Current programmed death‐1 ligand (PD‐L1)‐based therapy focuses on local tumors. However, circulating exosomal PD‐L1 possesses inherent anti‐PD‐L1 blockade resistance and dominates tumor metastasis, ...playing a critical role in systemic immunosuppression. Therefore, the efficacy of immune checkpoint therapy depends on simultaneously decreasing tumoral and circulating exosomal PD‐L1. However, such therapeutic platforms have never been reported so far. Herein, a PD‐L1 checkpoint‐regulatable immune niche created by an injectable hydrogel is reported to reprogram PD‐L1 of both tumor and circulating exosomes. Oxidized sodium alginate‐armored tumor membrane vesicle (O‐TMV) as a gelator, with Ca2+ channel inhibitor dimethyl amiloride (DMA) and cyclin‐dependent kinase 5 (Cdk5) inhibitor roscovitine formed hydrogel (O‐TMV@DR) in vivo, work as an antigen depot to create an immune niche. O‐TMV chelates Ca2+ within the tumor environment and DMA continuously prevents cellular Ca2+ influx, suppressing Ca2+‐governed exosome secretion with decreased exosome number. Roscovitine not only down‐regulates tumor cell PD‐L1 expression along with decreasing exosomal PD‐L1 expression inherited from parental tumor cells via a genetic blockade effect, but also blunts the cascade connection between PD‐L1 up‐regulation and interferon‐γ stimulation, achieving down‐regulated PD‐L1 expression in both tumor cells and exosomes. Therefore, a full‐scale reprogramming of both tumoral PD‐L1 and exosomal PD‐L1 is achieved, offering an innovative immune checkpoint‐regulatable cancer immunotherapy
A checkpoint‐regulatable immune niche created by a newly designed tumor membrane vesicle‐based injectable hydrogel demonstrates potent ability for simultaneously reprogramming tumoral programmed death‐1 ligand (PD‐L1) and exosomal PD‐L1, enabling powerful inhibition of tumor metastasis as well as inducing strong immunological memory via disrupting PD‐L1‐based immunosuppression. This study opens up a conceptually innovative avenue for PD‐L1‐based immune checkpoint therapy.
Morphology‐ and composition‐controlled synthesis of Au–Pd bimetallic particles was realized by a facile ionic liquid assisted route at room temperature. The morphologies of the synthesized particles, ...such as nanoflake‐constructed spheres with a core–shell structure, nanoparticle‐constructed spheres, and nanoparticle‐constructed dendrites, could be well controlled by the present route. The ionic liquid was found to play a key role in the formation of these interesting particles. Moreover, the composition (Au:Pd) of the particles could be modulated by means of the molar ratio of the metal precursors in the feeding solutions. The Au–Pd bimetallic particles exhibit high electrocatalytic activity toward oxidation of ethanol and formic acid. Furthermore, cyclic voltammetric studies on the as‐prepared Au–Pd bimetallic particles revealed good electroactivity for H2O2, which results in an effective amperometric H2O2 sensor.
Nanoflake‐constructed spheres with core–shell structure (see figure), nanoparticle‐constructed spheres, and nanoparticle‐constructed dendrites were obtained by a facile, ionic liquid assisted route for the morphology‐ and composition‐controlled synthesis of Au–Pd bimetallic particles that exhibit high electrocatalytic activity toward oxidation of ethanol and formic acid.
Hierarchically structured one-dimensional (1D) MoO2 is synthesized for the first time in ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (BMIMTf2N). The synthesis ...system is very simple (single BMIMTf2N solvent plus MoO2(acac)2 reactant). BMIMTf2N itself works as both the reaction medium and the template for the formation of these interesting 1D MoO2 particles with ultrathin nanosheet subunits. The as-synthesized hierarchically 1D MoO2_40 particles exhibit remarkable electrocatalytic activity with good long-term cycle stability for the hydrogen evolution reaction (HER) in acidic media. The HER activity of present synthesized MoO2 is comparable to those of the most active Mo-based electrocatalysts in acid media reported up to now. Therefore, the ionic liquid route provides us with a newly powerful tool for the synthesis of interesting alternative to noble metal catalysts for efficient electrocatalytic production of hydrogen in acidic environment.
