A "Zn2+ in Salt" Interphase Enabling High-Performance Zn Metal Anodes.

Zinc metal is a promising anode candidate for aqueous zinc ion batteries due to its high theoretical capacity, low cost, and high safety. However, its application is currently restricted by hydrogen evolution reactions (HER), by-product formation, and Zn dendrite growth. Herein, a "Zn2+ in salt" (ZIS) interphase is in situ constructed on the surface of the anode (ZIS@Zn). Unlike the conventional "Zn2+ in water" working environment of Zn anodes, the intrinsic hydrophobicity of the ZIS interphase isolates the anode from direct contact with the aqueous electrolyte, thereby protecting it from HER, and the accompanying side reactions. More importantly, it works as an ordered water-free ion-conducting medium, which guides uniform Zn deposition and facilitates rapid Zn2+ migration at the interface. As a result, the symmetric cells assembled with ZIS@Zn exhibit dendrite-free plating/striping at 4500 h and a high critical current of 14 mA cm-2. When matched with a vanadium-based (NVO) cathode, the full battery exhibits excellent long-term cycling stability, with 88% capacity retention after 1600 cycles. This work provides an effective strategy to promote the stability and reversibility of Zn anodes in aqueous electrolytes.

USP36 inhibits apoptosis by deubiquitinating cIAP1 and survivin in colorectal cancer cells.

Chemotherapeutic agents for treating colorectal cancer primarily induce apoptosis in tumor cells. The ubiquitin-proteasome system (UPS) is critical for apoptosis regulation. Deubiquitinating enzymes (DUBs) remove ubiquitin from substrates to reverse ubiquitination. Although over 100 DUB members have been discovered, the biological functions of only a small proportion of DUBs have been characterized. Here, we aimed to systematically identify the DUBs that contribute to the development of colorectal cancer. Among the DUBs, ubiquitin-specific protease 36 (USP36), is upregulated in colorectal cancer. We showed that the knockdown of USP36 induces intrinsic and extrinsic apoptosis. Through gene silencing and coimmunoprecipitation techniques, we identified survivin and cIAP1 as USP36 targets. Mechanistically, USP36 binds and removes lysine-11 (K11)-linked ubiquitin chains from cIAP1 and lysine-48 (K48)-linked ubiquitin chains from survivin to abolish protein degradation. Overexpression of USP36 disrupts the formation of the XIAP-Smac complex and promotes RIPK1 ubiquitination, validating USP36 as an inhibitor to intrinsic and extrinsic apoptosis through deubiquitinating survivin and cIAP1. Therefore, our results suggest that USP36 is involved in colorectal cancer progression and is a potential therapeutic target.

Digital inverse patterning solutions for fabrication of high-fidelity microstructures in spatial light modulator (SLM)-based projection lithography.

Digital mask projection lithography (DMPL) technology is gaining significant attention due to its characteristics of free-mask, flexibility, and low cost. However, when dealing with target layouts featuring sizes smaller than the wavelength scale, accurately producing resist patterns that closely match the target layout using conventional methods to design the modulation coefficients of digital masks produced by spatial light modulators (SLM) becomes challenging. Here, we present digital inversion lithography technology (DILT), which offers what we believe to be a novel approach to reverse engineer the modulation coefficients of digital masks. In the case of binary amplitude modulation, DILT achieves a remarkable reduction in pattern errors (PE), reaching the original 0.26. At the same time, in the case of the gray amplitude modulation, the PE can be reduced to the original 0.05, which greatly improves the high-fidelity transfer of the target layout. This significant improvement enhances the accuracy of target design transfer. By leveraging the capabilities of DILT, DMPL can now attain higher precision and reliability, paving the way for more advanced applications in the field of micro-nano device manufacturing.

Optical proximity correction of hot-spot patterns with subwavelength size in DMD maskless projection lithography.

