LINC00472 Regulates Ferroptosis of Neurons in Alzheimer's Disease via FOXO1.

INTRODUCTION: The objective of the study was to explore the molecular mechanism of long noncoding RNA (lncRNA) LINC00472 in Alzheimer's disease (AD) and identify potential novel targets for AD therapy. METHOD: Ferroptosis-related lncRNAs were screened by GEO database. AD mouse model was constructed for in vivo experiments. The content of Aß protein and tau protein hyperphosphorylation were examined in hippocampal tissue samples of mice. Subsequently, HT22 cells were induced with Aß25-35 to establish a neuronal injury model of AD in vitro. The expression of FOXO1, a key gene for ferroptosis, was verified by overexpressing/knocking down the LINC00472. The effects of LINC00472 on ROS and lipid peroxidation content, GPX4, and tau protein in AD model cells were examined by ROS assay, MDA assay, Western blot, and qRT-PCR. Subsequently, the expression of iron ion, FTH, TfRC, and Fpn protein were detected in AD cells. RESULTS: The level of FOXO1 was positively correlated with the degree of AD. In vivo experiments showed that the expression of Aß and tau hyperphosphorylated were significantly reduced in the inhibitor group and iron was significantly reduced relative to the AD group. In the AD cell model, the content of lipid peroxide was upregulated, GPX4 protein and mRNA were decreased, and phosphorylation of tau protein was enhanced in the AD cell model relative to the control group. Whereas knocking down LINC00472 inhibited the upregulation of lipid peroxide, decreased the level of GPX4, and enhanced tau protein phosphorylation, and reduced iron accumulation in AD cells. CONCLUSIONS: LINC00472 affects ferroptosis in AD by regulating iron accumulation in neuronal cells.

Effect of phenolics on soil microbe distribution, plant growth, and gall formation.

Phenolic compounds, abundant secondary metabolites in plants, profoundly influence soil ecosystems, plant growth, and interactions with herbivores. In this study, we explore the intricate relationships between phenolics, soil microbes, and gall formation in Ageratina adenophora (A. adenophora), an invasive plant species in China known for its allelopathic traits. Using metabolomic and microbial profiling, significant differences in soil microbial composition and metabolite profiles were observed between bulk and rhizosphere soil samples. Phenolics influenced bacterial communities, with distinct microbial populations enriched in each soil type. Additionally, phenolics impacted soil metabolic processes, with variations observed in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis between different soil treatments. Analysis of phenolic content in plant and soil samples revealed considerable variations, with higher concentrations observed in certain plant tissues and soil types. Bioactive phenols extracted from plant and soil samples were identified using gas chromatography/mass spectrometry (GC-MS), providing insights into the diverse chemical composition of these compounds. Furthermore, the effects of phenolics on plant growth and gall formation were investigated. Phenols exhibited both stimulatory and inhibitory effects on plant growth, with optimal concentrations promoting emergence but higher concentrations hindering growth. Gall formation was influenced by phenolic concentrations, leading to structural alterations in stem tissue and gall morphology. Histochemical analysis revealed starch and lipid accumulation in gall tissues, indicating metabolic changes induced by phenolics. The presence of phenolics disrupted tissue structures and influenced vascular bundle orientation in gall tissues. Overall, our study highlights the multifaceted roles of phenolic compounds in soil ecosystems, plant development, and gall formation, facilitating the utilization of secondary metabolites in agriculture.

Preliminary study on a novel biological scaffold loaded with Apelin-13 sustained-release microcapsules for promoting fallopian tube recanalization in rabbits. / è½½Apelin-13ç¼“é‡Šå¾®å›Šçš„æ–°åž‹ç”Ÿç‰©æ”¯æž¶ä¿ƒå ”è¾“åµç®¡å†é€šçš„åˆæ­¥ç ”ç©¶.

