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An efficient aminocatalytic enantioselective double-activation strategy has been developed that combines several different aminocatalytic modes in a cascade process, such as iminium ion, vinylogous iminium ion, trienamine, and dienamine activations. By using this strategy, 2-hydroxycinnamaldehydes worked well with various dienals via [4 + 2] cycloaddition and the oxa-Michael reaction-initiated cascade, respectively, leading to chiral polycyclic tetrahydrocarbazole and chromane derivatives with excellent diastereo- and enantioselectivities.

The use of cryoablation/cryosurgery in treating solid tumors has been proven as a unique technique that uses lethal temperatures to destroy the tumors and impart better functions for the affected organs. This novel technique recently demonstrated the best clinical results in chondrosarcoma (CSA) with faster recovery, less recurrence, and metastasis. Due to the resistant nature of CSA to chemo and radiation therapy, cryoablation comes to light as the best alternative approach. Therefore, for the first time, we aimed to compare CSA-untreated with cryoablation treated samples to discover some potential markers that may provide various clues in terms of diagnosis and pathophysiology and may facilitate the development of novel methods to treat sarcoma efficiently. To find the altered proteins among both groups, a mass-based label-free approach was employed and identified a total of 160 significantly altered proteins. Among these, 138 proteins were dysregulated with1- to -0.1-fold, 18 proteins were up-regulated with3 folds, and four proteins were similarly expressed in the untreated group compared to the treated. Interestingly, the differential expressions of proteins from the untreated group showed contrast expressions in the treated group. Furthermore, the functional enrichment analysis revealed that most of the identified proteins from this study were associated with various significant pathways such as glycolysis, MAPK activation, PI3K-Akt signaling, extracellular matrix degradation, etc. In addition, two protein expressions, such as fibronectin and annexin-1, were validated by immunoblot analysis. Therefore, this study signifies the most comprehensive discovery of altered protein expressions to date and the first large-scale detection of protein profiles from CSA-cryoablation treated compared to untreated. This work may serve as the basis for future research to open novel treatment options for chondrosarcoma.

Background Intervertebral disc degeneration contributes to low back pain. The avascular intervertebral disc consists of a central hypoxic nucleus pulpous (NP) surrounded by the more oxygenated annulus fibrosus (AF). Lactic acid, an abundant end-product of NP glycolysis, has long been viewed as a harmful waste that acidifies disc tissue and decreases cell viability and function. As lactic acid is readily converted into lactate in disc tissue, the objective of this study was to determine whether lactate could be used by AF cells as a carbon source rather than being removed from disc tissue as a waste byproduct. Methods Import and conversion of lactate to tricarboxylic acid (TCA) cycle intermediates and amino acids in rabbit AF cells were measured by heavy-isotope (13C-lactate) tracing experiments using mass spectrometry. Levels of protein expression of lactate converting enzymes, lactate importer and exporter in NP and AF tissues were quantified by Western blots. Effects of lactate on proteoglycan (35S-sulfate) and collagen (3H-proline) matrix protein synthesis and oxidative phosphorylation (Seahorse XFe96 Extracellular Flux Analyzer) in AF cells were assessed. Results Heavy-isotope tracing experiments revealed that AF cells imported and converted lactate into TCA cycle intermediates and amino acids using in vitro cell culture and in vivo models. Addition of exogenous lactate (4 mM) in culture media induced expression of the lactate importer MCT1 and increased oxygen consumption rate by 50%, mitochondrial ATP-linked respiration by 30%, and collagen synthesis by 50% in AF cell cultures grown under physiologic oxygen (2-5% O2) and glucose concentration (1-5 mM). AF tissue highly expresses MCT1, LDH-H, an enzyme that preferentially converts lactate to pyruvate, and PDH, an enzyme that converts pyruvate to acetyl-coA. In contrast, NP tissue highly expresses MCT4, a lactate exporter, and LDH-M, an enzyme that preferentially converts pyruvate to lactate. Conclusions These findings support disc lactate-dependent metabolic symbiosis in which lactate produced by the hypoxic, glycolytic NP cells is utilized by the more oxygenated AF cells via oxidative phosphorylation for energy and matrix production, thus shifting the current research paradigm of viewing disc lactate as a waste product to considering it as an important biofuel. These scientifically impactful results suggest novel therapeutic targets in disc metabolism and degeneration.

A Bronsted acid-catalyzed cascade acyclic N,O-hemiaminal formation/oxa-Michael reaction is developed for the synthesis of cis-2,6-disubstituted tetrahydropyrans bearing an exo amide group, that is, cyclic N,O-aminals. By using TsOH, various different amides including carboxyamides, carbamates, sulfonamides and even phosphoramides were applicable for the designed reaction sequence. By using chiral phosphoric acid, a wide range of enantioenriched cyclic N,O-aminal scaffolds were obtained. Detailed mechanistic investigations revealed that the good enantioselectivity can be attributed to a H2O controlled dynamic kinetic resolution of the in situ formed acyclic N,O-hemiaminal intermediate during the reaction process. Furthermore, a number of divergent transformations of the obtained products were investigated, leading to various synthetically useful heterocyclic architectures.

