Genomic Drivers of Coronary Artery Disease and Risk of Future Outcomes After Coronary Angiography.

Importance: Disease characteristics of genetically mediated coronary artery disease (CAD) on coronary angiography and the association of genomic risk with outcomes after coronary angiography are not well understood.

Objective: To assess the angiographic characteristics and risk of post-coronary angiography outcomes of patients with genomic drivers of CAD: familial hypercholesterolemia (FH), high polygenic risk score (PRS), and clonal hematopoiesis of indeterminate potential (CHIP).

Design, Setting, And Participants: A retrospective cohort study of 3518 Mass General Brigham Biobank participants with genomic information who underwent coronary angiography was conducted between July 18, 2000, and August 1, 2023.

Advances in physiological and clinical relevance of hiPSC-derived brain models for precision medicine pipelines.

Precision, or personalized, medicine aims to stratify patients based on variable pathogenic signatures to optimize the effectiveness of disease prevention and treatment. This approach is favorable in the context of brain disorders, which are often heterogeneous in their pathophysiological features, patterns of disease progression and treatment response, resulting in limited therapeutic standard-of-care. Here we highlight the transformative role that human induced pluripotent stem cell (hiPSC)-derived neural models are poised to play in advancing precision medicine for brain disorders, particularly emerging innovations that improve the relevance of hiPSC models to human physiology.

Exploring the antifungal potential of -derived stilbenoids and cannabinoids against novel targets through protein interaction profiling.

Cannabinoid and stilbenoid compounds derived from were screened against eight specific fungal protein targets to identify potential antifungal agents. The proteins investigated included Glycosylphosphatidylinositol (GPI), Enolase, Mannitol-2-dehydrogenase, GMP synthase, Dihydroorotate dehydrogenase (DHODH), Heat shock protein 90 homolog (Hsp90), Chitin Synthase 2 (CaChs2), and Mannitol-1-phosphate 5-dehydrogenase (M1P5DH), all of which play crucial roles in fungal survival and pathogenicity. This research evaluates the binding affinities and interaction profiles of selected cannabinoids and stilbenoids with these eight proteins using molecular docking and molecular dynamics simulations.

Phylogenetic signal in primate tooth enamel proteins and its relevance for paleoproteomics.

Ancient tooth enamel, and to some extent dentin and bone, contain characteristic peptides that persist for long periods of time. In particular, peptides from the enamel proteome (enamelome) have been used to reconstruct the phylogenetic relationships of fossil taxa. However, the enamelome is based on only about 10 genes, whose protein products undergo fragmentation in vivo and post mortem.

NTRC mediates the coupling of chloroplast redox rhythm with nuclear circadian clock in plant cells.

The intricate interplay between cellular circadian rhythms, primarily manifested in the chloroplast redox oscillations-characterized by diel hyperoxidation/reduction cycles of 2-Cys Peroxiredoxins-and the nuclear transcription/translation feedback loop (TTFL) machinery within plant cells, demonstrates a remarkable temporal coherence. However, the molecular mechanisms underlying the integration of these circadian rhythms remain elusive. Here, we elucidate that the chloroplast redox protein, NADPH-dependent thioredoxin reductase type-C (NTRC), modulates the integration of the chloroplast redox rhythms and nuclear circadian clocks by regulating intracellular levels of reactive oxygen species and sucrose.

Engineered CRISPR-Cas9 for Streptomyces sp. genome editing to improve specialized metabolite production.

The CRISPR-Cas9 system has frequently been used for genome editing in Streptomyces; however, cytotoxicity, caused by off-target cleavage, limits its application. In this study, we implement innovative modification to Cas9, strategically addressing challenges encountered during gene manipulation using Cas9 within strains possessing high GC content genome. The Cas9-BD, a modified Cas9 with the addition of polyaspartate to its N- and C-termini, is developed with decreased off-target binding and cytotoxicity compared with wild-type Cas9.

Construction and iterative redesign of synXVI a 903 kb synthetic Saccharomyces cerevisiae chromosome.

