Translatability of Stress for Predicting Deamidation and Oxidation Biotransformation on Biotherapeutics.

Biotransformation leading to single residue modifications (e.g., deamidation, oxidation) can contribute to decreased efficacy/potency, poor pharmacokinetics, and/or toxicity/immunogenicity for protein therapeutics.

Discovery and multimerization of cross-reactive single-domain antibodies against SARS-like viruses to enhance potency and address emerging SARS-CoV-2 variants.

Coronaviruses have been the causative agent of three epidemics and pandemics in the past two decades, including the ongoing COVID-19 pandemic. A broadly-neutralizing coronavirus therapeutic is desirable not only to prevent and treat COVID-19, but also to provide protection for high-risk populations against future emergent coronaviruses. As all coronaviruses use spike proteins on the viral surface to enter the host cells, and these spike proteins share sequence and structural homology, we set out to discover cross-reactive biologic agents targeting the spike protein to block viral entry.

In-depth size and charge variants characterization of monoclonal antibody with native mass spectrometry.

Although the reversed-phase liquid chromatography (RPLC) is the most used separation front for mass spectrometry, many other separation modes are critical for enabling characterization of the protein therapeutics. Specifically, chromatographic separations under native conditions, such as those based on size exclusion chromatography (SEC) and ion-exchange chromatography (IEX), are used for characterizing important biophysical properties of protein variants in drug substance and drug product. Because most native state separation modes use non-volatile buffers with high salt concentration, optical detection has been traditionally used.

A Spike-Control Approach that Evaluates High Resolution Mass Spectrometry-Based Sequence Variant Analytical Method Performance for Therapeutic Proteins.

An amino acid sequence variant (SV) is defined as an unintended amino acid substitution in protein drug products. SVs contribute to product heterogeneity and can potentially impact product quality, safety, immunogenicity, and efficacy. The analysis of biotherapeutics for SVs is important throughout the product life cycle including clone selection, development of nutrient feed strategies, commercial manufacturing process, and post-approval changes to monitor product quality.

Cold-hot nature identification of Chinese herbal medicines based on the similarity of HPLC fingerprints.

The nature theory of Chinese herbal medicines (CHMs) is the core theory of traditional Chinese medicine (TCM). Cold-hot nature is an important part of CHM nature. It is found that the material basis of cold-hot nature is CHM ingredients.

Capillary Isoelectric Focusing: Mass Spectrometry Method for the Separation and Online Characterization of Monoclonal Antibody Charge Variants at Intact and Subunit Levels.

Monoclonal antibodies (mAbs) are one of the most widely used types of protein therapeutics. Charge variants are important quality attributes for evaluating developability, activity, and safety for mAb therapeutics. Here, we report a novel online capillary isoelectric focusing-mass spectrometry (CIEF-MS) method for mAb charge variant analysis using an electrokinetically pumped sheath-flow nanospray ion source on a time-of-flight (TOF) MS with a pressure-assisted chemical mobilization.

Piezo1 initiates platelet hyperreactivity and accelerates thrombosis in hypertension.

Background: Thrombosis is the pathological basis of cardiovascular and cerebrovascular diseases, which seriously threaten human life and health. Among them, nearly half of cardiovascular disease patients suffer from severe hypertension complications. Hypertension is thought to cause abnormal platelet activation and increases the risk of thrombosis, but the related mechanism is still vague.

Porcine ubiquitin-like protein MNSFβ promotes cell apoptosis and covalently binds to BCL-G to enhance staurosporine-induced apoptosis.

Background: Monoclonal non-specific suppressor factor β (MNSFβ) is a ubiquitously expressed member of the ubiquitin-like family. It functions as a regulator of cell apoptosis and a potential tumor suppressor, playing a vital role in the processes of immune cell function and apoptosis.

Methods: The present study constructed GFP-pMNSFβ swine umbilical vein endothelial cell (SUVEC) lines and investigated the function of porcine MNSFβ (pMNSFβ) in apoptosis, as well as its interactions with pBCL-G.

Ethnic, geographic, and seasonal differences of vitamin D status among adults in south-west China.

Background: There are limited data on vitamin D status of Sichuan province, and no investigation has been carried out on the correlations of 25(OH)D and BTMs between healthy Hans and Tibetans of Sichuan province. This study aimed to examine 25(OH)D levels around Sichuan province and to assess differences by ethnicity, age, gender, sunlight exposure, geographic location, and seasons.

Methods: Blood samples from 2317 healthy adults aged of 18 to 75 years and of Han and Tibetan ethnicities were collected in six regions and during four seasons.

Molecular basis of the lipid-induced MucA-MucB dissociation in Pseudomonas aeruginosa.

MucA and MucB are critical negative modulators of sigma factor AlgU and regulate the mucoid conversion of Pseudomonas aeruginosa. Previous studies have revealed that lipid signals antagonize MucA-MucB binding. Here we report the crystal structure of MucB in complex with the periplasmic domain of MucA and polyethylene glycol (PEG), which unveiled an intermediate state preceding the MucA-MucB dissociation.

Identification of five types of forensic body fluids based on stepwise discriminant analysis.