OBJECTIVES: Tubal factor infertility severely impairs the natural fertility of women, and there is for genuine tubal recanalization, including restoration of both the anatomy and function of the diseased fallopian tubes. Currently, there is no effective treatment available. This study aims to explore methods for promoting the repair and recanalization of fallopian tubes from these 2 aspects. METHODS: Apelin-13 sustained-release microspheres and poly (lactic-co-glycolic acid) (PLGA) three-dimensional (3D) biodegradable scaffolds were prepared. The basic characteristics and in vivo degradation (mass loss rate) of the biodegradable scaffolds were tested, along with the in vitro drug release (cumulative release rate), the in vivo drug release (Apelin-13 plasma concentration), and in vitro degradation (degradation rate) of the microspheres. The Apelin-13 microspheres (microsphere group)/PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres (scaffold-microcapsule group) were injected/placed into the fallopian tubes of New Zealand rabbit of chronic salpingitis models. The patency, microscopic structure, and positive expression of estrogen receptor and progesterone receptor of the fallopian tubes in the control group, the model group, the microcapsule group, and the scaffold-microcapsule group was observed and compared. RESULTS: At the 4th week post-operation, the mass loss rate of the PLGA 3D scaffolds, the degradation rate of the microspheres, and the Apelin-13 sustained-release microspheres-generated cumulative release rate in vitro over 30 days were 98.66%, 70.58%, and 98.68% respectively. The plasma concentration of Apelin-13 reached its peak within 5 days and remained stable for 25 days. Compared with the model and microsphere groups, the scaffold-microsphere group showed a milder inflammatory reaction within the tubal lumen, a higher rate of fallopian tube patency, and higher expression levels of estrogen and progesterone receptors (all P<0.05). The indicators of the scaffold-microsphere group were close to those of the control group. CONCLUSIONS: The PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres can comprehensively repair the anatomical structure and physiological function of the fallopian tubes and hold promise for truly effective tubal recanalization.

PET/NIR Fluorescence Bimodal Imaging for Targeted Tumor Detection.

Cancer is one of the greatest threats to human health due to late diagnosis and incomplete resection. The bimodal probe combines positron emission tomography (PET) imaging for noninvasive whole-body scanning with intraoperative near-infrared fluorescence (NIRF) surgical guidance for preoperative tumor detection, tumor resection during surgery, and postoperative monitoring. We developed a new PET/NIRF bimodal imaging agent, [68Ga]Ga-DOTA-NPC, covalently coupled to DCDSTCY and DOTA via ethylenediamine and radiolabeled with gallium-68, and investigated it in vitro and in vivo. The probe was found to be preferential for colon cancer cells due to the organic anion-transporting polypeptide1B3 (OATP1B3). PET/NIRF imaging allowed us to confirm [68Ga]Ga-DOTA-NPC as a promising probe for tumor detection, as it provides good biosafety and high-contrast tumor accumulation. Orthotopic and subcutaneous colon tumors were successfully resected under real-time NIRF guidance. [68Ga]Ga-DOTA-NPC provides highly sensitive and unlimited tissue-penetrating PET/NIRF imaging, helping to visualize and differentiate tumors from adjacent tissue.

Context-aware single-cell multiome approach identified cell-type specific lung cancer susceptibility genes.

Genome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, the genetic mechanisms and target genes underlying these loci are largely unknown, as most risk-associated-variants might regulate gene expression in a context-specific manner. Here, we generated a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation. Accessible chromatin peak detection identified cell-type-specific candidate cis-regulatory elements (cCREs) from each lung cell type. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs prioritized the variants for 68% of the GWAS loci, a subset of which was also supported by transcription factor abundance and footprinting. cCRE colocalization and single-cell based trait relevance score nominated epithelial and immune cells as the main cell groups contributing to lung cancer susceptibility. Notably, cCREs of rare proliferating epithelial cell types, such as AT2-proliferating (0.13%) and basal cells (1.8%), overlapped with CCVs, including those in TERT. A multi-level cCRE-gene linking system identified candidate susceptibility genes from 57% of lung cancer loci, including those not detected in tissue- or cell-line-based approaches. cCRE-gene linkage uncovered that adjacent genes expressed in different cell types are correlated with distinct subsets of coinherited CCVs, including JAML and MPZL3 at the 11q23.3 locus. Our data revealed the cell types and contexts where the lung cancer susceptibility genes are functional.

Morphology of the male reproductive system and sperm ultrastructure of the green lacewing, Chrysopa pallens (Rambur, 1838) (Neuroptera: Chrysopidae).

