Promising natural products targeting protein tyrosine phosphatase SHP2 for cancer therapy.

The development of Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) inhibitors is a hot spot in the research and development of antitumor drugs, which may induce immunomodulatory effects in the tumor microenvironment and participate in anti-tumor immune responses. To date, several SHP2 inhibitors have made remarkable progress and entered clinical trials for the treatment of patients with advanced solid tumors. Multiple compounds derived from natural products have been proved to influence tumor cell proliferation, apoptosis, migration and other cellular functions, modulate cell cycle and immune cell activation by regulating the function of SHP2 and its mutants. However, there is a paucity of information about their diversity, biochemistry, and therapeutic potential of targeting SHP2 in tumors. This review will provide the structure, classification, inhibitory activities, experimental models, and antitumor effects of the natural products. Notably, this review summarizes recent advance in the efficacy and pharmacological mechanism of natural products targeting SHP2 in inhibiting the various signaling pathways that regulate different cancers and thus pave the way for further development of anticancer drugs targeting SHP2.

Fast kinetics of monoclinic VO2(B) bulk upon magnesiation via DFT+U calculations.

Although magnesium rechargeable batteries (MRBs) have gained considerable attention, research relating to MRBs is still in its infancy. One issue is that magnesium ions are difficult to reversibly (de)intercalate in most electrode materials. Among various available cathodes, VO2(B) is a promising layered cathode material for use in MRBs. Totally different from monolayer VO2, the magnesiation mechanism in monoclinic bulk VO2(B) has not been clearly clarified to this day. For the first time, we systematically investigated the influence of magnetism and van der Waals (vdW) forces on the electronic structure and diffusion kinetics of magnesium in bulk VO2(B) using a series of DFT+U calculations. The Mg diffusivity can reach a high value of 1.62 × 10-7 cm2 s-1 at 300 K, which is comparable to Li+. These results demonstrate that VO2(B) is a potential host material with high mobility and fast kinetics.

A review of nuclear Dbf2-related kinase 1 (NDR1) protein interaction as promising new target for cancer therapy.

Nuclear Dbf2-related kinase 1 (NDR1) is a nuclear Dbf2-related (NDR) protein kinase family member, which regulates cell functions and participates in cell proliferation and differentiation through kinase activity. NDR1 regulates physiological functions by interacting with different proteins. Protein-protein interactions (PPIs) are crucial for regulating biological processes and controlling cell fate, and as a result, it is beneficial to study the actions of PPIs to elucidate the pathological mechanism of diseases. The previous studies also show that the expression of NDR1 is deregulated in numerous human cancer samples and it needs the context-specific targeting strategies for NDR1. Thus, a comprehensive understanding of the direct interaction between NDR1 and varieties of proteins may provide new insights into cancer therapies. In this review, we summarize recent studies of NDR1 in solid tumors, such as prostate cancer and breast cancer, and explore the mechanism of action of PPIs of NDR1 in tumors.

Synthesis and performances of a ZnCo2O4@MnMoO4 composite for a hybrid supercapacitor.

To overcome the disadvantages of poor intrinsic conductivity and stability of ZnCo2O4, a ZnCo2O4@MnMoO4 composite as an emerging pseudocapacitor electrode material with high specific capacitance, environmental friendliness, morphological diversity, and unique hierarchical structure was synthesized via a simple two-step hydrothermal method. The research results indicate that the ZnCo2O4@MnMoO4 composite can present a high specific capacity of 1628 F g-1 at a current density of 1 A g-1 and good cycling stability with 69% capacity retention after 10 000 cycles at 10 A g-1. Hybrid supercapacitors (HSCs) assembled with the ZnCo2O4@MnMoO4 cathode and activated carbon anode can deliver an energy density of 48 W h kg-1 at a power density of 695 W kg-1, and their capacity retention reached 61% after 8000 charge-discharge cycles at a current density of 10 A g-1. This could be attributed to the synergistic effect of the specific surface area and electrical conductivity enhanced by compositing ZnCo2O4 with MnMoO4. As a result, the excellent electrochemical properties show that the ZnCo2O4@MnMoO4 composite has strong application potential for high-performance supercapacitors.

