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Black phosphorus (BP) is an emerging two-dimensional semiconductor material, which has interesting structural features and broad application prospects in the fields of optoelectronic devices, energy storage, and biomedicine. However, a large amount of evidence is still needed to clarify the potential mechanism for the synthesis of high-quality BP crystals in chemical vapor transport (CVT) reactions. In this work, High-purity BP crystal was synthesized by CVT method in amorphous Red Phosphorus (aRP), Sn and I2 system. We found that the synthesis of BP experienced three stages of structural transformation of aRP-P4-Hittorf’s Phosphorus (HP)-BP. First, the phase transition of aRP and P4 molecules was reversible in the sublimation stage; then, the P4 molecules were gradually transformed into the HP structure in the transportation and deposition stage; however, the nucleation of BP quickly inhibited the growth of HP and completed the phase transition quickly; Finally, the remaining P4 molecules were transformed into BP structure, which promoted the growth of BP crystals. This crystallization kinetics explained the nucleation mechanism during the formation of BP, and the competitive nucleation between HP and BP provided the possibility for the bottom-up preparation of BP nanobelts.

Mingji Jin,1,2,* Yan Hou,1– 3,* Xiuquan Quan,1,2,4,* Liqing Chen,1,2 Zhonggao Gao,1,2 Wei Huang1,2 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of China; 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of China; 3Department of Pharmacy, Yanbian University, Yanji, Jilin, 133000, People’s Republic of China; 4Department of Emergency Medicine, Affiliated Hospital of Yanbian University, Yanji, Jilin, 133000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhonggao Gao; Wei Huang Tel +86 010 63028096; +86 010 63026505Email zggao@imm.ac.cn; huangwei@imm.ac.cnBackground: The dual-loaded nano-delivery system can realize chemotherapeutic drug and small interfering RNA (siRNA) co-loading as well as enhance the therapeutic effect of drugs on tumors through a synergistic effect, while reducing their toxic and side effects on normal tissues.Methods: Previously, we developed layered smart nanoparticles (NPs) to co-deliver survivin siRNA as well as small molecule drugs for lung cancer. In this study, we used such smart NPs to co-deliver paclitaxel (PTX) and siRNA against vascular endothelial growth factor (VEGF) gene for breast cancer therapy in mice models. For the prepared NPs, characterizations such as particle size, zeta potential, gel electrophoresis imaging and in vitro stability were investigated. Then, 4T1 cells were used to evaluate the in vitro VEGF silencing capacity, tumor cell inhibitory and anti-apoptotic abilities. Finally, an orthotopic model of mouse breast cancer was established to evaluate the in vivo antitumor effects and safety properties of PTX-siRNAVEGF-NPs.Results: We prepared PTX-siRNAVEGF-NPs with particle size of 85.25 nm, PDI of 0.261, and zeta potential of 5.25 mV. The NPs with VEGF siRNA effectively knocked down the expression of VEGF mRNA. Cell counting kit-8 (CCK-8) and apoptosis assays revealed that the PTX-siRNAVEGF-NPs exhibited antiproliferation effect of PTX on 4T1 cells. The in vivo anti-tumor study indicated that PTX-siRNAVEGF-NPs could exert an antitumor effect by inhibiting the formation and development of new blood vessels in tumor tissues, thereby cutting off nutrient and blood supplies required for tumor tissue growth. Both the anti-tumor efficacy and in vivo safety of the PTX-siRNAVEGF-NPs group were better than that of the PTX-NPs and siRNAVEGF-NPs groups.Conclusion: The combination of PTX and VEGF siRNA exerts good antitumor effect on 4T1 tumor cells. This study provides a theoretical and practical basis for breast cancer therapy.Keywords: paclitaxel, VEGF siRNA, breast cancer, co-delivery

In this work, the adsorption parameters of n-butane vapor on an absorbent were tested following the fixed-bed method. According to the corresponding experiments, the maximum adsorption capacity and breakthrough time of activated carbon (AC) are 0.2674 g·g–1 and 924 min, respectively. According to the two-energy-state model formula and the classical adsorption heat formula, the values of theoretical and actual adsorption heat of AC adsorbing n-butane are 5.48 and 5.56 kJ·mol–1, respectively. The model for adsorption of n-butane by an AC fixed bed is based on the analytical solutions to the mass, momentum, and energy conservation equations. The model is built using porous media zone in ANSYS Fluent, the implementation of the model into ANSYS Fluent under user-defined functions (UDFs) is also described, the mass source term Si and energy source term ST are loaded into Fluent through UDF, and then the mass- and heat-transfer processes of AC in the absorption of n-butane are simulated. Furthermore, the predictions by ANSYS Fluent are compared with in situ experimental data, and the deviation rate of breakthrough time and temperature of six monitoring points is less than 5%. The results verify the accuracy and feasibility of computational fluid dynamics (CFD). Therefore, the model can be used to predict the engineering application of the adsorption of organic gases by various porous media.

Preeclampsia (PE), a common disorder of pregnancy, is characterized by insufficient trophoblast migration and inadequate vascular remodelling, such that promotion of trophoblast proliferation might ameliorate PE. In the current study, we sought to study the underlying mechanism of extracellular vesicle (EV)‐derived microRNA‐18 (miR‐18b) in PE. Human umbilical cord mesenchymal stem cells (HUCMSCs) isolated from placental tissues were verified through osteogenic, adipogenic and chondrogenic differentiation assays. Bioinformatics analyses and dual‐luciferase reporter gene assay were adopted to confirm the targeting relationship between miR‐18b and Notch2. The functional roles of EV‐derived miR‐18b and Notch2 in trophoblasts were determined using loss‐ and gain‐of‐function experiments, and trophoblast proliferation and migration were assayed using CCK‐8 and Transwell tests. In vivo experiments were conducted to determine the effect of EV‐derived miR‐18b, Notch2 and TIM3/mTORC1 in a rat model of PE, with monitoring of blood pressure and urine proteinuria. TUNEL staining was conducted to observe the cell apoptosis of placental tissues of PE rats. We found down‐regulated miR‐18b expression, and elevated Notch2, TIM3 and mTORC1 levels in the placental tissues of PE patients compared with normal placenta. miR‐18b was delivered to trophoblasts and targeted Notch2 and negatively its expression, whereas Notch2 positively mediated the expression of TIM3/mTORC1. EV‐derived miR‐18b or Notch2 down‐regulation enhanced trophoblast proliferation and migration in vitro and decreased blood pressure and 24 hours urinary protein in PE rats by deactivating the TIM3/mTORC1 axis in vivo. In summary, EV‐derived miR‐18b promoted trophoblast proliferation and migration via down‐regulation of Notch2‐dependent TIM3/mTORC1.

