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Explorations in the stereolithography fabricated polymer-derived ceramics are still far from maturity. Herein, a novel preceramic slurry, which consists of a photocurable epoxy-acrylic siloxane and particle-size gradated ZrO2 fillers, was digital light processing shaped into 3D preceramic precursors. By taking advantage of the high reactivity of in-situ formed silica from the polysiloxane, 3D-zircon product can be synthesized through the sintering reaction between the polysiloxane and ZrO2 particles in the precursor at a low temperature. During the sintering process, ZrSiO4 phase starts to appear at the temperature of 1200 °C. A proper particle-size distribution of the ZrO2 filler, 20 wt% of micropartciles and 4 wt% of nanoparticles, not only endowed the ceramic slurry with a low viscosity but also increase the purity of the zircon products. Besides, the addition of sintering aid NaF can promote the sintering reaction between the polysiloxane and ZrO2 particles while increase the crystalize degree of the 3D-zircon products.

Nowadays, 3D polymer-derived silicon oxycarbide ceramics (SiOC) can be fabricated by the stereolithography method successfully. However, due to their intrinsically poor ceramic content and the large thermal shrinkage during the pyrolysis, it is difficult for the bulk 3D polysiloxane precursors to be pyrolyzed into dense 3D-ceramics. Herein, the ceramic content of the photocurable polysiloxane precursors was increased by adding a large amount of SiO2 powders into the low solid content epoxy-acrylic siloxane. After being added with proper dispersant, the viscosity of the high solid loading polysiloxane/SiO2 slurry can reach a proper level. Bulk 3D-silica ceramics with the wall-thickness around 8 mm can be conveniently fabricated from the polysiloxane/SiO2 slurry by stereolithography and a two-step sintering process. The addition of a proper sintering aid NaF can promote the 3D-PSO/SiO2 precursor to be converted into dense and crack-free 3D-silica ceramics with good mechanical proprieties.

Exosomal miRNAs, as potential biomarkers in liquid biopsy for cancer early diagnosis, have aroused widespread concern. Herein, an electrochemical biosensor based on DNA “nano-bridge” was designed and applied to detect exosomal microRNA-21 (miR-21) derived from breast cancer cells. In brief, the target miR-21 can specifically open the hairpin probe 1(HP1) labeled on the gold electrode (GE) surface through strand displacement reaction. Thus the exposed loop region of HP1 can act as an initiator sequence to activate the hybridization chain reaction (HCR) between two kinetically trapped hairpin probes: HP2 immobilized on the GE surface and biotin labeled HP3 in solution. Cascade HCR leads to the formation of DNA “nano-bridge” tethered to the GE surface with a great deal of “piers”. Upon addition of avidin-modified horseradish peroxidase (HRP), numerous HRP were bound to the formed “nano-bridge” through biotin-avidin interaction to arouse tremendous current signal. In theory, only a single miR-21 is able to trigger the continuous HCR between HP2 and HP3 until all of the HP2 are exhausted. Therefore the proposed biosensor achieved ultrahigh sensitivity toward miR-21 with the detection limit down to 168 amol/L, as well as little cross-hybridization even at the single-base-mismatched level. Successful attempts were also made in the detection of exosomal miR-21 obtained from the MCF-7 of breast cancer cell line. To our knowledge, this is the first attempt to built horizontal DNA nano-structure on the electrode surface for exosomal miRNAs detection. In a word, the high sensitivity, selectivity, low cost make the proposed method hold great potential application for early point-of-care (POC) diagnostics of cancer.

Here, we report a two-phase crystalline NiWO4 /amorphous Co-B nanocomposite as an electrode material for supercapacitors, which is effectively synthesized via a simple hydrothermal method and chemical precipitation method. The obtained NiWO4 /Co-B exhibits crystal-amorphous contact, which makes it have more active sites than other crystalline-crystalline phase boundaries, thereby enhancing electron transport. The NiWO4 /Co-B electrode with the best mass ratio of crystalline and amorphous exhibits a great specific capacitance and excellent cycle durability. Compared to individual Co-B and NiWO4 , it also shows enhanced rate capability Besides, NiWO4 /Co-B/activated carbon supercapacitor device can provide a good specific capacitance and a maximum energy density of 10.92 Wh kg-1 at 200 W kg-1 . This work provides new insights to develop novel electrode materials for energy storage and conversion.

Photoelectrochemical (PEC) water splitting over TiO2 photoanodes is a promising strategy for hydrogen production due to its eco-friendly, energy-saving, and low-cost nature. However, the intrinsic drawbacks of TiO2, i.e., the too wide band gap and rapid exciton recombination, significantly limit further enhancement of its performance. Herein, we report a TiO2 nanotube array (TNA), which is implanted by Cu ions and decorated by polymeric carbon nitride (PCN) nanosheets, as a photoanode for the high-efficiency PEC water splitting. In such designed material, Cu-ion implantation can effectively tailor the electronic structure of TiO2, thus narrowing the band gap and enhancing the electronic conductivity. Meanwhile, the PCN decoration induces TiO2/PCN heterojunctions, enhancing the visible light absorption and accelerating the exciton separation. Upon this synergistic effect, the modified TNA photoanode shows significantly improved PEC capability. Its photocurrent density, solar-to-hydrogen efficiency, and applied bias photon-to-current efficiency achieve 1.89 mA cm-2 at 1.23 VRHE (V vs reversible hydrogen electrode), 2.31%, and 1.20% at 0.46 VRHE, respectively. Importantly, this modified TNA supported on a meshlike Ti substrate can be readily integrated with a perovskite solar cell to realize unassisted PEC water splitting.

By taking advantage of the low sintering temperatures of the preceramic polymers, stereolithography printed mullite components derived from preceramic polymer precursor containing alumina particles can be sintered at low temperatures. However, due to their high specific surface, nano alumina particles are difficult to be dispersed into the photocurable polysiloxane. Herein, to prepare mullite slurry, a photosensitive hydroxysiloxane was employed as the preceramic polymer matrix while γ-Al2O3 nanoparticle was added as the active filler. The introduction of photocurable hydroxysiloxane not only improved the homogeneity and rheological properties of mullite slurry but also shorted the ionic diffusion distance of Si-ion and Al-ion during the sintering process. Therefore, 3D mullite preceramic precursor stereolithography printed from hydroxysiloxane-Al2O3 slurry was endowed with a low sintering temperature around 1400 °C. During the sintering process of preceramic precursor, sintering aid AlF3 can participate in the reaction and further promote the formulation of mullite grains.

