Survival strategies: How tumor hypoxia microenvironment orchestrates angiogenesis.

During tumor development, the tumor itself must continuously generate new blood vessels to meet their growth needs while also allowing for tumor invasion and metastasis. One of the most common features of tumors is hypoxia, which drives the process of tumor angiogenesis by regulating the tumor microenvironment, thus adversely affecting the prognosis of patients. In addition, to overcome unsuitable environments for growth, such as hypoxia, nutrient deficiency, hyperacidity, and immunosuppression, the tumor microenvironment (TME) coordinates angiogenesis in several ways to restore the supply of oxygen and nutrients and to remove metabolic wastes. A growing body of research suggests that tumor angiogenesis and hypoxia interact through a complex interplay of crosstalk, which is inextricably linked to the TME. Here, we review the TME's positive contribution to angiogenesis from an angiogenesis-centric perspective while considering the objective impact of hypoxic phenotypes and the status and limitations of current angiogenic therapies.

Feasibility of endovascular stimulation of the femoral nerve using a stent-mounted electrode array.

OBJECTIVE: Electrical stimulation of peripheral nerves has long been a treatment option to restore impaired neural functions that cannot be restored by conventional pharmacological therapies. Endovascular neurostimulation with stent-mounted electrode arrays is a promising and less invasive alternative to traditional implanted electrodes, which typically require invasive implantation surgery. In this study, we investigated the feasibility of endovascular stimulation of the femoral nerve using a stent-mounted electrode array and compared its performance to that of a commercially available pacing catheter. Approach: In acute animal experiments, a quadripolar pacing catheter was implanted unilaterally in the femoral artery to stimulate the femoral nerve in a bipolar configuration. Electromyogram (EMG) of the quadriceps and electroneurogram (ENG) of a distal branch of the femoral nerve were recorded. After retrieval of the pacing catheter, a bipolar stent-mounted electrode array was implanted in the same artery and the recording sessions were repeated. Main Results: Stimulation of the femoral nerve was feasible with the stent-electrode array. Although the threshold stimulus intensities required with the stent-mounted electrode array (at 100-500µs increasing pulse width, 2.17 ± 0.87 mA - 1.00 ± 0.11 mA) were more than two times higher than the pacing catheter electrodes (1.05 ± 0.48 mA - 0.57 ± 0.28mA), we demonstrated that, by reducing the stimulus pulse width to 100 µs, the threshold charge per phase and charge density can be reduced to 0.22 ± 0.09 µC and 24.62 ± 9.81 µC/cm2, which were below the tissue-damaging limit, as defined by the Shannon criteria. Significance: The present study is the first to report in vivo feasibility and efficiency of peripheral nerve stimulation using an endovascular stent-mounted electrode array. .

Development and Validation of an Explainable Deep Learning Model to Predict In-Hospital Mortality for Patients With Acute Myocardial Infarction: Algorithm Development and Validation Study.

BACKGROUND: Acute myocardial infarction (AMI) is one of the most severe cardiovascular diseases and is associated with a high risk of in-hospital mortality. However, the current deep learning models for in-hospital mortality prediction lack interpretability. OBJECTIVE: This study aims to establish an explainable deep learning model to provide individualized in-hospital mortality prediction and risk factor assessment for patients with AMI. METHODS: In this retrospective multicenter study, we used data for consecutive patients hospitalized with AMI from the Chongqing University Central Hospital between July 2016 and December 2022 and the Electronic Intensive Care Unit Collaborative Research Database. These patients were randomly divided into training (7668/10,955, 70%) and internal test (3287/10,955, 30%) data sets. In addition, data of patients with AMI from the Medical Information Mart for Intensive Care database were used for external validation. Deep learning models were used to predict in-hospital mortality in patients with AMI, and they were compared with linear and tree-based models. The Shapley Additive Explanations method was used to explain the model with the highest area under the receiver operating characteristic curve in both the internal test and external validation data sets to quantify and visualize the features that drive predictions. RESULTS: A total of 10,955 patients with AMI who were admitted to Chongqing University Central Hospital or included in the Electronic Intensive Care Unit Collaborative Research Database were randomly divided into a training data set of 7668 (70%) patients and an internal test data set of 3287 (30%) patients. A total of 9355 patients from the Medical Information Mart for Intensive Care database were included for independent external validation. In-hospital mortality occurred in 8.74% (670/7668), 8.73% (287/3287), and 9.12% (853/9355) of the patients in the training, internal test, and external validation cohorts, respectively. The Self-Attention and Intersample Attention Transformer model performed best in both the internal test data set and the external validation data set among the 9 prediction models, with the highest area under the receiver operating characteristic curve of 0.86 (95% CI 0.84-0.88) and 0.85 (95% CI 0.84-0.87), respectively. Older age, high heart rate, and low body temperature were the 3 most important predictors of increased mortality, according to the explanations of the Self-Attention and Intersample Attention Transformer model. CONCLUSIONS: The explainable deep learning model that we developed could provide estimates of mortality and visual contribution of the features to the prediction for a patient with AMI. The explanations suggested that older age, unstable vital signs, and metabolic disorders may increase the risk of mortality in patients with AMI.

