Mechanistic Insights into the Excited-State Intramolecular Proton Transfer (ESIPT) Process of 2-(2-Aminophenyl)naphthalene.

The 2-(2-aminophenyl)naphthalene molecule attracted much attention due to excited-state intramolecular proton transfer (ESIPT) from an amino NH2 group to a carbon atom of an adjacent aromatic ring. The ESIPT mechanisms of 2-(2-aminophenyl)naphthalene are still unclear. Herein, the decay pathways of this molecule in vacuum were investigated by combining static electronic structure calculations and nonadiabatic dynamics simulations. The calculations indicated the existence of two stable structures (S0-1 and S0-2) in the S0 and S1 states. For the S0-1 isomer, upon excitation to the Franck-Condon point, the system relaxed to the S1 minimum quickly, and then there exist four decay pathways (two ESIPT ones and two decay channels with C atom pyramidalization). In the ESIPT decay pathways, the system encounters the S1S0-PT-1 or S1S0-PT-2 conical intersection, which funnels the system rapidly to the S0 state. In the other two pathways, the system de-excited from the S1 to the S0 state via the S1S0-1 or S1S0-2 conical intersection. For the S0-2 structure, the decay pathways were similar to those of S0-1. The dynamics simulations showed that 75 and 69% of trajectories experienced the two ESIPT conical intersections for the S0-1 and S0-2 structures, respectively. Our simulations showed that the lifetime of the S1 state of S0-1 (S0-2) is estimated to be 358 (400) fs. Notably, we not only found the detailed reaction mechanism of the system but also found that the different ground-state configurations of this system have little effect on the reaction mechanism in vacuum.

Corrigendum to "Emulsifying Lipiodol with pH-Sensitive DOX@HmA nanoparticles for hepatocellular carcinoma TACE treatment eliminate metastasis" Mater. Today Bio, 23, 2023, 100873, ISSN 2590-0064.

[This corrects the article DOI: 10.1016/j.mtbio.2023.100873.].

Construction of a prognostic model for hepatocellular carcinoma patients receiving transarterial chemoembolization treatment based on the Tumor Burden Score.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) may have varied outcomes based on their liver function and tumor burden diversity. This study aims to assess the prognostic significance of the tumor burden score (TBS) in these patients and develop a prognostic model for their overall survival. METHODS: The study involved a retrospective analysis of 644 newly diagnosed HCC patients undergoing TACE treatment. The individuals were assigned randomly to a training cohort (n = 452) and a validation cohort (n = 192). We utilized a multivariate Cox proportional risk model to identify independent preoperative predictive factors. We then evaluated model performance using the area under the curve (AUC), consistency index (c-index), calibration curve, and decision curve analysis (DCA) methods. RESULTS: The multivariate analysis revealed four prognostic factors associated with overall survival: Tumor Burden Score, Tumor Extent, Types of portal vein invasion (PVI), and Child-Pugh score. The total score was calculated based on these factors. The model demonstrated strong discriminative ability with high AUC values and c-index, providing high net clinical benefits for patients. Based on the model's scoring results, patients were categorized into high, medium, and low-risk groups. These results were validated in the validation cohort. CONCLUSIONS: The tumor burden score shows promise as a viable alternative prognostic indicator for assessing tumor burden in cases of HCC. The new prognostic model can place patients in one of three groups, which will estimate their individual outcomes. For high-risk patients, it is suggested to consider alternative treatment options or provide the best supportive care, as they may not benefit significantly from TACE treatment.

Towards inclusive green growth in China: Synergistic roles and mechanisms of new infrastructure construction.

Inclusive green growth (IGG) has been widely discussed for its emphasis on coordinating economic growth quality, social equity, as well as environmentally sustainable development. New infrastructure, representing network and information infrastructure construction, has emerged as a pivotal national strategy to stimulate socioeconomic progress, and its impact on the inclusive green growth deserves careful exploration. Employing the staggered difference-in-difference (staggered DID) approach, this study investigates the influence of new infrastructure on IGG based on Chinese prefecture-level city data from 2011 to 2019, taking advantage of the "Broadband China" strategy (BCS) as a quasi-natural experiment. The results indicate a significant enhancement in IGG due to new infrastructure construction, which remains tenable after rigorous robustness assessments. Further testing with the spatial Durbin DID method reveals that BCS has a significant positive spillover impact on IGG in neighboring areas. For its underlying mechanisms, new infrastructure construction enhances IGG mainly by reinforcing industrial structure supererogation, improving the urban innovation level, and developing digital inclusive finance. There is also evidence that heterogeneity highlights the advancing effects of IGG in the central region, non-aging industrial base cities and non-resource-based cities. This research sheds new light on the understanding of the effect of new infrastructure on promoting IGG through both conceptual and empirical aspects and is conducive to future policymaking for developing countries.

