Efficacy and safety of apatinib plus immune checkpoint inhibitors and transarterial chemoembolization for the treatment of advanced hepatocellular carcinoma.

PURPOSE: The evidence of apatinib plus immune checkpoint inhibitors (ICIs) and transarterial chemoembolization (TACE) for treating advanced hepatocellular carcinoma (HCC) is limited. This study aimed to compare the treatment efficacy and safety of apatinib plus ICIs and TACE with apatinib plus TACE in these patients. METHODS: This study retrospectively enrolled 90 patients with advanced HCC treated with apatinib plus TACE (A-TACE group, n = 52) or apatinib plus ICIs and TACE (IA-TACE group, n = 38). RESULTS: The objective response rate was numerically higher in IA-TACE group compared with A-TACE group without statistical significance (57.9% vs. 36.5%, P = 0.055). Disease control rate was not different between groups (86.8% vs. 76.9%, P = 0.248). Progression-free survival (PFS) was improved in IA-TACE group compared with A-TACE group (P = 0.018). The median PFS (95% confidence interval) was 12.5 (8.7-16.3) months in IA-TACE group and 8.5 (5.6-11.4) months in A-TACE group. Overall survival (OS) was also prolonged in IA-TACE group compared with A-TACE group (P = 0.007). The median OS (95% confidence interval) was 21.1 (15.8-26.4) months in IA-TACE group and 14.3 (11.5-17.1) months in A-TACE group. By multivariate Cox regression model, IA-TACE was independently associated with prolonged PFS (hazard ratio = 0.539, P = 0.038) and OS (hazard ratio = 0.447, P = 0.025). Most adverse events were not different between groups. Only the incidence of reactive cutaneous capillary endothelial proliferation was higher in IA-TACE group compared with A-TACE group (10.5% vs. 0.0%, P = 0.029). CONCLUSION: Apatinib plus ICIs and TACE may be an effective and safe treatment for patients with advanced HCC, but further large-scale studies are needed for verification.

Achieving Record C2H2 Packing Density for Highly Efficient C2H2/C2H4 Separation with a Metal-Organic Framework Prepared by a Scalable Synthesis in Water.

Adsorptive C2H2/C2H4 separation using metal-organic frameworks (MOFs) has emerged as a promising technology for the removal of C2H2 (acetylene) impurity (1%) from C2H4 (ethylene). The practical application of these materials involves the optimization of separation performance as well as development of scalable and green production protocols.Herein, we report the efficient C2H2/C2H4 separation in a MOF, Cu(OH)INA (INA: isonicotinate) which achieves a record C2H2 packing density of 351 mg cm-3 at 0.01 bar through high affinity towards C2H2. DFT (density functional theory) calculations reveal the synergistic binding mechanism through pore confinement and the oxygen sites in pore wall.The weakly basic nature of binding sites leads to a relatively low heat of adsorption (Qst) of approximately 36 kJ/mol, which is beneficial for material regeneration and thermal management. Furthermore, a scalable and environmentally friendly synthesis protocol with a high space-time yield of 544 kg m-3 day-1 has been developed without using any modulating agents. This material also demonstrates enduring separation performance for multiple cycles, maintaining its efficacy after exposure to water or air for three months.

IL-27 Gene Therapy Ameliorates IPEX Syndrome Caused by Germline Mutation of Foxp3 Gene: A Major Role for Induction of IL-10.

Inactivating mutations of Foxp3, the master regulator of regulatory T cell development and function, lead to immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome in mice and humans. IPEX is a fatal autoimmune disease, with allogeneic stem cell transplant being the only available therapy. In this study, we report that a single dose of adeno-associated virus (AAV)-IL-27 to young mice with naturally occurring Foxp3 mutation (Scurfy mice) substantially ameliorates clinical symptoms, including growth retardation and early fatality. Correspondingly, AAV-IL-27 gene therapy significantly prevented naive T cell activation, as manifested by downregulation of CD62L and upregulation of CD44, and immunopathology typical of IPEX. Because IL-27 is known to induce IL-10, a key effector molecule of regulatory T cells, we evaluated the contribution of IL-10 induction by crossing IL-10-null allele to Scurfy mice. Although IL-10 deficiency does not affect the survival of Scurfy mice, it largely abrogated the therapeutic effect of AAV-IL-27. Our study revealed a major role for IL-10 in AAV-IL-27 gene therapy and demonstrated that IPEX is amenable to gene therapy.