Elucidation of clinical implications Arising from circadian rhythm and insights into the tumor immune landscape in breast cancer.

Background: Circadian rhythm is an internal timing system generated by circadian-related genes (CRGs). Disruption in this rhythm has been associated with a heightened risk of breast cancer (BC) and regulation of the immune microenvironment of tumors. This study aimed to investigate the clinical significance of CRGs in BC and the immune microenvironment. Methods: CRGs were identified using the GeneCards and MSigDB databases. Through unsupervised clustering, we identified two circadian-related subtypes in patients with BC. We constructed a prognostic model and nomogram for circadian-related risk scores using LASSO and Cox regression analyses. Using multi-omics analysis, the mutation profile and immunological microenvironment of tumors were investigated, and the immunotherapy response in different groups of patients was predicted based on their risk strata. Results: The two circadian-related subtypes of BC that were identified differed significantly in their prognoses, clinical characteristics, and tumor immune microenvironments. Subsequently, we constructed a circadian-related risk score (CRRS) model containing eight signatures (SIAH2, EZR, GSN, TAGLN2, PRDX1, MCM4, EIF4EBP1, and CD248) and a nomogram. High-risk individuals had a greater burden of tumor mutations, richer immune cell infiltration, and higher expression of immune checkpoint genes, than low-risk individuals, indicating a "hot tumor" immune phenotype and a more favorable treatment outcome. Conclusions: Two circadian-related subtypes of BC were identified and used to establish a CRRS prognostic model and nomogram. These will be valuable in providing guidance for forecasting prognosis and developing personalized treatment plans for BC.

Physiological Investigation and Transcriptome Analysis Reveals the Mechanisms of Setaria italica's Yield Formation under Heat Stress.

Setaria italica is an important crop in China that plays a vital role in the Chinese dietary structure. In the last several decades, high temperature has become the most severe climate issue in the world, which causes great harm to the yield and quality formation of millet. In this study, two main cultivated varieties (ZG2 and AI88) were used to explore the photosynthesis and yield index of the whole plant under heat stress. Results implied that photosynthesis was not inhibited during the heat stress, and that the imbalance in sugar transport between different tissues may be the main factor that affects yield formation. In addition, the expression levels of seven SiSUT and twenty-four SiSWEET members were explored. Sugar transporters were heavily affected during the heat stress. The expression of SiSWEET13a was inhibited by heat stress in the stems, which may play a vital role in sugar transport between different tissues. These results provide new insights into the yield formation of crops under heat stress, which will provide guidance to crop breeding and cultivation.

LRPL-VIO: A Lightweight and Robust Visual-Inertial Odometry with Point and Line Features.

Visual-inertial odometry (VIO) algorithms, fusing various features such as points and lines, are able to improve their performance in challenging scenes while the running time severely increases. In this paper, we propose a novel lightweight point-line visual-inertial odometry algorithm to solve this problem, called LRPL-VIO. Firstly, a fast line matching method is proposed based on the assumption that the photometric values of endpoints and midpoints are invariant between consecutive frames, which greatly reduces the time consumption of the front end. Then, an efficient filter-based state estimation framework is designed to finish information fusion (point, line, and inertial). Fresh measurements of line features with good tracking quality are selected for state estimation using a unique feature selection scheme, which improves the efficiency of the proposed algorithm. Finally, validation experiments are conducted on public datasets and in real-world tests to evaluate the performance of LRPL-VIO and the results show that we outperform other state-of-the-art algorithms especially in terms of speed and robustness.

Effect of magnetic field mediated CaCl2 on the edible quality of low-sodium minced pork gels.

