Human umbilical cord mesenchymal stem cells alleviate fatty liver ischemia-reperfusion injury by activating autophagy through upregulation of IFNγ.

Liver ischemia-reperfusion injury (IRI) is an important factor affecting the prognosis of liver transplantation, and extended criteria donors (e.g., steatosis donor livers) are considered to be more sensitive to ischemia-reperfusion injury in liver transplantation. Currently, the application of human umbilical cord mesenchymal stem cells (hMSCs) has great promise in the treatment of various injuries in the liver. This study aimed to investigate the therapeutic role and mechanism of hMSCs in fatty liver IRI. After more than 8 weeks of high-fat chow feeding, we constructed a fatty liver mouse model and established ischemic injury of about 70% of the liver. Six hours after IRI, liver injury was significantly alleviated in hMSCs-treated mice, and the expression levels of liver enzyme, inflammatory factor TNF-α, and apoptotic proteins were significantly lower than those of the control group, which were also significant in pathological sections. Transcriptomics analysis showed that IFNγ was significantly upregulated in the hMSCs group. Mechanistically, IFNγ, which activates the MAPK pathway, is a potent agonist that promotes the occurrence of autophagy in hepatocytes to exert a protective function, which was confirmed by in vitro experiments. In summary, hMSCs treatment could slow down IRI in fatty liver by activating autophagy through upregulation of IFNγ, and this effect was partly direct.

[Bibliometrics Analysis of Studies on Hypertrophic Cardiomyopathy From 2018 to 2022].

Objective To analyze the research progress and hot topics in hypertrophic cardiomyopathy from 2018 to 2022.Methods The publications in the field of hypertrophic cardiomyopathy from January 1,2018 to December 31,2022 were retrieved from Web of Science core collection database and included for a bibliometric analysis.Results A total of 6355 publications were included,with an average citation frequency of 7 times.The year 2021 witnessed the most publications (1406).The analysis with VOSviewer showed that the research on sudden death related to hypertrophic cardiomyopathy,especially the predictive value of late gadolinium-enhanced cardiac MRI in sudden death,was a hot topic.In addition,gene detection and the new drug mavacamten became hot research topics.The United States was the country with the largest number of publications and the highest citation frequency in this field.Chinese scholars produced the second largest number of publications,which,however,included few high-quality research results.Conclusions Risk stratification and prevention of sudden death is still an important and hot research content in the field of hypertrophic cardiomyopathy.Chinese scholars should carry out multi-center cooperation in the future to improve the research results.

Circadian Rhythm Regulator REV-ERBα Attenuates Neuroapoptosis in Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats.

Subarachnoid hemorrhage (SAH) is associated with circadian rhythm abnormalities, in which REV-ERBα plays a major regulatory role. Our ambition was to investigate the capacity of REV-ERBα to inhibit neuronal neuroapoptosis induced by early brain injury (EBI) after SAH. The endovascular perforation model was used to produce experimental SAH in Sprague-Dawley rats. Specific small-interfering RNA was used to downregulate the expression REV-ERBα while SR9009 was used to upregulate the expression before assessments. Short- and long-term neurobehavior assessments, immunofluorescence staining, TUNEL staining, Nissl staining, brain water content, and Western blot were performed. The expression level of endogenous REVERBα tended to increase and then decrease after SAH and peaked at 48 h. REV-ERBα upregulation diminished neuronal apoptosis and enhanced neurological function deficits. Meanwhile, REV-ERBα downregulation aggravated the damage. Furthermore, the levels of downstream proteins of REV-ERBα (i.e., brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK)) changed accordingly with REV-ERBα regulation. REV-ERBα may attenuate neuronal apoptosis in EBI after SAH through the BMAL1/CLOCK pathway.

Isolation and antihyperglycemic effects of garcibractinols A-H, intricate polycyclic polyprenylated acylphloroglucinols from the fruits of Garcinia bracteata.

