Suhrmcdaniel7072

Mitochondria are highly involved in the metastasis of cancer cells. However, low permeability of mitochondria impedes the entry of anti-cancer drugs. Here, a self-assembled nanoparticle platform is designed that not only targets the DNA-intercalating agent doxorubicin to mitochondria but also enhances the specific penetration by opening the mitochondrial permeability transition pores (MPTPs). With drastic improvement in mitochondrial uptake, the drug delivery system results in substantial mitochondrial impairment leading to amplified induction of apoptosis, depletion of energy supply, and inhibition of numerous metastasis-associated proteins. As a consequence, the drug delivery system significantly inhibits the orthotopic tumor growth, and suppressed the metastasis of cancer cells detached from primary tumors. Additionally, the nanoparticle exhibits a potent effect on eradicating the metastasis of disseminated tumor cell from blood to lung. The results show that strategies of targeting mitochondria and unlocking MPTP are feasible and beneficial to mitigate both tumorigenesis and metastasis.Correlated electronic materials (CEMs) with strong electron-electron interactions are often associated with exotic properties, such as metal-insulator transition (MIT), charge density wave (CDW), superconductivity, and magnetoresistance (MR), which are fundamental to next generation condensed matter research and electronic devices. When the dimension of CEMs decreases, exposing extremely high specific surface area and enhancing electronic correlation, the surface states are equally important to the bulk phase. Therefore, surface/interface chemical interactions provide an alternative route to regulate the intrinsic properties of low-dimensional CEMs. Here, recent achievements in surface/interface chemistry engineering of low-dimensional CEMs are reviewed, using surface modification, molecule-solid interaction, and interface electronic coupling, toward modulation of conducting solids, phase transitions including MIT, CDW, superconductivity, and magnetism transition, as well as external-field response. Surface/interface chemistry engineering provides a promising strategy for exploring novel properties and functional applications in low-dimensional CEMs. Finally, the current challenge and outlook of the surface/interface engineering are also pointed out for future research development.The low immunogenicity, insufficient infiltration of T lymphocytes, and dismal response to immune checkpoint blockade therapy pose major difficulties in immunotherapy of pancreatic cancer. Photoimmunotherapy by photodynamic therapy (PDT) can induce an antitumor immune response by triggering immunogenic cell death in the tumor cells. Notwithstanding, PDT-driven oxygen consumption and microvascular damage can further aggravate hypoxia to exaggerates glycolysis, leading to lactate accumulation and immunosuppressive tumor microenvironment. Herein, a supramolecular prodrug nanoplatform codelivering a photosensitizer and a prodrug of bromodomain-containing protein 4 inhibitor (BRD4i) JQ1 for combinatory photoimmunotherapy of pancreatic cancer are demonstrated. The nanoparticles are fabricated by host-guest complexation between cyclodextrin-grafted hyaluronic acid (HA-CD) and adamantine-conjugated heterodimers of pyropheophorbide a (PPa) and JQ1, respectively. HA can achieve active tumor targeting by recognizing highly expressed CD44 on the surface of pancreatic tumors. PPa-mediated PDT can enhance the immunogenicity of the tumor cells and promote intratumoral infiltration of the cytotoxic T lymphocytes. Meanwhile, JQ1 combats PDT-mediated immune evasion through inhibiting expression of c-Myc and PD-L1, which are key regulators of tumor glycolysis and immune evasion. Collectively, this study presents a novel strategy to enhance photoimmunotherapy of the pancreatic cancer by provoking T cells activation and overcoming adaptive immune resistance.MnO2 nanoparticles have been widely employed in cancer immunotherapy, playing a subsidiary role in assisting immunostimulatory drugs by improving their pharmacokinetics and/or creating a favorable microenvironment. Here, the stereotype of the subsidiary role of MnO2 nanoparticles in cancer immunotherapy is challenged. This study unravels an intrinsic immunomodulatory property of MnO2 nanoparticles as a unique nutrient-responsive immunogenic cell death (ICD) inducer, capable of directly modulating immunosurveillance toward tumor cells. MnO2 nanoflowers (MNFs) constructed via a one pot self-assembly approach selectively induce ICD to nutrient-deprived but not nutrient-replete cancer cells, which is confirmed by the upregulated damage associated molecular patterns in vitro and a prophylactic vaccination in vivo. The underlying mechanism of the MNFs-mediated selective ICD induction is likely associated with the concurrently upregulated oxidative stress and autophagy. Built on their unique immunomodulatory properties, an innovative nanomaterials orchestrated cancer starvation-immunotherapy is successfully developed, which is realized by the in situ vaccination with MNFs and vascular disrupting agents that cut off intratumoral nutrient supply, eliciting potent efficacy for suppressing local and distant tumors. These findings open up a new avenue toward biomedical applications of MnO2 materials, enabling an innovative therapeutics paradigm with great clinical significance.Manganese (Mn)-based cathode materials have garnered huge research interest for rechargeable aqueous zinc-ion batteries (AZIBs) due to the abundance and low cost of manganese and the plentiful advantages of manganese oxides including their different structures, wide range of phases, and various stoichiometries. A novel in situ generated Mn-deficient ZnMn2O4@C (Mn-d-ZMO@C) nanoarchitecture cathode material from self-assembly of ZnO-MnO@C for rechargeable AZIBs is reported. Analytical techniques confirm the porous and crystalline structure of ZnO-MnO@C and the in situ growth of Mn