Bivalent Omicron BA.1 vaccine booster increases memory B cell breadth and neutralising antibodies against emerging SARS-CoV-2 variants.

Background: Current literature informs us that bivalent vaccines will generate a broader serum neutralizing antibody response to multiple SARS-CoV-2 variants, but studies on how this breadth relates to the memory B cell (MBC) and T cell responses are sparse. This study compared breadth of neutralising antibody, and memory B and T cell responses to monovalent or a bivalent ancestral/Omicron BA.1 COVID-19 booster vaccine.

Evaluate the Role of Phosphodiesterase, Myeloperoxidase and Iron in Oral Cancer.

Objective: The present study aimed to estimate the levels of phosphodiesterase (PDE), myeloperoxidase (MPO) and iron levels in patients with oral cancer.

Method: 50 patients reporting to the Department of Oral Medicine and Radiology A.B.

Rapidly Progressing and Early-Onset Forms of Amyotrophic Lateral Sclerosis Caused by a Novel Variant in a Lithuanian Family.

Objectives: To describe a novel familial variant of superoxide dismutase 1 (SOD1)-associated amyotrophic lateral sclerosis (ALS) in a Lithuanian family, highlighting its variable progression and implications for treatment inclusion criteria.

Methods: This study presents the clinical and genetic findings of a family with the novel variant, including one member diagnosed with early-onset ALS (onset <40 years) and one with a particularly rapidly progressing course of ALS.

Results: The variant NM_000454.

Resveratrol enhances the tolerance of to potassium deficiency stress.

Potassium (K) deficiency in plants can lead to metabolic disorders and growth retardation. Currently, nearly 50% of the arable land in China is experiencing a K resource deficit, significantly hindering the development of the apple industry. Resveratrol (Res), a phytoalexin, has been extensively reported to enhance plant resistance against various abiotic stresses.

CRISPR-Cas9-mediated genome editing delivered by a single AAV9 vector inhibits HSV-1 reactivation in a latent rabbit keratitis model.

Herpes simples virus 1 (HSV-1) keratitis is a major cause of blindness globally. During primary infection, HSV-1 travels to the trigeminal ganglia and establishes lifelong latency. Although some treatments can reduce symptom severity and recurrence, there is no cure for HSV-1 keratitis.

Proteolethargy is a pathogenic mechanism in chronic disease.

The pathogenic mechanisms of many diseases are well understood at the molecular level, but there are prevalent syndromes associated with pathogenic signaling, such as diabetes and chronic inflammation, where our understanding is more limited. Here, we report that pathogenic signaling suppresses the mobility of a spectrum of proteins that play essential roles in cellular functions known to be dysregulated in these chronic diseases. The reduced protein mobility, which we call proteolethargy, was linked to cysteine residues in the affected proteins and signaling-related increases in excess reactive oxygen species.

Energy metabolism in osteoprogenitors and osteoblasts: Role of the pentose phosphate pathway.

Bioenergetic preferences of osteolineage cells, including osteoprogenitors and osteoblasts (OBs), are a matter of intense debate. Early studies pointed to OB reliance on glucose and aerobic glycolysis while more recent works indicated the importance of glutamine as a mitochondrial fuel. Aiming to clarify this issue, we performed metabolic tracing of C-labeled glucose and glutamine in human osteolineage cells: bone marrow stromal (a.

Design and functional studies of xylene-based cyclic mimetics of SOCS1 protein.

Peptidomimetics of Suppressors of cytokine signaling 1 (SOCS1) protein demonstrated valid therapeutic potentials as anti-inflammatory agents. Indeed, SOCS1 has a small kinase inhibitory region (KIR) primarily involved in the inhibition of the JAnus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway Herein, on the basis of previous investigations on a potent mimetic of KIR-SOCS1, named PS5, we designed and evaluated the SAR (Structure Activity Relationship) features of two xylene-based macrocycles analogues of PS5. These novel compounds bear thiol-xylene linkages with mono- and bi-cyclic scaffolds: they were in vitro functionally investigated toward JAK2 catalytic domain, as ligands with microscale thermophoresis (MST) and as inhibitors through LC-MS analyses.

A high-efficiency and long-cycling aqueous indium metal battery enabled by synergistic In/K interactions.

Aqueous trivalent metal batteries are promising options for energy storage, owing to their ability to transfer three electrons during redox reactions. However, advances in this field have been limited by challenges such as incompatible M/M electrode potentials and salt hydrolysis. Herein, we identify the trivalent indium metal as a viable candidate and demonstrate a high-performance indium-Prussian blue hybrid battery using a K/In mixture electrolyte.

A Covalent Chemical Probe for nsP2 Cysteine Protease with Antialphaviral Activity and Proteome-wide Selectivity.