Electrochemical reduction of dinitrogen (N2) to ammonia (NH3) at the ambient condition is a promising alternative to the traditional Haber-Bosch process due its energy-saving and eco-friendly natures. However, the extremely stable N N triple-bonds in N2 molecules and the competitive hydrogen evolution reaction (HER) have been regarded as the two essential issues in the electrocatalytic nitrogen reduction reaction (eNRR), making the simultaneous achievement of a high NH3 yield rate and a satisfactory Faradaic efficiency (FE) very difficult. To address this issue, we herein report a metal-free electrocatalyst, the boron-doped carbon nanosphere, to effectively activate the N N triple-bonds and suppress the HER during the eNRR process. In this protocol, the B–C configurations can be easily tailored by simply changing the boron precursor amount, and the one that is (i.e., BC3) beneficial to the enhancement of eNRR can achieve the maximum relative content of ∼43% in the optimum sample. Under this boron-doping amount, the material simultaneously delivers a high NH3 yield of 33.8 μg h−1 mg−1cat and a high FE of 39.2% at −0.7 V vs. reversible hydrogen electrode, accompanied with a superior stability for a continuous eNRR. This study thus offers an efficient, stable, and low-cost carbon-based catalyst for eNRR.

Background and aims Hypercholesterolemia is characterized by the elevation of plasma total cholesterol level, especially low-density lipoprotein (LDL) cholesterol. This disease is usually caused by a mutation in genes such as LDL receptor, apolipoprotein B, or proprotein convertase subtilisin/kexin type 9. However, a considerable number of patients with hypercholesterolemia do not have any mutation in these candidate genes. In this study, we examined the difference in the metabolic level between patients with hypercholesterolemia and healthy subjects, and screened the potential biomarkers for this disease. Methods Analysis of plasma metabolomics in hypercholesterolemia patients and healthy controls was performed by gas chromatography-mass spectrometry and metabolic correlation networks were constructed using Gephi-0.9.2. Results First, metabolic profile analysis confirmed the distinct metabolic footprints between the patients and the healthy ones. The potential biomarkers screened by orthogonal partial least-squares discrimination analysis included l -lactic acid, cholesterol, phosphoric acid, d -glucose, urea, and d -allose (Variable importance in the projection > 1). Second, arginine and methionine metabolism were significantly perturbed in hypercholesterolemia patients. Finally, we identified that l -lactic acid, l -lysine, l -glutamine, and l -cysteine had high scores of centrality parameters in the metabolic correlation network. Conclusion Plasma l -lactic acid could be used as a sensitive biomarker for hypercholesterolemia. In addition, arginine biosynthesis and cysteine and methionine metabolism were profoundly altered in patients with hypercholesterolemia.

The aryl hydrocarbon receptor (AhR) is a ligand-binding protein that responds to environmental aromatic hydrocarbons and stimulates the transcription of downstream phase I enzyme–related genes by binding the cis element of dioxin-responsive elements (DREs)/xenobiotic-responsive elements. Dimethyl sulfoxide (DMSO) is a well-known organic solvent that is often used to dissolve phase I reagents in toxicology and oxidative stress research experiments. In the current study, we discovered that 0.1% DMSO significantly induced the activation of the AhR promoter via DREs and produced reactive oxygen species, which induced apoptosis in mouse embryonic fibroblasts (MEFs). Moreover, Jun dimerization protein 2 (Jdp2) was found to be required for activation of the AhR promoter in response to DMSO. Coimmunoprecipitation and chromatin immunoprecipitation studies demonstrated that the phase I–dependent transcription factors, AhR and the AhR nuclear translocator, and phase II–dependent transcription factors such as nuclear factor (erythroid-derived 2)–like 2 (Nrf2) integrated into DRE sites together with Jdp2 to form an activation complex to increase AhR promoter activity in response to DMSO in MEFs. Our findings provide evidence for the functional role of Jdp2 in controlling the AhR gene via Nrf2 and provide insights into how Jdp2 contributes to the regulation of ROS production and the cell spreading and apoptosis produced by the ligand DMSO in MEFs. Graphical abstract

The rapid development of portable and wearable electronics has called for novel flexible electrodes with superior performance. The development of flexible electrode materials with excellent mechanical and electrochemical properties has become one of the key factors for this goal. Here, a NixCoy-silicate@CNTs film is developed as a flexible anode for lithium ion batteries (LIBs). On this film, NixCoy-silicate nanosheets are firmly and intimately anchored on the surface of CNTs, which have a 3D network structure and link the adjacent nanosheets together. Benefitted from this, the composite film is not only sufficient to withstand various deformations due to its excellent flexibility but also has excellent electrochemical properties, in terms of high reversible capacity of 1047 mAh g-1 at 0.1 A g-1 as well as a high rate and cycling performance (capacity retention up to 78.13% after 140 cycles). The pouch-type full flexible LIB using this material can stably operate under various bending conditions, showing the great potential of this 3D NixCoy-silicate@CNTs film for flexible energy storage devices with high durability.

Identifying novel drug targets to overcome resistance to tyrosine kinase inhibitors (TKIs) and eradicating leukemia stem/progenitor cells are required for the treatment of chronic myelogenous leukemia (CML). Here, we show that ubiquitin-specific peptidase 47 (USP47) is a potential target to overcome TKI resistance. Functional analysis shows that USP47 knockdown represses proliferation of CML cells sensitive or resistant to imatinib in vitro and in vivo. The knockout of Usp47 significantly inhibits BCR-ABL and BCR-ABLT315I-induced CML in mice with the reduction of Lin−Sca1+c-Kit+ CML stem/progenitor cells. Mechanistic studies show that stabilizing Y-box binding protein 1 contributes to USP47-mediated DNA damage repair in CML cells. Inhibiting USP47 by P22077 exerts cytotoxicity to CML cells with or without TKI resistance in vitro and in vivo. Moreover, P22077 eliminates leukemia stem/progenitor cells in CML mice. Together, targeting USP47 is a promising strategy to overcome TKI resistance and eradicate leukemia stem/progenitor cells in CML., Resistance to tyrosine kinase inhibitors (TKI) is a limitation to their use in treating chronic myelogenous leukemia (CML). Here, the authors show that targeting the ubiquitin peptidase USP47 overcomes TKI resistance and eliminates leukaemia stem/progenitor cells in primary and xenograft CML murine models.

