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Immunotherapy has emerged as a revolutionizing therapeutic modality for cancer. However, its efficacy has been largely limited by a weak immune response and an immunosuppressive tumor microenvironment. Herein, we report a metal–organic framework (MOF)-derived titanium oxide nanoparticle (MCTxNP) as an immune booster that can greatly improve the immunotherapy efficacy by inducing “immunogenic cell death” (ICD) and remodeling the tumor microenvironment. The NPs, inheriting the characteristic structure of MIL-125 and enriched with oxygen vacancies (OVs), demonstrate both high photothermal conversion efficiency and a reactive oxygen species (ROS) generation yield upon near-infrared (NIR) activation. Moreover, the NPs can release O2and reduce glutathione (GSH) in the tumor environment, showcasing their potential to reverse the immunosuppressive microenvironment. In vitro/vivoresults demonstrate that MCTxNPs directly kill tumor cells and effectively eliminate primary tumors by exerting dual photodynamic/photothermal therapy under a single NIR irritation. At the same time, MCTxNPs augment the PD-L1 blockade efficacy by potently inducing ICDs and reversing the immunosuppressive tumor microenvironment, including promoting dendritic cell (DC) maturation, decreasing regulatory T cells (Tregs)’ infiltration, and increasing cytotoxic T lymphocytes (CTLs) and helper T cells (Ths), resulting in effective distant tumor suppression. This work highlights MCTxNP-mediated photodynamic- and photothermal-enhanced immunotherapy as an effective strategy for tumor treatment.

Rendering invisibility in the wide application scenarios has seen a surge in interest in recent years. Though various approaches have been proposed to realize concealments under different conditions, achieving polarization-independent invisibility for large objects remains a big challenge. Here, we propose to attain invisibility of a large dielectric slab with polarization constraints being totally lifted. This is accomplished by employing an antiscattering coating made of anisotropic metamaterials. We show that by tailoring the electric resonance of a triangular mushroom structure, antiphase electric dipole moment can be induced, resulting in an antipolarization response of the whole metamaterial coatings. By putting the proposed coatings on both sides of a large dielectric slab, a neutralization effect of the total polarization is observed, leading to the peculiar phenomenon of full-polarization invisibility. Our results are validated through full-wave simulations and experimental measurements. Remarkably, the intrinsic null-polarization property of the coating-slab-coating structure guarantees the invisibility feature of a large-scale bulk made by simply stacking the sandwiched composites, which facilitates the application of invisibility in practical scenarios such as the invisibility cloaks and the reflectionless antenna radomes.

Two-dimensional (2D) van der Waals magnets comprise rich physics that can be exploited for spintronic applications. We investigate the interplay between spin–phonon coupling and spin textures in a 2D van der Waals magnet by combining magneto-Raman spectroscopy with cryogenic Lorentz transmission electron microscopy. We find that when stable skyrmion bubbles are formed in the 2D magnet, a field-dependent Raman shift can be observed, and this shift is absent for the 2D magnet prepared in its ferromagnetic state. Correlating these observations with numerical simulations that take into account field-dependent magnetic textures and spin–-phonon coupling in the 2D magnet, we associate the Raman shift to field-induced modulations of the skyrmion bubbles and derive the existence of inhomogeneity in the skyrmion textures over the film thickness.

This paper investigates consensus of networked fractional-order systems over directed graph, with the networked double-integrator systems as its special case. An intermittent sampled position measurement distributed algorithm is proposed, which reduces the operation time and the update rates of controllers, and effectively responds to the circumstances if the information of agents’ velocity and current position cannot be measured. In order to reach consensus, some necessary and sufficient conditions with respect to the fractional order, communication width, coupling gains, and networked structure, are derived by applying the fractional Laplace transform and stability theory. Note that consensus can be reached only if some inequalities are fulfilled, which serves as a guide for selecting the appropriate communication width and sampling period to reach consensus. Finally, some simulation examples are illustrated to verify the theoretical results.

