Chaperone/Polymer Complexation of Protein-Based Fluorescent Nanoclusters against Silica Encapsulation-Induced Physicochemical Stresses.

Silica encapsulation under ambient conditions is commonly used to shield protein-based nanosystems from chemical stress. However, encapsulation-induced photo- and structural instabilities at elevated temperatures have been overlooked. Using bovine serum albumin-capped fluorescent gold nanoclusters (BSA-AuNCs) as a model, we demonstrated that chaperone/polymer layer-by-layer complexation can stabilize the template to resist encapsulation-induced fragmentation/reorganization and emission increases at 37 °C or higher temperatures.

Effect of human H3N2 influenza virus reassortment on influenza incidence and severity during the 2017-18 influenza season in the USA: a retrospective observational genomic analysis.

Background: During the 2017-18 influenza season in the USA, there was a high incidence of influenza illness and mortality. However, no apparent antigenic change was identified in the dominant H3N2 viruses, and the severity of the season could not be solely attributed to a vaccine mismatch. We aimed to investigate whether the altered virus properties resulting from gene reassortment were underlying causes of the increased case number and disease severity associated with the 2017-18 influenza season.

Preclinical evaluation of the SARS-CoV-2 M inhibitor RAY1216 shows improved pharmacokinetics compared with nirmatrelvir.

Although vaccines are available for SARS-CoV-2, antiviral drugs such as nirmatrelvir are still needed, particularly for individuals in whom vaccines are less effective, such as the immunocompromised, to prevent severe COVID-19. Here we report an α-ketoamide-based peptidomimetic inhibitor of the SARS-CoV-2 main protease (M), designated RAY1216. Enzyme inhibition kinetic analysis shows that RAY1216 has an inhibition constant of 8.

Inhibition of Endoplasmic Reticulum Stress Improves Chronic Ischemic Hippocampal Damage Associated with Suppression of IRE1α/TRAF2/ASK1/JNK-Dependent Apoptosis.

Chronic cerebral ischemia is a complex form of stress, of which the most common hemodynamic characteristic is chronic cerebral hypoperfusion (CCH). Lasting endoplasmic reticulum (ER) stress can drive neurological disorders. Targeting ER stress shows potential neuroprotective effects against stroke.

Safety Assessment and Probiotic Potential Comparison of subsp. BLI-02, LPL28, TYCA06, and ET-66.

subsp. BLI-02, ET-66, LPL28, and TYCA06, isolated from healthy breast milk, miso, and the healthy human gut, were assessed for safety in this study. BLI-02, LPL28, TYCA06, and ET-66 exhibited no antibiotic resistance and mutagenic activity in the Ames test at the highest dosage (5000 μg/plate).

High-performance peptide and disulfide mapping by direct injection of intact proteins using on-line coupled UV-liquid chromatography microdroplet mass spectrometry (UVLC-MMS).

Microdroplet mass spectrometry (MMS), achieving ultra-fast enzyme digestion in the ionization source, holds great promises for innovating protein analysis. Here, in-depth protein characterization is demonstrated by direct injection of intact protein mixtures via on-line coupling MMS with capillary C4 liquid chromatography (LC) containing UV windows (UVLC-MMS) through an enzyme introduction tee. We showed complete sets of peptides of individual proteins (hemoglobin, bovine serum albumin, and ribonuclease A) in a mixture could be obtained in one injection.

Bacoside a inhibits the growth of glioma by promoting apoptosis and autophagy in U251 and U87 cells.

Bacoside A (gypenoside, Gyp) is a potent bioactive compound derived from Gynostemma pentaphyllum, known to exert inhibitory effects on various malignant tumors. However, the effects of Gyp on glioma as well as the underlying mechanisms remain unclear. In the present study, we first conducted a comprehensive investigation into the anti-glioma potential of gypenosides using network pharmacology to identify potential glioma-related targets.

Instability Challenges and Stabilization Strategies of Pharmaceutical Proteins.

Maintaining the structure of protein and peptide drugs has become one of the most important goals of scientists in recent decades. Cold and thermal denaturation conditions, lyophilization and freeze drying, different pH conditions, concentrations, ionic strength, environmental agitation, the interaction between the surface of liquid and air as well as liquid and solid, and even the architectural structure of storage containers are among the factors that affect the stability of these therapeutic biomacromolecules. The use of genetic engineering, side-directed mutagenesis, fusion strategies, solvent engineering, the addition of various preservatives, surfactants, and additives are some of the solutions to overcome these problems.

Scientific opportunities in resilience research for cardiovascular health and wellness. Report from a National Heart, Lung, and Blood Institute workshop.

Exposure of biological systems to acute or chronic insults triggers a host of molecular and physiological responses to either tolerate, adapt, or fully restore homeostasis; these responses constitute the hallmarks of resilience. Given the many facets, dimensions, and discipline-specific focus, gaining a shared understanding of "resilience" has been identified as a priority for supporting advances in cardiovascular health. This report is based on the working definition: "Resilience is the ability of living systems to successfully maintain or return to homeostasis in response to physical, molecular, individual, social, societal, or environmental stressors or challenges," developed after considering many factors contributing to cardiovascular resilience through deliberations of multidisciplinary experts convened by the National Heart, Lung, and Blood Institute during a workshop entitled: "Enhancing Resilience for Cardiovascular Health and Wellness.

Label-free and de-conjugation-free workflow to simultaneously quantify trace amount of free/conjugated and protein-bound estrogen metabolites in human serum.

