EGB761 ameliorates mild cognitive impairment by inhibiting the pyroptosis and apoptosis in both in vivo and in vitro experiments.

Mild cognitive impairment (MCI) is a neurodegenerative condition that is clinically prevalent among the elderly. EGB761 is widely recognized for its promising therapeutic properties in both the prevention and treatment of neurodegenerative disorders. The aim of this study was to investigate the effects of EGB761 in MCI and the underlying molecular mechanism. Four-month-old SAMP8 mice were used as an in vivo MCI model, and BV2 microglial cells were treated with ß-amyloid (Aß) 1-42 to establish an in vitro model. First, the cognitive function was evaluated by the Morris water maze. Then, Aß levels were measured by enzyme-linked immunosorbent assay. Finally, the underlying molecular mechanism was investigated both in vivo and in vitro. It was found that EGB761 treatment improved the cognitive impairment of SAMP8 mice. In addition, EGB761 inhibited NOD-like receptor protein 3 inflammasome-mediated pyroptosis-related mRNAs and proteins and reduced pyroptosis markers, including gasdermin D fluorescence intensity, propidium iodide-positive cell count, and the lactate dehydrogenase content. Furthermore, EGB761 inhibited extrinsic and intrinsic apoptosis. Thus, EGB761 had protective effects against pyroptosis and apoptosis in BV2 microglial cells induced by Aß1-42 and SAMP8 mice.

Calpain: The regulatory point of cardiovascular and cerebrovascular diseases.

Calpain, a key member of the Calpain cysteine protease superfamily, performs limited protein hydrolysis in a calcium-dependent manner. Its activity is tightly regulated due to the potential for non-specific cleavage of various intracellular proteins upon aberrant activation. A thorough review of the literature from 2010 to 2023 reveals 121 references discussing cardiovascular and cerebrovascular diseases. Dysregulation of the Calpain system is associated with various pathological phenomena, including lipid metabolism disorders, inflammation, apoptosis, and excitotoxicity. Although recent studies have revealed the significant role of Calpain in cardiovascular and cerebrovascular diseases, the precise mechanisms remain incompletely understood. Exploring the potential of Calpain inhibition as a therapeutic approach for the treatment of cardiovascular and cerebrovascular diseases may emerge as a compelling area of interest for future calpain research.

MCC950 as a promising candidate for blocking NLRP3 inflammasome activation: A review of preclinical research and future directions.

The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key component of the innate immune system that triggers inflammation and pyroptosis and contributes to the development of several diseases. Therefore, blocking the activation of the NLRP3 inflammasome has therapeutic potential for the treatment of these diseases. MCC950, a selective small molecule inhibitor, has emerged as a promising candidate for blocking NLRP3 inflammasome activation. Ongoing research is focused on elucidating the specific targets of MCC950 as well as assessfing its metabolism and safety profile. This review discusses the diseases that have been studied in relation to MCC950, with a focus on stroke, Alzheimer's disease, liver injury, atherosclerosis, diabetes mellitus, and sepsis, using bibliometric analysis. It then summarizes the potential pharmacological targets of MCC950 and discusses its toxicity. Furthermore, it traces the progression from preclinical to clinical research for the treatment of these diseases. Overall, this review provides a solid foundation for the clinical therapeutic potential of MCC950 and offers insights for future research and therapeutic approaches.

A comprehensive review of deep learning in EEG-based emotion recognition: classifications, trends, and practical implications.

Emotion recognition utilizing EEG signals has emerged as a pivotal component of human-computer interaction. In recent years, with the relentless advancement of deep learning techniques, using deep learning for analyzing EEG signals has assumed a prominent role in emotion recognition. Applying deep learning in the context of EEG-based emotion recognition carries profound practical implications. Although many model approaches and some review articles have scrutinized this domain, they have yet to undergo a comprehensive and precise classification and summarization process. The existing classifications are somewhat coarse, with insufficient attention given to the potential applications within this domain. Therefore, this article systematically classifies recent developments in EEG-based emotion recognition, providing researchers with a lucid understanding of this field's various trajectories and methodologies. Additionally, it elucidates why distinct directions necessitate distinct modeling approaches. In conclusion, this article synthesizes and dissects the practical significance of EEG signals in emotion recognition, emphasizing its promising avenues for future application.

