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Metabolic interactions between different cell types in the tumor microenvironment (TME) often result in reprogramming of the metabolism to be totally different from their normal physiological processes in order to support tumor growth. Many studies have attempted to inhibit tumor growth and activate tumor immunity by regulating the metabolism of tumors and other cells in TME. However, metabolic inhibitors often suffer from the heterogeneity of tumors, since the favorable metabolic regulation of malignant cells and other cells in TME is often inconsistent with each other. Therefore, we reported the design of a pH-sensitive drug delivery system that targets different cells in TME successively. Outer membrane vesicles (OMVs) derived from Gram-negative bacteria were applied to coload paclitaxel (PTX) and regulated in development and DNA damage response 1 (Redd1)-siRNA and regulate tumor metabolism microenvironment and suppress tumor growth. Our siRNA@M-/PTX-CA-OMVs could first release PTX triggered by the tumor pH (pH 6.8). Then the rest of it would be taken in by M2 macrophages to increase their level of glycolysis. Great potential was observed in TAM repolarization, tumor suppression, tumor immune activation, and TME remolding in the triple-negative breast cancer model. The application of the OMV provided an insight for establishing a codelivery platform for chemical drugs and genetic medicines.

As a rapid proliferating tissue, tumor cells have to optimize nutrient utilization to withstand harsh conditions. Several approaches have been explored to inhibit the growth and metastasis of tumor by disrupting the reprogrammed tumor metabolism. However, nutrient limitations within solid tumors may induce the metabolic flexibility of malignant cells to sustain growth and survival using one nutrient to fill metabolite pools normally supplied by the other. To overcome this predicament, a promising click-nucleic-acid-containing platform for codelivery of rapamycin, anti-PFKFB4 siRNA, and targeting ligand aptamer AS1411 was applied. PFKFB4 could act as a promising target for tumor therapy for being a molecular fulcrum that could couple glycolysis to autophagy by promoting aggressive metastatic tumors. The downregulation of PFKFB4 can help inhibit the SRC3/Akt/mTOR pathway, leading autophagy to the direction of promoting apoptosis of tumor cells, which is induced by the collapse of tumor cellular homeostasis, while low dosages of rapamycin could decrease surgery-induced immune dysfunction. Enhanced tumor autophagy, favorable in vivo antitumor efficacy, and effective systematic immune activation are observed after treatment, suggesting that autophagy and glycolysis can serve as an integrated target for tumor treatment.

Efficient removal of deadly toxicants by blood purification remains predominant in poisoning treatment. Current strategies mainly rely on absorptive scavengers that normally have no selectivity to the adsorbates, which could result poor clinical outcomes to certain toxic species due to the passivity and inaccuracy of the detoxification procedure. Herein, a positive, accurate, and customized detoxification strategy was proposed. Based on the sophisticated molecule design and thoughtful structure analysis of the aimed toxicant paraquat, a supramolecular hunter stationed on red blood cells (RBC) is developed to continuously track paraquat in the blood. In this construct, a Janus dendrimer amphiphile (JDA) molecule was synthesized with the aim of facilely anchoring onto RBC membranes while bridging to load the antidote WP6 that could precisely recognize paraquat. In vitroand in vivoresults demonstrate the effective toxicant-hunting and harm-neutralizing capability of the system through a guest-exchange reaction. This strategy provides a different insight in designing scavengers that can actively, precisely, and continuously hunt toxicants through a supramolecular approach.

Pancreatic ductal adenocarcinoma (PDAC) is considered as one of the most aggressive malignancies due to its unique microenvironment of which the cardinal histopathological feature is the remarkable desmoplasia of the stroma, taking up about 80% of the tumor mass. The desmoplastic stroma negatively affects drug diffusion and the infiltration of T cells, leading to an immunosuppressive microenvironment. However, this unique microenvironment can limit the physical spread of pancreatic cancer via a neighbor suppression effect. Here, a tumor central stroma targeting and microenvironment responsive strategy was applied to generate a nanoparticle coloading paclitaxel and phosphorylated gemcitabine. The designed nanoparticle disrupted the central stroma while preserving the external stroma, thereby promoting the antitumor effectiveness of chemotherapeutics. Additionally, the resulting nanoparticle can modulate the tumor immunosuppressive microenvironment by augmenting the number of cytotoxic T cells and restraining the percentage of T regulatory cells. The relatively intact external stroma can effectively maintain the neighbor suppression effect and prevent tumor metastasis. Combining stroma targeting with the delivery of stimuli-responsive polymeric nanoparticles embodies an effective tumor-tailored drug delivery system.