Eight previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) were isolated from the fruits of Garcinia bracteata and named garcibractinols A-H. Garcibractinols A-F (compounds 1-6) were bicyclic polyprenylated acylphloroglucinols (BPAPs) sharing a rare bicyclo[4.3.1]decane core. On the other hand, garcibractinols G and H (compounds 7 and 8) shared an unprecedented BPAP skeleton bearing a 9-oxabicyclo[6.2.1]undecane core. The structures andabsolute configurations of compounds 1-8 were determined by spectroscopic analysis,single-crystal X-ray diffraction analysis, and quantum chemical calculation. The breakage of the C-3/C-4 linkage through the retro-Claisen reaction was a key step in the biosynthesis of compounds 7 and 8. The antihyperglycemic effects of the eight compounds were evaluated in insulin-resistant HepG2 cells. At a concentration of 10 µM, compounds 2 and 5-8 significantly increased the glucose consumption in the HepG2 cells. Furthermore, compound 7 was more effective than metformin (which was used as a positive control) in promoting glucose consumption in the cells. The findings of this study suggest that compounds 2 and 5-8 have anti-diabetic effects.

Response of anammox granules to the simultaneous exposure to macrolide and aminoglycoside antibiotics: Linking performance to mechanism.

Antibiotic pollution is becoming increasingly severe due to its extensive use. The potential application of the anaerobic ammonium oxidation (anammox) process in the treatment of wastewater containing antibiotics has attracted much attention. As common antibiotics, spiramycin (SPM) and streptomycin (STM) are widely used to treat human and animal diseases. However, their combined effects on the anammox process remain unknown. Therefore, this study systematically evaluated the response of the anammox process to both antibiotics. The half maximal inhibitory concentrations of SPM and STM were determined. The continuous-flow anammox system could adapt to SPM and STM at low concentrations, while antibiotics at high concentrations exhibited inhibitory effects. When the concentrations reached 5 mg L-1 SPM and 50 mg L-1 STM, the nitrogen removal efficiency dramatically decreased and then rapidly recovered within 8 days. Correspondingly, the abundances of dominant bacteria and genes also changed with antibiotic concentrations. In general, the anammox process showed a stable performance and a high resistance to SPM and STM, suggesting that acclimatization by elevating the concentrations was beneficial for the anammox process to obtain resistance to different antibiotics with high concentrations. This study provides guidance for the stable operation of anammox-based biological treatment of antibiotics containing wastewater.

DKK3 attenuates JNK and AP-1 induced inflammation via Kremen-1 and DVL-1 in mice following intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is the most devastating stroke subtype, with a poor prognosis and few proven treatments. Neuroinflammation is associated with ICH-induced brain injury and unfavorable outcomes. There is growing evidence that Dickkopf (DKK) 3 plays a key role in the adaptive anti-inflammatory and neuroprotective responses following intracerebral hemorrhage. This study aimed to evaluate the protective effects of DKK3 against brain edema and neuroinflammation in a mice model of ICH. METHODS: Male, adult CD1 mice were subjected to sham or ICH surgery using a collagenase injection model. ICH animals received either recombinant DKK3, Kremen-1 siRNA, or DVL-1 siRNA. The neurobehavioral deficits were evaluated at 24 h, 72 h, and 28 days after ICH induction. Western blot and immunofluorescence were employed to examine the expression and localization of DKK3, Kremen-1, Dishevelled-1 (DVL-1), c-JUN N-terminal kinase (JNK), Activator protein-1 (AP-1), cleaved caspase-1, NF-κB, and IL-1ß in the brain. RESULTS: The expression of endogenous DKK3 and DVL-1 was transiently decreased after ICH compared to that in the sham group. Compared to the mice of ICH, exogenous rDKK3 administration reduced the brain water content and affected the neurological functions in ICH mice. Moreover, DKK3 was colocalized with Kremen-1 in microglia. Using a Kremen-1 or DVL-1 siRNA-induced in vivo knockdown approach, we demonstrated that the effects of DKK3 against ICH were mediated, at least partly, by the Kremen-1 and DVL-1 pathways. CONCLUSIONS: DKK3 improves the neurological outcomes, potentially by decreasing JNK/AP-1-mediated inflammation, thereby ameliorating the short- and long-term sequelae after ICH.

