Search

Brown adipose tissues (BAT) burn lipids to generate heat through uncoupled respiration, thus representing a powerful target to counteract lipid accumulation and obesity. The tumor suppressor liver kinase b1 (Lkb1) is a key regulator of cellular energy metabolism; and adipocyte-specific knockout of Lkb1 (Ad-Lkb1 KO) leads to the expansion of BAT, improvements in systemic metabolism and resistance to obesity in young mice. Here we report the unexpected finding that the Ad-Lkb1 KO mice develop hindlimb paralysis at mid-age. Gene expression analyses indicate that Lkb1 KO upregulates the expression of inflammatory cytokines in interscapular BAT and epineurial brown adipocytes surrounding the sciatic nerve. This is followed by peripheral neuropathy characterized by infiltration of macrophages into the sciatic nerve, axon degeneration, reduced nerve conductance, and hindlimb paralysis. Mechanistically, Lkb1 KO reduces AMPK phosphorylation and amplifies mammalian target-of-rapamycin (mTOR)-dependent inflammatory signaling specifically in BAT but not WAT. Importantly, pharmacological or genetic inhibition of mTOR ameliorates inflammation and prevents paralysis. These results demonstrate that BAT inflammation is linked to peripheral neuropathy., Highlights • Adipocyte specific knockout Lkb1 mice develop late onset hindlimb paralysis despite better metabolism in young animals. • Lkb1 KO in brown adipocytes promotes expression of proinflammatory cytokines that are linked to sciatic nerve neuropathy. • Rapamycin or genetic inhibition of mTOR ameliorates BAT inflammation and prevents paralysis. Brown adipose tissues (BAT) burn lipids to dissipate heat, expansion of BAT is thus considered as an attractive strategy to counteract obesity. Here, we use a mouse model in which the Lkb1 gene is knockout in adipocytes to show that the knockout mice develop enlarged BAT, resulting in better systemic metabolism. However, the knockout mice later develop peripheral neuropathy and hindlimb paralysis due to inflammation of the enlarged BAT. Inhibition of a signaling cascade known as mTOR effectively blunted the inflammation of BAT and prevented hindlimb paralysis. Therefore, even though BAT is known to promote metabolic health in the context of obesity, chronic inflammation of BAT is linked to devastating peripheral neuropathy. This study further suggests that blockage of mTOR is an effective strategy to treat inflammation-induced peripheral neuropathy.

A simple and intuitive method for optimizing the chemical constituents of Coptis Chinensis Franch. is important to assess its quality and clinical efficacy. An high performance liquid chromatography and ultraviolet spectrophotometry method was developed for the determination of berberine hydrochloride, palmatine chloride, jatrorrhizine hydrochloride, epiberberine, coptisine, columbamine and magnoflorine in various tissues (i.e., phloem, xylem and medulla) and rizhome of C. Chinensis Franch. The transection of rhizome from outside-in includes cork layer, cortex, phloem, cambium, xylem and medulla. Cork layer consists of dead cells, and therefore is not of any research significance. Cortex, phloem and cambium were almost impossible to separate, therefore they were studied as a whole in our experiments. They were collectively referred to as "phloem". The analytes were separated on a Gemini-NX C18 (250 mm × 4.6 mm, 5 μm) reversed phase column using a gradient elution of acetonitrile-0.03 mol/L ammonium acetate solution (containing 0.1% triethylamine and 0.6% ammonium hydroxide) as the mobile phase at a flow rate of 1.0 mL/min and UV detection at 270 nm. The method allowing the simultaneous quantification of seven major active constituents was optimized and validated for linearity, precision, accuracy, limits of detection (LOD) and quantification. The LOD ranged from 0.102 to 0.651 mg/mL (r ≥ 0.9993). Accuracy, precision and recovery were all within the required limits. The average recovery was between 100.14% and 102.75% and the relative standard deviations were

A series of Er3+/Yb3+-codoped NaYF4 upconverting nanoparticles were synthesized via a hydrothermal method. By controlling the synthetic temperature, the phase transition and size manipulation of nanoparticles were simultaneously realized in the studied compounds. Upon the irradiation of near-infrared light, the prepared nanoparticles revealed dazzling visible emissions arising from the intra-4f transitions of Er3+ ions. Moreover, the pump power-dependent upconversion (UC) emission spectra were recorded to analyze the involved UC mechanism. Furthermore, the temperature sensing behaviors of the resultant compounds were investigated by analyzing the temperature-dependent green emission intensities from the thermally coupled levels of 2H11/2 and 4S3/2. It is found that the sensor sensitivity of the synthesized samples is dependent on the synthetic temperature which is further confirmed by the Judd–Ofelt theory. Additionally, the sensor sensitivity of the prepared nanoparticles is also found to be dependent on the laser pump power. The Er3+/Yb3+-codoped NaYF4 upconverting nanoparticles sintered at 160 °C exhibited the optimum thermometric properties with a maximum sensor sensitivity of 0044 K−1 at 637 K when the excitation pump power was 139 mW. The adjustment of the synthetic temperature and excitation pump power is a promising channel to manipulate the sensor sensitivity of the Er3+/Yb3+-codoped NaYF4 upconverting nanoparticles.

Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase essential for a diverse set of cellular functions. Current methods for monitoring FAK activity in response to an extracellular stimulus lack spatiotemporal resolution and/or the ability to perform multiplex detection. Here we report on a novel approach to monitor the real-time kinase phosphorylation activity of FAK in live single cells by fluorescence lifetime imaging.

