Unique sandwich-cookie-like nanosheet array heterojunction bifunctional electrocatalyst towards efficient overall water/seawater splitting.

Construction of multi-component heterostructures is an effective strategy for electrocatalysts to improve both the hydrogen evolution reaction (HER) at the cathode and the oxygen evolution reaction (OER) activity at the anode. Herein, an efficient bifunctional electrocatalyst towards overall water/seawater splitting (OW/SS) is reported with strategy of heterostructure construction (ruthenium/nickel phosphorus) on nickel hydroxide (Ni(OH)2). With the unique hydrolysis layer (Ni(OH)2), the processes of H2O hydrolysis and the adsorption/desorption of H*/O-containing intermediates (OH, O, OOH) were greatly boosted by Ru and P sites, which acted as the catalytic active centers of OER and HER, respectively. In addition, the electronic structure reconfiguration was realized through the strong interaction between multi-interfaces. For alkaline HER at the current density of 10 mA cm-2, the overpotential of Ru-P-Ni(OH)2/NF (denoted as RNPOH/NF) was 98 mV, whereas just 230 mV of overpotential was essential to stimulate alkaline OER at the current density of 20 mA cm-2. Specifically, as a bifunctional electrocatalyst towards overall water splitting, RNPOH/NF deserves cell voltages of 1.7/1.92 V and 1.75/1.94 V, respectively, to activate current densities of 50/100 mA cm-2 in alkaline water/seawater systems, together with a good durability of 12 h. This work contributes insights to the development of bifunctional electrocatalysts for overall water/seawater splitting.

Integrated Heterogeneous Engineering with the Vacancy Defect of Porous CoPv-MoxPv Nanosheets for an Accelerated Hydrogen Evolution Reaction.

Electrochemical water splitting is a possible way of realizing sustainable and clean hydrogen production but is challenging, because a highly active and durable electrocatalyst is essential. In this work, we integrated heterogeneous engineering and vacancy defect strategies to design and fabricate a heterostructure electrocatalyst (CoPv-MoxPv/CNT) with abundant phosphorus vacancies attached to carbon nanotubes (CNTs). The vacancy defects enabled the optimization of the electronic structure; thereby, the electron-rich low-valent metal sites enhanced the ability of nonmetallic P to capture proton H. Meanwhile, the heterogeneous interface between bimetallic phosphides and CNTs realized rapid electron transfer. In addition, the Co, Mo, and P active species in the electrocatalytic process exposed increased amounts of active sites featuring porous nanosheet structures, which facilitated the adsorption of reaction intermediates and thus enhanced the hydrogen evolution reaction performance. In particular, the optimized CoPv-MoxPv/CNT catalyst possesses an overpotential of 138 mV at a current density of 10 mA cm-2 and long-term stability for 24 h. This work offers insights and possibilities for the engineering and exploration of transition metal-based electrocatalysts through combining multiple synergistic strategies.

Analysis and monitoring of drug therapy in a patient with peptic ulcer complicated by infection: A case report.

BACKGROUND: The role of primary-level medical pharmacists in medical institutions in China is limited; therefore, it is necessary to explore the role of pharmacists in the process of drug treatment. CASE SUMMARY: A Chinese pharmacist participated in the complete treatment of a patient with a duodenal ulcer. The rationale for drug treatment was evaluated, and adjustments were made to the antacid and anti-infective regimen, as well as the dose and frequency of administration. Body temperature, routine blood examination, and adverse drug reactions were strictly monitored. During treatment, the pharmacist recommended anti-infective therapy with ampicillin-sulbactam, which effectively controlled the infection. Additionally, the pharmacist suggested changing famotidine to lansoprazole for acid suppression and gastroprotective treatment, combined with Chinese patent medicine such as Kangfuxin Liquid. This is the first case report of a pharmacist in primary-level medical institutions adjusting drug use for patients with duodenal ulcer and pulmonary infection. CONCLUSION: A pharmacist participated in the treatment process, provided individualized medication adjustment, and achieved good clinical results.

Interface Engineering with the Coupling of a 3D Porous Structure Enables MoP2-NiCoP Heterostructure Nanosheets for Enhanced Alkaline Hydrogen Evolution Reaction.