Semiconducting polymer dots (Pdots) recently have emerged as a new class of extraordinarily bright fluorescent probes with promising applications in biological imaging and sensing. Herein multicolor semiconducting polymer nanoparticles (Pdots) were designed using benzothiadiazole (BT) as the acceptor, and various types of donors were incorporated to modulate their emission wavelengths. Specific cellular targeting and in vivo biotoxicity as well as microangiography imaging on zebrafish indicated these BT-based Pdots are promising candidates for biological applications.

Cardiovascular diseases are the leading cause of morbidity and mortality throughout the world underlining the importance of efficient treatments including disease modeling and drug discovery by cardiac tissue engineering. However, the predictive power of these applications is currently limited by the immature state of the cardiomyocytes. Here, we developed gelatin hydrogels chemically crosslinked by genipin, a biocompatible crosslinker, as cell culture scaffolds. Neonatal rat cardiomyocytes appear synchronous beating within 2 days after seeding on hydrogels. Furthermore, we applied the electrical stimulation as a conditioning treatment to promote the maturation of cardiomyocytes cultured on the hydrogels. Our results show that electrical stimulation improves the organization of sarcomeres, establishment of gap junctions, calcium-handling capacity and propagation of pacing signals, thereby, increase the beating velocity of cardiomyocytes and responsiveness to external pacing. The above system can be applied in promoting physiological function maturation of engineered cardiac tissues, exhibiting promising applications in cardiac tissue engineering and drug screening.

Phosphodiesterase 5A1 (PDE5) is a key target for treating cardiovascular diseases and erectile dysfunction. Here, we report the crystal structure of PDE5 complexed with the sole second generation drug avanafil. Analysis of protein-drug interactions revealed the structural basis of avanafil's superior isoform selectivity. Moreover, a halogen bonding was observed between avanafil and a backbone carbonyl oxygen of an adjacent α-helix, whose contribution to inhibitory potency illustrates the feasibility of exploiting α-helix backbone in structure-based drug design.

Combining hierarchical nickel–cobalt oxides (NCO) with cost-effective glucose-based carbons could be attractive electrode materials for high-performance supercapacitor. The bimetallic nickel (Ni) and cobalt (Co) hydroxide was directly electrodeposited for 120, 180, 300, 480, and 600 s, respectively, on a conductive Ni foam as the NCO/Ni electrodes. The (NCO/Ni)-480 electrode showed the highest capacitance among NCO/Ni electrodes. Furthermore, an asymmetric supercapacitor (ASC) was assembled by utilizing (NCO/Ni)-480 as a positive electrode and glucose-based activated-carbon coated on Ni foam, (G-AC)/Ni, as a negative electrode in solid state carboxymethyl cellulose-lithium nitrate (CMC-LiNO3) gel electrolyte. At the potential window of 1.5 V, the device exhibits a prominent energy density of 45.3 Wh kg−1 at a power density of 0.743 kW kg−1 (1 A g−1) and excellent cycling stability of 89.7% of the initial capacity retention over 10,000 cycles. The outstanding electrochemical performances of the ASC can be ascribed to the synergistic effect of hierarchical Ni–Co oxides, mesoporous G-AC, three-dimensional Ni foam collector, and binder-free preparation, which facilitates a faster diffusion of the electrolyte ion into the electrode material and provides a stronger adhesion of active materials with the current collector.

The comparison of output powers between self-Raman Nd:YVO4 lasers and Nd:YVO4/KGW Raman lasers operating at lime and orange wavelengths is presented. We exploit the LBO crystal with cutting angle θ = 90° and φ = 8° for the lime wavelengths, and then we change the angle to θ = 90° and φ = 3.9° for the orange wavelengths. In self-Raman Nd:YVO4 lasers, experimental results reveal that thermal loading can impact on the output performances, especially at the high pump power. However, by using a KGW crystal as Raman medium can remarkably share the thermal loading from gain medium. Besides, the designed coating for high reflectively at the Stokes field on the surface of KGW also improved the beam quality and reduced the lasing threshold. For self-Raman Nd:YVO4 lasers, we have achieved the output powers of 6.54 W and 5.12 W at 559 nm and 588 nm, respectively. For Nd:YVO4/KGW Raman lasers, the output powers at 559 nm and 589 nm have been increased to 9.1 W and 7.54 W, respectively. All lasers operate at a quasi-CW regime with the repetition rate 50 Hz and the duty cycle 50%.

