Epigenetic Regulations in Autoimmunity and Cancer: from Basic Science to Translational Medicine.

Epigenetics, as a discipline that aims to explain the differential expression of phenotypes arising from the same gene sequence and the heritability of epigenetic expression, has received much attention in medicine. Epigenetic mechanisms are constantly being discovered, including DNA methylation, histone modifications, noncoding RNAs and m6A. The immune system mainly achieves an immune response through the differentiation and functional expression of immune cells, in which epigenetic modification will have an important impact. Because of immune infiltration in the tumor microenvironment, immunotherapy has become a research hotspot in tumor therapy. Epigenetics plays an important role in autoimmune diseases and cancers through immunology. An increasing number of drugs targeting epigenetic mechanisms, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, and drug combinations, are being evaluated in clinical trials for the treatment of various cancers (including leukemia and osteosarcoma) and autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis). This review summarizes the progress of epigenetic regulation for cancers and autoimmune diseases to date, shedding light on potential therapeutic strategies.

IL-33 Suppresses the Progression of Atherosclerosis via the ERK1/2-IRF1-VCAM-1 Pathway.

PURPOSE: This study was designed to explore the effects of interleukin 33 (IL-33) on the progression of atherosclerosis and the possible mechanism. METHODS: The adhesion assay was performed on isolated peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC). The expression of proteins and messenger RNA (mRNA) were detected by western blot and quantitative real-time polymerase chain reaction (PCR), including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin. The effect of IL-33 on the interaction of growth stimulation expressed gene 2 (ST2) with myeloid differentiation factor 88 (MyD88) and interleukin-1 receptor-associated kinase (IRAK) 1/4 were investigated using co-immunoprecipitation assay. An apolipoprotein (Apo) E-/- mice model was used to confirm the effect of IL-33 on atherosclerosis progression. Area of plaques was recorded by hematoxylin-eosin (H&E) staining. The severity of atherosclerosis plaque was evaluated using immunohistochemistry assay, and lipid accumulation was measured by an oil red O staining. In contrast, western blot was performed to detect the expression levels of VCAM-1, extracellular signal-regulated kinase (ERK) 1/2, and interferon regulatory factor 1 (IRF1). RESULTS: Our study observed that IL-33 suppressed cell adhesion and the expression of VCAM-1 in tumor necrosis factor-α (TNF-α) exposed HUVEC. Moreover, the addition of IL-33 significantly inhibited the expression of IRF1 and the binding level of IRF1 to VCAM-1 and also promoted the phosphorylation level of IRAK1/4 and ERK1/2 compared to TNF-α-stimulated HUVEC. The ST2 neutralizing antibody or ERK pathway inhibitor SCH772984 reversed the regulatory effects of IL-33 on HUVEC, suggesting that IL-33 suppressed IRF1 and VCAM-1 dependent on binding to ST2 and activating the ERK1/2 signaling pathway. Further investigation in vivo confirmed that IL-33 decreased the expressions of IRF1 and VCAM-1 by activating the phosphorylation of ERK1/2 in the thoracic aorta of Apo E-/- mice. CONCLUSION: In conclusion, our results demonstrated that IL-33 plays a protective role in the progression of atherosclerosis by inhibiting cell adhesion via the ERK1/2-IRF1-VCAM-1 pathway. This study may provide a potential therapeutic way to prevent the development of atherosclerosis.

Dynamically controllable multi-switch and slow light based on a pyramid-shaped monolayer graphene metamaterial.

Graphene, a new two-dimensional (2D) material, has attracted considerable attention in recent years because of the metallic characteristics at terahertz frequencies. The phase coupling of multilayer graphene-coupled grating structures is normally used to realize multiple plasmon-induced transparency (PIT) spectral responses. However, the device becomes more complicated with the increase in the number of graphene layers. In this work, we propose a five-step-coupled pyramid-shaped monolayer graphene metamaterial and predict a dynamically controllable PIT with four transparency peaks for the first time in the monolayer graphene metamaterial. A tunable multi-switch and good slow light effect is predicted over the wide PIT window, and the maximum modulation depth is high up to 16.89 dB, which corresponds to 97.95%, while the time delay of the induced transparent window is as high as 0.488 ps, where the corresponding group refractive index is 586. The electric field distributions and quantum level theory are used to explain the physical mechanism of the PIT with four transparency peaks. The coupled mode theory (CMT) is employed to establish the mathematical model of the PIT with four transparency peaks, and the consistency between the simulated and the calculated results is nearly perfect. We believe that the pyramid-shaped monolayer graphene metamaterial could be useful in efficient filters, switches, and slow light devices.