One of the crucial parts of the electrochemically focused energy conversion and storage system is the hydrogen evolution reaction. The further exploration of electrocatalysts made of nonprecious metals could help to bring the technology closer to industrialization. Here, we present an effective hydrogen evolution reaction (HER) electrocatalyst that employs hydrothermal and phosphorization steps to create three-dimensional (3D) porous MoP2-NiCoP heterostructure nanosheets on nickel foam (MoP2-NiCoP/NF). H2O-dissociation and H-adsorption were effectively achieved due to the distinctive interface engineering between NiCoP and MoP2, which functions as a channel for immediate electron transfer. Compared to the single-component MoP2 and NiCoP, the synergistic interaction between the heterogeneous components coupling and the 3D porous structure enables MoP2-NiCoP/NF to exhibit satisfactory catalytic activity with an ultralow overpotential of 50 mV at 10 mA cm-2, which is close to the commercial Pt/C catalyst in alkaline media. More importantly, it exhibits good stability, with the ability to be electrolyzed in 1.0 M KOH electrolyte for 24 h without a significant change in overpotential. This study offers directions for the design of low-cost, high-activity, transition metal phosphides (TMPs)-based HER catalyst alternatives for future practical applications.

Goldfish adiponectin: (I) molecular cloning, tissue distribution, recombinant protein expression, and novel function as a satiety factor in fish model.

Adiponectin (AdipoQ) is an adipokine involved in glucose homeostasis and lipid metabolism. In mammals, its role in appetite control is highly controversial. To shed light on the comparative aspects of AdipoQ in lower vertebrates, goldfish was used as a model to study feeding regulation by AdipoQ in fish species. As a first step, goldfish AdipoQ was cloned and found to be ubiquitously expressed at the tissue level. Using sequence alignment, protein modeling, phylogenetic analysis and comparative synteny, goldfish AdipoQ was shown to be evolutionarily related to its fish counterparts and structurally comparable with AdipoQ in higher vertebrates. In our study, recombinant goldfish AdipoQ was expressed in E. coli, purified by IMAC, and confirmed to be bioactive via activation of AdipoQ receptors expressed in HepG2 cells. Feeding in goldfish revealed that plasma levels of AdipoQ and its transcript expression in the liver and brain areas involved in appetite control including the telencephalon, optic tectum, and hypothalamus could be elevated by food intake. In parallel studies, IP and ICV injection of recombinant goldfish AdipoQ in goldfish was effective in reducing foraging behaviors and food consumption. Meanwhile, transcript expression of orexigenic factors (NPY, AgRP, orexin, and apelin) was suppressed with parallel rises in anorexigenic factors (POMC, CART, CCK, and MCH) in the telencephalon, optic tectum and/or hypothalamus. In these brain areas, transcript signals for leptin receptor were upregulated with concurrent drops in the NPY receptor and ghrelin receptors. In the experiment with IP injection of AdipoQ, transcript expression of leptin was also elevated with a parallel drop in ghrelin mRNA in the liver. These findings suggest that AdipoQ can act as a novel satiety factor in goldfish. In this case, AdipoQ signals (both central and peripheral) can be induced by feeding and act within the brain to inhibit feeding behaviors and food intake via differential regulation of orexigenic/anorexigenic factors and their receptors. The feeding inhibition observed may also involve the hepatic action of AdipoQ by modulation of feeding regulators expressed in the liver.

Constructing a Functionalized Electrocatalyst of a Transition Metal Chalcogenide on Accordion-Like MXene to Boost the Hydrogen Evolution Reaction.

MXenes exhibit unique layered structures and excellent electrical conductivity, and their multiple surface termination groups are favorable for hosting impressive performance for electrochemical reactions. Therefore, a two-dimensional (2D) layered MXene-based catalyst may become a novel high-efficiency electrocatalyst to replace traditional noble metal electrocatalysts. In this work, a transition metal chalcogenide (MoS2/CuS) and MXene are combined to prepare a 2D electrocatalyst (MoS2/CuS/MXene) for the hydrogen evolution reaction (HER). MXene exhibited a large specific surface area in the shape of an accordion, which was very beneficial for the growth of nanomaterials. CuS/MXene promoted electron transfer and improved the exposed active site for HER. The exposed MoS2 edges exhibited a high chemical adsorption capacity, which is conducive to HER. Electrochemical tests reveal that the MoS2/CuS/MXene electrocatalyst can reduce the charge transfer resistance toward the HER and increase active sites for HER, leading to enhancing the catalytic performance. The MoS2/CuS/MXene electrocatalyst affords an efficient HER with a low overpotential (115 mV@10 mA cm-2). This work offers a new idea to create layered transition metal chalcogenide- and MXene-based electrocatalysts for HER.