When the critical dimension (CD) of resist patterns nears the resolution limit of the digital micromirror device (DMD) maskless projection lithography (DMD-MPL), significant distortion can emerge in the silicon wafer due to the optical proximity effect (OPE). The significant distortion (breakpoints, line-end scaling, corner rounding, etc.) between resist patterns and target patterns results in reduced lithographic quality. To address this issue, we have proposed a pixel-based optical proximity correction (PB-OPC) method used for the hot-spot patterns with subwavelength sizes specifically designed for DMD-MPL. Employing an end-to-end learning neural network, the PB-OPC algorithm is both straightforward and efficient. A well-trained U-net framework facilitates the mapping from unoptimized masks to optimized masks. Experimental exposure trials have demonstrated that this method not only corrects OPC in general patterns but also effectively rectifies hot-spot patterns. The pattern error (PE) value can be reduced by about 30% in the design layouts. We believe this approach holds the potential to enhance the resolution and fidelity of resist patterns in DMD maskless lithography.

Latamoxef dosing regimen adjustments and pharmaceutical care in pediatrics.

Latamoxef is a semi-synthetic, broad-spectrum oxacephem antibiotic used primarily to treat infectious diseases, but the adverse drug reactions, such as the risk of fatal bleeding, once caused physicians to use it less frequently. However, with the rise of antibiotic-resistant bacterial strains, latamoxef is being used again to treat infectious diseases, especially in pediatrics. The pharmacokinetic parameters of latamoxef are highly variable, given the changes in body composition, organ maturation, and development that occurs in pediatrics. Therefore, an appropriate dosing regimen is essential. Latamoxef dosing optimization in pediatrics should adequately account for current body weight, postnatal age, postmenstrual age, and different minimum inhibitory concentration (MIC) values. In addition, attention should also be paid to some of the adverse reactions associated with latamoxef, such as coagulation disorders and bleeding risks, disulfiram-like reactions, as well as hypersensitivity and anaphylactic shock. This review summarizes the dosing regimens and some key points of pharmaceutical care for latamoxef in pediatrics in order to provide a better reference for its application in clinical practice.

Isolation, identification and characterization of Aeromonas jandaei from diseased Chinese soft-shell turtles.

Aeromonas jandaei is a gram-negative bacterium commonly found in aquatic environments and can induce illnesses in amphibians, reptiles and aquatic animals. In this study, a strain of bacteria was isolated from the diseased Chinese soft-shell turtle (Pelodiscus sinensis), then named strain JDP-FX. This isolate was identified as A. jandaei after analysis of morphological, physiological and biochemical characteristics, as well as 16S rRNA and gyrB gene sequences. Virulence genetic testing further detected temperature-sensitive protease (eprCAI), type III secretion system (TTSS) (ascv), nuclease (nuc), cytotonic enterotoxin (alt) and serine proteinase (ser) in JDP-FX. Compared with healthy Chinese soft-shell turtle, the serum levels of total protein (TP), albumin (ALB) and globulin (GLB) were significantly decreased in the diseased Chinese soft-shell turtle, while, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were significantly increased. Histopathological observations showed that multiple tissues, including intestinal mucosa, liver and kidney, were severely damaged in the diseased Chinese soft-shell turtle. Moreover, the diseased Chinese soft-shell turtle had significant cell degeneration, necrosis, sloughing and interstitial inflammatory cell infiltration. The pathogenicity of JDP-FX was tested via artificial infection. The median lethal dosage (LD50 ) of the strain was 1.05 × 105 colony forming units (CFU/g) per weight of Chinese soft-shell turtle. Drug susceptibility analysis revealed that JDP-FX was susceptible to ceftazidime, minocycline, cefoperazone, ceftriaxone and piperacillin. In addition, JDP-FX was resistant to doxycycline, florfenicol, sulfonamides, gentamicin, ampicillin and neomycin. Therefore, this study may provide guidance for further research into the diagnosis, prevention and treatment of JDP-FX infection.