Magnetic field combined with calcium chloride (CaCl2,) treatment is a highly promising technique for reducing sodium chloride (NaCl) in meat. Therefore, this paper investigated the effect of reducing NaCl addition (0-10%) by CaCl2 in combination with a magnetic field (3.8 mT) on the edible quality of low-salt pork mince. It is desired to drive the application of magnetic field and CaCl2 in low-sodium meat processing in this way. Results showed that the cooking yield, color, hardness, elasticity, mouthfeel, apparent texture, and orderliness of protein conformation of all minced pork were improved as compared to the control group, while the electron nose response values of their volatile sulfides and nitrogen oxides were decreased. In particular, the best edible quality and perceived salty intensity of minced pork gel was obtained by using CaCl2 in place of 5% NaCl under magnetic field mediation. In addition, energy dispersive X-ray spectroscopy scans showed that the reduced NaCl treatment by magnetic field combined with CaCl2 could increase the signal intensity of sodium in minced pork matrices to some extent. Magnetic field-mediated substitution of NaCl for CaCl2 treatment was also found to be favorable for inducing the transition of the protein secondary structure from an irregularly coiled to a ß-folded structure (demonstrated by infrared spectroscopy). In short, magnetic fields combined with CaCl2 instead of NaCl was a highly promising method of producing low-NaCl meats.

Research on waste gas treatment technology and comprehensive environmental performance evaluation for collaborative management of pollution and carbon in China's pharmaceutical industry based on life cycle assessment (LCA).

China is the largest industrial and pharmaceutical country in the world. The pharmaceutical industry, being a highly polluting sector, is the primary target of environmental regulation in the industry. The rapid development of pharmaceutical industry has posed a severe challenge to the environmental protection strategy of "carbon reduction and carbon neutrality" and the goal of "synergizing the reduction of pollution and carbon emissions" in China's "14th Five-Year Plan". Therefore, this paper starts from the whole industry, takes the life cycle of the whole production process of the pharmaceutical industry as the guidance, and selects a pharmaceutical company in Tianjin as the research object. Then using Life Cycle Assessment (LCA) to Characterization, Standardization, and Weighting the environmental impact of the waste gas treatment process before and after improvement based on waste gas emission characteristics from the pharmaceutical factory. LCA results show that GWP and AP are the most important environmental impact types, which account for >85 % of the total characterization value. I and II - Chemical Pharmaceutical Stage is the critical life cycle stage, accounting for over 80 % of the total characteristic values. This research proposes emission reduction countermeasures based on LCA results and simulates Emission reduction scenarios and economic evolution. If effectively implementing emission reduction countermeasures, reducing the environmental characterization value by 80 to 90 %, and generating economic benefit of 2.66 × 108 RMB/year. This research could guide improvement plans and emission reduction countermeasures of waste gas treatment in the pharmaceutical industry, which realizes collaborative management about efficient reduction of pollution and carbon and generates significant environmental, technological, economic, and social benefits.

Study on the interaction and gel properties of pork myofibrillar protein with konjac polysaccharides.

BACKGROUND: Natural myofibrillar protein (MP) is sensitive to changes in the microenvironment, such as pH and ionic strength, and therefore can adversely affect the final quality of meat products. The aim of this study was to modify natural MP as well as to improve its functional properties. Therefore, the quality improvement effect of konjac polysaccharides with different concentrations (0, 1.5, 3, 4.5 and 6 g kg-1 protein) on MP gels was investigated. RESULTS: With a concentration of konjac polysaccharides of 6 g kg-1 protein, the composite gel obtained exhibited a significant improvement of water binding (water holding capacity increased by 7.71%) and textural performance (strength increased from 29.12 to 37.55 N mm, an increase of 8.43 N mm). Meanwhile, konjac polysaccharides could help to form more disulfide bonds and non-disulfide covalent bonds, which enhanced the crosslinking of MP and maintained the MP gel network structure. Then, with the preservation of α-helix structure (a significant increase of 8.11%), slower protein aggregation and formation of small aggregates, this supported the formation of a fine and homogeneous network structure and allowed a reduction in water mobility. CONCLUSION: During the heating process, konjac polysaccharides could absorb the surrounding water and fill the gel system, which resulted in an increase in the water content of the gel network and enhanced the gel-forming ability of the gel. Meanwhile, konjac polysaccharides might inhibit irregular aggregation of proteins and promote the formation of small aggregates, which in turn form a homogeneous and continuous gel matrix by orderly arrangement. © 2023 Society of Chemical Industry.

