Disrupted de novo pyrimidine biosynthesis impairs adult hippocampal neurogenesis and cognition in pyridoxine-dependent epilepsy.

Despite seizure control by early high-dose pyridoxine (vitamin B6) treatment, at least 75% of pyridoxine-dependent epilepsy (PDE) patients with ALDH7A1 mutation still suffer from intellectual disability. It points to a need for additional therapeutic interventions for PDE beyond pyridoxine treatment, which provokes us to investigate the mechanisms underlying the impairment of brain hemostasis by ALDH7A1 deficiency. In this study, we show that ALDH7A1-deficient mice with seizure control exhibit altered adult hippocampal neurogenesis and impaired cognitive functions. Mechanistically, ALDH7A1 deficiency leads to the accumulation of toxic lysine catabolism intermediates, α-aminoadipic-δ-semialdehyde and its cyclic form, δ-1-piperideine-6-carboxylate, which in turn impair de novo pyrimidine biosynthesis and inhibit NSC proliferation and differentiation. Notably, supplementation of pyrimidines rescues abnormal neurogenesis and cognitive impairment in ALDH7A1-deficient adult mice. Therefore, our findings not only define the important role of ALDH7A1 in the regulation of adult hippocampal neurogenesis but also provide a potential therapeutic intervention to ameliorate the defective mental capacities in PDE patients with seizure control.

Improving Anti-HIV activity and pharmacokinetics of enfuvirtide (T20) by modification with oligomannose.

Dendritic cells (DCs) play a pivotal role in controlling HIV-1 infections of CD4+ T cells. DC-SIGN, which is expressed on the surface of DCs, efficiently captures HIV-1 virions by binding to the highly mannosylated membrane protein, gp120, and then the DCs transport the virus to target T cells in lymphoid organs. This study explored the modification of T20, a peptide inhibitor of HIV-1 fusion, by conjugation of the N-terminus with varying sizes of oligomannose, which are DC-SIGN-specific carbohydrates, aiming to create dual-targeting HIV inhibitors. Mechanistic studies indicated the dual-target binding of the conjugates. Antiviral assays demonstrated that N-terminal mannosylation of T20 resulted in increased inhibition of the viral infection of TZM-b1 cells (EC50 = 0.3-0.8 vs. 1.4 nM). Pentamannosylated T20 (M5-T20) exhibited a stronger inhibitory effect on virus entry into DC-SIGN+ 293T cells compared with T20 (67% vs. 50% inhibition at 500 µM). M5-T20 displayed an extended half-life in rats relative to T20 (T1/2: 8.56 vs. 1.64 h, respectively). These conjugates represent a potential new treatment for HIV infections with improved antiviral activity and pharmacokinetics, and this strategy may prove useful in developing dual-target inhibitors for other pathogens that require DC-SIGN involvement for infection.

Glycan-Modified Peptides for Dual Inhibition of Human Immunodeficiency Virus Entry into Dendritic Cells and T Cells.

Dendritic cells (DCs) play a crucial role in HIV-1 infection of CD4+ T cells. DC-SIGN, a lectin expressed on the surface of DCs, binds to the highly mannosylated viral membrane protein gp120 to capture HIV-1 virions and then transport them to target T cells. In this study, we modified peptide C34, an HIV-1 fusion inhibitor, at different sites using different sizes of the DC-SIGN-specific carbohydrates to provide dual-targeted HIV inhibition. The dual-target binding was confirmed by mechanistic studies. Pentamannose-modified C34 inhibited virus entry into both DC-SIGN+ 293T cells (52%-71% inhibition at 500 µM) and CD4+ TZM-b1 cells (EC50 = 0.7-1.7 nM). One conjugate, NC-M5, showed an extended half-life relative to C34 in rats (T1/2: 7.8 vs 1.02 h). These improvements in antiviral activity and pharmacokinetics have potential for HIV treatment and the development of dual-target inhibitors for pathogens that require the involvement of DC-SIGN for infection.

Coordination between circadian neural circuit and intracellular molecular clock ensures rhythmic activation of adult neural stem cells.

