Mitochondrial diseases are often caused by mutations in nuclear genes, affecting predominantly the CNS. Early intervention with AAV-PHP.eB-driven gene replacement successfully prevented the onset of encephalopathy in neuronal-knockouts of critical oxidative phosphorylation genes (Ndufs3 or Cox10).

Highly specific antibodies against the extracellular domain of LGR5 were developed as (i) a research tool to study LGR5 biology, (ii) for diagnostic use in multiple cancer types and (iii) as novel immunotherapeutics.

A novel approach, named AccuScan, was developed for molecular residual disease (MRD) detection and immunotherapy monitoring. This technology uses whole genome sequencing (WGS) with single-read error correction for circulating tumor DNA (ctDNA) analysis.

CLDN18-ARHGAP fusion gene of gastric cancer generates an immunogenic neoantigen, which induces neoantigen reactive T cells specifically targeting and eliminating gastric cancer cells with CLDN18-ARHGAP fusion gene.

Histidine-rich glycoprotein (HRG) was found to be increased in plasma following thrombolysis by tissue plasminogen activator (tPA) infusion, which counteracted the hemorrhagic-prone state through inhibiting neutrophil NETosis and migration, ultimately reducing the risk of hemorrhage.

Collecting duct carcinoma (CDC) is an aggressive kidney cancer without effective treatment. Our study not only enhanced our scientific understanding of the oncogenic alterations prevalent in Asian CDC, but has also identified cell-cycle machinery as a potential target for therapeutic intervention.

The two vaccines currently employed against malaria are based on a single Plasmodium antigen, require 4 shots and provide only limited protection. Attenuated whole parasite vaccines are currently in development but also require multiple injections of high numbers of parasites for protection.

Favorable safety profiles and persistent clinical improvements were observed in two patients with highly relapsed and refractory MG over 18 months after BCMA-targeting CAR-T therapy. Distinct characteristics of CAR-T cells in patients with MG were investigated by longitudinal single-cell analysis.

Genome-wide CRISPR screens revealed PKMYT1 as a genetic vulnerability for PDAC. Pharmacological inhibition of PKMYT1 was identified as a new therapeutic strategy for PKMYT1-expressing PDAC patients.

In this review, A. Xu & colleagues describe the molecular pathways whereby exerkine networks mediate the cardiometabolic adaptations to exercise and discuss the potential translation of exerkine-based discovery into therapeutic application and personalized medicine.

Necroptotic cell death is broadly linked to inflammation-associated diseases such as IBD. But, accurately identifying when and where necroptosis occurs in human disease has proven difficult. Using new methods to detect the key regulators of necroptosis - Caspase-8, RIPK1, RIPK3, MLKL - we find that:

In the circulation, platelets interact with blood monocytes enhancing their inflammatory capacity. Platelets are enriched in transcriptional regulators that support human monocyte inflammation. Thrombocytopenia, experimentally induced or as a result of autoimmune disease, renders monocytes anergic to immune stimulation, a state known as immunoparalysis, which weakens host defense programs and increases susceptibility to infection.

Angiogenesis supports tumor growth. Current antiangiogenic therapies have not significantly improved survival; there is a critical need for new approaches. Mechanisms that regulate transition from normal to tumor-associated endothelial cells and drive pathological angiogenesis are poorly understood.

The fat mass and obesity-associated (FTO) protein, an N⁶-methyladenosine (m⁶A) demethylase, influences endothelial cell (EC) function and retinal homeostasis in diabetic retinopathy (DR), thus providing a promising nanotherapeutic approach for DR.

A potent small molecule TSLPR inhibitor was identified as a novel therapeutic option for atopic diseases.