BMSCs alleviate liver cirrhosis by regulating Fstl1/Wnt/ß-Catenin signaling pathway.

Researchers have shown that bone mesenchymal stem cells (BMSCs) can alleviate the progression of liver cirrhosis; however, it is unclear how exactly BMSCs function to cure liver disease. In this study, we used bioinformatics methods to assess differentially expressed genes (DEGs) in liver cirrhosis and found a significantly upregulated gene, Fstl1, in liver cirrhosis. In vivo and in vitro experiments showed that compared with those in the disease model group, the mRNA, and protein expression levels of Fstl1 were significantly reduced after BMSCs treatment, and the ß-Catenin protein level was also significantly reduced after BMSCs treatment. Subsequently, we downregulated Fstl1 in activated hepatic stellate cells (HSCs) and found that Wnt and ß-Catenin protein expression levels also decreased. Finally, we found that in BMSCs-treated activated HSCs, overexpression of Fstl1 reversed the inhibitory effect of BMSCs on the Wnt/ß-Catenin signaling pathway to a certain extent. In summary, our results show that BMSCs can inhibit Wnt/ß-Catenin signaling pathway activation by downregulating the protein expression level of Fstl1, thus alleviating cirrhosis. Therefore, targeted regulation of Fstl1 may provide a new therapeutic strategy for the progression of liver cirrhosis.

Subverted macrophages in the triple-negative breast cancer ecosystem.

Tumor-associated macrophages (TAMs) are the most critical effector cells of innate immunity and the most abundant tumor-infiltrating immune cells. They play a key role in the clearance of apoptotic bodies, regulation of inflammation, and tissue repair to maintain homeostasis in vivo. With the progression of triple-negative breast cancer（TNBC）, TAMs are "subverted" from tumor-promoting immune cells to tumor-promoting immune suppressor cells, which play a significant role in tumor development and are considered potential targets for cancer therapy. Here, we explored how macrophages, as the most important part of the TNBC ecosystem, are "subverted" to drive cancer evolution and the uniqueness of TAMs in TNBC progression and metastasis. Similarly, we discuss the rationale and available evidence for TAMs as potential targets for TNBC therapy.

Asymmetric Measurement-Device-Independent Quantum Key Distribution through Advantage Distillation.

Measurement-device-independent quantum key distribution (MDI-QKD) completely closes the security loopholes caused by the imperfection of devices at the detection terminal. Commonly, a symmetric MDI-QKD model is widely used in simulations and experiments. This scenario is far from a real quantum network, where the losses of channels connecting each user are quite different. To adapt such a feature, an asymmetric MDI-QKD model is proposed. How to improve the performance of asymmetric MDI-QKD also becomes an important research direction. In this work, an advantage distillation (AD) method is applied to further improve the performance of asymmetric MDI-QKD without changing the original system structure. Simulation results show that the AD method can improve the secret key rate and transmission distance, especially in the highly asymmetric cases. Therefore, this scheme will greatly promote the development of future MDI-QKD networks.

A simulation study of the decomposition, biotoxicity, and transfer of LCMs in LCD panels after being in contact with sulfuric acid and extraction/stripping agents.

For indium recycling from LCD panels, the decomposition of 9 commonly used liquid crystal monomers (LCMs) that were in contact with sulfuric acid (i.e., leaching agent) and extraction/stripping agents, has been investigated in the present study. Also their biological toxicity changes and transfer have been studied. The results showed that 7 of the 9 LCMs were decomposed in the sulfuric acid agent, while the reaction time and temperature had no effect on the types of the decomposition products. The maximum decomposition rate was 96% when the concentration of the sulfuric acid was increased to 12 M. The time required for a 100% decomposition of the various LCMs in a 5 M sulfuric acid ranged from 41 h to 150 h. Also, Estimation Programs Interface (EPI) and ECOSAR calculations were used to compare the biotoxicity of the LCMs and the decomposition products. The results from the EPI calculations showed that the biological half-lives of the decomposition products were significantly reduced as compared with the LCMs, from the original highest value of 329.2 days-92.71 days. Furthermore, the ECOSAR calculations showed that the biological toxicity of the decomposition products for aquatic organisms was lower than for the LCMs, but they were still toxic and harmful substances. In addition, the transfer rates of the undecomposed LCMs and decomposition products in different extractants remained above 90%, and reached 100% at most. After stripping with hydrochloric acid, more than 70% of the undecomposed LCMs became enriched in the aqueous solution, while the products were enriched in the extractant.

