Advances in immunotyping of colorectal cancer

Immunotherapy has transformed treatment for various types of malignancy. However, the benefit of immunotherapy is limited to a minority of patients with mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) (dMMR-MSI-H) colorectal cancer (CRC). Understanding the complexity and heterogeneity of the tumor immune microenvironment (TIME) and identifying immune-related CRC subtypes will improve antitumor immunotherapy. Here, we review the current status of immunotherapy and typing schemes for CRC. Immune subtypes have been identified based on TIME and prognostic gene signatures that can both partially explain clinical responses to immune checkpoint inhibitors and the prognosis of patients with CRC. Identifying immune subtypes will improve understanding of complex CRC tumor heterogeneity and refine current immunotherapeutic strategies

Variations of Tongue Coating Microbiota in Patients with Gastric Cancer

The physical status of humans can be estimated by observing the appearance of the tongue coating, known as tongue diagnosis. The goals of this study were to reveal the relationship between tongue coating appearance and the oral microbiota in patients with gastric cancer and to open a novel research direction supporting tongue diagnosis. We used a tongue manifestation acquisition instrument to analyse the thickness of the tongue coating of patients with gastric cancer and that of healthy controls, and high-throughput sequencing was used to describe the microbial community of the tongue coating by sequencing the V2–V4 region of the 16S rDNA. The tongue coatings of 74 patients with gastric cancer were significantly thicker than those of 72 healthy controls (343.11 ± 198.22 versus 98.42 ± 48.25,P&lt;0.001); 51.35% of the patients were assessed as having thick tongue coatings, whereas all healthy controls were assessed as having thin tongue coatings. Thick tongue coatings presented lower microbial community diversity than thin tongue coatings. The tongue coating bacterial community is associated with the appearance of the tongue coating. The tongue coating may be a potential source for diagnosing gastric cancer, but its sensitivity needs to be further improved.</jats:p

Munc13-1 is a Ca2+-phospholipid-dependent vesicle priming hub that shapes synaptic short-term plasticity and enables sustained neurotransmission

During ongoing presynaptic action potential (AP) firing, transmitter release is limited by the availability of release-ready synaptic vesicles (SVs). The rate of SV recruitment (SVR) to release sites is strongly upregulated at high AP frequencies to balance SV consumption. We show that Munc13-1-an essential SV priming protein-regulates SVR via a Ca2+-phospholipid-dependent mechanism. Using knockin mouse lines with point mutations in the Ca2+-phospholipid-binding C2B domain of Munc13-1, we demonstrate that abolishing Ca2+-phospholipid binding increases synaptic depression, slows recovery of synaptic strength after SV pool depletion, and reduces temporal fidelity of synaptic transmission, while increased Ca2+-phospholipid binding has the opposite effects. Thus, Ca2+-phospholipid binding to the Munc13-1-C2B domain accelerates SVR, reduces short-term synaptic depression, and increases the endurance and temporal fidelity of neurotransmission, demonstrating that Munc13-1 is a core vesicle priming hub that adjusts SV re-supply to demand

Advances in reprogramming of energy metabolism in tumor T cells

Cancer is a leading cause of human death worldwide, and the modulation of the metabolic properties of T cells employed in cancer immunotherapy holds great promise for combating cancer. As a crucial factor, energy metabolism influences the activation, proliferation, and function of T cells, and thus metabolic reprogramming of T cells is a unique research perspective in cancer immunology. Special conditions within the tumor microenvironment and high-energy demands lead to alterations in the energy metabolism of T cells. In-depth research on the reprogramming of energy metabolism in T cells can reveal the mechanisms underlying tumor immune tolerance and provide important clues for the development of new tumor immunotherapy strategies as well. Therefore, the study of T cell energy metabolism has important clinical significance and potential applications. In the study, the current achievements in the reprogramming of T cell energy metabolism were reviewed. Then, the influencing factors associated with T cell energy metabolism were introduced. In addition, T cell energy metabolism in cancer immunotherapy was summarized, which highlighted its potential significance in enhancing T cell function and therapeutic outcomes. In summary, energy exhaustion of T cells leads to functional exhaustion, thus resulting in immune evasion by cancer cells. A better understanding of reprogramming of T cell energy metabolism may enable immunotherapy to combat cancer and holds promise for optimizing and enhancing existing therapeutic approaches

Geochronology, geochemistry, and tectonic significance of the Shirenshan gneiss in the southern margin of the North China Block