TIMELESS promotes reprogramming of glucose metabolism in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC), the predominant malignancy of the oral cavity, is characterized by high incidence and low survival rates. Emerging evidence suggests a link between circadian rhythm disruptions and cancer development. The circadian gene TIMELESS, known for its specific expression in various tumors, has not been extensively studied in the context of OSCC. This study aims to explore the influence of TIMELESS on OSCC, focusing on cell growth and metabolic alterations. METHODS: We analyzed TIMELESS expression in OSCC using western blot, immunohistochemistry, qRT-PCR, and data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE). The role of TIMELESS in OSCC was examined through clone formation, MTS, cell cycle, and EdU assays, alongside subcutaneous tumor growth experiments in nude mice. We also assessed the metabolic impact of TIMELESS by measuring glucose uptake, lactate production, oxygen consumption, and medium pH, and investigated its effect on key metabolic proteins including silent information regulator 1 (SIRT1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), recombinant lactate dehydrogenase A (LDHA) and glucose transporter-1 (GLUT1). RESULTS: Elevated TIMELESS expression in OSCC tissues and cell lines was observed, correlating with reduced patient survival. TIMELESS overexpression enhanced OSCC cell proliferation, increased glycolytic activity (glucose uptake and lactate production), and suppressed oxidative phosphorylation (evidenced by reduced oxygen consumption and altered pH levels). Conversely, TIMELESS knockdown inhibited these cellular and metabolic processes, an effect mirrored by manipulating SIRT1 levels. Additionally, SIRT1 was positively associated with TIMELESS expression. The expression of SIRT1, HK2, PKM2, LDHA and GLUT1 increased with the overexpression of TIMELESS levels and decreased with the knockdown of TIMELESS. CONCLUSION: TIMELESS exacerbates OSCC progression by modulating cellular proliferation and metabolic pathways, specifically by enhancing glycolysis and reducing oxidative phosphorylation, largely mediated through the SIRT1 pathway. This highlights TIMELESS as a potential target for OSCC therapeutic strategies.

A pharmacovigilance study of association between proton-pump inhibitors and rhabdomyolysis event based on FAERS database.

BACKGROUND AND AIM: The association between proton-pump inhibitors (PPIs) and rhabdomyolysis were unclear. The aim of this study was to explore and systematically analyze the potential link between five PPIs and the rhabdomyolysis events using the FDA Adverse Event Reporting System (FAERS) database. METHODS: Suspected rhabdomyolysis events associated with PPIs were identified by data mining with the reporting odds ratio (ROR), proportional reporting ratio (PRR), the information component (IC), and Empirical Bayes Geometric Mean (EBGM). Demographic information, drug administration, and outcomes of PPI-induced rhabdomyolysis events were also analyzed. RESULTS: There were 3311 reports associated with PPI-induced rhabdomyolysis that were identified. After removing duplicates, 1899 cases were determined to contain complete patient demographic data. The average age was 65 ± 18 year and 57% were male. Omeprazole and pantoprazole had the same largest percentage of reports. Lansoprazole had the highest ROR index of 12.67, followed by esomeprazole (11.18), omeprazole (10.27), rabeprazole (10.06), and pantoprazole (9.24). PRR, IC, and EBGM showed similar patterns. This suggested that lansoprazole exhibited the strongest correlation with rhabdomyolysis. In rhabdomyolysis events, PPIs were mainly "concomitant" (>60%), and only a few cases were "primary suspects" (<15%). Rabeprazole showed the lowest death rate while lansoprazole showed the highest. CONCLUSIONS: The study suggested that significant rhabdomyolysis signals were associated with PPIs. Further research should be performed in drug safety evaluation for a more comprehensive association.

Neoadjuvant chemoimmunotherapy shows major pathological response and low recurrence in head and neck squamous cell carcinoma.

BACKGROUND: The study aimed to investigate the efficacy and survival outcomes of neoadjuvant chemotherapy combined with programmed cell death protein 1 (PD-1) blockade (neoadjuvant chemoimmunotherapy) for patients with resectable head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was conducted. Patients with initially diagnosed, resectable HNSCCs who received the neoadjuvant chemoimmunotherapy and radical surgery were included. Correlation analysis between patients' clinical characteristics and pathological responses, and survival analysis were performed. RESULTS: A total of 79 patients were included. The majority of patients (55, 69.6%) were diagnosed at locally advanced stages and most of them (58, 73.4%) had tumor located at the oral cavity. Nearly half of patients (35, 44.3%) received two cycles of neoadjuvant chemoimmunotherapy and the rest had three or more cycles. The R0 resection rate was 98.7%. In the pathological evaluation, 53.1% of patients reached pathological complete responses or major pathological responses. After a median follow-up of 17.0 months, the 1-year disease-free survival (DFS) and overall survival (OS) rates were 87.2% and 97.4%, respectively. The pathological response showed a significantly positive association with survival benefits (p < 0.001). Patients with human papillomavirus (HPV)-positive oropharyngeal cancer had the best pathological response and survival outcomes. Besides, history of radiation at head and neck region and poor pathological response were found to be independent risk factors of DFS for patients receiving such treatments. CONCLUSION: Neoadjuvant chemoimmunotherapy of HNSCC showed high rate of pathological response and low recurrence rate, holding promise for becoming the new standard of care for resectable HNSCC.

