Research progress on intestinal microbiota regulating cognitive function through the gut-brain axis.

The intestinal microbiota community is a fundamental component of the human body and plays a significant regulatory role in maintaining overall health and in the management disease states.The intestinal microbiota-gut-brain axis represents a vital connection in the cognitive regulation of the central nervous system by the intestinal microbiota.The impact of intestinal microbiota on cognitive function is hypothesized to manifest through both the nervous system and circulatory system. Imbalances in intestinal microbiota during the perioperative period could potentially contribute to perioperative neurocognitive dysfunction. This article concentrates on a review of existing literature to explore the potential influence of intestinal microbiota on brain and cognitive functions via the nervous and circulatory systems.Additionally, it summarizes recent findings on the impact of perioperative intestinal dysbacteriosis on perioperative neurocognitive dysfunction and suggests novel approaches for prevention and treatment of this condition.

Modulator of TMB-associated immune infiltration (MOTIF) predicts immunotherapy response and guides combination therapy.

Patients with high tumor mutational burden (TMB) levels do not consistently respond to immune checkpoint inhibitors (ICIs), possibly because a high TMB level does not necessarily result in adequate infiltration of CD8+ T cells. Using bulk ribonucleic acid sequencing (RNA-seq) data from 9311 tumor samples across 30 cancer types, we developed a novel tool called the modulator of TMB-associated immune infiltration (MOTIF), which comprises genes that can determine the extent of CD8+ T cell infiltration prompted by a certain TMB level. We confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity cycle. By analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors, we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8+ T cell infiltration. Using pretreatment RNA-seq data from 13 ICI-treated cohorts, we validated the use of MOTIF in predicting CD8+ T cell infiltration and ICI efficacy. Among the components of MOTIF, we identified EMC3 as a negative regulator of CD8+ T cell infiltration, which was validated via in vivo studies. Additionally, MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8+ T cell infiltration and improve ICI efficacy.

Decrotonylation of AKT1 promotes AKT1 phosphorylation and activation during myogenic differentiation.

INTRODUCTION: Myogenic differentiation plays an important role in pathophysiological processes including muscle injury and regeneration, as well as muscle atrophy. A novel type of posttranslational modification, crotonylation, has been reported to play a role in stem cell differentiation and disease. However, the role of crotonylation in myogenic differentiation has not been clarified. OBJECTIVES: This study aims to find the role of crotonylation during myogenic differentiation and explore whether it is a potential target in myogenic dysfunction disease. METHODS: C2C12 cell line and skeletal muscle mesenchymal progenitors of Mus musculus were used for myogenic process study in vitro, while muscle injury model of mice was used for in vivo muscle regeneration study. Mass spectrometry favored in discovery of potential target protein of crotonylation and its specific sites. RESULTS: We confirmed the gradual decrease in total protein crotonylation level during muscle differentiation and found decreased crotonylation of AKT1, which facilitated an increase in AKT1 phosphorylation. Then we verified that crotonylation of AKT1 at specific sites weakened its binding with PDK1 and impaired its phosphorylation. In addition, we found that increased expression of the crotonylation eraser HDAC3 decreased AKT1 crotonylation levels during myogenic differentiation, jointly promoting myogenic differentiation. CONCLUSION: Our study highlights the important role of decrotonylation of AKT1 in the process of muscle differentiation, where it aids the phosphorylation and activation of AKT1 and promotes myogenic differentiation. This is of great significance for exploring the pathophysiological process of muscle injury repair and sarcopenia.

A novel approach on designing ultrahigh burnup metallic TWR fuels: Upsetting the current technological limits.

Abstract: The grand challenge of "net-zero carbon" emission calls for technological breakthroughs in energy production. The traveling wave reactor (TWR) is designed to provide economical and safe nuclear power and solve imminent problems, including limited uranium resources and radiotoxicity burdens from back-end fuel reprocessing/disposal. However, qualification of fuels and materials for TWR remains challenging and it sets an "end of the road" mark on the route of R&D of this technology. In this article, a novel approach is proposed to maneuver reactor operations and utilize high-temperature transients to mitigate the challenges raised by envisioned TWR service environment. Annular U-50Zr fuel and oxidation dispersion strengthened (ODS) steels are proposed to be used instead of the current U-10Zr and HT-9 ferritic/martensitic steels. In addition, irradiation-accelerated transport of Mn and Cr to the cladding surface to form a protective oxide layer as a self-repairing mechanism was discovered and is believed capable of mitigating long-term corrosion. This work represents an attempt to disruptively overcome current technological limits in the TWR fuels. Impact statement: After the Fukushima accident in 2011, the entire nuclear industry calls for a major technological breakthrough that addresses the following three fundamental issues: (1) Reducing spent nuclear fuel reprocessing demands, (2) reducing the probability of a severe accident, and (3) reducing the energy production cost per kilowatt-hour. An inherently safe and ultralong life fast neutron reactor fuel form can be such one stone that kills the three birds. In light of the recent development findings on U-50Zr fuels, we hereby propose a disruptive, conceptual metallic fuel design that can serve the following purposes at the same time: (1) Reaching ultrahigh burnup of above 40% FIMA, (2) possessing strong inherent safety features, and (3) extending current limits on fast neutron irradiation dose to be far beyond 200 dpa. We believe that this technology will be able to bring about revolutionary changes to the nuclear industry by significantly lowering the operational costs as well as improving the reactor system safety to a large extent. Supplementary information: The online version contains supplementary material available at 10.1557/s43577-022-00420-4.

Infection-Associated Thymic Atrophy.

The thymus is a vital organ of the immune system that plays an essential role in thymocyte development and maturation. Thymic atrophy occurs with age (physiological thymic atrophy) or as a result of viral, bacterial, parasitic or fungal infection (pathological thymic atrophy). Thymic atrophy directly results in loss of thymocytes and/or destruction of the thymic architecture, and indirectly leads to a decrease in naïve T cells and limited T cell receptor diversity. Thus, it is important to recognize the causes and mechanisms that induce thymic atrophy. In this review, we highlight current progress in infection-associated pathogenic thymic atrophy and discuss its possible mechanisms. In addition, we discuss whether extracellular vesicles/exosomes could be potential carriers of pathogenic substances to the thymus, and potential drugs for the treatment of thymic atrophy. Having acknowledged that most current research is limited to serological aspects, we look forward to the possibility of extending future work regarding the impact of neural modulation on thymic atrophy.

Human African trypanosomiasis: the current situation in endemic regions and the risks for non-endemic regions from imported cases.

Human African trypanosomiasis (HAT) is caused by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense and caused devastating epidemics during the 20th century. Due to effective control programs implemented in the last two decades, the number of reported cases has fallen to a historically low level. Although fewer than 977 cases were reported in 2018 in endemic countries, HAT is still a public health problem in endemic regions until it is completely eliminated. In addition, almost 150 confirmed HAT cases were reported in non-endemic countries in the last three decades. The majority of non-endemic HAT cases were reported in Europe, USA and South Africa, due to historical alliances, economic links or geographic proximity to disease-endemic countries. Furthermore, with the implementation of the 'Belt and Road' project, sporadic imported HAT cases have been reported in China as a warning sign of tropical diseases prevention. In this paper, we explore and interpret the data on HAT incidence and find no positive correlation between the number of HAT cases from endemic and non-endemic countries. This data will provide useful information for better understanding the imported cases of HAT globally in the post-elimination phase.