardiovascular system, immune system, and sensory organs. Due to their widespread tissue distribution, Ks contribute to many physiological and pathophysiological processes including anesthesia, pain, arrythmias, ischemia, hypertension, migraine, intraocular pressure regulation, and lung injury responses. Read More

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Cell-Specific Drug Targeting in the Lung.

Biochem Pharmacol 2021 Apr 19:114577. Epub 2021 Apr 19.

Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada. Electronic address:

Non-targeteddrug delivery systems have several limitations including the decreased bioavailability of the drug, poor stability and rapid clearance in addition to off-target distribution. Cell-specific targeted delivery approaches promise to overcome some of these limitations and enhance therapeutic selectivity. In this review, we aim to discuss cell-specific targeted approachesin the lung at the biochemical and molecular levels. Read More

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Drug Development Research in Pregnant and Lactating Women.

Am J Obstet Gynecol 2021 Apr 19. Epub 2021 Apr 19.

Obstetric and Pediatric Pharmacology and Therapeutics Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.

Pregnant and lactating women are "therapeutic orphan" as they have been generally excluded from clinical drug research and drug development process due to legal, ethical and safety concerns. The majority of medications prescribed for pregnant and lactating women are used "off label" as most of the clinical approved medications do not have appropriate drug labeling information for pregnant and lactating women. Medications that lack human safety data in pregnancy and lactation may pose potential risks of adverse effects to pregnant women and lactating women as well as teratogenic effects to their unborn and newborn babies. Read More

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Thorium-227-Labeled Anti-CD22 Antibody (BAY 1862864) in Relapsed/Refractory CD22-Positive Non-Hodgkin Lymphoma: A First-in-Human, Phase I Study.

Cancer Biother Radiopharm 2021 Apr 21. Epub 2021 Apr 21.

Department of Haematology, University College London Hospital, London, United Kingdom.

BAY 1862864 is an α-particle emitting thorium-227-labeled CD22-targeting antibody. This first-in-human dose-escalation phase I study evaluated BAY 1862864 in patients with CD22-positive relapsed/refractory B cell non-Hodgkin lymphoma (R/R-NHL). BAY 1862864 intravenous injections were administered at the starting thorium-227 radioactivity dose of 1. Read More

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Visualization of Protein Coding, Long Noncoding, and Nuclear RNAs by Fluorescence in Situ Hybridization in Sections of Shoot Apical Meristems and Developing Flowers1[OPEN].

Plant Physiol 2020 Jan;182(1):147-158

Sainsbury Laboratory, University of Cambridge, Cambridge CB2 1LR, United Kingdom.

In addition to transcriptional regulation, gene expression is further modulated through mRNA spatiotemporal distribution, by RNA movement between cells, and by RNA localization within cells. Here, we have adapted RNA fluorescence in situ hybridization (FISH) to explore RNA localization in Arabidopsis (Arabidopsis thaliana). We show that RNA FISH on sectioned material can be applied to investigate the tissue and subcellular localization of meristem and flower development genes, cell cycle transcripts, and plant long noncoding RNAs. Read More

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January 2020

The impact of cytochrome P450 3A genetic polymorphisms on tacrolimus pharmacokinetics in ulcerative colitis patients.

PLoS One 2021 22;16(4):e0250597. Epub 2021 Apr 22.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Tacrolimus (Tac) is an effective remission inducer of refractory ulcerative colitis (UC). Gene polymorphisms result in interindividual variability in Tac pharmacokinetics. In this study, we aimed to examine the relationships between gene polymorphisms and the metabolism, pharmacokinetics, and therapeutic effects of Tac in patients with UC. Read More

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Complex effects of whole body cryostimulation on hematological markers in patients with obesity.

PLoS One 2021 22;16(4):e0249812. Epub 2021 Apr 22.

Institute for Basics Sciences, Faculty of Physiotherapy, University of Physical Education in Krakow, Krakow, Poland.

Background: Adaptation, including changes in blood properties, to whole-body cryostimulation may depend on many factors, including body mass.

Aim: This study investigates whether hematological parameters change similarly in a group of people with obesity and a group of men with normal body weight after 10 and 20 cryostimulation treatments.

Methods: In our non-randomized trial, the participants were divided into two groups based on their body fat percentage: 14 men with a high (HBF = 29. Read More

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How close are we to personalized mitotane dosing in the treatment of adrenocortical carcinoma? State of the art and future perspectives.

Expert Opin Drug Metab Toxicol 2021 Apr 22. Epub 2021 Apr 22.

