Qualitative Transcriptional Signature for Predicting the Pathological Response of Colorectal Cancer to FOLFIRI Therapy.

FOLFIRI (5-FU, leucovorin, irinotecan) is the first-line chemotherapy for metastatic colorectal cancer (mCRC), but response rates are under 50%. This study aimed to develop a predictive signature for FOLFIRI response in mCRC patients. Firstly, Spearman's rank correlation and Wilcoxon rank-sum test were used to select chemotherapy response genes and gene pairs, respectively.

High Prevalence of 5'UTR Mutations in Anaplastic Thyroid Cancer.

Anaplastic thyroid cancer (ATC) is a rare but one of the most lethal types of human cancer. Although increasing evidence demonstrated that ATC tumors had a high mutation burden, little is known about the aberrancy of the noncoding genome of ATC except the well-investigated () promoter mutations. The mutational statuses of 5' untranslated region (5'UTR), intron 6, and promoters, as well as the promoter and mutations were determined using Sanger sequencing in 28 patients with ATC (19 women and 9 men) with a median (interquartile range) age of 64 (55-71) years, 14 thyroid cancer cell lines and a normal thyroid cell line.

Near-Infrared Optogenetic Nanosystem for Spatiotemporal Control of CRISPR-Cas9 Gene Editing and Synergistic Photodynamic Therapy.

Controlling CRISPR/Cas9 gene editing at the spatiotemporal resolution level, especially for in vivo applications, remains a great challenge. Here, we developed a near-infrared (NIR) light-activated nanophotonic system (UCPP) for controlled CRISPR-Cas9 gene editing and synergistic photodynamic therapy (PDT). Lanthanide-doped upconversion nanoparticles are not only employed as carriers for intracellular plasmid delivery but also serve as the nanotransducers to convert NIR light (980 nm) into visible light with emission at 460 and 650 nm, which could result in simultaneous activation of gene editing and PDT processes, respectively.

Wearable Systems of Reconfigurable Microneedle Electrode Array for Subcutaneous Multiplexed Recording of Myoelectric and Electrochemical Signals.

The real-time monitoring of in vivo electrophysiological and biochemical signals provides critical insights into the activities of tissues and organs. As the activity and metabolic state of different sites in the muscle vary, multichannel detection is necessary to capture the functional state of the whole muscle, yet the access to the bio-information in subcutaneous space remained challenging. This work reports the development of a reconfigurable microneedle electrode array integrated system designed to achieve painless and minimally invasive monitoring of subcutaneous electromyogram (EMG), oxygen species, and pH through an array of thumbtack-shaped microneedle (TSMN) electrode.

Promising Pharmacological Interventions for Posterior Capsule Opacification: A Review.

Phacoemulsification combined with intraocular lens implantation is the primary treatment for cataract. Although this treatment strategy benefits patients with cataracts, posterior capsule opacification (PCO) remains a common complication that impairs vision and affects treatment outcomes. The pathogenesis of PCO is associated with the proliferation, migration, and fibrogenesis activity of residual lens epithelial cells, with epithelial-mesenchymal transition (EMT) serving as a key mechanism underlying the condition.

Probing the Mesenchymal Stem Cell Aging through In silico Assessment of Extracellular Vesicle-mediated miRNAs.

Introduction: During mesenchymal stem cell (MSCs) aging, a decrease in its proliferation and regenerative capacity occurs, which is implicated in human aging. The MSCs aging process is regulated by genetics, metabolism, the external environment, and various complex pathways.

Method: The aging of MSCs during in vitro culture poses a major challenge for developing cell therapy aimed at combating human diseases and aging.

Advancing precision medicine through the integration of clinical cardiovascular genetics - An Asian perspective.

Purpose: The integration of cardiovascular genetic (CVG) testing into clinical practice is gaining recognition, but its implementation in the Asian setting has not been widely reported. We present our experience developing a clinical CVG service and analyze its impact on patient care at our center.

Methods: In 2020, the National Heart Centre Singapore collaborated with SingHealth Duke-NUS Genomic Medicine Centre, to establish a comprehensive clinical CVG service.