To buffer the volume variation of sulfur and suppress the shuttle effect of long-chain lithium polysulfides during the cycling of Li-S batteries, it is essential to simultaneously design suitable pore structures and tune the surface chemistry of carbon-based sulfur hosts. However, the associated low yield and high cost of such delicately constructed carbon materials have been the major bottleneck for their practical utilization. Herein, we present a hundred-gram fabrication of a graphitic carbon nitride@hierarchical porous carbon (g-C3N4@HPC) composite, which is derived from low-cost biomass and used as the sulfur host for Li-S batteries. On this material, interconnected and hierarchical porosity of HPC physically traps the polysulfides and buffers the volume variation, and in the meantime, the uniformly dispersed g-C3N4 nanoparticles and N dopants on it provide strong chemical affinity to further immobilize the polysulfides. Therefore, the g-C3N4@HPC/S cathode delivers a high initial capacity of 1150.1 mAh g-1 and excellent cycling stability with a very small capacity decay of 0.024% cycle-1 for 250 cycles, at a high sulfur loading of 64.5 wt.%. Importantly, this g-C3N4@HPC composite is derived from very cheap and eco-friendly precursors, enabling the hundred-gram production at bench-top scale, which shows significant viability for practical Li-S battery application.

Interfacial engineering is one of the feasible pathways to tune the characteristics and functions of nanomaterials. In this report, we successfully synthesized crystalline CoWO4/amorphous Co–B hete...

Herein, an unprecedented bimetallic bis-NHC Cp*Ir complex 1 bearing 2-arylbenzo[d]oxazolyl and NHC ligands is reported. A significant increase in activity was observed for N-methylation of amines a...

Due to the sufficient ion diffusion channels provided by the large interlayer spacing, layered silicates are widely considered as potential anode materials for lithium ion and sodium ion batteries. However, due to the poor electronic conductivity, the application of layered silicates for electrochemical energy storage has been greatly limited. Carbon nanotube (CNT) film has excellent electrical conductivity and a unique interconnected network, making it an ideal matrix for composite electrochemical material. We herein report a CNT@nickel silicate composite film (CNT@NiSiO) fabricated by a SiO2-mediated hydrothermal conversion process, for sodium storage with excellent electrochemical properties. The obtained composite possesses a cladding structure with homogeneous nanosheets as the outermost and CNT film as the inner network matrix, providing abundant ion diffusion channels, high electronic conductivity, and good mechanical flexibility. Due to these merits, this material possesses an excellent electrochemical performance for sodium storage, including a high specific capacity up to 390 mAh g−1 at 50 mA g−1, good rate performance up to 205 mAh g−1 at 500 mA g−1, and excellent cycling stability. On this basis, this work would bring a promising material for various energy storage devices and other emerging applications.

Hematite is a promising photoanode for solar water splitting because of its favorable bandgap, excellent chemical stability and low cost. However, it suffers from both severe bulk and surface-charge recombinations, resulting in photoactivities much lower than the theoretical value. In this work, a facile new strategy is proposed by annealing hematite in the presence of potassium chloride (KCl) flux at 800°C. The photocurrent density of the annealed hematite, denoted ‘KCl-hematite’, increases from 0·34 mA/cm2 for pristine hematite to 0·54 mA/cm2 at 1·23 VRHE and further to 0·90 mA/cm2 after cobalt–phosphate (Co-Pi) deposition. Moreover, the photocurrent onset potential of KCl-hematite shows a cathodic shift of 120 mV compared with that of pristine hematite. It is demonstrated that potassium chloride flux can enhance the crystallinity and orderliness of hematite on the surface, reducing surface recombinations. This facile strategy by a flux offers a new insight to passivate surface recombinations of photoelectrodes and can be easily extended to other materials to enhance their photoactivities.

Photoelectrochemical (PEC) water splitting is recognized as a sustainable strategy for hydrogen generation due to its abundant hydrogen source, utilization of inexhaustible solar energy, high‐purity product, and environment‐friendly process. To actualize a practical PEC water splitting, it is paramount to develop efficient, stable, safe, and low‐cost photoelectrode materials. Recently, graphitic carbon nitride (g‐C3N4) has aroused a great interest in the new generation photoelectrode materials because of its unique features, such as suitable band structure for water splitting, a certain range of visible light absorption, nontoxicity, and good stability. Some inherent defects of g‐C3N4, however, seriously impair further improvement on PEC performance, including low electronic conductivity, high recombination rate of photogenerated charges, and limited visible light absorption at long wavelength range. Construction of g‐C3N4‐based nanosized heteroarrays as photoelectrodes has been regarded as a promising strategy to circumvent these inherent limitations and achieve the high‐performance PEC water splitting due to the accelerated exciton separation and the reduced combination of photogenerated electrons/holes. Herein, we summarize in detail the latest progress of g‐C3N4‐based nanosized heteroarrays in PEC water‐splitting photoelectrodes. Firstly, the unique advantages of this type of photoelectrodes, including the highly ordered nanoarray architectures and the heterojunctions, are highlighted. Then, different g‐C3N4‐based nanosized heteroarrays are comprehensively discussed, in terms of their fabrication methods, PEC capacities, and mechanisms, etc. To conclude, the key challenges and possible solutions for future development on g‐C3N4‐based nanosized heteroarray photoelectrodes are discussed.

Vanadium sulfide (VS2) nanomaterials have been deposited on surface-modified stainless steel mesh (SMSSM) by facial hydrothermal method and subsequent effects of acidic etching on surface morphology and supercapacitive performance of the electrode were studied. The acid etching process improves the coupling interaction between the stainless steel mesh and active materials. The optimized 1% etched SMSSM with VS2 (1%/VS2) loaded electrode reveals the porous fine nanoparticles composed surface nanostructure. The prepared 1%/VS2 electrode exhibited an excellent areal capacitance of 45.83 mF/cm2, which is two times higher than that of a non-etched VS2 loaded electrode. These results showed that the acidic etching process significantly improved the surface nanostructure of the VS2 material that improved the capacitance of the SMSSM substrate.