KLF12 interacts with TRIM27 to affect cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma by regulating L1CAM expression.

Krüppel-like factor 12 (KLF12) has been characterized as a transcriptional repressor, and previous studies have unveiled its roles in angiogenesis, neural tube defect, and natural killer (NK) cell proliferation. However, the contribution of KLF12 to cancer treatment remains undefined. Here, we show that KLF12 is downregulated in various cancer types, and KLF12 downregulation promotes cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma (ESCC). Mechanistically, KLF12 binds to the promoters of L1 Cell Adhesion Molecule (L1CAM) and represses its expression. Depletion of L1CAM abrogates cisplatin resistance and cancer metastasis caused by KLF12 loss. Moreover, the E3 ubiquitin ligase tripartite motif-containing 27 (TRIM27) binds to the N-terminal region of KLF12 and ubiquitinates KLF12 at K326 via K33-linked polyubiquitination. Notably, TRIM27 depletion enhances the transcriptional activity of KLF12 and consequently inhibits L1CAM expression. Overall, our study elucidated a novel regulatory mechanism involving TRIM27, KLF12 and L1CAM, which plays a substantial role in cisplatin resistance and cancer metastasis in ESCC. Targeting these genes could be a promising approach for ESCC treatment.

[Non-targeted metabolomics of spleen and liver metabolism in mice treated with Pruni Semen processed with different methods].

Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to investigate the impacts of Pruni Semen processed with different methods(raw and fried) on the liver and spleen metabolism in mice. A total of 24 male mice were randomly assigned to three groups: raw Pruni Semen group, fried Pruni Semen group, and control(deionized water) group. Mice in the three groups were orally administrated with 0.01 g·mL~(-1) Pruni Semen decoction or deionized water for one week. After that, the liver and spleen tissues were collected, and liquid chromatography-mass spectrometry(LC-MS)-based metabolomic analysis was carried out to investigate the impact of Pruni Semen on the liver and spleen metabolism in mice. Compared with thte control group, the raw Pruni Semen group showed up-regulation of 11 metabolites and down-regulation of 57 metabolites in the spleen(P<0.05), as well as up-regulation of 15 metabolites and down-regulation of 58 metabolites in the liver(P<0.05). The fried Pruni Semen group showed up-regulation of 31 metabolites and down-regulation of 10 metabolites in the spleen(P<0.05), along with up-regulation of 26 metabolites and down-regulation of 61 metabolites in the liver(P<0.05). The differential metabolites identified in the raw Pruni Semen group were primarily associated with alanine, aspartate, and glutamate metabolism, purine metabolism, amino sugar and nucleotide sugar metabolism, and D-glutamine and D-glutamate metabolism. The differential metabolites identified in the fried Pruni Semen group predominantly involved riboflavin metabolism, amino sugar and nucleotide sugar metabolism, purine metabolism, alanine, aspartate, and glutamate metabolism, D-glutamine and D-glutamate metabolism, and glutathione metabolism. The findings suggest that both raw and fried Pruni Semen have the potential to modulate the metabolism of the liver and spleen in mice by influencing the glutamine and glutamate metabolism.

TGF-ß signaling in health, disease, and therapeutics.

Transforming growth factor (TGF)-ß is a multifunctional cytokine expressed by almost every tissue and cell type. The signal transduction of TGF-ß can stimulate diverse cellular responses and is particularly critical to embryonic development, wound healing, tissue homeostasis, and immune homeostasis in health. The dysfunction of TGF-ß can play key roles in many diseases, and numerous targeted therapies have been developed to rectify its pathogenic activity. In the past decades, a large number of studies on TGF-ß signaling have been carried out, covering a broad spectrum of topics in health, disease, and therapeutics. Thus, a comprehensive overview of TGF-ß signaling is required for a general picture of the studies in this field. In this review, we retrace the research history of TGF-ß and introduce the molecular mechanisms regarding its biosynthesis, activation, and signal transduction. We also provide deep insights into the functions of TGF-ß signaling in physiological conditions as well as in pathological processes. TGF-ß-targeting therapies which have brought fresh hope to the treatment of relevant diseases are highlighted. Through the summary of previous knowledge and recent updates, this review aims to provide a systematic understanding of TGF-ß signaling and to attract more attention and interest to this research area.

Smart Hydrogels for Tissue Regeneration.