The Sc2.0 global consortium to design and construct a synthetic genome based on the Saccharomyces cerevisiae genome commenced in 2006, comprising 16 synthetic chromosomes and a new-to-nature tRNA neochromosome. In this paper we describe assembly and debugging of the 902,994-bp synthetic Saccharomyces cerevisiae chromosome synXVI of the Sc2.

Innovating chitosan-based bioinks for dermal wound healing: Current progress and future prospects.

The field of three-dimensional (3D) bio/printing, known as additive manufacturing (AM), heavily relies on bioinks possessing suitable mechanical properties and compatibility with living cells. Among the array of potential hydrogel precursor materials, chitosan (CS) has garnered significant attention due to its remarkable physicochemical and biological attributes. These attributes include biodegradability, nontoxicity, antimicrobial properties, wound healing promotion, and immune system activation, making CS a highly appealing hydrogel-based bioink candidate.

Three-dimensional genome architecture in intrahepatic cholangiocarcinoma.

Purpose: Intrahepatic cholangiocarcinoma (ICC) is a common primary hepatic tumors with a 5-year survival rate of less than 20%. Therefore, it is crucial to elucidate the molecular mechanisms of ICC. Recently, the advance of high-throughput chromosome conformation capture (Hi-C) technology help us look insight into the three-dimensional (3D) genome structure variation during tumorigenesis.

Glucocorticoids Alter Bone Microvascular Barrier via MAPK/Connexin43 Mechanisms.

Glucocorticoids (GCs) are standard-of-care treatments for inflammatory and immune disorders, and their long-term use increases the risk of osteoporosis. Although GCs decrease bone functionality, their role in bone microvasculature is incompletely understood. Herein, the study investigates the mechanisms of bone microvascular barrier function via osteoblast-endothelial interactions in response to GCs.

Systematic evaluation of intratumoral and peripheral BCR repertoires in three cancers.

The current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or may develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are believed to be significantly influenced by the tumor microenvironment through secretory factors and biased cell-cell interactions. To explore the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (draining LNs), and tumors in 14 patients with three human cancers.

Does coenzyme Q10 improve semen quality and circulating testosterone level? a systematic review and meta-analysis of randomized controlled trials.

Background: Seminal oxidative stress has been shown to be a key factor in the development of male infertility. However, the benefits of infertility treatments with antioxidants such as coenzyme Q10 (CoQ10) remains controversial.

Objectives: The aim of the present study was to assess the effects of CoQ10 supplementation on semen quality, i.

An overview of the use of non-titanium MXenes for photothermal therapy and their combinatorial approaches for cancer treatment.

Since the initial publication on the first TiCT MXene in 2011, there has been a significant increase in the number of reports on applications of MXenes in various domains. MXenes have emerged as highly promising materials for various biomedical applications, including photothermal therapy (PTT), drug delivery, diagnostic imaging, and biosensing, owing to their fascinating conductivity, mechanical strength, biocompatibility and hydrophilicity. Through surface modification, MXenes can mitigate cytotoxicity, enhance biological stability, and improve histocompatibility, thereby enabling their potential use in biomedical applications.

Exploring the therapeutic potential of acorn extract in papillomavirus-induced lesions.

Background And Aim: Papillomaviruses (PVs) infections have been documented in numerous animal species across different regions worldwide. They often exert significant impacts on animal health and livestock production. Scientists have studied natural products for over half a century due to their diverse chemical composition, acknowledging their value in fighting cancer.

Gold Nanoparticle-Modified Molecularly Imprinted Polymer-Coated Pencil Graphite Electrodes for Electrochemical Detection of Bisphenol A.

The sensitive Bisphenol A (BPA) detection by an electrochemical sensor based on gold nanoparticle-doped molecularly imprinted polymer was successfully improved. This study describes the development of a method for BPA detection in both aqueous solution and real water samples using N-methacroyl-(L)-cysteine methyl ester and N-methacryloyl-(L)-phenylalanine methyl ester coated pencil graphite electrodes modified with AuNPs by differential pulse voltammetry (DPV). Importantly, AuNPs, which increase the electroactivity, were used to increase the surface area of a BPA-imprinted pencil graphite electrode (MIP PGE) sensor.