In this paper, we propose a flexible wire-type hybrid supercapacitor (FWHSC) endowed with superior electrochemical properties of transition metal sulfide nano-flakes. The electrodeposition method was conducted for coating of electroactive transition metal sulfide (CoS, NiCo2S4, CoS/NiCo2S4 and ZnCo2S4) nanomaterials on the current collector (Cu-wire), which makes it possible to store the electrochemical energy. The electrochemical study of NiCo2S4 and ZnCo2S4 electrodes revealed excellent charge storage features with areal capacitance of 245.5 and 104.6 mF cm−2, respectively, at a scan rate of 2 mV s−1. The FWHSC assembled from Cu@CoS/NiCo2S4 and Cu@ZnCo2S4 electrodes and KOH/PVA gel electrolyte operates in a voltage range of 1.5 V and delivers a specific energy of 6 W h kg−1 at the specific power of 4500 W kg−1 and a cycling stability of over 2000 cycles.

Flexible and free-standing electrode materials are prerequisite and key components for next-generation flexible energy storage and conversion devices. However, it is still a chanllenge to fabricate these materials from a continuous, straightforward, and facile method. Herein, we report a flexible composite film with silicon oxides decorated on few-walled carbon nanotubes, which can be continuously fabricated and directly drawn from the hot zone of the reactor. The composite film can be readily used for electrochemical lithium ion storage with high and reversible specific capacity, good rate capability, and excellent cycling performance. These exceptional characteristics make it very promising for flexible energy storage and other emerging applications.

The superhydrophobic surface has received significant attention in both academic research and industrial applications. Several polymer-based functional films have been reported to produce superhydrophobic water-repellent films with optical transmittance over the years. However, most polymer materials have an aging issue when they exposed to sunlight for a long time. Herein, we propose a facile and cost-effective fabrication method for the preparation of a flexible and transparent highly hydrophobic PUA film. The intrinsic hydrophilicity of PUA has been successfully modified by forming the microstructures and surface modifications with low surface energy siloxane. The siloxane functionalized µ-patterned PUA film was investigated in detail by various material characterization techniques. The obtained results are consistent and confirm the successful formation of the siloxane functionalized µ-patterned PUA film. The siloxane functionalized PUA film achieved the highest water contact angle (WCA) of ∼146°. Also, the fabricated PUA film maintained the WCAs more than 140° even after 50 times bending motions at the bending angle of ∼60° demonstrating the high flexibility of the proposed hydrophobic structure. Furthermore, the suitability of the as-fabricated siloxane functionalized PUA film as a protection layer for a solar cell, and CMOS camera was also systematically proved by the almost unchanged photovoltaic conversion efficiency (PCE) of the solar panel and the high fidelity of the recorded video.

To achieve preferential effects against cancer cells but less damage to normal cells is one of the main challenges of cancer research. In this review, we explore the roles and relationships of oxidative stress-mediated apoptosis, DNA damage, ER stress, autophagy, metabolism, and migration of ROS-modulating anticancer drugs. Understanding preferential anticancer effects in more detail will improve chemotherapeutic approaches that are based on ROS-modulating drugs in cancer treatments.

Summary Bacteriophages of the Podoviridae family densely package their genomes into precursor capsids alongside internal virion proteins called ejection proteins. In phage T7 these proteins (gp14, gp15, and gp16) are ejected into the host envelope forming a DNA-ejectosome for genome delivery. Here, we describe the purification and characterization of recombinant gp14, gp15, and gp16. This protocol was used for high-resolution cryo-EM structure analysis of the T7 periplasmic tunnel and can be adapted to study ejection proteins from other phages. For complete details on the use and execution of this protocol, please refer to Swanson et al. (2021)., Graphical abstract, Highlights • Expression and purification of phage T7 ejection proteins in mg quantities • Reconstitution of gp15:gp16 DNA-ejectosome periplasmic tunnel in vitro • Pore formation assay reveals gp14 forms a constitutive pore • Vitrification of gp15:gp16 complex for cryo-EM single particle analysis, Bacteriophages of the Podoviridae family densely package their genomes into precursor capsids alongside internal virion proteins called ejection proteins. In phage T7 these proteins (gp14, gp15, and gp16) are ejected into the host envelope forming a DNA-ejectosome for genome delivery. Here, we describe the purification and characterization of recombinant gp14, gp15, and gp16. This protocol was used for high-resolution cryo-EM structure analysis of the T7 periplasmic tunnel and can be adapted to study ejection proteins from other phages.

Triple-negative breast cancer (TNBC) remains a significant clinical challenge because of its high vascularity and metastatic and recurrent rates. Tumor angiogenesis is considered an important mediator in the regulation of tumor cell survival and metastasis in TNBC. Angiogenesis is induced by the binding of vascular endothelial growth factor to vascular endothelial growth factor receptor 2 (VEGFR2). Focal adhesion kinase (FAK) plays an important role in regulating various cell functions in normal and cancer cells. Previous studies have focused on investigating the function of endothelial FAK in tumor cell angiogenesis. However, the association between tumor FAK and VEGFR2 in tumor angiogenesis and the possible mechanisms of this remain unclear. In this study, we used a public database and human specimens to examine the association between FAK and VEGFR2. At the same time, we verified the association between FAK and VEGFR2 through several experimental methods, such as quantitative real-time polymerase chain reaction, Western blotting, and next-generation sequencing. In addition, we used the endothelial cell model, zebrafish, and xenograft animal models to investigate the role of FAK in TNBC angiogenesis. We found that FAK and VEGFR2 were positively correlated in patients with TNBC. VEGFR2 and several other angiogenesis-related genes were regulated by FAK. In addition, FAK regulated VEGFR2 and VEGF protein expression in TNBC cells. Functional assays showed that FAK knockdown inhibited endothelial tube formation and zebrafish angiogenesis. An animal model showed that FAK inhibitors could suppress tumor growth and tumor vascular formation. FAK promotes angiogenesis in TNBC cells by regulating VEGFR2 expression. Therefore, targeting FAK could be another antiangiogenic strategy for TNBC treatment.