Peripheral blood, menstrual blood, semen, saliva and vaginal secretions are the five most common body fluids found at crime scenes, and the identification of these five body fluids is of great significance to the reconstruction of a crime scene and resolution of the case. However, accurate identification of these five body fluids is still a challenge. To address this problem, a mathematical model for differentiating five types of forensic body fluids based on the differential expression characteristics of multiple miRNAs in five body fluids (peripheral blood, menstrual blood, semen, saliva and vaginal secretions) was developed.

Novel potent antiplatelet thrombotic agent derived from biguanide for ischemic stroke.

Platelet thrombosis is the main pathogeny resulting in the low curability of ischemic stroke, a leading cause of mortality and disability worldwide. Metformin, a biguanide derivative that is the first-line oral medicine for type 2 diabetes, alleviates the severity of ischemic stroke in diabetic patients and suppresses platelet activation in experimental animal model. However, the clinical implementation of commercial biguanide analogs for stroke related to platelet thrombosis remains challenging due to its weak potency, poor pharmacokinetic characteristics and possible hypoglycemia.

Study on the antibacterial activities of emodin derivatives against clinical drug-resistant bacterial strains and their interaction with proteins.

Background: Novel haloemodin (HEI2) synthesized by modifying emodin, a traditional Chinese medicine component, possesses remarkable antibacterial activity, being much more effective than its parent nucleus, emodin.

Methods: Firstly, we discovered that HEI2 increases bacterial cell membrane permeability to potassium ions more drastically than emodin. We thus further investigated the interaction of haloemodin and protein using a fluorescence quenching and circular dichroism (CD) study based on bovine serum albumin (BSA).

Tunable magnetic and half-metallic properties of the two-dimensional electron gas in LaAlO/SrTiO(111) heterostructures.

Half-metallic materials have gained a lot of attention because of their unique properties and applications in spintronic devices. Despite the fact that these materials have been studied by several research groups there are very limited studies on their heterostructure (HS) systems. In the current study we have investigated the electronic and magnetic properties of (LaAlO3)6.

Dihydrodiosgenin inhibits endothelial cell-derived factor VIII and platelet-mediated hepatocellular carcinoma metastasis.

Our previous studies have demonstrated that diosgenin and diosgenin derivatives exhibit excellent antithrombotic activity via regulating platelet function and coagulation factor level. Platelets and blood coagulation system are highly associated with tumor hematogenous metastasis. Therefore, the purpose of this study was to evaluate whether dihydrodiosgenin (dydio) mediated-platelet inhibition or coagulation factor level modulation is involved in hepatocellular carcinoma cell (HCC) metastasis.

The influence of porcine epidemic diarrhea virus on pig small intestine mucosal epithelial cell function.

Porcine epidemic diarrhea (PED) is a highly contagious, acute enteric tract infectious disease of pigs (Sus domesticus) caused by porcine epidemic diarrhea virus (PEDV). PED is characterized by watery diarrhea, dehydration, weight loss, vomiting and death. PEDV damages pig intestinal epithelial tissue, causing intestinal hyperemia and atrophy of intestinal villi, with formation of intestinal epithelial cell cytoplasmic vacuoles.

Infection, genetic and virulence characteristics of porcine epidemic diarrhea virus in northwest China.

From September 2015 to May 2016, epidemic outbreaks of a diarrheal disease caused severe economic losses to the swine industry in northwest China. Typical clinical symptoms of the disease included severe diarrhea, vomiting, dehydration and death. In order to identify the pathogen, 27 intestinal samples were collected from dead piglets in Shaanxi, Gansu and Qinghai provinces and from Ningxia Hui Autonomous Region.

The diosgenin prodrug nanoparticles with pH-responsive as a drug delivery system uniquely prevents thrombosis without increased bleeding risk.

Thrombosis is the leading cause of death in patients with cardiovascular disease in the world. Current antithrombotic agent aspirin has serious side effects such as higher bleeding risk and serious gastrointestinal ulcers. Diosgenin reported in clinical research could prevent thrombosis without side effects.

Xanthohumol isolated from Humulus lupulus prevents thrombosis without increased bleeding risk by inhibiting platelet activation and mtDNA release.

Aim: As the global population has reached 7 billion and the baby boom generation reaches old age, thrombosis has become the major contributor to the global disease burden. It has been reported that, in moderate doses, beer may protect against thrombosis. Xanthohumol (XN), an antioxidant, is found at high concentrations in hop cones (Humulus lupulus L.

Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release.

Thrombosis and its complications are the leading cause of death in patients with diabetes. Metformin, a first-line therapy for type 2 diabetes, is the only drug demonstrated to reduce cardiovascular complications in diabetic patients. However, whether metformin can effectively prevent thrombosis and its potential mechanism of action is unknown.

Preventive effect of a novel diosgenin derivative on arterial and venous thrombosis in vivo.

Current therapy for blood vessel thrombosis has the risk of leading to gastrointestinal bleeding and thrombocytopenia. We previously reported that a new derivative of diosgenin, compound 5, had significant anti-inflammatory activity superior to that of aspirin, prolonged bleeding time, and inhibited platelet aggregation in vitro. In the present study, we investigated the in vivo efficacy and safety of compound 5 using the ferric chloride (FeCl3)-induced arterial and venous thrombosis models in rats as well as its toxicity in mice.