Department of Internal Medicine, Máxima MC, Veldhoven, Eindhoven, the Netherlands.

Introduction: : Mitotane is the only drug registered specifically for adrenocortical carcinoma. Finding the optimal dose for a patient is difficult due to large differences in bioavailability, toxicity and effect. We therefore look to improve personalized dosing of mitotane. Read More

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LC-MS/MS method for determination of seneciphylline and its metabolite, seneciphylline N-oxide in rat plasma and its application to a rat pharmacokinetic study.

Biomed Chromatogr 2021 Apr 22:e5145. Epub 2021 Apr 22.

Department of pharmacy, Maternal and child health care hospital of Zaozhuang, Zaozhuang, China.

A rapid and sensitive ultra-performance liquid chromatography tandem electrospray ionization mass spectrometry (UPLC-ESI/MS) method was established and validated for simultaneous determination of seneciphylline and its main metabolite in rat plasma. Plasma sample was prepared by simple methanol mediated precipitation. Chromatographic separation was achieved within 3 min by gradient elution using acetonitrile and water containing 0. Read More

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Evaluation of the in vivo behavior of antibacterial gold nanoparticles for potential biomedical applications.

J Mater Chem B 2021 Apr 22;9(13):3025-3031. Epub 2021 Mar 22.

School of Life Science and Technology, Harbin Institute of Technology, 2 Yikuang Road, Nangang District, Harbin 150001, P. R. China.

The pharmacokinetics is a critical factor determining the clinical applicability of nanomaterials. Systematic study of the pharmacokinetics of functional nanomaterials is thus significant for promoting their applications. Herein, we take aminophenylboronic acid and mercaptophenylboronic acid-co-modified gold nanoparticles (A/M-Au NPs) with potent and tunable antibacterial activity as an example to study their behaviors in vitro and in vivo. Read More

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Semi-supervised planning method for breast electronic tissue compensation treatments based on breast radius and separation.

Radiol Oncol 2020 Dec 22;55(1):106-115. Epub 2020 Dec 22.

State University of New York at Buffalo, Department of Medical Physics, Buffalo, New York, United States.

Background: The aim of the study was to develop and assess a technique for the optimization of breast electronic tissue compensation (ECOMP) treatment plans based on the breast radius and separation.

Materials And Methods: Ten ECOMP plans for 10 breast cancer patients delivered at our institute were collected for this work. Pre-treatment CT-simulation images were anonymized and input to a framework for estimation of the breast radius and separation for each axial slice. Read More

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December 2020

Sensitive LC-MS/MS method for quantification of Rivaroxaban in plasma: application to pharmacokinetic studies.

Biomed Chromatogr 2021 Apr 22:e5147. Epub 2021 Apr 22.

Universidade São Francisco, Programa de Pós-graduação Stricto Sensu em Ciências da Saúde, Bragança Paulista, SP, Brazil.

Rivaroxaban is an anticoagulant (orally active direct Xa inhibitor) indicated to reduce the risk of stroke and systemic embolism, for treatment and prophylaxis of deep vein thrombosis, for treatment of pulmonary embolism, as well as other cardiovascular complications. Bioanalytical methods for rivaroxaban quantification in plasma are necessary for application in pharmacokinetic studies, as well as in drug therapeutic monitoring. This work developed and validated a sensitive bioanalytical method by LC-MS/MS for rivaroxaban quantification in human plasma using a one-step liquid-liquid extraction. Read More

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Pharmacokinetics of Ginsenoside Compound K From a Compound K Fermentation Product, CK-30, and From Red Ginseng Extract in Healthy Korean Subjects.

Clin Pharmacol Drug Dev 2021 Apr 21. Epub 2021 Apr 21.

Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.

Natural protopanaxadiol ginsenosides exhibit low absorption in the human intestine. However, ginsenoside compound K (CK) with 1 conjugated glucose molecule exhibits favorable absorption. The purpose of this study was to compare the pharmacokinetics of ginsenoside CK from a CK fermentation product, CK-30, and from a red ginseng extract. Read More

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Validation of a perioperative population factor VIII pharmacokinetic model with a large cohort of pediatric hemophilia A patients.

Br J Clin Pharmacol 2021 Apr 22. Epub 2021 Apr 22.

Department of Pediatric Hematology, Erasmus University Medical Center - Sophia Children's Hospital Rotterdam, Rotterdam, the Netherlands.