Characteristics of vertebral CT Hounsfield units in elderly patients with acute vertebral fragility fractures.

OBJECTIVE: To explore the characteristics of vertebral CT Hounsfield units (HU) in elderly patients with acute vertebral fragility fractures. METHODS: A total of 299 patients aged ≥ 65 years with acute vertebral fragility fractures were retrospectively reviewed, and 77 patients of them were age- and sex-matched with 77 control patients without any fractures. The vertebral HU value of L1(L1-HU) was measured, and T12 and L2 were used as alternatives for L1 in the case of L1 fracture. RESULTS: There were 460 thoracic and lumbar vertebral fractures in the 299 elderly patients, including 349 acute vertebral fragility fractures and 111 chronic fractures. The average L1-HU value was 66.0 ± 30.6 HU and showed significant difference among patients having different numbers of vertebral fractures (one fracture: 73.3 ± 27.0 HU, two fractures: 58.7 ± 32.5 HU, three or more fractures: 40.7 ± 28.8 HU; P < 0.001). As for the 1:1 age- and sex-matched patients, the L1-HU of the 77 patients with fractures was lower than that of the control patients (70.6 ± 23.4 HU vs. 101.5 ± 36.2 HU, P < 0.001). The area under the receiver operating characteristic curve of using L1-HU to differentiate patients with fractures from controls was 0.77(95% CI 0.70-0.85, P < 0.001). The cutoff value had high specificity of 90% or high sensitivity of 90% to identify patients with fractures of 60 HU and 100 HU, respectively. CONCLUSIONS: The elderly patients with acute vertebral fragility fractures have much lower HU values than those without fractures. Moreover, the lower the vertebral HU value is, the more likely the patients have more than one vertebral fracture. These slides can be retrieved under Electronic Supplementary Material.

High Trophinin-Associated Protein Expression Is an Independent Predictor of Poor Survival in Liver Cancer.

BACKGROUND: Trophinin-associated protein (TROAP) is a cytoplasmic protein that functions as an adhesion molecule in processes such as embryo implantation, spindle formation, and cancer. OBJECTIVE: To evaluate the relationship of TROAP expression in hepatocellular carcinoma (HCC) tissue with clinicopathologic parameters and survival time in liver cancer patients based on an analysis of The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) data. METHODS: RNA-sequencing (RNA-Seq) expression data and clinical information were downloaded for the TCGA-LIHC cohort. Associations between TROAP expression in HCC tissues and clinical parameters were evaluated by Chi-square tests. Differences in survival between high and low expression groups (median expression cutoff) from Cox regression analysis were compared, and P values were calculated by a log-rank test. Kaplan-Meier curves were compared with the log-rank test. RESULTS: Analysis of RNA-Seq gene expression data for 373 patients with primary tumors revealed overexpression of TROAP in liver cancer. High TROAP expression was associated with survival status (P = 0.015), T stage (P = 0.049), clinical stage (P = 0.048), and gender (P = 0.033). Patients with high TROAP-expressing liver cancers had a shorter median overall survival of 3.83 years compared with 5.80 years for patients with low TROAP-expressing liver cancers (P = 0.00422). Multivariate analysis identified TROAP expression as an independent prognostic variable for overall survival in liver cancer patients. CONCLUSION: TROAP expression is an independent predictor of poor survival in liver cancer.

Cardioprotective effects of the novel curcumin analogue C66 in diabetic mice is dependent on JNK2 inactivation.