The state of nursing research from 2000 to 2019: A global analysis.

AIM: This study aims to present a general bibliometric overview of the development status of global nursing research from 2000 to 2019. DESIGN: A longitudinal bibliometric analysis of nursing research was conducted. METHODS: Nursing research publications (N = 88,665) were obtained from Web of Science. Bibliometric method was used to map the output and citation impact trends of countries/regions, institutions, disciplines, and journals and analyse the research collaboration among countries/regions and institutions. RESULTS: The global paper output in nursing research increased steadily over the past two decades and it varied in different countries/regions with the USA being far ahead of the others. The paper output and cross-border collaboration are mainly distributed in several developed countries like the USA, the UK, Australia, and Canada. The University of Pennsylvania, Harvard University, University of Toronto, and University of North Carolina at Chapel Hill have high academic influence in the field of nursing. Increasing attention from academic fields has been paid to research on nursing. Journal of Advanced Nursing is the most prolific and most cited journal in nursing field. CONCLUSION: Nursing research has developed steadily over the last two decades. Both the scientific output and research collaboration are disproportionally distributed between high-income countries/regions and low- and middle-income countries/regions. Most research and collaboration have taken place in a few developed countries across North America, Europe, and Oceania. IMPACT: The study highlighted the need for policy makers and funding agencies, especially those from low- and middle-income countries/regions, to allocate research funding that supports the nursing higher education and international cooperation so as to promote the development of high-quality nursing research in those countries/regions. At the same time, researchers from non-English-speaking countries/regions should attach more importance to publishing papers in English, strengthening the academic exchanges with international nursing colleagues and better integrating into the international academic community.

Reducible Fraction Dominates the Mobility of Vanadium in Soil Around an Iron Smelter.

Soil samples were collected to determine the pollution status, spatial distribution and mobility of Vanadium (V) in soil around an iron smelter in Panzhihua. The results showed that the topsoils and deep soils were unpolluted to moderately polluted and the subsurface soils was unpolluted with V. V concentrations in the topsoils decreased with the increase of the altitudes and the distances to the smelter. There was a great potential mobility of V in soil and the reductive dissolution of reducible V in the topsoils was responsible for the high concentration of V in the deep soils. Therefore, more attention should be paid to the reducible V when evaluating the mobility of V in soil.

Autophagy Contributes to Liver Regeneration After Portal Vein Ligation in Rats.

BACKGROUND This study investigated the effect of 70% portal vein ligation (PVL), a widely used procedure for inducing rapid liver regeneration, on the expression of autophagy-related proteins in non-ligated liver lobes in rats. MATERIAL AND METHODS Rats were subjected to either sham (n=30, major portal vein branches were exposed but kept intact) or PVL (n=30, major portal vein branches were double-ligated) operations. Liver samples were collected 12, 24, 48, 72, and 168 h after the operation. Liver volume, liver color, non-ligated liver percentage, and the expressions of light chain (LC) 3, beclin 1, and cyclin D1 in the non-ligated liver lobes were determined. RESULTS When compared to sham rats, increased (P<0.001) growth of the non-ligated liver lobes was observed in PVL rats as early as 12 h after surgery; an increased (P≤0.001) LC3 II/I ratio was observed in the non-ligated lobes of PVL rats as early as 24 h after surgery. Increased expressions of beclin 1 (P≤0.001) and cyclin D1 (P<0.001) were observed in the non-ligated lobes of PVL rats from 12 to 72 h after surgery and from 12 to 168 h after surgery, respectively, when compared to sham rats. In the non-ligated lobes, the expressions of beclin 1 and cyclin D1 were linearly and positively correlated with the LC3 II/I ratio. CONCLUSIONS Autophagy is activated in the non-ligated liver after PVL. Both beclin 1 and cyclin D1 are linearly and positively correlated with autophagy activity in the PVL-induced rapid liver regeneration model.