Efficient conversion of glucose and cellulose to 5-hydroxymethylfurfural (HMF) is one of the most successful and promising routes in the field of biomass transformation. In recent years, many kinds ...of catalysts have been developed for this important reaction, and much progress has been achieved. Compared with homogeneous catalysts, heterogeneous acidic catalysts have attracted much more interest for dehydration of glucose and cellulose to HMF due to their separable and reusable nature. This review focuses on efficient and selective conversion of glucose and cellulose to HMF catalyzed by heterogeneous catalysts in various solvent systems, including water, organic solvents, ionic liquids, mixed solvents, and biphasic systems. At the end of this review, an outlook is provided to highlight the challenges and opportunities related to this interesting and important route for HMF production from glucose and cellulose.
This review provides a holistic overview of the developed heterogeneous catalysts for HMF production from dehydration of glucose and cellulose in various solvent systems.
Hyperlipidemia-associated lipid disorders are considered the cause of atherosclerotic cardiovascular disease. Reverse cholesterol transport (RCT) is a mechanism by which excess peripheral cholesterol ...is transported to the liver and further converted into bile acid for excretion from the body in feces, which contributes to reducing hyperlipidemia as well as cardiovascular disease. We previously found that the recombinant humanized IgG1 antibody promotes macrophages to engulf lipids and increases cholesterol efflux to high-density lipoprotein (HDL) through ATP-binding cassette sub-family A1 (ABCA1), one of the key proteins related to RCT. In the present study, we explored other RCT related proteins expression on hepatocytes, including scavenger receptor class B type I (SR-BI), apolipoprotein A-I (ApoA-I), and apolipoprotein A-II (ApoA-II), and its modulation mechanism involved. We confirmed that the recombinant humanized IgG1 antibody selectively activated ERK1/2 to upregulate SR-BI, ApoA-I, and ApoA-II expression in mice liver and human hepatocellular carcinoma cell lines HepG2 cells. The rate-limiting enzymes of bile acid synthesis, including cholesterol 7α-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1), exhibited a significant increase when treated with the recombinant humanized IgG1 antibody, as well as increased excretion of bile acids in feces. Besides, abolishment or mutation of peroxisome proliferator-activated receptor α (PPARα)/RXR binding site on SR-BI promoter eliminated SR-BI reporter gene luciferase activity even in the presence of the recombinant humanized IgG1 antibody. Knock down the neonatal Fc receptor (FcRn) on hepatocytes impaired the effect of recombinant humanized IgG1 antibody on activation of ERK1/2, as well as upregulation of SR-BI, ApoA-I, and ApoA-II expression. In conclusion, one of the mechanisms on the recombinant humanized IgG1 antibody attenuates hyperlipidemia in ApoE
mice model fed with high-fat-diet might be through reinforcement of liver RCT function in an FcRn-ERK1/2-PPARα dependent manner.
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•The micelles showed sustained, reduction sensitive and programmed release profile.•The micelles could completely restrain the efflux activity of p-gp and reverse MDR.•The micelles ...prolonged the in vivo circulation and enhanced the drug accumulation.
The clinical usage of docetaxel (DTX) has been blocked in the clinic because of its poor solubility and tumour multi-drug resistance (MDR). The dominating mechanism of MDR is the over-expression of p-gp on tumour cells. Traditional nano-medicines, such as nanoparticles and micelles, have been used to physically entrap DTX to improve their solubility, while the drug loading content was very low and the tumour resistance was neglected. In this study, the synthesized reduction-sensitive mPEG-PLGA-SS-DTX conjugate was utilized to load the p-gp inhibitor veraparmil (VRP) to prepare DTX and VRP co-delivered mPEG-PLGA-SS-DTX/VRP (PP-SS-DTX/VRP) multi-functional micelles to reverse MDR and enhance the anti-tumour effect of DTX. The micelles had a high drug loading content and showed an obvious reduction-sensitive release property for both DTX and VRP. In addition, an in vitro anti-tumour assay revealed that the micelles markedly inhibited the efflux activity of p-gp and accelerated cell apoptosis, resulting in the improvement of anti-tumour activity and reversal of MDR. The PP-SS-DTX micelles markedly enhanced the in vivo circulation time and increased the drug accumulation in tumour tissues. Therefore, the PP-SS-DTX/VRP micelle is a desirable drug delivery system for multi-drug resistance therapy of DTX and is very promising for clinical usage.
