The impact of Benzophenone-3 on osteoarthritis pathogenesis: a network toxicology approach.

Background: Arthritis is a degenerative joint disease influenced by various environmental factors, including exposure to Benzophenone-3 (BP3), a common UV filter. This study aims to elucidate the toxicological impact of BP3 on arthritis pathogenesis using network toxicology approaches.

Method: We integrated data from the Comparative Toxicogenomics Database (CTD) and Gene Expression Omnibus (GEO) to identify differentially expressed BP3-related toxicological targets in osteoarthritis (OA).

Diagnostic Power of Serum Creatinine/Cystatin C Ratio for Identifying Low MRI-Muscle Volume and Low Grip Strength: Data From 9 731 to 149 707 UK Biobank Older Adults.

Background: Biomarkers for sarcopenia are lacking. We examined the diagnostic power of serum creatinine to cystatin C ratio for identifying low magnetic resonance imaging-muscle volume and low grip strength in a large observational study of UK Biobank older adults.

Methods: Serum creatinine and cystatin C were measured via immunoassays (Beckman Coulter AU5800 and Siemens Advia 1800, respectively) and grip strength by hydraulic hand dynamometer at baseline visit (2008-2010).

Comparative long-term outcomes of unicompartmental and total knee arthroplasty in knee osteoarthritis patients: a systematic review and meta-analysis.

Background: Long-term outcomes for knee osteoarthritis patients undergoing unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) remain inconclusive.

Objectives: This study aims to evaluate the long-term outcomes over five years, including Knee Society Pain Scores (KSPS), Knee Society Scores (KSS), Knee Society Function Scores (KSFS), range of motion (ROM), and survival rates-of UKA vs. TKA in knee osteoarthritis patients.

A proteomic signature of healthspan.

The focus of aging research has shifted from increasing lifespan to enhancing healthspan to reduce the time spent living with disability. Despite significant efforts to develop biomarkers of aging, few studies have focused on biomarkers of healthspan. We developed a proteomics-based signature of healthspan (healthspan proteomic score (HPS)) using data from the UK Biobank Pharma Proteomics Project (53,018 individuals and 2920 proteins).

Comparative Analysis and Regeneration Strategies for Three Types of Cartilage.

Cartilage tissue, encompassing hyaline cartilage, fibrocartilage, and elastic cartilage, plays a pivotal role in the human body because of its unique composition, structure, and biomechanical properties. However, the inherent avascularity and limited regenerative capacity of cartilage present significant challenges to its healing following injury. This review provides a comprehensive analysis of the current state of cartilage tissue engineering, focusing on the critical components of cell sources, scaffolds, and growth factors tailored to the regeneration of each cartilage type.

Proteomic aging clock (PAC) predicts age-related outcomes in middle-aged and older adults.

Beyond mere prognostication, optimal biomarkers of aging provide insights into qualitative and quantitative features of biological aging and might, therefore, offer useful information for the testing and, ultimately, clinical use of gerotherapeutics. We aimed to develop a proteomic aging clock (PAC) for all-cause mortality risk as a proxy of biological age. Data were from the UK Biobank Pharma Proteomics Project, including 53,021 participants aged between 39 and 70 years and 2923 plasma proteins assessed using the Olink Explore 3072 assay®.

MiR-98-5p plays suppressive effects on IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting CASP3.

Background: This study aims to explore how miR-98-5p affects osteoarthritis, focusing on its role in chondrocyte inflammation, apoptosis, and extracellular matrix (ECM) degradation.

Methods: Quantitative real-time PCR was used to measure miR-98-5p and CASP3 mRNA levels in OA cartilage tissues and IL-1β-treated CHON-001 cells. We predicted miR-98-5p and CASP3 binding sites using TargetScan and confirmed them via luciferase reporter assays.

Leukocyte telomere length is associated with MRI-thigh fat-free muscle volume: data from 16 356 UK Biobank adults.

Background: Telomere attrition may share common biological mechanisms with bone and muscle loss with aging. Here, we investigated the association between these hallmarks of aging using data from UK Biobank, a large observational study.

