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Immunotherapy has shifted the clinical paradigm of cancer management. However, despite promising initial progress, immunotherapeutic approaches to cancer still suffer from relatively low response rates and the possibility of severe side effects, likely due to the low inherent immunogenicity of tumor cells, the immunosuppressive tumor microenvironment, and significant inter- and intratumoral heterogeneity. Recently, nanoformulations of prodrugs have been explored as a means to enhance cancer immunotherapy by simultaneously eliciting antitumor immune responses and reversing local immunosuppression. Prodrug nanomedicines, which integrate engineering advances in chemistry, oncoimmunology, and material science, are rationally designed through chemically modifying small molecule drugs, peptides, or antibodies to yield increased bioavailability and spatiotemporal control of drug release and activation at the target sites. Such strategies can help reduce adverse effects and enable codelivery of multiple immune modulators to yield synergistic cancer immunotherapy. 7ACC2 In this review article, recent advances and translational challenges facing prodrug nanomedicines for cancer immunotherapy are overviewed. Last, key considerations are outlined for future efforts to advance prodrug nanomedicines aimed to improve antitumor immune responses and combat immune tolerogenic microenvironments.The rise of 2D transition-metal dichalcogenides (TMDs) materials has enormous implications for the scientific community and beyond. Among TMDs, ReX2 (X = S, Se) has attracted significant interest regarding its unusual 1T' structure and extraordinary properties in various fields during the past 7 years. For instance, ReX2 possesses large bandgaps (ReSe2 1.3 eV, ReS2 1.6 eV), distinctive interlayer decoupling, and strong anisotropic properties, which endow more degree of freedom for constructing novel optoelectronic, logic circuit, and sensor devices. Moreover, facile ion intercalation, abundant active sites, together with stable 1T' structure enable them great perspective to fabricate high-performance catalysts and advanced energy storage devices. In this review, the structural features, fundamental physicochemical properties, as well as all existing applications of Re-based TMDs materials are comprehensively introduced. Especially, the emerging synthesis strategies are critically analyzed and pay particular attention is paid to its growth mechanism with probing the assembly process of domain architectures. Finally, current challenges and future opportunities regarding the controlled preparation methods, property, and application exploration of Re-based TMDs are discussed.Usage of nonhalide lead sources for fabricating perovskite solar cells (PSCs) has recently attracted increasing attention as a promising route toward realizing high quality PSC devices. However, the unique role of nonhalide lead sources in improving perovskite film morphology and PSC performance has largely remained unexplored, impeding broader application of these materials. Here, it is demonstrated that by using a new nonhalide lead source, lead formate (Pb(HCOO)2), good control of perovskite film morphology can be achieved. With the usage of lead formate, PbI2 can nicely border the perovskite grain boundaries (GBs) and form domain "walls" that segregate the individual perovskite crystal domains. The PbI2 at the GBs lead to significant improvement in film quality and device performance through passivating the defects at the perovskite GBs and suppressing lateral carrier diffusion. An impressive carrier lifetime at the microsecond scale (τ2 = 1714 ns) is achieved, further with an optimal power conversion efficiency of 20.3% for the resulting devices. This work demonstrates a promising and effective method toward fabricating high-quality perovskites and high-efficiency PSCs.Actin plays fundamental roles in both the cytoplasm and the cell nucleus. In the nucleus, β-actin regulates neuronal reprogramming by consolidating a heterochromatin landscape required for transcription of neuronal gene programs, yet it remains unknown whether it has a role in other differentiation models. To explore the potential roles of β-actin in osteogenesis, β-actin wild-type (WT) and β-actin knockout (KO) mouse embryonic fibroblasts (MEFs) are reprogrammed to osteoblast-like cells using small molecules in vitro. It is discovered that loss of β-actin leads to an accelerated mineralization phenotype (hypermineralization), accompanied with enhanced formation of extracellular hydroxyapatite microcrystals, which originate in the mitochondria in the form of microgranules. This phenotype is a consequence of rapid upregulation of mitochondrial genes including those involved in oxidative phosphorylation (OXPHOS) in reprogrammed KO cells. It is further found that osteogenic gene programs are differentially regulated between WT and KO cells, with clusters of genes exhibiting different temporal expression patterns. A novel function for β-actin in osteogenic reprogramming through a mitochondria-based mechanism that controls cell-mediated mineralization is proposed.Canavan disease (CD) is a fatal leukodystrophy caused by mutation of the aspartoacylase (ASPA) gene, which leads to deficiency in ASPA activity, accumulation of the substrate N-acetyl-L-aspartate (NAA), demyelination, and spongy degeneration of the brain. There is neither a cure nor a standard treatment for this disease. In this study, human induced pluripotent stem cell (iPSC)-based cell therapy is developed for CD. A functional ASPA gene is introduced into patient iPSC-derived neural progenitor cells (iNPCs) or oligodendrocyte progenitor cells (iOPCs) via lentiviral transduction or TALEN-mediated genetic engineering to generate ASPA iNPC or ASPA iOPC. After stereotactic transplantation into a CD (Nur7) mouse model, the engrafted cells are able to rescue major pathological features of CD, including deficient ASPA activity, elevated NAA levels, extensive vacuolation, defective myelination, and motor function deficits, in a robust and sustainable manner. Moreover, the transplanted mice exhibit much prolonged survival.
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