Hepatic TM6SF2 activates antitumour immunity to suppress metabolic dysfunction-associated steatotic liver disease-related hepatocellular carcinoma and boosts immunotherapy.

Background: Transmembrane 6 superfamily member 2 (TM6SF2) has a protective role against metabolic dysfunction-associated steatotic liver disease (MASLD).

Objective: We aim to investigate the mechanistic role and therapeutic potential of hepatic TM6SF2 in MASLD-related hepatocellular carcinoma (HCC).

Design: Hepatocyte-specific knockout ( ) mice were fed with high-fat/high-cholesterol (HFHC) diet or diethylnitrosamine plus HFHC diet to induce MASLD-HCC.

Loss of Notch dimerization perturbs intestinal homeostasis by a mechanism involving HDAC activity.

A tri-protein complex containing NICD, RBPj and MAML1 binds DNA as monomer or as cooperative dimers to regulate transcription. Mice expressing Notch dimerization-deficient alleles (NDD) of Notch1 and Notch2 are sensitized to environmental insults but otherwise develop and age normally. Transcriptomic analysis of colonic spheroids uncovered no evidence of dimer-dependent target gene miss-regulation, confirmed impaired stem cell maintenance in-vitro, and discovered an elevated signature of epithelial innate immune response to symbionts, a likely underlying cause for heightened sensitivity in NDD mice.

NIR-II Ratiometric Optical Theranostic Capsule for Diagnosis and Precise Therapy of Intestinal Inflammation.

Capsules were widely used in clinical settings for the oral delivery of various drugs, although it remains challenging to trace real-time drug release behavior and adjust dosages based on the therapeutic effect. To address these issues, we developed theranostic capsules that loaded two kinds of fluorescence nanoparticles, HO-responsive Janus Ag/AgS nanoparticles (Ag/AgS JNPs) and the downconversion nanoparticles (DCNPs), and the dexamethasone (Dex) drug. The Ag/AgS JNPs exhibit a highly sensitive fluorescence (FL) signal at 1250 nm in response to HO, while the FL signal from the DCNPs at 1550 nm remains stable under physiological conditions.

Multi-Omics Biomarkers for Predicting Efficacy of Biologic and Small-Molecule Therapies in Adults With Inflammatory Bowel Disease: A Systematic Review.

The heterogeneity and suboptimal efficacy of biological treatments and small molecule drugs necessitate their precise selection based on biomarkers that predict therapeutic responses in inflammatory bowel disease. Recent studies have identified numerous novel biomarkers predictive of responses to biologics and small molecule modulators, utilizing a variety of omics approaches in inflammatory bowel disease. In this review, we systematically examine baseline omics biomarkers that predict responses to biological therapies and small molecule drugs, drawing on literature from PubMed.

Identify critical genes of breast cancer and corresponding leading natural product compounds of potential therapeutic targets.

Breast cancer is a leading cause of cancer mortality among women globally, with over 2.26 million new cases annually, according to GLOBOCAN 2020. This accounts for approximately 25% of all new female cancers and 15.

Aberrant METTL1-mediated tRNA mG modification alters B-cell responses in systemic autoimmunity in humans and mice.

Upon activation, naive B cells exit their quiescent state and enter germinal center (GC) responses, a transition accompanied by increased protein synthesis. How protein translation efficiency is adequately adjusted to meet the increased demand requires further investigation. Here, we identify the methyltransferase METTL1 as a translational checkpoint during GC responses.

Receptor tyrosine kinase inhibition leads to regression of acral melanoma by targeting the tumor microenvironment.

Background: Acral melanoma (AM) is an aggressive melanoma variant that arises from palmar, plantar, and nail unit melanocytes. Compared to non-acral cutaneous melanoma (CM), AM is biologically distinct, has an equal incidence across genetic ancestries, typically presents in advanced stage disease, is less responsive to therapy, and has an overall worse prognosis.

Methods: An independent analysis of published sequencing data was performed to evaluate the frequency of receptor tyrosine kinase (RTK) ligands and adapter protein gene variants and expression.

SULT2B1: a novel therapeutic target in colorectal cancer via modulation of AKT/PKM2-mediated glycolysis and proliferation.