Background Microbial fermentation significantly affects the flavor and efficacy of tea. It is generally believed that fermented tea is more effective in lowering lipids, while unfermented tea can more effectively inhibit inflammation. However, there is not sufficient evidence to support this claim. To systematically compare the hypolipidemic, anti‐inflammatory, and anti‐atherosclerotic effects of tea before and after microbial fermentation, hyperlipidemic rats and inflammatory injury cells were treated with Monascus purpureus‐fermented pu‐erh tea water extract (MPT) and sun‐dried green tea water extract (SGT), respectively. Results MPT, with higher levels of theabrownins, flavonoids, gallic acid (GA), and lovastatin, was more effective in reducing serum triglyceride (TG), total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), and inflammatory cytokines (TNF‐α, IL‐1β, and IL‐6), while SGT, with higher levels of tea polyphenols, amino acids, (‐)‐epigallocatechin gallate (EGCG), and theaflavins, was more effective in increasing serum high‐density lipoprotein cholesterol (HDL‐C) in hyperlipidemic rats. The foam cells on the arterial wall of the rats in the MPT group were visibly less, and the thrombosis time was longer than that in the SGT group. Cell experiments showed that MPT was more effective in protecting endothelial cells from damage than SGT. Conclusion Surprisingly, Monascus purpureus‐fermented pu‐erh tea not only had better hypolipidemic and anti‐atherosclerotic effects than its raw material (sun‐dried green tea), but also was superior in anti‐inflammatory effects to the latter, which was possibly attributable to the great changes in functional ingredients during microbial fermentation., Surprisingly, Monascus purpureus‐fermented pu‐erh tea not only had better hypolipidemic and anti‐atherosclerotic effects than its raw material (sun‐dried green tea), but also was superior in anti‐inflammatory effects to the latter, which was attributable to the great changes in functional ingredients during microbial fermentation.

Nano titanium implants induce osteogenesis, but how osteoblasts respond to this physical stimulation remains unclear. In this study, we tried to reveal the role of the mitochondrial fission-fusion of osteoblasts in response to a nano titanium surface during the process of osteogenesis, which is important for the design of the surface structure of titanium implants. A TiO2 nanotube array (nano titanium, NT) was fabricated by anodization, and a smooth surface (smooth titanium, ST) was used as a control. We investigated changes in the mitochondrial fission-fusion (MFF) dynamics in MC3T3-E1 cells on the NT surface with those on the ST surface by performing transmission electron microscopy (TEM), confocal laser scanning microscope (CLSM) and real-time PCR. At the same time, we also detected changes in the MFF and osteogenic differentiation of MC3T3-E1 cells after DRP1 downregulation with RNA interference. Cells on the NT surface exhibited more mitochondrial fusion than those on the ST surface, and DRP1 was the key regulatory molecule. Interestingly, DRP1 increased for only a short time at the early stage on the NT surface, and when DRP1 was inhibited by siRNA at the early stage, the osteogenic differentiation of MC3T3-E1 cells significantly decreased. In conclusion, DRP1-regulated mitochondrial dynamics played a key role in the nanotopography-accelerated osteogenic differentiation of MC3T3-E1 cells.

This study aimed to investigate the inhibitory effect of EM-2, a natural active monomer purified from Elephantopusmollis H.B.K., on the proliferation of human hepatocellular carcinoma cells and the molecular mechanism involved. The results from the MTT assay revealed that EM-2 significantly inhibited the proliferation of human hepatocellular carcinoma (HCC) cells in a dose-dependent manner but exhibited less cytotoxicity to the normal liver epithelial cell line LO2. EdU staining and colony formation assays further confirmed the inhibitory effect of EM-2 on the proliferation of Huh-7 hepatocellular carcinoma cells. According to the RNA sequencing and KEGG enrichment analysis results, EM-2 markedly activated the MAPK pathway in Huh-7 cells, and the results of Western blotting further indicated that EM-2 could activate the ERK and JNK pathways. Meanwhile, EM-2 induced apoptosis in a dose-dependent manner and G2/M phase arrest in Huh-7 cells, which could be partially reversed when treated with SP600125, a JNK inhibitor. Further study indicated that EM-2 induced endoplasmic reticulum stress and blocked autophagic flux in Huh-7 cells by inhibiting autophagy-induced lysosome maturation. Inhibition of autophagy by bafilomycin A1 could reduce cell viability and increase the sensitivity of Huh-7 cells to EM-2. In conclusion, our findings revealed that EM-2 not only promoted G2/M phase arrest and activated ER stress but also induced apoptosis by activating the JNK pathway and blocked autophagic flux by inhibiting autolysosome maturation in Huh-7 hepatocellular carcinoma cells. Therefore, EM-2 is a potential therapeutic drug with promising antitumor effects against hepatocellular carcinoma and fewer side effects.

In this research, by using the metalloligands approach, a new heterometallic–organic framework has been successfully prepared by one-step synthesis of reacting H4L with metal acetate in water and EtOH mixed solvent, and its chemical formula is {CdNa2(H2O)3[(CoL)2Na(OH)(H2O)]}·6H2O (1, H4L = 3,3′-((1E,1′E)-(cyclohexane-1,2-diylbis(azanylylidene))bis(methanylylidene))bis(4-hydroxybenzoic acid)). In the biological study, the CCK-8 method was exploited to determine the survival rate of MCF7 breast cancer cells after compound treatment. The plate colony formation test was used to confirm the inhibitory effect of this compound on the proliferation of MCF7 cancer cell. Besides, the Annexin V-FITC/PI assay were performed to evaluate the apoptosis of compound-treated MCF7 cells in flow cytometer, the intracellular ROS level was also measured via Reactive Oxygen Species Assay Kit in this study.