Toxoplasma gondii is a serious hazard to public health and animal husbandry. Due to the current dilemma of treatment of toxoplasmosis, it is urgent to find new anti-T. gondii drugs to treat toxoplasmosis. In this study, the anti-T. gondii activity of Origanum vulgare essential oil (Ov EO) was firstly studied, and then, carvanol (Ca), the main ingredient of Ov EO was evaluated using the MTT assay on human foreskin fibroblast (HFF) cells in vitro. The cytotoxicity was evaluated using the MTT assay on HFF cells. The CC50 of Ov EO and Ca was 134.9 and 43.93 μg/ml, respectively. Both of them exhibited anti-parasitic activity, and inhibited the growth of T. gondii in a dose-dependent manner. For the inhibition effect, Ca was better than Ov EO at the same concentration, the IC50 of Ov EO and Ca was 16.08 and 7.688 μg/ml, respectively. In addition, treatment with Ca, was found to change the morphology of T. gondii tachyzoites and made their shapes curl up. These results showed that Ca was able to inhibit the proliferation of T. gondii by reducing invasion, which may be due to its detrimental effect on the mobility of tachyzoites. Our results indicated that Ca could be a potential new and effective drug for treating toxoplasmosis.

The current methods of treating toxoplasmosis have a number of side effects, and these therapies are only effective against the acute stage of the disease. Thus, development of new low toxicity and efficient anti-Toxoplasma drugs is extremely important. Natural products are important sources for screening new drugs; among them, essential oils (EOs) have efficacy in anti-bacterial, anti-inflammatory, anti-insect, and other aspects. In this study, 16 EOs were screened for their anti-T. gondii activity. Lavandula angustifolia essential oil (La EO)was found to have an anti-parasitic effect on T. gondii. The cytotoxicity of La EO was firstly evaluated using the MTT assay on human foreskin fibroblast (HFF) cells, and then the anti-T. gondii activity was evaluated by plaque assay. Finally, the invasion experiment and electron microscope observation were used to study the mechanism of La EO in anti-toxoplasma activity. The results indicated that the CC50 of La EO was 4.48 mg/ml and that La EO had activity against T. gondii and the inhibition was in a dose-dependent manner under safe concentrations. La EO was able to reduce T. gondii invasion, which may be due to its detrimental effect on changes of the morphology of tachyzoites. These findings indicated that La EO could be a potential drug for treating toxoplasmosis.

Background The cerebellum is the sensitive region of the brain to developmental abnormalities related to the effects of oxidative stresses. Abnormal cerebellar lobe formation, found in Jun dimerization protein 2 (Jdp2)-knockout (KO) mice, is related to increased antioxidant formation and a reduction in apoptotic cell death in granule cell progenitors (GCPs). Here, we aim that Jdp2 plays a critical role of cerebellar development which is affected by the ROS regulation and redox control. Objective Jdp2-promoter-Cre transgenic mouse displayed a positive signal in the cerebellum, especially within granule cells. Jdp2-KO mice exhibited impaired development of the cerebellum compared with wild-type (WT) mice. The antioxidation controlled gene, such as cystine-glutamate transporter Slc7a11, might be critical to regulate the redox homeostasis and the development of the cerebellum. Methods We generated the Jdp2-promoter-Cre mice and Jdp2-KO mice to examine the levels of Slc7a11, ROS levels and the expressions of antioxidation related genes were examined in the mouse cerebellum using the immunohistochemistry. Results The cerebellum of Jdp2-KO mice displayed expression of the cystine-glutamate transporter Slc7a11, within the internal granule layer at postnatal day 6; in contrast, the WT cerebellum mainly displayed Sla7a11 expression in the external granule layer. Moreover, development of the cerebellar lobes in Jdp2-KO mice was altered compared with WT mice. Expression of Slc7a11, Nrf2, and p21Cip1 was higher in the cerebellum of Jdp2-KO mice than in WT mice. Conclusion Jdp2 is a critical regulator of Slc7a11 transporter during the antioxidation response, which might control the growth, apoptosis, and differentiation of GCPs in the cerebellar lobes. These observations are consistent with our previous study in vitro.

Background Cyclin-dependent kinases (CDKs) are regarded as promising targets for cancer therapy. CDK2 and CDK4 are the core molecules in the G0 and G1 phases of the cell cycle. Exploring the molecular mechanism of CDK2 and CDK4 protein degradation will provide clues and solutions to control the G0 and G1 phases in tumor cells. Methods The expression levels of CDK2 and CDK4 were assessed by Western blotting and qRT-PCR. Cell viability, cell proliferation and growth were evaluated in CCK-8 and flow cytometric analysis. Protein interactions were analysed by immunoprecipitation and immunofluorescence methods. Results NVP-BEZ235 induced neuroblastoma cell arrest at the G0/G1 phase, and proliferation inhibition was associated with a significant reduction in the CDK2 and CDK4 proteins in a dose-dependent manner at nanomolar concentrations. Surprisingly, we found that the NVP-BEZ235-induced downregulation of CDK2 and CDK4 was dramatically rescued by autophagy-lysosome inhibitors. Additionally, the blockade of autophagy-related genes contributed to the remarkable rescue of CDK2 and CDK4, which thus strikingly improved NVP-BEZ235-induced G0/G1 arrest and growth inhibition of neuroblastoma cells. Subsequently, we observed the first evidence that NVP-BEZ235 induced the interaction of p62/SQSMT1 with CDK2 or CDK4 and the autophagic degradation of CDK2 and CDK4 in a cathepsin B-dependent manner. Analogous results regarding autophagy and the antiproliferative effects of NVP-BEZ235 were observed in a neuroblastoma xenograft mouse model in vivo. Conclusions These results not only established the pivotal role of the autophagy pathway in G0/G1 cell cycle-related protein turnover but also suggest the potential application of NVP-BEZ235 for cancer treatment by modulating elements of the autophagic machinery to promote degradation of G0/G1 cell cycle-related proteins.

Nitrogen, one of most important elements on the Earth, plays an essential role in shaping the modern society. The natural nitrogen looping, however, is insufficient to satisfy the high demand of the large‐scale human activities. To achieve a more sustainable and efficient utilization of nitrogen, artificial nitrogen looping by photo(electro)catalytic processes has been considered as a feasible strategy. In this context, the rational design on the high‐performance catalysts for nitrogen looping becomes increasingly important and urgent. On this basis, herein, we provide a timely review on the recent progress, achievements, and essential challenges for the artificial nitrogen looping process, mainly including photo(electro)catalytic transformations among dinitrogen, ammonia, gaseous nitrogen oxides, nitrate, and so on. Especially, the photo(electro)catalysts used in various reactions involved in nitrogen looping, including nitrogen reduction reaction, nitrogen oxidation reaction, ammonia oxidation reaction, ammonia decomposition reaction, etc., are systematically introduced. Finally, we hope that this review will help us deepen the understanding of nitrogen looping‐related photo(electro)catalysts, and further pave a way toward the sustainable development on energy and environment.

