Hepatocellular carcinoma (HCC) stands as the fifth most prevalent malignant tumor on a global scale and presents as the second leading cause of cancer-related mortality. DNA damage-based radiotherapy (RT) plays a pivotal role in the treatment of HCC. Nevertheless, radioresistance remains a primary factor contributing to the failure of radiation therapy in HCC patients. In this study, we investigated the functional role of transketolase (TKT) in the repair of DNA double-strand breaks (DSBs) in HCC. Our research unveiled that TKT is involved in DSB repair, and its depletion significantly reduces both non-homologous end joining (NHEJ) and homologous recombination (HR)-mediated DSB repair. Mechanistically, TKT interacts with PARP1 in a DNA damage-dependent manner. Furthermore, TKT undergoes PARylation by PARP1, resulting in the inhibition of its enzymatic activity, and TKT can enhance the auto-PARylation of PARP1 in response to DSBs in HCC. The depletion of TKT effectively mitigates the radioresistance of HCC, both in vitro and in mouse xenograft models. Moreover, high TKT expression confers resistance of RT in clinical HCC patients, establishing TKT as a marker for assessing the response of HCC patients who received cancer RT. In summary, our findings reveal a novel mechanism by which TKT contributes to the radioresistance of HCC. Overall, we identify the TKT-PARP1 axis as a promising potential therapeutic target for improving RT outcomes in HCC.

Radiation-induced damages are difficult to heal than normal wounds. This is because radiation therapy could lead to an imbalanced inflammatory response, oxidative stress response, lack of angiogenesis, and a high risk of bacterial infection, which are considered to be the greatest challenges in radiation-induced damages treatment. Hydrogels are semi-occlusive and are composed of complex hydrophilic polymers with a higher water content. Due to their excellent mechanical and biochemical property (such as adhesiveness, antibacterial, and antioxidant abilities), hydrogels represent a promising strategy that has achieved potent therapeutic efficacy in the treatment of radiation-induced skin and mucosa damages. This review systematically and comprehensively summarizes the recent progress of various types of hydrogels such as natural biopolymer, synthetic polymer, composite hydrogels and commodity dressings for the treatment of radiation-induced skin and mucosa damages.

Hypoxia can aggravate the conditions of many oxygen-deficiency-aggravated diseases (ODAD), such as cancer, ischemic heart disease, and chronic wounds. Photosynthetic microalgae can alleviate the hepatotoxicity of the local microenvironment by producing oxygen. In addition, microalgae extracts have antitumor, anti-inflammatory, antibacterial, and antioxidant effects. These properties make them attractive candidates for developing methods to treat ODAD. Although researchers have exploited the advantages of microalgae and developed a variety of microalgae-based biomaterials to treat ODAD, a comprehensive review of this topic has not been presented previously. Therefore, in this review, we summarize the development and progress made in the field of developing microalgae-based biomaterials toward the treatment of ODAD. The challenges and prospects of this field are also discussed.

Genetic factors are the major causes of epilepsies, such as developmental and epileptic encephalopathy (DEE) and idiopathic generalized epilepsy (IGE). However, the etiology of most patients remains elusive. This study performed exon sequencing in a cohort of 173 patients with IGE. Additional cases were recruited from the matching platform in China. The excess and damaging effect of variants, the genotype-phenotype correlation, and the correlation between gene expression and phenotype were studied to validate the gene-disease association. CSMD1 compound heterozygous variants were identified in four unrelated cases with IGE. Additional CSMD1 variants were identified in five cases with DEE featured by generalized seizures from the matching platform, including two with de novo and three with compound heterozygous variants. Two patients were refractory to antiseizure medications and all patients were on long-term therapy. The CSMD1 variants presented a significantly high excess of variants in the case-cohort. Besides de novo origination, the DEE cases had each of the paired variants located closer to each other than the IGE cases or more significant alterations in hydrophobicity. The DEE-associated variants were all absent in the normal population and presented significantly lower minor allele frequency than the IGE-associated variants, suggesting a minor allele frequency-phenotype severity correlation. Gene expression analysis showed that CSMD1 was extensively expressed throughout the brain, particularly in the cortex. The CSMD1 temporal expression pattern correlated with the disease onset and outcomes. This study suggests that CSMD1 is associated with epilepsy and is a novel causative gene of DEE and generalized epilepsies.

Skin cancer is a common malignant tumor that poses significant global health and economic burdens. The main clinical types include malignant melanoma and non-melanoma. Complications such as post-surgical recurrence, wound formation, or disfigurement can severely impact the patient’s mental well-being. Traditional treatments such as surgery, chemotherapy, radiation therapy, and immunotherapy often face limitations. These challenges not only reduce the effectiveness of treatments but also negatively impact patients’ quality of life. Phototherapy, a widely used and long-standing method in dermatology, presents a promising alternative for skin cancer treatment. Light-triggered nanomaterials further enhance the potential of phototherapy by offering advantages such as improved therapeutic precision, controlled drug release, minimal invasiveness, and reduced damage to surrounding healthy tissues. This review summarizes the application of light-triggered nanomaterials in skin cancer treatment, focusing on the principles, advantages, and design strategies of photodynamic therapy (PDT), photothermal therapy (PTT), and photoacoustic therapy (PAT). In this manuscript we have an in-depth discussion on overcoming translational barriers, including strategies to enhance light penetration, mitigate toxicity, reduce production costs, and optimize delivery systems. Additionally, we discuss the challenges associated with their clinical translation, including limited light penetration in deep tissues, potential toxicity, high production costs, and the need for advanced delivery systems.