With the popularity of cryptocurrencies and the remarkable development of blockchain technology, decentralized applications emerged as a revolutionary force for the Internet. Meanwhile, decentralized applications have also attracted intense attention from the online gambling community, with more and more decentralized gambling platforms created through the help of smart contracts. Compared with conventional gambling platforms, decentralized gambling has transparent rulesand a low participation threshold, attracting a substantial number of gamblers. In order to discover gambling behaviors and identify the contracts and addresses involved in gambling, we propose a tool termed ETHGamDet. The tool is able to automatically detect the smart contracts and addresses involved in gambling by scrutinizing the smart contract code and address transaction records. Interestingly, we present a novel LightGBM model with memory components, which possesses the ability to learn from its own misclassifications. As a side contribution, we construct and release a large-scale gambling dataset at https://github.com/AwesomeHuang/Bitcoin-Gambling-Datasetto facilitate future research in this field. Empirically, ETHGamDetachieves a F1-score of 0.72 and 0.89 in address classificationand contract classificationrespectively, and offers novel and interesting insights.

Aberrant energy metabolism not only endows tumor cells with unlimited proliferative capacity but also contributes to the establishment of the glucose-deficient/lactate-rich immunosuppressive tumor microenvironment (ITM) impairing antitumor immunity. Herein, a novel metabolic nanoregulator (D/B/CQ@ZIF-8@CS) was developed by enveloping 2-deoxy-d-glucose (2-DG), BAY-876, and chloroquine (CQ) into zeolitic imidazolate framework-8 (ZIF-8) to simultaneously deprive the energy/nutrition supply of tumor cells and relieve the ITM for synergetic tumor starvation-immunotherapy. Aerobic glycolysis, glucose uptake, and autophagy flux could be concurrently blocked by D/B/CQ@ZIF-8@CS, cutting off the nutrition/energy supply and the source of lactate. Furthermore, inhibition of glucose uptake and aerobic glycolysis could effectively reverse the glucose-deficient/lactate-rich ITM, thus functionally inactivating regulatory T cells and augmenting anti-CTLA-4 immunotherapy. Such a two-pronged strategy would provide new insights for the design of metabolic intervention-based synergistic cancer therapy.

Transformation optics (TO) provides an unprecedented technique to control electromagnetic (EM) waves by engineering the constitutive parameters of the surrounding medium through a proper spatial transformation. In general, ideal transformation optical devices require simultaneous electric and magnetic responses along all three dimensions. To ease the practical implementation, previous studies usually made use of reduced parameters or other simplified approaches, which inevitably introduce extra reflection or unwanted phase shift. Up to today, experimental realizations of full-parameter transformation optical devices in free space are still quite limited. Here, a general design strategy is proposed to solve this problem. As a specific example, a full-parameter spatial-compression TO medium with constitutive parameters taking the diagonal form diag(a, a, 1/a) for the TM wave incidence was designed and realized experimentally. Such spatial-compression TO media were then applied to the implementation of an ideal omnidirectional invisibility cloak capable of concealing a large-scale object over a wide range of illumination angles. Both the simulation and experiment confirm that the cloak allows for nearly unity transmission of EM waves in the forward direction without introducing extra scattering or phase shift. This work constitutes an important stepping stone for future practical implementation of arbitrary full-parameter omnidirectional transformation optical devices.Using a judiciously designed full-parameter transformation optical metamaterial, an ideal omnidirectional invisibility cloak capable of concealing a large-scale object in the free space is implemented experimentally.

The recent convergence of chiral molecules with metal halide perovskite frameworks gives rise to an interesting family of chiral systems: two-dimensional, chiral hybrid organic–inorganic perovskites (chiral-HOIPs). While possessing photovoltaic properties of traditional HOIPs, this class of materials is endowed with chirality through its organic ligands in which the degeneracy of the electron spin in charge transport is broken. That is, the chirality-induced spin selectivity (CISS) effect manifests, making it a promising platform to bridge opto-spintronic studies and the CISS effect. In this work, chiral-HOIP/NiFe heterostructures are studied by means of the magneto-optical Kerr effect using a Sagnac interferometer. Upon illumination of the chiral-HOIPs, the Kerr signal at the chiral-HOIP/NiFe interface changes, and a linear dependence of the response on the magnetic field is observed. The sign of the slope was found to depend on the chirality of the HOIPs. The results demonstrate the utility of chiral-HOIP materials for chiral opto-spintronic applications.

