Machine learning-enabled performance prediction and optimization for iron-chromium redox flow batteries.

Iron-chromium flow batteries (ICRFBs) are regarded as one of the most promising large-scale energy storage devices with broad application prospects in recent years. However, transitioning from laboratory-scale development to industrial-scale deployment can be a time-consuming process due to the multitude of complex factors that impact ICRFB stack performance. Herein, a data-driven optimization methodology applying active learning, informed by an extensive survey of the literature encompassing diverse experimental conditions, is proposed to enable exceptional precision in predicting ICRFB system performance considering both operation conditions and key materials selection. Specifically, multitask ML models are trained on experimental data with a high prediction accuracy (R2 > 0.92) to link ICRFB properties to energy efficiency, coulombic efficiency, and capacity. We also interpret the ML models based on Shapley additive explanations and extract valuable insights into the importance of descriptors. It is noted that the operation conditions (current density and cycle number) and the electrode type are the most critical descriptors affecting the voltage efficiency and coulombic efficiency while the electrode size strongly affects the capacity. Moreover, active learning is used to explore the most optimized cases considering the highest energy efficiency and capacity. The versatility and robustness of the approach are demonstrated by the successful validation between ML prediction and our experiments of energy efficiency (±0.15%) and capacity (±0.8%). This work not only affords fruitful data-driven insight into the property-performance relationship, but also unveils the explainability of critical properties on the performance of ICRFBs, which accelerates the rational design of next-generation ICRFBs.

Tumor vaccine based on extracellular vesicles derived from γδ-T cells exerts dual antitumor activities.

γδ-T cells are innate-like T cells with dual antitumor activities. They can directly eradicate tumor cells and function as immunostimulatory cells to promote antitumor immunity. Previous studies have demonstrated that small extracellular vesicles (EVs) derived from γδ-T cells (γδ-T-EVs) inherited the dual antitumor activities from their parental cells. However, it remains unknown whether γδ-T-EVs can be designed as tumors vaccine to improve therapeutic efficacy. Here, we found that γδ-T-EVs had immune adjuvant effects on antigen-presenting cells, as revealed by enhanced expression of antigen-presenting and co-stimulatory molecules, secretion of pro-inflammatory cytokines and antigen-presenting ability of DCs after γδ-T-EVs treatment. The γδ-T-EVs-based vaccine was designed by loading tumor-associated antigens (TAAs) into γδ-T-EVs. Compared with γδ-T-EVs, the γδ-T-EVs-based vaccine effectively promoted more tumor-specific T-cell responses. In addition, the vaccine regimen preserved direct antitumor effects and induced tumor cell apoptosis. Interestingly, the allogeneic γδ-T-EVs-based vaccine showed comparable preventive and therapeutic antitumor effects to their autologous counterparts, indicating a better way of centralization and standardization in clinical practice. Furthermore, the allogeneic γδ-T-EVs-based vaccine displayed advantages over the DC-EVs-based vaccine through their dual antitumor activities. This study provides a proof-of-concept for using the allogeneic γδ-T-EVs-based vaccine in cancer control.

Arctigenin Suppresses the Proliferation and Metastasis, and Induces Apoptosis and Cycle Arrest of Osteosarcoma Cells by inhibiting HMOX1 Expression.

BACKGROUND: Osteosarcoma is the most common malignant bone tumor, with highly proliferative and metastatic properties. Previous studies have reported that arctigenin (Arc), a bioactive lignin compound, showed excellent anti-tumor activities in a variety of human cancers. However, its role in osteosarcoma has not been studied. OBJECTIVE: We aimed to investigate the anti-tumor effects of Arc on osteosarcoma cell proliferation, migration, invasion, apoptosis, and cell cycle. METHODS: Effects of Arc on osteosarcoma cell proliferation were detected by MTT and colony formation assay. Flow cytometry analysis was performed to assess the cell apoptosis and cycle arrest. Transwell assay was used to evaluate the capability of migration and invasion. qRT-PCR and Western blot were employed to determine the changes in mRNA and protein levels. RESULTS: Arc could significantly suppress the proliferation, colony formation, and induce cell apoptosis and S phase cycle arrest of MG63 and U-2 OS cells in a dose-dependent manner. In addition, we also observed an inhibitory effect of Arc treatment on osteosarcoma cell invasion, migration, and epithelial-mesenchymal transition (EMT). HMOX1, encoding enzyme heme oxygenase-1, was predicted to be a candidate target of Arc using STITCH. Arc treatment significantly reduced the mRNA and protein levels of HMOX1. Furthermore, overexpression of HMOX1 could partly reverse the inhibitory effects of Arc on osteosarcoma cell malignant phenotypes. CONCLUSION: Our results suggest that Arc inhibits the proliferation, metastasis and promotes cell apoptosis and cycle arrest of osteosarcoma cells by downregulating HMOX1 expression.