The rapid growth in the portion of the aging population has led to a consequent increase in demand for biomedical hydrogels, together with an assortment of challenges that need to be overcome in this field. Smart hydrogels can autonomously sense and respond to the physiological/pathological changes of the tissue microenvironment and continuously adapt the response according to the dynamic spatiotemporal shifts in conditions. This along with other favorable properties, make smart hydrogels excellent materials for employing toward improving the precision of treatment for age-related diseases. The key factor during the smart hydrogel design is on accurately identifying the characteristics of natural tissues and faithfully replicating the composition, structure, and biological functions of these tissues at the molecular level. Such hydrogels can accurately sense distinct physiological and external factors such as temperature and biologically active molecules, so they may in turn actively and promptly adjust their response, by regulating their own biological effects, thereby promoting damaged tissue repair. This review summarizes the design strategies employed in the creation of smart hydrogels, their response mechanisms, as well as their applications in field of tissue engineering; and concludes by briefly discussing the relevant challenges and future prospects.

Inflammatory signaling pathways in the treatment of Alzheimer's disease with inhibitors, natural products and metabolites (Review).

The intricate nature of Alzheimer's disease (AD) pathogenesis poses a persistent obstacle to drug development. In recent times, neuroinflammation has emerged as a crucial pathogenic mechanism of AD, and the targeting of inflammation has become a viable approach for the prevention and management of AD. The present study conducted a comprehensive review of the literature between October 2012 and October 2022, identifying a total of 96 references, encompassing 91 distinct pharmaceuticals that have been investigated for their potential impact on AD by inhibiting neuroinflammation. Research has shown that pharmaceuticals have the potential to ameliorate AD by reducing neuroinflammation mainly through regulating inflammatory signaling pathways such as NF­κB, MAPK, NLRP3, PPARs, STAT3, CREB, PI3K/Akt, Nrf2 and their respective signaling pathways. Among them, tanshinone IIA has been extensively studied for its anti­inflammatory effects, which have shown significant pharmacological properties and can be applied clinically. Thus, it may hold promise as an effective drug for the treatment of AD. The present review elucidated the inflammatory signaling pathways of pharmaceuticals that have been investigated for their therapeutic efficacy in AD and elucidates their underlying mechanisms. This underscores the auspicious potential of pharmaceuticals in ameliorating AD by impeding neuroinflammation.

A Metal-Organic Framework-Incorporated Hydrogel for Delivery of Immunomodulatory Neobavaisoflavone to Promote Cartilage Regeneration in Osteoarthritis.

The treatment of osteoarthritis (OA)-related cartilage defects is a great clinical challenge due to the complex pathogenesis of OA and poor self-repair ability of cartilage tissue. Combining local and long-term anti-inflammatory therapies to promote cartilage repair is an effective method to treat OA. In this study, a zinc-organic framework-incorporated extracellular matrix (ECM)-mimicking hydrogel platform was constructed for the inflammatory microenvironment-responsive delivery of neobavaisoflavone (NBIF) to promote cartilage regeneration in OA. The NBIF was encapsulated in situ in zeolitic imidazolate frameworks (ZIF-8 MOFs). The NBIF@ZIF-8 MOFs were decorated with polydopamine and incorporated into a methacrylate gelatin/hyaluronic acid hybrid network to form the NBIF@ZIF-8/PHG hydrogel. The hydrogel featured excellent cell/tissue affinity, providing a favorable microenvironment for recruiting cells and cytokines to the defect sites. The hydrogel enabled the on-demand NBIF released in response to a weakly acidic microenvironment at the injured joint site to resolve inflammatory responses during the early stages of OA. Consequently, the cooperativity of the loaded NBIF and hydrogel synergistically modulated the immune response and assisted in cartilage defect repair. In summary, the NBIF@ZIF-8/PHG hydrogel delivery platform represents an effective treatment strategy for OA-related cartilage defects and may attract attentions for applications in other inflammatory diseases.

Melatonin as a therapeutic agent for alleviating endothelial dysfunction in cardiovascular diseases: Emphasis on oxidative stress.