The circadian clock throughout the day organizes the activity of neural stem cells (NSCs) in the dentate gyrus (DG) of adult hippocampus temporally. However, it is still unclear whether and how circadian signals from the niches contribute to daily rhythmic variation of NSC activation. Here, we show that norepinephrinergic (NEergic) projections from the locus coeruleus (LC), a brain arousal system, innervate into adult DG, where daily rhythmic release of norepinephrine (NE) from the LC NEergic neurons controlled circadian variation of NSC activation through ß3-adrenoceptors. Disrupted circadian rhythmicity by acute sleep deprivation leads to transient NSC overactivation and NSC pool exhaustion over time, which is effectively ameliorated by the inhibition of the LC NEergic neuronal activity or ß3-adrenoceptors-mediated signaling. Finally, we demonstrate that NE/ß3-adrenoceptors-mediated signaling regulates NSC activation through molecular clock BMAL1. Therefore, our study unravels that adult NSCs precisely coordinate circadian neural circuit and intrinsic molecular circadian clock to adapt their cellular behavior across the day.

Adult neurogenesis research in China.

Neural stem cells are multipotent stem cells that generate functional newborn neurons through a process called neurogenesis. Neurogenesis in the adult brain is tightly regulated and plays a pivotal role in the maintenance of brain function. Disruption of adult neurogenesis impairs cognitive function and is correlated with numerous neurologic disorders. Deciphering the mechanisms underlying adult neurogenesis not only advances our understanding of how the brain functions, but also offers new insight into neurologic diseases and potentially contributes to the development of effective treatments. The field of adult neurogenesis is experiencing significant growth in China. Chinese researchers have demonstrated a multitude of factors governing adult neurogenesis and revealed the underlying mechanisms of and correlations between adult neurogenesis and neurologic disorders. Here, we provide an overview of recent advancements in the field of adult neurogenesis due to Chinese scientists.

Glomerular filtration rate in patients with type 2 diabetes mellitus: is serum isthmin-1 level a possible link?

INTRODUCTION: Isthmin-1 (Ism-1) is a novel adipokine. However, little is known regarding the association between Ism-1 and type 2 diabetes mellitus (T2DM). This study aimed to investigate the relationship between serum Ism-1 levels and glomerular filtration rate (GFR) in patients with T2DM. RESEARCH DESIGN AND METHODS: A total of 209 patients with T2DM were recruited into this retrospective study. Clinical data were collected. Fasting blood samples were collected for serum Ism-1 testing using ELISA kits. Based on the estimated glomerular filtration rate (eGFR), participants were divided into the normal eGFR group (n=167) and the decreased eGFR group (n=42). The relationship between Ism-1 and eGFR was assessed using linear and binary logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was employed to examine the predictive efficacy of Ism-1 for distinguishing patients with eGFR <60 mL/min/1.73 m2. RESULTS: Compared with patients with normal eGFR, serum Ism-1 levels were increased in patients with decreased eGFR (p<0.001). Serum Ism-1 levels were negatively correlated with eGFR in patients with T2DM even after multiple adjustments (p<0.001). For each 0.1 ng/mL increment of Ism-1, the odds of having an eGFR <60 mL/min/1.73 m2 increased by 54.5% (OR=1.545; p<0.001) in patients with T2DM. ROC analysis showed that higher serum Ism-1 levels (>1.297 ng/mL) had predictive efficacy in patients with eGFR <60 mL/min/1.73 m2, with an area under the curve of 0.908. CONCLUSIONS: Serum Ism-1 levels were inversely associated with eGFR, and high Ism-1 levels may be used as a potential biomarker for predicting kidney function impairment in patients with T2DM.

Proteomic Profiling and Tumor Microenvironment Characterization Reveal Molecular and Immunological Hallmarks of Left-Sided and Right-Sided Colon Cancer Tumorigenesis.

Left-sided and right-sided colon cancer (LSCC and RSCC) display different biological and clinical characteristics. However, the differences in their tumorigenesis and tumor microenvironment remain unclear. In this study, we profiled the proteomic landscapes of LSCC and RSCC with data-independent acquisition mass spectrometry (DIA-MS) using fresh tumor and adjacent normal tissues from 24 patients. A total of 7403 proteingroups were primarily identified with DIA-MS. After quality control, 7212 proteingroups were used for further analysis. Through comparing the difference in proteomic profiles between LSCC and RSCC samples, 2556 commonly and 1982 region-type-specific regulated proteingroups were characterized. During the development of LSCC and RSCC, metabolic, growth, cell division, cell adhesion, and migration pathways were found to be significantly dysregulated (P < 0.05), which was further confirmed by transcriptome data from TCGA. Compared to RSCC, most parts of the immune-related signatures, immune cell infiltration scores, and overall immune scores of LSCC were higher. The systematic elucidation of proteomic and transcriptomic profiles in this work improves our understanding of tumorigenesis and immune microenvironment characteristics of LSCC and RSCC.