Recovery of High-Purity SF6 from Humid SF6/N2 Mixture within a Co(II)-Pyrazolate Framework.

Sulfur hexafluoride (SF6) is extensively employed in the power industry. However, its emissions significantly contribute to the greenhouse effect. The direct recovery of high purity SF6 from industrial waste gases would benefit its sustainable use, yet this represents a considerable challenge. Herein, we report the enrichment of SF6 from SF6/N2 mixtures via adsorptive separation in a stable Co(II)-pyrazolate MOF BUT-53 (BUT: Beijing University of Technology), which features dynamic molecular traps. BUT-53 exhibits an excellent SF6 adsorption uptake of 2.82 mmol/g at 0.1 bar and 298 K, as well as an unprecedented SF6/N2 (10:90) selectivity of 2485. Besides, the remarkable SF6/N2 selectivity of BUT-53 enables recovery of high purity (>99.9%) SF6 from a low concentration (10%) mixture through a breakthrough experiment. The excellent SF6/N2 separation efficiency was also well maintained under humid conditions (RH = 90%) over multiple cycles. Molecular simulation, single-crystal diffraction, and adsorption kinetics studies elucidate the associated adsorption mechanism and water tolerance.

Evaluation of Open-Source Large Language Models for Metal-Organic Frameworks Research.

Along with the development of machine learning, deep learning, and large language models (LLMs) such as GPT-4 (GPT: Generative Pre-Trained Transformer), artificial intelligence (AI) tools have been playing an increasingly important role in chemical and material research to facilitate the material screening and design. Despite the exciting progress of GPT-4 based AI research assistance, open-source LLMs have not gained much attention from the scientific community. This work primarily focused on metal-organic frameworks (MOFs) as a subdomain of chemistry and evaluated six top-rated open-source LLMs with a comprehensive set of tasks including MOFs knowledge, basic chemistry knowledge, in-depth chemistry knowledge, knowledge extraction, database reading, predicting material property, experiment design, computational scripts generation, guiding experiment, data analysis, and paper polishing, which covers the basic units of MOFs research. In general, these LLMs were capable of most of the tasks. Especially, Llama2-7B and ChatGLM2-6B were found to perform particularly well with moderate computational resources. Additionally, the performance of different parameter versions of the same model was compared, which revealed the superior performance of higher parameter versions.

Preparation and Application of Apatite-TiO2 Composite Opacifier: Preventing Titanium Glaze Yellowing through Pre-Combination.

In order to enhance the degree of binding reaction of TiO2 in titanium-containing ceramic glazes and prevent the reaction of its transformation into rutile to eliminate the yellowing phenomenon of the glaze surface, an apatite-TiO2 composite opacifier (ATO) was prepared through the mechanical grinding of hydroxyapatite and anatase TiO2. The properties, opacification mechanism, and yellowing inhibition of the prepared ceramic glazes were studied. The results show that the ATO is characterized by a uniform coating of TiO2 on the surface of the apatite and the formation of close chemical bonding between the apatite and TiO2. The ceramic glaze surface when using an ATO has a white appearance and excellent opacification performance. When an ATO was used, the L*, a*, and b* values of the glaze were 89.99, -0.85, and 3.37, respectively, which were comparable to those of a ZrSiO4 glaze (L*, a*, and b* were 88.24, -0.02, and 2.29, respectively). The opacification of the glaze was slightly lower than that of the TiO2 glaze (L* value was 92.13), but the appearance changed from yellow to the white of the TiO2 glaze (b* value was 9.18). The ceramic glaze layer when using an ATO mainly consists of titanite, glass phase, and a small amount of quartz, and the opacification mechanism is the crystallization of the generated titanite. ATOs can play an active role in solving the critical problem that arises when TiO2 replaces ZrSiO4 as an opacifier.