In situ vaccines have revolutionized immunotherapy as they can stimulate tumor‐specific immune responses, with the cancer being the antigen source. However, the heterogeneity of tumor antigens and insufficient dendritic cells (DCs) activation result in low cancer immunogenicity and hence poor vaccine response. Herein, a new in situ vaccine composed of acid‐responsive liposome‐coated polydopamine (PDA) nanoparticles modified with mannose and loaded with resiquimod (R848) is designed to promote the efficacy of immunotherapy. The in situ vaccine can actively target the tumor site based on the decomposition of the liposome, while the PDA nanoparticles promote photothermal therapy and capture the immunogenic cell‐death–induced tumor‐associated antigens based on the adsorption effect of dopamine‐mimetic mussels. The PDA nanoparticles, which are modified with a mannose ligand, target the DCs and release R848 for activated antigen presentation. As a result, the in situ vaccine not only effectively activates the maturation of the DCs but also significantly enhances their effect on cytotoxic T lymphocyte cells. Furthermore, the vaccine effectively inhibits the distant recurrence and metastasis of tumors via long‐term immune memory effects. Therefore, the in situ vaccine provides a potential strategy for improving the efficacy of cancer immunotherapy. An in situ vaccine composed of acid‐responsive liposome‐coated polydopamine (PDA) nanoparticles modified with mannose and loaded with resiquimod is developed to promote cancer immunotherapy. It can actively target the tumor site based on the decomposition of the liposome, while the PDA nanoparticles promote photothermal therapy and capture the immunogenic cell‐death–induced tumor‐associated antigens based on the adsorption effect of dopamine‐mimetic mussels.

MicroRNAs (miRNAs) are small noncoding RNAs that have a pivotal role in the post-transcriptional regulation of gene expression by sequence-specifically targeting multiple mRNAs. Although miR-33a was recently reported to play an important role in lipid homeostasis, atherosclerosis, and hepatic fibrosis, the functions of miR-33a in tumor progression and metastasis are largely unknown. Here, we found that downregulated miR-33a in breast cancer tissues correlates with lymph node metastasis. MiR-33a expression is significantly lower in the highly metastatic breast cancer cell lines than the noncancerous breast epithelial cells and non-metastatic breast cancer cells. Moreover, the overexpression of miR-33a in metastatic breast cancer cells remarkably decreases cell proliferation and invasion in vitroand significantly inhibits tumor growth and lung metastasis in vivo, whereas its knockdown in non-metastatic breast cancer cells significantly enhances cell proliferation and invasion in vitroand promotes tumor growth and lung metastasis in vivo. Combining bioinformatics prediction and biochemical analyses, we showed that ADAM9 and ROS1 are direct downstream targets of miR-33a. These findings identified miR-33a as a negative regulator of breast cancer cell proliferation and metastasis.

Periostin actively contributes to tissue injury, fibrosis, atherosclerosis, and inflammatory diseases; however, its role in hepatic fibrosis is unclear. Herein, we revealed that periostin expression was significantly up-regulated in carbon tetrachloride– and bile duct ligation–induced mice with acute and chronic liver fibrosis. Deficiency in periostin abrogated the development of liver fibrosis in mice. Carbon tetrachloride treatment significantly increased α-smooth muscle actin, fibronectin, and collagen I levels in wild-type mice, which were unaffected in periostin-knockout mice. Periostin-deficient mice showed a significantly reduced area of collagen deposition and decreased levels of serum alanine aminotransferase and aspartate aminotransferase compared with wild-type mice after 2 weeks of carbon tetrachloride administration. Chemokine ligand 2, IL-6, IL-1β, tumor necrosis factor-α, and tissue inhibitor of metalloproteinases 1 mRNA levels were significantly lower in periostin-deficient mice than in wild-type mice after carbon tetrachloride treatment. Periostin colocalized with hepatic stellate cell–derived collagen I and α-smooth muscle actin in mouse acute and chronic fibrotic liver tissues. Transforming growth factor (TGF)-β1 markedly induced periostin expression in primary mouse hepatic stellate cells. Periostin-deficient mice showed significantly lower levels of TGF-β1 and TGF-β2 compared with wild-type mice after carbon tetrachloride treatment. High levels of periostin in patients with acute or chronic hepatitis correlated with TGF-β1 and TGF-β2 expression in serum from patients with hepatitis. Data indicate that periostin is a novel mediator of hepatic fibrosis development.