Effect of Huaier granule on recurrence after curative resection of HCC: a multicentre, randomised clinical trial.

OBJECTIVE: There is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of Trametes robinophila Murr (Huaier granule) to address this unmet need. DESIGN AND RESULTS: A total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI -12.59 to -2.50; p=0.0018), respectively. CONCLUSIONS: This is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group. TRIAL REGISTRATION: NCT01770431; Post-results.

Design and validation of an early scoring system for predicting early outcomes of type III biliary atresia after Kasai's operation.

BACKGROUND/PURPOSE: The purpose of this study was to determine reliable predictors of outcome of biliary atresia (BA) after Kasai's operation. PATIENTS AND METHODS: This study included two consecutive stages of infants with biliary atresia. First stage, 200 BA cases who underwent Kasai's operation at our institution between May 2006 and May 2010 were retrospectively reviewed. In the first stage, we wanted to calculate a clinical scoring system by logistic regression. For cut-off determination, receiver operating characteristic (ROC) analysis was employed. Second stage (validation of scoring system), we used our scoring system to prospectively predict the outcomes of patients underwent a Kasai operation from inspecting the accuracy of our system. RESULTS: Early cholangitis, age at operation, JC time, post-operative TB, DB, AST, ALT and surgical method entered into our scoring system. The most reliable cut-offs determined by ROC analysis were 7.71 (sensitivity: 86.0%, specificity: 98.0%). We used our scoring system to predict the prognosis of the 15 BA patients and found that 13 of 15 patients were correctly predicted at the cut-off value of 7.71. CONCLUSION: Our scoring system is considered to be a reliable and useful predictor of the prognosis of biliary atresia.

Effectiveness of adaptive optics system in satellite-to-ground coherent optical communication.

Adaptive optics (AO) systems can suppress the signal fade induced by atmospheric turbulence in satellite-to-ground coherent optical communication. The lower bound of the signal fade under AO compensation was investigated by analyzing the pattern of aberration modes for a one-stage imaging AO system. The distribution of the root mean square of the residual aberration is discussed on the basis of the spatial and temporal characteristics of the residual aberration of the AO system. The effectiveness of the AO system for improving the performance of coherent optical communication is presented in terms of the bit error rate and system availability.

Preconditioning with glutamine protects against ischemia/reperfusion-induced hepatic injury in rats with obstructive jaundice.

OBJECTIVE: To ascertain whether glutamine (Gln) pretreatment protects rats with obstructive jaundice from hepatic ischemia/reperfusion (I/R) injury and to determine the underlying molecular mechanisms. METHODS: An obstructive jaundice rat model was developed by bile duct ligation. On the first day after the operation, all rats were randomized into two groups and received oral Gln or normal saline (NS) daily for 7 days. Then both groups underwent a 15-min liver ischemia via the Pringle maneuver. Blood samples as well as liver and intestinal tissues were harvested and measured after 1, 6 and 24 h of reperfusion. RESULTS: The results showed that the histological morphology of the liver and intestinal tissues significantly improved in the Gln group after I/R injury compared with the NS group. Serum proteins and enzymes associated with hepatic function also significantly improved in the Gln group. The level of glutathione increased and the levels of malondialdehyde and myeloperoxidase decreased in the Gln group. The levels of interleukin-1ß and tumor necrosis factor-α decreased in the Gln group. Moreover, bcl-2 protein expression was upregulated and intercellular adhesion molecule 1 and bax protein expression downregulated in the Gln group; the caspase 3 mRNA level significantly increased in the Gln group. CONCLUSIONS: The study demonstrates that preconditioning with Gln significantly improves hepatic structure and function after I/R injury in rats with obstructive jaundice. The protective effect of Gln was mediated by the inhibition of reactive oxygen species and inflammation as well as a reduction in hepatocyte apoptosis.

Enhanced performance of InGaN/GaN based solar cells with an In(0.05)Ga(0.95)N ultra-thin inserting layer between GaN barrier and In(0.2)Ga(0.8)N well.