Objectives:Galla chinensiswater extract (GCE) has been demonstrated to inhibit dental caries by favorably shifting the demineralization/remineralization balance of enamel and inhibiting the biomass and acid formation of dental biofilm. The present study focused on the comparison of composition and anticaries effect ofGalla chinensisextracts with different isolation methods, aiming to improve the efficacy of caries prevention.Methods:The composition of water extract (GCE), ethanol extract (eGCE) and commercial tannic acid was compared. High performance liquid chromatography coupled to electrospray ionization-time of flight-mass spectrometry (HPLC-ESI-TOF-MS) analysis was used to analyze the main ingredients.In vitropH-cycling regime and polymicrobial biofilms model were used to assess the ability of differentGalla chinensisextracts to inhibit enamel demineralization, acid formation and biofilm formation.Results:All the GCE, eGCE and tannic acid contained a high level of total phenolics. HPLC-ESI-TOF-MS analysis showed that the main ingredients of GCE were gallic acid (GA), while eGCE mainly contained 4-7 galloylglucopyranoses (GGs) and tannic acid mainly contained 5-10 GGs. Furthermore, eGCE and tannic acid showed a better effect on inhibiting enamel demineralization, acid formation and biofilm formation compared to GCE.Conclusions:Galla chinensisextracts with higher tannin content were suggested to have higher potential to prevent dental caries.

Nerve cells secrete neurotrophic factors that play a critical role in neuronal survival, proliferation, and regeneration. However, their role in regulating myoblast behavior and skeletal muscle repair remains largely unexplored. In the present study, we investigated the effects of PC12 secreted signaling factors in modulating C2C12 myoblast behavior under physiologically relevant conditions. We showed that PC12 conditioned media modulated myoblast proliferation and differentiation in both 2D culture and 3D aligned electrospun fiber scaffold system in a dose-dependent manner. We further developed a biomimetic, tunable hydrogel consisting of hyaluronic acid, chondroitin sulfate, and polyethylene glycol as a 3D matrix encapsulating PC12 cells. The hydrogel-encapsulated PC12 cells promoted survival and proliferation of myoblasts in co-culture. Further proteomics analysis identified a total of 2,088 proteins from the secretome of the encapsulated PC12 cells and revealed the biological role and overlapping functions of nerve-secreted proteins for skeletal muscle regeneration, potentially through regulating myoblast behavior, nerve function, and angiogenesis. These experiments provide insights into the nerve-muscle interactions and pave the way for developing advanced biomaterials strategies incorporating nerve cell secretome for accelerated skeletal muscle regeneration.

Due to the large number of parts and connections etc. in complex electronic equipment, it always takes a lot of time to carry out the pre-processing work in the finite element simulation with workbench. In addition, problems such as constraint loss, over-constraint caused by automatic constraint generation and material loss are easy to occur with the model update, which will lead to a lot of repetitive works. The pre-processing is always time-consuming and error-prone especially for complex model. In view of the characteristics of pretreatment in finite element simulation, plug-ins are developed to simplify the pre-processing work for workbench with IronPython, which could realize the automatic recognition of circular holes and the setting up of beam elements, as well as, automatically repair the contact, connection, material settings and other pre-processing work after the model modification. It would avoid the repetitive work in pre-processing which would improve the efficiency of pre-processing and reduce the intensity of finite element simulation works.

A synthetically challenging tetracyclic tertiary amine framework in the Daphniphyllum alkaloid daphenylline was established in a six-step sequence featuring an intermolecular Diels-Alder cycloaddition/oxidative aromatization sequence. The utilization of an amine-borane complexation strategy is the key to successful transformations on our tertiary amine substrates.

The possible effect of the National Plan on the development of special education has not been examined, and there is no published evidence concerning both national and international readership about the realisation of this policy document in China. Given this, we conducted a before&ndash, after design study at a 7-year interval including six variables of special education: number of schools, total enrolment, new enrolment, graduates, educational personnel, and full-time teachers. The data were retrieved from the National Bureau of Statistics of China (NBSC). The results indicated two patterns of special education development in China. First, the National Plan has quantitatively affected some special education services (schools, new enrolments, educational personnel, and full-time teachers). Second, the National Plan has possibly resulted into better control of the quality of special education&mdash, evidenced by an insignificant increase in total enrolment and graduates at the two compared intervals.

In this paper, surface acoustic wave devices were fabricated using aluminum nitride (AlN) film as piezoelectric layer, molybdenum (Mo) film as bottom electrode, and polyimide (PI) film as flexible substrate. The crystalline quality of Mo and AlN films was characterized by X-ray Diffraction (XRD), atomic force microscope (AFM) and scanning electron microscope (SEM). Furthermore, the interdigital transducer (IDT) was fabricated by Ultraviolet Exposure and Electron Beam Exposure, and the resulting SAW device structure was IDTs/AlN/Mo/PI, the center frequency reaches GHz. After bending 100 times, the center frequency can still be kept at GHz, this shows that the flexible surface acoustic wave device shows better performance.

In order to improve the crystal quality of AlN films grown on Si substrate, ZnO buffer layers with different thickness (20, 40, 60, 80, 160 nm) were introduced. The structure, elemental composition, crystalline orientation and surface morphology of AlN/ZnO films were studied in this paper. The results show that ZnO buffer layer improves the crystal quality of AlN films and the optimal thickness of ZnO buffer layer is 60 nm, which yields the best c-axis orientation, uniform grain size and obvious columnar growth. This work makes AlN films on Si substrate more helpful for the preparation of SAW devices.