Four new noble metal-free hybrids are reported with a maximum photocatalytic hydrogen evolution rate of 12245.59 μmol g−1 h−1, which outperform all known polyoxometalate (POM)-based metal–organic photocatalysts.

The assembly of snRNP cores, in which seven Sm proteins, D1/D2/F/E/G/D3/B, form a ring around the nonameric Sm site of snRNAs, is the early step of spliceosome formation and essential to eukaryotes. It is mediated by the PMRT5 and SMN complexes sequentially in vivo. SMN deficiency causes neurodegenerative disease spinal muscular atrophy (SMA). How the SMN complex assembles snRNP cores is largely unknown, especially how the SMN complex achieves high RNA assembly specificity and how it is released. Here we show, using crystallographic and biochemical approaches, that Gemin2 of the SMN complex enhances RNA specificity of SmD1/D2/F/E/G via a negative cooperativity between Gemin2 and RNA in binding SmD1/D2/F/E/G. Gemin2, independent of its N-tail, constrains the horseshoe-shaped SmD1/D2/F/E/G from outside in a physiologically relevant, narrow state, enabling high RNA specificity. Moreover, the assembly of RNAs inside widens SmD1/D2/F/E/G, causes the release of Gemin2/SMN allosterically and allows SmD3/B to join. The assembly of SmD3/B further facilitates the release of Gemin2/SMN. This is the first to show negative cooperativity in snRNP assembly, which provides insights into RNA selection and the SMN complex’s release. These findings reveal a basic mechanism of snRNP core assembly and facilitate pathogenesis studies of SMA.

The interaction of platelet GPIbα with von Willebrand factor (VWF) is essential to initiate platelet adhesion and thrombosis, particularly under high shear stress conditions. However, no drug targeting GPIbα has been developed for clinical practice. Here we characterized anfibatide, a GPIbα antagonist purified from snake (Deinagkistrodon acutus) venom, and evaluated its interaction with GPIbα by surface plasmon resonance and in silico modeling. We demonstrated that anfibatide interferds with both VWF and thrombin binding, inhibited ristocetin/botrocetin- and low-dose thrombin-induced human platelet aggregation, and decreased thrombus volume and stability in blood flowing over collagen. In a single-center, randomized, and open-label phase I clinical trial, anfibatide was administered intravenously to 94 healthy volunteers either as a single dose bolus, or a bolus followed by a constant rate infusion of anfibatide for 24 h. Anfibatide inhibited VWF-mediated platelet aggregation without significantly altering bleeding time or coagulation. The inhibitory effects disappeared within 8 h after drug withdrawal. No thrombocytopenia or anti-anfibatide antibodies were detected, and no serious adverse events or allergic reactions were observed during the studies. Therefore, anfibatide was well-tolerated among healthy subjects. Interestingly, anfibatide exhibited pharmacologic effects in vivo at concentrations thousand-fold lower than in vitro, a phenomenon which deserves further investigation.Trial registration: Clinicaltrials.gov NCT01588132.

To investigate the relationship between the structures of polyoxometalate host–guest materials and their energy-storage performance, three novel polyoxometalate-based metal–organic compounds, [Ag10...

Fe3O4@C composites for use in alkaline nickel-iron rechargeable batteries are synthesized via a spray drying method. SEM and TEM confirm that the Fe3O4@C composite is a secondary particle microsphere formed by many primary particles uniformly coated with carbon. The particles aggregate with each other, which is equivalent to forming a three-dimensional conductive mesh. The electrochemical properties of the bare Fe3O4 and Fe3O4@C composites as anode materials for alkaline nickel-iron batteries are investigated. The results show that the Fe3O4@C composite synthesized by spray drying exhibits considerably high discharge capacities and an excellent rate capability. The specific discharge capacity of the Fe3O4@C composite reaches 693.7 mAh g−1 at a current density of 300 mA g−1, with a charging efficiency of 92.5%. Moreover, the Fe3O4@C composite exhibits an admirable cycling stability with a superior capacity retention of 92.0% for 100 cycles at a current density of 300 mA g−1. In addition, discharge capacities of 556.7 and 420.1 mAh g−1 are achieved at high current densities of 1200 and 2400 mA g−1, respectively.

Organophosphorus pesticides (OPs) are frequently for pest control in the agriculture industry. Accumulation of OPs is harmful to the environment and human health. Thus, facile and portable detection of organophosphorus pesticides is of great importance. Among these methods, the fluorescence assay holds the advantages of high sensitivity, simplicity, nondestructive properties. Conventional fluorophores have the drawbacks of poor photostability and low signal-to-noise ratio due to their aggregation-caused quenching drawbacks at high concentration or in the aggregate state. Aggregation-induced emission fluorogens (AIEgens) are one key to develop next-generation fluorescence sensor due to their high emission efficiency in the aggregated state. 1,2-bis[4-(3-sulfonatopropoxyl) phenyl]-1,2-diphenylethene (BSPOTPE) is a typical AIE molecule containing two hydroxyl group. In this study, a fluorescence sensor based on BSPOTPE-SiO2–MnO2 sandwich nanocomposites was fabricated. Thiocholine (TCh), which produced from acetylthiocholine(ATCh) by the hydrolysis of acetylcholinesterase (AChE), can “turn on” the fluorescence sensor. Based on the inhibition effect of OPs on AChE activity and the corresponding “turn off” effect on the fluorescence sensor, an AIE-based assay for OPs determination was developed. The fabricated sensor for paraoxon determination has a good linear relationship in the range of 1–100 μg/L and the LOD of 1 μg/L. Moreover, a simple, convenient fluorescence strip for visual semi-quantitative of OPs was fabricated, indicating this “on-off” fluorescent sensor is promising for on-site and infield detection.

The polymerization of C5 fraction without separation and concentration by using a commercial available Nd(P204)3/ AliBu3/AlEt2Cl has afforded for the first time a new kind of 1,3-pentadiene-isoprene random copolymers as rubber materials. Isoprene (IP) and E-1,3-pentadiene (EPD) acted as polymerization monomers, cyclopentadiene acted as poison, and other substances like alkanes, monoolefins, Z-1,3-pentadiene acted as solvents in this multicomponent C5 fraction polymerization system. The data of kinetic experiments, NMR, and DSC indicated that the polymerization of C5 fraction by Nd(P204)3/AliBu3/AlEt2Cl afforded the IP-EPD random copolymers. By controlling polymerization conditions such as [Al]/[Nd]/[Cl] molar ratio and polymerization temperature, the random EPD-IP copolymers containing high cis-1,4-poly(IP) (with selectivity 96%) and moderate cis-1,4-poly(EPD) (with selectivity 60%) units with a low glass transition temperature (about −60 °C), controllable molecular weight (Mn = 3.8 × 104‒14.3 × 104), and moderate molecular weight distribution (Mw/Mn = 2.17‒2.78) were obtained in a high yield.