AIM: Diabetic cardiomyopathy is an independent cardiac injury that can develop in diabetic individuals. Our previous study showed that C66, a curcumin analogue, protects against diabetes-induced cardiac damage. The present study sought to reveal the underlying mechanisms of C66-mediated cardioprotection. METHODS: An experimental diabetic model was established using JNK2-/- and wild-type (WT) mice. C66 (5 mg/kg) was administered orally every other day for 3 months. Body weight, plasma glucose levels, cardiac function, and structure were measured. Masson trichrome and TUNEL staining were used to assess myocardial fibrosis and apoptosis, respectively. mRNA and protein levels of inflammation, fibrosis, oxidative stress, and apoptosis molecules were measured by quantitative PCR and Western blot, respectively. RESULTS: Neither C66 treatment nor JNK2 knockout affected body weight or plasma glucose levels. Cardiac inflammation, fibrosis, oxidative stress, and apoptosis were increased in WT diabetic compared to WT control mice, all of which were attenuated by C66 treatment. However, these pathological and molecular changes induced by diabetes were eliminated in JNK2-/- diabetic mice compared to JNK2-/- control mice, and C66 treatment did not further affect these parameters in JNK2-/- diabetic mice. CONCLUSIONS: Our results indicate that C66 ameliorates diabetic cardiomyopathy by inhibiting JNK2 relative pathways.

Isoalantolactone induces apoptosis through reactive oxygen species-dependent upregulation of death receptor 5 in human esophageal cancer cells.

Esophageal cancer is the eighth most prevalent cancer and has high mortality in our society. Isoalantolactone, extracted from Inula helenium L, has shown potent anticancer effects on a variety of cancers. However, its effect on human esophageal cancer, and the underlying molecular mechanism, remain to be investigated. In the present study, we demonstrated that isoalantolactone induced apoptosis in esophageal cancer cells. Treatment with isoalantolactone activated caspases-3, -7, and -10, and upregulated death receptor (DR)5. Furthermore, DR5 knockdown partially reversed the effect of isoalantolactone. These results indicated the extrinsic apoptosis was induced by isoalantolactone. In addition, intracellular reactive oxygen species (ROS) were significantly elevated after treatment with isoalantolactone. N-Acetylcysteine, an ROS scavenger, blocked both the apoptosis and decreased cell viability caused by isoalantolactone. In vivo, significant suppression of tumor growth by isoalantolactone was observed in an ECA109 cell xenograft mouse model. Isoalantolactone showed no obvious adverse effects on mouse weight and histology of heart, liver, spleen, lung, and kidney. In conclusion, our results revealed that isoalantolactone induced apoptosis through the extrinsic pathway via upregulation of DR5 and elevation of ROS in human esophageal cancer cells. Isoalantolactone, therefore, could be a potential candidate in developing anticancer agents for esophageal cancer patients.

Adropin preserves the blood-brain barrier through a Notch1/Hes1 pathway after intracerebral hemorrhage in mice.

Adropin is expressed in the CNS and plays a crucial role in the development of stroke. However, little is currently known about the effects of adropin on the blood-brain barrier (BBB) function after intracerebral hemorrhage (ICH). In this study, the role of adropin in collagenase-induced ICH was investigated in mice. At 1-h post-ICH, mice were administered with recombinant human adropin by intranasal. Brain water +content, BBB permeability, and neurological function were measured at different time intervals. Proteins were quantified using western blot analysis, and the localizations of adropin and Notch1 were visualized via immunofluorescence staining. It is shown that adropin reduced brain water content and improved neurological functions. Adropin preserved the functionality of BBB by increasing N-cadherin expression and reducing extravasation of albumin. Moreover, in vivo knockdown of Notch1 and Hes1 both abolished the protective effects of adropin. Taken together, our data demonstrate that adropin constitutes a potential treatment value for ICH by preserving BBB and improving functional outcomes through the Notch1 signaling pathway.

Few-shot bronze vessel classification via siamese fourier networks.