The Shirenshan Block is a complex geological body located in the southern margin of the North China Block (NCB). From south to north, it can be divided into the Taihua Group migmatite, and the Shirenshan gneiss and magmatic rocks. The petrographic features, tectonic setting, provenance, and geological age of the Shirenshan gneiss using comprehensive field investigations, microstructural analysis, zircon U-Pb radioactive dating, and geochemical analyses were investigated for this study. The petrology, geochemistry, and geochronology of the Shirenshan gneiss suggests that it is mainly a felsic rock and its protolith was a high-K calc-alkaline series A-type granite. The protolith is high in SiO2, Al2O3, K2O, Na2O, and low in CaO and MgO. Overall, the Sr-Nd isotope composition of the samples showed no significant difference, indicating that the Taihua Group migmatite and the Shirenshan gneiss have the same source material. The Shirenshan block may be partially melted from the Taihua group and formed during activity of the Luo-Luan Fault. By the method of zircon dating analysis, the protolith age of the Shirenshan block was determined as 1559±16Ma (Early Proterozoic). Then, the crystallization age of the syntectonic migmatite is 439.2±7.6Ma, which was formed by subduction of the Taihua Group. During the early Cretaceous (119.5±1.3Ma), the Shirenshan gneiss may have experienced regional migmatization and formed the zircon rims age of the Yanshanian period. Litho-geochemical features of the Shirenshan block are similar to A1-type granites indicating that they are post-orogenic. Therefore, the metamorphic deformation of the Shirenshan gneiss reflects the tectonics in the southern margin of the NCB.</p

Overexpression of MsSAG113 gene promotes leaf senescence in alfalfa via participating in the hormone regulatory network

IntroductionAlfalfa (Medicago sativa) is a kind of high quality leguminous forage species, which was widely cultivated in the world. Leaf senescence is an essential process in plant development and life cycle. Here, we reported the isolation and functional analysis of an alfalfa SENESCENCE-ASSOCIATED GENE113 (MsSAG113), which belongs to the PP2C family and mainly plays a role in promoting plant senescence.MethodsIn the study, Agrobacterium-mediated, gene expression analysis, next generation sequencing, DNA pull-down, yeast single hybridization and transient expression were used to identify the function of MsSAG113 gene.ResultsThe MsSAG113 gene was isolated from alfalfa, and the transgenic plants were obtained by Agrobacterium-mediated method. Compared with the wildtype, transgenic plants showed premature senescence in leaves, especially when cultivated under dark conditions. Meanwhile, application of exogenous hormones ABA, SA, MeJA, obviously acclerated leaf senescence of transgenic plants. Furthermore, the detached leaves from transgenic plants turned yellow earlier with lower chlorophyll content. Transcriptome analysis identified a total of 1,392 differentially expressed genes (DEGs), involving 13 transcription factor families. Of which, 234 genes were related to phytohormone synthesis, metabolism and transduction. Pull-down assay and yeast one-hybrid assay confirmed that alfalfa zinc finger CCCH domain-containing protein 39 (MsC3H-39) could directly bind the upstream of MsSAG113 gene. In conclusion, the MsSAG113 gene plays a crucial role in promoting leaf senescence in alfalfa via participating in the hormone regulatory network.DiscussionThis provides an essential basis for further analysis on the regulatory network involving senescence-associated genes in alfalfa

Metagenomics profiling of the microbial community and functional differences in solid-state fermentation vinegar starter (seed Pei) from different Chinese regions

IntroductionThe starter used in solid-state fermentation (SSF) vinegar, known as seed Pei is a microbial inoculant from the previous batch that is utilized during the acetic acid fermentation stage. The seed Pei, which has a notable impact on vinegar fermentation and flavor, is under-researched with comparative studies on microorganisms.MethodsHerein metagenomics was employed to reveal the microbes and their potential metabolic functions of four seed Pei from three regions in China.ResultsThe predominant microbial taxa in all four starters were bacteria, followed by viruses, eukaryotes, and archaea, with Lactobacillus sp. or Acetobacter sp. as main functional taxa. The seed Pei used in Shanxi aged vinegar (SAV) and Sichuan bran vinegar (SBV) exhibited a higher similarity in microbial composition and distribution of functional genes, while those used in two Zhenjiang aromatic vinegar (ZAV) differed significantly. Redundancy analysis (RDA) of physicochemical factors and microbial communities indicated that moisture content, pH, and reducing sugar content are significant factors influencing microbial distribution. Moreover, seven metagenome-assembled genomes (MAGs) that could potentially represent novel species were identified.ConclusionsThere are distinctions in the microbiome and functional genes among different seed Pei. The vinegar starters were rich in genes related to carbohydrate metabolism. This research provides a new perspective on formulating vinegar fermentation starters and developing commercial fermentation agents for vinegar production

Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression

T helper cells that produce IL-17 (Th17 cells) have recently been identified as the third distinct subset of effector T cells. Emerging data suggests that Th17 cells play an important role in the pathogenesis of many liver diseases by regulating innate immunity, adaptive immunity, and autoimmunity. In this study, we examine the role and mechanism of Th17 cells in the pathogenesis of autoimmune hepatitis (AIH). The serum levels of IL-17 and IL-23, as well as the frequency of IL-17+ cells in the liver, were significantly elevated in patients with AIH, compared to other chronic hepatitis and healthy controls. The hepatic expressions of IL-17, IL-23, ROR-γt, IL-6 and IL-1β in patients with AIH were also significantly increased and were associated with increased inflammation and fibrosis. IL-17 induces IL-6 expression via the MAPK signaling pathway in hepatocytes, which, in turn, may further stimulate Th17 cells and forms a positive feedback loop. In conclusion, Th17 cells are key effector T cells that regulate the pathogenesis of AIH, via induction of MAPK dependent hepatic IL-6 expression. Blocking the signaling pathway and interrupting the positive feedback loop are potential therapeutic targets for autoimmune hepatitis