Background: Sulfotransferase family 2B member 1 (SULT2B1) is involved in regulating cell proliferation, migration and metabolism. However, there is still dispute regarding whether SULT2B1 acts as an oncogene or a suppressor, and the intrinsic mechanisms in modulating tumor progression need to be further elucidated.

Methods: This work aims to reveal the relationship among SULT2B1, AKT, PKM2 signaling and glycolytic pathways, and provided a theoretical basis for SULT2B1 as a potential therapeutic target for CRC.

A histopathology-based artificial intelligence system assisting the screening of genetic alteration in intrahepatic cholangiocarcinoma.

Background: Targeted therapy for intrahepatic cholangiocarcinoma (ICC) shows superior survival outcomes but patients with certain targetable alterations are no more than 20%. Genetic alteration screening for all ICC patients is of high cost and not routinely performed. This study intends to develop a histopathology-based artificial intelligence (AI)-assisted system for predicting genetic alteration of ICC.

Permeability-Engineered Compartmentalization System Promises Next-Generation Single-Cell Analysis.

Single-cell analysis, including sequencing, imaging, and biochemical assays, has become a fundamental strategy in biomedical research. Microplates, with their open system design, facilitate multistep reagent addition, subtraction, and buffer exchange, while their physically isolated wells prevent cross-contamination between biomolecules, establishing them as foundational compartmentalized platform for single-cell analysis. In contrast, water-in-oil droplets, produced by microfluidic systems, create nanoliter/picoliter-sized droplets that act as advanced compartmentalized platform.

Self-Assembled Nanoparticles with Well-Defined Oligosaccharide Promote Osteogenesis by Regulating Golgi Stress Response.

Osteoporosis, a prevalent disease characterized by low bone density and increased fracture risk, poses significant health challenges for the elderly. Current treatments offer short-term benefits but are limited by long-term efficacy and adverse effects, highlighting the need for new strategies. Chondroitin sulfate polysaccharides (CS), a major component of the bone matrix, are crucial for bone and cartilage health.

Exome sequencing of Singapore Chinese anti-citrullinated-protein-antibody-positive rheumatoid arthritis patients.

Objective: More than 130 susceptibility loci for rheumatoid arthritis (RA) have been identified with genome-wide association studies (GWAS). To investigate the genetic predisposition of Chinese anti-cyclic-citrullinated-peptides-antibody-positive RA, we carried out an exome sequencing study.

Methods: Patients were recruited from three major public hospitals in Singapore, Tan Tock Seng Hospital (TTSH), Singapore General Hospital and National University Health System.

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.

Hydrogel-to-Nanoparticle Transition with Immune Cell Activation Controlled by Dual Supramolecular Interactions.

Biomolecules may undergo dynamic transitions between different aggregation states in order to adapt to the microenvironment. As a result, appropriate biofunctions can be performed only under certain states. This feature inspires exploration for constructing and regulating environmentally adaptive materials through supramolecular ways.

Audiovestibular Dysfunction Related to Anti-Phospholipid Syndrome: A Systematic Review.

Anti-phospholipid syndrome (APS) has emerged as a significant issue in autoimmune diseases over recent decades. Its hallmark feature is thromboembolic events, potentially affecting any vascularized area including the microcirculation of the inner ear. Since the first case report of APS-related audiovestibular dysfunction described in 1993, numerous reports have explored the association between APS-related antibodies and audiovestibular dysfunction.

Assessing the unmet needs of genomic testing in Australia: a geospatial exploration.

The role of genomic testing in rare disease clinical management is growing. However, geographical and socioeconomic factors contribute to inequitable uptake of testing. Geographical investigations of genomic testing across Australia have not been undertaken.

Low CXCL11 expression is indicative of poor prognosis in rectal cancer patients undergoing preoperative chemoradiotherapy: a retrospective cohort study.

Introduction: Neoadjuvant concurrent chemoradiotherapy (CCRT) is routinely used before surgery in patients with locally advanced rectal cancer to reduce tumor size and decrease the risk of local recurrence. However, the disease-specific survival has not improved in most cases due to distant metastases. In selected individuals exhibiting a clinical complete response, non-operative management may be allowed; however, those who presented no or little response tend to have an inferior prognosis.