Exploring ancient Chinese artifacts is crucial for analyzing East Asian technological development, with bronze vessel being the critical element. Bronze vessels, typically featuring intricate carvings, hold historical significance and provide valuable insights into past civilizations. However, identifying bronze patterns can be challenging for human vision, and most RGB-domain methods fail to capture periodic designs. Addressing these issues, we propose the Siamese Fourier Networks (SFN), a parallel network model designed for few-shot regular pattern classification. The Siamese network can differentiate between intricate shapes, while Fourier features enable the extraction of regular textures. To optimize parallel networks, we combine the BCE loss and focal contrastive loss, balancing positive and negative samples. Moreover, we introduce the Bronze Vessel Dataset, featuring 527 samples with diverse shapes and unbalanced distributions. Extensive experiments with advanced few-shot methods demonstrate the superiority of SFN and focal mechanism, significantly improving accuracy.

Analysis and evaluation of patient-specific three-dimensional printing in complex septal myectomy.

OBJECTIVES: This study aimed to assess the effectiveness of three-dimensional printing (3DP) in patients with complex hypertrophic cardiomyopathy requiring combined transaortic and transapical septal myectomy. METHODS: We created 3DP models for 7 patients undergoing this surgery approach between June and October 2022 using silicone-like resin and conducted mock operations. The models were compared with echocardiography to identify abnormal muscle bundles and heart structures. These patients were then compared with a 1:2 matched group without 3DP, considering age, sex and additional operations. RESULTS: The models mostly presenting with midventricular obstruction showed high consistency with original computed tomography data (r = 0.978, P < 0.001). 3DP identified more abnormal muscle bundles than echocardiography, primarily between the interventricular septum and apex. Excised specimens in mock operations mirrored those in actual myectomies. While cardiopulmonary bypass time was not significantly different, a near-20-min decrease was observed in the 3DP group (135.5 ± 31.1 vs 154.4 ± 36.6 min, P = 0.054). CONCLUSIONS: While no significant differences in surgical outcomes were observed, 3DP appeared to enhance the visualization and understanding of spatial structures (average Likert scale score 4.0), potentially contributing to surgical proficiency (overall rating score 3.9). The use of 3DP may offer additional value in the preparation and execution of operations for complex hypertrophic cardiomyopathy cases.

Chemical Constituents from Berchemia polyphylla var. Leioclada.

One previously undescribed naphthoquinone-benzisochromanquinone dimer berpolydiquinone A (1), along with two previously undescribed naphthoquinone-anthraquinone dimers berpolydiquinones B and C (2-3), and one previously undescribed dimeric naphthalene berpolydinaphthalene A (4), were isolated from the stems and leaves of Berchemia polyphylla var. leioclada. The chemical structures of these compounds were determined using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS), spectroscopic data, the exciton chirality method (ECM), and quantum chemical calculation. Notably, compounds (1-2 and 5) are dimeric quinones that share the same naphthoquinone moiety, specifically identified as 2-methoxystypandron. Compound (4) is a derivative of dimeric naphthalene with a symmetrical structure, which is a new structure type isolated from B. polyphylla var. leioclada for the first time. These findings suggest that B. polyphylla var. leioclada serves as a significant reservoir of structurally diverse phenolic compounds. This study provides a scientific foundation for regarding B. polyphylla var. leioclada as a potential source of "Tiebaojin".

Evaluation of liver regeneration after hemi-hepatectomy by combining computed tomography and post-operative liver function.