Novel rhombic dodecahedral SnS nanocrystals were prepared via a facile one-pot hydrothermal method for the first time, which exhibit a large extinction coefficient of 36.8 L g-1 cm-1 and a high photothermal conversion efficiency of 39.4% under irradiation with a 785 nm laser. Moreover, they show good performance for photothermal therapy of HeLa tumors.

The single-celled trichomes of Arabidopsis thaliana have long served as an elegant model for elucidating the mechanisms of cell differentiation and morphogenesis due to their unique growth patterns. To identify new components in the genetic network that governs trichome development, we carried out exhaustive screens for additional Arabidopsis mutants with altered trichome morphology. Here, we report one mutant, aberrantly branched trichome1-1 (abt1-1), with a reduced trichome branching phenotype. After positional cloning, a point mutation in the SPIKE1 (SPK1) gene was identified in abt1-1. Further genetic complementation experiments confirmed that abt1-1 is a new allele of SPK1, so abt1-1 was renamed as spk1-7 according to the literatures. spk1-7 and two other spk1 mutant alleles, covering a spectrum of phenotypic severity, highlighted the distinct responses of developmental programs to different SPK1 mutations. Although null spk1 mutants are lethal and show defects in plant stature, trichome and epidermal pavement cell development, only trichome branching is affected in spk1-7. Surprisingly, we found that SPK1 is involved in the positioning of nuclei in the trichome cells. Lastly, through double mutant analysis, we found the coordinated regulation of trichome branching between SPK1 and two other trichome branching regulators, ANGUSTIFOLIA (AN) and ZWICHEL (ZWI). SPK1 might serve for the precise positioning of trichome nuclei, while AN and ZWI contribute to the formation of branch points through governing the cMTs dynamics. In summary, this study presented a fully viable new mutant allele of SPK1 and shed new light on the regulation of trichome branching and other developmental processes by SPK1.

In this paper, scandium molybdate microstructures have been prepared from solution via a microwave heating method. By controlling the experimental parameters such as molar ratio of reagent and reaction time, scandium molybdates with tunable phase and diverse morphologies including snowflakes, microflowers, microsheets, and branched spindles were obtained. The density of states and surface energies of Sc2Mo3O12 were primarily studied from first-principles calculations. An indirect band gap of 3.56 eV was observed for crystalline Sc2Mo3O12, and the surface energies of various facets were determined to be 0.27–0.91 J/m2. The influence of n(Sc3+):n(Mo7O246–) (short for Sc/Mo) molar ratio was systematically investigated and well-characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and UV–vis absorption spectroscopy (UV–vis). Results indicate that the Sc/Mo molar ratio has a great effect on the phase and morphology. Diffuse reflection spectra ...

Purpose: We examined the development of correctional education in China with reference to the National Plan (2010-2020)

How the nervous system regulates bone remodeling is an exciting area of emerging research in bone biology. Accumulating evidence suggest that neurotransmitter-mediated inputs from neurons may act directly on osteoclasts. Dopamine is a neurotransmitter that can be released by hypothalamic neurons to regulate bone metabolism through the hypothalamic-pituitary-gonadal axis. Dopamine is also present in sympathetic nerves that penetrate skeletal structures throughout the body. It has been shown that dopamine suppresses osteoclast differentiation via a D2-like receptors (D2R)-dependent manner, but the intracellular secondary signaling pathway has not been elucidated. In this study, we found that cAMP-response element binding protein (CREB) activity responds to dopamine treatment during osteoclastogenesis. Considering the critical role of CREB in osteoclastogenesis, we hypothesize that CREB may be a critical target in dopamine’s regulation of osteoclast differentiation. We confirmed that D2R is also present in RAW cells and activated by dopamine. Binding of dopamine to D2R inhibits the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway which ultimately decreases CREB phosphorylation during osteoclastogenesis. This was also associated with diminished expression of osteoclast markers that are downstream of CREB. Pharmacological activation of adenylate cyclase (to increase cAMP production) and PKA reverses the effect of dopamine on CREB activity and osteoclastogenesis. Therefore, we have identified D2R/cAMP/PKA/CREB as a candidate pathway that mediates dopamine’s inhibition of osteoclast differentiation. These findings will contribute to our understanding of how the nervous and skeletal systems interact to regulate bone remodeling. This will enable future work toward elucidating the role of the nervous system in bone development, repair, aging, and degenerative disease.

In firefighting situations, firefighters will encounter multiple flame exposures during go through the fireground several times. In this study, the effects of multiple flame exposures on thermal shrinkage and thermal protective performance of three fabrics used in firefighting clothing were investigated. The fabric surface morphology after flame exposure was obtained by a handy scanner, and further processed in ArcGis software. The thermal shrinkage of fabrics was characterized by ten shrinkage parameters and then quantified by using principal component analysis. The results showed that flame exposure frequency had influence on the thermal shrinkage of fabrics. As compared to several short-duration exposures, a long-duration continuous exposure resulted greater thermal shrinkage. The correlation analysis showed that there was no significant correlation between thermal shrinkage of the fabric and its thermal protective performance. The findings in this study indicated that the effects of multiple flame exposures on thermal shrinkage and thermal protective performance of firefighters clothing should be considered during clothing design and performance prediction.