Oridonin could induce NB (neuroblastoma) cells growth inhibition by inducing apoptosis and cell cycle arrest, and the molecular mechanisms behind the effects deserve to be further explored. Here, oridonin was confirmed to cause the reactivation of p53 (cellular tumor antigen p53) to promote the expression of a series of apoptosis‐ and cell cycle arrest‐related proteins for the biological effects. During the process, oridonin relied on the caspase activation to cleave p53‐induced Mdm2 (E3 ubiquitin‐protein ligase Mdm2) to generate Mdm2‐p60. The generation of Mdm2‐p60 stabilized p53, and resulted in p53 accumulation for p53 continuous activation. In our research, it was also found that the reactivation of p53 induced by oridonin was closely related with the generation of ROS (reactive oxygen species). Taken together, these findings explain that oridonin exerts its anticancer activity partially by targeting the Mdm2‐p53 axis in NB cells, which lay an experimental base for future research of exploring the effects and molecular mechanisms of oridonin.

Reaction active surface area and energy band structure determine the visible-light photocatalytic property of semiconductor catalyst such as graphitic carbon nitride (CN). Herein, synchronization iodine surface modified and doped porous carbon nitride (CNI) was prepared. The self-assembly precursors from urea and ammonium iodide were firstly obtained by liquid nitrogen-assisted rapid re-crystallization and lyophilization technology. After the heat treatment of above precursors, CNI was easily synthesized. Compared with bulk CN, CNI shows large specific surface area (57.59 m2 g−1), due to freeze-drying treatment and thermal decomposition of ammonium iodide. As electron donors, iodine species can enrich the electron density in the carbon nitride network and tune the electronic band structure. It is important the surface iodine modification can bound the positive charge holes to inhibit the recombination of photogenerated carriers. As a result, CNI exhibits prompted photocatalytic hydrogen evolution rate of 114.0 μmol h−1 under visible-light irradiation (λ > 420 nm), better than that of bulk CN. This work may provide a promising rapid method for designing another porous and effective semiconductor photocatalysts.

Two novel lead ion imprinted adsorbents were prepared based on tridentate functionalized mesoporous silica material. Adsorption sites and behaviors were investigated. The adsorbent BPMA-Pb-IIMS pos...

Nepenthes plants are regarded as a kind of Traditional Chinese Medicine for several diseases but its anticancer activity remain unclear. The subject of this study is to evaluate the antiproliferation effects on oral cancer cells by Nepenthes plants using ethyl acetate extract of Nepenthes adrianii x clipeata (EANA). Cell viability was detected using MTS assay. Its detailed mechanisms including cell cycle, apoptosis, oxidative stress, and DNA damage were explored by flow cytometry or western blotting. For 24 hours EANA treatment, five kinds of oral cancer cells (CAL 27, Ca9-22, OECM-1, HSC-3, and SCC9) show IC50 values of cell viability ranging from 8 to 17 μg/mL but the viability of normal oral cells (HGF-1) remains over 80%. Subsequently, CAL 27 and Ca9-22 cells with high sensitivity to EANA were chosen to investigate the detailed mechanism. EANA displays the time course and concentration effects for inducing apoptosis based on flow cytometry (subG1 and annexin V analyses) and western blotting [cleaved poly (ADP-ribose) polymerase (c-PARP)]. Oxidative stress and DNA damage were induced by EANA treatments in oral cancer cells through reactive oxygen species (ROS), mitochondrial membrane potential disruption, mitochondrial superoxide, and γH2AX. All these changes of EANA treatments in oral cancer cells were reverted by the ROS scavenger N-acetylcysteine pretreatment. Therefore, EANA induces preferential killing, apoptosis, and DNA damage against oral cancer cells through oxidative stress.

Sodium has attracted an increasing amount of attention as an alternative element to lithium for energy storage due to its low cost and wide distribution, although the intercalation problem for sodium ions in conventional anode materials, due to their larger ionic size, still has to be overcome in order to utilize this element. Herein, we report a carbon-based hybrid material that is composed of stacked reduced graphene oxide/carbon nanotubes (rGO/CNTs) with a hierarchical and open structure to accommodate Na ions, which was fabricated by a liquid-phase oxidative exfoliation and subsequent reduction. This rGO/CNTs hybrid material features a hierarchical nanostructure with rGO nanosheets homogeneously spaced by monodisperse CNTs. The increased interlayer space between individual rGO nanosheets, which resulted from the inserted CNTs, is beneficial for highly efficient and reversible Na ion intercalation, leading to a high and stable capacity of 295 mAhg−1 at 50 mAg−1 for 200 cycles.

The biosynthetic gene cluster of antitumor antibiotic LL-D49194α1 (LLD) was identified and comparatively analyzed with that of trioxacarcins. The tailoring genes encoding glycosyltransferase, methyltransferase and cytochrome P450 were systematically deleted, which led to the discovery of eight compounds from the mutants. Preliminary pharmaceutical evaluation revealed two intermediates exhibiting higher cytotoxicity, stability and solubility. These results highlighted the modification pathway for LLD biosynthesis, and provided highly potent, structurally simplified "unnatural" natural products with improved druggability.