To address the large structural and volume changes of commercial WO3 during charge/discharge, which make this material unsuitable for use in Li-ion batteries (LIBs), we herein prepared oxygen deficient WO3-x nanosheets on a large scale by thermal treatment of ammonium paratungstate in a reducing atmosphere followed by sonication and freeze-drying. The above nanosheets were employed as LIB anode materials and exhibited a specific capacity and cycling stability significantly exceeding those of oxygen-deficient WO3-x nanoparticles and commercial WO3. In addition, we investigated the effect of nanosheet loading on electrode performance, demonstrating that the best results (Li storage capacity of ∼628 mAh g−1 after 100 cycles at 100 mA g−1) were obtained at a nanosheet content of 20 wt%. This excellent performance was ascribe to the good exposure of defects caused by the comparatively small size of WO3-x nanosheets, which resulted in an increased number of sites and diffusion paths available for Li-ion storage and transfer. The novel electrode-optimized strategy may be extended to the fabrication of other electrodes that use nanomaterials as active substances due to its superior comprehensive performance and low cost.

A new polyoxometalate (POM)-based inorganic-organic compound [Cu2(bimb)2(ox)](W6O19)·4H2O [bimb = 1,3-bis(1-imidazoly)benzene, ox = oxalic acid] (1), has been synthesized by hydrothermal reaction, and characterized by IR spectroscopy, single crystal X-ray diffraction, and powder X-ray diffraction. It consists by porous metal-organic 2D positive layers [Cu2(bimb)2(ox)]n2n+ and the W6O192− clusters serving as anionic pillars that make [Cu2(bimb)2(ox)]n2n+ positive layers aggregating around W6O192− clusters to achieve a novel porous intercalation structure. The compound 1 show high electrocatalytic activity for hydrogen evolution reaction (HER) with low overpotential (η) of 146 mV at a current density of 10 mA·cm−2, which is superior than the most of reported POM-based electrocatalysts. This is probable due to its unique porous intercalation structure that H+ can diffuse easily through the pores. Also, the HER mechanism was discussed, and the electrocatalytic reduction of NO2− ions was studied.

Due to their low yield and easy aggregation during the electrode preparation process, exfoliated MoS2 monolayers cannot fulfill the requirements of alkali-metal-ion battery tests. Hence, we have developed a facile process to fabricate powder exfoliated MoS2 nanosheets capable of large-scale production and having highly monolayer-rich structures. This process contains two steps: liquid-phase exfoliation of the edge-rich MoS2 precursor and a freeze-drying procedure. The proposed MoS2 precursors contain rich edge fractions that are easily exfoliated by this method, and the freeze-drying procedure can maintain the unique monolayer-rich structure of MoS2 in the powder phase. The electrochemical evaluations of both lithium- and sodium-ion batteries reveal that the proposed powder exfoliated monolayer-rich MoS2 electrode exhibits remarkable specific capacities and stable cyclic performances. In particular, the monolayer-rich MoS2 nanosheet electrode delivers a superior lithium-storage capacity of ∼1400 mA h g-1. The exfoliated MoS2 nanosheet electrode can withstand over 1000 cycles even at 1 A g-1. The mechanism reveals that these unique MoS2 nanosheets not only have a large surface area but also their inclusive monolayer structures exhibit much higher charge mobility than those of bulk MoS2.

Despite the widespread use of graphene oxide (GO) in diverse applications and increasing interest in its inclusion in some water treatment devices, mechanistic understanding of photochemical GO transformations is limited. This is an important knowledge gap relevant to GO performance and durability. We examined the reaction pathways and products of a GO suspension under UV irradiation in the presence of nitrate, a common anion in water and wastewater treatment processes. As the nitrate concentration increased, the dominant pathway of GO transformation changed from direct photolysis to indirect photolysis enhanced by the production of hydroxyl radicals (˙OH) during UV irradiation of nitrate. At environmentally relevant concentrations (e.g., 1 mM), nitrate induced significant fragmentation of the GO nanostructure. The significant effects of ˙OH on GO morphology and surface properties were verified by negative-control tests, including deoxygenation of the suspension, reactive oxygen species (ROS) inhibition and radical trapping, and by γ-radiolysis, known to generate a single ROS: ˙OH. Supplemental photolysis experiments conducted using graphite demonstrated that the main reaction pathways of the indirect photolysis of GO not only include the oxidation reactions between ˙OH and the oxidized domains of GO, but also the electrophilic addition reaction between ˙OH and the aromatic domains. These findings have significant implications for GO integrity and durability in systems involving incidental or purposeful exposure to UV irradiation.

Casein kinase-2 interaction protein-1 (Ckip-1) is a negative regulator of bone formation. The identification of novel Ckip-1-related targets and their associated signaling pathways that regulate mesenchymal stem cell (MSC) osteogenic differentiation is required. The present study aimed to evaluate the effects of Ckip-1 knockdown on C3H10T1/2 MSC proliferation and osteogenic differentiation, and to explore the role of the canonical Wnt-signaling receptor Lrp5. Ckip-1-knockdown (shCkip-1), Ckip-1-overexpression (Ckip-1) and their corresponding control [shCtrl and empty vector (EV), respectively] cell groups were used in the present study. Immunofluorescence localization of Ckip-1 was observed. The expression of the key molecules of the canonical Wnt signaling pathway was examined in C3H10T1/2 cells following osteogenic induction. Moreover, the effects of Lrp5 knockdown in the presence or absence of Ckip-1 knockdown were examined on C3H10T1/2 cell proliferation and osteogenic differentiation. The results indicated an increase in cell proliferation and osteogenic differentiation in the shCkip-1 group compared with the shCtrl group. The expression levels of LDL receptor related protein 5 (Lrp5), lymphoid enhancer binding factor 1 (Lef1) and transcription factor 1 in C3H10T1/2 cells were significantly increased in shCkip-1 cells following 7-day osteoinduction compared with shCtrl cells. Moreover, the involvement of Lrp5 in shCkip-1-induced osteogenic differentiation of C3H10T1/2 cells was further verified. The results indicated that Ckip-1 reduced C3H10T1/2 MSC proliferation and osteogenic differentiation via the canonical Wnt-signaling receptor Lrp5, which is essential for the improvement of bone tissue engineering.