The effect of ultra-thin inserting layer (UIL) on the photovoltaic performances of InGaN/GaN solar cells is investigated. With UIL implemented, the open-circuit voltage was increased from 1.4 V to 1.7 V, short-circuit current density was increased by 65% and external quantum efficiency was increased by 59%, compared to its counterparts at room temperature under 1-sun AM1.5G illumination. The improvements in electrical and photovoltaic properties are mainly attributed to the UIL which can boost the crystal quality and alleviate strain. Moreover, it can act as a transition layer for higher indium incorporation and an effective light sub-absorption layer in multiple quantum wells.

Self-inflicted intravesical insertion of 83 magnetic balls in a 10-year-old boy: a case report and literature review.

BACKGROUND: A magnetic ball is a toy for children that can cause physical injury when used improperly. The injury of urethra and bladder caused by magnetic ball is rarely reported. CASE: Here we present a case of self-inflicted intravesical insertion of 83 magnetic balls by a 10-year-old boy. Preliminary diagnosis was made by a plain radiograph of the pelvis and ultrasonic examination of bladder and all the magnetic balls were removed under cystoscopy successfully. CONCLUSIONS: For children with recurrent bladder irritation, the possibility of bladder foreign body should be considered. Surgery is an effective method. For patients without serious complications, cystoscopy is the gold standard for diagnosis and treatment.

The relationship between exercise motivation and exercise behavior in college students: The chain-mediated role of exercise climate and exercise self-efficacy.

Objective: This study explored the relationship between college students' physical activity motivation and exercise behavior and constructed a chain mediation model through the mediating roles of exercise climate and exercise self-efficacy. Methods: By random sampling, 1,032 college students were investigated using the Exercise Motivation Scale, Physical Exercise Rating Scale, Exercise Climate Scale, and Exercise Self-Efficacy Scale. Results: (1) There was a huge positive correlation between exercise motivation and exercise behavior (r = 0.240, p < 0.01), and the immediate ways of linking exercise motivation to exercise behavior were critical (ß = 0.068, t = 0.040, p < 0.01). (2) Exercise motivation could positively predict exercise climate (ß = 0.373, t = 0.061, p < 0.01) and exercise self-efficacy (ß = 0.174, t = 0.039, p < 0.01), and exercise climate could emphatically foresee exercise behavior (ß = 0.302, t = 0.051, p < 0.01). Exercise self-efficacy could foresee exercise behavior decidedly (ß = 0.190, t = 0.048, p < 0.01). (3) Exercise climate and exercise self-efficacy play a critical intervening role between exercise motivation and exercise behavior. The intercession impact is explicitly made out of aberrant impacts created in three ways: exercise motivation → exercise climate → exercise behavior (mediating effect value: 0.113); exercise motivation → exercise self-efficacy → exercise behavior (mediating effect value: 0.033); exercise motivation → exercise climate → exercise self-efficacy → exercise behavior (mediating effect value: 0.027). Conclusion: (1) Exercise climate, exercise self-efficacy, and exercise behavior can all be significantly predicted by exercise motivation, suggesting that exercise motivation may help to enhance these variables. (2) In addition to having a direct impact on exercise behavior, exercise motivation can also have an indirect impact through the separate mediating effects of exercise climate and exercise self-efficacy as well as the chain mediating effect of exercise climate and exercise self-efficacy, which is crucial for encouraging college students to engage in physical activity.

Artificial Downregulation of Ribosomal Protein L34 Restricts the Proliferation and Metastasis of Colorectal Cancer by Suppressing the JAK2/STAT3 Signaling Pathway.

The highly conserved ribosomal protein L34 (RPL34) has been reported to play an essential role in the progression of diverse malignancies. RPL34 is aberrantly expressed in multiple cancers, although its significant in colorectal cancer (CRC) is currently unclear. Here, we demonstrated that RPL34 expression was higher in CRC tissues than in normal tissues. Upon RPL34 overexpression, the ability of proliferation, migration, invasion, and metastasis of CRC cells were significantly enhanced in vitro and in vivo. Furthermore, high expression of RPL34 accelerated cell cycle progression, activated the JAK2/STAT3 signaling pathway, and induced the epithelial-to-mesenchymal transition (EMT) program. Conversely, RPL34 silencing inhibited the CRC malignant progression. Utilizing immunoprecipitation assays, we identified the RPL34 interactor, the cullin-associated NEDD8-dissociated protein 1 (CAND1), which is a negative regulator of cullin-RING ligases. CAND1 overexpression reduced the ubiquitin level of RPL34 and stabilized RPL34 protein. CAND1 silencing in CRC cells resulted in a decrease in the ability of proliferation, migration, and invasion. CAND1 overexpression promoted CRC malignant phenotypes and induced EMT, and RPL34 knockdown rescued CAND1-induced CRC progression. In summary, our study indicates that RPL34 acts as a mediator, is stabilized by CAND1, and promotes proliferation and metastasis, in part, through the activation of the JAK2/STAT3 signaling pathway and induction of EMT in CRC.