deficient ZnMn2O4@C. The Zn/Mn-d-ZMO@C cell displays a promising capacity of 194 mAh g-1 at a current density of 100 mA g-1 with 84% of capacity retained after 2000 cycles (at 3000 mA g-1 rate). The improved performance of this cathode originates from in situ orientation, porosity, and carbon coating. Additionally, first-principles calculations confirm the high electronic conductivity of Mn-d-ZMO@C cathode. Importantly, a good capacity retention (86%) is obtained with a year-old cell (after 150 cycles) at 100 mA g-1 current density. This study, therefore, indicates that the in situ grown Mn-d-ZMO@C nanoarchitecture cathode is a promising material to prepare a durable AZIB.Real-time, high signal intensity, and prolonged detection is challenging because of the rarity of fluorophores with both high photostability and luminescence efficiency. In this work, new donor-acceptor (D-A) molecules for overcoming these limitations are reported. A hybridized local and an intramolecular charge-transfer excited state is demonstrated to afford high photoluminescence efficiency of these D-A molecules in solution (≈100%). The twisted molecular structure and bulky alkyl chains effectively suppress π-π and dipole-dipole interactions, enabling high luminescence efficiency of 1 and 2 in the solid state (≈94% and 100%). Nafamostat concentration Furthermore, two D-A aggregates exhibit high photostability as evidenced by 4% and 8% of the fluorescence decreasing after 6 h of continuous irradiation in air, which is in sharp contrast to ≈95% of fluorescence decreasing in a reference compound. Importantly, with these molecules, ultrasensitive detection of sulfur mustard (SM) with a record limit of 10 ppb and selective detection of SM in complex matrices are achieved.Ischemia impacts multiple organ systems and is the major cause of morbidity and mortality in the developed world. Ischemia disrupts tissue homeostasis, driving cell death, and damages tissue structure integrity. Strategies to heal organs, like the infarcted heart, or to replace cells, as done in pancreatic islet β-cell transplantations, are often hindered by ischemic conditions. Here, it is discovered that the basement membrane glycoprotein nidogen-1 attenuates the apoptotic effect of hypoxia in cardiomyocytes and pancreatic β-cells via the αvβ3 integrin and beneficially modulates immune responses in vitro. It is shown that nidogen-1 significantly increases heart function and angiogenesis, while reducing fibrosis, in a mouse postmyocardial infarction model. These results demonstrate the protective and regenerative potential of nidogen-1 in ischemic conditions.Cellular senescence can either support or inhibit cancer progression. Here, it is shown that intratumoral infiltration of CD8+ T cells is negatively associated with the proportion of senescent tumor cells in colorectal cancer (CRC). Gene expression analysis reveals increased expression of C-X-C motif chemokine ligand 12 (CXCL12) and colony stimulating factor 1 (CSF1) in senescent tumor cells. Senescent tumor cells inhibit CD8+ T cell infiltration by secreting a high concentration of CXCL12, which induces a loss of CXCR4 in T cells that result in impaired directional migration. CSF1 from senescent tumor cells enhance monocyte differentiation into M2 macrophages, which inhibit CD8+ T cell activation. Neutralization of CXCL12/CSF1 increases the effect of anti-PD1 antibody in allograft tumors. Furthermore, inhibition of CXCL12 from senescent tumor cells enhances T cell infiltration and results in reducing the number and size of tumors in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC. These findings suggest senescent tumor cells generate a cytokine barrier protecting nonsenescent tumor cells from immune attack and provide a new target for overcoming the immunotherapy resistance of CRC.A metal-complex-modified graphitic carbon nitride (g-C3N4) bulk heterostructure is presented here as a promising alternative to high-cost noble metals as artificial photocatalysts. Theoretical and experimental studies of the spectral and physicochemical properties of three structurally similar molecules Fo-D, Pt-D, and Pt-P confirm that the Pt(II) acetylide group effectively expands the electron delocalization and adjusts the molecular orbital levels to form a relatively narrow bandgap. Using these molecules, the donor-acceptor assemblies Fo-D@CN, Pt-D@CN, and Pt-P@CN are formed with g-C3N4. Among these assemblies, the Pt(II) acetylide-based composite materials Pt-D@CN and Pt-P@CN with bulk heterojunction morphologies and extremely low Pt weight ratios of 0.19% and 0.24%, respectively, exhibit the fastest charge transfer and best light-harvesting efficiencies. Among the tested assemblies, 10 mg Pt-P@CN without any Pt metal additives exhibits a significantly improved photocatalytic H2 generation rate of 1.38 µmol h-1 under simulated sunlight irradiation (AM1.5G, filter), which is sixfold higher than that of the pristine g-C3N4.Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) often leads to aggressive local recurrence and increased metastasis, and vascular integrity and platelets are implicated in tumor metastasis. However, whether interactions between endothelial cells and platelets induce endothelial permeability in HCC after insufficient RFA remains unclear. Here, significantly increased CD62P-positive platelets and sP-selectin in plasma are observed in HCC patients after RFA, and tumor-associated endothelial cells (TAECs) activate platelets and are susceptible to permeability after heat treatment in the presence of platelets in vitro. In addition, tumors exhibit enhanced vascular permeability after insufficient RFA in mice; heat treatment promotes platelets-induced endothelial permeability through vascular endothelial (VE)-cadherin, and ICAM-1 upregulation in TAECs after heat treatment results in platelet activation and increased endothelial permeability in vitro. Moreover, the binding interaction between upregulated ICAM-1 and Ezrin downregulates VE-cadherin expression.