Background: ADAMTS5has different roles in multiple types of cancers and participates in various molecular mechanisms. However, the prognostic value of ADAMTS5in patients with hepatocellular carcinoma (HCC) still remains unclear. We carried the study to evaluate the prognostic value and identified underlying molecular mechanisms in HCC.Methods: Firstly, the association of ADAMTS5expression and clinicopathological parameters was evaluated by in GSE14520. Next, ADAMTS5expression in HCC was performed using GSE14520, GSE36376, GSE76427 and The Cancer Genome Atlas (TCGA) profile. Furthermore, Kaplan-Meier analysis, Univariate and Multivariate Cox regression analysis, subgroup analysis was performed to evaluate the prognostic value of ADAMTS5in HCC. Finally, GO enrichment analysis, gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were performed to revealed underlying molecular mechanisms.Result: The expression of ADAMTS5was positively correlated with the development of HCC. Next, high ADAMTS5expression was significantly associated with poorer survival (all P< 0.05) and the impact of ADAMTS5on all overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), disease specific survival (DSS) and progression free interval (PFI) was specific for HCC among other 29 cancer types. Subgroup analysis showed that ADAMTS5overexpression was significantly associated with poorer OS in patients with HCC. Finally, ADAMTS5might participate in the status conversion from metabolic-dominant to extracellular matrix-dominant, and the activation of ECM-related biological process might contribute to high higher mortality risk for patients with HCC.Conclusion: ADAMTS5may play an important role in the progression of HCC, and may be considered as a novel and effective biomarker for predicting prognosis for patients with HCC.

Periostin is a multifunctional extracellular matrix protein involved in various inflammatory diseases and tumor metastasis; however, evidence regarding whether and how periostin actively contributes to inflammation-associated tumorigenesis remains elusive. Here, we demonstrate that periostin deficiency significantly inhibits the occurrence of colorectal cancer in azoxymethane/dextran sulfate sodium-treated mice and in ApcMin/+mice. Moreover, periostin deficiency attenuates the severity of colitis and reduces the proliferation of tumor cells. Mechanistically, stromal fibroblast-derived periostin activates FAK-Src kinases through integrin-mediated outside-in signaling, which results in the activation of YAP/TAZ and, subsequently, IL-6 expression in tumor cells. Conversely, IL-6 induces periostin expression in fibroblasts by activating STAT3, which ultimately facilitates colorectal tumor development. These findings provide the evidence that periostin promotes colorectal tumorigenesis, and identify periostin- and IL-6-mediated tumor-stroma interaction as a promising target for treating colitis-associated colorectal cancer.

Periostin (POSTN) is a multifunctional extracellular component that regulates cell-matrix interactions and cell-cell crosstalk. POSTN deletion significantly decreases leukemia burden in mice; however, the underlying mechanisms by which POSTN promotes B cell acute lymphoblastic leukemia (B-ALL) progression remain largely unknown. Here, we demonstrate that bone marrow (BM)-derived mesenchymal stromal cells (BM-MSCs) express higher levels of POSTN when co-cultured with B-ALL cells in vitroand in vivo. POSTN deficiency in BM-MSCs significantly decreases CCL2 expression in co-cultured B-ALL cells in vitroand in vivo. Moreover, POSTN treatment increases expression of CCL2 in B-ALL cells by activating the integrin-ILK-NF-κB pathway. Conversely, CCL2 treatment upregulates expression of POSTN in BM-MSCs via STAT3 activation. Furthermore, there is a positive correlation between POSTN expression and CCL2 level in the BM of mice and patients with B-ALL. These findings suggest that B-ALL cell-derived CCL2 contributes to the increased leukemia burden promoted by BM-MSC-derived POSTN.