Immunogenicity Risk Assessment of Process-Related Impurities in An Engineered T Cell Receptor Cellular Product.

Cell therapies such as genetically modified T cells have emerged as a promising and viable treatment for hematologic cancers and are being aggressively pursued for a wide range of diseases and conditions that were previously difficult to treat or had no cure. The process development requires genetic modifications to T cells to express a receptor (engineered T cell receptor (eTCR)) of specific binding qualities to the desired target. Protein reagents utilized during the cell therapy manufacturing process, to facilitate these genetic modifications, are often present as process-related impurities at residual levels in the final drug product and can represent a potential immunogenicity risk upon infusion.

Novel PTCH1 Mutation Causes Gorlin-Goltz Syndrome.

Objective: To analyse the aetiology and pathogenesis of Gorlin-Goltz syndrome (GS; also known as nevoid basal cell carcinoma syndrome [NBCCS] or basal cell nevus syndrome [BCNS]) in a Chinese family.

Methods: Whole-exome sequencing (WES) was performed on genomic DNA samples from the subjects in a family, followed by the investigation of pathogenesis via bioinformatic approaches and conformational analysis.

Results: A novel heterozygous non-frameshift deletion patched 1 (PTCH1) [NM_000264: c.

The efficacy of nursing interventions in preventing surgical site infections in patients undergoing surgery for congenital heart disease.

Surgical site infections (SSIs) pose significant risks to patients undergoing surgery for congenital heart disease (CHD), impacting recovery and increasing healthcare burdens. This study assesses the efficacy of targeted nursing interventions in reducing SSIs and enhancing wound healing in this vulnerable patient group. A prospective cohort study was conducted from January 2022 to August 2023 at a single institution, involving 120 paediatric patients divided into control (standard postoperative care) and observation (specialized nursing interventions) groups.

Polypropylene/Poly(butylene adipate-co-terephthalate) Breathing Film for Inhibiting and Maintaining Microbial Communities and Postharvest Quality of Regel during Storage.

Regel () is a healthy edible plant but highly perishable with a short shelf life of 1-2 d. Modified atmosphere packaging (MAP) could inhibit the postharvest senescence and decay of the vegetables. Thus, the aim of this study was to apply MAP with different gas permeabilities to the storage of and evaluate its effects on maintaining microbial communities and the postharvest quality of .

Biomass partitioning and ionomics of with high manganese and low phosphorus concentrations.

Knowledge of the ionome of plant organs helps us understand a plant's nutritional status. However, the ionome of Macadamia (Proteaceae), which is an important nut-producing tree, remains unknown. We aimed to characterise the allocation of biomass and nutrient-partitioning patterns in three macadamia genotypes.

Structural and functional dysbiosis of gut microbiota in Tibetan subjects with coronary heart disease.

The gut microbiota plays a crucial role in coronary heart disease (CHD). However, only a few studies focusing on the relationship between gut microbiota and CHD in ethnic populations are available. Here, we employed shotgun sequencing of the gut metagenome to analyze the taxonomic composition and functional annotation of the gut microbiota of 14 CHD patients, 13 patients with non-stenosis coronary heart disease (NCHD), and 18 healthy controls (HT) in Tibetan subjects.

Time and space catch up with restoration programs that ignore ecosystem service trade-offs.

In response to extreme societal consequences of ecosystem degradation and climate change, attention to ecological restoration is increasing globally. In China, investments in restoration exceeded USD 378.5 billion over the past decade.

Design, synthesis, biological evaluation and molecular dynamics studies of 4-thiazolinone derivatives as protein tyrosine phosphatase 1B (PTP1B) inhibitors.

Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin signaling pathway, and more and more studies have shown that it is a potential target for the treatment of type 2 diabetes mellitus (T2DM). In this study, 17 new 4-thiazolinone derivatives were designed and synthesized as novel PTP1B inhibitors, and ADMET prediction confirmed that these compounds were to be drug-like. enzyme activity experiments were performed on these compounds, and it was found that a plurality of compounds had good inhibitory activity and high selectivity against PTP1B protein.

Chinese Herbal Medicine Hepatotoxicity: The Evaluation and Recognization Based on Large-scale Evidence Database.

Background: Due to the special nature of Chinese Herbal medicine and the complexity of its clinical use, it is difficult to identify and evaluate its toxicity and resulting herb induced liver injury (HILI).

Methods: First, the database would provide full profile of HILI from the basic ingredients to clinical outcomes by the most advanced algorithms of artificial intelligence, and it is also possible that we can predict possibilities of HILI after patients taking Chinese herbs by individual patient evaluation and prediction. Second, the database would solve the chaos and lack of the relevant data faced by the current basic research and clinical practice of Chinese Herbal Medicine.

Exploring the Q-marker of "sweat soaking method" processed radix Wikstroemia indica: Based on the "effect-toxicity-chemicals" study.

Background: Radix Wikstroemia indica (RWI), named "Liao Ge Wang" in Chinese, is a kind of toxic Chinese herbal medicine (CHM) commonly used in Miao nationality of South China. "Sweat soaking method" processed RWI could effectively decrease its toxicity and preserve therapeutic effect. However, the underlying mechanism of processing is still not clear, and the Q-markers database for processed RWI has not been established.

Prediction of the Hydrogen Peroxide-Induced Methionine Oxidation Propensity in Monoclonal Antibodies.

Methionine oxidation in therapeutic antibodies can impact the product's stability, clinical efficacy, and safety and hence it is desirable to address the methionine oxidation liability during antibody discovery and development phase. Although the current experimental approaches can identify the oxidation-labile methionine residues, their application is limited mostly to the development phase. We demonstrate an in silico method that can be used to predict oxidation-labile residues based solely on the antibody sequence and structure information.