BACKGROUND: Chrysopa pallens is one of the most beneficial and effective natural predators, and is famous for its extensive distribution, wide prey spectrum, and excellent reproductive performance. This study examined the anatomy and fine structure of the C. pallens reproductive system and spermatogenesis. RESULTS: The male reproductive system of C. pallens comprises a pair of testes, a vas deferens, seminal vesicles, accessory glands, and short ejaculatory ducts. The testes were already mature on the day of emergence, but the accessory glands did not mature until 5 days post-emergence. In early spermatids, the flagellum had an axoneme on one side of the two mitochondrial derivatives. The nucleus was surrounded by parallel crystalline and paracrystalline materials. The spermatid envelope extends towards the paracrystalline material in a tail-shaped wing. In mature spermatids, the axoneme is located between the two accessory bodies and mitochondrial derivative sets. The parallel-crystalline and paracrystalline materials disappeared. In the testes, the wall of seminal cysts consists of a layer of epithelium, a muscular-connective sheath, and several vesicles of different sizes. The mature seminal cysts contained 128 spermatozoa. The accessory gland is composed of six parts: ventral papilla-like protuberance, anterior glandular lobe, lateral glandular lobe, seminal cyst, posterior kidney-shaped lobe, and posterior papilla-like protuberance. Muscle fibers and secretory granules are extensive. CONCLUSIONS: This study provides information on the reproductive system of C. pallens and offers a resource for taxonomy and reproductive biology.

Endogenous glutathione-activated DNA nanoprobes for spatially controllable imaging of microRNA in living cells.

A DNA nanoprobe, activated by glutathione (GSH), was designed to enable spatially selective sensing and imaging of miRNA in living cells. The nanoprobe was constructed using nano-sized metal-organic frameworks (MOFs) and DNA hairpin probes tethered to the surface of the MOFs, with the loop portion of the hairpin structure containing a disulfide bond. Cleavage of the disulfide bond by GSH triggers a strand-displacement reaction with target miRNAs, facilitating in situ readout of the fluorescence signal. The synergy of endogenous GSH activation and MOF improves the spatial resolution of miRNA detection and imaging.

Copper coordination-based conjugated polymer nanoparticles for synergistic photodynamic and chemodynamic therapy.

In this work, we presented a copper coordination-based conjugated polymer nanoparticle (PPE-Cu NPs) for synergistic PDT/CDT. Upon irradiation, PPE-Cu NPs exhibited good singlet oxygen generation capability (ΦΔ = 0.33). Meanwhile, PPE-Cu NPs were able to generate ˙OH in the presence of GSH and H2O2. Cellular experiments demonstrated that PPE-Cu NPs can serve as effective agents for synergistic PDT/CDT therapy.

Distribution pattern, removal effect, transfer behavior of ten pesticides and one metabolite during the processing of grapes.

Grapes' growth and processing conditions have various effects on pesticides with different physicochemical properties. Therefore, it is important for the healthy human diet to investigate pesticide residue behavior. To explore the relationship between pesticide residue behavior and physicochemical properties, the distribution of ten pesticides and one metabolite on grape peel and pulp was examined and the results showed that pesticides with low octanol-water partition coefficient (Kow) were more likely to be transferred to the pulp as the harvest interval increases. The removal methods were ranked according to pesticide removal effectiveness as follows: peeling > ozone water washing > tap water washing. Furthermore, the logKow played a key role in pesticide transfer rates during the juicing and winemaking. Notably, drying was the process of increasing pesticide residues. Additionally, the prediction models for the PFs of the pesticides in the juicing and winemaking processes were constructed as PFj = 0.952-0.116logKow (r = 0.886) and PFw = 0.736-0.143logKow (r = 0.959) by stepwise regression analysis. The prediction models recommended that Kow could be used to predict pesticide residues in grape juice and wine, which can predict the effect of pesticide physicochemical properties on PFs.

Evaluation and validation of the prognostic value of platelet indices in patients with leukemia.

Platelets (PLTs) are believed to play a role in the process by which tumors can accelerate their growth rate, as well as offer the physical and mechanical support necessary to evade the immunological system and metastasis. There is, however, no literature available if PLTs have a role in leukemia. It is significant for PLTs to play a part in hematological malignancies from a therapeutic standpoint and to have the capacity to serve as a prognostic marker in the evolution of leukemia. This is because PLTs play a crucial role in the development of cancer and tumors. In this study, it will be shown that PLT count can be used to predict long-term prognosis after chemotherapy especially in the case of acute myeloid leukemia patients. Furthermore, low PLT-to-lymphocyte ratio and mean PLT volume, as well as high PLT distribution width, are associated with poor prognosis and may represent a novel independent prognostic factor.