PCRMLP: A Two-Stage Network for Point Cloud Registration in Urban Scenes.

Point cloud registration plays a crucial role in 3D mapping and localization. Urban scene point clouds pose significant challenges for registration due to their large data volume, similar scenarios, and dynamic objects. Estimating the location by instances (bulidings, traffic lights, etc.) in urban scenes is a more humanized matter. In this paper, we propose PCRMLP (point cloud registration MLP), a novel model for urban scene point cloud registration that achieves comparable registration performance to prior learning-based methods. Compared to previous works that focused on extracting features and estimating correspondence, PCRMLP estimates transformation implicitly from concrete instances. The key innovation lies in the instance-level urban scene representation method, which leverages semantic segmentation and density-based spatial clustering of applications with noise (DBSCAN) to generate instance descriptors, enabling robust feature extraction, dynamic object filtering, and logical transformation estimation. Then, a lightweight network consisting of Multilayer Perceptrons (MLPs) is employed to obtain transformation in an encoder-decoder manner. Experimental validation on the KITTI dataset demonstrates that PCRMLP achieves satisfactory coarse transformation estimates from instance descriptors within a remarkable time of 0.0028 s. With the incorporation of an ICP refinement module, our proposed method outperforms prior learning-based approaches, yielding a rotation error of 2.01° and a translation error of 1.58 m. The experimental results highlight PCRMLP's potential for coarse registration of urban scene point clouds, thereby paving the way for its application in instance-level semantic mapping and localization.

From Phenomenon to Essence: A Newly Involved lncRNA Kcnq1ot1 Protective Mechanism of Bone Marrow Mesenchymal Stromal Cells in Liver Cirrhosis.

Bone marrow mesenchymal stromal cells (BMSCs) have a protective effect against liver cirrhosis. Long noncoding RNAs (lncRNAs) play crucial roles in the progression of liver cirrhosis. Therefore, it is aimed to clarify the lncRNA Kcnq1ot1 involved protective mechanism of BMSCs in liver cirrhosis. This study found that BMSCs treatment attenuates CCl4 -induced liver cirrhosis in mice. Additionally, the expression of lncRNA Kcnq1ot1 is upregulated in human and mouse liver cirrhosis tissues, in addition to TGF-ß1-treated LX2 cells and JS1 cells. The expression of Kcnq1ot1 in liver cirrhosis is reversed with BMSCs treatment. The knockdown of Kcnq1ot1 alleviated liver cirrhosis both in vivo and in vitro. Fluorescence in situ hybridization (FISH) confirms that Kcnq1ot1 is mainly distributed in the cytoplasm of JS1 cells. It is predicted that miR-374-3p can directly bind with lncRNA Kcnq1ot1 and Fstl1, which is verified via luciferase activity assay. The inhibition of miR-374-3p or the overexpression of Fstl1 can attenuate the effect of Kcnq1ot1 knockdown. In addition, the transcription factor Creb3l1 is upregulated during JS1 cells activation. Moreover, Creb3l1 can directly bind to the Kcnq1ot1 promoter and positively regulate its transcription. In conclusion, BMSCs alleviate liver cirrhosis by modulating the Creb3l1/lncRNA Kcnq1ot1/miR-374-3p/Fstl1 signaling pathway.

Boosting the performance of loss-tolerant measurement-device-independent quantum key distribution.

Measurement-device-independent quantum key distribution can remove all possible detector side channels, and is robust against state preparation flaws when further combined with the loss-tolerant method. However, the secure key rate in this scenario is relatively low, thus hindering its practical application. Here, we first present a four-intensity decoy-state protocol where the signal intensity is modulated only in Z basis for key generation while the decoy intensities are modulated in both Z and X bases for parameter estimation. Moreover, we adopt collective constraint and joint-study strategy in statistical fluctuation analysis. We have also experimentally demonstrated this protocol and the result indicates high performance and good security for practical applications.

Comparative Transcriptome Analysis Reveals OsBGs and OsGSLs Influence Sugar Transport through Callose Metabolism under Heat Stress in Rice.