ANGPTL4 functions as an oncogene through regulation of the ETV5/CDH5/AKT/MMP9 axis to promote angiogenesis in ovarian cancer.

BACKGROUND: Angiopoietin-like 4 (ANGPTL4) is highly expressed in a variety of neoplasms and promotes cancer progression. Nevertheless, the mechanism of ANGPTL4 in ovarian cancer (OC) metastasis remains unclear. This study aimeds to explore whether ANGPTL4 regulates OC progression and elucidate the underlying mechanism. METHODS: ANGPTL4 expression in clinical patient tumor samples was determined by immunohistochemistry (IHC) and high-throughput sequencing. ANGPTL4 knockdown (KD) and the addition of exogeneous cANGPTL4 protein were used to investigate its function. An in vivo xenograft tumor experiment was performed by intraperitoneal injection of SKOV3 cells transfected with short hairpin RNAs (shRNAs) targeting ANGPTL4 in nude mice. Western blotting and qRT-PCR were used to detect the levels of ANGPTL4, CDH5, p-AKT, AKT, ETV5, MMP2 and MMP9 in SKOV3 and HO8910 cells transfected with sh-ANGPTL4 or shRNAs targeting ETV5. RESULTS: Increased levels of ANGPTL4 were associated with poor prognosis and metastasis in OC and induced the angiogenesis and metastasis of OC cells both in vivo and in vitro. This tumorigenic effect was dependent on CDH5, and the expression levels of ANGPTL4 and CDH5 in human OC werepositively correlated. In addition, CDH5 activated p-AKT, and upregulated the expression of MMP2 and MMP9. We also found that the expression of ETV5 was upregulated by ANGPTL4, which could bind the promoter region of CDH5, leading to increased CDH5 expression. CONCLUSION: Our data indicated that an increase in the ANGPTL4 level results in increased ETV5 expression in OC, leading to metastasis via activation of the CDH5/AKT/MMP9 signaling pathway.

CD137 Costimulation Enhances the Antitumor Activity of Vγ9Vδ2-T Cells in IL-10-Mediated Immunosuppressive Tumor Microenvironment.

Although γδ-T cell-based tumor immunotherapy using phosphoantigens to boost γδ-T cell immunity has shown success in some cancer patients, the clinical application is limited due to the rapid exhaustion of Vγ9Vδ2-T cells caused by repetitive stimulation from phosphoantigens and the profoundly immunosuppressive tumor microenvironment (TME). In this study, using a cell culture medium containing human and viral interleukin-10 (hIL-10 and vIL-10) secreted from EBV-transformed lymphoblastoid B cell lines (EBV-LCL) to mimic the immunosuppressive TEM, we found that the antitumor activity of Vγ9Vδ2-T cells was highly suppressed by endogenous hIL-10 and vIL-10 within the TME. CD137 costimulation could provide an anti-exhaustion signal to mitigate the suppressive effects of IL-10 in TME by suppressing IL-10R1 expression on Vγ9Vδ2-T cells. CD137 costimulation also improved the compromised antitumor activity of Vγ9Vδ2-T cells in TME with high levels of IL-10 in Rag2-/- γc-/- mice. In humanized mice, CD137 costimulation boosted the therapeutic effects of aminobisphosphonate pamidronate against EBV-induced lymphoma. Our study offers a novel approach to overcoming the obstacle of the hIL-10 and vIL-10-mediated immunosuppressive microenvironment by costimulating CD137 and enhancing the efficacy of γδ-T cell-based tumor therapy.