Serum Isthmin-1 is negatively correlated with HDL-C in type 2 diabetes mellitus.

BACKGROUND: Isthmin-1 (Ism-1) is a newly identified insulin-like adipokine that increases glucose uptake by adipocytes and inhibits hepatic lipid synthesis. Recent studies have shown that Ism-1 can improve the metabolic disorders associated with type 2 diabetes mellitus (T2DM) and improve lipid metabolism. The classic function of high-density lipoprotein cholesterol (HDL-C) is to transport cholesterol from extra-hepatic tissues to the liver for metabolism. In contrast, disorders of lipid metabolism and inflammation are the leading causes of atherosclerosis (As). Atherosclerosis often manifests as loss of elasticity, lipid accumulation, fibrous tissue proliferation and calcium deposits in the affected arteries, eventually forming plaques. AIM: To illustrate the correlation between HDL-C and Ism-1 in T2DM, and the relationship between lipoprotein cholesterol and carotid plaque. METHODS: A total of 128 patients with T2DM were enrolled in the study and basic information was collected. HDL-C levels were measured chemically. Serum Ism-1 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Linear regression analysis was used to assess the correlation between serum Ism-1 levels and HDL-C in patients with T2DM. Basic information was again collected from 226 patients with T2DM. Independent sample t-tests were performed to explore the relationship between carotid plaque formation and lipids. RESULTS: HDL-C was divided into four groups according to quartiles and there was a between-group difference in Ism-1 (p = 0.040). Multivariable linear regression showed a negative association between Ism-1 and HDL-C in T2DM (ß = -0.235, p < 0.001), even after adjusting for related factors (ß = -0.165, p = 0.009). Low-density lipoprotein cholesterol (LDL-C) and HDL-C showed significant differences between the carotid plaque group and the non-carotid plaque group (pLDL-C = 0.007, pHDL-C = 0.003). CONCLUSION: Serum Ism-1 and HDL-C are negatively correlated in T2DM. LDL-C is significantly higher in carotid plaque group than non-carotid plaque group, while HDL-C is significantly lower than in the non-carotid plaque group.

Technological Development and Application of Plant Genetic Transformation.

Genetic transformation is an important strategy for enhancing plant biomass or resistance in response to adverse environments and population growth by imparting desirable genetic characteristics. Research on plant genetic transformation technology can promote the functional analysis of plant genes, the utilization of excellent traits, and precise breeding. Various technologies of genetic transformation have been continuously discovered and developed for convenient manipulation and high efficiency, mainly involving the delivery of exogenous genes and regeneration of transformed plants. Here, currently developed genetic transformation technologies were expounded and compared. Agrobacterium-mediated gene delivery methods are commonly used as direct genetic transformation, as well as external force-mediated ways such as particle bombardment, electroporation, silicon carbide whiskers, and pollen tubes as indirect ones. The regeneration of transformed plants usually involves the de novo organogenesis or somatic embryogenesis pathway of the explants. Ectopic expression of morphogenetic transcription factors (Bbm, Wus2, and GRF-GIF) can significantly improve plant regeneration efficiency and enable the transformation of some hard-to-transform plant genotypes. Meanwhile, some limitations in these gene transfer methods were compared including genotype dependence, low transformation efficiency, and plant tissue damage, and recently developed flexible approaches for plant genotype transformation are discussed regarding how gene delivery and regeneration strategies can be optimized to overcome species and genotype dependence. This review summarizes the principles of various techniques for plant genetic transformation and discusses their application scope and limiting factors, which can provide a reference for plant transgenic breeding.

Targeted ablation of signal transducer and activator of transduction 1 alleviates inflammation by microglia/macrophages and promotes long-term recovery after ischemic stroke.