China has developed a three-tier special education service delivery system consisting of an array of placement options of special schools, special classes and learning in regular classrooms (LRC) (with the LRC as the major initiative) to serve students with disabilities after 1980s responding to the international trend of inclusive education mandate. How to balance the development of special education schools (classes) and inclusive education remains controversial. The authors found that special education provision in China has been improved in scale and quality with the expansion of special schools and LRC programmes both to have formed a parallel special education system. The authors argue that the boundaries between special and regular education system are enlarged and blurred in different situations. This reflects that the move towards inclusive education in China has been largely underpinned by its specific cultural values and conflicts between the pursuit of academic excellence and new goal of universalising basic education for all. The Chinese pragmatic practice of inclusive education shows that special schools should be a part of, instead of apart from, inclusive education, and thus should be re-empowered with new roles to support and facilitate inclusive education.

The aim of this study was to develop and validate an instrument of inclusive teachers’ competencies for teaching students with special educational needs in China. Data were obtained from a preliminary and large-scale investigation in Beijing. The primary analyses included exploratory factor analysis and confirmatory factor analysis. The findings indicated that Chinese inclusive teachers’ competency is underpinned by four factors: teaching and instruction; communication and cooperation; attitudes and beliefs; and reflection and development. The four-factor model was obtained with satisfactory reliability and validity. The validated questionnaire generated a theoretical understanding of inclusive education teachers’ competency in China. In addition, the findings of the study provided knowledge that will allow for the development of professional standards and teacher education programmes for inclusive education.

SummaryUnderstanding the negative regulators of antiviral immune responses will be critical for advancing immune-modulated antiviral strategies. NLRX1, an NLR protein that negatively regulates innate immunity, was previously identified in an unbiased siRNA screen as required for HIV infection. We find that NLRX1 depletion results in impaired nuclear import of HIV-1 DNA in human monocytic cells. Additionally, NLRX1 was observed to reduce type-I interferon (IFN-I) and cytokines in response to HIV-1 reverse-transcribed DNA. NLRX1 sequesters the DNA-sensing adaptor STING from interaction with TANK-binding kinase 1 (TBK1), which is a requisite for IFN-1 induction in response to DNA. NLRX1-deficient cells generate an amplified STING-dependent host response to cytosolic DNA, c-di-GMP, cGAMP, HIV-1, and DNA viruses. Accordingly, Nlrx1−/− mice infected with DNA viruses exhibit enhanced innate immunity and reduced viral load. Thus, NLRX1 is a negative regulator of the host innate immune response to HIV-1 and DNA viruses.

Musculoskeletal tissue loss or damage resulting from trauma, surgery, or disease presents a significant medical challenge. Current therapies involving grafts are hindered by concerns over donor site morbidity and limited functional improvement. Regenerative engineering emerges as a promising transdisciplinary strategy for tissue repair and regeneration based on the convergence of tissue engineering, advanced materials science, stem cell science, and developmental biology. Of particular interest is the development of cell-instructive matrices that closely mimic the properties of the native tissues. Electrospinning provides a versatile technology platform for the design and fabrication of nanofiber-based scaffolds that are similar to natural extracellular matrix. Biodegradable polymers constitute an attractive class of biomaterials for the development of electrospun structures due to flexibility in chemistry and the ability to be excreted or resorbed by the body. Here, we highlight the importance of material cues on cellular responses and discuss recent advances in the development of electrospun polymeric structures as biomimetic matrices to regenerate musculoskeletal tissues with a focus on the work involving bone, tendon, skeletal muscle, and their interfaces. Scaffold-based regenerative engineering represents a clinical translational strategy for tissue regeneration. A scaffold offers an engineered cell microenvironment to direct cell migration, growth, differentiation, and organization to form regenerated tissue. Successful tissue regeneration critically depends on the development of scaffolds that mimic the hierarchical architecture of native tissue extracellular matrix. In particular, electrospun polymer nanofibers provide an enabling technology platform to engineer a scaffold system with an appropriate combination of physical, chemical, and biological properties for regeneration of various musculoskeletal tissues.

Our recent investigation on the antiviral activities against tobacco mosaic virus (TMV) of phenanthroindolizidine alkaloid analogues preliminarily revealed that the basic skeleton and substitution pattern at the C13a position of the molecule, which are closely related to the spatial arrangement of the molecule, have great effects on the biological activity. To further study the in-depth influence of spatial configuration and three-dimensional (3D) conformation of the molecules on their anti-TMV activities and related structure-activity relationship (SAR), a series of D-ring opened derivatives 3, 4, 5a-5j, 6, and 7, chiral 13a- and/or 14-substituted phenanthroindolizidine analogues 10-12 and 18-20, and their enantiomers ent-10-ent-12 and ent-18-ent-20 were synthesized and evaluated for their anti-TMV activities. Bioassay results showed that most of the chiral phenanthroindolizidines displayed good to excellent in vivo anti-TMV activity. Among these compounds, ent-11 showed more potent activity than Ningnanmycin (one of the most successful commercial antiviral agents), thus emerging as a potential inhibitor of the plant virus. Further SARs were also discussed for the first time under the chiral scenario, demonstrating that both spatial configuration and 3D conformation of the molecules are crucial for keeping high anti-TMV activity.