Glucose metabolism controls human γδ T-cell-mediated tumor immunosurveillance in diabetes.

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of cancer. The effect of glucose metabolism on γδ T cells and their impact on tumor surveillance remain unknown. Here, we showed that high glucose induced Warburg effect type of bioenergetic profile in Vγ9Vδ2 T cells, leading to excessive lactate accumulation, which further inhibited lytic granule secretion by impairing the trafficking of cytolytic machinery to the Vγ9Vδ2 T-cell-tumor synapse by suppressing AMPK activation and resulted in the loss of antitumor activity in vitro, in vivo and in patients. Strikingly, activating the AMPK pathway through glucose control or metformin treatment reversed the metabolic abnormalities and restored the antitumor activity of Vγ9Vδ2 T cells. These results suggest that the impaired antitumor activity of Vγ9Vδ2 T cells induced by dysregulated glucose metabolism may contribute to the increased cancer risk in T2DM patients and that metabolic reprogramming by targeting the AMPK pathway with metformin may improve tumor immunosurveillance.

Carbon Dots in Biomedicine: A Review.

Despite the rapid development of science and technology, the effective treatment of cancer still threatens human life and health. However, the success of cancer treatment is closely related to early diagnosis, identification, and effective treatment. In recent years, with the strengthening of the development and research of nanomaterials for cancer diagnosis and treatment, researchers have found that carbon dots (CDs) have the advantages of wide absorption, excellent biocompatibility, diverse imaging characteristics, and photostability and are widely used in various fields, such as sensing, imaging, and drug/gene transportation. Recently, researchers also discovered that CDs could be used as an effective photosensitizer to generate active oxygen or convert light energy into heat under the stimulation of the external lasers, making them have the effects of photothermal and photodynamic therapy for cancer. In this review, we first outline the single-modal and multimodal imaging analysis of CDs in cancer cells. After introducing diversified imaging functions, we focused on the design and the latest research progress of CDs in phototherapy and introduced in detail the strategies of CDs in phototherapy treatment and the challenges faced by clinical applications. We hope that this overview can provide important insights for researchers and accelerate the pace of research on CDs in imaging-guided phototherapy treatment.

Exosomes derived from γδ-T cells synergize with radiotherapy and preserve antitumor activities against nasopharyngeal carcinoma in immunosuppressive microenvironment.

BACKGROUND: Radiotherapy is the first-line treatment for patients nasopharyngeal carcinoma (NPC), but its therapeutic efficacy is poor in some patients due to radioresistance. Adoptive T cell-based immunotherapy has also shown promise to control NPC; however, its antitumor efficacy may be attenuated by an immunosuppressive tumor microenvironment. Exosomes derived from γδ-T cells (γδ-T-Exos) have potent antitumor potentials. However, it remains unknown whether γδ-T-Exos have synergistic effect with radiotherapy and preserve their antitumor activities against NPC in an immunosuppressive tumor microenvironment. METHODS: γδ-T-Exos were stained with fluorescent membrane dye, and their interactions with NPC were determined both in vitro and in vivo. NPC cell deaths were detected after treatment with γδ-T-Exos and/or irradiation. Moreover, effects of γδ-T-Exos on radioresistant cancer stem-like cells (CSCs) were determined. The therapeutic efficacy of combination therapy using γδ-T-Exos and irradiation on NPC tumor progression was also monitored in vivo. Finally, the tumor-killing and T cell-promoting activities of γδ-T-Exos were determined under the culture in immunosuppressive NPC supernatant. RESULTS: γδ-T-Exos effectively interacted with NPC tumor cells in vitro and in vivo. γδ-T-Exos not only killed NPC cells in vitro, which was mainly mediated by Fas/Fas ligand (FasL) and death receptor 5 (DR5)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathways, but also controlled NPC tumor growth and prolonged tumor-bearing mice survival in vivo. Furthermore, γδ-T-Exos selectively targeted the radioresistant CD44+/high CSCs and induced profound cell apoptosis. The combination of γδ-T-Exos with radiotherapy overcame the radioresistance of CD44+/high NPC cells and significantly improved its therapeutic efficacy against NPC in vitro and in vivo. In addition, γδ-T-Exos promoted T-cell migration into NPC tumors by upregulating CCR5 on T cells that were chemoattracted by CCR5 ligands in the NPC tumor microenvironment. Although NPC tumor cells secreted abundant tumor growth factor beta to suppress T-cell responses, γδ-T-Exos preserved their direct antitumor activities and overcame the immunosuppressive NPC microenvironment to amplify T-cell antitumor immunity. CONCLUSIONS: γδ-T-Exos synergized with radiotherapy to control NPC by overcoming the radioresistance of NPC CSCs. Moreover, γδ-T-Exos preserved their tumor-killing and T cell-promoting activities in the immunosuppressive NPC microenvironment. This study provides a proof of concept for a novel and potent strategy by combining γδ-T-Exos with radiotherapy in the control of NPC.