Osteosarcoma is a highly malignant musculoskeletal tumor that is commonly noticed in adolescent children, young children, and elderly adults. Due to advances in surgery, chemotherapy and imaging technology, survival rates have improved to 70–80%, but chemical treatments do not enhance patient survival, in addition, the survival rate after chemical treatments is still low. The most obvious clinical feature of osteosarcoma is new bone formation, which is called “sun burst”. Estrogen receptor alpha (ERα) is an essential feature of osteogenesis and regulates cell growth in various tumors, including osteosarcoma. In this study, we sought to investigate the role of ERα in osteosarcoma and to determine if ERα can be used as a target to facilitate the chemosensitivity of osteosarcoma to current treatments. The growth rate of each cell clone was assayed by MTT and trypan blue cell counting, and cell cycle analysis was conducted by flow cytometry. Osteogenic differentiation was induced by osteogenic induction medium and quantified by ARS staining. The effects of ERα on the chemoresponse of OS cells treated with doxorubicin were evaluated by colony formation assay. Mechanistic studies were conducted by examining the levels of proteins by Western blot. The role of ERα on OS prognosis was investigated by an immunohistochemical analysis of OS tissue array. The results showed an impaired growth rate and a decreased osteogenesis ability in the ERα-silenced P53(+) OS cell line U2OS, but not in P53(−) SAOS2 cells, compared with the parental cell line. Cotreatment with tamoxifen, an estrogen receptor inhibitor, increased the sensitivity to doxorubicin, which decreased the colony formation of P53(+) U2OS cells. Cell cycle arrest in the S phase was observed in P53(+) U2OS cells cotreated with low doses of doxorubicin and tamoxifen, while increased levels of apoptosis factors indicated cell death. Moreover, patients with ER−/P53(+) U2OS showed better chemoresponse rates (necrosis rate &gt, 90%) and impaired tumor sizes, which were compatible with the findings of basic research. Taken together, ERα may be a potential target of the current treatments for osteosarcoma that can control tumor growth and improve chemosensitivity. In addition, the expression of ERα in osteosarcoma can be a prognostic factor to predict the response to chemotherapy.

Recycled autografts have been commonly used in biological reconstruction in conjunction with wide bone resection. Extracorporeal irradiation (ECIR) and freezing are the two major options for pretreating tumor-bearing autografts before transplant. This study, for the first time, compared the effects of these two techniques on bone morphogenetic protein (BMP)-2 activity. Bone tissue extracted from human femoral heads were treated through either ECIR at different doses (5000, 15,000, and 30,000 rad) or liquid nitrogen (LN) freezing for different durations (5, 10, and 15 min). The amount of BMP was analyzed through enzyme-linked immunosorbent assay (ELISA assay). Furthermore, we also used tandem mass spectrometry to analyze change of BMP-2 and BMP-7 expression after high dosage of irradiation (30,000 rad) and long-time of freezing (15 min). To directly evaluate the effect of ECIR or LN freezing treatment on the activity of BMP, commercial recombinant human BMP-2 (rhBMP-2) was added to the culture of human mesenchymal stem cells (hMSCs). The post-treatment activity of rhBMP-2 was quantitated by measuring the osteogenic differentiation of hMSCs with Alizarin Red S staining. Through Western blotting, the activation of the BMP signaling pathway by phospho-Smad antibodies was analyzed. Our results showed that post-treatment levels of BMP did not differ among the ECIR and LN freezing treatments in ELISA assay, but tandem mass spectrometry showed significantly lower expression of BMP-2 after 30,000 rad of irradiation. Both ECIR and freezing lowered the expression of regulatory factors involved in the BMP-activated signaling cascades and similar results were also observed in osteogenic differentiation of hMSCs. However, LN freezing preserved better bioactivity of rhBMP-2 whereas dosage-dependent declination was observed in ECIR groups. In conclusion, considering BMP-2 activity, LN freezing-treated autografts may result in a better osteoinduction outcomes than those treated using ECIR. Further investigation of the factors involved in bone formation is required.

The detection of 3- and 2-MCPD ester and glycidyl ester was transformed from selected ion monitoring (SIM) mode to multiple reaction monitoring (MRM) mode by gas chromatography triple quadrupole spectrometry. The derivatization process was adapted from AOCS method Cd 29a-13. The results showed that the coefficient of determination (R2) of all detected compounds obtained from both detection mode was comparable, which falls between 0.997 and 0.999. The limit of detection and quantification (LOD and LOQ) were improved in MRM mode as compared to SIM mode. In MRM mode, the LOD of 3- and 2-MCPD ester was achieved 0.01 mg/kg while the LOQ was 0.05 mg/kg. Besides, LOD and LOQ of glycidyl ester were 0.024 and 0.06 mg/kg respectively. A blank spiked with MCPD esters (0.03, 0.10 and 0.50 mg/kg) and GE (0.06, 0.24 and 1.20 mg/kg) were chosen for repeatability and recovery tests. MRM mode showed better repeatability in area ratio and recovery with relative standard deviation (RSD %)