Intragraft immune cells: accomplices or antagonists of recipient-derived macrophages in allograft fibrosis?

Organ fibrosis caused by chronic allograft rejection is a major concern in the field of transplantation. Macrophage-to-myofibroblast transition plays a critical role in chronic allograft fibrosis. Adaptive immune cells (such as B and CD4+ T cells) and innate immune cells (such as neutrophils and innate lymphoid cells) participate in the occurrence of recipient-derived macrophages transformed to myofibroblasts by secreting cytokines, which eventually leads to fibrosis of the transplanted organ. This review provides an update on the latest progress in understanding the plasticity of recipient-derived macrophages in chronic allograft rejection. We discuss here the immune mechanisms of allograft fibrosis and review the reaction of immune cells in allograft. The interactions between immune cells and the process of myofibroblast formulation are being considered for the potential therapeutic targets of chronic allograft fibrosis. Therefore, research on this topic seems to provide novel clues for developing strategies for preventing and treating allograft fibrosis.

Loneliness, depression and sleep quality among the type 2 diabetic patients during COVID-19 local epidemic: A mediation analysis.

AIMS: To investigate loneliness, depression and sleep quality in patients with Type 2 Diabetes (T2DM) and to examine the mediating role of depression between loneliness and sleep quality among this group of patients with T2DM. DESIGN: A cross-sectional study. METHODS: A group of T2DM patients was recruited from a tertiary hospital affiliated with a university in Wuhu City, Anhui Province from May to October 2021 by convenient sampling. Pearson correlation analysis and structural equation modelling were used for data analysis in this study. RESULTS: The direct effect of loneliness on sleep quality was not statistically significant, but the indirect effect of depression on sleep quality was statistically significant. Depression mediated the relationship between loneliness and sleep quality. Depression can affect emotional health and reduce sleep quality. We should reduce the loneliness of patients, prevent the occurrence of depression and improve the quality of sleep.

Enhancement of fungichromin production of Streptomyces sp. WP-1 by genetic engineering.

Fungichromin is a polyene macrolide antibiotic with potent killing activity against a broad range of agricultural pathogens and filamentous fungi and a wide range of potential applications. The production of fungichromin is still hampered by poor fermentation yield and high cost. In this study, the whole genome sequencing of fungichromin-producing Streptomyces sp. WP-1 was conducted, and the fungichromin biosynthetic gene cluster was identified. Comparative analysis revealed that the fungichromin biosynthetic gene cluster contains two regulatory genes, ptnF, and ptnR. The roles of ptnF and ptnR were determined through knockout and complementation. The yield of fungichromin was increased by overexpressing these two regulatory genes, as well as the crotonyl CoA reductase/carboxylase gene ptnB in Streptomyces sp. WP-1. The yield of fungichromin was increased to 8.5 g/L using a combination of genetic engineering and a medium optimization strategy, which is the highest fermentation titer recorded. KEY POINTS: • Confirmation of the positive regulation of ptnF and ptnR on fungichromin. • Improvement of fungichromin production by the construction of ptnF, ptnR, and ptnB overexpression strains. • Improvement of fungichromin production by the addition of soybean oil and copper ions at optimal concentration.

Generating an M2 × N2 spot array with a dual-period hybrid Dammann grating fabricated using maskless projection lithography.

The Dammann grating (DG), which redistributes a collimated laser beam into a spot array with a uniform intensity, is a widely adopted approach for profile measurement. Conventional DGs for dense spot projection are binary phase gratings with precisely designed groove structures, which suffer from low efficiency, poor uniformity, and a hard-to-fabricate fine feature size when utilized for a large field of view (FOV). Here, we propose a new, to the best of our knowledge, hybrid DG architecture consisting of two different grating periods which effectively generates an engineering M2 × N2 spot array with a non-complex structural design. As a proof-of-concept, a dual-period hybrid DG with a two-scale grating period ratio of 11.88 µm/95.04 µm (∼1/8) is designed and fabricated as a means to generate a dense 72 × 72 diffraction spot array with a FOV of 17° × 17°. In addition, the DG exhibits superior performance, with a high efficiency (>60%) and a low non-uniformity (<18%) at a wavelength of 532 nm. This kind of hybrid DG constructed from photoresist patterns with a minimum feature size of ∼1.2 µm can be perfectly fabricated by maskless projection lithography for large-scale and low-cost production. The proposed dual-period hybrid DG can pave the way for depth-perception-related applications such as face unlocking and motion sensing.