Predictors of visual recovery in patients with macular edema secondary to central retinal vein occlusion after treatment with Conbercept.

BACKGROUND: The use of Spectral domain optical coherence tomography (SD-OCT) to evaluate the predictors of visual acuity-recovery in patients treated with conbercept for macular edema (ME) secondary to central retinal vein occlusion (CRVO) has rarely been seen. We collected 26 CRVO-ME patients with different OCT measures at 6 months follow-up to identify the factors that are most strongly correlated with the best-corrected visual acuity (BCVA) post-treatment in CRVO-ME patients treated with conbercept. PURPOSE: To evaluate the effectiveness of intravitreal conbercept injections for the treatment of CRVO-ME and to determine the major predictors of best-corrected visual acuity (BCVA) post-treatment. METHODS: A retrospective study methodology was used. Twenty-six eyes from 26 patients with CRVO-ME were enrolled in the study. After an initial intravitreal injection of conbercept (0.5 mg/0.05 ml), monthly injections for up to 6 months were given following a 1 + PRN (pro re nata) regimen. Data collected at monthly intervals included measurements of the logMAR BCVA, central subfield thickness (CST), macular volume (MV), photoreceptor layer thickness (PLT), outer nuclear layer thickness (ONLT), and the disrupted ellipsoid zone (DEZ). The correlation between BCVA, before and after injections, and each of CST, MV, PLT, ONLT, DEZ was analyzed. RESULTS: The logMAR BCVA in months 3 and 6 post-injection was significantly improved relative to the baseline. In this same period the CST, MV, PLT, ONLT and DEZ were also significantly improved relative to the baseline. There was a negative correlation between PLT and logMAR BCVA at months 3 and 6 after treatment (r = - 0.549, P < 0.001; r = - 0.087, P < 0.001). CONCLUSION: Intravitreal injection of conbercept is an effective treatment for CRVO-ME. With 6 months of follow-up, logMAR BCVA and CST, MV, PLT, ONLT, DEZ improved. PLT was negatively correlated with the visual function in CRVO-ME patients after conbercept treatment, which may be a predictor of vision recovery in patients with CRVO-ME.

Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell.

Immune memory represents the most efficient defense against invasion and transmission of infectious pathogens. In contrast to memory T and B cells, the roles of innate immunity in recall responses remain inconclusive. In this study, we identified a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection. These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. Different from memory-like NK cells reported previously, these NKp46+ NKG2A+ memory NK cells exhibited HA-specific silence of cytotoxicity but increase of gamma interferon (IFN-γ) response against influenza virus-infected cells, which could be reversed by pifithrin-µ, a p53-heat shock protein 70 (HSP70) signaling inhibitor. During recall responses, splenic NKp46+ NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ T cell distribution, resulting in improved clinical outcomes. This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.IMPORTANCE In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46+ NKG2A+ NK cell subset induced by influenza A virus infection. These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection.

Anti-angiogenic therapy in ovarian cancer: current situation & prospects.