To meet the growing demand of β-cyclodextrin (CD), innovative approaches are being developed to improve the production of β-CD by β-cyclodextrin glucose-transferase (CGTase). Considering the low production and efficacy of wild-type β-CGTase-producing strains, to obtain the strains suitable for industrial production of β-CGTase, the recombinant engineered bacteria strain DF257 is constructed by transfecting with the plasmid expressing His tagged β-CGTase. The fermentation of β-CGTase-expressing DF257 was optimized in the presence of different metal ions, amino acids, and incubated at a certain temperature and pH condition. The results showed that when Mg2+and isoleucine were added into the culture medium at 0.5 mM and 0.5 g/L, respectively, the enzyme activity of β-CGTase increased significantly after incubation at 37 °C with the initial pH of 7.5. In addition, the optimal temperature for β-CGTase with the addition of Mg2+and isoleucine was also determined. The T half of β-CGTase under 50, 55, 60 and 65 °C was 9.5, 8.8, 6.2 and 1.2 h, respectively. Further investigation showed that β-CGTase kept stable under the pH 6.0–10.0, and pH 7.5 was identified as the optimal pH condition of β-CGTase. With the addition of Mg2+and isoleucine, the kinetic properties of β-CGTase in the cyclization reaction had a similar form with Michaelis equation under 50 °C and pH 7.5, and Vmax, Km, and Kcat was 3.74 mg/mL/min, 3.28 mg/mL, and 31.17/s, respectively. The possible underlying mechanism by which Mg2+and isoleucine synergistically improved the thermostability of β-CGTase was investigated by the surface hydrophobicity index analysis, Fourier transform infrared spectroscopy and differential scanning calorimetry (DSC) analysis. The results indicated that addition of Mg2+and isoleucine maintained the spatial structure and enhanced the thermostability of β-CGTase. These findings provided a theoretical basis for realizing the industrialization application of β-CGTase in promoting the generation of β-CD.

The cyclodextrin glycosyltransferase (CGTase) was used to catalyze the conversion of starch into cyclodextrins (CD) in industry. Improving the activity of CGTase to produce more CD with relative low cost is intensely interesting and has drawn wide attention. Amino acid mutation of His167 into Cys significantly enhanced β-CGTase activity; however, optimization of culture conditions for β-CGTase-H167C remains unclear. To determine this, the medium and culture conditions for β-CGTase-H167C were optimized with response surface methodology. Maximum activity of β-CGTase-H167C was obtained with the medium containing 1.1% corn starch, 4.4% corn steep liquor, 1.1% peptone, 0.02% MgSO4·7H2O and 0.1% K2HPO4·3H2O that were cultured with the initial pH 8.4, incubation temperature at 37.4 °C, with 5% inoculation size and shaking speed at 202 r/min. Under the optimal conditions, the activity of β-CGTase-H167C was up to 4355 U/mL, which is 1.93-fold in comparison with the initial activity. Our results established the promising culture strategy for the production of cyclodextrins by β-CGTase-H167C.

How to improve our episodic memory is an important issue in the field of memory. In the present study, we used a discriminative learning paradigm that was similar to a paradigm used in animal studies. In Experiment 1, a picture (e.g., a dog) was either paired with an identical picture, with a similar picture of the same concept (e.g., another dog), or with a picture of a different concept (e.g., a cat). Then, after intervals of 10 min, 1 d, and 1 wk, participants were asked to perform a 2-alternative forced-choice (2AFC) task to discriminate between a repeated and a similar picture, followed by the contextual judgment. In Experiment 2, eye movements were measured when participants encoded the pairs of pictures. The results showed that by discriminative learning, there was better memory performance in the 2AFC task for the “same” and “similar” conditions than for the “different” condition. In addition, there was better contextual memory performance for the “similar” condition than for the other two conditions. With regard to the eye movements, the participants were more likely to fixate on the lure objects and made more saccades between the target and lure objects in the “similar” (versus “different”) condition. The number of saccades predicted how well the targets were remembered in both the 2AFC and contextual memory tasks. These results suggested that with discriminative learning of similar objects, detailed information could be better encoded by distinguishing the object from similar interferences, making the details and the contexts better remembered and retained over time.