Methods: Leukocyte telomere length (LTL as T/S ratio) was measured using a multiplex qPCR assay at baseline (2006-2010).

Are the tests overpowered or underpowered? A unified solution to correctly specify type I errors in design of clinical trials for two sample proportions.

As one of the most commonly used data types, methods in testing or designing a trial for binary endpoints from two independent populations are still being developed until recently. However, the power and the minimum required sample size comparisons between different tests may not be valid if their type I errors are not controlled at the same level. In this article, we unify all related testing procedures into a decision framework, including both frequentist and Bayesian methods.

Proteomic aging clock (PAC) predicts age-related outcomes in middle-aged and older adults.

Beyond mere prognostication, optimal biomarkers of aging provide insights into qualitative and quantitative features of biological aging and might, therefore, offer useful information for the testing and, ultimately, clinical use of gerotherapeutics. We aimed to develop a proteomic aging clock (PAC) for all-cause mortality risk as a proxy of biological age. Data were from the UK Biobank Pharma Proteomics Project, including 53,021 participants aged between 39 and 70 years and 2,923 plasma proteins assessed using the Olink Explore 3072 assay.

A comprehensive strategy for the identification of biologics by liquid-chromatography-mass spectrometry for release testing in a regulated environment.

Identification (ID) testing is a regulatory requirement for biopharmaceutical manufacturing, requiring robust, GMP-qualified assays that can distinguish the therapeutic from any other in the facility. Liquid Chromatography-Mass Spectrometry (LC-MS) is a powerful analytical tool used to identify and characterize biologics. While routinely leveraged for characterization, LC-MS is relatively rare in Quality Control (QC) settings due to its perceived complexity and scarcity of MS-trained personnel.

Long-term probabilistic temperature projections for all locations.

The climate change projections of the Intergovernmental Panel on Climate Change are based on scenarios for future emissions, but these are not statistically-based and do not have a full probabilistic interpretation. Raftery et al. (Nat Clim Change 7:637-641, 2017) and Liu and Raftery (Commun Earth Environ 2:1-10, 2021) developed probabilistic forecasts for global average temperature change to 2100, but these do not give forecasts for specific parts of the globe.

Probabilistic Estimation and Projection of the Annual Total Fertility Rate Accounting for Past Uncertainty: A Major Update of the bayesTFR R Package.

The package for R provides a set of functions to produce probabilistic projections of the total fertility rates (TFR) for all countries, and is widely used, including as part of the basis for the UN's official population projections for all countries. Liu and Raftery (2020) extended the theoretical model by adding a layer that accounts for the past TFR estimation uncertainty. A major update of implements the new extension.

Attribute Analytics Performance Metrics from the MAM Consortium Interlaboratory Study.

The multi-attribute method (MAM) was conceived as a single assay to potentially replace multiple single-attribute assays that have long been used in process development and quality control (QC) for protein therapeutics. MAM is rooted in traditional peptide mapping methods; it leverages mass spectrometry (MS) detection for confident identification and quantitation of many types of protein attributes that may be targeted for monitoring. While MAM has been widely explored across the industry, it has yet to gain a strong foothold within QC laboratories as a replacement method for established orthogonal platforms.

Country-based rate of emissions reductions should increase by 80% beyond nationally determined contributions to meet the 2 °C target.

The 2015 Paris Agreement aims to keep global warming by 2100 to below 2°C, with 1.5°C as a target. To that end, countries agreed to reduce their emissions by nationally determined contributions (NDCs).

ACCOUNTING FOR UNCERTAINTY ABOUT PAST VALUES IN PROBABILISTIC PROJECTIONS OF THE TOTAL FERTILITY RATE FOR MOST COUNTRIES.

Since the 1940s, population projections have in most cases been produced using the deterministic cohort component method. However, in 2015, for the first time, in a major advance, the United Nations issued official probabilistic population projections for all countries based on Bayesian hierarchical models for total fertility and life expectancy. The estimates of these models and the resulting projections are conditional on the UN's official estimates of past values.

