A Novel Nanozyme to Enhance Radiotherapy Effects by Lactic Acid Scavenging, ROS Generation, and Hypoxia Mitigation.

Uveal melanoma (UM) is a leading intraocular malignancy with a high 5-year mortality rate, and radiotherapy is the primary approach for UM treatment. However, the elevated lactic acid, deficiency in ROS, and hypoxic tumor microenvironment have severely reduced the radiotherapy outcomes. Hence, this study devised a novel CoMnFe-layered double oxides (LDO) nanosheet with multienzyme activities for UM radiotherapy enhancement. On one hand, LDO nanozyme can catalyze hydrogen peroxide (H2O2) in the tumor microenvironment into oxygen and reactive oxygen species (ROS), significantly boosting ROS production during radiotherapy. Simultaneously, LDO efficiently scavenged lactic acid, thereby impeding the DNA and protein repair in tumor cells to synergistically enhance the effect of radiotherapy. Moreover, density functional theory (DFT) calculations decoded the transformation pathway from lactic to pyruvic acid, elucidating a previously unexplored facet of nanozyme activity. The introduction of this innovative nanomaterial paves the way for a novel, targeted, and highly effective therapeutic approach, offering new avenues for the management of UM and other cancer types.

Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy.

Adoptive immunotherapy in the T cell landscape exhibits efficacy in cancer treatment. Over the past few decades, genetically modified T cells, particularly chimeric antigen receptor T cells, have enabled remarkable strides in the treatment of hematological malignancies. Besides, extensive exploration of multiple antigens for the treatment of solid tumors has led to clinical interest in the potential of T cells expressing the engineered T cell receptor (TCR). TCR-T cells possess the capacity to recognize intracellular antigen families and maintain the intrinsic properties of TCRs in terms of affinity to target epitopes and signal transduction. Recent research has provided critical insight into their capability and therapeutic targets for multiple refractory solid tumors, but also exposes some challenges for durable efficacy. In this review, we describe the screening and identification of available tumor antigens, and the acquisition and optimization of TCRs for TCR-T cell therapy. Furthermore, we summarize the complete flow from  laboratory to clinical applications of TCR-T cells. Last, we emerge future prospects for improving therapeutic efficacy in cancer world with combination therapies or TCR-T derived products. In conclusion, this review depicts our current understanding of TCR-T cell therapy in solid neoplasms, and provides new perspectives for expanding its clinical applications and improving therapeutic efficacy.

Common variants in FAN1, located in 15q13.3, confer risk for schizophrenia and bipolar disorder in Han Chinese.

Multiple genetic risk factors have been associated with psychiatric disorders which provides the genetic insight to these disorders; however, the etiology of these disorders is still elusive. 15q13.3 was previously associated with schizophrenia, bipolar and other neurodevelopmental disorders. Whereas, the FAN1 which encodes the Fanconi anemia associated nuclease 1 was suggested to be causal gene for 15q13.3 related psychiatric disorders. This study aimed to investigate the association of FAN1 with three major psychiatric disorders. Herein, we conducted a case-control study with the Chinese Han population. Three single nucleotide polymorphisms (SNPs) of FAN1 were genotyped in 1248 schizophrenia cases, 1344 bipolar disorder cases, 1056 major depressive disorder cases and 1248 normal controls. We found that SNPs rs7171212 was associated with bipolar (pallele = 0.023, pgenotype = 0.022, OR = 0.658) and schizophrenia (pallele = 0.021, pgenotype = 0.019, OR = 0.645). Whereas, rs4779796 was associated with schizophrenia (pgenotype = 0.001, adjusted pgenotype = 0.003, OR = 1.089). In addition, rs7171212 (adjusted pallele = 0.018, adjusted pgenotype = 0.018, OR = 0.652) and rs4779796 (adjusted pgenotype = 0.024, OR = 1.12) showed significantly associated with combined cases of schizophrenia and bipolar disorder. Further, meta-analysis was performed with the case-control data and dataset extracted from previously reported genome-wide association study to validate the promising SNPs. Our results provide the new evidence that FAN1 may be a common susceptibility gene for schizophrenia and bipolar disorder in Han Chinese. These novel findings need further validation with larger sample size and functional characterization to understand the underlying pathogenic mechanism behind FAN1 in the prevalence of schizophrenia and bipolar disorders.