Coordination Mechanism and Bio-Evidence: Reactive γ-Ketoenal Intermediated Hepatotoxicity of Psoralen and Isopsoralen Based on Computer Approach and Bioassay.

Psoralen and isopsoralen are secondary plant metabolites found in many fruits, vegetables, and medicinal herbs. Psoralen-containing plants ( L.) have been reported to cause hepatotoxicity.

Rapid screening the potential mechanism-based inhibitors of CYP3A4 from Tripterygium wilfordi based on computer approaches combined with in vitro bioassay.

CYP3A4 is the main human metabolizing enzyme, and many clinically relevant drug/herb-drug interactions (DDIs/HDIs) involving CYP3A4 are due to mechanism-based inhibition. In this study, pharmacophore model together with molecular docking (MD) are used to rapidly screen the potential CYP3A4 mechanism-based inhibitors from Tripterygium wilfordii, and in vitro experiments are conducted to validate the computational data. The results showed that the rate of computational prediction could be improved based on a combination of pharmacophore model and MD, and a combination of computational approaches might be a useful tool to identify potential mechanism-based inhibitor of CYP3A4 from herbal medicines.

HIV testing and preventive services accessibility among men who have sex with men at high risk of HIV infection in Beijing, China.

The HIV epidemic among men who have sex with men (MSM) has been increasing at an alarming rate in most areas of China in recent years. Many Chinese MSM still lack sufficient access to HIV prevention services, despite ongoing scale-up of comprehensive HIV testing and intervention services. The purpose of this study was to investigate utilization of HIV testing and prevention services, and related factors that influence the MSM people to access HIV test or other services to prevent HIV among MSM in Beijing, China.

Structural analysis of diheme cytochrome c by hydrogen-deuterium exchange mass spectrometry and homology modeling.

A lack of X-ray or nuclear magnetic resonance structures of proteins inhibits their further study and characterization, motivating the development of new ways of analyzing structural information without crystal structures. The combination of hydrogen-deuterium exchange mass spectrometry (HDX-MS) data in conjunction with homology modeling can provide improved structure and mechanistic predictions. Here a unique diheme cytochrome c (DHCC) protein from Heliobacterium modesticaldum is studied with both HDX and homology modeling to bring some definition of the structure of the protein and its role.

Functional analysis and expression of the mono-heme containing cytochrome c subunit of Alternative Complex III in Chloroflexus aurantiacus.

The filamentous anoxygenic phototrophic bacterium Chloroflexus aurantiacus possesses an unusual electron transfer complex called Alternative Complex III instead of the cytochrome bc or bf type complex found in nearly all other known groups of phototrophs. Earlier work has confirmed that Alternative Complex III behaves as a menaquinol:auracyanin oxidoreductase in the photosynthetic electron transfer chain. In this work, we focus on elucidating the contribution of individual subunits to the overall function of Alternative Complex III.

Expression and characterization of the diheme cytochrome c subunit of the cytochrome bc complex in Heliobacterium modesticaldum.

Heliobacterium modesticaldum is a Gram-positive, anaerobic, anoxygenic photoheterotrophic bacterium. Its cytochrome bc complex (Rieske/cyt b complex) has some similarities to cytochrome b(6)f complexes from cyanobacteria and chloroplasts, and also shares some characteristics of typical bacterial cytochrome bc(1) complexes. One of the unique factors of the heliobacterial cytochrome bc complex is the presence of a diheme cytochrome c instead of the monoheme cytochrome f in the cytochrome b(6)f complex or the monoheme cytochrome c(1) in the bc(1) complex.

Hemodynamics model of fluid-solid interaction in internal carotid artery aneurysms.

The objective of this study is to present a relatively simple method to reconstruct cerebral aneurysms as 3D numerical grids. The method accurately duplicates the geometry to provide computer simulations of the blood flow. Initial images were obtained by using CT angiography and 3D digital subtraction angiography in DICOM format.

Energy metabolism of Heliobacterium modesticaldum during phototrophic and chemotrophic growth.

Background: Heliobacterium modesticaldum is a gram-positive nitrogen-fixing phototrophic bacterium that can grow either photoheterotrophically or chemotrophically but not photoautotrophically. Surprisingly, this organism is lacking only one gene for the complete reverse tricarboxylic acid (rTCA) cycle required for autotrophic carbon fixation. Along with the genomic information reported recently, we use multiple experimental approaches in this report to address questions regarding energy metabolic pathways in darkness, CO2 fixation, sugar assimilation and acetate metabolism.

3-Bromo-1-(3-chloro-pyridin-2-yl)-N-(4-eth-oxy-phen-yl)-1H-pyrazole-5-carbox-amide.

In the title compound, C(17)H(14)BrClN(4)O(2), the pyrazole ring is almost coplanar with the benzene ring [dihedral angle = 0.5 (2)°], whereas the pyrazole ring is close to perpendicular to the 3-chloro-pyridine ring [dihedral angle = 73.7 (2)°].

Trends in prevalence of HIV, syphilis, hepatitis C, hepatitis B, and sexual risk behavior among men who have sex with men. Results of 3 consecutive respondent-driven sampling surveys in Beijing, 2004 through 2006.

Background: Studies tracking trends in HIV prevalence and risk behavior among men who have sex with men (MSM) in China are rare. We report on 3 consecutive cross-sectional surveys measuring the prevalence of HIV, other infectious diseases, and related risk behavior among MSM in Beijing in 2004, 2005, and 2006.

Methods: We applied respondent-driven sampling (RDS) to recruit MSM for a structured face-to-face interview on demographic characteristics and HIV risk-related behavior.