Attenuation of reperfusion-induced hepatocyte apoptosis is associated with reversed bcl-2/bax ratio in hemi-hepatic artery-preserved portal occlusion.

BACKGROUND: This study aimed to examine the hepatocyte apoptosis in a hepatic blood inflow occlusion rat model without hemi-hepatic arterial control and its association with the expressions of the apoptosis-regulating genes bcl-2 and bax. MATERIALS AND METHODS: Wistar rats were equally and randomly assigned to undergo sham operation (control group, n = 8), Pringle's maneuver (group PR, n = 32), hemi-hepatic occlusion (group HH, n = 32), or hemi-hepatic artery-preserved portal occlusion (group HP, n = 32). The hepatic blood inflow was interrupted for 30 min using a microvascular clip in the three experimental groups. The clips were removed to achieve hepatic reperfusion for up to 24 h. Blood samples and liver specimens were collected following reperfusion to perform pathologic examination, serum transferase assay, apoptosis analysis, and determination of bcl-2 and bax mRNA and protein expressions. RESULTS: The reperfusion-related hepatocytic injuries were more severe in the PR group than in the HH and HP groups, both pathologically and biochemically. More reperfused hepatocytes became apoptotic in the PR group than in the HH and HP groups. However, the values of the HH and HP groups were comparable in cellularity, levels of serum transferases, and apoptosis rate following reperfusion. The ratios of bcl-2/bax were reversed, which was more evident in the HH and HP groups than in the PR group. CONCLUSION: Hemi-hepatic artery-preserved portal occlusion had little effect on hepatocyte apoptosis compared with Pringle's maneuver and caused minor ischemia-reperfusion injury as shown by the reversed bcl-2/bax ratio.

Pediatric unicystic cystic partially differentiated nephroblastoma: The first case report.

Cases of patients with cystic partially differentiated nephroblastoma (CPDN) have been reported to date, which presented as polycystic renal tumor in all of them. It is a special pathological type of nephroblastoma. Here, we report the first case of a unicystic CPDN in a child. The patient was diagnosed with a simple renal cyst and underwent laparoscopic decortication. The naive nephron was found in the pathological section, and the diagnosis of CPDN was confirmed. The patient then underwent a radical nephrectomy and six cycles of postoperative chemotherapy. There was no recurrence or metastasis after 2 years of follow-up. Pediatric CPDN presenting as a unicystic renal tumor poses a new challenge to the diagnosis, differential diagnosis, and treatment of unicystic renal tumor.

Duodenal Dieulafoy lesion: a rare pathogeny of gastrointestinal bleeding in children.

BACKGROUND: Dieulafoy lesion is a calibre persistent submucosal artery associated with a minuter mucosal defect. Dieulafoy lesion has been reported to account for 1-5.8% of acute nonvariceal upper gastrointestinal bleeding in adults, but it is rarely reported in children. CASE: Here we report a case of duodenal Dieulafoy lesion in a 13-year-old boy. After endoscopy and laparotomy, he still had no definite diagnosis and effective treatment. The duodenal Dieulafoy lesion was finally identified by selective angiography and was effectively treated by intravascular embolization. CONCLUSIONS: For unexplained upper gastrointestinal bleeding, the possibility of duodenal Dieulafoy lesion should be considered. A combination of multiple diagnosis and treatment methods can improve the success rate of diagnosis and treatment when a single test or treatment method cannot provide definitive diagnosis or effective treatment.

Assessing the performance of sustainable entrepreneurship and environmental corporate social responsibility: revisited environmental nexus from business firms.