The vascular endothelium is vital in maintaining cardiovascular health by regulating vascular permeability and tone, preventing thrombosis, and controlling vascular inflammation. However, when oxidative stress triggers endothelial dysfunction, it can lead to chronic cardiovascular diseases (CVDs). This happens due to oxidative stress-induced mitochondrial dysfunction, inflammatory responses, and reduced levels of nitric oxide. These factors cause damage to endothelial cells, leading to the acceleration of CVD progression. Melatonin, a natural antioxidant, has been shown to inhibit oxidative stress and stabilize endothelial function, providing cardiovascular protection. The clinical application of melatonin in the prevention and treatment of CVDs has received widespread attention. In this review, based on bibliometric studies, we first discussed the relationship between oxidative stress-induced endothelial dysfunction and CVDs, then summarized the role of melatonin in the treatment of atherosclerosis, hypertension, myocardial ischemia-reperfusion injury, and other CVDs. Finally, the potential clinical use of melatonin in the treatment of these diseases is discussed.

H3K4 trimethylation regulates cancer immunity: a promising therapeutic target in combination with immunotherapy.

With the advances in cancer immunity regulation and immunotherapy, the effects of histone modifications on establishing antitumor immunological ability are constantly being uncovered. Developing combination therapies involving epigenetic drugs (epi-drugs) and immune checkpoint blockades or chimeric antigen receptor-T cell therapies are promising to improve the benefits of immunotherapy. Histone H3 lysine 4 trimethylation (H3K4me3) is a pivotal epigenetic modification in cancer immunity regulation, deeply involved in modulating tumor immunogenicity, reshaping tumor immune microenvironment, and regulating immune cell functions. However, how to integrate these theoretical foundations to create novel H3K4 trimethylation-based therapeutic strategies and optimize available therapies remains uncertain. In this review, we delineate the mechanisms by which H3K4me3 and its modifiers regulate antitumor immunity, and explore the therapeutic potential of the H3K4me3-related agents combined with immunotherapies. Understanding the role of H3K4me3 in cancer immunity will be instrumental in developing novel epigenetic therapies and advancing immunotherapy-based combination regimens.

KLF12 overcomes anti-PD-1 resistance by reducing galectin-1 in cancer cells.

BACKGROUNDS: Immune checkpoint blockade has revolutionized cancer treatment and has improved the survival of a subset of patients with cancer. However, numerous patients do not benefit from immunotherapy, and treatment resistance is a major challenge. Krüppel-like factor 12 (KLF12) is a transcriptional inhibitor whose role in tumor immunity is unclear. METHODS: We demonstrated a relationship between KLF12 and CD8+ T cells in vivo and in vitro by flow cytometry. The role and underlying mechanism that KLF12 regulates CD8+ T cells were investigated using reverse transcription and quantitative PCR, western blot FACS, chromatin immunoprecipitation-PCR and Dual-Luciferase reporter assays, etc, and employing small interfering RNA (siRNA) and inhibitors. In vivo efficacy studies were conducted with multiple mouse tumor models, employing anti-programmed cell death protein 1 combined with KLF12 or galectin-1 (Gal-1) inhibitor. RESULTS: Here, we found that the expression of tumor KLF12 correlates with immunotherapy resistance. KLF12 suppresses CD8+ T cells infiltration and function in vitro and in vivo. Mechanistically, KLF12 inhibits the expression of Gal-1 by binding with its promoter, thereby improving the infiltration and function of CD8+ T cells, which plays a vital role in cancer immunotherapy. CONCLUSIONS: This work identifies a novel pathway regulating CD8+ T-cell intratumoral infiltration, and targeting the KLF12/Gal-1 axis may serve as a novel therapeutic target for patients with immunotherapy resistance.

Therapeutic Candidates for Alzheimer's Disease: Saponins.

Drug development for Alzheimer's disease, the leading cause of dementia, has been a long-standing challenge. Saponins, which are steroid or triterpenoid glycosides with various pharmacological activities, have displayed therapeutic potential in treating Alzheimer's disease. In a comprehensive review of the literature from May 2007 to May 2023, we identified 63 references involving 40 different types of saponins that have been studied for their effects on Alzheimer's disease. These studies suggest that saponins have the potential to ameliorate Alzheimer's disease by reducing amyloid beta peptide deposition, inhibiting tau phosphorylation, modulating oxidative stress, reducing inflammation, and antiapoptosis. Most intriguingly, ginsenoside Rg1 and pseudoginsenoside-F11 possess these important pharmacological properties and show the best promise for the treatment of Alzheimer's disease. This review provides a summary and classification of common saponins that have been studied for their therapeutic potential in Alzheimer's disease, showcasing their underlying mechanisms. This highlights the promising potential of saponins for the treatment of Alzheimer's disease.