Background: Accurate evaluation of postoperative liver regeneration is essential to prevent postoperative liver failure. Aims: To analyze the predictors that affect liver regeneration after hemi-hepatectomy. Method: Patients who underwent hemi-hepatectomy in Hangzhou First People's Hospital and Hangzhou Shulan Hospital from January 2016 to December 2021 were enrolled in this study. The regeneration index (RI) was calculated by the following equation: RI = [(postoperative total liver volume {TLVpost} - future liver remnant volume {FLRV}/FLRV] × 100 %. Hepatic dysfunction was defined according to the "TBilpeak>7" standard, which was interpreted as (peak) total bilirubin (TBil) >7.0 mg/dL. Good liver regeneration was defined solely when the RI surpassed the median with hepatic dysfunction. Logistic regression analyses were performed to estimate prognostic factors affecting liver regeneration. Result: A total of 153 patients were enrolled, with 33 in the benign group and 120 patients in the malignant group. In the entire study population, FLRV% [OR 4.087 (1.405-11.889), P = 0.010], international normalized ratio (INR) [OR 2.763 (95%CI, 1.008-7.577), P = 0.048] and TBil [OR 2.592 (95%CI, 1.177-5.710), P = 0.018] were independent prognostic factors associated with liver regeneration. In the benign group, only the computed tomography (CT) parameter FLRV% [OR, 11.700 (95%CI, 1.265-108.200), P = 0.030] predicted regeneration. In the malignant group, parenchymal hepatic resection rate (PHRR%) [OR 0.141 (95%CI, 0.040-0.499), P = 0.002] and TBil [OR 3.384 (95%CI, 1.377-8.319), P = 0.008] were independent prognostic factors. Conclusion: FLRV%, PHRR%, TBil and INR were predictive factors associated with liver regeneration.

Heterogeneity of hepatocellular carcinoma that responds differently to combination therapy with TACE and Sorafenib as determined by digital spatial gene expression profiling.

BACKGROUND: The combination of Sorafenib and transcatheter arterial chemoembolization (TACE) exhibits limited efficacy in the treatment of certain advanced hepatocellular carcinomas (HCC), and the molecular mechanisms underlying resistance to this combination remain unclear. OBJECTIVE: This study aims to underscore the distinctive contribution of GeoMx DSP technology in elucidating the molecular intricacies of HCC resistance to the Sorafenib and TACE combination. METHODS: Patients with advanced HCC during the waiting period before liver transplantation were classified into sensitive and resistant groups based on their response to Sorafenib and TACE combination therapy. Employing GeoMx DSP technology for comprehensive gene expression profiling, we identified pivotal molecular targets linked to resistance against combination therapy. RESULTS: The investigation scrutinized intra-tumoral and inter-individual variances, unveiling a spectrum of crucial molecular targets, such as PLG, PLVAP, immunoglobulin genes, ORM1, and NR4A1, among others. Additionally, we explored signaling pathways associated with treatment responsiveness, including the PPAR signaling pathway. Notably, we emphasized the significance of the immune microenvironment characterized by heightened SPP1 expression in HCC resistance to combination therapy. In the resistant group, SPP1+ tumor-associated macrophage (TAM) infiltration was notably pronounced (p = 0.037), while T-cell depletion showed a mitigated presence (p = 0.013). CONCLUSION: The study reveals intra- and inter-individual heterogeneity in HCC that is differentially responsive to the combination of Sorafenib and TACE, highlighting multiple key molecular targets associated with treatment resistance. The immune microenvironment is important, and in particular, SPP1+ TAM infiltration may play a key role. Meanwhile, the introduction of immunotherapy in patients resistant to combination therapy may lead to positive results.

Impact of preoperative infection on the outcomes of liver transplant recipients: a national propensity score-matched retrospective cohort study in China.