Mi-BMSCs alleviate inflammation and fibrosis in CCl4-and TAA-induced liver cirrhosis by inhibiting TGF-ß/Smad signaling.

Cirrhosis is an aggressive disease, and over 80 % of liver cancer patients are complicated by cirrhosis, which lacks effective therapies. Transplantation of mesenchymal stem cells (MSCs) is a promising option for treating liver cirrhosis. However, this therapeutic approach is often challenged by the low homing ability and short survival time of transplanted MSCs in vivo. Therefore, a novel and efficient cell delivery system for MSCs is urgently required. This new system can effectively extend the persistence and duration of MSCs in vivo. In this study, we present novel porous microspheres with microfluidic electrospray technology for the encapsulation of bone marrow-derived MSCs (BMSCs) in the treatment of liver cirrhosis. Porous microspheres loaded with BMSCs (Mi-BMSCs) exhibit good biocompatibility and demonstrate better anti-inflammatory properties than BMSCs alone. Mi-BMSCs significantly increase the duration of BMSCs and exert potent anti-inflammatory and anti-fibrosis effects against CCl4 and TAA-induced liver cirrhosis by targeting the TGF-ß/Smad signaling pathway to ameliorate cirrhosis, which highlight the potential of Mi-BMSCs as a promising therapeutic approach for early liver cirrhosis.

Crosstalk between endothelial progenitor cells and HCC through periostin/CCL2/CD36 supports formation of the pro-metastatic microenvironment in HCC.

Metastasis causes most cancer-related deaths, and the role and mechanism of periostin (POSTN) in the metastasis of hepatocellular carcinoma (HCC) remain undiscovered. In this study, DEN and HTVi HCC models were performed in hepatic-specific Postn ablation and Postn knock-in mouse to reveal the role of POSTN in HCC metastasis. Furthermore, POSTN was positively correlated with circulating EPCs level and promoted EPC mobilization and tumour infiltration. POSTN also mediated the crosstalk between HCC and EPCs, which promoted metastasis ability and upregulated CD36 expression in HCC through indirect crosstalk. Chemokine arrays further revealed that hepatic-derived POSTN induced elevated CCL2 expression and secretion in EPCs, and CCL2 promoted prometastatic traits in HCC. Mechanistic studies showed that POSTN upregulated CCL2 expression in EPCs via the αvß3/ILK/NF-κB pathway. CCL2 further induced CD36 expression via the CCR2/STAT3 pathway by directly binding to the promoter region of CD36. Finally, CD36 was verified to have a prometastatic role in vitro and to be correlated with POSTN expression, metastasis and recurrence in HCC in clinical samples. Our findings revealed that crosstalk between HCC and EPCs is mediated by periostin/CCL2/CD36 signalling which promotes HCC metastasis and emphasizes a potential therapeutic strategy for preventing HCC metastasis.

The impact of environmental regulatory instruments on agribusiness technology innovation-A study of configuration effects based on fsQCA.

This paper investigates the complex causal relationships between various types of environmental regulatory instruments (ERI) and agri-firms' technological innovation employing fuzzy set qualitative comparative analysis (fsQCA). The study finds a well-designed set of ERI can promote technological innovation in agribusiness; control-command ERI cannot promote technological innovation in agribusiness solely, market-incentivized ERI is indispensable in promoting firms' innovation performance, implicit ERI plays an important role in promoting firms' innovation and voluntary ERI does not play a significant role in promoting firms' technological innovation. The government should coordinate among various types of ERI and improve the design of ERI to achieve a win-win situation for both economic and environmental performance in the agriculture sector.

Botrytis cinerea hypovirulent strain △BcSpd1 induced Panax ginseng defense.