BACKGROUND: Brain microglia and macrophages (Mi/MΦ) can shift to a harmful or advantageous phenotype following an ischemic stroke. Identification of key molecules that regulate the transformation of resting Mi/MΦ could aid in the development of innovative therapies for ischemic stroke. The transcription factor signal transducer and activator of transduction 1 (STAT1) has been found to contribute to acute neuronal death (in the first 24 h) following ischemic stroke, but its effects on Mi/MΦ and influence on long-term stroke outcomes have yet to be determined. METHODS: We generated mice with tamoxifen-induced, Mi/MΦ-specific knockout (mKO) of STAT1 driven by Cx3cr1CreER. Expression of STAT1 was examined in the brain by flow cytometry and RNA sequencing after ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). The impact of STAT1 mKO on neuronal cell death, Mi/MΦ phenotype, and brain inflammation profiles were examined 3-5 days after MCAO. Neurological deficits and the integrity of gray and white matter were assessed for 5 weeks after MCAO by various neurobehavioral tests and immunohistochemistry. RESULTS: STAT1 was activated in Mi/MΦ at the subacute stage (3 days) after MCAO. Selective deletion of STAT1 in Mi/MΦ did not alter neuronal cell death or infarct size at 24 h after MCAO, but attenuated Mi/MΦ release of high mobility group box 1 and increased arginase 1-producing Mi/MΦ 3d after MCAO, suggesting boosted inflammation-resolving responses of Mi/MΦ. As a result, STAT1 mKO mice had mitigated brain inflammation at the subacute stage after MCAO and less white matter injury in the long term. Importantly, STAT1 mKO was sufficient to improve functional recovery for at least 5 weeks after MCAO in both male and female mice. CONCLUSIONS: Mi/MΦ-targeted STAT1 KO does not provide immediate neuroprotection but augments inflammation-resolving actions of Mi/MΦ, thereby facilitating long-term functional recovery after stroke. STAT1 is, therefore, a promising therapeutic target to harness beneficial Mi/MΦ responses and improve long-term outcomes after ischemic stroke.

Effect of biodrying of lignocellulosic biomass on humification and microbial diversity.

By optimizing the carbon to nitrogen (C/N) ratio, this study accomplished an improved level of humification and microbial diversity in the biodrying process of lignocellulosic biomass. The results demonstrated that C/N ratio of 20 accelerated the decomposition of refractory lignocellulose, resulting in lower greenhouse gas emissions and the production of highly mature fertilizer with a germination index of 119.0% and a humic index of 3.2. Moreover, C/N ratio of 20 was found to diversify microbial communities, including Pseudogracilibacillus, Sinibacillus, and Georgenia, which contributed to the decomposition of lignocellulosic biomass and the production of humic acid. Hence, it is recommended to regulate the C/N ratio to 20:1 during the biodrying of biogas residue and wood chips to promote the economic feasibility and bioresource recycling.

Construction and Characterization of Severe Fever with Thrombocytopenia Syndrome Virus with a Fluorescent Reporter for Antiviral Drug Screening.

Severe fever with thrombocytopenia syndrome (SFTS) caused by a novel bunyavirus (SFTSV) is an emerging infectious disease with up to 30% case fatality. Currently, there are no specific antiviral drugs or vaccines for SFTS. Here, we constructed a reporter SFTSV in which the virulent factor nonstructural protein (NSs) was replaced by eGFP for drug screening. First, we developed a reverse genetics system based on the SFTSV HBMC5 strain. Then, the reporter virus SFTSV-delNSs-eGFP was constructed, rescued, and characterized in vitro. SFTSV-delNSs-eGFP showed similar growth kinetics with the wild-type virus in Vero cells. We further detected the antiviral efficacy of favipiravir and chloroquine against wild-type and recombinant SFTSV by the quantification of viral RNA, and compared the results with that of fluorescent assay using high-content screening. The results showed that SFTSV-delNSs-eGFP could be used as a reporter virus for antiviral drug screening in vitro. In addition, we analyzed the pathogenesis of SFTSV-delNSs-eGFP in interferon receptor-deficient (IFNAR-/-) C57BL/6J mice and found that unlike the fatal infection of the wild-type virus, no obvious pathological change or viral replication were observed in SFTSV-delNSs-eGFP-infected mice. Taken together, the green fluorescence and attenuated pathogenicity make SFTSV-delNSs-eGFP a potent tool for the future high-throughput screening of antiviral drugs.

lncRNA RMST suppresses the progression of colorectal cancer by competitively binding to miR-27a-3p/RXRα axis and inactivating Wnt signaling pathway.