Ultrasonic in-situ reduction preparation of SBA-15 loaded ultrafine RuCo alloy catalysts for efficient hydrogen storage of various LOHCs.

SBA-15-loaded RuCo alloy nanoparticle catalysts (RuxCoy/S15-SU) for the efficient catalysis of hydrogen storage by various liquid organic hydrogen carriers (LOHCs) were prepared via strong electrostatic adsorption (SEA)-ultrasonic in-situ reduction (UR) technology. The above prepared catalysts were subjected to a series of characterization, such as XPS, H2-TPD/TPR, N2 adsorption-desorption, ICP, CO-chemisorption, FT-IR, XRD and TEM. Ru3+ and Co2+ were evenly anchored on the surface of SBA-15 by SEA, and ultrafine RuCo alloy nanoparticles were formed by UR without any chemical reducing or stabilizing agents. The addition of Co enhanced the dispersion and antioxidant capacity of the RuCo alloy NPs with an average particle size of 2.07 nm and increased the number of catalytically active sites. The synergistic effect of ultrafine particle size and electron transfer between Co and Ru improved the catalytic performance of monobenzyltoluene (MBT) for hydrogen storage. SEA-UR technology strengthened the coordination effect between RuCo alloy NPs and Si-OH, which enhanced the catalytic stability. H2-TPD and H2-TPR indicated that the addition of Co led to more activated H2 to produce hydrogen overflow. For the hydrogenation of MBT, the produced Ru2Co1/S15-SU showed excellent catalytic performance. The hydrogen storage efficiency of MBT was 99.98 % under 110 °C and 6 MPa H2 for 26 min, and the TOF was 145 min-1, which is significantly superior to that of Ru/S15-SU catalyst and that reported in the literature. The hydrogen storage efficiency was still as high as 99.7 % after ten cycles, which was much better than that of Ru/S15-SU and commercial 5 wt% Ru/Al2O3. Ru2Co1/S15-SU is also suitable for efficiently catalyzing hydrogen storage of N-ethylcarbazole, dibenzyltoluene and acenaphthene.

Therapeutic Immunomodulation in Gastric Cancer.

Gastric carcinoma, being one of the most prevalent types of solid tumors, has emerged as the third leading cause of death worldwide. The symptoms of gastric cancer (GC) are typically complex, which makes early detection challenging. Immune checkpoint inhibition has become the new standard targeted therapy for advanced or metastatic GC. It is currently being explored in various combinations, both with and without chemotherapy, across multiple therapies in clinical trials. Immunotherapy can stimulate immune responses in GC patients, leading to the destruction of cancer cells. Compared with traditional therapies, immunotherapy has shown strong effectiveness with tolerable toxicity levels. Hence, this innovative approach to the treatment of advanced GC has gained popularity. In this review, we have outlined the recent advancements in immunotherapy for advanced GC, including immune checkpoint inhibitors, cancer vaccines, vascular endothelial growth factor-A inhibitors, and chimeric antigen receptor T-cell therapy. Our current emphasis is on examining the immunotherapies presently employed in clinical settings, addressing the existing challenges associated with these therapeutic approaches, and exploring promising strategies to overcome their limitations.

Ultrasound-assisted preparation of PdCo bimetallic nanoparticles loaded on beta zeolite for efficient catalytic hydrogen production from dodecahydro-N-ethylcarbazole.

Research and development of high-performance catalysts is a key technology to realize hydrogen energy storage and transportation based on liquid organic hydrogen carriers. Co/beta was prepared using beta zeolite as a carrier via an electrostatic adsorption (ESA)-chemical reduction method, and it was used as the template and reducing agent to prepare bimetallic catalysts via an ultrasonic assisted galvanic replacement process (UGR). The fabricated PdCo/beta were characterized by TEM, XPS, FT-IR, XRD, H2-TPR, and H2-TPD. It was shown that the ultrafine PdCo nanoparticles (NPs) are evenly distributed on the surface of the beta zeolite. There is electron transfer between metal NPs and strong-metal-support-interaction (SMSI), which results in highly efficient catalytic dodecahydro-N-ethylcarbazole (12H-NEC) dehydrogenation performance of PdCo bimetallic catalysts. The dehydrogenation efficiency reached 100 % in 4 h at 180 °C and 95.3 % in 6 h at 160 °C. The TOF of 146.22 min-1 is 7 times that of Pd/beta. The apparent activation energy of the reaction is 66.6 kJ/mol, which is much lower than that of Pd/beta. Under the action of ultrasonic waves, the galvanic replacement reaction is accelerated, and the intermetal and metal-carrier interactions are enhanced, which improves the catalytic reaction performance.