Hippocampal proteins discovery of Panax quinquefolius and Acorus gramineus ameliorating cognitive impairment in diabetic rats.

RATIONALE: Early diagnosis of diabetic cognitive impairment (DCI) and investigation of effective medicines are significant to prevent or delay the occurrence of irreversible dementia. OBJECTIVES: In this study, proteomics was applied to investigate the changes of hippocampal proteins after administration of Panax quinquefolius-Acorus gramineus (PQ-AG) to DCI rats, with a view to discover the differentially expressed proteins of PQ-AG action and elucidated the potential biological relationships. METHODS: The model and PQ-AG group rats were injected intraperitoneally with streptozotocin, and the PQ-AG group rats were continuously administered with PQ-AG. Social interaction and Morris water maze were performed to evaluate the behavior of rats on the 17th week after the model was established, and DCI rats were screened out from the model group by a screening approach. The hippocampal protein differences were investigated with proteomics in DCI and PQ-AG-treated rats. RESULTS: The learning and memory abilities and contact duration of DCI rats were improved after 16 weeks of PQ-AG administration. Altogether, 9 and 17 differentially expressed proteins were observed in control versus DCI rats and in DCI versus PQ-AG-treated rats, respectively. Three proteins were confirmed with western blotting analyses. These proteins were mainly involved in the pathways of JAK-STAT, apoptosis, PI3K/AKT, fork-head box protein O3, fructose, and mannose metabolism. CONCLUSIONS: This suggested that PQ-AG ameliorated cognitive impairment of diabetic rats by influencing the above pathways and providing an experimental basis for the mechanism of DCI and PQ-AG.

Impact of the extent of recurrent laryngeal nerve lymphadenectomy on thoracic esophageal squamous cell carcinoma: a real-world multicentre study.

OBJECTIVES: To determine the impact of recurrent laryngeal nerve (RLN) lymph node (LN) dissection on survival and postoperative complications in patients with oesophageal squamous cell carcinoma (ESCC). METHODS: Patients with cT1-4N0-3M0 thoracic ESCC who underwent oesophagectomy and two-field lymphadenectomy from three institutions were included. The entire cohort was divided into three groups that underwent the total two-field lymphadenectomy (T-2FL), standard two-field lymphadenectomy (S-2FL) or unilateral RLN-LN dissection plus S-2FL (U-2FL) based on the extent of RLN-LN dissection. Subgroup analyses were also performed and were stratified by treatment modality. RESULTS: Both the U-2FL and T-2FL groups had significantly superior outcomes compared with the S-2FL group (overall survival: U-2FL versus S-2FL: P = 0.002; T-2FL versus S-2FL: P < 0.001; recurrence-free survival: U-2FL versus S-2FL: P = 0.01; T-2FL versus S-2FL: P < 0.001). Moreover, no significant differences were observed between U-2FL and T-2FL regarding overall survival (P > 0.05) and recurrence-free survival (P > 0.05), irrespective of administration of neoadjuvant therapy plus oesophagectomy or upfront oesophagectomy. Additionally, the extent of RLN-LN dissection was not an independent predictor of stage migration (P = 0.14) but was for postoperative nodal upstaging (P = 0.02). Notably, S-2FL brought significantly lowered risk in postoperative complications, especially for RLN palsy, when compared with T-2FL (P = 0.002) but not U-2FL (P = 0.72). CONCLUSIONS: Adequacy of RLN-LN dissection is an important prognosticator for improved overall survival and recurrence-free survival in patients with thoracic ESCC. U-2FL may serve as an alternative to T-2FL in selected populations.

Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review).

