The considerable performance enhancement of small molecule‐sieving nanofiltration membrane has been achieved by the functional combination between host–guest chemistry and interfacial polymerization ...(IP) for the first time in this work. First, the water‐insolubility of cucurbit6uril (CB6) was ameliorated by constructing host–guest complex (CB6‐PIP) with piperazine. Second, the incorporation of water‐soluble CB6‐PIP in the selective layer via IP leads to the generation of not only the enlarged conventional polyamide network tunnels but also rotaxane tunnels. Such enrichment of solvent transport tunnels contributes to an amazing pure water permeability of 15.5–25.4 Lm−2bar−1h−1, three times higher than that of traditional polyamide membranes, with a high R/MgSO4 of 99.5–92.5%, perfect SO42−/Cl− selectivity due to the electronegative contribution of CB6, as well as untapped potential in organic solvent nanofiltration. This work not only provides a fire‐new strategy to design new type of NF materials but also promotes the application of CBs in many other fields.
Sufficient pore size, appropriate stability, and hierarchical porosity are three prerequisites for open frameworks designed for drug delivery, enzyme immobilization, and catalysis involving large ...molecules. Herein, we report a powerful and general strategy, linker thermolysis, to construct ultrastable hierarchically porous metal–organic frameworks (HP-MOFs) with tunable pore size distribution. Linker instability, usually an undesirable trait of MOFs, was exploited to create mesopores by generating crystal defects throughout a microporous MOF crystal via thermolysis. The crystallinity and stability of HP-MOFs remain after thermolabile linkers are selectively removed from multivariate metal–organic frameworks (MTV-MOFs) through a decarboxylation process. A domain-based linker spatial distribution was found to be critical for creating hierarchical pores inside MTV-MOFs. Furthermore, linker thermolysis promotes the formation of ultrasmall metal oxide nanoparticles immobilized in an open framework that exhibits high catalytic activity for Lewis acid-catalyzed reactions. Most importantly, this work provides fresh insights into the connection between linker apportionment and vacancy distribution, which may shed light on probing the disordered linker apportionment in multivariate systems, a long-standing challenge in the study of MTV-MOFs.
Nowadays, drug resistance still represents a major obstacle to successful acute myeloid leukemia (AML) treatment and the underlying mechanism is not fully elucidated. Here, we found that high ...expression of c-Myc was one of the cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc over-expression in leukemic cells induced resistance to chemotherapeutic drugs, enhanced colony formation capacity and inhibited cell differentiation induced by all-trans retinoic acid (ATRA). Meanwhile, inhibition of c-Myc by shRNA or specific c-Myc inhibitor 10058-F4 rescued the sensitivity to cytotoxic drugs, restrained the colony formation ability and promoted differentiation. RT-PCR and western blotting analysis showed that down-regulation of C/EBPβ contributed to the poor differentiation state of leukemic cells induced by c-Myc over-expression. Importantly, over-expression of C/EBPβ could reverse c-Myc induced drug resistance. In primary AML cells, the c-Myc expression was negatively correlated with C/EBPβ. 10058-F4, displayed anti-proliferative activity and increased cellular differentiation with up-regulation of C/EBPβ in primary AML cells. Thus, our study indicated that c-Myc could be a novel target to overcome drug resistance, providing a new approach in AML therapy.
Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of ...Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high correlation with these proteins, indicating that the PI3K‐AKT signaling pathway might play a key role in GC. From these studies, we selected human epidermal growth factor receptor 2 (HER2) and programmed cell death 1‐ligand 1 (PD‐L1) for docking; the results showed that 385 and 189 compounds had high docking scores with HER2 and PD‐L1, respectively. Six compounds were selected for microscale thermophoresis (MST). Daidzein/quercetin and isorhamnetin/formononetin had the highest binding affinity for HER2 and PD‐L1, with Kd values of 3.7 μmol/L and 490, 667, and 355 nmol/L, respectively. Molecular dynamics simulation studies based on the docking complex structures as the initial conformation yielded the binding free energy between daidzein/quercetin with HER2 and isorhamnetin/formononetin with PD‐L1, calculated by molecular mechanics Poisson‐Boltzmann surface area, of −26.55, −14.18, −19.41, and −11.86 kcal/mol, respectively, and were consistent with the MST results. In vitro experiments showed that quercetin, daidzein, and isorhamnetin had potential antiproliferative effects in MKN‐45 cells. Enzyme activity assays showed that quercetin could inhibit the activity of HER2 with an IC50 of 570.07 nmol/L. Our study provides a systematic investigation to explain the material basis and molecular mechanism of traditional Chinese medicine in treating diseases.