Ovarian cancer (OC) is one of five leading causes of cancer related death among women worldwide. Although treatment has been improving, the survival rate has barely improved over the past 30 years. The fatality rate is due to asymptomatic early signs and the lack of long-term effective treatment strategies for advanced disease. Angiogenesis is an important process in tumour growth and metastasis and is the creation of new blood vessels from existing blood vessels. It is a dynamic and complex process involving various molecular regulatory pathways and multiple mechanisms. The inhibition of angiogenesis has become a recognized therapeutic strategy for many solid tumours. While benefits in progression-free survival have been observed, the OS is far from satisfactory for OC patients who receive antiangiogenic therapy. In this article, the present research status of angiogenesis in OC was reviewed and the reasons for poor antiangiogenic therapeutic effects was explored with the aim to identify potential therapeutic targets that may improve the effect of antiangiogenic therapies.

LncRNA NEAT1 Sponges MiRNA-148a-3p to Suppress Choroidal Neovascularization and M2 macrophage polarization.

PURPOSE: Long noncoding RNAs (lncRNAs) have emerged as essential regulators in many biological processes; however, little is known about the role of lncRNAs in choroidal neovascularization (CNV). The aim of this study was to investigate the role of lncRNA NEAT1 in CNV formation, and assessed whether inhibition of lncRNA NEAT1 could suppress M2-type macrophage polarization and CNV. METHODS: The expression profiles of lncRNAs in a CNV mice model were accessed via microarray analysis. The role of lncRNA NEAT1 on macrophage polarization was assessed both in vitro and vivo. The interaction between lncRNA NEAT1, miR-148a-3p, and PTEN was assessed using a dual-luciferase reporter assay and RNA immunoprecipitation assay. Additionally, to evaluate the role of lncRNA NEAT1 on CNV development, eyes of mice in the mice CNV model were examined by Fluorescein Angiography (FA) and choroidal flatmounts on days 3 and 7 after intravitreal injection. RESULTS: The results revealed that 128 lncRNAs were significantly altered in the RPE-choroid-sclera complexes of CNV mice (P < 0.05, fold change > 2.0). Additionally, lncRNA NEAT1 increased in CNV formation and M2 macrophage polarization. LncRNA NEAT1 sponging miRNA-148a-3p targeting PTEN can modulate M2 macrophage polarization in mice CNV models as well as in bone marrow-derived macrophages cultured in vitro. Inhibition of lncRNA NEAT1 can suppress M2 macrophage both in vitro and vivo. Moreover, the intravitreal injection of a lncRNA NEAT1 Smart Silencer can inhibit CNV leakage and neovascularization. CONCLUSION: LncRNA NEAT1 via miRNA-148a-3p targeting PTEN plays a significant role in M2 macrophage polarization, while the inhibition of lncRNA NEAT1 can suppress choroidal neovascularization by inhibiting M2 macrophage polarization.

Exosomes derived from Vδ2-T cells control Epstein-Barr virus-associated tumors and induce T cell antitumor immunity.

Treatment of life-threatening Epstein-Barr virus (EBV)-associated tumors remains a great challenge, especially for patients with relapsed or refractory disease. Here, we found that exosomes derived from phosphoantigen-expanded Vδ2-T cells (Vδ2-T-Exos) contained death-inducing ligands (FasL and TRAIL), an activating receptor for natural killer (NK) cells (NKG2D), immunostimulatory ligands (CD80 and CD86), and antigen-presenting molecules (MHC class I and II). Vδ2-T-Exos targeted and efficiently killed EBV-associated tumor cells through FasL and TRAIL pathways and promoted EBV antigen-specific CD4 and CD8 T cell expansion. Administration of Vδ2-T-Exos effectively controlled EBV-associated tumors in Rag2-/-γc-/- and humanized mice. Because expanding Vδ2-T cells and preparing autologous Vδ2-T-Exos from cancer patients ex vivo in large scale is challenging, we explored the antitumor activity of allogeneic Vδ2-T-Exos in humanized mouse cancer models. Here, we found that allogeneic Vδ2-T-Exos had more effective antitumor activity than autologous Vδ2-T-Exos in humanized mice; the allogeneic Vδ2-T-Exos increased the infiltration of T cells into tumor tissues and induced more robust CD4 and CD8 T cell-mediated antitumor immunity. Compared with exosomes derived from NK cells (NK-Exos) with direct cytotoxic antitumor activity or dendritic cells (DC-Exos) that induced T cell antitumor responses, Vδ2-T-Exos directly killed tumor cells and induced T cell-mediated antitumor response, thus resulting in more effective control of EBV-associated tumors. This study provided proof of concept for the strategy of using Vδ2-T-Exos, especially allogeneic Vδ2-T-Exos, to treat EBV-associated tumors.