Studies have identified the potential of chemopreventive effects of sulforaphane (SFN); however, the underlying mechanisms of its effect on breast cancer require further elucidation. This study investigated the anticancer effects of SFN that specifically induces G1/S arrest in breast ductal carcinoma (ZR-75-1) cells. The proliferation of the cancer cells after treatment with SFN was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. DNA content and cell cycle status were analyzed through flow cytometry. Our results demonstrated the inhibition of growth in ZR-75-1 cells upon SFN exposure. In addition, SERTAD1 (SEI-1) caused the accumulation of SFN-treated G1/S-phase cells. The downregulation of SEI-1, cyclin D2, and histone deacetylase 3 suggested that in addition to the identified effects of SFN against breast cancer prevention, it may also exert antitumor activities in established breast cancer cells. In conclusion, SFN can inhibit growth of and induce cell cycle arrest in cancer cells, suggesting its potential role as an anticancer agent.

Thermal, photochemical, and metal-facilitated routes to aryl nitrenes via the extrusion of dinitrogen from aryl azides adsorbed on a single-crystal copper surface have been investigated. Only by ir...

Porous manganese cobalt oxide (MCO) films were prepared directly on a conductive stainless steel (SS) mesh substrate via electrodeposition and an annealing treatment as composite air electrodes. The electrodeposition time ratio markedly influenced the surface morphological and electrochemical catalytic activities of MCO/SS electrodes. The sample 04 (− 0.8 V for 480 s followed by − 0.9 V for 240 s and annealed at 400 °C for 2 h) exhibited the highest reduction current among all electrodes. The electrochemical catalytic activity of the sample 04 as the air electrode for rechargeable zinc–air batteries was evaluated using galvanostatic charge and discharge cycling measurements in a solution of 6 M KOH. After 1000 cycles, sample 04 exhibited excellent cycling stability, with an overall potential gap of 0.75 V. The excellent performance of MCO/SS electrode in terms of stability and overall potential gap might be due to the ratio of Co oxide and Mn oxide, and its porous structure.

A rechargeable zinc-air battery shows great promise because of its high energy density, low cost, greater safety, and its environment-friendly properties. However, rechargeable zinc-air battery development has been hindered by the lack of a satisfactory bi-functional electrode. In this research, we report on a solution which uses electro-deposition to dope nickel into manganese on the stainless-steel mesh. The result shows the hydroxyl group on the prepared samples improving its oxygen reduction reaction and oxygen evolution reaction performance, as well as boosting the ion diffusion rate and stabilizing the zinc-air battery charge-discharge performance (overall potential gap dropped from 0.84 V to 0.82 V after 1000 cycles). This study contributes to our understanding of a new method for the improvement of bi-functional electrodes.

Harnessing biomaterials for in vitro tissue construction has long been a research focus because of its powerful potentials in tissue engineering and pharmaceutical industry. Myocardium is a critical cardiac tissue with complex multiple muscular layers. Considering the specific characters of native cardiac tissues, it is necessary to design a biocompatible and biomimetic platform for cardiomyocyte culture and myocardium formation with sustained physiological function. In this study, we developed gelatin-based hydrogels chemically cross-linked by genipin, a biocompatible cross-linker, as cell culture scaffolds. Moreover, to achieve and maintain the functionality of myocardium, for instance, well-organized cardiomyocytes and synchronized contractile behavior, we fabricated gelatin-based hydrogels with patterned microstructure using a microcontact printing technique. Furthermore, graphene oxide (GO), with unprecedented physical and chemical properties, has also been incorporated into gelatin for culturing cardiomyocytes. Our results show that micropatterned genipin-cross-linked gelatin hydrogels are very helpful to promote alignment and maturation of neonatal rat ventricular cardiomyocytes. More interestingly, the presence of GO significantly enhances the functional performance of cardiomyocytes, including an increase in contraction amplitude and cardiac gene expression. The cultured cardiomyocytes reach a well-synchronized contraction within 48 h of cell seeding and keep beating for up to 3 months. Our study provides a new and easy-to-use gelatin-based scaffold for improving physiological function of engineered cardiac tissues, exhibiting promising applications in cardiac tissue engineering and drug screening.

