Enzyme-Activated Prodrug-Based Smart Liposomes Specifically Enhance Tumor Hemoperfusion with Efficient Drug Delivery to Pancreatic Cancer Cells and Stellate Cells

Tumor-specific enhanced delivery of chemotherapeutics and modulators to tumor cells and activated pancreatic stellate cells (aPSCs), respectively, represents safer and more effective therapy for pancreatic cancer. Herein, a membrane type 1-matrix metalloproteinase (MT1-MMP)-cleavable spacer is used to assemble low-density cRGDfK onto thermosensitive liposomes loaded with phosphorylated calcipotriol (PCAL) and doxorubicin (DOX), yielding MR-T-PD. The liposome-linked cRGDfK prodrug on MR-T-PD surface is first activated by MT1-MMP, which is selectively expressed on tumor endothelial cells, to release cRGDfK. The free cRGDfK specifically promotes tumor angiogenesis, leading to 3.4-fold higher accumulation and a wider distribution of MR-T-PD in tumors. Furthermore, MR-T-PD rapidly releases PCAL and DOX into the interstitium under heat treatment. The released DOX enters tumor cells to induce apoptosis, whereas the PCAL prodrug is converted to CAL by alkaline phosphatase on the surface of aPSCs; CAL can then enter aPSCs to induce quiescence and promote the antitumor effect of DOX. Finally, by enhancing the exposure of DOX and CAL to tumor cells and aPSCs, respectively, in a tumor-specific manner, MR-T-PD exerts superior efficacy (a 5.9-fold decrease in tumor weight) without causing additional side effects. Overall, this prodrug-based smart liposome system represents a promising paradigm for pancreatic cancer therapy.     

Nanocrystallization and optical properties of CsPbBr3−xIx perovskites in chalcogenide glasses

The confinement of CsPbX₃ (X = Cl, Br, and I) perovskite nanocrystals (NCs) in a stabilized inorganic glass matrix is a new strategy for improving their long-term stability and promoting their applications in the optoelectronic field. Here, in situ nanocrystallization strategy is developed to precipitate CsPbBr_3?xI_x NCs with arbitrary I/Br ratio among an elaborately designed GeS₂–Sb₂S₃-based chalcogenide glass matrix. Spherical CsPbBr_3?xI_x NCs are homogeneously distributed in the glass matrix after thermal treatment. The photoluminescence (PL) spectra show that the emission peaks of CsPbBr_3?xI_x NCs can be tuned from 570 nm to 722 nm with the replacement of Br by I. The fs transient absorption (TA) spectra reveal that there exists some structural defects in the NCs, leading to short PL decay life. This work would shed light on confining CsPbX₃ NCs into glassy matrices, facilitating their future applications in photoelectronic fields.     

Effects of Agaricus bisporus on gel properties of chicken myofibrillar protein

The gel-forming ability of myofibrillar protein (MP) is highly correlated with the characteristics of emulsified meat products. Incorporation of Agaricus bisporus (Ab) powder into MP gels may enhance its gel properties to facilitate the development of a novel and safe meat product. Therefore, this study investigated the effects of Ab powder on gel strength, water holding capacity (WHC), texture, rheological behaviour, LF-NMR spin–spin relaxation (T₂), microstructure and protein secondary structure of the MP gel system. The results indicated that the gel strength, WHC, G' value and G" value were significantly improved when the addition of Ab powder increased from 0% to 6% (P < 0.05). Meanwhile, the T₂ relaxation time was shortened, and free water was transformed into immobilised water. The texture of the gel was improved when 1%–4% Ab powder was added compared to the control. Furthermore, Ab filled in the gel network and promoted the unfolding of MP α-helix and the formation of MP β-sheet during the thermal denaturation of MP, leading to a dense aggregated network structure. The study suggested that Ab could be a promising ingredient in improving chicken MP's gel properties and developing fat-reduced meat products.     

Indoor solid fuel use for heating and cooking with blood pressure and hypertension: A cross-sectional study among middle-aged and older adults in China

A cross-sectional study was conducted to investigate the impact of solid fuel use for heating and cooking on blood pressure (BP) and hypertension, using data from the China Health and Retirement Longitudinal Study (CHARLS). The primary fuels used for indoor heating and cooking were collected by questionnaires, respectively. Hypertension was defined based on self-report of physician's diagnosis, and/or measured BP, and/or anti-hypertensive medication use. Multivariate logistic regression models were constructed to assess the associations. Among 10 450 eligible participants, 68.2% and 57.2% used indoor solid fuel for heating and cooking, respectively. Compared with none/clean fuel users, solid fuel for heating was associated with elevated BP (adjusted β: 2.02, 95% CI: 1.04–3.01 for systolic BP; adjusted β: 1.36, 95% CI: 0.78–1.94 for diastolic BP) and increased risk of hypertension (adjusted odds ratio: 1.15, 95% CI: 1.03–1.29). The impact of indoor solid fuel for heating on BP was more evident in rural and north residents, and hypertensive patients. We did not detect any significant associations between solid fuel use for cooking and BP/hypertension. Indoor solid fuel use is prevalent in China, especially in the rural areas. Its negative impact on BP suggested that modernization of household fuel use may help to reduce the burden of hypertension in China.     