We are committed to establishing a systematic research method based on network pharmacology, multitarget molecular docking, molecular dynamics simulation, and protein and experimental verification in vitro and in vivo, to establish a systematic analysis method for traditional Chinese medicine (TCM) treatment of diseases. We aim to provide a possible theoretical and experimental basis for the standardization and internationalization of TCM.
At high levels, copper in grape mash can inhibit yeast activity and cause stuck fermentations. Wine yeast has limited tolerance of copper and can reduce copper levels in wine during fermentation. ...This study aimed to understand copper tolerance of wine yeast and establish the mechanism by which yeast decreases copper in the must during fermentation. Three strains of Saccharomyces cerevisiae (lab selected strain BH8 and industrial strains AWRI R2 and Freddo) and a simple model fermentation system containing 0 to 1.50 mM Cu2+ were used. ICP-AES determined Cu ion concentration in the must decreasing differently by strains and initial copper levels during fermentation. Fermentation performance was heavily inhibited under copper stress, paralleled a decrease in viable cell numbers. Strain BH8 showed higher copper-tolerance than strain AWRI R2 and higher adsorption than Freddo. Yeast cell surface depression and intracellular structure deformation after copper treatment were observed by scanning electron microscopy and transmission electron microscopy; electronic differential system detected higher surface Cu and no intracellular Cu on 1.50 mM copper treated yeast cells. It is most probably that surface adsorption dominated the biosorption process of Cu2+ for strain BH8, with saturation being accomplished in 24 h. This study demonstrated that Saccharomyces cerevisiae strain BH8 has good tolerance and adsorption of Cu, and reduces Cu2+ concentrations during fermentation in simple model system mainly through surface adsorption. The results indicate that the strain selected from China's stress-tolerant wine grape is copper tolerant and can reduce copper in must when fermenting in a copper rich simple model system, and provided information for studies on mechanisms of heavy metal stress.
Abnormal tumor metabolism causes the hypoxic microenvironment, which greatly limits the efficacy of photodynamic therapy (PDT). In this work, a strategy of metabolic reprogramming is proposed to ...economize O2 for enhanced PDT against hypoxic tumors. The carrier‐free O2‐economizer (designated as LonCe) is prepared based on the metabolic antitumor drug of Lonidamine (Lon) and the photosensitizer of chlorin e6 (Ce6). By virtue of intermolecular interactions, Lon and Ce6 self‐assemble into nanosized LonCe with favorable stability and high drug contents. Compared with Ce6, LonCe exhibits an improved cellular uptake and photodynamic property for tumor treatment. Moreover, LonCe is capable of inhibiting cell metabolism and mitochondrial respiration to remit the tumor hypoxia, which would promote reactive oxygen species (ROS) production and elevate the PDT efficacy on tumor suppression. In vivo experiments indicate that intravenously injected LonCe prefers to accumulate at the tumor site for highly efficient PDT regardless of the hypoxic environment. Besides, the self‐delivery LonCe is fabricated without any carriers, which avoids the excipients induced system toxicity and immunogenicity in vivo. This carrier‐free nanomedicine with cell respiratory inhibition mechanism would expedite the development and clinical translation of photodynamic nanoplatforms in tumor treatment.
A carrier‐free O2‐economizer (designated as LonCe) is developed based on the metabolic drug Lonidamine (Lon) and photosensitizer chlorin e6 (Ce6), which can interrupt cell metabolism and depress mitochondrial respiration to remit the tumor hypoxia. Experiments show that LonCe will greatly improve the antitumor effect by O2‐economized photodynamic therapy regardless of the hypoxic microenvironment.