IL-27 in combination with anti-PD-1 can be anti-cancer or pro-cancer.

Interleukin-27 (IL-27) is known to play opposing roles in immunology. The present paper considers, specifically, the role IL-27 plays in cancer immunotherapy when combined with immune checkpoint inhibitor anti-PD-1. We first develop a mathematical model for this combination therapy, by a system of Partial Differential Equations, and show agreement with experimental results in mice injected with melanoma cells. We then proceed to simulate tumor volume with IL-27 injection at a variable dose F and anti-PD-1 at a variable dose g. We show that in some range of "small" values of g, as f increases tumor volume decreases as long as fFc(g), where Fc(g) is a monotone increasing function of g. This demonstrates that IL-27 can be both anti-cancer and pro-cancer, depending on the ranges of both anti-PD-1 and IL-27.

New insights into the downregulation of cytochrome P450 2E1 via nuclear factor κB-dependent pathways in immune-mediated liver injury.

The extent of immune-mediated hepatic damage (such as in viral hepatitis) is characterised by the downregulation of cytochrome P450s (CYPs), a class of drug-metabolising enzymes. However, whether this downregulation aids liver cells in maintaining their homeostasis or whether the damage is aggravated remains largely unexplored. Herein, we evaluated the effects of phosphorylation mediated by the protein kinase C (PKC)/cAMP-response element binding protein (CREB) and nitration mediated by inducible nitric oxide synthase (iNOS) on the downregulation of CYP2E1 during immune-mediated liver injury. Additionally, we investigated the regulatory mechanism mediated by the nuclear factor κB (NF-κB). The rat model of immune-mediated liver injury was replicated by administering a single i.v. injection of Bacillus Calmette-Guerin (BCG, 125 mg/kg) vaccine and three i.p. injections of ammonium pyrrolidine dithiocarbamate (25, 50, 100 mg/kg/d, days 11, 12, and 13); blood was then collected on day 14. Subsequently, the livers were extracted to identify the different pharmacokinetic and biochemical indicators involved in the process. Our study reports new findings on the dependence between PKC-mediated CREB phosphorylation in the anti-inflammatory pathway and nitration emergency induced by iNOS in pro-inflammatory pathways in the NF-κB pathway. The interaction of these two pathways leads to the downregulation and recovery of CYP2E1, thus alleviating inflammation and nitration stress. Our results confirm that BCG-mediated downregulation of CYP2E1 is linked to iNOS-induced nitration and PKC/NF-κB-mediated CREB phosphorylation, and that NF-κB is an important molecular target in this process. These findings suggest that the downregulation of CYP2E1 may be an autonomous process characteristic of liver cells, helping them adapt to environmental changes, alleviate further hypoxia in inflamed tissues, and minimise exposure to toxic and harmful metabolites.

Microbiota Alters and Its Correlation with Molecular Regulation Underlying Depression in PCOS Patients.