Background: Gray mold, caused by Botrytis cinerea, is one of the major fungal diseases in agriculture. Biological methods are preferred over chemical fungicides to control gray mold since they are less toxic to the environment and could induce the resistance to pathogens in plants. In this work, we try to understand if ginseng defense to B. cinerea could be induced by fungal hypovirulent strain △BcSpd1. BcSpd1 encodes Zn(II)2Cys6 transcription factor which regulates fungal pathogenicity and we recently reported △BcSpd1 mutants reduced fungal virulence. Methods: We performed transcriptomic analysis of the host to investigate the induced defense response of ginseng treated by B. cinerea △BcSpd1. The metabolites in ginseng flavonoids pathway were determined by UPLC-ESI-MS/MS and the antifungal activates were then performed. Results: We found that △BcSpd1 enhanced the ginseng defense response when applied to healthy ginseng leaves and further changed the metabolism of flavonoids. Compared with untreated plants, the application of △BcSpd1 on ginseng leaves significantly increased the accumulation of p-coumaric acid and myricetin, which could inhibit the fungal growth. Conclusion: B. cinerea △BcSpd1 could effectively induce the medicinal plant defense and is referred to as the biological control agent in ginseng disease management.

Emulsifying Lipiodol with pH-sensitive DOX@HmA nanoparticles for hepatocellular carcinoma TACE treatment eliminate metastasis.

Lipiodol-based transcatheter arterial chemoembolization (TACE) is currently the predominant and first-line treatment option recommended by the global standard for unresectable hepatocellular carcinoma (HCC). However, the unstable emulsion of Lipiodol causes a substantial proportion of chemotherapy drugs to enter the circulation system, leading to poor accumulation in cancer tissues and unexpected side effects of chemotherapy drugs. Herein, we emulsified Lipiodol with a pH-sensitive drug delivery system assembled from hexahistidine and zinc ions (HmA) with a super-high loading capacity of doxorubicin (DOX) and a promising ability to penetrate bio-barriers for the effective treatment of HCC by TACE. In vitro tests showed that DOX@HmA was comparable to free DOX in killing HCC cells. Impressively, during the in vivo TACE treatment, the anti-tumor efficacy of DOX@HmA was significantly greater than that of free DOX, indicating that DOX@HmA increased the accumulation of DOX in tumor. Emulsifying Lipiodol with pH-sensitive DOX@HmA significantly inhibited cell regeneration and tumor angiogenesis and decreased the systemic side effects of chemotherapy, especially by suppressing pulmonary metastasis in liver VX2 tumors in rabbits by inhibiting epithelial-mesenchymal transition (EMT). Emulsifying tumor microenvironment-responsive drug delivery systems (DDSs) with Lipiodol could be a new strategy for clinical TACE chemotherapy with potentially enhanced HCC treatment.

Transcriptome and Lipidomic Analysis Suggests Lipid Metabolism Reprogramming and Upregulating SPHK1 Promotes Stemness in Pancreatic Ductal Adenocarcinoma Stem-like Cells.

Cancer stem cells (CSCs) are considered to play a key role in the development and progression of pancreatic ductal adenocarcinoma (PDAC). However, little is known about lipid metabolism reprogramming in PDAC CSCs. Here, we assigned stemness indices, which were used to describe and quantify CSCs, to every patient from the Cancer Genome Atlas (TCGA-PAAD) database and observed differences in lipid metabolism between patients with high and low stemness indices. Then, tumor-repopulating cells (TRCs) cultured in soft 3D (three-dimensional) fibrin gels were demonstrated to be an available PDAC cancer stem-like cell (CSLCs) model. Comprehensive transcriptome and lipidomic analysis results suggested that fatty acid metabolism, glycerophospholipid metabolism, and, especially, the sphingolipid metabolism pathway were mostly associated with CSLCs properties. SPHK1 (sphingosine kinases 1), one of the genes involved in sphingolipid metabolism and encoding the key enzyme to catalyze sphingosine to generate S1P (sphingosine-1-phosphate), was identified to be the key gene in promoting the stemness of PDAC. In summary, we explored the characteristics of lipid metabolism both in patients with high stemness indices and in novel CSLCs models, and unraveled a molecular mechanism via which sphingolipid metabolism maintained tumor stemness. These findings may contribute to the development of a strategy for targeting lipid metabolism to inhibit CSCs in PDAC treatment.

HELLS modulates the stemness of intrahepatic cholangiocarcinoma through promoting senescence-associated secretory phenotype.