The instinct feature of π-bridges of donor-π-acceptor (D-π-A) conjugated polymers plays a critical role in tailoring the polymer basic properties as well as the photovoltaic performance. In this work, we designed two new D-π-A polymers PSeBDDIDT and PTzBDDIDT based on donor unit indacenodithiophene (IDT), acceptor unit benzo[1,2-c:4,5-c’]dithiophene-4,8-dione (BDD) with varying π-conjugated bridges of selenophene and thiazole units. Compared to the counterpart polymer PThBDDIDT with thiophene π-bridge, polymers PSeBDDIDT and PTzBDDIDT exhibited enhanced intermolecular interactions, expanded absorption range and better molecular planarity arising from the suppressed steric hindrance between the respective bridge and the adjacent BDD moiety. Conventional polymer solar cells were fabricated with PC71BM as the acceptor. The results witness a greatly improved efficiency for PSeBDDIDT based solar cell compared to PThBDDIDT based counterpart device (7.04%). As a result, the champion PCE of 8.65% was recorded with VOC of 0.899 V, JSC of 16.04 mA cm−2 and FF of 0.60. It is worth highlighting that this is the highest efficiency among all IDT-based polymeric donors reported till now. As a contrast, the devices fabricated from PTzBDDIDT demonstrated a low efficiency of 2.75%, with increased VOC of 0.968 V, JSC of 8.12 mA cm−2 and FF of 0.35. The inferior photocurrent and fill factor of PTzBDDIDT based device was in accord with the poor exciton dissociation probability (38%) and low hole and electron charge transport inside the polymer solar cell. In conclusion, this work demonstrates a state of the art IDT-based polymeric donor with selenophene π-bridge and the importance of rational regulation of π-bridges on polymer properties and photovoltaic efficiency of polymer solar cells.

Carbon nanotubes (CNTs) are an excellent electrode material for capacitive deionization (CDI), due to their excellent electronic conductivity and outstanding chemical/physical stability. Their powder form and easy aggregation, however, have greatly limited their practical CDI performance. Aiming to address this issue, the authors report a freestanding CNT film which was fabricated by floating-catalyst chemical vapor deposition, as a binder-free electrode for CDI. By simply adjusting the pyrrole content in the precursor, the morphology of the resulting CNT film can be tuned to meet the requirements of CDI. In the presence of 2 wt.% pyrrole, the CNT film with a mesoporous structure exhibited a large specific surface area of 198 m2/g and an increased electric double-layer capacity (40 F/g), which is more than two times as large as that of the pristine CNT film. Due to these merits, the electrosorption capacity for sodium chloride (NaCl) of the CNT film electrode (11·39 mg/g) has been greatly improved compared with that of the pristine CNT film (4·52 mg/g), showing a good potential for large-scale practical CDI.

Non-metallic boron modified graphitic carbon nitrogen (BCN) tube was prepared by a simple hydrothermal method using melamine as initial material and boric acid as boron source. Through thermal treatment, boron was directly introduced into g-C3N4 tube structure. Boron modified could increase the specific surface area of g-C3N4 and enhance its visible-light responsiveness. Importantly, the separation of the photogenerated electrons and holes in BCN tube was significantly enhanced, which can contribute to the improvement of photocatalytic activity. The photocatalytic activity of BCN tube was evaluated by degrading Rhodamine B (RhB) and Methylene blue (MB) experiments under visible light irradiation. The prepared BCN-3 sample (B: 0.36 mol %) showed the best photocatalytic activity when the initial material molar ratio of melamine to boric acid was 1:1. The degradation rate of BCN-3 to RhB was 99.3% under visible light irradiation for 90 min. The catalyst also showed good degradation effect for MB.

The BCR-ABL fusion protein with strong tyrosine kinase activity is one of the molecular biological bases of leukemia. Imatinib (Gleevec), a specific targeted drug for the treatment of chronic myeloid leukemia (CML), was developed for inhibiting the kinase activity of the BCR-ABL fusion protein. Despite the positive clinical efficacy of imatinib, the proportion of imatinib resistance has gradually increased. The main reason for the resistance is a decrease in sensitivity to imatinib caused by mutation or amplification of the BCR-ABL gene. In response to this phenomenon, the new generation of tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL fusion protein was developed to solve the problem. However this strategy only selectively inhibits the tyrosine kinase activity of the BCR-ABL protein without eliminating the BCR-ABL protein, it does not fundamentally cure the BCR-ABL-positive leukemia patients. With the accumulation of the knowledge of cellular molecular biology, it has become possible to specifically eliminate certain proteins by cellular proteases in a specific way. Therefore, the therapeutic strategy to induce the degradation of the BCR-ABL fusion protein is superior to the strategy of inhibiting its activity. The protein degradation strategy is also a solution to the TKI resistance caused by different BCR-ABL gene point mutations. In order to provide possible exploration directions and clues for eliminating the BCR-ABL fusion protein in tumor cells, we summarize the significant molecules involved in the degradation pathway of the BCR-ABL protein, as well as the reported potent compounds that can target the BCR-ABL protein for degradation.

2-Arylbenzo[d]oxazole is an important structural motif in pharmaceutical chemistry, while its regioselective halogenation still remains challenging due to the many possible reaction sites on the two aromatic systems. Herein, we report a transition metal catalysed chlorination, bromination and iodination of 2-arylbenzo[d]oxazole with N-halosuccinimide, in which ruthenium-catalysed halogenation occurred on the C7-position and rhodium-catalysed halogenation occurred on the ortho-position. The C7 halogenation was only observed for 5-methyl-2-(p-substituted)arylbenzo[d]oxazoles under rhodium catalysis. Preliminary mechanistic experiments and density functional theory (DFT) calculations suggested that the C7-halogenation catalysed by Ru might have a single-electron-transfer (SET) radical process, while the ortho-selective halogenation catalysed by Rh proceeds probably through a redox-neutral SN2-type mechanism. The different selectivity of Rh catalysed halogenation could be due to the charge difference between benzo[d]oxazolyl and aryl rings. The two kinds of halogenated products were proved to be versatile by constructing aryl and alkynyl groups on the C–X site via Suzuki and Sonogashira cross-coupling reactions.

Transition metal compounds have a high theoretical capacity, and thus they are also promising candidates for application as supercapacitors. In this work, a cobalt boride–activated carbon composite has been synthesized and applied as an electrode material of a supercapacitor for the first time. The cobalt boride–carbon composite was prepared using activated carbon (AC) as an additive and cobalt dichloride/sodium borohydride as starting materials. The addition of a small amount of activated carbon greatly improved the electrochemical performance of cobalt boride. By compositing cobalt boride with AC, the challenge of the low electrical conductivity of CoB can be addressed. In a 6 M KOH alkaline aqueous electrolyte, CoB–AC was used as the positive electrode material for an asymmetric supercapacitor (ASC) in order to carry out the electrochemical test. At 0.5 A g−1, compared with the bare cobalt boride, introducing activated carbon could increase the specific capacitance by 49.5%, up to 193.64 C g−1. Furthermore, an asymmetric supercapacitor was prepared, utilizing positive CoB–AC and negative activated carbon, respectively. The electrochemical behaviors of the prepared asymmetric supercapacitor were evaluated by cyclic voltammetry, alternating current impedance, and galvanostatic charge–discharge techniques. This showed a wide potential window of 1.6 V and after 10 000 charge/discharge cycles, an outstanding cycling stability retention rate of 80% was maintained at 2 A g−1. The as-fabricated ASC device could achieve a maximum energy density of 19.14 W h kg−1 at a power density of 200.59 W kg−1. We hope that our present work will provide a new solution for designing high specific capacity supercapacitors.