Discovery and biological evaluation of 4,6-pyrimidine analogues with potential anticancer agents as novel colchicine binding site inhibitors.

Novel 4,6-pyrimidine analogues were designed and synthesized as colchicine binding site inhibitors (CBSIs) with potent antiproliferative activities. Among them, compound 17j has the most potent activities against 6 human cancer cell lines with IC50 values from 1.1 nM to 4.4 nM, which was 76 times higher than the lead compound 3 in A549 cells. The co-crystal structure of 17j in complex with tubulin confirms the key binding mode at the colchicine binding site. Moreover, 17j inhibited the tubulin polymerization in biochemical assays, depolymerized cellular microtubules, induced the G2/M arrest, inhibited the cell migration, and promoted the initiation of apoptosis. In vivo, 17j effectively inhibits primary tumor growth with tumor growth inhibition rates of 42.51% (5 mg/kg) and 65.42% (10 mg/kg) in A549 xenograft model. Taken together, 17j represents a promising new generation of CBSIs.

The green lacewing Chrysopa formosa as a potential biocontrol agent for managing Spodoptera frugiperda and Spodoptera litura.

Understanding predator-prey interactions is essential for successful pest management by using predators, especially for the suppression of novel invasive pest. The green lacewing Chrysopa formosa is a promising polyphagous predator that is widely used in the biocontrol of various pests in China, but information on the control efficiency of this predator against the seriously invasive pest Spodoptera frugiperda and native Spodoptera litura is limited. Here we evaluated the predation efficiency of C. formosa adults on eggs and first- to third-instar larvae of S. frugiperda and S. litura through functional response experiments and determined the consumption capacity and prey preference of this chrysopid. Adults of C. formosa had a high consumption of eggs and earlier instar larvae of both prey species, and displayed a type II functional response on all prey stages. Attack rates of the chrysopid on different prey stages were statistically similar, but the handling time increased notably as the prey developed. The highest predation efficiency and shortest-handling time were observed for C. formosa feeding on Spodoptera eggs, followed by the first-instar larvae. C. formosa exhibited a significant preference for S. litura over S. frugiperda in a two-prey system. In addition, we summarized the functional response and predation efficiency of several chrysopids against noctuid pests and made a comparison with the results obtained from C. formosa. These results indicate that C. formosa has potential as an agent for biological control of noctuid pests, particularly for the newly invasive pest S. frugiperda in China.

AAV-mediated gene therapy produces fertile offspring in the Lhcgr-deficient mouse model of Leydig cell failure.

Leydig cell failure (LCF) caused by gene mutation results in testosterone deficiency and infertility. Serum testosterone levels can be recovered via testosterone replacement; however, established therapies have shown limited success in restoring fertility. Here, we use a luteinizing hormone/choriogonadotrophin receptor (Lhcgr)-deficient mouse model of LCF to investigate the feasibility of gene therapy for restoring testosterone production and fertility. We screen several adeno-associated virus (AAV) serotypes and identify AAV8 as an efficient vector to drive exogenous Lhcgr expression in progenitor Leydig cells through interstitial injection. We observe considerable testosterone recovery and Leydig cell maturation after AAV8-Lhcgr treatment in pubertal Lhcgr-/- mice. Of note, this gene therapy partially recovers sexual development, substantially restores spermatogenesis, and effectively produces fertile offspring. Furthermore, these favorable effects can be reproduced in adult Lhcgr-/- mice. Our proof-of-concept experiments in the mouse model demonstrate that AAV-mediated gene therapy may represent a promising therapeutic approach for patients with LCF.

Application of Fluorescence In Situ Hybridization Assisted by Fluorescence Microscope in Detection of Her2 Gene in Breast Cancer Patients.