Giant cell tumors of bone (GCT) are benign tumors that show a locally aggressive nature and affect bones&rsquo, architecture. Recently, cryoablation and irradiation treatments have shown promising results in GCT patients with faster recovery and less recurrence and metastasis. Therefore, it became a gold standard surgical treatment for patients. Hence, we have compared GCT-untreated, cryoablation, and irradiation-treated samples to identify protein alterations using high-frequency liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Our label-free quantification analysis revealed a total of 107 proteins (p &lt, 0.01) with 26 up-regulated (&lt, 2-folds to 5-fold), and 81 down-regulated (&gt, 0.1 to 0.5 folds) proteins were identified from GCT-untreated and treated groups. Based on pathway analysis, most of the identified up-regulated proteins involved in critical metabolic functions associated with tumor proliferation, angiogenesis, and metastasis. On the other hand, the down-regulated proteins involved in glycolysis, tumor microenvironment, and apoptosis. The observed higher expressions of matrix metalloproteinase 9 (MMP9) and TGF-beta in the GCT-untreated group associated with bones&rsquo, osteolytic process. Interestingly, both the proteins showed reduced expressions after cryoablation treatment, and contrast expressions identified in the irradiation treated group. Therefore, these expressions were confirmed by immunoblot analysis. In addition to these, several glycolytic enzymes, immune markers, extracellular matrix (ECM), and heat shock proteins showed adverse expressions in the GCT-untreated group were identified with favorable regulations after treatment. Therefore, the identified expression profiles will provide a better picture of treatment efficacy and effect on the molecular environment of GCT.

Background The abnormal expression of lncRNA LINC00466 (LINC00466) has been demonstrated in several tumor types. However, the expression pattern and functions of LINC00466 in glioma remain uninvestigated. Methods A reverse transcriptase-polymerase chain reaction (RT-PCR) was utilized to analyze LINC00466 in human glioma tissues and cell lines. Luciferase reporter assays were performed to explore whether YY1 could bind to the promoter region of LINC00466. Cell counting kit-8, flow cytometry, colony-formation, transwell migration and invasion assays were carried out to determine the involvement of INC00466 in glioma. Luciferase assays and pulldown assays were conducted to verify the binding sites. Results We report that LINC00466 expression is increased in glioma cells and tissues. YY1 transcription factor (YY1) can bind directly to the LINC00466 promoter region. Clinical studies revealed that the elevated expression of LINC00466 is closely correlated with an advanced World Health Organization grade (p = 0.008), Karnofsky Performance Status score (p = 0.004) and a short overall survival (p = 0.0035) of glioma patients. Functional assays revealed that LINC00466 knockdown distinctly suppresses glioma cell proliferation, migration, invasion and epithelial-mesenchymal progress, and also promotes apoptosis. Moreover, dual-luciferase reporter assays indicated that LINC00466 acts as an endogenous sponge via binding to miR-508 and decreasing its expression. Luciferase assays and RT-PCR assays demonstrated that checkpoint kinase 1 (CHEK1) is a target of miR-508, and LINC00466 modulates CHEK1 levels by competing for miR-508. LINC00466 may exhibit its anti-oncogenic roles through targeting the miR-508/CHEK1 axis. Conclusions Our findings identified a novel glioma-related long non-coding RNA, LINC00466, which may provide a potential novel prognostic and therapeutic target for glioma.

Previously, we reported that persistent DNA damage accelerates ageing of the spine, but the mechanisms behind this process are not well understood. Ataxia telangiectasia mutated (ATM) is a protein kinase involved in the DNA damage response, which controls cell fate, including cell death. To test the role of ATM in the human intervertebral disc, we exposed human nucleus pulposus (hNP) cells directly to the DNA damaging agent cisplatin. Cisplatin‐treated hNP cells exhibited rapid phosphorylation of ATM and subsequent increased NF‐κB activation, aggrecanolysis, decreased total proteoglycan production and increased expression of markers of senescence, including p21, γH2AX and SA‐ß‐gal. Treating cisplatin‐exposed hNP cells with an ATM‐specific inhibitor negated these effects. In addition, genetic reduction of ATM reduced disc cellular senescence and matrix proteoglycan loss in the progeroid Ercc1−/∆ mouse model of accelerated ageing. These findings suggest that activation of ATM signalling under persistent genotoxic stress promotes disc cellular senescence and matrix homeostatic perturbation. Thus, the ATM signalling pathway represents a therapeutic target to delay the progression of age‐associated spine pathologies., Persistent DNA damage causes chronic activation of ATM signaling, leading to disc cellular senescence and degeneration. Attenuation of ATM signaling mitigates disc cellular senescence and intervertebral disc degeneration.

Ultrasound is a method for enhancing neurite outgrowth because of its thermal effect. In order to reach the working temperature to enhance neurite outgrowth, long-time treatment by ultrasound is necessary, while acknowledging that the treatment poses a high risk of damaging nerve cells. To overcome this problem, we developed a method that shortens the ultrasonic treatment time with a warming biomaterial. In this study, we used Fe3O4 nanoparticle-embedded polycaprolactone (PCL) as a sonosensitized biomaterial, which has an excellent heating rate due to its high acoustic attenuation. With this material, the ultrasonic treatment time for enhancing neurite outgrowth could be effectively shortened. Ultrasonic treatment could also increase neuronal function combined with the warming biomaterial, with more promoter neuronal function than only ultrasound. Moreover, the risk of overexposure can be avoided by the use of the warming biomaterial by reducing the ultrasonic treatment time, providing better effectiveness.