Elevated cholesterol is an established risk factor for ischemic stroke. The value of statins for stroke prevention has been clear for more than a decade. However, the use of new medication combinations such as ezetimibe or proprotein convertase subtilisin–kexin type 9 inhibitors plus statins is increasing and the value for reducing stroke has been shown for these combination therapies. Recent data also support the strategy of lowering triglycerides for stroke prevention. A modern approach to dyslipidemia treatment and its relation to stroke prevention is summarized in this paper.

Long non-coding RNAs (lncRNAs) have been ascertained as vital modulators in abdominal aortic aneurysm (AAA) development. In this research, the function and molecular mechanisms of the lncRNA X-inactive specific transcript (XIST) in the evolution of vascular smooth muscle cells (VSMCs) were assessed. Results showed that XIST expression was increased but miR-1264 expression level was reduced in the serum of AAA patients. XIST depletion impeded human aorta VSMCs (HA-VSMCs’) ability to proliferate and stimulate apoptosis, while repressing miR-1264 expression through an unmediated interaction. Additionally, the influence of XIST knockdown on apoptosis and proliferation could be rescued by an miR-1264 inhibitor. Subsequent molecular investigations indicated that WNT5A was miR-1264’s target, and XIST functioned as a competing endogenous RNA (ceRNA) of miR-1264 to raise WNT5A expression. Further, an miR-1264 inhibitor stimulated the proliferation and suppressed the apoptosis of HA-VSMCs through the activation of WNT/β-catenin signaling. Taken together, XIST impeded the apoptosis and stimulated the proliferation of HA-VSMCs via the WNT/β-catenin signaling pathway through miR-1264, demonstrating XIST’s underlying role in AAA.

Carbohydrate concentrations are important indicators of the internal quality of Phalaenopsis. In this study, near-infrared (NIR) spectroscopy was used for quantitative analyses of fructose, glucose, sucrose, and starch in Phalaenopsis plants. Both modified partial least-squares regression (MPLSR) and stepwise multiple linear regression (SMLR) methods were used for spectral analysis of 302 Phalaenopsis samples in the full visible NIR wavelength range (400–2498 nm). Calibration models built by MPLSR were better than those built by SMLR. For fructose, the smoothed first derivative MPLSR model provided the best results, with a correlation coefficient of calibration (Rc) of 0.96, standard error of calibration (SEC) of 0.22% dry weight (DW), standard error of validation (SEV) of 0.28% DW, and bias of -0.01% DW. For glucose, the MPLSR model based on the smoothed first derivative spectra was the best (Rc = 0.96; SEC = 0.26% DW; SEV = 0.32% DW; and bias = 0.01% DW). The best MPLSR model of sucrose was developed using the smoothed first derivative spectra (Rc = 0.96; SEC = 0.24% DW; SEV = 0.31% DW; bias = -0.03% DW). Regarding starch, the smoothed first derivative MPLSR model showed the best effects (Rc = 0.91; SEC = 0.47% DW; SEV = 0.56% DW; bias = -0.02% DW). Both the MPLSR and SMLR models showed satisfactory predictability, indicating that NIR has the potential to be adopted as an effective method of rapid and accurate inspection of the carbohydrate concentrations of Phalaenopsis plants. This technique could contribute substantially to quality management of Phalaenopsis.

Clean fuels are recommended for ships at berth to reduce air pollutant emissions. This study aimed to evaluate the feasibility of waste cooking oil (WCO) biodiesel application on board with regard to particle matter (PM) and polycyclic aromatic hydrocarbon (PAH) emissions. An experiment was conducted on a marine auxiliary engine for three different fuels: WCO biodiesel, formulation blends with marine gas oil (MGO) and neat MGO. Results revealed that WCO biodiesel could reduce PM and PAHs emissions. WCO exhaust also exhibited differences in PAH profile and phase distribution as compared to MGO, depending on the operation modes and the proportion of biodiesel in the formulation blends. Consequently, WCO biodiesel could dramatically reduce the total carcinogenic potencies related to PAHs of exhausts. Moreover, PAH source recognition pair ratios of tested fuels were observed to deviate from the widely accepted values. This study highlights that WCO biodiesel is a cleaner fuel for operating ship auxiliary engines with respect to PM and PAHs emissions and has the potential to moderate the severe effects of PM and PAHs on an air of coastal areas.

Unique hierarchical mulberry-shaped Na3V2(PO4)2O2F@C nanocomposite was fabricated by a rapid microwave-assisted low-temperature refluxing strategy. The V(acac)3 reverse micelle systems in the water-in-oil microemulsions played key roles in forming the self-assembly architectures. The prepared Na3V2(PO4)2O2F@C nanoparticles with the anisotropic growth along the [002] direction were in - situ encapsulated in carbon shells, which greatly contribute to fast Na+/e− transfer in electrodes. And the self-assemblies with high structure stability help to improve the cycle performance and mitigate voltage fading. The initial discharge capacity of Na3V2(PO4)2O2F@C as cathode for sodium ion batteries is about 127.9 mA h g−1 at 0.1 C. Besides, a high rate performance with a capacity of 88.1 mA h g−1 at 20 C has been achieved, and the capacity retains 82.1% after 2,000 cycles. In addition, the reaction kinetics and Na+ transportation mechanism of Na3V2(PO4)2O2F@C were preliminarily investigated by the ex situ X-ray diffraction, X-ray photoelectron spectroscopy and galvanostatic intermittent titration technique. More interestingly, when coupled with Li, the fabricated hybrid Li/Na-ion batteries also exhibit excellent rate and cycling performances. The proposed rapid refluxing strategy to synthesize mulberry-shaped Na3V2(PO4)2O2F@C opens up a new opportunity to develop high-performance electrode materials for the energy storage systems.