Galla chinensis extract (GCE), a naturally-derived agent, has a significant inhibitory effect on cariogenic bacteria. The present study aims to evaluate the antibacterial effect and shear bond strength of an orthodontic adhesive cement containing GCE. A resin-modified glass ionomer cement incorporated GCE at five mass fractions (0, 0.1, 0.2, 0.4, and 0.8%) to prepare GCE-containing cement for analysis. For the agar diffusion test, cement specimens were placed on agar disk inoculated with Streptococcus mutans (strain ATCC 25175). Following 48 h incubation, the inhibition halo diameter was measured. To assess bacteria colonization susceptibility, S. mutans adhesion to cement specimens was detected by scanning electron microscopy (SEM) following 48 h incubation. To evaluate bond strength, a total of 50 metal brackets were bonded on premolar surfaces by using cement (10 teeth/group). Following immersion in an artificial saliva for 3 days, shear bond strength (SBS) was measured. The results demonstrated that GCE-containing samples exhibited a larger bacterial inhibition halo than control, and the inhibition zone increased as the GCE mass fraction increased. SEM analysis demonstrated that S. mutans presented a weaker adherent capacity to all GCE-containing cements compared with control, but the difference between each GCE-containing group was not significant. SBS values of each GCE-containing group exhibited no difference compared with the control. In conclusion, GCE-containing adhesive cement exhibits a promising inhibitory effect on S. mutans growth and adhesion. Without compromising bond strength, adding GCE in adhesive cement may be an attractive option for preventing white spot lesions during orthodontic treatment.

Nanoscopic imaging or characterizing is the mainstay of the development of advanced materials. Despite great progress in electronic and atomic force microscopies, label-free and far-field characterization of materials with deep sub-wavelength spatial resolution has long been highly desired. Herein, we demonstrate far-field super-resolution transient absorption (TA) imaging of two-dimensional material with a spatial resolution of sub-50 nm. By introducing a donut-shaped blue saturation laser, we effectively suppress the TA transition driven by near-infrared (NIR) pump–probe photons, and push the NIR-TA microscopy to sub-diffraction-limited resolution. Specifically, we demonstrate that our method can image the individual nano-grains in graphene with lateral resolution down to 36 nm. Further, we perform super-resolution TA imaging of nano-wrinkles in monolayer graphene, and the measured results are very consistent with the characterization by an atomic force microscope. This direct far-field optical nanoscopy holds great promise to achieve sub-20 nm spatial resolution and a few tens of femtoseconds temporal resolution upon further improvement and represents a paradigm shift in a broad range of hard and soft nanomaterial characterization.

Currently, about 30% of new approved drugs contained fluorine atoms and most of them are made through fluorination reactions using various kinds of fluorinating reagents. In the current work, we report a facile and more accessible way to probe the fluorination evolution at different stages using a newly developed fluorinating reagent (1-ethyl-3-methylimmidazolium fluoride-ethylene glycol, [C2C1im]F-EG). Benzyl bromide was converted to benzyl fluoride using this fluorinating reagent under mild conditions. A more accessible Raman method, compared to NMR, was used to probe the reaction process due to the products having their own characteristic Raman vibrational frequencies because of the formation of different C-X bonds. Thus the yield of the product at different time scales could be then quantified based on their relative intensities, providing a fresh insight into the fluorination process. This method could be applied in other reactions to reflect the important fluorination process, which methodologically reports a facile way to probe reaction processes.

Graphene resting on a silicon-on-insulator platform offers great potential for optoelectronic devices. In the paper, we demonstrate all-optical modulation on the graphene–silicon hybrid waveguides (GSHWs) with tens of micrometers in length. Owing to strong interaction between graphene and silicon strip waveguides with compact light confinement, the modulation depth reaches 22.7% with a saturation threshold down to 1.38 pJ per pulse and a 30-μm-long graphene pad. A response time of 1.65 ps is verified by a pump–probe measurement with an energy consumption of 2.1 pJ. The complementary metal-oxide semiconductor compatible GSHWs with the strip configuration exhibit great potential for ultrafast and broadband all-optical modulation, indicating that employing two-dimensional materials has become a complementary technology to promote the silicon photonic platform.

Over the past three decades, the international community has witnessed China’s increasing integration into the global economy and dramatic changes to every aspect of its social life (Postiglione GA (ed). Education and social change in China: inequality in a market economy. M.E. Sharpe, Armonk, 2006). Shanghai, as the largest metropolis and economic centre in China, has been widely expected to play a leading role in the modernisation process of the national economy and technological innovation. As early as the 1990s, the Shanghai government set the goal of establishing itself as a global city and in its 10th Five-Year Plan (2001–2005), declared its aim to become a centre of international commerce, finance, trade and shipping by 2020 (Leman, China Bus Rev 29(5): 7–15, 2002). The Central Committee of the Chinese Communist Party, a dominant force in the governance of China, encouraged Shanghai to play a prominent role “leading to change the mode of economic growth, leading to improve the capability of independent innovation, leading to promote reform and opening to the world, and leading to building a harmonious socialist society” (Xinhua News, ‘Four centers’ and ‘four leaders’ (in Chinese). Retrieved from http://www.sh.xinhuanet.com/misc/2007-05/23/content_10097532.htm, 2007). To realise these goals, the Shanghai Municipal Government (The outline of the Eleventh Five-Year Plan of Shanghai for national economic and social development (in Chinese). Retrieved from http://www.shanghai.gov.cn/shanghai/node2314/node2315/node4411/userobject21ai141039.html, 2006) advocated development of innovation to enhance the international competitiveness of the city and the use of science and education as the major strategy to achieve development of the city.