In this study, recycled polymer feedstocks (high-density polyethylene, HDPE and polypropylene, PP) were added with different percentages of activated carbon (AC) made from coconut fiber waste – 0, 2, 4, 6, and 8%. The melting temperatures of the recycled HDPE and HDPE/PP filaments were 113 and 170°C, respectively. The addition of AC improved the thermal stability of the recycled filaments up to 28% while decreased the crystallinity of the filament produced, resulting in a more uniform surface with less crazing. Incompatibility of the recycled HDPE and AC was observed. However, the presence of PP greatly enhanced the compatibility of AC with the HDPE polymer. With the addition of 8% AC to the recycled HDPE/PP, the elongation at break of the recycled HDPE/PP filament reached 54.2%, about 10 times higher than that without AC, which could be due to the passive local interfacial bonding of AC with the methyl group of the PP matrix. The improved elongation at break would in turn aid in 3D printing of products with better elasticity.

Background/aim Drynaria fortunei (Gusuibu; GSB) is a popular traditional Chinese medicine used for bone repair. An increasing number of studies have reported that GSB induces osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). These results provide insight into the application of GSB for bone tissue engineering techniques used to repair large bone defects. However, few studies have described the molecular mechanisms of GSB. Materials and methods In the present study, the effects of GSB and naringin, a marker compound, on the binding of BMP-2 to BMPR and BMP-2-derived signal transduction were investigated using surface plasmon resonance (SPR) and coculturing with BMPR- expressed cell line, C2C12, respectively. Furthermore, naringin was also used to prepare naringin contained scaffolds for bone tissue engineering. The physical and chemical properties of these scaffolds were analysed using scanning electron microscopy (SEM) and highperformance liquid chromatography (HPLC). These scaffolds were cocultured with rabbit BMSCs in vitro and implanted into rabbit calvarial defects for bone repair assessment. Results The results showed that GSB and naringin affect the binding of BMP and BMPR in SPR experiments. GSB is a subtle BMP modulator that simultaneously inhibits the binding of BMP-2 to BMPR-1A and enhances its binding to BMPR-1B. In contrast, naringin inhibited BMP-2 binding to BMPR-1A. In vitro studies involving the phosphorylation of signals downstream of BMPR and Smad showed that GSB and naringin affected stem cell differentiation by inhibiting BMPR-1A signalling. When using GSB for bone tissue engineering, naringin exhibited a higher capacity for slow and gradual release from the scaffold, which promotes bone formation via osteoinduction. Moreover, control and naringin scaffolds were implanted into rabbit calvarial defects for 4 weeks, and naringin enhanced bone regeneration in vivo significantly. Conclusions GSB and its marker compound (naringin) could inhibit the binding of BMP-2 and BMPR-1A to control cell differentiation by blocked BMPR-1A signalling and enhanced BMPR-1B signalling. GSB and naringin could be good natural BMP regulators for bone tissue engineering.

Environmental-friendly three-dimensional (3D) multiwalled carbon nanotubes (CNTs) grown from the montmorillonite (MMT) and graphene oxide (GO) without adding metal catalysts are the first investigation for the supercapacitor electrode application, which dramatically reduces the noble and rare metal needs. Growth mechanisms of as-synthesized CNT-based MMTs (MCNTs) and CNT-based GOs- (GCNTs) via thermal chemical vapor deposition are suggested that the Ni ion nuclear seeds are self-arranged and intercalated spontaneously into the substrate surfaces and template layers. In addition, the maximum energy densities of MCNT and GCNT electrodes are 63.8 Wh/kg at 0.02 kW/kg and 147 Wh/kg at 0.09 kW/kg, respectively. The electrochemical impedance spectroscopy spectrum exhibits the charge transfer resistance significantly decreases with fabricating 3D active composite materials, indicating the mass transfer limitation in the low-frequency area and the charge transfer of kinetic controlling in the high-frequency domain. The Bode-phase angle at 78.6° of the GCNT electrode indicates ideal capacitive behavior. Frequencies of MCNT and GCNT electrodes at a phase angle of 45° are 0.27 and 0.11 Hz, corresponding to the calculated time relaxation constants of 3.70 and 9.09, respectively. MCNT and GCNT composites are clear to enhance a more surface accessible region for electrolyte ions and electron conductivity with the increasing CNT content. After 2000 continuous cyclic voltammetry and galvanostatic charge-discharge cyclic experiments, specific capacitance retentions with a 5% error bar of 3D MCNT and GCNT electrodes achieve 122.3 and 75.2%, 127.6 and 85.3%, respectively. As both electrodes, less metal usage is friendly to the environment, and in addition, layered fabrication is beneficial for production and further follow-up recycle separation of energy devices. Non-blending 3D MCNT and GCNT composites possess the potential to be the prospective materials for further energy storage application.