Aim: Population pharmacokinetic (PK) models are increasingly applied to perform individualized dosing of factor VIII (FVIII) concentrates in hemophilia A patients. To guarantee accurate performance of a population PK model in dose individualization, validation studies are of importance. However, external validation of population PK models requires independent data sets and is, therefore, seldomly performed. Read More

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Rational Clinical Dose Selection of Adeno-Associated Virus-Mediated Gene Therapy Based on Allometric Principles.

Clin Pharmacol Ther 2021 Apr 21. Epub 2021 Apr 21.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA.

One of the challenges in translational medicine is to select first-in-human doses of investigational drugs based on findings in preclinical studies. Despite substantial progress in the optimization of recombinant adeno-associated virus (AAV) vectors of in vivo gene therapy for treating various diseases, there remain significant limitations to the use of preclinical data to guide dose selection in clinical trials. Here we introduce a novel concept of gene efficiency factor (GEF) to describe the efficiency of the gene transfer system and describe and apply the concept of GEF in AAV-mediated in vivo gene transfer systems. Read More

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Current applications and prospects of nanoparticles for antifungal drug delivery.

EXCLI J 2021 8;20:562-584. Epub 2021 Mar 8.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Currently, the significance of fungi as human pathogens is not medically concealed in the world. Consequently, suitable recognition and treatment of such infections are of great importance and necessitate the need for comprehensive information in this regard. The introduction of new antifungals and their use today, especially in the last two decades, have revolutionized the treatment of fungal infections. Read More

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Establishment and Verification of UPLC-MS/MS Technique for Pharmacokinetic Drug-Drug Interactions of Selinexor with Posaconazole in Rats.

Drug Des Devel Ther 2021 15;15:1561-1568. Epub 2021 Apr 15.

School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471023, People's Republic of China.

Background: A method for the determination of selinexor by UPLC-MS/MS was established to study the effect of posaconazole on the pharmacokinetics of selinexor in rats.

Methods: The experiment rats were divided into group A (0.5% CMC-Na) and group B (posaconazole, 20 mg/kg), 6 rats in each group. Read More

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Development and evaluation of physiologically based pharmacokinetic drug-disease models for predicting captopril pharmacokinetics in chronic diseases.

Sci Rep 2021 Apr 21;11(1):8589. Epub 2021 Apr 21.

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.

The advancement in the processing speeds of computing machines has facilitated the development of complex physiologically based pharmacokinetic (PBPK) models. These PBPK models can incorporate disease-specific data and could be used to predict pharmacokinetics (PK) of administered drugs in different chronic conditions. The present study aimed to develop and evaluate PBPK drug-disease models for captopril after incorporating relevant pathophysiological changes occurring in adult chronic kidney disease (CKD) and chronic heart failure (CHF) populations. Read More

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[Consideration of Lens of the Eye Protection during Mammography with the Eyelid and the Face Guard].

Nihon Hoshasen Gijutsu Gakkai Zasshi 2021 ;77(4):358-364

Department of Radiology, Chiba University Hospital.

Purpose: In 2011, the International Commissionon Radiological Protection (ICRP) recommended reducing the threshold dose for the lens. Therefore, it is important to reduce the lens exposure dose in medical exposures. In a cranio-caudal (CC) view of mammography, the patient' s lens receives scattered radiation. Read More

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January 2021

Parallel evolution of UbiA superfamily proteins into aromatic -prenyltransferases in plants.

Proc Natl Acad Sci U S A 2021 Apr;118(17)

Laboratory of Plant Gene Expression, Research Institute for Sustainable Humanosphere, Kyoto University, Uji 611-0011, Japan;

Plants produce ∼300 aromatic compounds enzymatically linked to prenyl side chains via C-O bonds. These -prenylated aromatic compounds have been found in taxonomically distant plant taxa, with some of them being beneficial or detrimental to human health. Although their -prenyl moieties often play crucial roles in the biological activities of these compounds, no plant gene encoding an aromatic -prenyltransferase (-PT) has been isolated to date. Read More

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Randomised study of PF-06410293, an adalimumab (ADL) biosimilar, compared with reference ADL for the treatment of active rheumatoid arthritis: results from weeks 26-52, including a treatment switch from reference ADL to PF-06410293.

RMD Open 2021 Apr;7(2)

University Medicine, Schlosspark Klinik, Berlin, Germany.

Objective: To investigate the efficacy, safety, immunogenicity and pharmacokinetics of biosimilar adalimumab (ADL) PF-06410293 (ADL-PF; adalimumab-afzb) versus EU-sourced reference ADL (ADL-EU) in patients with active rheumatoid arthritis (RA) on longer-term treatment and after being switched from ADL-EU to ADL-PF.