Defect engineering with N-doped carbon hybrid cobalt-molybdenum phosphide nanosheets wrapped molybdenum oxide nanorods for alkaline hydrogen evolution reaction.

Regulating the electrocatalytic hydrogen evolution reaction (HER) performance through defect engineering of the surface of the catalysts is an effective pathway. Herein, cobalt-molybdenum phosphide (CoMoP) nanosheets wrapped molybdenum oxide (MoO3) core-shell nanorods (MoO3@CoMoP), as alkaline electrocatalysts with ligand-derived N-doped carbon hybrid and oxygen-vacancies, were synthesized via solvothermal approaches and followed by phosphorization. As expected, the MoO3@MoCoP affords efficient HER with a low overpotential (η) of 84.2 ± 0.4 mV at 10 mA cm-2. After phosphorization, not only the MoCoP active species are incorporated into the catalyst, but also the defects sites are achieved. Impressively, the metal-ligand-derived MoCoP are distributed uniformly in the N-doped carbon hybrid matrix, exhibiting well-exposed active sites. Benefiting from the synergy effect of MoCoP active species and oxygen-vacancy, the MoO3@MoCoP showed increased conductivity and stability, which can deliver a current density of 10 mA cm-2 over 40 h. MoO3@MoCoP exhibits an optimal electronic structure on the surface by charge redistribution at the interface, thereby optimizing the hydrogen adsorption energy and accelerating the hydrogen evolution kinetics. This work paves the way for the design of transition metal electrocatalysts with desirable properties through a promising strategy in the field of energy conversion.

Pt-Doped Biomass Carbon Decorated with MoS2 Nanosheets as an Electrocatalyst for Hydrogen Evolution.

It is necessary to develop an efficient hydrogen evolution catalyst to improve the efficiency of the hydrogen evolution reaction (HER). Herein, a MoS2 nanosheet is decorated on the Pt-doping biomass yeast cells (MoS2@Pt/YC) via a simple hydrothermal process. Reducing the noble metal loading without compromising its performance is a challenging task. The smooth surface of YCs is conducive to the growth of MoS2 nanosheets, and its functional groups provide attachment sites for metal Pt. The Pt/YC is covered with MoS2 nanosheets, thus improving the exposed active sites for HER. The obtained MoS2@Pt/YC delivers a competitive overpotential of 118 mV at the benchmark current density of 10 mA cm-2 and achieves a small Tafel slope of 74 mV dec-1, indicating the great HER performance of MoS2@Pt/YC. Moreover, MoS2@Pt/YC shows robust stability after 24 h of continuous operation toward HER in acidic solution. By introducing transition metal sulfides with high specific surface area, the loading of precious metals can be reduced without compromising properties. This work provides a method to design Pt-doping HER electrocatalysts through a simple method. The facile preparation process for MoS2@Pt/YC and its outstanding performance allow it to be a promising electrocatalyst for practical HER application.

ZIF-67-Derived (NiCo)S2@NC Nanosheet Arrays Hybrid for Efficient Overall Water Splitting.

Electrocatalytic water splitting is considered a promising approach to obtain clean and sustainable hydrogen energy. The integration of optimal nanoarchitecture and multicomponent synergy has been a significant factor for designing a bifunctional electrocatalyst to promote the cathodic hydrogen evolution reaction (HER) and anodic oxygen evolution reaction (OER). In particular, the charge migration, mass transfer, and gas release rate in the catalyzing process are closely correlated with the architecture of the catalyst. Here, ZIF-67-derived N-doped carbon nanofiber-supported (NiCo)S2 nanosheet [(NiCo)S2/NCNF] as a bifunctional electrocatalyst was synthesized using electrospinning, template etching, and subsequent gas sulfidation method. The hierarchical hybrid nanofiber with inner hollow cubes and outer nanosheets provides easy electron penetration, high charge/mass transportation efficiency, and robust structure stability. Furthermore, the MOF-derived carbon-encapsuled bimetal-sulfide and the synergistic effect of double active centers are conducive to an exceptional performance, showing low overpotentials of 177 and 203 mV to drive a current density of 10 mA cm-2 and robust stability for the HER and OER, respectively. Meanwhile, the (NiCo)S2/NCNF electrodes exhibit a small voltage of 1.61 V for overall water splitting activity with an electrolyzer cell at current densities of 10 mA cm-2 over 12 h. This work presents novel insights into the bifunctional catalyst for promoting the overall water splitting via a MOF-derived nanoarchitecture and multicomponent synergy.