The senescence-associated secretory phenotype (SASP) is closely associated with the tumorigenesis and progression of intrahepatic cholangiocarcinoma (ICC). However, it remains unclear its relation to stemness of ICC. In the study, the stemness indices of ICC were calculated using one-class linear regression (OCLR) and single-sample gene set enrichment analysis (ssGSEA) algorithms. A total of 14 senescence-related stemness genes (SRSGs) were identified using Pearson correlation analysis in ICC. Subsequently, a SRSGs-related classification was established using a consensus clustering for ICC. Different types of ICC exhibit distinct prognosis, immunity, metabolisms, and oncogenic signatures. Additionally, we constructed a risk score model for ICC using principal component analysis (PCA). The risk score was positively correlated with stemness, immune infiltration, metabolisms and oncogenic signatures, but negatively with prognosis in ICC. Patients with a high risk score may respond well to immunotherapy. Furthermore, we employed 3D fibrin gels to select tumor-repopulating cells (TRC) with stemness features. We found that HELLS, belonging to the 14 SRSGs, was up-regulated in ICC-TRC. And silencing HELLS significantly reduced the colony size, inhibited migration and invasion, and attenuated SASP in ICC-TRC. In summary, we provided a novel classification and risk score for ICC and uncovered a molecular mechanism via which CSLCs could obtain an active SASP.

Tuneable Schottky contact of MoSi2N4/TaS2 van der Waals heterostructure.

The two-dimensional MoSi2N4 monolayer is an emerging semiconductor material that offers considerable promise due to its ultra-thin profile, tuneable mechanical properties, excellent optoelectronic properties and exceptional environmental stability. The van der Waals (vdW) heterostructure formed by stacking such two-dimensional monolayers has demonstrated superior performance across various domains. In this study, a vdW heterostructure combining the two-dimensional MoSi2N4 and TaS2 monolayers is examined using first-principles density functional theory. In its ground state, this van der Waals heterostructure establishes an ohmic contact with an exceptionally low potential barrier height. By modulating the vdW heterostructure with an applied electric field of -0.1 V/Å and under vertical stress, we discovered that MoSi2N4 and TaS2 can transition from an ohmic contact to a p-type Schottky with an ultra-low Schottky barrier height (SBH). Our observations may give valuable insights for designing reconfigurable, tuneable Schottky nano-devices with enhanced electronic and optical properties based on MoSi2N4/TaS2.

Novel risk model based on angiogenesis-related lncRNAs for prognosis prediction of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death due to early metastasis or recurrence. Tumor angiogenesis plays an essential role in the tumorigenesis of HCC. Accumulated studies have validated the crucial role of lncRNAs in tumor angiogenesis. Here, we established an angiogenesis-related multi-lncRNAs risk model based on the machine learning for HCC prognosis prediction. Firstly, a total of 348 differential expression angiogenesis-related lncRNAs were identified by correlation analysis. Then, 20 of these lncRNAs were selected through univariate cox analysis and used for in-depth study of machine learning. After 1,000 random sampling cycles calculating by random forest algorithm, four lncRNAs were found to be highly associated with HCC prognosis, namely LUCAT1, AC010761.1, AC006504.7 and MIR210HG. Subsequently, the results from both the training and validation sets revealed that the four lncRNAs-based risk model was suitable for predicting HCC recurrence. Moreover, the infiltration of macrophages and CD8 T cells were shown to be closely associated with risk score and promotion of immune escape. The reliability of this model was validated by exploring the biological functions of lncRNA MIR210HG in HCC cells. The results showed that MIR210HG silence inhibited HCC growth and migration through upregulating PFKFB4 and SPAG4. Taken together, this angiogenesis-related risk model could serve as a reliable and promising tool to predict the prognosis of HCC.

Transcriptome and metabolite analyses indicated the underlying molecular responses of Asian ginseng (Panax ginseng) toward Colletotrichum panacicola infection.

Panax ginseng Meyer is one of the most valuable plants and is widely used in China, while ginseng anthracnose is one of the most destructive diseases. Colletotrichum panacicola could infect ginseng leaves and stems and causes serious anthracnose disease, but its mechanism is still unknown. Here, transcriptome and metabolism analyses of the host leaves were conducted to investigate the ginseng defense response affected by C. panacicola. Upon C. panacicola infection, ginseng transcripts altered from 14 to 24 h, and the expression of many defense-related genes switched from induction to repression. Consequently, ginseng metabolites in the flavonoid pathway were changed. Particularly, C. panacicola repressed plant biosynthesis of the epicatechin and naringin while inducing plant biosynthesis of glycitin, vitexin/isovitexin, and luteolin-7-O-glucoside. This work indicates C. panacicola successful infection of P. ginseng by intervening in the transcripts of defense-related genes and manipulating the biosynthesis of secondary metabolites, which might have antifungal activities.