Correct sensible heat curve (virtual baseline) during phase change is a must for accurate evaluation of latent heat. In this article, the dynamically moving interface (DMI) model for any phase change material (PCM) measured with a differential scanning calorimeter (DSC) is devised not only for elucidating the complex mechanisms of transient heat transfer in the five stages from solid phase to liquid phase, but also for constructing a correct sensible heat curve during phase change. We derive all the governing relations in exact or analytic form to describe the corresponding heat currents in the five stages of transient heat transfer together with the correct sensible heat curve during phase change inside any tiny PCM sample. The error budget analysis for the expanded uncertainty of specific latent heat about the tiny indium sample is detailed after the full assessment to specific latent heats of several PCMs.

An l-pyroglutamic acid-derived bifunctional organocatalyst was designed and applied in an organocatalytic asymmetric direct aldol reaction between isatins and cyclohexanone, in which an erosion of enantiomeric excess of aldol adduct was unexpectedly observed. Through closely monitoring the reaction and performing extensive control experiments, it was determined that the erosion of ee was attributed to a rare stereospecific retro-aldol process. Moreover, effective manipulation of the retro-aldol process by tuning the use of starting materials was ultimately accomplished, leading to evidently upgraded enantioselectivity and functional group tolerance. This study demonstrates the impact of the hidden reaction pathway on the enantioselectivity in asymmetric transformation.

This study aims to elucidate the effect of magnetic graphene oxide (GO) alignment in a polymer matrix on the ionic conduction and methanol barrier properties of the resulting composites. Magnetic iron oxide (Fe3O4) nanoparticles were fabricated and anchored on GO nanosheets. The magnetic GO-Fe3O4 nanofillers were incorporated into a quaternized polyvinyl alcohol (QPVA) matrix to form a polymeric composite. By applying a magnetic field (MF) along the in-plane direction during the drying and film formation steps, the GO-Fe3O4 nanosheets were aligned in an orientation parallel to the direction of the MF and connected to each other in elongated domains, as confirmed using transmission electron microscopy, field emission scanning electron microscopy/energy dispersive X-ray spectroscopy mapping, and laser scanning microscopy. The MF-aligned QPVA/GO-Fe3O4 electrolyte possessed higher conductivity and lower permeability than the un-aligned QPVA/GO-Fe3O4 membrane and pristine QPVA film. The aligned QPVA/GO-Fe3O4 composite exhibited a peak power density of 172.4 mW cm−2 at 60 °C, which is higher than those of the composite without the MF treatment (67.7 mW cm−2) and the pristine QPVA (50.3 mW cm−2). This research demonstrates the extraordinary benefits of MF assisted GO-Fe3O4 nanofillers in facilitating the ion conduction and barrier property of a polymeric composite at 0.1% filler loading.

A facile and enantioselective access to a functionalized octahydroacridine scaffold was developed via an organocatalytic domino sequence between cyclohexenone and 2- N-substituted benzaldehyde. High levels of yields (up to 99%) and enantioselectivities (up to 99:1 er) were readily achieved in this developed organocatalytic transformation, which holds promising applications in the construction of complex multicyclic systems for further pharmacological studies.

Freezing nitrogen ethanol composite (FNEC) showed effective cryoablative ability for bone tumor ex vivo and in vivo comparable to liquid nitrogen (LN). We therefore wished to compare the radiant cooling damage of the surrounding tissue between FNEC and LN. The evaluation of the radiant cooling damage was demonstrated human bone xenograft transplantation (HXT) in a mouse model. Characterizations and quantifications of the damaging effects on morphologic features and apoptosis of the cryoablative surrounding bone tissue, muscle and epidermal layer of skin were compared. The radiant cooled damaging effects including epidermal rupture, hair follicle atrophy, dermis and subcutaneous crystal vacuolation of skin were significantly greater in LN than FNEC. Muscular apoptosis, structural shrinkage and bone cellular apoptosis were supposedly 15%-33% destroying degrees of LN more than FNEC. We concluded that FNEC is an innovative cryogenic material, and it could cause less cryoablative damage to surrounding normal tissue than LN. The findings might support the safety of FNEC being applied in clinical cryoablation therapy.