Preparation and desalination performance of porous planar cordierite membranes using industrial solid waste as main silica source

Silica is a main component of cordierite ceramic, in the present work, industrial solid waste was used as main silica source to prepare porous planar cordierite membranes by a solid-phase sintering process with starch as pore-forming agent. It is shown that the concentration of starch plays a critical role in the pore structure and mechanical property and the cordierite membranes with a starch concentration of 40?wt% (M-40) have a desirable pore structure and flexural strength after sintering at 1300?°C for 5?h. After grafted with 1H,1H,2H,2H-perfluorooctyltriethoxysilane (FAS, C₈), the ceramic membranes were used for desalination by vacuum membrane distillation (VMD). The results show that the membranes(M-40) possess an average flux of 11.43?kg/m² h, a high salt rejection of 99.9% under the following operation conditions: a NaCl concentration of 3.5?wt%, a feed rate of 300?ml/min and a temperature of 80?°C. After desalination for 120?h, the water contact angle decreases to 130°. The cordierite membranes exhibit poor resistance to thermal acid/alkali solution(boiling, pH?=?1 and 14, respectively, soaked for 8?h) but excellent resistance to ambient temperature acid/alkali solution (25?°C, pH?=?1 and 14, respectively, soaked for 120?h).     

Synergy of Immunostimulatory Genetherapy with Immune Checkpoint Blockade Motivates Immune Response to Eliminate Cancer

Normalizing the tumor-induced immune deficiency in the immunosuppressive tumor microenvironment (TME) through increasing the efficient infiltration and activation of antitumoral immunity in TME is the core of promising immunotherapy. Herein, a Cyclo(Arg-Gly-Asp-d -Phe-Lys) (RGD) peptides-modified combinatorial immunotherapy system based on the self-assembly of the nanoparticles named RGD-DMA composed of RGD-PEG-PLA, methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) and 1,2-Dioleoyl-3-trimethylammonium-propane (DOTAP) is used to codeliver the immunostimulatory chemokine CCL19-encoding plasmid DNA (CCL19 pDNA) and immune checkpoint ligand PD-L1 inhibitor (BMS-1). The RGD-DMA/pCCL19-BMS-1 system not only exhibited significant inhibition of tumor progression but also induced locally high concentrations of immunostimulatory cytokines at tumor sites without causing an obviously systemic inflammatory response. The immunosuppressive TME is efficaciously reshaped by the coadministration of RGD-DMA/pCCL19 and BMS-1, as indicated by the activated T lymphocytes, increased intratumoral-infiltration of mature dendritic cells (DCs), and the repolarization of macrophages from pro-tumoral M2-phenotype toward tumoricidal M1-phenotype. The upregulated PD-L1 expression at tumor sites caused by the increased IFN-γ levels after immunostimulatory gene therapy further demonstrated the synergistic effects of BMS-1 in counteracting the inhibitory role of PD-L1 expression in antitumor immunity. Therefore, the combination of immunostimulating therapy and immune checkpoint inhibitor that synergistically target multiple immune regulatory pathways demonstrates significant potential as a novel immunotherapy approach.     

TiO2/MXene-Assisted LDI-MS for Urine Metabolic Profiling in Urinary Disease

Cancer remains an intractable medical problem. Rapid diagnosis and identification of cancer are critical to differentiate it from nonmalignant diseases. High-throughput biofluid metabolic analysis has potential for cancer diagnosis. Nevertheless, the present metabolite analysis method does not meet the demand for high-throughput screening of diseases. Herein, a high-throughput, cost-effective, and noninvasive urine metabolic profiling method based on TiO₂/MXene-assisted laser desorption/ionization mass spectrometry (LDI-MS) is presented for the efficient screening of bladder cancer (BC) and nonmalignant urinary disease. Combined with machine learning, TiO₂/MXene-assisted LDI-MS enables high diagnostic accuracy (96.8%) for the classification of patient groups (including 47 BC and 46 ureteral calculus (UC) patients) from healthy controls (113 cases). In addition, BC patients can also be identified from noncancerous UC individuals with an accuracy of 88.3% in the independent test cohort. Furthermore, metabolite variations between BC and UC individuals are investigated based on relative quantification, and related pathways are also discussed. These results suggest that this method, based on urine metabolic patterns, provides a potential tool for rapidly distinguishing urinary diseases and it may pave the way for precision medicine.     

Rayleigh-Type Wave in A Rotated Piezoelectric Crystal Imperfectly Bonded on a Dielectric Substrate

Propagation characteristics of Rayleigh-type wave in a piezoelectric layered system are theoretically investigated. The piezoelectric layer is considered as a cubic crystal with finite thickness rotated about Y-axis and is imperfectly bonded onto a semi-infinite dielectric substrate. The imperfect interface between the two constituents is assumed to be mechanically compliant and dielectrically weakly conducting. The exact dispersion relations for electrically open or shorted boundary conditions are obtained. The numerical results show that the phase velocity of Rayleigh-type wave is symmetric with respect to the cut orientation of 45。 and can achieve the maximum propagation speed in this orientation. The mechanical imperfection plays an important role in the dispersion relations, further the normal imperfection can produce a significant reduction of phase velocity comparing with the tangential imperfection. Comparing with the mechanical imperfection the electrical imperfection makes a relatively small reduction of phase velocity of Rayleigh-type wave. The obtained results can provide some fundamentals for understanding of piezoelectric semiconductor and for design and application of piezoelectric surface acoustic wave devices.