Treatment outcomes of mucosal melanoma of the head and neck: Analysis of 190 cases from a single institution.

Objectives: To analyze the treatment outcomes and prognostic factors of mucosal melanoma of the head and neck (MMHN) from a single institution. Methods: From December 1989 to November 2018, 190 patients diagnosed with MMHN were included. Survival analysis was performed using the Kaplan-Meier method for univariate analysis with a log-rank test for significance and Cox regression for multivariate analysis. Results: With a median follow-up time of 43.5 months, 126 (68.5%) patients died. The median DSS was 35 months. The 3- and 5-year disease-specific survival (DSS) rates were 48.1% and 33.7%, respectively. The median overall survival (OS) was 34 months. The 3- and 5-year OS rates were 47.0% and 32.9%, respectively. In univariate analysis, the T3 stage, received surgery, R0 resection, and combined therapy (surgery+biotherapy/biochemotherapy) were significantly associated with better survival. Multivariable Cox regression analysis revealed that the T4 stage (HR = 1.692; 95% CI, 1.175-2.438; p = .005) and the N1 stage (HR = 1.600; 95% CI, 1.023-2.504; p = .039) were strong prognostic factors for poor survival, and that combined therapy (surgery+biotherapy/biochemotherapy) was a strong prognostic factor for better survival outcome (HR = 0.563; 95% CI, 0.354-0.896; p = .015). Conclusion: The prognosis of MMHN remains poor. Systemic treatment is warranted to reduce MMHN progression. Surgery combined with biotherapy may improve survival.

Reciprocal costimulatory molecules control the activation of mucosal type 3 innate lymphoid cells during engagement with B cells.

Innate lymphoid cells (ILCs) are the counterpart of T helper cells in the innate immune system and share multiple phenotypes with T helper cells. Inducible T-cell costimulator (ICOS) is recognized on T cells and participates in T-cell activation and T and B-cell engagement in lymphoid tissues. However, the role of ICOS in ILC3s and ILC3-involved interactions with the immune microenvironment remains unclear. Here, we found that ICOS expression on human ILC3s was correlated with the activated state of ILC3s. ICOS costimulation enhanced the survival, proliferation, and capacity of ILC3s to produce cytokines (IL-22, IL-17A, IFN-γ, TNF, and GM-CSF). Via synergistic effects of ICOS and CD40 signaling, B cells promoted ILC3 functions, and ILC3-induced T-cell-independent B-cell IgA and IgM secretion primarily required CD40 signaling. Hence, ICOS is essential for the nonredundant role of ILC3s and their interaction with adjacent B cells.

Hydrogen peroxide enhanced photoinactivation of Candida albicans by a novel boron-dipyrromethene (BODIPY) derivative.

Photodynamic inactivation (PDI) has received increasing attention as a promising approach to combat Candida albicans infections. This study aimed to evaluate the synergistic effect of a new BODIPY (4,4-difluoro-boradiazaindacene) derivative and hydrogen peroxide on C. albicans. BDP-4L in combination with H2O2 demonstrated enhanced photokilling efficacy. In suspended cultures of C. albicans, the maximum decrease was 6.20 log and 2.56 log for PDI using BDP-4L (2.5 µM) with or without H2O2, respectively. For mature C. albicans biofilms, 20 µM BDP-4L plus H2O2 eradicated C. albicans, causing an over 6.7 log count reduction in biofilm-associated cells, while only a reduction of ~ 1 log count was observed when H2O2 was omitted. Scanning electron microscopy analysis and LIVE/DEAD assays suggested that PDI using BDP-4L plus H2O2 induced more damage to the cell membrane. Correspondingly, amplification of nucleic acids release was observed in biofilms treated with the combined PDI. Additionally, we also discovered that the addition of hydrogen peroxide potentiated the generation of 1O2 in PDI using the singlet oxygen sensor green probe. Collectively, BDP-4L combined with H2O2 presents a promising approach in the treatment of C. albicans infections.