Cancer cell resistance to current anticancer therapeutics as well as the side effects are still obstacles to successful cancer therapy. Hence, the development of novel anticancer agents or therapeutics is of vital significance, and especially rational adjuvant therapies containing low-cost natural products with multiple targets have attracted great interests. Triptolide, the main biocomponent of Tripterygium wilfordii Hook F, is restricted in clinical applications mainly due to its severe systemic toxicities, although it has shown strong antitumor activities in preclinical studies. Mounting evidence suggests that triptolide at low doses as an adjuvant therapeutic agent circumvents resistance to current anticancer therapies, enhances the anticancer effectiveness, and relieves toxicities of both triptolide and anticancer therapies. Furthermore, several unique antitumor targets of triptolide make it superior to other therapeutics. The molecular mechanisms of triptolide-induced anti-resistance and sensitization effects include changes in ATP-binding cassette transporters, induction of apoptosis pathways, increase in tumor suppressors and decrease in oncogenic factors, and interactions with the RNA polymerase II complex; targeting cancer stem cells and tumor-microenvironment-mediated resistance are also involved. Besides, some synthetic derivatives and novel delivery systems of triptolide are also developed to enhance the water-solubility and reduce the toxicity, which will also be discussed.

In this article, highly [010]-oriented self-assembled LiCoPO4/C nanoflakes were prepared through simple and facile solution-phase strategies at low temperature and ambient pressure. The formation of 5-hydroxylmethylfurfural and levoglucosan via the dehydration of glucose during the reaction played a key role in mediating the morphology and structure of the resulting products. LiCoPO4 highly oriented along the (010)-facets exposed Li+ ion transport channels, facilitating ultrafast lithium ion transportation. In turn, the unique assembled mesoporous structure and the flake-like morphology of the prepared products benefit lithium ion batteries constructed using two-dimensional (2D) LiCoPO4/C nanoflakes self-assembles as cathodes and commercial Li4Ti5O12 as anodes. The tested batteries provide high capacities of 154.6 mA·h·g−1 at 0.1 C (based on the LiCoPO4 weight of 1 C = 167 mA·h·g−1) and stable cycling with 93.1% capacity retention after 100 cycles, which is outstanding compared to other recently developed LiCoPO4 cathodes.

The preparation and dielectric properties of silver-polydopamine/poly(vinylidene fluoride) (Ag-PDOP/PVDF) composite films with suppressed dielectric loss are reported. The dielectric loss tangents ...

Rapid and large-scale synthesis of metal–organic frameworks (MOFs) materials is of great significance for their practical applications. For the first time, we have electrochemically synthesized IRMOF-3 at room temperature by applying a voltage to a zinc electrode immersed in electrolyte containing 2-aminoterephthalic acid (NH2-H2BDC). The reaction conditions, including the ratio of solvent (electrolyte), the applied voltage, and different reaction times, were investigated and optimized. The degree of crystallinity and nanomorphology of the synthesized IRMOF-3 can be controlled by changing the reaction conditions. More importantly, we demonstrated that the electrochemical synthesis strategy can rapidly obtain nanoscale IRMOF-3 with high crystallinity on a gram scale. In addition, in comparison with the product of solvothermal synthesis, the electrochemically synthesized nanoscale IRMOF-3 exhibits improved fluorescent detection ability to 2,4,6-trinitrophenol (TNP) with a detection limit of about 0.1 ppm.

A novel helical compound, Zn(Htib)(tib)PMo12O40 (1) (tib = 1, 3, 5-tris-(1-imidazolyl)-benzene) was hydrothermally synthesized. The structure has been determined by single-crystal X-ray diffraction analyses and characterized by IR, XPS, UV–Vis and XRD and elemental analyses. Single crystal X-ray analysis reveals that compound 1 possesses entangled double helixes, which is formed by a pair of right- and left- handed double helixes sharing Zn atoms and a part of tib ligands. The adjacent entangled double helixes are further fused together, and thus a wavy Zn-tib metal-organic layer is constructed. Finally, through hydrogen bonds, the neighboring Zn-tib metal-organic layers are interconnected in a staggering peak-load manner to give birth to a porous 3D supramolecular framework with large rhombus-like apertures, in which the [PMo12O40]3- (PMo12) anions were encapsulated into the open channel structure and sandwiched by the Zn-tib layers. Additionally, compound 1 exhibits high efficiency and stability, and well reproducibility towards photocatalytic degradation of RhB dye under UV irradiation. The fluorescence property of 1 was also investigated.

Circular RNAs (circRNAs) exert crucial regulatory effects in the pathogenesis of multiple tumors. This work aimed to probe into the role of circ_0000094 in T cell acute lymphoblastic leukemia (T-ALL). In this work, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to quantify circ_0000094, miR-223-3p, and F-box and WD repeat domain containing 7 (FBW7) mRNA expressions in lymph node samples from T-ALL patients; Western blot was adopted to examine FBW7 protein expression in T-ALL cells; cell proliferation was detected by cell counting kit-8 (CCK-8) experiment; apoptosis was examined by flow cytometry; Transwell experiments were applied to assess T-ALL cell migration and invasion; the interactions among circ_0000094 and miR-223-3p, and miR-223-3p and FBW7 were validated by bioinformatics prediction, dual-luciferase reporter gene assay, and RNA immunoprecipitation experiment. We reported that, circ_0000094 expression was markedly reduced in T-ALL and circ_0000094 was predominantly located in the cytoplasm; gain-of-function and loss-of-function assays verified that circ_0000094 overexpression remarkably suppressed T-ALL cell proliferation, migration, and invasion, and enhanced apoptosis while knocking down circ_0000094 enhanced the malignant phenotypes of T-ALL cells; "rescue experiments" implied that miR-223-3p mimics partly reversed the inhibitory effects on the malignant phenotype of T-ALL cells due to the circ_0000094 up-regulation; circ_0000094 was proved to be a molecular sponge for miR-223-3p, and it could up-regulate the expression of FBW7 via repressing miR-223-3p expression. Taken together, it was concluded that circ_0000094 impedes T-ALL progression by modulating the miR-223-3p/FBW7 axis.