Hierarchical Coralline-like (NiCo)S2@MoS2 Nanowire Arrays to Accelerate H2 Release for an Efficient Hydrogen Evolution Reaction.

The hydrogen evolution reaction (HER) is significantly influenced by the evolved H2 bubble diffusion rate on the surface of the electrode, which involves the blocking and release of the active site at the catalytic interface. Rational design of nanostructured catalysts could not only sharply enhance the specific surface area but also provide large amounts of channels for gas release. Herein, NiCo-nanowire-derived multimetal chalcogenides grown in situ on carbon cloth [denoted as (NiCo)S2@MoS2/CC] are presented by serial hydrothermal methods. The obtained hierarchical nanowire array architecture affords abundant surface-active sites and is conducive to permeate electrolytes. The surface adsorption/desorption behavior of the heterostructure catalyst was optimized through regulating MoS2 concentration. Owing to the synergistic effect of metal Ni and Co and the interaction of the (NiCo)S2@MoS2 heterostructure, (NiCo)S2@MoS2/CC-2 delivers a relatively low overpotential of 74 mV at a current density of 10 mA cm-2 and displays a small Tafel slope of 54 mV dec-1 for HER catalysis, surpassing that of the recently reported MoS2-based electrocatalysts. Such a strategy through nanostructure optimization and electron interaction of the heterostructure could improve the electrocatalytic HER performance for multimetal chalcogenides in an alkaline medium.

Design, Synthesis, and Bioactivity Evaluation of Dual-Target Inhibitors of Tubulin and Src Kinase Guided by Crystal Structure.

Klisyri (KX01) is a dual tubulin/Src protein inhibitor that has shown potential therapeutic effects in several tumor models. However, a phase II clinical trial in patients with bone-metastatic castration-resistant prostate cancer was halted because of lack of efficacy. We previously reported that KX01 binds to the colchicine site of ß-tubulin and its morpholine group lies close to α-tubulin's surface. Thus, we hypothesized that enhancing the interaction of KX01 with α-tubulin could increase tubulin inhibition and synthesized a series of KX01 derivatives directed by docking studies. Among these derivatives, 8a exhibited more than 10-fold antiproliferation activity in several tumor cells than KX01 and significantly improved in vivo antitumor effects. The X-ray crystal structure suggested that 8a both bound to the colchicine site and extended into the interior of α-tubulin to form potent interactions, presenting a novel binding mode. A potential clinical candidate for cancer therapy was identified in this study.

Synthesis and evaluation of new compounds bearing 3-(4-aminopiperidin-1-yl)methyl magnolol scaffold as anticancer agents for the treatment of non-small cell lung cancer via targeting autophagy.

Magnolol and honokiol are the two major active ingredients with similar structure and anticancer activity from traditional Chinese medicine Magnolia officinalis, and honokiol is now in a phase I clinical trial (CTR20170822) for advanced non-small cell lung cancer (NSCLC). In search of potent lead compounds with better activity, our previous study has demonstrated that magnolol derivative C2, 3-(4-aminopiperidin-1-yl)methyl magnolol, has better activity than honokiol. Here, based on the core of 3-(4-aminopiperidin-1-yl)methyl magnolol, we synthesized fifty-one magnolol derivatives. Among them, compound 30 exhibited the most potent antiproliferative activities on H460, HCC827, H1975 cell lines with the IC50 values of 0.63-0.93 µM, which were approximately 10- and 100-fold more potent than those of C2 and magnolol, respectively. Besides, oral administration of 30 and C2 on an H460 xenograft model also demonstrated that 30 has better activity than C2. Mechanism study revealed that 30 induced G0/G1 phase cell cycle arrest, apoptosis and autophagy in cancer cells. Moreover, blocking autophagy by the autophagic inhibitor enhanced the anticancer activity of 30in vitro and in vivo, suggesting autophagy played a cytoprotective role on 30-induced cancer cell death. Taken together, our study implied that compound 30 combined with autophagic inhibitor could be another choice for NSCLC treatment in further investigation.

Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of ß-tubulin explains KXO1's low clinical toxicity.