A superior mulberry-like nanoparticle NiB binary catalyst for borohydride oxidation.

A NiB binary catalyst with a unique mulberry-like nanoparticle morphology has been prepared by one-step electrodeposition. The NiB-0.2 catalyst exhibits excellent catalytic activity, selectivity, and stability for the borohydride oxidation reaction. Moreover, a direct borohydride fuel cell using the NiB-0.2 catalyst anode can deliver a peak power density of 453 mW cm-2 and open-circuit voltage of 1.96 V at 343 K. The improved performances are due to the introduction of B. This study may inspire the development of efficient noble-metal-free anode catalysts for DBFCs.

Construction and application of NiCo2O4@MnS composite with hierarchical structure for hybrid supercapacitor.

The development of an electrochemical energy storage system with exceptional performance is an important way to address the energy crisis and environmental pollution of the modem world. In this study, an NiCo2O4@MnS composite with a unique hierarchical structure has been successfully synthesized on an NF substrate using the hydrothermal-electrodeposition method. The results indicate that NiCo2O4@MnS possesses superior specific capacitance and excellent cycling stability. At a current density of 2 A g-1, its specific capacitance can reach 2100 F g-1, while the capacitance retention is still 76% after 10 000 cycles at 10 A g-1. Moreover, when the current density is 1 A g-1, the assembled NiCo2O4@MnS//AC device can deliver a specific capacitance of 203 F g-1, and the energy density is up to 55 W h kg-1 at a power density of 697 W kg-1. These outstanding electrochemical properties of NiCo2O4@MnS can be ascribed to the increase in ion diffusion, specific surface area and electronic conductivity due to its unique hierarchical structure and introduction of MnS.

Danshensu inhibits SARS-CoV-2 by targeting its main protease as a specific covalent inhibitor and discovery of bifunctional compounds eliciting antiviral and anti-inflammatory activity.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to human. Since there are still no effective treatment options against the new emerging variants of SARS-CoV-2, it is necessary to devote a continuous endeavor for more targeted drugs and the preparation for the next pandemic. Salvia miltiorrhiza and its active ingredients possess wide antiviral activities, including against SARS-CoV-2. Danshensu, as one of the most important active ingredients in Salvia miltiorrhiza, has been reported to inhibit the entry of SARS-CoV-2 into ACE2 (angiotensin-converting enzyme 2)-overexpressed HEK-293T cells and Vero-E6 cells. However, there is a paucity of information regarding its detailed target and mechanism against SARS-CoV-2. Here, we present Danshensu as a covalent inhibitor of 3-chymotrypsin-like protease (3CLpro) against SARS-CoV-2 by the time-dependent inhibition assay (TDI) and mass spectrometry analysis. Further molecular docking, site-directed mutagenesis, circular dichroism (CD) and fluorescence spectra revealed that Danshensu covalently binds to C145 of SARS-CoV-2 3CLpro, meanwhile forming the hydrogen bonds with S144, H163 and E166 in the S1 site. Structure-based optimization of Danshensu led to the discovery of the promising compounds with good inhibitory activity and microsomal stability in vitro. Due to Danshensu inhibiting lung inflammation in the mouse model, we found that Danshensu derivatives also showed better anti-inflammatory activity than Danshensu in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Thus, our study provides not only the clue of the efficacy of Salvia miltiorrhiza against SARS-CoV-2, but also a detailed mechanistic insight into the covalent mode of action of Danshensu for design of covalent inhibitors against SARS-CoV-2 3CLpro, highlighting its potential as a bifunctional molecule with antivirus and anti-inflammation.