Oxidized low-density lipoprotein (oxLDL)-induced oxidative stress and apoptosis are considered as critical contributors to cardiovascular diseases. Methionine sulfoxide reductase A (MSRA) is a potent ...intracellular oxidoreductase and serves as an essential factor that protects cells against oxidative damage. Here, we firstly provide evidence that recombinant humanized IgG1 antibody treatment upregulated the expression of MSRA in THP-1 cells to defend against oxLDL-induced oxidative stress and apoptosis. It was also observed that the upregulation of MSRA is regulated by the forkhead box O transcription factor (FOXO1), and the acetylation of FOXO1 increased when exposed to oxLDL but declined when treated with recombinant humanized IgG1 antibody. In addition, we identified that silent information regulator 1 (SIRT1) suppresses FOXO1 acetylation. Importantly, SIRT1 or FOXO1 deficiency impaired the anti-oxidative stress and anti-apoptotic effect of recombinant humanized IgG1 antibody. Together, our results suggest that recombinant humanized IgG1 antibody exerts its anti-oxidative stress and anti-apoptotic function by upregulation of MSRA via the Sirt1-FOXO1 axis.
Although there have been a lot of studies on landslides in geologic hazards in China, the study on tuff landslides in southeast coastal areas is relatively lack. In view of this, based on the ...landslide of Xiageliao Mountain in Jinshui Village, Zhenbu Township, Qingtian County, by using automatic monitoring technology and analyzing the monitoring data of landslide deformation and rainfall, the deformation law and influencing factors of tuff landslide are discussed, which provides a basis for landslide stability analysis and landslide geologic hazards warning. The results show that: (1) tuff belongs to volcanic ash composition, with physical properties such as unstable mineral composition, high porosity and permeability, and easy fracture of thin layers, resulting in its strength and stability varying with water content. (2) The sliding deformation is mainly concentrated in the parts below the “primary and secondary platforms” (Zone I); The deformation of parts above “Level 1 and Level 2 platforms” (Zone II) is relatively small; There is basically no deformation in the trailing edge crack area (Zone III). (3) The overall annual movement speed of Xiageliao landslide is 10–15 cm/a. Affected by continuous rainfall or heavy rainstorm, the deformation curves of division I and II show a stepped evolution feature, that is, obvious growth occurs first, then gradually returns to stability, and the overall deformation is slow. (4) The total deformation amount is positively correlated with the sum of rainfall 15 days before the initiation of accelerated deformation and during accelerated deformation; the duration of deformation is positively correlated with the rainfall 10 days before the accelerated deformation stops.
A substrate with microstructure can increase the light extraction efficiency of OLEDs. However, the present preparation methods for micro- and nanostructures are not suited for broad-area ...manufacturing. In this research, we suggested an electrochemical etching approach to patterning Si substrates and effectively generated a vast area of micro-/nanostructures on the surface of Si. We created OLEDs using this patterned substrate. It was discovered through this study that when the current density is 100 mA/cm
, the brightness increases by 1.67 times and the efficiency increases by 1.43 times, over a planar equivalent. In the future, this electrochemical etching process for patterned silicon substrates might give rise to a new approach to the large-scale manufacture of microstructured silicon substrates.
The extracellular matrix (ECM) within the brain possesses a distinctive composition and functionality, influencing a spectrum of physiological and pathological states. Among its constituents, ...perineuronal nets (PNNs) are unique ECM structures that wrap around the cell body of many neurons and extend along their dendrites within the central nervous system (CNS). PNNs are pivotal regulators of plasticity in CNS, both during development and adulthood stages. Characterized by their condensed glycosaminoglycan-rich structures and heterogeneous molecular composition, PNNs not only offer neuroprotection but also participate in signal transduction, orchestrating neuronal activity and plasticity. Interfering with the PNNs in adult animals induces the reactivation of critical period plasticity, permitting modifications in neuronal connections and promoting the recovery of neuroplasticity following spinal cord damage. Interestingly, in the adult brain, PNN expression is dynamic, potentially modulating plasticity-associated states. Given their multifaceted roles, PNNs have emerged as regulators in the domains of learning, memory, addiction behaviors, and other neuropsychiatric disorders. In this review, we aimed to address how PNNs contribute to the memory processes in physiological and pathological conditions.