Surgically Derived Cancer Cell Membrane-Coated R837-Loaded Poly(2-Oxazoline) Nanoparticles for Prostate Cancer Immunotherapy.

Cancer cell membranes (CCMs) are widely used as sources of tumor-associated antigens (TAAs) for the development of cancer vaccines. To improve the CCM-associated cancer vaccine efficiency, personalized cancer vaccines and effective delivery systems are required. In this study, we employed surgically harvested cancer tissues to prepare personalized CCMs for use as TAAs. Thioglycolic-acid-grafted poly(2-methyl-2-oxazoline)-block-poly(2-butyl-2-oxazoline-co-2-butenyl-2-oxazoline) (PMBEOx-COOH) was synthesized to load imiquimod (R837) efficiently. The personalized CCMs were then coated onto R837-loaded PMBEOx-COOH nanoparticles (POxTA NPs/R837) to obtain surgically derived CCM-coated POxTA NPs (SCNPs/R837). SCNPs/R837 efficiently travelled to the draining lymph nodes and were taken up and presented by plasmacytoid dendritic cells to elicit enhanced antitumor immune responses. When combined with programmed cell death-1 antibodies, SCNPs/R837 exhibited high efficiency corresponding to antitumor progression. Therefore, SCNP/R837 might represent a promising personalized cancer vaccine with significant potential for cancer immunotherapy.

BAX as the mediator of C-MYC sensitizes acute lymphoblastic leukemia to TLR9 agonists.

BACKGROUND: The prognosis of B-cell acute lymphoblastic leukemia (B-ALL) has improved significantly with current first-line therapy, although the recurrence of B-ALL is still a problem. Toll-like receptor 9 (TLR9) agonists have shown good safety and efficiency as immune adjuvants. Apart from their immune regulatory effect, the direct effect of TLR9 agonists on cancer cells with TLR9 expression cannot be ignored. However, the direct effect of TLR9 agonists on B-ALL remains unknown. METHODS: We discussed the relationship between TLR9 expression and the clinical characteristics of B-ALL and explored whether CpG 685 exerts direct apoptotic effect on B-ALL without inhibiting normal B-cell function. By using western blot, co-immunoprecipitation, immunofluorescence co-localization, and chromatin immunoprecipitation, we explored the mechanism of the apoptosis-inducing effect of CpG 685 in treating B-ALL cells. By exploring the mechanism of CpG 685 on B-ALL, the predictive biomarkers of the efficacy of CpG 685 in treating B-ALL were explored. These efficiencies were also confirmed in mouse model as well as clinical samples. RESULTS: High expression of TLR9 in B-ALL patients showed good prognosis. C-MYC-induced BAX activation was the key to the effect of CpG oligodeoxynucleotides against B-ALL. C-MYC overexpression promoted P53 stabilization, enhanced Bcl-2 associated X-protein (BAX) activation, and mediated transcription of the BAX gene. Moreover, combination therapy using CpG 685 and imatinib, a BCR-ABL kinase inhibitor, could reverse resistance to CpG 685 or imatinib alone by promoting BAX activation and overcoming BCR-ABL1-independent PI3K/AKT activation. CONCLUSION: TLR9 is not only a prognostic biomarker but also a potential target for B-ALL therapy. CpG 685 monotherapy might be applicable to Ph- B-ALL patients with C-MYC overexpression and without BAX deletion. CpG 685 may also serve as an effective combinational therapy against Ph+ B-ALL.

Biomarker discovery and application-An opportunity to resolve the challenge of liver cancer diagnosis and treatment.

Liver cancer is one of the most common malignancies, with severe morbidity and mortality. While considerable progress has been made in liver cancer treatment, the 5-year overall survival (OS) of patients has not improved significantly. Reasons include the inadequate capability of early screening and diagnosis, a high incidence of recurrence and metastasis, a high degree of tumor heterogeneity, and an immunosuppressive tumor microenvironment. Therefore, the identification and validation of specific and robust liver cancer biomarkers are of major importance for early screening, timely diagnosis, accurate prognosis, and the prevention of tumor progression. In this review, we highlight some of the latest research progress and potential applications of liver cancer biomarkers, describing hotspots and prospective directions in biomarker discovery.