A novel prognostic signature based on immunogenic cell death score predicts outcomes and response to transcatheter arterial chemoembolization and immunotherapy in hepatocellular carcinoma.

PURPOSE: The phenomenon of immunogenic cell death (ICD) is intricately linked to numerous antitumor treatments and exerts a profound regulatory function in the tumor immune microenvironment (TIME). We aimed to establish a prognostic signature from the ICD-related biomarkers to differentiate the TIME in hepatocellular carcinoma and predict diverse outcomes for patients with liver cancer. METHODS: ICD score-related genes (ICDSGs) were identified using the weighted gene co-expression network analysis (WGCNA). The ICD score-related signature (ICDSsig) was established by applying LASSO and Cox regression. Model precision was verified using the external datasets. We used independent prognostic variables in clinicopathologic factors to develop a nomogram. Further, clinical characteristics, immune and molecular landscapes, the responses of transcatheter arterial chemoembolization (TACE) and immunotherapy, and chemotherapy sensitivity were analyzed for high- and low-risk patients. RESULTS: ICD score-calculated using the single-sample gene set enrichment analysis (ssGSEA)-displayed strong associations with the TIME in HCC. We identified 34 ICDSGs after integrating the TCGA and GSE104580 datasets. Then, three novel ICDSGs (DNASE1L3, KLRB1, and LILRB1) were screened out to construct the ICDSsig; the prognostic signature performed well in the external databases. The high-risk patients had worse outcomes owing to their advanced pathological state, non-response of TACE, and immune-cold phenotype in the immune landscapes. The immune checkpoint genes, N6-methyladenosine-relevant genes, and microsatellite instability score were increased in the high-risk subgroup, thereby indicating a favorable sensitivity to immunotherapy. Common chemotherapy drugs were more effective in high-risk patients due to low half-maximal inhibitory concentration values. CONCLUSION: The ICDSsig can potentially predict outcomes and therapeutic responses for patients with liver cancer and may assist clinicians in designing individualized treatment strategies.

Comprehensive Metabolic Profiling and Genome-wide Analysis Reveal Therapeutic Modalities for Hepatocellular Carcinoma.

Understanding the details of metabolic reprogramming in hepatocellular carcinoma (HCC) is critical to improve stratification for therapy. Both multiomics analysis and cross-cohort validation were performed to investigate the metabolic dysregulation of 562 HCC patients from 4 cohorts. On the basis of the identified dynamic network biomarkers, 227 substantial metabolic genes were identified and a total of 343 HCC patients were classified into 4 heterogeneous metabolic clusters with distinct metabolic characteristics: cluster 1, the pyruvate subtype, associated with upregulated pyruvate metabolism; cluster 2, the amino acid subtype, with dysregulated amino acid metabolism as the reference; cluster 3, the mixed subtype, in which lipid metabolism, amino acid metabolism, and glycan metabolism are dysregulated; and cluster 4, the glycolytic subtype, associated with the dysregulated carbohydrate metabolism. These 4 clusters showed distinct prognoses, clinical characteristics and immune cell infiltrations, which was further validated by genomic alterations, transcriptomics, metabolomics, and immune cell profiles in the other 3 independent cohorts. Besides, the sensitivity of different clusters to metabolic inhibitors varied depending on their metabolic features. Importantly, cluster 2 is rich in immune cells in tumor tissues, especially programmed cell death protein 1 (PD-1)-expressing cells, which may be due to the tryptophan metabolism disorders, and potentially benefiting more from PD-1 treatment. In conclusion, our results suggest the metabolic heterogeneity of HCC and make it possible to treat HCC patients precisely and effectively on specific metabolic characteristics.

A novel nomogram to predict survival of patients with hepatocellular carcinoma after transarterial chemoembolization: a tool for retreatment decision making.