Methyl rosmarinate is an allosteric inhibitor of SARS-CoV-2 3 CL protease as a potential candidate against SARS-cov-2 infection.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been ongoing for more than three years and urgently needs to be addressed. Traditional Chinese medicine (TCM) prescriptions have played an important role in the clinical treatment of patients with COVID-19 in China. However, it is difficult to uncover the potential molecular mechanisms of the active ingredients in these TCM prescriptions. In this paper, we developed a new approach by integrating the experimental assay, virtual screening, and the experimental verification, exploring the rapid discovery of active ingredients from TCM prescriptions. To achieve this goal, 4 TCM prescriptions in clinical use for different indications were selected to find the antiviral active ingredients in TCMs. The 3-chymotrypsin-like protease (3CLpro), an important target for fighting COVID-19, was utilized to determine the inhibitory activity of the TCM prescriptions and single herb. It was found that 10 single herbs had better inhibitory activity than other herbs by using a fluorescence resonance energy transfer (FRET) - based enzymatic assay of SARS-CoV-2 3CLpro. The ingredients contained in 10 herbs were thus virtually screened and the predicted active ingredients were experimentally validated. Thus, such a research strategy firstly removed many single herbs with no inhibitory activity against SARS-CoV-2 3CLpro at the very beginning by FRET-based assay, making our subsequent virtual screening more effective. Finally, 4 active components were found to have stronger inhibitory effects on SARS-CoV-2 3CLpro, and their inhibitory mechanism was subsequently investigated. Among of them, methyl rosmarinate as an allosteric inhibitor of SARS-CoV-2 3CLpro was confirmed and its ability to inhibit viral replication was demonstrated by the SARS-CoV-2 replicon system. To validate the binding mode via docking, the mutation experiment, circular dichroism (CD), enzymatic inhibition and surface plasmon resonance (SPR) assay were performed, demonstrating that methyl rosmarinate bound to the allosteric site of SARS-CoV-2 3CLpro. In conclusion, this paper provides the new ideas for the rapid discovery of active ingredients in TCM prescriptions based on a specific target, and methyl rosmarinate has the potential to be developed as an antiviral therapeutic candidate against SARS-CoV-2 infection.

Lattice strain controlled Ni@NiCu efficient anode catalysts for direct borohydride fuel cells.

We successfully fabricated a novel tensile lattice strained Ni@NiCu catalyst with a popcorn-like morphology, which is composed of a crystalline Ni core and a NiCu alloy shell. It exhibits outstanding catalytic activity, selectivity, and stability towards borohydride electrooxidation. Moreover, a direct borohydride fuel cell (DBFC) with a Ni@NiCu anode can deliver a power density of 433 mW cm-2 and an open circuit voltage of 1.94 V, much better than the performances of DBFCs employing other anode catalysts reported in the literature. This could be attributed to the fact that the tensile lattice strain generated by the introduction of Cu leads to a rise in the d-band center of the Ni metal and promotes the final B-H decoupling, which is the rate-determining step in the borohydride oxidation reaction, thus improving remarkably the catalytic performances of Ni@NiCu.

Mg doping of NiMn-LDH with a three-dimensional porous morphology for an efficient supercapacitor.

As a promising supercapacitor electrode material, NiMn-LDH has attracted great attention due to its high theoretical capacity and easy preparation. However, the development and application of NiMn-LDH in supercapacitors are limited because of its poor cycling stability and low electrical conductivity. To solve these problems, a NiMnMg-LDH with a three-dimensional porous morphology has been successfully fabricated by doping with Mg to improve its electrochemical properties. Experimental results indicate that NiMnMg-LDH-7 delivers a specific capacitance of 1772 F g-1 at a current density of 1 A g-1. Moreover, it can still reach 1080 F g-1 when the current density is increased 10 times, suggesting excellent rate capability. The asymmetric supercapacitor (ASC) NiMnMg-LDH-7//AC can provide a high energy density of 28 W h kg-1 at a power density of 700 W kg-1. Furthermore, the energy density can still reach 16 W h kg-1 even if the power density is increased to close to 3500 W kg-1. The capacity retention of this ASC device can reach 74% after 3000 cycles at a current density of 3 A g-1. These excellent properties of NiMnMg-LDH can be attributed to the obvious improvement of its specific surface area and electrical conductivity owing to doping with the element magnesium. We believe that this work could provide a new idea for the preparation of high-performance electrode materials for supercapacitors.

