Yuanbing Yao

Glioblastoma (GBM) is a highly aggressive brain tumour with a poor prognosis. Mitochondrial dysfunction, including changes in oxidative phosphorylation, reactive oxygen species (ROS) production, and cristae organisation, plays a key role in the progression of GBM. However, the role of mitochondrial protein complexes in GBM biology is poorly understood. Bioinformatics analyses of GBM datasets and mitochondrial complexome profiling (‘MitCOM’) identified mitochondrial protein complex genes (MitCOMGs) with prognostic significance. A six-gene prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) regression and validated in independent cohorts. GLUD1, the most significant gene, was further validated through in vitro assays, including Blue Native PAGE, metabolomic profiling, and various cell assays. GLUD1 expression was downregulated in GBM and associated with poor survival. Functional studies showed that GLUD1 regulates mitochondrial crista organisation and metabolic reprogramming. GLUD1 overexpression disrupted mitochondrial integrity, impaired respiratory chain complex assembly, and reduced adenosine triphosphate production. Metabolomic profiling revealed altered amino acid metabolism and tricarboxylic acid cycle intermediates that inhibited GBM cell proliferation and invasion. GLUD1 is a key mitochondrial regulator in GBM, and its downregulation contributes to tumour progression through mitochondrial dysfunction and metabolic reprogramming. The six-gene MitCOMG model offers robust prognostic value and identified GLUD1 as a potential therapeutic target for GBM.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. The hypoxic microenvironment in HCC enhances glycolysis and co-directed lactate accumulation, which leads to increased lactylation. However, the exact biological pattern remains to be elucidated. Therefore, we sought to identify hypoxia-glycolysis-lactylation (HGL) prognosis-related signatures and validate this in vitro. Methods: Transcriptomic data of patients with HCC were collected from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases. Differentially expressed HGL genes between HCC and normal tissues were obtained by DEseq2. The consensus clustering algorithm was employed to stratify patients into two distinct clusters. Subsequently, the single sample Gene Set Enrichment Analysis (ssGSEA), Tumor Immune Estimation Resource (TIMER) and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms were utilized to assess immune infiltration and immune evasion. Least Absolute Shrinkage and Selection Operator (LASSO) and COX regression analysis were used to identify an HGL prognosis-related signature. Based on spatial transcriptome and histological data, we analyzed the expression of these genes in HCC and explored the function of Homer Scaffold Protein 1 (HOMER1) in HCC cells. Results: We identified 72 differentially expressed HGL genes and two HGL clusters. Cluster2, with better survival (p < 0.001), was significantly enriched in metabolic-related pathways. The HGL prognosis-related signature exhibited great predictive efficacy for patients in TCGA, ICGC, and GSE148355 databases (3-year area under the curve (AUC) = 0.822, 0.738, and 0.707, respectively). The elevated expression of HOMER1 in HCC was revealed by the combination of spatial transcriptome and histological data. Knocking down HOMER1 significantly inhibited the malignant progression of HCC cells. Conclusions: We identified a signature with great predictive efficacy and discovered a gene, HOMER1, that influences the malignant progression of HCC with the potential to become a novel therapeutic target.

The MRE11-RAD50-NBS1 (MRN) complex plays a crucial role in DNA double-strand breaks (DSBs) sensing and initiation of signaling cascades. However, the precise mechanisms by which the recruitment of MRN complex is regulated has yet to be elucidated. Here, we identified TRIpartite motif-containing protein 24 (TRIM24), a protein considered as an oncogene overexpressed in cancers, as a novel signaling molecule in response to DSBs. TRIM24 is essential for DSBs-induced recruitment of MRN complex and activation of downstream signaling. In the absence of TRIM24, MRN mediated DSBs repair is remarkably diminished. Mechanistically, TRIM24 is phosphorylated by ataxia-telangiectasia mutated (ATM) and then recruited to DSBs sites, facilitating the accumulation of the MRN components to chromatin. Depletion of TRIM24 sensitizes human hepatocellular carcinoma cells to cancer therapy agent-induced apoptosis and retards the tumor growth in a subcutaneous xenograft tumor mouse model. Together, our data reveal a novel function of TRIM24 in response to DSBs through regulating the MRN complex, which suggests that TRIM24 may be a potential therapeutic molecular target for tumor treatment.

Background Expensive cost of surgery has limited the use of surgical robot in China. The emergence of “Micro Hand S” surgical robot provides more choices for surgical treatment. Our study was to evaluate the safety and feasibility of “Micro Hand S” surgical robotic gastrectomy for gastric cancer. Methods Perioperative data of 75 patients who underwent “Micro Hand S” surgical robotic gastrectomy (RG) or laparoscopic gastrectomy (LG) at the Department of General Surgery, Third Xiangya Hospital, Central South University from June 2017 to January 2019 were collected to compare the short-term outcomes between the two groups. Results No statistically significant difference was found in baseline characteristics between the two groups (P > 0.05). RG group had longer operation time (P < 0.01). The harvested lymph nodes were comparable between the two groups (P = 0.084). There were five positive margins in the LG group, and the R0 resection rate was comparable between the two groups (P = 0.247). 16 complications occurred in the RG group according to the Clavien-Dindo classification system, 6 in grade I, and 10 in grade II. 68 complications happened in the LG group, 22 in grade I, 44 in grade II, 1 in grade IIIa and 1 in grade IVa. The comprehensive complications index (CCI) was similar between the two groups (P = 0.895). Intraoperative blood loss, surgical resection, reconstruction of the digestive tract intraoperative blood transfusion, Chemoradiotherapy, pathological type, degree of differentiation, proximal resection margin, time of first flatus, time of liquid diet, time of abdominal drainage tube extraction, and hospital stay for RG and LG were similar too (P > 0.05). Conclusion “Micro Hand S” surgical robotic gastrectomy is safe and feasible. Keywords Surgical robot; Gastric cancer; Gastrectomy; Safety; Feasibility

A Phase I clinical study of a Chinese surgical robot, Micro Hand S, was completed recently. The purpose of this research was to evaluate the feasibility and safety of the Micro Hand S surgical robot in the clinical application of general surgery. March 2014 to January 2019, 81 cases of robotic surgery were performed at Third Xiangya Hospital of Central South University. Clinical characteristics, operative outcomes, and postoperative results were collected and analyzed. Patients were followed up with for one month. The results of 81 patients were as follows. The range of operation times was 100-495 min. The range of blood loss was 20-1200 ml, and the docking time range was 7-54 min. The range of first flatus times was 1-7 d, the range of fluid diet times was 1-13 d, and the range of hospital stays was 4-30 d. Three patients (3.7%) required conversion to laparoscopic or open-laparotomy surgery. Two patients (2.5%) needed intraoperative blood transfusions, and one patient (1.2%) required a postoperative blood transfusion. Intraoperative complications occurred in two patients (2.5%), which were bladder injury and ureteral injury. Three patients (3.7%) had postoperative complications, including anastomotic leakage, anastomotic hemorrhage, and wound infection. There were no reoperations during hospitalization, and all 81 patients were discharged smoothly. No readmission or death occurred within 30 d after surgery. The Micro Hand S surgical robot is reliable and safe for the clinical application of general surgery.