By introducing mixed-ligands en and ox, $$\hbox {Cu}^{2+}$$ and different polyoxotungstates as synthons, two new polyoxotungstate-based inorganic-organic hybrid compounds $$\{[\hbox {Cu}_{2}\hbox {(en)}_{2}\hbox {(ox)}]\hbox {[HPW}_{12}\hbox {O}_{40}]\}\cdot \hbox {(en)}_{2}\cdot \hbox {2H}_{2}\hbox {O}$$ (1) and $$\{[\hbox {Cu}_{2}\hbox {(en)}_{2}\hbox {(ox)}]$$ [ $$\hbox {H}_{3}\hbox {BW}_{12}\hbox {O}_{40}]\}\cdot \hbox {(en)}_{2}\cdot \hbox {2H}_{2}\hbox {O}$$ (2) (en = ethylenediamine and ox = oxalate), were obtained in identical hydrothermal conditions and further characterized by elemental analyses, IR spectroscopy and single-crystal X-ray diffraction. Structural analyses revealed that both compounds are isostructural, and show one-dimensional (1D) chain constructed by $$\hbox {[XW}_{12}\hbox {O}_{40}]^{\mathrm{n}-}$$ (X = P 1, B 2) Keggin-type polyoxoanions and $$[\hbox {Cu}_{2}\hbox {(en)}_{2}\hbox {(ox)}]^{2+}$$ dinuclear copper subunits. The electrochemical experiments indicated that 1-based carbon paste electrode possesses high catalytic efficiency and selectivity towards reduction of $$\hbox {H}_{2}\hbox {O}_{2}$$ , and thus 1 has potential to detect $$\hbox {H}_{2}\hbox {O}_{2}$$ . SYNOPSIS Two new hybrids based on polyoxoanions and dinuclear copper complexes have been synthesized and characterized. The results of electrocatalytic experiments indicate that the hybrid-based electrode possesses high catalytic efficiency and selectivity towards reduction of $$\hbox {H}_{2}\hbox {O}_{2}$$ .

Danshen, an efficacious agent for cardiovascular diseases, has been found to play an essential role in kidney injury. In the present study, the effect of Danshen on cisplatin-induced renal dysfunction was investigated in a mouse model. Danshen was administered to mice at a dose of 3 g/kg 4 days before and 3 days after cisplatin treatment. A single intraperitoneal injection of 20 mg/kg cisplatin was used to induce nephrotoxicity. The mice were sacrificed 72 h after cisplatin intoxication. Biochemical parameters including serum creatinine and blood urea nitrogen were analyzed. Histopathological changes of kidney tissues were detected using HE staining. Antioxidant enzymes (GSH-Px and SOD) and peroxidative product (MDA) were detected. Protein expressions of Nrf2 and its target genes including HO-1 and NQO1 were measured by Western blotting. The results showed that pretreatment with Danshen significantly reduced serum creatinine and blood urea nitrogen in the cisplatin-treated mice. Histopathological examination showed that Danshen mitigated the renal damage induced by cisplatin. Moreover, Danshen restored the activities of antioxidant enzymes (GSH-Px and SOD) and normalized the MDA contents in renal tissues. Western blotting revealed that Danshen enhanced the expressions of Nrf2 and its target genes in cisplatin-exposed mice. It was suggested that Danshen protects against the cisplatin-induced renal impairment in the mice, which is potentially associated with the upregulation of Nrf2-mediated signaling pathway.

Three illudin sesquiterpenoids, craterellins A–C, and one gymnomitrane sesquiterpenoids, gymnomitr-3-en-10 β ,15-diol, were isolated from cultures of the basidiomycete Craterellus cornucopioides , along with four previously reported compounds: illudin F, illudin M, illudin T and illudalenol. Structures of new compounds were elucidated on the basis of extensive spectroscopic analysis and their cytotoxic activities on five tumor cell lines were evaluated.

Triptolide (TP) is an active ingredient isolated from Tripterygium wilfordii Hook. f. (TWHF), which is a traditional herbal medicine widely used for the treatment of rheumatoid arthritis and autoimmune disease in the clinic. However, its adverse reactions of hepatotoxicity and nephrotoxicity have been frequently reported which limited its clinical application. The aim of this study was to investigate the mechanism of glycyrrhetinic acid (GA) effecting on the elimination of TP in HK-2 cells and the role of the efflux transporters of P-gp and multidrug resistance-associated proteins (MRPs) in this process. An ultra performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) analytical method was established to determine the intracellular concentration of TP. In order to study the role of efflux transporters of P-gp and MRPs in GA impacting on the accumulation of TP, the inhibitors of efflux transporters (P-gp: verapamil; MRPs: MK571) were used in this study. The results showed that GA could enhance the elimination of TP and reduce the TP accumulation in HK-2 cells. Verapamil and MK571 could increase the intracellular concentration of TP; in addition, GA co-incubation with verapamil significantly increased the TP cellular concentration compared with the control group. In conclusion, GA could reduce the accumulation of TP in HK-2 cells, which was related to P-gp. This is probably one of the mechanisms that TP combined with GA to detoxify its toxicity. Copyright © 2017 John Wiley & Sons, Ltd.

A robust and highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of pericyazine in human plasma. The plasma sample was alkalized with sodium hydroxide solution and handled by liquid-liquid extraction with ethyl acetate after adding perphenazine as an internal standard (IS). The analytes were separated on an Ultimate™ AQ-C18 analytical column at 40°C, with a gradient elution consisting of A (aqueous phase: 5mM ammonium acetate buffer solution containing 0.1% formic acid) and B (organic phase: acetonitrile) at a flow rate of 0.350mL/min. The detection was conducted on an API 4000 tandem mass spectrometer coupled with electrospray ionization (ESI) source in positive ion mode. The multiple reaction monitoring (MRM) transitions, m/z 366.5>142.4 for pericyazine, m/z 382.5>142.4 for its 7-hydroxy and sulphoxide metabolites and m/z 404.3>171.3 for IS were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity (LLOQ of 0.021ng/mL) and good linearity over the concentration range of 0.021-9.90ng/mL. The intra- and inter-day precision, accuracy, and stability results were within the acceptable limits and no matrix effect was observed. This method was successfully applied in a bioequivalence study to evaluate the pharmacokinetics in 20 healthy male Chinese volunteers. Additional exploratory analyses of 7-hydroxy and sulphoxide metabolites of pericyazine in the same samples suggest that the unchanged drug is predominant in the plasma and suitable for the bioequivalence comparison after a single oral administration of 10mg pericyazine.