The inflammasome regulates innate immunity by serving as a signaling platform. The Nod­like receptor protein 3 (NLRP3) inflammasome, equipped with NLRP3, the adaptor protein apoptosis­associated speck­like protein (ASC) and pro­caspase­1, is by far the most extensively studied and well­characterized inflammasome. A variety of stimuli can activate the NLRP3 inflammasome. When activated, the NLRP3 protein recruits the adaptor ASC protein and activates pro­caspase­1, resulting in inflammatory cytokine maturation and secretion, which is associated with inflammation and pyroptosis. However, the aberrant activation of the NLRP3 inflammasome has been linked to various inflammatory diseases, including atherosclerosis, ischemic stroke, Alzheimer's disease, diabetes mellitus and inflammatory bowel disease. Therefore, the NLRP3 inflammasome has emerged as a promising therapeutic target for inflammatory diseases. In the present review, systematic searches were performed using 'NLRP3 inhibitor(s)' and 'inflammatory disease(s)' as key words. By browsing the literature from 2012 to 2022, 100 articles were retrieved, of which 35 were excluded as they were reviews, editorials, retracted or unavailable online, and 65 articles were included. According to the retrieved literature, the current understanding of NLRP3 inflammasome pathway activation in inflammatory diseases was summarize, and inhibitors of the NLRP3 inflammasome pathway targeting the NLRP3 protein and other inflammasome components or products were highlighted. Additionally, the present review briefly discusses the current novel efforts in clinical research.

Ginsenoside Rg1 attenuates cerebral ischemia-reperfusion injury through inhibiting the inflammatory activation of microglia.

It is recognized that the cerebral ischemia/reperfusion (I/R) injury triggers inflammatory activation of microglia and supports microglia-driven neuronal damage. Our previous studies have shown that ginsenoside Rg1 had a significant protective effect on focal cerebral I/R injury in middle cerebral artery occlusion (MCAO) rats. However, the mechanism still needs further clarification. Here, we firstly reported that ginsenoside Rg1 effectively suppressed the inflammatory activation of brain microglia cells under I/R conditions depending on the inhibition of Toll-likereceptor4 (TLR4) proteins. In vivo experiments showed that the ginsenoside Rg1 administration could significantly improve the cognitive function of MCAO rats, and in vitro experimental data showed that ginsenoside Rg1 significantly alleviated neuronal damage via inhibiting the inflammatory response in microglia cells co-cultured under oxygen and glucose deprivation/reoxygenation (OGD/R) condition in gradient dependent. The mechanism study showed that the effect of ginsenoside Rg1 depends on the suppression of TLR4/MyD88/NF-κB and TLR4/TRIF/IRF-3 pathways in microglia cells. In a word, our research shows that ginsenoside Rg1 has great application potential in attenuating the cerebral I/R injury by targeting TLR4 protein in the microglia cells.

DEEP DAG LEARNING OF EFFECTIVE BRAIN CONNECTIVITY FOR FMRI ANALYSIS.

Functional magnetic resonance imaging (fMRI) has become one of the most common imaging modalities for brain function analysis. Recently, graph neural networks (GNN) have been adopted for fMRI analysis with superior performance. Unfortunately, traditional functional brain networks are mainly constructed based on similarities among region of interests (ROIs), which are noisy and can lead to inferior results for GNN models. To better adapt GNNs for fMRI analysis, we propose DABNet, a Deep DAG learning framework based on Brain Networks for fMRI analysis. DABNet adopts a brain network generator module, which harnesses the DAG learning approach to transform the raw time-series into effective brain connectivities. Experiments on two fMRI datasets demonstrate the efficacy of DABNet. The generated brain networks also highlight the prediction-related brain regions and thus provide interpretations for predictions.

Glycolysis in tumor microenvironment as a target to improve cancer immunotherapy.

Cancer cells and immune cells all undergo remarkably metabolic reprogramming during the oncogenesis and tumor immunogenic killing processes. The increased dependency on glycolysis is the most typical trait, profoundly involved in the tumor immune microenvironment and cancer immunity regulation. However, how to best utilize glycolytic targets to boost anti-tumor immunity and improve immunotherapies are not fully illustrated. In this review, we describe the glycolytic remodeling of various immune cells within the tumor microenvironment (TME) and the deleterious effects of limited nutrients and acidification derived from enhanced tumor glycolysis on immunological anti-tumor capacity. Moreover, we elucidate the underlying regulatory mechanisms of glycolytic reprogramming, including the crosstalk between metabolic pathways and immune checkpoint signaling. Importantly, we summarize the potential glycolysis-related targets that are expected to improve immunotherapy benefits. Our understanding of metabolic effects on anti-tumor immunity will be instrumental for future therapeutic regimen development.