Depression is one of the complications in patients with polycystic ovary syndrome (PCOS) that leads to considerable mental health. Accumulating evidence suggests that human gut microbiomes are associated with the progression of PCOS and depression. However, whether microbiota influences depression development in PCOS patients is still uncharacterized. In this study, we employed metagenomic sequencing and transcriptome sequencing (RNA-seq) to profile the composition of the fecal microbiota and gene expression of peripheral blood mononuclear cells in depressed women with PCOS (PCOS-DP, n = 27) in comparison to mentally healthy women with PCOS (PCOS, n = 18) and compared with healthy control (HC, n = 27) and patients with major depressive disorder (MDD, n = 29). Gut microbiota assessment revealed distinct patterns in the relative abundance in the PCOS-DP compared to HC, MDD, and PCOS groups. Several gut microbes exhibited uniquely and significantly higher abundance in the PCOS-DP compared to PCOS patients, inducing EC Ruminococcus torques, Coprococcus comes, Megasphaera elsdenii, Acidaminococcus intestini, and Barnesiella viscericola. Bacteroides eggerthii was a potential gut microbial biomarker for the PCOS-DP. RNA-seq profiling identified that 35 and 37 genes were significantly elevated and downregulated in the PCOS-DP, respectively. The enhanced differential expressed genes (DEGs) in the PCOS-DP were enriched in pathways involved in signal transduction and endocrine and metabolic diseases, whereas several lipid metabolism pathways were downregulated. Intriguingly, genes correlated with the gut microbiota were found to be significantly enriched in pathways of neurodegenerative diseases and the immune system, suggesting that changes in the microbiota may have a systemic impact on the expression of neurodegenerative diseases and immune genes. Gut microbe-related DEGs of CREB3L3 and CCDC173 were possible molecular biomarkers and therapeutic targets of women with PCOS-DP. Our multi-omics data indicate shifts in the gut microbiome and host gene regulation in PCOS patients with depression, which is of possible etiological and diagnostic importance.

AgingReG: a curated database of aging regulatory relationships in humans.

Aging and cellular senescence are characterized by a progressive loss of physiological integrity, which could be triggered by aging factors such as physiological, pathological and external factors. Numerous studies have shown that gene regulatory events play crucial roles in aging, increasing the need for a comprehensive repository of regulatory relationships during aging. Here, we established a manually curated database of aging factors (AgingReG, https://bio.liclab.net/Aging-ReG/), focusing on the regulatory relationships during aging with experimental evidence in humans. By curating thousands of published literature, 2157 aging factor entries (1345 aging gene entries, 804 external factor entries and eight aging-related pathway entries) and related regulatory information were manually curated. The regulatory relationships were classified into four types according to their functions: (i) upregulation, which indicates that aging factors upregulate the expression of target genes during aging; (ii) downregulation, which indicates that aging factors downregulate the expression of target genes during aging; (iii) activation, which indicates that aging factors influence the activity of target genes during aging and (iv) inhibition, which indicates that aging factors inhibit the activation of target molecule activity, leading to declined or lost target activity. AgingReG involves 651 upregulating pairs, 632 downregulating pairs, 330 activation-regulating pairs and 34 inhibition-regulating pairs, covering 195 disease types and more than 800 kinds of cells and tissues from 1784 published literature studies. AgingReG provides a user-friendly interface to query, browse and visualize detailed information about the regulatory relationships during aging. We believe that AgingReG will serve as a valuable resource database in the field of aging research. Database URL: https://bio.liclab.net/Aging-ReG/.

Hippophae rhamnoides reverses decreased CYP2D6 expression in rats with BCG-induced liver injury.

In this study, we investigated the effect of Hippophae rhamnoides L. (HRP) on the activity of CYP2D6 via the CAMP/PKA/NF-κB pathway in rats with Bacille Calmette-Guerin (BCG)-induced immunological liver injury. BCG (125 mg/kg) was injected to establish the rat model of liver injury. HRP was administered intragastrically for one week as the intervention drug. Proteomics techniques were used to analyze protein expression levels, obtaining a comprehensive understanding of the liver injury process. ELISA or western blotting was used to detect specific protein levels. Dextromethorphan was detected using high-performance liquid chromatography to reflect the metabolic activity of CYP2D6. BCG downregulated the expression of CYP2D6, cAMP, PKA, IκB, and P-CREB and upregulated that of NF-κB, IL-1ß, TNF-α, and CREB in the liver; HRP administration reversed these effects. Therefore, HRP may restore the metabolic function of the liver by reversing the downregulation of CYP2D6 through inhibition of NF-κB signal transduction and regulation of the cAMP/PKA/CREB/CYP2D6 pathway. These findings highlight the role of HRP as an alternative clinical drug for treating hepatitis B and other immune-related liver diseases.