An experimental trial was conducted to investigate the effects of high dietary starch levels on growth, hepatic glucose metabolism enzyme, antioxidant capacity and immune responses of largemouth bass, Micropterus salmoides. Fish (initial body weight: 16.9 ± 0.24 g) were fed three isonitrogenous and isoenergetic semi-purified diets containing 5%, 10% and 20% wheat starch, respectively. The results indicated that fish fed 5% and 10% starch diets showed significantly better weight gain, specific growth rate (SGR), protein efficiency ratio (PER) and feed conversion ratio (FCR) compared with that fed 20% starch diet. Meanwhile, fish fed 20% starch diet had a significantly higher hepatic glycogen and muscle glycogen contents than those fed the other diets. The alanine amiotransferase (ALT) and aspartate transaminase (AST) activities, glucose and insulin contents in plasma increased significantly with dietary starch levels, whereas triglyceride content showed the opposite trend. In addition, the highest glucokinase (GK), pyruvate kinase (PK) and phosphofructokinase (PFK) activities in liver were also observed in fish fed 20% starch diet. However, both fructose-1,6-bisphosphatase (FBPase) and pyruvate carboxylase (PC) activities in liver decreased significantly as dietary starch levels increased. Moreover, the lower superoxide dismutase (SOD) and catalase (CAT), the higher malondialdehyde (MDA) contents in liver were observed in fish fed 20% starch diets. Compared to the 5% and 10% starch, the 20% starch could enhance the content of plasma nitric oxide (NO) and the activities of inducible nitric oxide synthase (iNOS) and alkaline phosphatase (ALP). Results demonstrate that the starch levels may affect growth performance and metabolic changes, which suggest that high-starch diets were inefficiently used as an energy source by M. salmoides juveniles. Excessive dietary starch contents could result in oxidative stress, suppress innate immunity, and thus affect the health status of M. salmoides.

Breast cancer is a major public health problem throughout the world. In this report, we investigated whether CHM-1, a novel synthetic antimitotic agent could be developed into a potent antitumor agent for treating human breast cancer. CHM-1 induced growth inhibition in MDA-MB-231, MDA-MB-453 and MCF-7 cells in a concentration-dependent manner. Importantly, CHM-1 is less toxic to normal breast (HBL-100) cells. CHM-1 interacted with tubulin, markedly inhibited tubulin polymerization, and disrupted microtubule organization. Proteins from control and CHM-1-treated animal tumor specimens were analyzed by two-dimensional electrophoresis and MALDI-TOF mass spectrometry. Our results indicated that CHM-1 increased the expression of SIRT2 protein, an NAD-dependent tubulin deacetylase. A prodrug strategy was also investigated to address the problem of low aqueous solubility and low bioavailability of the antitumor agent CHM-1. The water-soluble prodrug of CHM-1 (CHM-1-P) was synthesized. After oral and intravenous administration, CHM-1-P induced a dose-dependent inhibition of tumor growth. The aforementioned excellent anti-tumor activity profiles of CHM-1 and its prodrug CHM-1-P, suggests that CHM-1-P deserves to further develop as a clinical trial candidate for treating human breast carcinoma.

The present research investigates the ionic transport and interfacial interaction of iodide (I−)/tri-iodide (I3−) redox couple in an agarose and titanium oxide (TiO2) nanoparticles electrolyte to improve the photovoltaic efficiency of dye-sensitized solar cells (DSSCs). In this work, TiO2 nanoparticles and agarose gel are added into an I−/I3− electrolyte containing a 3-methoxypropionitrile (MPN)/1-methyl-2-pyrrolidinone (NMP) mixed solvent to prepare colloidal electrolytes for a DSSC. Although the addition of agarose into the electrolyte lowers the electrolyte conductivity and decreases I−/I3− ions diffusivity coefficients, the agarose is beneficial for facilitating uniform dispersion of the TiO2 nanoparticles in the electrolyte. The presence of agarose can provide an effective surface for the formation of triiodide ions or other higher polyiodides. The synergistic effect of TiO2 and agarose on polyiodide formation is profound, as shown in the highest I5− peak intensity among tested electrolytes. The TiO2 nanoparticles in the gel agarose electrolyte exhibit Grothuss-type ion transfer channels and provide I−/I3−/I5− ionic conduction paths to hasten the ion transfer rates between the electrodes, improving the ion diffusivities and electrolyte conductivity. The novel electrolyte improves the DSSC efficiency and results in higher photocurrent density than the control liquid electrolyte and agarose electrolyte without TiO2 nanoparticles.

Increasing evidence supports the anti-estrogenic and/or anti-proliferative properties of luteolin, which is a natural flavonoid existing in herbs, vegetables and fruits. However, the molecular mechanisms responsible for these effects are only partially explored. In the present study, estrogen receptor-alpha (ER-α) was identified as a potential molecular target for luteolin. Our data indicated that treatment with luteolin engendered suppression of ER-α protein and mRNA expression in ER-α-positive breast cancer cells. Y-box binding protein-1 (YB-1) is a known transcriptional regulator of ER-α expression. In this studies it was demonstrated that luteolin decreased YB-1 protein and mRNA expression. Integrin-linked kinase (ILK) is able to phosphorylate many downstream effectors that have the potential to regulate YB-1 transcription. We provided evidence for a mechanism by which luteolin suppressed YB-1 expression through the downregulation of ILK/Akt/STAT3-regulated Twist expression in ER-α-positive breast cancer cells. Our data also showed that luteolin inhibited cancer migration and invasion through the inhibition of epithelial-mesenchymal transition (EMT). Taken together, these data indicate that the antitumorigenic effects of luteolin in ER-α-positive breast cancer cells may arise from its ability to reduce ER-α expression.