KXO1 (tirbanibulin or KX2-391) is as a non-ATP-competitive inhibitor of SRC proto-oncogene nonreceptor tyrosine kinase (SRC) and is being clinically investigated for the management of various cancers and actinic keratosis. Recently, KXO1 has also been shown to strongly inhibit tubulin. Interestingly, unlike conventional tubulin-targeting drugs, KXO1 has exhibited low toxicity in preclinical and clinical studies, but the reason for this remains elusive, as are the KXO1-binding site and other details of the interaction of KXO1 with tubulin. Here, cell-based experiments revealed that KXO1 induces tubulin depolymerization and G2/M phase cell cycle arrest at low nanomolar concentrations, similar to colchicine, used as a positive control. Results from biochemical experiments, including an N,N-ethylenebis(iodoacetamide) competition assay, disclosed that KXO1 binds to the colchicine-binding site on ß-tubulin, further confirmed by the crystal structure of the tubulin-KXO1 complex at 2.5-Å resolution. A high-quality electron density map of the crystallographic data enabled us to unambiguously determine the position and orientation of KXO1 in the colchicine-binding site, revealing the detailed interactions between KXO1 and tubulin. We also found that KXO1 binds reversibly to purified tubulin, induces a totally reversible cellular effect (G2/M cell cycle arrest), and possesses no cellular toxicity 5 days after drug washout, explaining KXO1's low toxicity. In summary, we show that KXO1 binds to the colchicine-binding site of tubulin and resolved the crystal structure of the tubulin-KXO1 complex. Importantly, KXO1's reversible binding to tubulin explains its clinically low toxicity, an insight that could guide further clinical applications of KXO1.

Identification and characterization of a novel calmodulin binding site in Drosophila TRP C-terminus.

Transient receptor potential (TRP) channels are a group of essential cation channels involved in many important sensory signal transduction processes, such as light, temperature, tastes and pressure sensing. Drosophila TRP channel is the first discovered family member and plays important roles in photo-transduction in Drosophila. Calmodulin (CaM), an important downstream effector of Ca2+ signal, was considered as a vital regulator of TRP activities. In this study, we discovered a novel Ca2+ dependent CaM binding site (TRP 783-862) in between the previously reported two calmodulin binding sites (CBSs). The isothermal titration calorimetry (ITC) and the size exclusion chromatography coupled with multi-angle static light scattering (SEC-MALS) results showed that the dissociation constant (Kd) between TRP 783-862 and Ca2+-CaM is 0.10 ±â€¯0.04 µM and their binding stoichiometry is 1:1. In addition, the shortest Ca2+-CaM interaction region and core CaM binding sequences in TRP 783-862 were dissected by the boundary mapping and mutagenesis experiments. More interestingly, by comparing the circular dichroism (CD) spectra before and after Ca2+-CaM binding, the TRP 783-862 fragment showed Ca2+-CaM binding dependent secondary structure changes, indicating that the interaction between CaM and Drosophila TRP channel may have a conformational impact on TRP structure. In summary, by identifying and characterizing a novel CaM binding site in TRP C-terminus, our findings provided a biochemical and structural basis for further in vivo functional studies of Ca2+-mediated TRP channel regulation through CaM/TRP interaction.

Systematic biochemical characterization of the SAM domains in Eph receptor family from Mus Musculus.

The Eph receptor family is the largest subfamily of receptor tyrosine kinases and well-known for their pivotal roles in axon guidance, synaptogenesis, artery/venous differentiation and tumorigenesis, etc. Activation of the Eph receptor needs multimerization of the receptors. The intracellular C-terminal SAM domain of Eph receptor was reported to mediate self-association of Eph receptors via the homo SAM-SAM interaction. In this study, we systematically expressed and purified the SAM domain proteins of all fourteen Eph receptors of Mus musculus in Escherichia coli. The FPLC (fast protein liquid chromatography) results showed the recombinant SAM domains were highly homogeneous. Using CD (circular dichroism) spectrometry, we found that the secondary structure of all the SAM domains was typically alpha helical folded and remarkably similar. The thermo-stability tests showed that they were quite stable in solution. SEC-MALS (size exclusion chromatography coupled with multiple angle light scattering) results illustrated 200 µM Eph SAM domains behaved as good monomers in the size-exclusion chromatography. More importantly, DLS (dynamic light scattering) results revealed the overwhelming majority of SAM domains was not multimerized in solution either at 200 µM or 2000 µM protein concentration, which indicating the SAM domain alone was not sufficient to mediate the polymerization of Eph receptor. In summary, our studies provided the systematic biochemical characterizations of the Eph receptor SAM domains and implied their roles in Eph receptor mediated signaling pathways.