Society is currently contemplating sustainable growth strategies, which have become somewhat apprehensive by associating entrepreneurship, innovation, and sustainable development. In this perspective, this article's objective is to connect sustainable development to environmentally sensitive entrepreneurship via scientific proof of developing nations. Therefore, this research objective is to confirm the hypothesis of corporate social responsibility (CSR) to confirm that Pakistan achieves its objectives for sustainable development. The combined average estimator and pooled mean group (PMG) model of the self-release lag model determines a lengthy-term combination of factors and environmental analysis in the Kuznets. We can see the U-shaped ecological arcs in Pakistan. Further results show that the pooled mean group autoregressive distributed lag (PMG-ARDL) estimator has a long-term relationship. This indicates that a 1% rise in per-capita income at some stage of industrial growth will reduce environmental emissions by 2.88%, 4.54%, and 2.48%. The results show that (1) CSR has a substantial and robust link to the two factors of organizational success (employee engagement and credibility); (ii) respectively socio-cultural and ecological CSR make a positive contribution to the success of Pakistani companies; (iii) the ecological dimensions of CSR being the essential relevance to Pakistani companies' credibility and engagement of employees. This research attempts to include additional analytical information on the contribution of CSR to profitable growth. This also has academic and empirical ramifications, showing how domestic and international companies in developing countries can do CSR. This research is expected to give guidance to policymakers.

2D MXene Nanomaterials as Electrocatalysts for Hydrogen Evolution Reaction (HER): A Review.

MXenes, a novel family of 2D transition metal carbide, nitride and carbonitride materials, have been gaining tremendous interest in recent days as potential electrocatalysts for various electrochemical reactions, including hydrogen evolution reaction (HER). MXenes are characterized by their etchable metal layers, excellent structural stability, versatility for heteroatoms doping, excellent electronic conductivity, unique surface functional groups and admirable surface area, suitable for the role of electrocatalyst/support in electrochemical reactions, such as HER. In this review article, we summarized recent developments in MXene-based electrocatalysts synthesis and HER performance in terms of the theoretical and experimental point of view. We systematically evaluated the superiority of the MXene-based catalysts over traditional Pt/C catalysts in terms of HER kinetics, Tafel slope, overpotential and stability, both in acidic and alkaline electrolytic environments. We also pointed out the motives behind the electro catalytic enhancements, the effect of synthesis conditions, heteroatom doping, the effect of surface terminations on the electrocatalytic active sites of various MXenes families. At the end, various possible approaches were recommended for a deeper understanding of the active sites and catalytic improvement of MXenes catalysts for HER.

Development and validation of an immune-related prognosis signature associated with hypoxia and ferroptosis in hepatocellular carcinoma.

BACKGROUND: Hypoxia and ferroptosis are crucial in the occurrence and development of hepatocellular carcinoma (HCC), and they both affect the immune status of the tumor microenvironment. Previous studies have also shown a link between hypoxia and ferroptosis. PATIENTS AND METHODS: In all, 814 HCC cases from The Cancer Genome Atlas and Gene Expression Omnibus databases were used as the discovery cohort, and 230 HCC cases from the International Cancer Genome Consortium database were used as the validation cohort. Hypoxia subtypes and ferroptosis subtypes were identified by consensus cluster analysis according to 174 hypoxia-related genes and 193 ferroptosis-related genes. The prognostic signature was constructed using the Cox and LASSO regression analyses, and two risk groups were identified. A comprehensive analysis of the clinical and immune characteristics between the two risk groups was further performed. RESULTS: Two hypoxia subtypes and two ferroptosis subtypes were distinguished and verified; subsequently, a five-gene prognostic signature was constructed and the risk score could be acquired by the following formula: risk score = 0.0604*Expression (CA9)-0.0714*Expression (ANXA10) + 0.1501*Expression (CDC20)-0.0853*Expression (CYP7A1) + 0.0530*Expression (SPP1). Compared with the low-risk group, the high-risk group had a worse prognosis. The high-risk group also showed a higher level of immune infiltration than the low-risk group, and immune checkpoints were generally upregulated in the high-risk group. The antigen presentation ability of the low-risk group was poor, which may be related to the immune escape mechanism. Drug sensitivity analysis indicated that the high- and low-risk groups were sensitive to tyrosine kinase inhibitors and chemotherapeutic drugs, respectively. CONCLUSION: The hypoxia-, ferroptosis-, and immune-associated prognostic signature we constructed could stratify patients with HCC and guide precise treatment.