Hydrogen sulfide (H2S) is an extremely toxic gas and comes under the classification of chemical asphyxiants. To date, numerous metal oxide-based gas sensors have been developed for the detection and quantification of H2S. However, high sensing temperature, low sensitivity, humidity dependence, and very high response/recovery time severely limit their practical applications. Herein, we prepared hierarchical mesoporous nickel oxide (NiO) nanodisks and boron–nitrogen co-doped reduced graphene oxide (rGO)-NiO (NiOBNG) nanodisk composites for H2S sensing. The as-prepared materials were investigated by several techniques to determine their morphologies, crystal structures, phase purity, and compositions. The sensing response of the NiOBNG sensor to 100 ppm H2S at 150 °C was ∼82, and the detection limit of the sensor was ∼24 ppb. The NiOBNG sensor showed 2- and 3-fold stronger response compared to pristine rGO incorporated NiO and bare NiO nanodisk sensors. The enhanced sensing performance of the NiOBNG sensor is attributed to the presence of several catalytically active sites provided by boron and nitrogen doped rGO in the NiOBNG nanocomposite. The ease of the synthesis procedure, excellent sensitivity, selectivity, rapid response, high stability, and ambient temperature operation make for intriguing, promising practical applications of our NiOBNG sensor, especially in explosive environments and medical diagnosis.

Abnormal levels of guanine closely associated with plenty of diseases are usually used as a biomarker for clinical diagnosis. In order to detect guanine and its derivatives accurately, in this paper, a defective G-quadruplex (DGQ) containing a G-vacancy at one of its G-quartet layers, and two kinds of G-quadruplex specific indicators including thioflavine T (ThT) and hemin were used for constructing a fluorescent and an electrochemical biosensor, respectively. In brief, a G-rich DNA probe is designed to form either hairpin or DGQ structure. In the absence of guanine, G-rich probes prefer to maintain hairpin structure and nearly have no interaction with ThT or hemin, leading to almost negligible signals. Upon addition of guanine, the G-rich probe fold into DGQ structure and then the G-vacancy in it is filled up immediately by guanine via Hoogsteen hydrogen bonds, resulting canonical G-quadruplex formation. Accordingly, ThT or hemin can selectively combine with G-quadruplex, giving rise to distinct fluorescent or current signal changes for label-free detection of guanine. Benefiting from the perfect discriminative ability of guanine towards DGQ and ThT/hemin against standard G-quadruplex, the fluorescent and electrochemical biosensors present better sensitivity and selectivity for guanine detection with the limit of detection (LOD) as low as 18.26 and 0.36 nM, respectively. Successful attempts were also made in applying the proposed electrochemical biosensor to detect guanine in drugs and urine, obtaining satisfactory recovery rates of 99~104% and 96~106%, respectively.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by fibroblast proliferation and extracellular matrix remodeling; however, the molecular mechanisms underlying its occurrence and development are not yet fully understood. Despite it having a variety of beneficial pharmacological activities, the effects of catalpol (CAT), which is extracted from Rehmannia glutinosa, in IPF are not known. In this study, the differentially expressed genes, proteins, and pathways of IPF in the Gene Expression Omnibus database were analyzed, and CAT was molecularly docked with the corresponding key proteins to screen its pharmacological targets, which were then verified using an animal model. The results show that collagen metabolism imbalance, inflammatory response, and epithelial-mesenchymal transition (EMT) are the core processes in IPF, and the TGF-β1/Smad3 and Wnt/β-catenin pathways are the key signaling pathways for the development of pulmonary fibrosis. Our results also suggest that CAT binds to TGF-βR1, Smad3, Wnt3a, and GSK-3β through hydrogen bonds, van der Waals bonds, and other interactions to downregulate the expression and phosphorylation of Smad3, Wnt3a, GSK-3β, and β-catenin, inhibit the expression of cytokines, and reduce the degree of oxidative stress in lung tissue. Furthermore, CAT can inhibit the EMT process and collagen remodeling by downregulating fibrotic biomarkers and promoting the expression of epithelial cadherin. This study elucidates several key processes and signaling pathways involved in the development of IPF, and suggests the potential value of CAT in the treatment of IPF.

Visfatin, an adipocytokine highly expressed in breast tumor tissues, is associated with breast cancer progression. Recent studies showed that adipocytokines mediate tumor development through adipocytokine tumor&ndash, stromal interactions in the tumor microenvironment. This study focused on the interaction between one key stromal constituent&mdash, tumor-associated macrophages&mdash, and visfatin. Pretreatment of THP-1 and peripheral blood mononuclear cells (PBMCs) with recombinant visfatin resulted in M2-polarization determined by CD163 and CD206 expression. Indirect co-culture with visfatin-treated THP-1 (V-THP-1) promoted the viability, migration, tumorsphere formation, EMT, and stemness of breast cancer cells. Cytokine array identified an increased CXCL1 secretion in V-THP-1 conditioned medium and recombinant CXCL1 enhanced cell migration and invasion, which were abrogated by the CXCL1-neutralizing antibody. Additionally, visfatin induced pERK in THP-1 cells and clinical samples confirmed a positive CXCL1/pERK correlation. In an orthotopic mouse model, the tumor bioluminescent signal of luciferase-expressing MDA-MB-231 (Luc-MDA-MB-231) cells co-cultured with V-THP-1 and the expression of proliferation marker Ki67 were significantly higher than that co-cultured with THP-1. Furthermore, tail vein-injected Luc-MDA-MB-231 pretreated with V-PBMCs conditioned medium metastasized to lungs more frequently compared to control, and this was reversed by CXCL1 blocking antibody. In summary, this study demonstrated that visfatin enhanced breast cancer progression via pERK/CXCL1 induction in macrophages.