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BackgroundArginine deprivation therapy (ADT) hinders glioma cells’ access to nutrients by reducing peripheral blood arginine, showing great efficacy in various studies, which suggests it as a potentially promising treatment for glioma. The aim of this systematic review was to explore the mechanism of ADT for gliomas, the therapeutic effect based on existing research, and possible combination therapies.MethodsWe performed a systematic literature review of PubMed, ScienceDirect and Web of Science databases according to PRISMA guidelines, searching for articles on the efficacy of ADT in glioma.ResultsWe identified 17 studies among 786 search results, among which ADT therapy mainly based on Arginine free condition, Arginine Deiminase and Arginase, including three completed clinical trials. ADT therapy has shown promising results in vivo and in vitro, with its safety confirmed in clinical trials. In the early phase of treatment, glioblastoma (GBM) cells develop protective mechanisms of stress and autophagy, which eventually evolve into caspase dependent apoptosis or senescence, respectively. The immunosuppressive microenvironment is also altered by arginine depletion, such as the transformation of microglia into a pro-inflammatory phenotype and the activation of T-cells. Thus, ADT therapy demonstrates glioma-killing effect in the presence of a combination of mechanisms. In combination with various conventional therapies and investigational drugs such as radiotherapy, temozolomide (TMZ), cyclin-dependent kinase inhibitors (CDK) inhibitors and autophagy inducers, ADT therapy has been shown to be more effective. However, the phenomenon of drug resistance due to re-expression of ASS1 rather than stem cell remains to be investigated.ConclusionDespite the paucity of studies in the literature, the available data demonstrate the therapeutic potential of arginine deprivation therapy for glioma and encourage further research, especially the exploration of its combination therapies and the extrapolation of what we know about the effects and mechanisms of ADT from other tumors to glioma.

Aim: A multifunctional nanoplatform has been developed to enhance the targeting capability and biosafety of drug/siRNA for better diagnosis and treatment of myocardial infarction (MI). Materials & methods: The nanoplatform's chemical properties, biodistribution, cardiac magnetic resonance imaging (MRI) capabilities, therapeutic effects and biocompatibility were investigated. Results: The nanoplatform exhibited MI-targeting properties and pH-sensitivity, allowing for effective cardiac MRI and delivery of drugs to the infarcted myocardium. The GCD/Qt@ZIF-RGD demonstrated potential as a reliable MRI probe for MI diagnosis. Moreover, the GCD/si-SHP1/Qt@ZIF-RGD effectively suppressed SHP-1 expression, increased pro-angiogenesis gene expression and reduced cell apoptosis in HUVECs exposed to hypoxia/reoxygenation. Conclusion: Our newly developed multifunctional drug delivery system shows promise as a nanoplatform for both the diagnosis and treatment of MI. Graphical Abstract Article highlights The BSA-RGD-modified ZIF-8 nanoplatform is constructed. The nanoplatform encapsulates quercetin and SHP-1 siRNA as the therapeutic agents, and GCD as the MRI contrast agent. The nanoplatform is infarct-targeting and pH-sensitive, resulting in efficient drug/siRNA delivery. The GCD/si-SHP1/Qt@ZIF-RGD nanoparticles produce efficient gene silencing of SHP-1 in vitro and in vivo. The GCD/si-Con/Qt@ZIF-RGD promote angiogenesis and alleviate cell apoptosis on HUVECs under H/R. The GCD/si-SHP1/Qt@ZIF-RGD display better performance on promoting angiogenesis and alleviating cell apoptosis on HUVECs under H/R. The GCD/Qt@ZIF-RGD can serve as a promising MRI probe for MI imaging. The GCD/si-SHP1/Qt@ZIF-RGD nanoparticles show good biocompatibility. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) is demonstrated to trigger the systemic immune response of the organism and facilitate the treatment of metastatic tumors. However, SDT‐mediated neutrophil extracellular traps (NETs) formation can promote tumor cell spread, thus weakening the therapeutic effectiveness of metastatic tumors. Herein, the amorphous CoW‐layered double hydroxide (a‐CoW‐LDH) nanosheets are functionalized with a peptidyl arginine deiminase 4 (PAD4) inhibitor, i.e., YW3‐56, to construct a multifunctional nanoagent (a‐LDH@356) for synergistic SDT/immunotherapy. Specifically, a‐CoW‐LDH nanosheets can act as a sonosensitizer to generate abundant reactive oxygen species (ROS) under US irradiation. After loading with YW3‐56, a‐LDH@356 plus US irradiation not only effectively induces ROS generation and immunogenic cell death, but also inhibits the elevation of citrullinated histone H3 (H3cit) and the release of NETs, enabling a synergistic enhancement of anti‐tumor metastasis effect. Using 4T1 tumor model, it is demonstrated that combining a‐CoW‐LDH with YW3‐56 stimulates an anti‐tumor response by upregulating the proportion of immune‐activated cells and inducing polarization of M1 macrophages, and inhibits immune escape by downregulating the expression of PD‐1 on immune cells under US irradiation, which not only arrests primary tumor progression with a tumor inhibition rate of 69.5% but also prevents tumor metastasis with the least number of lung metastatic nodules. [ABSTRACT FROM AUTHOR]