BACKGROUND: Impact of preoperative infection on liver transplantation (LT) needs further investigation. MATERIALS AND METHODS: From 1 January 2015 to 31 December 2022, 24 122 eligible patients receiving LT were enrolled from the China Liver Transplant Registry database. The outcomes of LT were compared after using the propensity score-matched analysis. RESULTS: Compared to the noninfection group, patients in the infection group were more likely to have postoperative effusion, infection, abdominal bleeding, and biliary complications (all P <0.01), and they had shorter 30-day, 90-day survival, and overall survival (all P <0.01). Cox proportional hazards regression analysis revealed that MELD score and cold ischemia time were risk factors for the overall survival in the infection group (both P <0.05). Besides, compared to the nonpulmonary group, patients in the pulmonary group were more likely to have postoperative effusion and infection (both P <0.0001), and less likely to have postoperative abscess and early allograft dysfunction (both P <0.05). Patients in the nonabdominal group also had a higher proportion of postoperative infection than those in the abdominal group ( P <0.05). Furthermore, compared to the number=1 group, patients in the number ≥2 group were more prone to postoperative effusion and infection (both P <0.01), and they also had shorter 30-day and 90-day survival (both P <0.05). CONCLUSION: Preoperative infection can result in a higher incidence of early postoperative complications and shorter survival in liver transplant recipients. The types and number of infection sites will also influence the prognosis of liver transplant recipients.

Arouse potential stemness: Intrinsic and acquired stem cell therapeutic strategies for advanced liver diseases.

Liver diseases are a major health issue, and prolonged liver injury always progresses. Advanced liver disorders impair liver regeneration. Millions of patients die yearly worldwide, even with the available treatments of liver transplantation and artificial liver support system. With its abundant cell resources and significant differentiative potential, stem cell therapy is a viable treatment for various disorders and offers hope to patients waiting for orthotopic liver transplantation. Considering such plight, stem cell therapeutic strategies deliver hope to the patients. Moreover, we conclude intrinsic and acquired perspectives based on stem cell sources. The properties and therapeutic uses of these stem cells' specific types or sources were then reviewed. Owing to the recent investigations of the above cells, a safe and effective therapy will emerge for advanced liver diseases soon.

Identification of a brand intratumor microbiome signature for predicting prognosis of hepatocellular carcinoma.

PURPOSE: Given that prognosis of hepatocellular carcinoma (HCC) differs dramatically, it is imperative to uncover effective and available prognostic biomarker(s). The intratumor microbiome plays a significant role in the response to tumor microenvironment, we aimed to identify an intratumor microbiome signature for predicting the prognosis of HCC patients accurately and investigate its possible mechanisms subsequently. METHODS: The TCGA HCC microbiome data (TCGA-LIHC-microbiome) was downloaded from cBioPortal. To create an intratumor microbiome-related prognostic signature, univariate and multivariate Cox regression analyses were used to quantify the association of microbial abundance and patients' overall survival (OS), as well as their diseases specific survival (DSS). The performance of the scoring model was evaluated by the area under the ROC curve (AUC). Based on the microbiome-related signature, clinical factors, and multi-omics molecular subtypes on the basis of "icluster" algorithm, nomograms were established to predict OS and DSS. Patients were further clustered into three subtypes based on their microbiome-related characteristics by consensus clustering. Moreover, deconvolution algorithm, weighted correlation network analysis (WGCNA) and gene set variation analysis (GSVA) were used to investigate the potential mechanisms. RESULTS: In TCGA LIHC microbiome data, the abundances of 166 genera among the total 1406 genera were considerably associated with HCC patients' OS. From that filtered dataset we identified a 27-microbe prognostic signature and developed a microbiome-related score (MRS) model. Compared with those in the relatively low-risk group, patients in higher-risk group own a much worse OS (P < 0.0001). Besides, the time-dependent ROC curves with MRS showed excellent predictive efficacy both in OS and DSS. Moreover, MRS is an independent prognostic factor for OS and DSS over clinical factors and multi-omics-based molecular subtypes. The integration of MRS into nomograms significantly improved the efficacy of prognosis prediction (1-year AUC:0.849, 3-year AUC: 0.825, 5-year AUC: 0.822). The analysis of microbiome-based subtypes on their immune characteristics and specific gene modules inferred that the intratumor microbiome may affect the HCC patients' prognosis via modulating the cancer stemness and immune response. CONCLUSION: MRS, a 27 intratumor microbiome-related prognostic model, was successfully established to predict HCC patients overall survive independently. And the possible underlying mechanisms were also investigated to provide a potential intervention strategy.