Succulent-plant-like Ni-Co alloy efficient catalysts for direct borohydride fuel cells.

A Ni-Co alloy catalyst with a unique succulent-plant-like morphology is prepared by a simple electrodeposition method, while the effects of deposition conditions on its performance are also investigated systematically. The research results show that the Ni0.889-Co0.111 catalyst exhibits excellent activity, selectivity, and stability to the borohydride oxidation reaction. Moreover, when Ni0.889-Co0.111 is assembled as the anode catalyst, the direct borohydride fuel cell delivers a peak power density of 490 mW cm-2 and an open-circuit voltage of 1.87 V at 343 K and can run stably for dozens of hours. The significant improvement in Ni-Co catalyst performance can be attributed to its unique succulent-plant-like morphology and the introduction of an appropriate amount of Co.

FXR agonists for colorectal and liver cancers, as a stand-alone or in combination therapy.

Farnesoid X receptor (FXR, NR1H4) is generally considered as a tumor suppressor of colorectal and liver cancers. The interaction between FXR, bile acids (BAs) and gut microbiota is closely associated with an increased risk of colorectal and liver cancers. Increasing evidence shows that FXR agonists may be potential therapeutic agents for colorectal and liver cancers. However, FXR agonists alone do not produce the desired results due to the complicated pathogenesis and single therapeutic mechanism, which suggests that effective treatments will require a multimodal approach. Based on the principle of improvingefficacy andreducingside effects, combination therapy is currently receiving considerable attention. In this review, colorectal and liver cancers are grouped together to discuss the effects of FXR agonists alone or in combination for combating the two cancers. We hope that this review will provide a theoretical basis for the clinical application of novel FXR agonists or combination with FXR agonists against colorectal and liver cancers.

A new zinc-ion battery cathode with high-performance: Loofah-like lanthanum manganese perovskite.

Due to high safety and excellent rate performance, the aqueous Zn-ion battery is a promising energy storage battery for practical application. However, most manganese-based compounds suffer from poor cycling and rate performance. Herein, a new concept of Zn-ions battery is assembled with the loofah-like LaMnO3 perovskite as a novel cathode, achieving fast ion kinetics through the co-intercalation of Zn2+ and H+ cations. In this work, the Ni-doping strategy is adopted to improve the electrochemical performance of LaMnO3 perovskite as a cathode material for Zn-ion batteries. The resultant LaNixMn1-xO3 (x = 0.2) exhibits a superior capacity of 226 mAh g-1 after 80 cycles at 100 mA g-1 and high working voltages at 1.4 V and 1.26 V vs. Zn2+/Zn in the electrolyte of 2 M ZnSO4 + 0.2 M MnSO4. Even at 500 mA g-1, the new Zn/LaNixMn1-xO3 battery still delivers a discharge capacity of 113 mAh g-1 after 1000 cycles. At medium current density, the electrochemical process of the LaNixMn1-xO3 (x = 0.2) electrode is co-controlled by the solid diffusive and surface-capacitive process with a fast ion diffusion rate. The lanthanum manganese perovskite is a potential cathode material for Zn-ion batteries with long cycle performance and high rate cyclability. This work significantly opens up the way of perovskite materials as new cathodes for high-rate ZIBs.

Porous Ni-Cu Alloy Dendrite Anode Catalysts with High Activity and Selectivity for Direct Borohydride Fuel Cells.

A porous Ni-Cu alloy dendrite catalyst covered by Ni nanoparticles (Ni-np@NC) has been fabricated by an ultrafast and controllable strategy. The research results show that the morphology of the Ni-Cu alloy depends strongly on the Cu2+concentration. Moreover, the Ni-np@NC catalyst demonstrates excellent selectivity and activity toward the borohydride oxidation reaction (BOR). Furthermore, on the Ni-np@NC catalyst electrode, the overpotential merely requires 169 mV at a current density of 10 mA cm-2 for BOR, and the fuel efficiency may reach 70%. The direct borohydride fuel cell using the Ni-np@NC/C anode can export a maximum power density of 218 mW cm-2, much higher than that using the noble-based anode reported in the literature. The remarkable enhancement of Ni-np@NC catalyst performances is on the back of the unique morphology of porous dendrite covered by nanoparticles and the introduction of Cu.