CD137 costimulation enhances the antiviral activity of Vγ9Vδ2-T cells against influenza virus.

Influenza epidemics and pandemics are constant threats to global public health. Although strategies including vaccines and antiviral drugs have achieved great advances in controlling influenza virus infection, the efficacy of these strategies is limited by the highly frequent mutations in the viral genome and the emergence of drug-resistant strains. Our previous study indicated that boosting the immunity of human Vγ9Vδ2-T cells with the phosphoantigen pamidronate could be a therapeutic strategy to treat seasonal and avian influenza virus infections. However, one notable drawback of γδ-T cell-based immunotherapy is the rapid exhaustion of proliferation and effector responses due to repeated treatments with phosphoantigens. Here, we found that the expression of CD137 was inducible in Vγ9Vδ2-T cells following antigenic stimulation. CD137+ Vγ9Vδ2-T cells displayed more potent antiviral activity against influenza virus than their CD137- counterparts in vitro and in Rag2-/- γc-/- mice. We further demonstrated that CD137 costimulation was essential for Vγ9Vδ2-T cell activation, proliferation, survival and effector functions. In humanized mice reconstituted with human peripheral blood mononuclear cells, CD137 costimulation with a recombinant human CD137L protein boosted the therapeutic effects of pamidronate against influenza virus. Our study provides a novel strategy of targeting CD137 to improve the efficacy of Vγ9Vδ2-T cell-based immunotherapy.

RNA sequencing analysis reveals apoptosis induction by hydrogen treatment in endometrial cancer via TNF and NF-κB pathways.

BACKGROUND: To evaluate the activity of hydrogen in endometrial cancer and elucidate its underlying molecular mechanisms. METHODS: Ishikawa, HEC1A and AN3CA cells were incubated in DMEM medium with or without hydrogen. RNA sequencing was used to explore the association of hydrogen treatment with signaling pathways and functional genes in endometrial cancer cells. The apoptotic rates of the three endometrial cancer cells were evaluated by fluorescein isothiocyanate (FITC) Annexin V and Annexin V-allophycocyanin (APC)/propidium iodide double staining. RESULTS: RNA sequencing analysis revealed that hydrogen induced TNF/NF-κB and apoptosis pathways in endometrial cancer cells. The gene sets between hydrogen treatment groups and non-treated groups were mapped in accordance with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms. Hydrogen treatment significantly increased the apoptotic rates of endometrial cancer cells. CONCLUSIONS: Taken together, our data indicate that hydrogen can serve as a therapeutic target for endometrial cancer via TNF/NF-κB pathway and apoptosis induction.

Porous Se@SiO2 nanospheres attenuate cisplatin-induced acute kidney injury via activation of Sirt1.

Cisplatin (CDDP) is the most commonly used chemotherapeutic drug and has an irreplaceable role in cancer treatment. However, CDDP-induced acute kidney injury (AKI) greatly limits its use. Abundant evidence has confirmed that apoptosis contributes to AKI caused by CDDP administration. The nanoparticle form of selenium, also known as Se@SiO2 nanocomposites (NPs), has been proven to be a potential agent to prevent apoptotic cell death. In this article, we established acute kidney injury models in vivo via a single injection of CDDP and used human kidney 2 (HK-2) cells for experiments in vitro. We demonstrated that NPs can improve CDDP-induced renal dysfunction. In addition, therapy with NPs attenuated apoptosis in cells and kidney tissues treated with CDDP. In terms of mechanism, we discovered that Sirt1, a deacetylase with an important role in CDDP-induced acute kidney injury, was remarkedly increased after NPs pretreatment, and the anti-apoptotic effect of the NPs was markedly abrogated after the inhibition of Sirt1. The results linked the protective effect of NPs on nephrotoxicity with Sirt1, suggesting the potential clinical importance of nanomaterials in alleviating the side effects of chemotherapy.