Methods: In this multinational, double-blind study, patients with active RA were initially randomised to ADL-PF or ADL-EU for 26 weeks (treatment period (TP) 1). At the start of TP2 (weeks 26-52), patients in the ADL-EU arm were blindly re-randomised 1:1 to remain on ADL-EU (ADL-EU/ADL-EU; n=135) or switched to ADL-PF (ADL-EU/ADL-PF; n=134); patients receiving ADL-PF continued blinded treatment (ADL-PF/ADL-PF; n=283). Read More

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XYZeq: Spatially resolved single-cell RNA sequencing reveals expression heterogeneity in the tumor microenvironment.

Sci Adv 2021 Apr 21;7(17). Epub 2021 Apr 21.

Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA 94143, USA.

Single-cell RNA sequencing (scRNA-seq) of tissues has revealed remarkable heterogeneity of cell types and states but does not provide information on the spatial organization of cells. To better understand how individual cells function within an anatomical space, we developed XYZeq, a workflow that encodes spatial metadata into scRNA-seq libraries. We used XYZeq to profile mouse tumor models to capture spatially barcoded transcriptomes from tens of thousands of cells. Read More

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Safety, pharmacokinetics and exploratory pro-cognitive effects of HTL0018318, a selective M receptor agonist, in healthy younger adult and elderly subjects: a multiple ascending dose study.

Alzheimers Res Ther 2021 Apr 21;13(1):87. Epub 2021 Apr 21.

Sosei Heptares, Steinmetz Building, Granta Park, Great Abington, Cambridge, CB21 6DG, UK.

Background: The cholinergic system and M receptor remain an important target for symptomatic treatment of cognitive dysfunction. The selective M receptor partial agonist HTL0018318 is under development for the symptomatic treatment of Dementia's including Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). We investigated the safety, tolerability, pharmacokinetics and exploratory pharmacodynamics of multiple doses of HTL0018318 in healthy younger adults and elderly subjects. Read More

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Improvements in HOMA indices and pancreatic endocrinal tissues in type 2-diabetic rats by DPP-4 inhibition and antioxidant potential of an ethanol fruit extract of Withania coagulans.

Nutr Metab (Lond) 2021 Apr 21;18(1):43. Epub 2021 Apr 21.

Department of Agriculture and Environmental Sciences (AES), National Institute of Food Technology Entrepreneurship and Management (NIFTEM), Sonepat, 131028, Haryana, India.

Context: Withania coagulans (Stocks) Dunal fruits are used in the therapeutics of several ailments due to possessing of potent phytoconstituents which is also used traditionally for curing the diabetes.

Objective: The present study was assessing the amelioration potential of the phytochemicals of an ethanol fruit extract of W. coagulans (Stocks) Dunal in the HOMA (Homeostatic model assessment) indices and pancreatic endocrinal tissues by inhibition of DPP-4 and antioxidants activities. Read More

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Residual effects of abomasal 5-hydroxytryptophan administration on serotonin metabolism in cattle.

Domest Anim Endocrinol 2021 Mar 23;76:106627. Epub 2021 Mar 23.

Department of Animal and Food Science, University of Kentucky, Lexington, KY. Electronic address:

Studies of serotonin in animal husbandry has received growing interest. However, there is limited information about serotonin manipulation using 5-HTP administered postruminally and its residual effects in cattle. The objective of this study was to evaluate the effectiveness of 5-HTP infused into the abomasum for enhancing circulating serotonin in cattle. Read More

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Novel Water Soluble Sterile Natamycin Formulation (Natasol) for Fungal Keratitis.

Eur J Pharm Sci 2021 Apr 18:105857. Epub 2021 Apr 18.

Ocular Pharmacology and Pharmacy Division, All India Institute of Medical Sciences, New Delhi, INDIA 110029.

The purpose of this study was to develop, characterize and evaluate novel water soluble formulation for its topical and intrastromal application. Natamycin complexed with cyclodextrin was characterized by Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The complexed powder was used to formulate 1% w/v aqueous natamycin formulation (Natasol 1%) for topical use. Read More

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Cloning, Expression, Characterization, and Tissue Distribution of Cystatin C from Silver Carp ().

J Agric Food Chem 2021 Apr 21. Epub 2021 Apr 21.

Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki, Helsinki 00014, Finland.

Cystatins are proteins, which inhibit cysteine proteases, such as papain. In this study, the 336-bp gene (family II, Hm) of silver carp () was cloned and expressed in BL21 (DE3). Hm encodes the mature peptide of cystatin C (HmCystatin C), with 111 amino acids. Read More

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