Pseudocapacitance multiporous vanadyl phosphate/graphene thin film electrode for high performance electrochemical capacitors.

Supercapacitors are being considered as promising electricity storage devices with green sustainable energy conversion. To efficiently develop and optimize pseudocapacitive material of vanadyl phosphate, herein, multiporous vanadyl phosphate/graphene (denoted as MP-VOPO4@rGO) is fabricated for the first time with phytic acid as a phosphorus source by extremely simple sol-gel and drop coating methods, and used as the free binder thin film electrode of supercapacitors. The smart combination of honeycomb-like architecture and graphene incorporation results in more active sites and low internal resistance, significantly improving energy storage performance. The effect of introducting polystyrene (denoted as PS) template and rGO on the performance of the nanocomposite is systematically analyzed by comparing the performance of the corresponding thin film electrodes. The MP-VOPO4@rGO thin film electrode delivers superior pseudocapacitive performance of 672 F g-1 at 1 A g-1 as well as a remarkable rate capability of 552 F g-1 at 5 A g-1, and it presents a remarkable longterm cycling stability, with a capacitance retention of 83.5% after 5000 cycles. Very interestingly, the results of surface capacitance contribution dominance clearly demonstrates its rapid capacitive response. In addition, based on MP-VOPO4@rGO thin film as positive and negative electrodes, the corresponding assembled symmetric supercapacitors exihibits outstanding energy density of 26.3 Wh kg-1 at power density of 249.9 W kg-1. This investigation can not only provide a versatile strategy to design other thin film electrode materials but also open up a new insight into the development of polyanion phosphate composites for next-generation high performance energy storage systems.

Constructing highly active Co sites in Prussian blue analogues for boosting electrocatalytic water oxidation.

High-valence cobalt sites are considered as highly active centers for the oxygen evolution reaction (OER) and their corresponding construction is thus of primary importance in the pursuit of outstanding performance. Herein, we report the design and facile synthesis of abundant high-valence cobalt sites by introducing Zn2+ into CoFe Prussian blue analogues (PBAs). The modification results in the drastic morphological transformation from a pure phase (CoFe-PBA) to a three-phase composite (CoFeZn-PBA), with a significant increase not only the amount of highly oxidized Co sites but the specific surface area (by up to 4 times). Moreover, the obtained sample also exhibits outstanding electric conductivity. Consequently, an excellent OER performance with an overpotential of 343 mV@10 mA cm-2 and a Tafel slope of 75 mV dec-1 was achieved in CoFeZn-PBA, which outperforms the commercial IrO2 catalyst. Further analysis reveals that CoFeZn-PBA becomes (oxyhydr)oxides after the OER.

An efficient Ni-P amorphous alloy electrocatalyst with a hierarchical structure toward borohydride oxidation.

Nickel has been widely researched in the electrooxidation of borohydride due to its low cost and abundant reserves, but its catalytic activity and stability need to be improved for practical application. In this work, a Ni and P deposited nickel foam (Ni-P@NF) catalyst electrode with a unique hierarchical structure is prepared by a simple one-step electrodeposition method. The structure, morphology, and catalytic performances of Ni-P@NF are investigated systematically. The results show that Ni-P@NF exhibits excellent catalytic activity, stability, and durability during borohydride electrooxidation. On the Ni-P@NF catalyst electrode, the current density for borohydride oxidation can reach 225 mA cm-2; the fuel utilization is up to 84% and 97% of the initial current is maintained even after 500 cycles of cyclic voltammetry (CV), while a traditional H-type direct sodium borohydride fuel cell (DBFC) assembled with a Ni-P@NF catalyst anode can deliver a maximum power density of 52.5 mW cm-2 and an open circuit potential of 1.87 V. These merits can be attributed to the unique hierarchical structure of the Ni-P catalyst and the introduction of phosphorus. The results also show that the Ni-P@NF catalyst has certain application potential in DBFCs.