As an important herbaceous plant, Scutellaria baicalensis Georgi (Chinese skullcap) is geographically widespread and commonly used throughout the world. In the Chinese medicine market, S. baicalensis has been divided into two primary types, "Ku Qin" (WXR) and "Tiao Qin" (TST). Moreover, TST is also divided into different grades according to the diameter of roots. To explore the distribution patterns of the contents of five biologically activate ingredients (FBAI), we used six-year-old cultivated S. baicalensis and analyzed its growth characteristics as well as the quality difference among different types and diameters in roots. Throughout the entire root, we discovered that contents of the FBAI all initially increased and subsequently decreased from the top to the bottom of the roots. The baicalin content of WXR was less than that of TST. On the contrary, the contents of baicalein, wogonin, and oroxylin A in WXR were up to about two times higher than that in TST. We also found that the 0 to 40 cm part of the S. baicalensis root possessed about 87% of the root biomass and about 92% of the contents of the active ingredients.

The droplet analysis technology and the detection principles of water quality parameters are combined to achieve quantitative detection of multi-parameter of water. The detection platform is designed based on fiber and capacitance droplet analysis technology, which is mainly composed of the droplet sensor, dissolved oxygen probe, liquid supply pump, photoelectric conversion elements, and the signal processing circuit. The detection of three quality parameters (refractive index, turbidity and dissolved oxygen) is carried out on this platform through experiments. For the turbidity of the water, the sample’s rainbow-peak value of the fingerprint obtained with the droplet sensor is proved to be highly correlated with turbidity. And the prediction model of turbidity is established by regression analysis method with Formazine standard solution, with he maximum relative error 3.9%. The measurement model of dissolved oxygen is researched by collecting the fluorescence signal excited by the dissolved oxygen probe and the sample’s temperature, and the performance of the BP neural network model and the regression model is compared. And it shows that BP neural network model performs better in the detection of dissolved oxygen. The measurement model of refractive index is determined through regression analysis, and the value of the rainbow-peak is selected as the key factor through the experiments with NaCl solution. The establishment of the three parameters’ detection model shows us a method to realize multi-parameter detection for environmental water quality.

Diverse derivatives of amino acids with different steric configurations are important biosynthetic building blocks. In biology, epimerization is an important way to generate steric diversity. MarH catalyzes the epimerization of the β-position of (3R)-β-methyl-indolepyruvate (MeInPy), forming (3S)-β-MeInPy. Both compounds are derivatives of l-tryptophan (l-Trp) and are important precursors of bioactive natural products. Here, we report the crystal structures of MarH and the NMR structure of its complex with l-Trp, an analogue of its native substrate, (3R)-β-MeInPy. Structural analysis and mutagenesis studies indicated that His25 acts as a base to remove Hβ and generate a planar carbanion intermediate, which is then putatively reprotonated on the opposite face by a water molecule to form (3S)-β-MeInPy in a stereospecific manner. The details of β-site isomerization at the atomic level provide deeper insights into the epimerization mechanism of MarH and will facilitate further enzyme design to extend the substrate scope.

Background In the present work, we investigated the effects of aqueous extract of Maca (AEM) on energy metabolism and immunoregulation in spleen-deficient mice. Method We established a cyclophosphamide-induced spleen-deficiency model with ginseng, a herb that strengthens splenic function, as a control. Sixty male Kunming mice were randomly divided among 5 groups: normal, model, ginseng control (1.5 g/kg), AEM high dose (1.5 g/kg), and AEM low dose (0.75 g/kg). All animals, except those in the normal group, were injected with cyclophosphamide to induce spleen deficiency. Furthermore, we investigated differences in the thermotropic behaviors of mice using the Animal Thermotropism Behavior Surveillance System to detect energy metabolism-related assays and immune regulation assays. Results Mice given AEM exhibited tropism in response to hot plate exposure. AEM inhibited loss of body weight and immune organ atrophy caused by cyclophosphamide, increased the cAMP/cGMP ratio in blood, and enhanced the activities of Na+–K+-ATPase, Ca2+–Mg2+-ATPase, lactate dehydrogenase, and hepatic glycogen. AEM significantly reversed declining white blood cells and platelet counts, and increased the hemoglobin content within peripheral blood cells. AEM improved the protein levels of IFN-γ, TNF-β, IL-2, and IL-4 in the spleen. Conclusions Maca possesses the Traditional Chinese Medicine (TCM) property of warm and appears to strengthen spleen function.

Piezoelectric polymer composite films have attracted extensive attention due to their comprehensive characteristics such as low cost, good flexibility, mechanical property and excellent processability. Among the known polymers, poly (vinylidene fluoride) (PVDF) is an ideal piezoelectric polymer because the β-crystalline form of PVDF has the highest polarization per unit cell. However, initial PVDF mostly suffers from the lack of a β phase, restricting its potential applications. Few-layer MoS2 is predicted to be strongly piezoelectric owing to the opposite orientations of adjacent atomic layers. In this work, we report an efficient approach to enhance the piezoelectric property of PVDF-based nanocomposites by combining few-layer MoS2 with PVDF. The product yield for few-layer MoS2 reached a value as high as 83.3% via a unique liquid-exfoliation technique. For a few-layer MoS2/PVDF composite film with 1 wt.% few-layer MoS2, a high piezoelectric performance enhancement of 360% was achieved compared with the initial PVDF film. In addition, due to the intrinsic lubrication of MoS2, the highest elongation of the piezoelectric composite film was found to be four times higher than that of the pure PVDF film.

Therapeutic proteins are a rapidly growing class of drugs in clinical settings. The pharmacokinetics (PK) of therapeutic proteins relies on their absorption, distribution, metabolism, and excretion (ADME) properties. Moreover, the ADME properties of therapeutic proteins are impacted by their physicochemical characteristics. Comprehensive evaluation of these characteristics and their impact on ADME properties are critical to successful drug development. This chapter summarizes all relevant physicochemical characteristics and their effect on ADME properties of therapeutic proteins.