New Peak Detection Performance Metrics from the MAM Consortium Interlaboratory Study.

The Multi-Attribute Method (MAM) Consortium was initially formed as a venue to harmonize best practices, share experiences, and generate innovative methodologies to facilitate widespread integration of the MAM platform, which is an emerging ultra-high-performance liquid chromatography-mass spectrometry application. Successful implementation of MAM as a purity-indicating assay requires new peak detection (NPD) of potential process- and/or product-related impurities. The NPD interlaboratory study described herein was carried out by the MAM Consortium to report on the industry-wide performance of NPD using predigested samples of the NISTmAb Reference Material 8671.

On-column disulfide bond formation of monoclonal antibodies during Protein A chromatography eliminates low molecular weight species and rescues reduced antibodies.

Disulfide bond reduction, which commonly occurs during monoclonal antibody (mAb) manufacturing processes, can result in a drug substance with high levels of low molecular weight (LMW) species that may fail release specifications because the drug's safety and the efficiency may be affected by the presence of this material. We previously studied disulfide reoxidation of mAbs and demonstrated that disulfide bonds could be reformed from the reduced antibody via redox reactions under an optimal redox condition on Protein A resin. The study here implements a redox system in a manufacturing setting to rescue the reduced mAb product and to further eliminate LMW issues in downstream processing.

Subunit mass analysis for monitoring multiple attributes of monoclonal antibodies.

Rationale: Multi-Attribute Methods (MAMs) are appealing due to their ability to provide data on multiple molecular attributes from a single assay. If fully realized, such tests could reduce the number of assays required to support a product control strategy while providing equivalent or greater product understanding relative to the conventional approach. In doing so, MAMs have the potential to decrease development and manufacturing costs by reducing the number of tests in a release panel.

Study of Guanxinning Injection on Regulatory Mechanism of Bcl-2 and Bax by Liquid Nitrogen Freezing-Mediated Femoral Head Necrosis.

The objective of this study was to investigate the impact of femoral head perfusion by traditional Chinese medicine Guanxinning injection promoting blood circulation for removing blood stasis on the expression of Bcl-2 and Bax induced by liquid nitrogen freezing-mediated femoral head necrosis. 90 rabbits were randomized into three groups. Normal control group was not subjected to any medication.

Less Than 2 °C Warming by 2100 Unlikely.

The recently published Intergovernmental Panel on Climate Change (IPCC) projections to 2100 give likely ranges of global temperature increase in four scenarios for population, economic growth and carbon use. However these projections are not based on a fully statistical approach. Here we use a country-specific version of Kaya's identity to develop a statistically-based probabilistic forecast of CO2 emissions and temperature change to 2100.

Characterization of mutants of a tyrosine ammonia-lyase from Rhodotorula glutinis.

In the phenylpropanoid production process, p-coumaric acid is the most important intermediate metabolite. It is generally accepted that the activity of tyrosine ammonia-lyase (TAL), which converts L-tyrosine to p-coumaric acid, represents the rate-limiting step. Therefore, an error-prone PCR-based random mutagenesis strategy was utilized for screening variants with higher catalytic activity.

Identification and application of keto acids transporters in Yarrowia lipolytica.

Production of organic acids by microorganisms is of great importance for obtaining building-block chemicals from sustainable biomass. Extracellular accumulation of organic acids involved a series of transporters, which play important roles in the accumulation of specific organic acid while lack of systematic demonstration in eukaryotic microorganisms. To circumvent accumulation of by-product, efforts have being orchestrated to carboxylate transport mechanism for potential clue in Yarrowia lipolytica WSH-Z06.

Identification of membrane proteins associated with phenylpropanoid tolerance and transport in Escherichia coli BL21.

Unlabelled: Phenylpropanoids are phytochemicals produced by some plants and possess a wide variety of biological activities. These compounds exist in plants in low amounts. Production of them in genetically engineered microorganisms has many advantages.