In order to study the important factors for evaluating the prognosis of breast cancer patients, a fluorescence microscopy-assisted fluorescence in situ hybridization technique was proposed. Compared with other detection techniques, fluorescence in situ hybridization (FISH) technology assisted by a fluorescence microscope has gradually gained favor in related fields due to its advantages of high detection specificity, high sensitivity, and strong experimental period. Combined with the basic overview of fluorescence microscopy and FISH technology, the advantages and application points of FISH technology assisted by fluorescence microscopy in the detection of the Her2 gene in breast cancer patients were studied and discussed. The results show that IHC can be used as the primary screening for HER2 gene status detection; IHC (2+) and IHC (3+) have false positives, which are related to chromosome 17 polysomy, so FISH should be done to confirm the diagnosis.

Tumor-Targeting NIRF/MR Dual-Modal Molecular Imaging Probe for Surgery Navigation.

Multimodality imaging recognized as a promising monitoring strategy can serve the needs of accurate diagnosis and treatment of cancer by providing molecular and anatomic information about tumor sites. However, the probes based on multiple imaging modalities for surgery navigation remain limited due to poor biocompatibility and tumor targeting specificity. Herein, we present a small-molecule near-infrared fluorescence/magnetic resonance (NIRF/MR) imaging probe, Gd-NMC-3, covalently coupled with DCDSTCY and Gd-DOTA via butane diamine, for precise detection and intraoperative visualization. The in vitro and in vivo studies demonstrated that Gd-NMC-3 could be effectively accumulated in tumor sites as a bimodal imaging molecule exhibiting significant fluorescence accumulation and reasonable relaxation property in tumors with low cytotoxicity and good biocompatibility. Furthermore, Gd-NMC-3 was successfully applied to provide real-time visual navigation in LM3 orthotopic and subcutaneous tumor models to guide the resection of tumors. Importantly, no more fluorescence was observed in mice after operation, implying the total removal of tumor tissues. In conclusion, Gd-NMC-3 has great potential to be applied in the clinic based on its high resolution and sensitivity in tumor imaging.

A retrospective single-center analysis of G-CSF-mobilized donor lymphocyte infusion in hematologic malignancies after unmanipulated allogenic PBSCT.

To explore the efficacy and safety of G-SCF-mobilized donor lymphocyte infusion (DLI) for treatment of relapse of hematologic malignancies after allogeneic peripheral blood stem cell transplantation, we performed a retrospective analysis in a cohort of patients with morphologic (n = 36) or molecular (n = 22) relapse post transplantation. The 3-year post-DLI survival rates for therapeutic and preemptive DLI recipients were 16.7% and 33.3%, respectively. The occurrence of DLI-associated acute graft-versus-host disease predicted longer survival, whereas diagnosis of T cell acute lymphoblastic leukemia/lymphoma or myelodysplastic syndromes or early relapse after transplant (< 6 months) predicted shorter survival after therapeutic DLI. Cumulative incidence of progression to hematologic relapse and non-relapse mortality after preemptive DLI were 46.8% and 29.1%, respectively. Active disease prior to transplant and early molecular relapse after transplant (< 4 months) were the strongest predictors of non-relapse mortality after preemptive DLI. In conclusion, although therapeutic DLI had limited efficacy against T cell acute lymphoblastic leukemia/lymphoma or myelodysplastic syndromes or early post-transplant relapse, patients who developed DLI-associated acute graft-versus-host disease would benefit from this procedure in the setting of G-SCF-mobilized DLI. Furthermore, preemptive DLI could protect half of patients from hematologic relapse after transplantation with acceptable toxicity.

Recent progress in DNA methyltransferase inhibitors as anticancer agents.

DNA methylation mediated by DNA methyltransferase is an important epigenetic process that regulates gene expression in mammals, which plays a key role in silencing certain genes, such as tumor suppressor genes, in cancer, and it has become a promising therapeutic target for cancer treatment. Similar to other epigenetic targets, DNA methyltransferase can also be modulated by chemical agents. Four agents have already been approved to treat hematological cancers. In order to promote the development of a DNA methyltransferase inhibitor as an anti-tumor agent, in the current review, we discuss the relationship between DNA methylation and tumor, the anti-tumor mechanism, the research progress and pharmacological properties of DNA methyltransferase inhibitors, and the future research trend of DNA methyltransferase inhibitors.

Cathepsin L Contributes to Reproductive Diapause by Regulating Lipid Storage and Survival of Coccinella septempunctata (Linnaeus).