TSHR-based chimeric antigen receptor T cell specifically deplete auto-reactive B lymphocytes for treatment of autoimmune thyroid disease.

Graves' disease (GD) is a prominent antibody-mediated autoimmune disorder characterized by stimulating antibodies (TRAb) that target the thyroid-stimulating hormone receptor (TSHR). Targeting and eliminating TRAb-producing B lymphocytes hold substantial therapeutic potential for GD. In this study, we engineered a novel chimeric antigen receptor T cell (CAR-T) therapy termed TSHR-CAR-T. This CAR-T construct incorporates the extracellular domain of the TSH receptor fused with the CD8 transmembrane and intracellular signal domain (4-1BB). TSHR-CAR-T cells demonstrated the ability to recognize and effectively eliminate TRAb-producing B lymphocytes both in vitro and in vivo. Leveraging this autoantigen-based chimeric receptor, our findings suggest that TSHR-CAR-T cells offer a promising and innovative immunotherapeutic approach for the treatment of antibody-mediated autoimmune diseases, including GD.

Preparation of Ni@Pd Core-Shell Nanoparticles Supported on KIT-6 by Ultrasound-Assisted Galvanic Replacement for Dodecahydro-N-ethylcarbazole Dehydrogenation.

Using Ni as a template and reductant, Ni core-Pd shell nanoparticles (Ni@Pd NPs) supported on KIT-6 (Ni@Pd/K6) were prepared by a galvanic replacement reaction under ultrasonic radiation. The characterization results show that the Ni@Pd core-shell NPs with an average diameter of 1.9 ± 0.3 nm are uniformly dispersed on KIT-6. The d-band center position of Pd in Ni@Pd core-shell NPs can be affected by both ligand and strain effects. The relationship between the d-band center of Pd and the selectivity of intermediates is a nearly straight curve. The dehydrogenation efficiency of dodecahydro-N-ethylcarbazole on Ni@Pd(6:1)/K6 is 100% only for 3 h at 180 °C and 95.5% for 6 h at 160 °C, which is better than the reported catalysts. The outstanding catalytic dehydrogenation performance of Ni@Pd(6:1)/K6 can be attributed to the synergistic effect of the ligand and strain effect, the high dispersion of core-shell NPs, and the weak H2 binding ability of the catalyst.

Preparation of SBA-15 supported Ru nanocatalysts by electrostatic adsorption-ultrasonic in situ reduction method and its catalytic performance for hydrogen storage of N-ethylcarbazole.

N-ethylcarbazole (NEC) is an ideal liquid organic hydrogen storage carrier. The development of efficient hydrogen storage catalysts can promote the large-scale application of this process. In this paper, SBA-15 supported Ru nanocatalysts (Ru/S15-SU) were synthesized by strong electrostatic adsorption (SEA)-ultrasonic in situ reduction method (UR). Ru/S15-SU was characterized by N2 adsorption-desorption, TEM, H2 temperature program reduction, FT-IR, XRD, and XPS analysis measures. The results showed that ultrafine Ru NPs were evenly distributed on the surface of SBA-15, and ultrasonic in situ reduction not only reduced Ru3+ to Ru0, but also produced a coordination effect between Ru and O, enhancing the interaction between Ru NPs and the carrier. Ru/S15-SU exhibited excellent catalytic performance in the hydrogenation reaction of NEC, and the hydrogen storage efficiency reached 99.31% at 130°C and 6 MPa H2 pressure, which is superior to that of commercial 5wt%Ru/Al2O3. The excellent catalytic hydrogenation performance can be attributed to the selective anchoring of ruthenium ions on the surface of SBA-15 via electrostatic adsorption, preventing the aggregation of Ru NPs and enhancing the interaction between SBA-15 and Ru NPs by ultrasonic in situ reduction. Ru/S15-SU had a lower NEC hydrogenation apparent activated energy (Ea) of 68.45 kJ/mol than 5wt%Ru/Al2O3 catalyst. This method provides a new approach for the green preparation of nanocatalysts without using any chemical reducing agents.