Cell encapsulation within 3D hydrogels is an attractive approach to develop effective cell-based therapies. However, little is known about how cells respond to the dynamic microenvironment resulting from hydrogel gelation-based cell encapsulation. Here, a tunable biomimetic hydrogel system that possesses alterable gelation kinetics and biologically relevant matrix stiffness is developed to study 3D dynamic cellular responses during encapsulation. Hydrogels are synthesized by cross-linking thiolated hyaluronic acid and thiolated chondroitin sulfate with polyethylene glycol diacrylate under cell-compatible conditions. Hydrogel properties are tailored by altering thiol substitution degrees of glycosaminoglycans or molecular weights of cross-linkers. Encapsulation of human mesenchymal stem cells through hydrogel gelation reveals high cell viability as well as a three-stage gelation-dependent cellular response in real-time focal adhesion kinase (FAK) phosphorylation in live single cells. Furthermore, stiffer hydrogels result in higher equilibrium FAK activity and enhanced actin protrusions. Our results demonstrate the promise of hydrogel-mediated cellular responses during cell encapsulation.

A series of thieno[3,2-d]pyrimidine derivatives as phosphatidylinositol 3-kinase (PI3K) inhibitors was designed using the combination strategy. The synthesis and biological evaluation of the derivatives demonstrated their potent inhibition of PI3K, culminating in the discovery of 7 and 21. Determination of a co-crystal structure of 7 complexed with PI3Kα provided the structural basis for the high enzymatic activity. Furthermore, cellular investigation of compounds 7 and 21 revealed that they efficiently suppressed cancer cell lines proliferation through inhibition of intracellular PI3K/AKT/mammalian target of rapamycin pathway. The results provided potent simplified inhibitors of PI3K with a promising overall profile and a chemical series for further optimization to progress into vivo experiments.

Plant trichome has long been selected as a model system to study the regulatory mechanism during cell development due to its unique growth characteristics. In an effort to explore new components that contribute to trichome development, we performed large-scale forward genetic screening in Arabidopsis, and found two recessive mutants with significant trichome branching defects, both of which display one branched trichomes. After map-based cloning, genetic complementation experiments, we confirmed that they are new alleles of STICHEL (STI) that has been reported to act as a key regulator of trichome branching. The predicted product of STI gene is comprised by three functional domains including a large domain with sequence similarity to eubacterial DNA polymerase III γ-subunit in the middle, two PEST domains in the N terminal, and two nuclear localization signals (NLS) at the very N terminal and C terminal, respectively. Our biochemistry and molecular analysis indicated that a PEST domain in the N-terminal could be important for STI functioning in regulating trichome branching. It can directly interact with BRACHLESS TRICHOME (BLT), an important linker of cell shape and endoreplication. Because the previously data showed that the function of STI in regulating trichome branching was not linked to DNA replication and actin or microtubule cytoskeleton configuration, our findings of the direct interaction domains between STI and BLT veiled the probable roles of STI in cell morphogenesis.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

NLRC3 limits inflammatory signaling in myeloid cells, but its role in T cells has been unclear. Uchimura et al. reveal that T cell expression of Nlrc3 restricts autoimmune and virus-specific CD4 + T cell responses by attenuating T cell signaling and metabolic pathways in CD4 + T cells. �� 2018 Elsevier Inc.Appropriate immune responses require a fine balance between immune activation and attenuation. NLRC3, a non-inflammasome-forming member of the NLR innate immune receptor family, attenuates inflammation in myeloid cells and proliferation in epithelial cells. T lymphocytes express the highest amounts of Nlrc3 transcript where its physiologic relevance is unknown. We show that NLRC3 attenuated interferon-�� and TNF expression by CD4 + T cells and reduced T helper 1 (Th1) and Th17 cell proliferation. Nlrc3 ���/��� mice exhibited increased and prolonged CD4 + T cell responses to lymphocytic choriomeningitis virus infection and worsened experimental autoimmune encephalomyelitis (EAE). These functions of NLRC3 were executed in a T-cell-intrinsic fashion: NLRC3 reduced K63-linked ubiquitination of TNF-receptor-associated factor 6 (TRAF6) to limit NF-��B activation, lowered phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and diminished glycolysis and oxidative phosphorylation. This study reveals an unappreciated role for NLRC3 in attenuating CD4 + T cell signaling and metabolism.

Data from clinical trials for hemophilia B using adeno-associated virus (AAV) vectors have demonstrated decreased transgenic coagulation factor IX (hFIX) expression 6-10 weeks after administration of a high vector dose. While it is likely that capsid-specific cytotoxic T lymphocytes eliminate vector-transduced hepatocytes, thereby resulting in decreased hFIX, this observation is not intuitively consistent with restored hFIX levels following prednisone application. Although the innate immune response is immediately activated following AAV vector infection via TLR pathways, no studies exist regarding the role of the innate immune response at later time points after AAV vector transduction. Herein, activation of the innate immune response in cell lines, primary human hepatocytes, and hepatocytes in a human chimeric mouse model was observed at later time points following AAV vector transduction. Mechanistic analysis demonstrated that the double-stranded RNA (dsRNA) sensor MDA5 was necessary for innate immune response activation and that transient knockdown of MDA5, or MAVS, decreased IFN-�� expression while increasing transgene production in AAV-transduced cells. These results both highlight the role of the dsRNA-triggered innate immune response in therapeutic transgene expression at later time points following AAV transduction and facilitate the execution of effective strategies to block the dsRNA innate immune response in future clinical trials.

