Exploring multivalency-driven sensitivity modulation for optimization and fine-tuning of avidity-based biosensors.

The development of multivalent nanoprobes has garnered considerable interest due to their enhanced sensitivity and precision in diagnosing and monitoring diverse diseases. Despite significant advances in nanobiotechnology, the optimal density of binding motifs to maximize the diagnostic efficacy of biosensors remains incompletely understood. Herein, we investigate the influence of multivalency in the functional performance of avidity-based biosensors.

Targeted degradation of METTL3 against acute myeloid leukemia and gastric cancer.

Accumulating evidence reveals the oncogenic role of methyltransferase-like 3 (METTL3) in a variety of cancers, either dependent or independent of its mA methyl transferase activity. We have explored PROTACs targeting METTL3 and identified KH12 as a potent METTL3 degrader. Treatment of KH12 on MOLM-13 cells causes degradation of METTL3 with a DC value of 220 nM in a dose-, time- and ubiquitin-dependent fashion.

Wearable heart rate sensing and critical power-based whole-body fatigue monitoring in the field.

Whole-body fatigue (WBF) presents a concerning risk to construction workers, which can impact function and ultimately lead to accidents and diminished productivity. This study proposes a new WBF monitoring technique by applying the Critical Power (CP) model, a bioenergetic model, with a wrist-worn heart rate sensor. The authors modified the CP model to calculate WBF from the percentage of heart rate reserve (%HRR) and generated a personalized model via WBF perception surveys.

Epsti1 Regulates the Inflammatory Stage of Early Muscle Regeneration through STAT1-VCP Interaction.

During muscle regeneration, interferon-gamma (IFN-) coordinates inflammatory responses critical for activation of quiescent muscle stem cells upon injury via the Janus kinase (JAK) - signal transducer and activator of transcription 1 (STAT1) pathway. Dysregulation of JAK-STAT1 signaling results in impaired muscle regeneration, leading to muscle dysfunction or muscle atrophy. Until now, the underlying molecular mechanism of how JAK-STAT1 signaling resolves during muscle regeneration remains largely elusive.

Farnesol prevents aging-related muscle weakness in mice through enhanced farnesylation of Parkin-interacting substrate.

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis. Reduced PGC-1α abundance is linked to skeletal muscle weakness in aging or pathological conditions, such as neurodegenerative diseases and diabetes; thus, elevating PGC-1α abundance might be a promising strategy to treat muscle aging. Here, we performed high-throughput screening and identified a natural compound, farnesol, as a potent inducer of PGC-1α.

Targeted kinase degradation via the KLHDC2 ubiquitin E3 ligase.

Chemically induced protein degradation is a powerful strategy for perturbing cellular biochemistry. The predominant mechanism of action for protein degrader drugs involves an induced proximity between the cellular ubiquitin-conjugation machinery and a target. Unlike traditional small molecule enzyme inhibition, targeted protein degradation can clear an undesired protein from cells.

Cdon ablation in motor neurons causes age-related motor neuron degeneration and impaired sciatic nerve repair.

Background: The functional deterioration and loss of motor neurons are tightly associated with degenerative motor neuron diseases and aging-related muscle wasting. Motor neuron diseases or aging-related muscle wasting in turn contribute to increased risk of adverse health outcomes in the elderly. Cdon (cell adhesion molecule-downregulated oncogene) belongs to the immunoglobulin superfamily of cell adhesion molecule and plays essential roles in multiple signalling pathways, including sonic hedgehog (Shh), netrin, and cadherin-mediated signalling.

The impact of cancer cachexia on gut microbiota composition and short-chain fatty acid metabolism in a murine model.

This study investigates the relationship between cancer cachexia and the gut microbiota, focusing on the influence of cancer on microbial composition. Lewis lung cancer cell allografts were used to induce cachexia in mice, and body and muscle weight changes were monitored. Fecal samples were collected for targeted metabolomic analysis for short chain fatty acids and microbiome analysis.

PRMT7 ablation in cardiomyocytes causes cardiac hypertrophy and fibrosis through β-catenin dysregulation.

Angiotensin II (AngII) has potent cardiac hypertrophic effects mediated through activation of hypertrophic signaling like Wnt/β-Catenin signaling. In the current study, we examined the role of protein arginine methyltransferase 7 (PRMT7) in cardiac function. PRMT7 was greatly decreased in hypertrophic hearts chronically infused with AngII and cardiomyocytes treated with AngII.

ZNF746/PARIS overexpression induces cellular senescence through FoxO1/p21 axis activation in myoblasts.

Various stresses, including oxidative stress, impair the proliferative capacity of muscle stem cells leading to declined muscle regeneration related to aging or muscle diseases. ZNF746 (PARIS) is originally identified as a substrate of E3 ligase Parkin and its accumulation is associated with Parkinson's disease. In this study, we investigated the role of PARIS in myoblast function.

Satellite cell-specific ablation of Cdon impairs integrin activation, FGF signalling, and muscle regeneration.

Background: Perturbation in cell adhesion and growth factor signalling in satellite cells results in decreased muscle regenerative capacity. Cdon (also called Cdo) is a component of cell adhesion complexes implicated in myogenic differentiation, but its role in muscle regeneration remains to be determined.

Methods: We generated inducible satellite cell-specific Cdon ablation in mice by utilizing a conditional Cdon allele and Pax7 .

PRMT7 deficiency enhances adipogenesis through modulation of C/EBP-β.

Obesity that is critically correlated with the initiation and development of metabolic syndrome and cardiovascular diseases has increased worldwide. Adipogenesis is coordinated through multi-steps involving adipogenic commitment, mitotic clonal expansion (MCE) and differentiation. Recently, protein arginine methyltransferase 4 (PRMT4) and PRMT5 have been implicated in modulation of adipogenesis via regulation of C/EBP-β activity or PPAR-γ2 expression.

CDO, an Hh-coreceptor, mediates lung cancer cell proliferation and tumorigenicity through Hedgehog signaling.

Hedgehog (Hh) signaling plays essential roles in various developmental processes, and its aberrant regulation results in genetic disorders or malignancies in various tissues. Hyperactivation of Hh signaling is associated with lung cancer development, and there have been extensive efforts to investigate how to control Hh signaling pathway and regulate cancer cell proliferation. In this study we investigated a role of CDO, an Hh co-receptor, in non-small cell lung cancer (NSCLC).