Stretchable electrochemical sensors are conceivably a powerful technique that provides important chemical information to unravel elastic and curvilinear living body. However, no breakthrough was made ...in stretchable electrochemical device for biological detection. Herein, we synthesized Au nanotubes (NTs) with large aspect ratio to construct an effective stretchable electrochemical sensor. Interlacing network of Au NTs endows the sensor with desirable stability against mechanical deformation, and Au nanostructure provides excellent electrochemical performance and biocompatibility. This allows for the first time, real‐time electrochemical monitoring of mechanically sensitive cells on the sensor both in their stretching‐free and stretching states as well as sensing of the inner lining of blood vessels. The results demonstrate the great potential of this sensor in electrochemical detection of living body, opening a new window for stretchable electrochemical sensor in biological exploration.
Biomedical sensor: A highly controllable strategy has been developed for synthesizing Au nanotubes with a large aspect ratio. The nanotubes were used to construct an effective stretchable electrochemical sensor and to realize real‐time monitoring of mechanically sensitive cells and tissues.
The bacterial infections have always a serious problem to public health. Scientists are developing new antibacterial materials to overcome this problem. Polysaccharides are promising biopolymers due ...to their diverse biological functions, low toxicity, and high biodegradability. Chitin and chitosan have antibacterial properties due to their cationic nature, while cellulose/bacterial cellulose does not possess any antibacterial activity. Moreover, the insolubility of chitin in common solvents, the poor solubility of chitosan in water, and the low mechanical properties of chitosan have restricted their biomedical applications. In order to solve these problems, chemical modifications such as quaternization, carboxymethylation, cationization, or surface modification of these polymers with different antimicrobial agents, including metal and metal oxide nanoparticles, are carried out to obtain new materials with improved physiochemical and biological properties. This mini review describes the recent progress in such derivatives and composites with potential antibacterial applications.
Design and synthesis of high-efficiency and low-cost photocatalysts is essential for converting solar energy into clean hydrogen energy. Herein, we report a novel TiO2 nanocrystal photocatalyst ...confined by ZIF-67-templated porous CoSx, with conductive Ti3C2 boosting the transport efficiency of the charge carriers. TiO2–CoSx and TiO2–Ti3C2–CoSx exhibit a photocatalytic H2-production activity 2.8 and 5.8 times larger than that of pristine TiO2, respectively, because of the existence of the highly porous MOF-templated CoSx hydrogen evolution reaction cocatalyst and highly conductive Ti3C2. This study will provide a practical reference for the design and preparation of efficient photocatalysts with high transport and utilization efficiency of charge carriers.
Adopting self‐healing, robust, and stretchable materials is a promising method to enable next‐generation wearable electronic devices, touch screens, and soft robotics. Both elasticity and ...self‐healing are important qualities for substrate materials as they comprise the majority of device components. However, most autonomous self‐healing materials reported to date have poor elastic properties, i.e., they possess only modest mechanical strength and recoverability. Here, a substrate material designed is reported based on a combination of dynamic metal‐coordinated bonds (β‐diketone–europium interaction) and hydrogen bonds together in a multiphase separated network. Importantly, this material is able to undergo self‐healing and exhibits excellent elasticity. The polymer network forms a microphase‐separated structure and exhibits a high stress at break (≈1.8 MPa) and high fracture strain (≈900%). Additionally, it is observed that the substrate can achieve up to 98% self‐healing efficiency after 48 h at 25 °C, without the need of any external stimuli. A stretchable and self‐healable dielectric layer is fabricated with a dual‐dynamic bonding polymer system and self‐healable conductive layers are created using polymer as a matrix for a silver composite. These materials are employed to prepare capacitive sensors to demonstrate a stretchable and self‐healable touch pad.
Dynamic metal‐coordinated bonds (β‐diketone–europium interaction) and hydrogen bonds, are combined in a multiphase separated network, in a new strategy to enable a robust and elastic capacitive sensor with autonomous self‐healing properties.
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