Exosomes in cancer: Small transporters with big functions.

Exosomes are nanosized membrane-bound vesicles containing abundant proteins, DNA, mRNA, and non-coding RNAs. Exosomes are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Increasing studies have shown that exosomes play an important role in tumour initiation, growth, progression, metastasis, drug resistance and immune escape. In this article, we review recent advances in the biology of exosomes. We elaborate the specific mechanism by which exosomes affect the communication between tumours and the microenvironment. Finally, we report that exosomes may provide promising biomarkers for cancer diagnosis and represent new targets for cancer therapy.

Human Vγ9Vδ2-T Cells Synergize CD4+ T Follicular Helper Cells to Produce Influenza Virus-Specific Antibody.

Human Vγ9Vδ2-T cells recognize nonpeptidic antigens and exert effector functions against microorganisms and tumors, but little is known about their roles in humoral immune response against influenza virus infection. Herein, in the coculture of autologous human B cells, dendritic cells and/or naïve CD4 T cells, and Vγ9Vδ2-T cells, we demonstrated that Vγ9Vδ2-T cells could facilitate H9N2 influenza virus-specific IgG and IgM productions in a CD4 T cell-dependent manner. Vγ9Vδ2-T cells promoted the differentiation of CXCR5+PD1+CD4+ T follicular helper (Tfh) cells, CD19+IgD-CD38++ plasma cells (PCs), and drove B cell proliferation as well as immunoglobulin class switching. Interestingly, Vγ9Vδ2-T cells acquired Tfh-associated molecules such as CXCR5, PD1, CD40L, and ICOS during influenza virus stimulation, especially in the presence of CD4 T cells. Moreover, Vγ9Vδ2-T cells promoted CD4 T cells to secrete IL-13 and IL-21, and neutralizing IL-13 and IL-21 significantly reduced the number of CD19+IgD-CD38++ PCs. Using humanized mice, we further demonstrated that Vγ9Vδ2-T cells could synergize CD4 T cells to produce influenza virus-specific antibody. Our findings provide a greater scope for Vγ9Vδ2-T cells in adaptive immunity, especially for the Tfh development and humoral immune responses against influenza virus infection.

PD-1/PD-L1 Pathway Mediates the Alleviation of Pulmonary Fibrosis by Human Mesenchymal Stem Cells in Humanized Mice.

Pulmonary fibrosis is a chronic progressive lung disease with few treatments. Human mesenchymal stem cells (MSCs) have been shown to be beneficial in pulmonary fibrosis because they have immunomodulatory capacity. However, there is no reliable model to test the therapeutic effect of human MSCs in vivo. To mimic pulmonary fibrosis in humans, we established a novel bleomycin-induced pulmonary fibrosis model in humanized mice. With this model, the benefit of human MSCs in pulmonary fibrosis and the underlying mechanisms were investigated. In addition, the relevant parameters in patients with pulmonary fibrosis were examined. We demonstrate that human CD8+ T cells were critical for the induction of pulmonary fibrosis in humanized mice. Human MSCs could alleviate pulmonary fibrosis and improve lung function by suppressing bleomycin-induced human T-cell infiltration and proinflammatory cytokine production in the lungs of humanized mice. Importantly, alleviation of pulmonary fibrosis by human MSCs was mediated by the PD-1/programmed death-ligand 1 pathway. Moreover, abnormal PD-1 expression was found in circulating T cells and lung tissues of patients with pulmonary fibrosis. Our study supports the potential benefit of targeting the PD-1/programmed death-ligand 1 pathway in the treatment of pulmonary fibrosis.