Background: The strong invasiveness and rapid expansion of dengue virus (DENV) pose a great challenge to global public health. However, dengue epidemic patterns and mechanisms at a genetic scale, particularly in term of cross-border transmissions, remain poorly understood. Importation is considered as the primary driver of dengue outbreaks in China, and since 1990 a frequent occurrence of large outbreaks has been triggered by the imported cases and subsequently spread to the western and northern parts of China. Therefore, this study aims to systematically reveal the invasion and diffusion patterns of DENV-1 in Guangdong, China from 1990 to 2019. Methods: These analyses were performed on 179 newly assembled genomes from indigenous dengue cases in Guangdong, China and 5152 E gene complete sequences recorded in Chinese mainland. The genetic population structure and epidemic patterns of DENV-1 circulating in Chinese mainland were characterized by phylogenetics, phylogeography, phylodynamics based on DENV-1 E-gene-based globally unified genotyping framework. Results: Multiple serotypes of DENV were co-circulating in Chinese mainland, particularly in Guangdong and Yunnan provinces. A total of 189 transmission clusters in 38 clades belonging to 22 subgenotypes of genotype I, IV and V of DENV-1 were identified, with 7 Clades of Concern (COCs) responsible for the large outbreaks since 1990. The epidemic periodicity was inferred from the data to be approximately 3 years. Dengue transmission events mainly occurred from Great Mekong Subregion-China (GMS-China), Southeast Asia (SEA), South Asia Subcontinent (SASC), and Oceania (OCE) to coastal and land border cities respectively in southeastern and southwestern China. Specially, Guangzhou was found to be the most dominant receipting hub, where DENV-1 diffused to other cities within the province and even other parts of the country. Genome phylogeny combined with epidemiological investigation demonstrated a clear local consecutive transmission process of a 5C1 transmission cluster (5C1-CN4) of DENV-1 in Guangzhou from 2013 to 2015, while the two provinces of Guangdong and Yunnan played key roles in ongoing transition of dengue epidemic patterns. In contextualizing within Invasion Biology theories, we have proposed a derived three-stage model encompassing the stages of invasion, colonization, and dissemination, which is supposed to enhance our understanding of dengue spreading patterns. Conclusions: This study demonstrates the invasion and diffusion process of DENV-1 in Chinese mainland within a global genotyping framework, characterizing the genetic diversities of viral populations, multiple sources of importation, and periodic dynamics of the epidemic. These findings highlight the potential ongoing transition trends from epidemic to endemic status offering a valuable insight into early warning, prevention and control of rapid spreading of dengue both in China and worldwide. [ABSTRACT FROM AUTHOR]

Highly regioselective C−H alkylation reactions of tertiary anilines and tertiary alkyl amines with simple alkenes have been achieved by the use of imidazolin‐2‐iminato scandium alkyl complexes. This protocol provided an efficient and atom‐economical route to structurally diverse tertiary amine derivatives. The basic ligand, a coordinating THF in the catalyst and the substitution of alkene substrates were found to switch the regioselectivity of the C−H alkylation reactions of tertiary anilines presumably due to the generation of different types of catalytically active species or the formation of relatively stable intermediates. On the basis of the deuterium labeling experiments and KIE experiments, possible catalytical cycles were provided to understand the reaction mechanism as well as the regioselectivity. [ABSTRACT FROM AUTHOR]