Heat or high temperature stress have caused huge damage to many crops and have become the largest threat in terms of the future. Although a huge amount of research has been conducted to explore the mechanisms of heat tolerance and many achievements were accomplished, the mechanism by which how heat stress (HS) influences the yield is still unclear. In this study, RNA-seq analysis indicated that nine 1,3-ß-glucanases (BGs) belonging to the carbohydrate metabolic pathway were expressed differently during heat treatment. Therefore, we identified the BGs and glucan-synthase-likes (GSLs) in three rice ecotypes and processed the analyses of gene gain and loss, phylogenetic relationship, duplication, and syntenic relationship. We found the possibility of an environmental adaption based on BGs and GSLs during evolution. Submicrostructure and dry matter distribution analysis confirmed that HS might block the endoplasmic sugar transport pathway by increasing callose synthesis, which may lead to decreased yield and quality in rice production. This study provides a new clue regarding rice yield and quality under HS and provides guidance to rice cultivation and heat tolerance breeding.

Oxidative-antioxidant imbalance in chronic sialadenitis of submandibular gland in human and rat.

OBJECTIVES: This study aimed to evaluate the level of oxidative stress (OS) in human and rat chronic sialadenitis (CS) of the submandibular gland (SMG). METHOD: We collected human SMG tissues and established a rat CS model using Wharton's duct partial ligation (PL). Morphological changes in the SMG were evaluated by HE, Sirius Red, AB/PAS, TUNEL and immunohistochemical (IHC) staining. Oxidative damage and antioxidant capacity were detected by ELISA, commercial assay kits and IHC staining to evaluate their expression levels and locations in the SMG. RESULTS: Histopathological damage were observed in the human and rat CS. In rat PL group, the oxidative damage products (8-OHdG, AOPP, 8-iso-PGF2α and H2 O2 ) were significantly increased. For antioxidants, the PL group had markedly decreased T-AOC and CAT activity, but markedly increased SOD activity. 3-NT, 4-HNE and MDA expression changed during the process of CS, and antioxidant enzymes (CAT, SOD1, SOD2, GPX1 and GPX4) were mainly expressed in ducts. CONCLUSIONS: The oxidative-antioxidant imbalance of CS in human and rats was revealed, the different expression of oxidative damage during the process of CS was detected, and the different antioxidant reaction in acinar and ductal cells was demonstrated.

The preliminary efficacy of virtual agent-assisted intelligent rehabilitation treatment (Echo app v2.0) in patients with alcohol use disorders: Study protocol for a randomized controlled trial.

Background: Alcohol use disorder (AUD) is one of the most common substance use disorders. People with AUD are in great need of highly accessible and comprehensive management, involving medicine, exercise, and psychotherapy. However, due to limited resources, providing comprehensive treatment for every patient is challenging. Virtual agent-assisted intelligent rehabilitation treatment can improve the accessibility of comprehensive management. Objectives: This randomized controlled trial aims to test whether the virtual agent-assisted intelligent rehabilitation treatment (Echo-app-v2.0) plus treatment as usual (TAU) has greater efficacy than only TAU in AUD. Methods: One hundred participants with AUD will be recruited and randomly assigned to either TAU or virtual agent-assisted intelligent rehabilitation treatment plus TAU based on the 1:1 ratio. The virtual agent-assisted intelligent rehabilitation treatment is delivered by the Echo app v2.0 developed by our research team. Participants will be assessed at baseline, week 4 of treatment, one month, and three months after the end of treatment. The primary outcome is the participants' craving for alcohol, measured by Visual Analogue Scale. Other outcomes include the use of alcohol, motivation for treatment, coping style, depression, anxiety, impulsivity, stress, and sleep quality. Discussion: The virtual agent, with vivid human image, high privacy, and the ability to interact with users, has the potential to play an important role in the delivery of digital psychotherapy. The development of Echo app v2.0 has the possibility to raise the availability of comprehensive treatment for people with AUD.

Galectin-9 in cancer therapy: from immune checkpoint ligand to promising therapeutic target.

Galectin-9 (Gal-9) is a vital member of the galectin family, functioning as a multi-subtype galactose lectin with diverse biological roles. Recent research has revealed that Gal-9's interaction with tumors is an independent factor that influences tumor progression. Furthermore, Gal-9 in the immune microenvironment cross-talks with tumor-associated immune cells, informing the clarification of Gal-9's identity as an immune checkpoint. A thorough investigation into Gal-9's role in various cancer types and its interaction with the immune microenvironment could yield novel strategies for subsequent targeted immunotherapy. This review focuses on the latest advances in understanding the direct and indirect cross-talk between Gal-9 and hematologic malignancies, in addition to solid tumors. In addition, we discuss the prospects of Gal-9 in tumor immunotherapy, including its cross-talk with the ligand TIM-3 and its potential in immune-combination therapy.