Colorectal cancer (CRC) ranks the 3rd in cancer types globally. Long noncoding RNAs (lncRNAs) are related to the initiation and progression of CRC. The current study plans to reveal the action of rhabdomyosarcoma 2-associated transcript (RMST) in CRC. The results show that RMST is downregulated in CRC specimens and cell lines relative to normal specimens and a fetal normal colon cell line (FHC), respectively. Elevation of RMST represses cell proliferation and colony formation and induces cell apoptosis in CRC cells. Bioinformatic analysis reveals a binding site in RMST for miR-27a-3p. The direct association between RMST and miR-27a-3p is confirmed by dual luciferase reporter assay, RNA pull-down assay, and real time-quantitative polymerase chain reaction (RT-qPCR). miR-27a-3p is upregulated in CRC tumor specimens relative to normal specimens, and there is a negative correlation between RMST and miR-27a-3p in CRC tumor specimens. In addition, the effects of RMST overexpression are weakened by the elevation of miR-27a-3p. RMST and retinoid X receptor (RXRα) share the same complementary site with miR-27a-3p. The direct association between RXRα and miR-27a-3p is confirmed by RNA pull-down assay, RT-qPCR and western blot analysis. Overexpression of RMST induces RXRα expression and inactivates the Wnt signaling pathway by decreasing ß-catenin levels in CRC cells. Collectively, our findings reveal a pivotal role of RMST in regulating miR-27a-3p/RXRα axis and counteracting Wnt signaling pathway during the progression of CRC.

From waste to wealth: Innovations in organic solid waste composting.

Organic solid waste (OSW) is not only a major source of environmental contamination, but also a vast store of useful materials due to its high concentration of biodegradable components that can be recycled. Composting has been proposed as an effective strategy for recycling OSW back into the soil in light of the necessity of a sustainable and circular economy. In addition, unconventional composting methods such as membrane-covered aerobic composting and vermicomposting have been reported more effective than traditional composting in improving soil biodiversity and promoting plant growth. This review investigates the current advancements and potential trends of using widely available OSW to produce fertilizers. At the same time, this review highlights the crucial role of additives such as microbial agents and biochar in the control of harmful substances in composting. Composting of OSW should include a complete strategy and a methodical way of thinking that can allow product development and decision optimization through interdisciplinary integration and data-driven methodologies. Future research will likely concentrate on the potential in controlling emerging pollutants, evolution of microbial communities, biochemical composition conversion, and the micro properties of different gases and membranes. Additionally, screening of functional bacteria with stable performance and exploration of advanced analytical methods for compost products are important for understanding the intrinsic mechanisms of pollutant degradation.

Effect of B-Doping and Manifestation on TiO2-Supported IrO2 for Oxygen Evolution Reaction in Water Electrolysis.

To commercialize hydrogen production by proton exchange membrane (PEM) electrolysis, the amount of rare and precious metal (iridium) required for anodic oxygen evolution reaction (OER) must be greatly reduced. In order to solve the problem, carrier loading is used to reduce the amount of iridium. Unlike the carrier modified by conventional metal element doping, this work doped the carrier with the nonmetallic element and then prepared IrO2/TiBxO2 composite catalyst using the Adams melting method. B-doped TiO2 supports with different doping amounts show the main phase rutile structure. Among them, the conductivity of B-doped carrier shows an increasing trend with the increase of doping amount, because boron can form holes and negative centers after doping, and more carriers improve the conductivity of the support. In addition, since element B is manifested from inside to outside on the support, B can affect the catalytic process. After the manifestation of element B, the carrier loaded with IrO2 exhibited superior electrocatalytic properties. The voltammetric charge per unit mass of 40IrO2/TiB0.3O2#2 (where #2 represents B after manifestation) reaches 1970 mC (cm2 mg)-1, the corresponding overpotential is 273 mV at a current density of 10 mA/cm-2, and the Tafel slope is 61.9 mV/dec Also, the charge transfer resistance is only 15 Ω. Finally, in the stability test, the composite catalyst is also better than pure IrO2 in the 20 000 s operation. Therefore, element B has an unexpectedly positive effect on the catalytic progress on the surface of the support after its manifestation.

L-arginine homeostasis governs adult neural stem cell activation by modulating energy metabolism in vivo.