PI5P4K inhibitors: promising opportunities and challenges.

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4K), also known as type II PIPKs or PIPKIIs, convert the lipid second messenger PI5P to PI(4,5)P. The PI5P4K family consists of three isozymes in mammals-PI5P4Kα, β, and γ-which notably utilize both GTP and ATP as phosphodonors. Unlike the other two isozymes, which can utilize both ATP and GTP, PI5P4Kβ exhibits a marked preference for GTP over ATP, acting as an intracellular GTP sensor that alters its kinase activity in response to physiological changes in GTP concentration.

Liquid Crystalline Networks Hamper the Malignancy of Cancer Cells.

Mimicking compositions and structures of extracellular matrix is widely studied to create in vitro tumor models, to deepen the understanding of the pathogenesis of the different types of cancer, and to identify new therapies. On the other hand, the use of synthetic materials to modulate cancer cell biology and, possibly, to reduce the malignancy of cancer cells through their exploitation is far less explored. Here, the study evaluates the effects of Liquid Crystalline Networks (LCNs) based scaffolds on the growth of A375 metastatic melanoma cells.

Biology-inspired dynamic microphysiological system approaches to revolutionize basic research, healthcare and animal welfare.

The regular workshops held by the Center for Alternatives to Animal Testing (CAAT) on biology-inspired microphysiological systems (MPS) taking place every four years, have become a reliable measure to assess fundamental scientific, industrial and regulatory trends for translational science in the MPS-field from a bird's eye view. The 2023 workshop participants at that time concluded that the technology as used within academia has matured significantly, underlined by the broad use of MPS and the steadily increasing number of high quality research publications - yet, broad industry adoption of MPS has been slow, despite strong interest. Academic research using MPS primarily aims to accurately recapitulate human biology in MPS-based organ models in areas where traditional models have been lacking key elements of human physiology, thereby enabling breakthrough discoveries for life sciences.

Longitudinal investigation of neurobiological changes across pregnancy.

Pregnancy is a period of profound biological transformation. However, we know remarkably little about pregnancy-related brain changes. To address this gap, we chart longitudinal changes in brain structure during pregnancy and explore potential mechanisms driving these changes.

Incomplete human reference genomes can drive false sex biases and expose patient-identifying information in metagenomic data.

As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples.

A Comprehensive Review on Exploring the Potential of Phytochemicals and Biogenic Nanoparticles for the Treatment of Antimicrobial-Resistant Pathogenic Bacteria.

Antimicrobial resistance (AMR) is an escalating global health concern that results in approximately 700,000 deaths annually owing to drug-resistant infections. It compromises the effectiveness of conventional antibiotics, as well as fundamental medical procedures, such as surgery and cancer treatment. Phytochemicals, natural plant constituents, and biogenic nanoparticles synthesized through biological processes are pharmacological alternatives for supplementing or replacing traditional antibiotics.

A multi-stage weakly supervised design for spheroid segmentation to explore mesenchymal stem cell differentiation dynamics.

Unlabelled: There is a growing interest in utilizing 3D culture models for stem cell and cancer cell research due to their closer resemblance to in vivo environments. In this study, human mesenchymal stem cells (MSCs) were cultured using adipocytes and osteocytes as differentiative mediums on varying concentrations of chitosan substrate. Light microscopy was employed to capture cell images from the first day to the 21st day of differentiation.

Challenges and opportunities for digital twins in precision medicine from a complex systems perspective.

Digital twins (DTs) in precision medicine are increasingly viable, propelled by extensive data collection and advancements in artificial intelligence (AI), alongside traditional biomedical methodologies. We argue that including mechanistic simulations that produce behavior based on explicitly defined biological hypotheses and multiscale mechanisms is beneficial. It enables the exploration of diverse therapeutic strategies and supports dynamic clinical decision-making through insights from network science, quantitative biology, and digital medicine.