Background: There is still no standardized policy regarding how to identify patients who are not benefiting from transarterial chemoembolization (TACE). We aimed to establish and validate a nomogram model to predict the survival rate of hepatocellular carcinoma (HCC) patients after TACE. Methods: A total of 578 HCC patients undergoing initial TACE at the First Affiliated Hospital of Wenzhou Medical University were retrospectively recruited to the study. The patients were randomly divided into 2 cohorts: a training cohort (n=405) and a validation cohort (n=173). To develop the nomogram, Cox regression analyses were used to identify independent risk factors. The performances of the nomogram were assessed by concordance index (C-index), calibration curves, and decision curve analysis (DCA), and were compared to 4 developed prognostic models. Results: We used 5 independent risk factors including postoperative albumin-bilirubin (ALBI) grade, tumor diameter, number of tumors, portal vein invasion, and tumor response to develop the nomogram. Calibration curves showed consistency between the nomogram and the actual observation. The C-index of the nomogram was 0.753 [95% confidence interval (CI): 0.722, 0.784], which was higher than the other prognostic models (P<0.001). The DCA showed that the nomogram had the highest net benefit among the models. According to predicted survival risk, the nomogram could divide patients into 3 groups (P<0.001). All the results were verified in the validation cohort. Conclusions: This study developed and validated a nomogram model for HCC patients undergoing TACE, which could predict the survival rate and provide support for further treatment strategies.

Engineered Apoptosis-Bioinspired Nanoparticles Initiate Immune Cascade for Cancer Immunotherapy of Malignant Ascites.

Malignant ascites (MA) is a common symptom of peritoneal metastasis in liver cancer. Cancer immunotherapy can modulate immune cells to induce antitumor immune efficiency. Reprogramming tumor immune microenvironment (TIME) is a momentous strategy to overcome immunosuppression and achieve immune functional normalization. Inspired by the inherent apoptotic bodies and vesicles, we proposed and systematically studied engineered apoptosis-bioinspired nanoparticles (EBN) for cancer immunotherapy of MA. Using both in vitro and in vivo experimental validations, we elucidated that EBN could be efficiently engulfed by the tumor-associated macrophages (TAMs) and manipulate their polarization. Moreover, a boosted immune cascade response as a result of heightening cytotoxic T-lymphocytes (CTLs) activity was investigated. Based on these results, EBN was confirmed to have strong immune cascade activation capability. Remarkably, the injection of EBN further reduced ascites volume and reformed immune cell subtypes, compared to the injection of either PBS or free TMP195 alone. In short, this novel nanodrug delivery system (NDDS) represents a prospective immunotherapeutic approach for clinical therapeutics of hepatoma ascites and other malignant effusion.

Loss of GABARAPL1 confers ferroptosis resistance to cancer stem-like cells in hepatocellular carcinoma.

Cancer stem-like cells (CSLC) are considered a major contributor to the development and progression of hepatocellular carcinoma (HCC). Previous studies indicated that CSLC are characterized by resistance to ferroptosis, a type of lipid peroxidation-dependent cell death. Here, we identified a set of ferroptosis-related stemness genes (FRSG) and found that these genes may be involved in immune infiltration in HCC. A four-FRSG (CDKN2A, GABARAPL1, HRAS, RPL8) risk model with prognostic prediction was constructed by a Cox analysis in HCC. Among these four genes, GABARAPL1 was downregulated in HCC tumor-repopulating cells (TRC; a type of CSLC). Its downregulation decreased the sensitivity of HCC TRC to erastin- or sorafenib-triggered ferroptosis. Together, we uncovered a molecular mechanism via which CSLC could achieve tolerance to ferroptosis. Further studies may provide potential therapeutic strategies targeting CSLC in HCC.

Construction of a tumor immune infiltration macrophage signature for predicting prognosis and immunotherapy response in liver cancer.

Liver cancer is an extraordinarily heterogeneous malignant disease. The tumor microenvironment (TME) and tumor-associated macrophages (TAMs) are the major drivers of liver cancer initiation and progression. It is critical to have a better understanding of the complicated interactions between liver cancer and the immune system for the development of cancer immunotherapy. Based on the gene expression profiles of tumor immune infiltration cells (TIICs), upregulated genes in TAMs and downregulated genes in other types of immune cells were identified as macrophage-specific genes (MSG). In this study, we combined MSG, immune subtypes, and clinical information on liver cancer to develop a tumor immune infiltration macrophage signature (TIMSig). A four-gene signature (S100A9, SLC22A15, TRIM54, and PPARGC1A) was identified as the TAM-related prognostic genes for liver cancer, independent of multiple clinicopathological parameters. Survival analyses showed that patients with low TIMSig had a superior survival rate than those with high TIMSig. Additionally, clinical immunotherapy response and TIMSig was observed as highly relevant. In addition, TIMSig could predict the response to chemotherapy. Collectively, the TIMSig could be a potential tool for risk-stratification, clinical decision making, treatment planning, and oncology immunotherapeutic drug development.