[Analysis of correlation between insulin resistance, blood lipids and Alzheimer's disease].

OBJECTIVE: To investigate the relationship between Alzheimer' s disease(AD) and insulin resistance and blood lipids. METHODS: Serum samples collected from 45 AD patients and 44 healthy controls were analyzed by automatic biochemical analyzer to detect the levels of blood glucose, insulin, blood lipids. The variables were evaluated statistically by SPSS 11.0. RESULTS: Serum total cholesterol (TC), insulin (INS), insulin sensitivity index (IAI) and body mass index (BMI) from AD patients were significantly higher than those from health controls (P < 0.05), whereas the insulin resistance index (IR) and insulin secretion index (IS) from AD patients were significantly lower than those from healthy controls (P < 0.05). CONCLUSION: The abnormality of blood lipids and insulin might have potentially harmful effects on central nervous system, of which especially the neurotoxic effect on amyloid (Abeta) neurotoxicity and tau protein phosphorylation might result in memory impairment. These suggested that high blood lipids and insulin resistance were probable risk factors of Alzheimer's disease.

Hierarchical NiMoO4@Co3V2O8 hybrid nanorod/nanosphere clusters as advanced electrodes for high-performance electrochemical energy storage.

Herein, a synergistic strategy to construct hierarchical NiMoO4@Co3V2O8 (denoted as NMO@CVO) hybrid nanorod/nanosphere clusters is proposed for the first time, where Co3V2O8 nanospheres (denoted as CVO) have been uniformly immobilized on the surface of the NiMoO4 nanorods (denoted as NMO) via a facile two-step hydrothermal method. Due to the surface recombination effect between NMO and CVO, the as-prepared NMO@CVO effectively avoids the aggregation of CVO nanosphere clusters. The unique hybrid architecture can make the most of the large interfacial area and abundant active sites for storing charge, which is greatly beneficial for the rapid diffusion of electrolyte ions and fast electron transport. The optimized NMO@CVO-8 composite nanostructure displays battery-like behavior with a maximum specific capacity of 357 C g-1, excellent rate capability (77.8% retention with the current density increasing by 10 times) and remarkable cycling stability. In addition, an aqueous asymmetric energy storage device is assembled based on the NMO@CVO-8 hybrid nanorod/nanosphere clusters and activated carbon. The device shows an ultrahigh energy density of 48.5 W h kg-1 at a power density of 839.1 W kg-1, good rate capability (20.9 W h kg-1 even at 7833.7 W kg-1) and excellent cycling stability (83.5% capacitance retention after 5000 cycles). More notably, two charged devices in series can light up a red light-emitting diode (LED) for 20 min, demonstrating its potential in future energy storage applications. This work indicates that the hierarchical NiMoO4@Co3V2O8-8 hybrid nanorod/nanosphere clusters are promising energy storage materials for future practical applications and also provides a rational strategy for fabricating novel nanostructured materials for high-performance energy storage.

Hydrothermal Synthesis of a New Kind of N-Doped Graphene Gel-like Hybrid As an Enhanced ORR Electrocatalyst.

In this work, g-C3N4@GO gel-like hybrid is obtained by assembling intentionally exfoliated g-C3N4 sheets on graphene oxide (GO) sheets under a hydrothermal condition. A specific N-doping process is first designed by heating the g-C3N4@GO interlaced hybrid in vacuum to form nitrogen-doped graphene nanosheets (NGS) with high level of pyridinic-N (56.0%) and edge-rich defect structure. The prepared NGS exhibited a great electrocatalysis for oxygen reduction reaction (ORR) in terms of the activity, durability, methanol tolerance, and the reaction kinetics. And the excellent electrocatalytic performance stems from the effective N-doped sites that the nitrogen atom is successfully doped at the defective edges of graphene, and the annealing temperature can play significant role of the doping pattern and location of N. The research provides a new insight into the enhancement of electrocatalysis for ORR based on nonmetal carbons by using the novel N-doping method.