RA-0003022 () was identified as a high-quality covalent chemical probe for nsP2 cysteine protease (nsP2pro). Isoxazole covalently captured the active site C478 and inactivated the enzyme with a / ratio of 6000 Ms. A negative control analog RA-0025453 () retained the covalent warhead but demonstrated >100-fold decrease in enzyme inhibition.

The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the Clinical Validity of 111 Gene-Disease Relationships.

Purpose: The Clinical Genome Resource (ClinGen) Gene Curation Expert Panels (GCEPs) have historically focused on specific organ systems or phenotypes; thus, the ClinGen Syndromic Disorders GCEP (SD-GCEP) was formed to address an unmet need.

Methods: The SD-GCEP applied ClinGen's framework to evaluate the clinical validity of genes associated with rare syndromic disorders. 111 Gene-Disease Relationships (GDRs) associated with 100 genes spanning the clinical spectrum of syndromic disorders were curated.

Accurate design of high-affinity protein binding macrocycles using deep learning.

The development of macrocyclic binders to therapeutic proteins typically relies on large-scale screening methods that are resource-intensive and provide little control over binding mode. Despite considerable progress in physics-based methods for peptide design and deep-learning methods for protein design, there are currently no robust approaches for design of protein-binding macrocycles. Here, we introduce RFpeptides, a denoising diffusion-based pipeline for designing macrocyclic peptide binders against protein targets of interest.

Genotype-immunophenotype relationships in -mutant AML clonal evolution uncovered by single cell multiomic analysis.

Acute myeloid leukemia (AML) is a multi-clonal disease, existing as a milieu of clones with unique but related genotypes as initiating clones acquire subsequent mutations. However, bulk sequencing cannot fully capture AML clonal architecture or the clonal evolution that occurs as patients undergo therapy. To interrogate clonal evolution, we performed simultaneous single cell molecular profiling and immunophenotyping on 43 samples from 32 -mutant AML patients at different stages of disease.

Modi-2 a vaccine stimulating CD4 responses to homocitrullinated self epitopes as therapy for solid cancers.

Stresses within the tumour microenvironment can mediate post-translational modifications of self-proteins. Homocitrullination is the conversion of lysine to homocitrulline which generates neoepitopes and bypasses self-tolerance. In this study a vaccine targeting homocitrullinated antigens was assessed for stimulation of anti-tumour immunity.

Phenotypic findings associated with variation in elastin.

Variation in the elastin gene (ELN) may contribute to connective tissue disease beyond the known disease associations of supravalvar aortic stenosis and cutis laxa. Exome data from MyCode Community Health Initiative participants were analyzed for ELN rare variants (mean allele frequency <1%, not currently annotated as benign). Participants with variants of interest underwent phenotyping by dual chart review using a standardized abstraction tool.

Personalized Medicine: Leave no Patient Behind; Report From the 2024 Coffey-Holden Prostate Cancer Academy Meeting.

Introduction: The 11th Annual 2024 Coffey - Holden Prostate Cancer Academy (CHPCA) Meeting, was themed "Personalized Medicine: Leave No Patient Behind," and was held from June 20 to 23, 2024 at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA.

Methods: The CHPCA Meeting is an academy-styled annual conference organized by the Prostate Cancer Foundation, to focus discussion on the most critical emerging research that have the greatest potential to advance knowledge of prostate cancer biology and treatment. The 2024 CHPCA Meeting was attended by 75 academic investigators and included 37 talks across 8 sessions.

Wellness Influencer Responses to COVID-19 Vaccines on Social Media: A Longitudinal Observational Study.

Background: Online wellness influencers (individuals dispensing unregulated health and wellness advice over social media) may have incentives to oppose traditional medical authorities. Their messaging may decrease the overall effectiveness of public health campaigns during global health crises like the COVID-19 pandemic.

Objective: This study aimed to probe how wellness influencers respond to a public health campaign; we examined how a sample of wellness influencers on Twitter (rebranded as X in 2023) identified before the COVID-19 pandemic on Twitter took stances on the COVID-19 vaccine during 2020-2022.

Design requirements of a spectropolarimeter for solar extreme-ultraviolet observations and characterization of a K-mirror based on Brewster's angle.

Measuring the linear polarization signal in extreme-ultraviolet (EUV) spectral lines, produced by the Hanle effect, offers a promising technique for studying magnetic fields in the solar corona. The required signal-to-noise ratio for detecting the Hanle polarization signals is on the order of 10 (off-limb) to 10 (disk center). Measuring such low signals in the photon starved observations demands highly efficient instruments.

Therapeutic Monoclonal Antibody─Antidrug Antibody Affinity Constant Determination Using Capillary Electrophoresis-Tandem Mass Spectrometry.

Monoclonal antibody (mAbs) therapeutics cannot evade the occurrence of adverse effects. Thus, mAbs are commonly triggering immune responses corresponding to the expression of antidrug antibodies. Antidrug antibodies can neutralize mAbs, leading to their inhibition and hasten clearance, which dramatically hampers their therapeutic effects.