Aim The aim was to evaluate the incidence and type of defects that occurred with K3 rotary nickel–titanium instruments during routine clinical use. Methodology A total of 2397 K3 (G-PACKS, SybronEndo, West Collins, Orange, CA, USA) instruments were collected from a graduate endodontic clinic over 21 months. All the instruments were limited to a maximum use of 30 canal preparations. The collected instruments were measured by a digital caliper to determine whether any fractures had occurred and then were visually inspected for deformation and fracture under a stereomicroscope. The surfaces of fractured instruments were further evaluated under a scanning electron microscope. Data were analysed using chi-square test and Kruskal–Wallis test. Results The incidence of instrument defect was 5.63%, consisting of 3.59% fractures and 2.05% deformations. The defect rates of 0.04 and 0.06 files were statistically higher than the other taper groups (P 0.05). For the fractured instruments, 63.95% failed from flexural fatigue, whilst 36.05% failed from torsion. Conclusion Flexural fracture was the major mode of fracture for instruments with larger taper. A routine check for instrument integrity particularly for 0.04 and 0.06 files at high magnification is recommended after each clinical use.

Inclusive education focuses on addressing marginalisation, segregation and exclusion within policy and practice. The purpose of this article is to use critical discourse analysis to examine how inclusion is represented in the education policy and professional documents of two countries, Australia and China. In particular, teacher professional standards from each country are examined to determine how an expectation of inclusive educational practice is promoted to teachers. The strengthening of international partnerships to further support the implementation of inclusive practices within both countries is also justified. Refereed/Peer-reviewed

The role of SOST/sclerostin in mediating tissue fibrogenic response to injury/inflammation remains largely unknown. Thus, we conducted this study to determine whether SOST/sclerostin plays a role in renal interstitial fibrosis (RIF) for the first time.Unilateral ureteral obstruction (UUO) was performed to create obstructive kidney injury model. Twelvemale SOST knockout (SOST KO) mice and 12 age-matched wild-type (WT) mice were divided into three groups: sham surgery, UUO 3 d and UUO 7 d. The mice were sacrificed at each time point and kidney tissues were collected. Histopathological changes were evaluated by hematoxylin and eosin and Masson staining, while α-smooth muscle actin (α-SMA), type I collagen (Col-I) and fibronectin (FN) expression levels were detected by RT-PCR and western-blot.In sham control group, neither WT nor SOST KO exhibited fibrotic change. On 3 days after UUO, total renal histopathological score and fibrotic area were aggravated and α-SMA, Col-I and FN expressions were upregulated, but no difference was observed between WT and SOST KO. On 7 days after UUO, compared with WT, SOST KO mice showed higher total renal histopathological score and fibrotic area percentage, as well as a higher level of fibrogenic marker mRNA/protein expression (except for α-SMA mRNA and FN mRNA).It is supposed that SOST gene is involved in the regulation of RIF progression. In obstructive kidney injury, SOST gene deletion would probably enhance renal fibrogenic response and promote the progression of RIF. But more evidences are needed to further identify the role of SOST/sclerostin in mediating RIF progression.

Attitudes, knowledge, and skills are widely recognised as the three pillars of professional competence of inclusive education teachers. Studies emerging from the Chinese context consider these three pillars important for the practice of Learning in Regular Classroomsan idiosyncratic Chinese form of inclusive education. Our mixed methods study reveals that agency is the fourth pillar of the professional competence for inclusive education teachers in Beijing, China. Results from comparative analysis indicate that the level of teachers' agency is significantly lower than that of their attitudes, knowledge, and skills. We offer some implications for policy and practice in inclusive education. Refereed/Peer-reviewed

Classroom support plays a salient role in successful inclusive education, hence it has been widely debated in the literature. Much extant work has only focused on a particular aspect of classroom support. A comprehensive, systematic discussion of classroom support is sporadic in the literature. Relevant research concerning the Chinese context is even more limited. To address this gap, our study developed and validated a multidimensional classroom support model conducive to teachers' inclusive education practices. Data were drawn from our large-scale survey with inclusive education teachers in Beijing. Further analyses were conducted to compare different dimensions within the classroom support model. Drawing insights from the results, we provide some recommendations for practice and research. Refereed/Peer-reviewed

A series of rare-earth metal bis(alkyl) complexes bearing pyrrolidinyl-functionalized cyclopentadienyl, indenyl and fluorenyl ligands were prepared and characterized. Alkane elimination of Ln(CH2SiMe3)3(THF)2 with 1 equiv. of the corresponding ancillary ligand precursors in THF at room temperature afforded the rare-earth metal bis(alkyl) complexes LLn(CH2SiMe3)2(THF)2 (L = C5Me4SiMe2NC4H8, Ln = Y (1), Lu (2); L = C9H6SiMe2NC4H8, Lu (4)). Intramolecular C–H activation occurred when Sc(CH2SiMe3)3(THF)2 was treated with 1 equiv. of C5Me4HSiMe2NC4H8, leading to the generation of the scandium mono(alkyl) complex (C5Me4SiMe2NC4H7)Sc(CH2SiMe3)(THF) (3). One-pot salt metathesis reaction of LnCl3 with 1 equivalent of fluorenyl lithium C13H8SiMe2NC4H8Li, followed by the addition of 2 equivalents of LiCH2SiMe3 in THF at room temperature, gave the mono-fluorenyl-ligated rare-earth metal bis(alkyl) complexes (C13H8SiMe2NC4H8)Ln(CH2SiMe3)2(THF) (Ln = Y (5), Lu (6)). All these complexes were characterized by elemental analysis and NMR spectroscopy. 3, 5 and 6 were subjected to X-ray single crystal determination. Upon activation with one equivalent of [Ph3C][B(C6F5)4] and excess AliBu3, the rare-earth metal bis(alkyl) complexes 1, 2, 4–6 were active for cis-1,4-selective polymerization of isoprene in toluene at room temperature. The ligand effect on the polymerization activity was observed, with a sterically more bulky ligand providing higher activity (fluorenyl > indenyl > Cp). Moreover, employing 6/[Ph3C][B(C6F5)4]/AliBu3 as the catalyst system, polymerization proceeded in a controllable fashion.