β-Cyclodextrin glycosyltransferase (β-CGTase) belongs to the α-amylase family of enzymes and converts starch to cyclic oligosaccharides called β-cyclodextrins (β-CD). The β-CGTase from alkalophilic Bacillussp. N-227was separately mutagenized to give three site-directed β-CGTase mutants, Y127F, R254F and D355R, that showed enhanced cyclization activity towards a starch substrate from 1.64 to 2.1-folds. Kinetic studies indicate that the mutants had higher affinity towards the substrate than the wild type β-CGTase. The Y127F mutant had the highest affinity which was indicated by the lowest Kmof 15.30 mM and the highest catalytic activity. Increasing hydrophobicity around the catalytic center appeared to favor the cyclization activity of the mutants. The β-CGTase and the three mutants showed optimal enzyme activity at 60 °C and pH 6.0. All the enzymes were stable for at least 60 min across a wide pH range (5.0–7.0).

The catalytic oxidation performance toward ethylene oxide (EO) and the consequent mechanism were investigated on the Pt-Ru/CuCeOxbimetallic catalyst, which was prepared by a distinct method combining stepwise adsorption and subsequent impregnation. The catalytic tests show that the introduction of Ru into the Pt catalyst, so as to form Pt-Ru bimetallic active sites, can greatly increase the oxidation activity of the catalyst, as evidenced by the extremely lower full oxidation temperature (120 °C) when compared with that of the Pt/CeO2catalyst (160 °C). The XPS spectra show that the Ru species (mainly RuOx) have strong interaction with the CuCeOxsupport, which can therefore affect the electron transfer between the Pt species and the support. As a result, the oxygen activation on Pt species is obviously facilitated and catalytic activity is enhanced. Finally, in situdiffuse reflectance infrared Fourier transform spectroscopy (DRIFTs) was used to track the reaction mechanism. It is found that the catalytic oxidation process follows the MvK catalytic mechanism at low temperature and the L-H catalytic mechanism when the temperature moves to higher range.

Are associative memories forgotten more quickly than item memories, and does the level of original learning differentially influence forgetting rates? In this study, we addressed these questions by having participants learn single words and word pairs once (Experiment 1), three times (Experiment 2), and six times (Experiment 3) in a massed learning (ML) or a distributed learning (DL) mode. Then they were tested for item and associative recognition separately after four retention intervals: 10 min, 1 d, 1 wk, and 1 mo. The contribution of recollection and familiarity processes were assessed by participants’ remember/know judgments. The results showed that for both item and associative memories, across different degrees of learning, recollection decreased significantly and was the main source of forgetting over time, whereas familiarity remained relatively stable over time. Learning multiple times led to slower forgetting at shorter intervals, depending on recollection and familiarity processes. Compared with massed learning, distributed learning (six times) especially benefited associative memory by increasing recollection, leading to slower forgetting at longer intervals. This study highlighted the importance of process contribution and learning experiences in modulating the forgetting rates of item and associative memories. We interpret these results within the framework of a dual factor representational model of forgetting (as noted in a previous study) in which recollection is more prone to decay over time than familiarity.

The rapid postoperative recurrence and short survival time of glioblastoma (GBM) patients necessitate immediate and effective postoperative treatment. Herein, an immediate and mild postoperative local treatment strategy is developed that regulates the postoperative microenvironment and delays GBM recurrence. Briefly, an injectable hydrogel system (imGEL) loaded with Zn(II)2‐AMD3100 (AMD‐Zn) and CpG oligonucleotide nanoparticles (CpG NPs) is injected into the operation cavity, with long‐term function to block the recruitment of microglia/ macrophages and activate cytotoxic T cells. The finding indicated that the imGEL can regulate the immune microenvironment, inhibit GBM recurrence, and gain valuable time for subsequent adjuvant clinical chemotherapy. Based on the current clinical dilemma of glioblastoma, this study describes a simple and mild postoperative local treatment strategy with clinical transformation prospects. Specifically, it is an injectable hydrogel system with the function of regulating the immune post‐operative micro‐environment to kill the residual tumor cells in the empty window period, which has gained valuable time for subsequent adjuvant treatment.