Neurogenesis in the developing and adult brain is intimately linked to remodeling of cellular metabolism. However, it is still unclear how distinct metabolic programs and energy sources govern neural stem cell (NSC) behavior and subsequent neuronal differentiation. Here, we found that adult mice lacking the mitochondrial urea metabolism enzyme, Arginase-II (Arg-II), exhibited NSC overactivation, thereby leading to accelerated NSC pool depletion and decreased hippocampal neurogenesis over time. Mechanistically, Arg-II deficiency resulted in elevated L-arginine levels and induction of a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) caused by impaired attachment of hexokinase-I to mitochondria. Notably, selective inhibition of OXPHOS ameliorated NSC overactivation and restored abnormal neurogenesis in Arg-II deficient mice. Therefore, Arg-II-mediated intracellular L-arginine homeostasis directly influences the metabolic fitness of neural stem cells that is essential to maintain neurogenesis with age.

Antiviral effects and tissue exposure of tetrandrine against SARS-CoV-2 infection and COVID-19.

Tetrandrine (TET) has been used to treat silicosis in China for decades. The aim of this study was to facilitate rational repurposing of TET against SARS-CoV-2 infection. In this study, we confirmed that TET exhibited antiviral potency against SARS-CoV-2 in the African green monkey kidney (Vero E6), human hepatocarcinoma (Huh7), and human lung adenocarcinoma epithelial (Calu-3) cell lines. TET functioned during the early-entry stage of SARS-CoV-2 and impeded intracellular trafficking of the virus from early endosomes to endolysosomes. An in vivo study that used adenovirus (AdV) 5-human angiotensin-converting enzyme 2 (hACE2)-transduced mice showed that although TET did not reduce pulmonary viral load, it significantly alleviated pathological damage in SARS-CoV-2-infected murine lungs. The systemic preclinical pharmacokinetics were investigated based on in vivo and in vitro models, and the route-dependent biodistribution of TET was explored. TET had a large volume of distribution, which contributed to its high tissue accumulation. Inhaled administration helped TET target the lung and reduced its exposure to other tissues, which mitigated its off-target toxicity. Based on the available human pharmacokinetic data, it appeared feasible to achieve an unbound TET 90% maximal effective concentration (EC90) in human lungs. This study provides insights into the route-dependent pulmonary biodistribution of TET associated with its efficacy.

Development and validation of a mitochondrial energy metabolism-related risk model in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and ranks third inmortality. Mitochondria are the energy manufacturers of cells. Disruption of mitochondrial energy metabolism pathways is strongly correlated with the onset and progression of HCC. Aberrant genes in mitochondrial energy metabolism pathways may represent a unique diagnostic and therapeutic targets that act as indicators for HCC. METHODS: Gene expression data from 374 HCC patients and 50 controls were acquired from TCGA database. A total of 188 mitochondrial energy metabolism-related genes (MMRGs) were obtained from KEGG PATHWAY database. A total of 368 patients with survival data were randomly split into training and validation groups in a 7: 3 ratio. Prognosis-related MMRGs were selected by univariate Cox and LASSO analyses. Kaplan-Meier and ROC curves were employed to analyze the model precision, whereas the validation set was used for model verification. Furthermore, clinical examinations, immune infiltration analysis, GSVA, and immunotherapy analysis were conducted in the high- and low-risk groups. Finally, the risk model was combined with the clinical variables of HCC patients to perform univariate and multivariate Cox regression analyses to obtain independent risk indicators and draw a nomogram. Therefore, we evaluated the accuracy of the predictions using calibration curves. RESULTS: A total of 6032 differentially expressed genes (DEGs) were detected in the HCC and control samples. After overlapping DEGs with 188 MMRGs, 42 mitochondrial energy metabolism-related DEGs (DEMMRGs) were identified. A 17 specific genes-based risk score model of HCC was created, which revealed effectiveness in each TCGA training and validation dataset. Moreover, patients categorized by risk scores exhibited distinct immune infiltration status, immunotherapy responsiveness, and functional properties. Finally, univariate and multivariate Cox regression analyses revealed that risk score and stage T were independent predictive variables. Based on the T stage and risk score, a nomogram for estimating the survival of HCC patients was created. The calibration curves demonstrated that the prediction model had a high level of accuracy. CONCLUSIONS: Our study constructed a mitochondrial energy metabolism-related risk model, that may be utilized to anticipate HCC prognosis and represent the immunological microenvironment of HCC.