IL-27 Gene Therapy Induces Stat3-Mediated Expansion of CD11b+Gr1+ Myeloid Cells and Promotes Accumulation of M1 Macrophages in the Tumor Microenvironment.

IL-27 is a pleiotropic cytokine that exhibits stimulatory/regulatory functions on multiple lineages of immune cells and has a potential to be used as a therapeutic for cancer. We have recently demonstrated that administration of IL-27 producing adeno-associated virus (AAV-IL-27) exhibits potent inhibition of tumor growth in mouse models. In this study, we demonstrate that AAV-IL-27 treatment leads to significant expansion of CD11b+Gr1+ myeloid cells. AAV-IL-27-induced expansion of CD11b+Gr1+ cells is IL-27R-dependent and requires Stat3 signaling, but it is inhibited by Stat1 signaling. AAV-IL-27 treatment does not increase the self-renewal capacity of CD11b+Gr1+ cells but induces significant expansion of Lin-Sca1+c-Kit+ (LSK) and granulocyte-monocyte progenitor cells. Despite exhibiting significant suppression of T cells in vitro, IL-27-induced CD11b+Gr1+ cells lost the tumor-promoting activity in vivo and overall play an antitumor role. In tumors from AAV-IL-27-treated mice, CD11b+Gr1+ cells are largely F4/80+ and express high levels of MHC class I/II and M1 macrophage markers. Thus, IL-27 gene therapy induces Stat3-mediated expansion of CD11b+Gr1+ myeloid cells and promotes accumulation of M1 macrophages in the tumor microenvironment.

ANXA13 promotes cell proliferation and invasion and attenuates apoptosis in renal cell carcinoma.

Purpose: Emerging evidences have demonstrated that annexin A13 (ANXA13) is closely related to the occurrence and development of malignant tumors. However, the functions and underlying molecular mechanisms of ANXA13 in Clear cell renal cell carcinoma (ccRCC) have not been defined. Therefore, this study aimed to clarify the potential role of ANXA13 in regulating the proliferation, migration, invasion, cell cycle, and apoptosis of ccRCC cells. Patients and methods: The quantitative real-time PCR (qRT-PCR) and western blotting was performed for detecting the ANXA13 expression in ccRCC tissues at the mRNA and protein levels, respectively. The GEPIA2 databases were used to derive data for analyzing the ANXA13 expression in pan-cancer and ccRCC clinical features. Cell Counting and colony formation assays, as well as flow cytometry, were used to detect cell proliferation, apoptosis, or cell cycle. The wound healing assay was used to evaluate the migration ability of cells, and the Trans-well assay was conducted to determine the cell invasiveness. Results: ANXA13 was upregulated in ccRCC cells and human ccRCC tissues. Furthermore, siANXA13 inhibited ccRCC cell proliferation, migration, invasion and induced cell apoptosis. Conclusion: ANXA13 was upregulated in ccRCC. ANXA13 promotes tumorigenic traits of ccRCC cell lines in vitro. ANXA13 is a potential novel biomarker and a potential therapeutic target in ccRCC.

CD200R signaling contributes to unfavorable tumor microenvironment through regulating production of chemokines by tumor-associated myeloid cells.

CD200 is overexpressed in many solid tumors and considered as an immune checkpoint molecule dampening cancer immunity. In this study, we found that CD200R-/- mice were significantly more potent in rejecting these CD200+ tumors. scRNA sequencing demonstrated that tumors from CD200R-/- mice had more infiltration of CD4+ and CD8+ T cells, and NK cells but less infiltration of neutrophils. Antibody depletion experiments revealed that immune effector cells are crucial in inhibiting tumor growth in CD200R-/- mice. Mechanistically, we found that CD200R signaling regulates the expression of chemokines in tumor-associated myeloid cells (TAMCs). In the absence of CD200R, TAMCs increased expression of CCL24 and resulted in increased infiltration of eosinophils, which contributes to anti-tumor activity. Overall, we conclude that CD200R signaling contributes to unfavorable TME through chemokine-dependent recruitment of immune suppressive neutrophils and exclusion of anti-cancer immune effectors. Our study has implications in developing CD200-CD200R targeted immunotherapy of solid tumors.