The objectives of this study were to evaluate poloxamer as a slow release carrier for morphine (M) and potential tissue irritation after subcutaneous (SC) poloxamer-morphine (PM) injection in a rat model. Based on the result of a previous in vitro work, 25% poloxamer, with and without morphine, and saline were administered in 14 rats’ flanks. Blood for morphine concentrations was automatically sampled at multiple preprogrammed time points using the CulexTM unit for 48 hours. Skin tissues from the injection sites were harvested and evaluated for histopathological changes. Following M or PM administration, it was determined that the half-life (t½) was significantly longer in the PM (5.5 ±7.2 hr) than M (0.7± 0.8 hr) indicated a slow dissolution of poloxamer with morphine. The tmax was within 15 minutes and Cmax was approximately 3 times higher with M than with PM, reaching 716.8 (±153.7 ng/ml) of plasma morphine concentrations. There was no significant difference in total area under the curve and clearance of M vs PM. Histology inflammatory scores were similar between M, PM, and poloxamer but were significantly higher than saline control. We concluded that 25% poloxamer was capable of increasing the t½ of morphine, without a significant tissue irritation.

Brevilin A is a sesquiterpene lactone isolated from Centipeda minima and possesses inhibitory effects on proliferation of various tumor cells. In this study, Brevilin A inhibitory effect on proliferation and its molecular mechanism of action were investigated both in vivo and in vitro in colon adenocarcinoma CT26 cells. The results indicated that the inhibitory effect of Brevilin A in CT26 proliferation was dose-dependent and this effect was due to apoptosis. Furthermore, Brevilin A increased ROS levels, decreased mitochondrial membrane potential (MMP) and induced apoptosis of CT26 cell in a dose-dependent manner. Apoptosis induced by Brevilin A was higher than that induced by adriamycin under the same dose. Cleaved-caspase-8, cleaved-caspase-9 and cleaved-caspase-3 were up-regulated after Brevilin A treatment, together with an increase of Bax protein expression, while Bcl-2 was reduced. Further investigation revealed that Brevilin A inhibited the phosphorylation of PI3K, AKT and mTOR and promoted the expressions of autophagy-related proteins LC3-II, Beclin1 and Atg5 and consequent formation of autophagosomes, whereas 3-methyladenine (3-MA), a type III PI3K inhibitor, inhibited autophagosomes formation induced by Brevilin A. In vivo investigation suggested that Brevilin A significantly inhibited the growth of CT26 tumor compared to adriamycin and concurrently promoted the expressions of LC3-II and cleaved-caspase-3 in tumor tissues. Our results demonstrated that the anti-tumor activity of Brevilin A was mainly achieved by the induction of cell apoptosis and autophagy, suggesting a promising potential as antitumor drug against colon adenocarcinoma.

Previous study revealed that Se-GP11 could exhibited its antitumor activity by improving the immune functions. 5-Fu, as a chemotherapeutic drugs, can kill many immune cells in addition to tumor cells. Accordingly, the enhanced antitumor and reduced toxicity of Se-GP11 on 5-Fu were estimated in this study. The results demonstrated that Se-GP11 could evidently increase the antitumor activity of 5-Fu. Furthermore, Se-GP11 could enhance the immune functions during the tumor inhibition process of 5-Fu for increasing the cytokines secretion (IL-2 and TNF-α) and immune organs weights. In addition, Se-GP11 could reduce the toxicity of 5-Fu on liver by improving the hematological and biochemical parameters and up-regulating the SOD activities and down-regulating the MDA levels. Taken together, the results indicated that Se-GP11 may develop as an auxiliary preparation to chemical antitumor drugs.

Catechol 1,2-dioxygenase is the key enzyme that catalyzes the cleavage of the aromatic ring of catechol. We explored the genetic diversity of catechol 1,2-dioxygenase in the fecal microbial metagenome by PCR with degenerate primers. A total of 35 gene fragments of C12O were retrieved from microbial DNA in the feces of pygmy loris. Based on phylogenetic analysis, most sequences were closely related to C12O sequences from Acinetobacter. A full-length C12O gene was directly cloned, heterologously expressed in Escherichia coli, and biochemically characterized. Purified catPL12 had optimum pH and temperature pH 8.0 and 25 °C and retained 31 and 50% of its maximum activity when assayed at 0 and 35 °C, respectively. The enzyme was stable at 25 and 37 °C, retaining 100% activity after pre-incubation for 1 h. The kinetic parameters of catPL12 were determined. The enzyme had apparent Km of 67 µM, Vmax of 7.3 U/mg, and kcat of 4.2 s-1 for catechol, and the cleavage activities for 3-methylcatechol, 4-methylcatechol, and 4-chlorocatechol were much less than for catechol, and no activity with hydroquinone or protocatechuate was detected. This study is the first to report the molecular and biochemical characterizations of a cold-adapted catechol 1,2-dioxygenase from a fecal microbial metagenome.