Different chemical forms of sex hormones including free/conjugated metabolites as well as their protein/DNA adducts in human serum are a panel of important indicators of health conditions. It is, however, hard to quantify all species simultaneously due to the lack of general extraction, derivatization, and de-conjugation methods. Here we developed a label-free and de-conjugation-free workflow to quantify 11 free/conjugated estrogen metabolites including depurinating DNA and protein adduct forms of 4-hydroxyestradiol (4OHE2) in human serum.

A review on biofilms and the currently available antibiofilm approaches: Matrix-destabilizing hydrolases and anti-bacterial peptides as promising candidates for the food industries.

Biofilms are communities of microorganisms that can be harmful and/or beneficial, depending on location and cell content. Since in most cases (such as the formation of biofilms in laboratory/medicinal equipment, water pipes, high humidity-placed structures, and the food packaging machinery) these bacterial and fungal communities are troublesome, researchers in various fields are trying to find a promising strategy to destroy or slow down their formation. In general, anti-biofilm strategies are divided into the plant-based and non-plant categories, with the latter including nanoparticles, bacteriophages, enzymes, surfactants, active peptides and free fatty acids.

Mechanisms behind the Fibrillation and Toxicity of Insulin Fibrils on Neuron Cells by Engineered Curcumin Analogs.

Among foods, the use of plant derivatives as promising drugs and/or excipients has been considered from various perspectives. In the present study, curcumin, which is one of the most important plant derivatives for biological uses, and four curcumin-based pyrido[2,3-]pyrimidine analogs (C2-C5) were used for investigating the mechanism of insulin fibrillation and evaluating the cytotoxicity of insulin fibrils. The synthesized analogs differed in terms of hydrophobicity and electrostatic charge.

Critical Test Result Recall Supporting System (CTR RSS) Improves Follow-Up among Patients in the Community.

Follow-up care of patients in the community is an important topic for improving patient outcomes, especially when medical personnel receives a notification of the critical test result (CTR) when the CTR becomes available after patients have been out of hospital; how to recall the patient back to the hospital and follow-up treatment is essential for preventing the healthcare risk of neglecting or delayed intervention with respect to the patient’s CTR. We are concerned that the follow-up of CTR and timely recall of our patients in the community improves and facilitates patient safety. We built the CTR Recall Supporting System (RSS) to follow up and recall our patients in the community.

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution.

Microsatellite Instability, Epstein-Barr Virus, and Programmed Cell Death Ligand 1 as Predictive Markers for Immunotherapy in Gastric Cancer.

Immunotherapy benefits selected cases of gastric cancer (GC), but the correlation between biomarkers and prognosis is still unclear. Fifty-two patients with GC who underwent immunotherapy were enrolled from June 2016 to December 2020. Their clinical features and biomarkers-microsatellite instability-high (MSI-H), programmed cell death ligand 1 (PD-L1) combined positive score (CPS), and Epstein-Barr encoding region (EBER)-were analyzed.

Selective and predicable amine conjugation sites by kinetic characterization under excess reagents.

The site selectivity for lysine conjugation on a native protein is difficult to control and characterize. Here, we applied mass spectrometry to examine the conjugation kinetics of Trastuzumab-IgG (Her-IgG) and α-lactalbumin under excess linker concentration ([L]) based on the modified Michaelis-Menten equation, in which the initial rate constant per amine (k = V/K) was determined by the maximum reaction rate (V) under saturated accessible sites and initial amine-linker affinity (1/K). Reductive amination (RA) displayed 3-4 times greater V and a different panel of conjugation sites than that observed for N-hydroxysuccinimide ester (NHS) chemistry using the same length of polyethylene glycol (PEG) linkers.

Microdroplet mass spectrometry: Accelerating reaction and application.

Electrospray ionization (ESI) and desorption electrospray ionization (DESI) are common soft ionization method of mass spectrometry (MS). However, recent studies revealed that some chemical reactions can be induced or greatly accelerated in the sprayed microdroplets compared to the same reaction in the bulk. These open a new area in using microdroplet MS to explore new chemistry and develop new applications.

Quantification of the Endogenous Adduction Level on Hemoglobin and Correlation with Albumin Adduction Proteomics: Multiple Exposure Markers of Catechol Estrogen.

Catechol estrogens (CEs) are genotoxic metabolites whose detection is challenging due to their low concentrations and high variability in the blood. By intact protein and free CE measurement of the spiked hemolysate, endogenous CEs were revealed to mainly (>99%) exist as hemoglobin (Hb) adducts in red blood cells. In order to detect endogenous CE-Hb adducts, we developed a two-step method that involved protein precipitation and solid phase extraction to purify Hb from red blood cells, and the method was coupled with proteomics using liquid chromatography-tandem mass spectrometry.

Expression, methylation and prognostic feature of EMILIN2 in Low-Grade-Glioma.

Low-grade gliomas (LGGs) are slow-growing brain cancer in central nervous system neoplasms. EMILIN2 is an extracellular matrix (ECM) protein which could influence the progress of some tumour which is unclear in LGG. In our study, the methylation, expression, prognosis and immune value of EMILIN2 in LGG were analysed through bioinformatics analysis.

Design, synthesis, and biological evaluation of novel dual inhibitors targeting lysine specific demethylase 1 (LSD1) and histone deacetylases (HDAC) for treatment of gastric cancer.

LSD1 and HDAC are physical and functional related to each other in various human cancers and simultaneous pharmacological inhibition of LSD1 and HDAC exerts synergistic anti-cancer effects. In this work, a series of novel LSD1/HDAC bifunctional inhibitors with a styrylpyridine skeleton were designed and synthesized based on our previously reported LSD1 inhibitors. The representative compounds 5d and 5m showed potent activity against LSD1 and HDAC at both molecular and cellular level and displayed high selectivity against MAO-A/B.