Cathepsin L protease, which belongs to the papain-like cysteine proteases family, is an important player in many physiological and pathological processes. However, little was known about the role of cathepsin L in ladybird beetles (Coccinella septempuctata Linnaeus) during diapause. Here, we analyzed the characteristics of cathepsin L (CsCatL) in the females of C. septempunctata and its role during the diapause of the ladybeetle. CsCatL was cloned and identified from beetle specimens by rapid amplification of cDNA-ends (RACE). The cDNA sequence of CsCatL was 971 bp in length, including an 843 bp open reading frame encoding a protein of 280 amino acids. It was identified as the cathepsin L group by phylogenetic analysis. Knockdown of CsCatL by RNA interference led to decreased expression levels of fatty acid synthase 2 (fas 2) genes and suppressed lipid accumulation. Furthermore, silencing the CsCatL gene distinctly reduced diapause-related features and the survival of female C. spetempunctata under diapause-inducing conditions. The results suggested that the CsCatL gene was involved in fatty acid biosynthesis and played a crucial role in the survival of adult C. septempunctata during the diapause preparation stage.

MiR-18a-5p Promotes Proliferation, Migration, and Invasion of Endometrial Cancer Cells by Targeting THBD.

The purpose of this study was to elucidate the role that the miR-18a-5p/THBD regulatory pathway plays in endometrial cancer (EC), which could provide a theoretical basis for potential therapeutic targets. Differentially expressed genes in EC tissue and normal tissue were determined by bioinformatics analysis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to compare the expression of miR-18a-5p and THBD mRNA in normal human endometrial cells and human EC cells. CCK-8 assay was used to compare the proliferative ability of EC cells in different treatment groups. Transwell assay was used to detect the migratory and invasive abilities of EC cells in different treatment groups. Dual-luciferase assay was used to verify the targeting relationship between miR-18a-5p and THBD. Western blot assay was used to detect THBD protein expression level. qRT-PCR results showed that miR-18a-5p was significantly upregulated in EC cells, and expression of its target gene, THBD, was significantly downregulated. CCK-8 and transwell assays showed that miR-18a-5p could enhance the proliferative, migratory, and invasive abilities of EC cells, whereas THBD could weaken those abilities. Dual-luciferase assay confirmed that miR-18a-5p could negatively regulate THBD expression. In addition, rescue experiments revealed that the oncogenic effect of miR-18a-5p on EC cells was inhibited by THBD overexpression. We conclude that miR-18a-5p could promote the proliferation, migration, and invasion of EC cells by targeting and downregulating THBD expression, and the miR-18a-5p/THBD regulatory pathway might be a therapeutic target. The results of this study may serve as a theoretical basis for related drug development.

Combination Foretinib and Anti-PD-1 Antibody Immunotherapy for Colorectal Carcinoma.

Immune checkpoint inhibitors have achieved unprecedented success in cancer immunotherapy. However, the overall response rate to immune checkpoint inhibitor therapy for many cancers is only between 20 and 40%, and even less for colorectal cancer (CRC) patients. Thus, there is an urgent need to develop an efficient immunotherapeutic strategy for CRC. Here, we developed a novel CRC combination therapy consisting of a multiple receptor tyrosine kinase inhibitor (Foretinib) and anti-PD-1 antibody. The combination therapy significantly inhibited tumor growth in mice, led to improved tumor regression without relapse (83% for CT26 tumors and 50% for MC38 tumors) and prolonged overall survival. Mechanistically, Foretinib caused increased levels of PD-L1 via activating the JAK2-STAT1 pathway, which could improve the effectiveness of the immune checkpoint inhibitor. Moreover, the combination therapy remodeled the tumor microenvironment and enhanced anti-tumor immunity by further increasing the infiltration and improving the function of T cells, decreasing the percentage of tumor-associated macrophages (TAMs) and inhibiting their polarization toward the M2 phenotype. Furthermore, the combination therapy inhibited the metastasis of CT26-Luc tumors to the lung in BALB/c mouse by reducing proportions of regulatory T-cells, TAMs and M2 phenotype TAMs in their lungs. This study suggests that a novel combination therapy utilizing both Foretinib and anti-PD-1 antibody could be an effective combination strategy for CRC immunotherapy.