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The Legionella pneumophila type II secretion system can promote bacterial growth under a wide variety of conditions and mediates the secretion of more than 25 proteins, including the uncharacterized effector Lpg2622. Here, we determined the crystal structures of apo‐Lpg2622 and Lpg2622 in complex with the cysteine protease inhibitor E64. Structural analysis suggests that Lpg2622 belongs to the C1 family peptidases. Interestingly, unlike the other structurally resolved papain‐like cysteine proteases, the propeptide of Lpg2622 forms a novel super‐secondary structural fold (hairpin‐turn‐helix) and can be categorized into a new group. In addition, the N‐terminal β‐sheet of the Lpg2622 propeptide plays a regulatory role on enzymatic activity. This study enhances our understanding of the classification and regulatory mechanisms of the C1 family peptidases. [ABSTRACT FROM AUTHOR]

Air pollution and climate change are issues of worldwide concern. Synergizing air pollution control and climate mitigation have been an important national policy of China. This study develops bivariate and integrated synergy indexes (BSI and ISI) to investigate the synergy states between air pollution and CO 2 emission. The synergy indexes are based on the correlation coefficient and established from exploiting the internal comparability of the data. Using the BSI and ISI , we evaluated the correlation and synergy states between air pollution (involving ambient PM 2.5 and ozone) and CO 2 emission in Chinese cities from 2015 to 2020. The results present the city-level trends and heterogeneities of synergy between air pollution and CO 2 emission. The averaged value of BSI PM2.5-ozone , BSI PM2.5-CO2 , and BSI ozone-CO2 for all cities and assessing years were −0.239, −0.291, and −0.242, indicating a generally and globally weak synergy. The synergy states between air pollution and CO 2 emission were relatively significant and complex in specific regions. Combined with the local spatial association and decoupling analysis, we further identified the primary variables and key areas for synergistic control. This study provides a systematic idea and case demonstration for city-level synergy assessment through transforming and expanding the data usage capacity. The method and process are applicable to various scales and regions, which would be of reference value for synergy assessments in other countries and regions. [Display omitted] • We developed the bivariate and integrated synergy indexes. • We evaluated the synergy between air pollution and CO 2 emission at the city-level. • Local spatial association and decoupling analysis supported the synergy assessment. • Most Chinese cities show insignificant synergy of air pollution and CO 2. • BTHS, YRD, and the JJAH are key areas. [ABSTRACT FROM AUTHOR]

Life cycle assessment methodology was used to quantify the environmental impacts and resource use of milk production on the North China Plain, the largest milk production area in China. Variation in environmental burden caused by cow productivity was evaluated, as well as scenario analysis of the effects of improvement practices. The results indicated that the average environmental impact potential and resource use for producing 1 kg of fat and protein corrected milk was 1.34 kg CO 2 eq., 9.27 g PO 4 3 − eq., 19.5 g SO 2 eq., 4.91 MJ, 1.83 m 2 and 266 L for global warming potential (GWP), eutrophication potential (EP), acidification potential (AP), non-renewable energy use (NREU), land use (LU) and blue water use (BWU; i.e. water withdrawal), respectively. Feed production was a significant determinant of GWP, NREU, LU and BWU, while AP and EP were mainly affected by manure management. Scenario analysis showed that reducing use of concentrates and substituting with alfalfa hay decreased GWP, EP, AP, NREU and LU (by 1.0%–5.5%), but caused a significant increase of BWU (by 17.2%). Using imported soybean instead of locally-grown soybean decreased LU by 2.6%, but significantly increased GWP and NREU by 20% and 6.9%, respectively. There was no single perfect manure management system, with variable effects from different management practices. The environmental burden shifting observed in this study illustrates the importance of assessing a wide range of impact categories instead of single or limited indicators for formulating environmental policies, and the necessity of combining multiple measures to decrease the environmental burden. For the North China Plain, improving milking cow productivity and herd structure (i.e. increased proportion of milking cows), combining various manure management systems, and encouraging dairy farmers to return manure to nearby crop lands are promising measures to decrease multiple environmental impacts. [ABSTRACT FROM AUTHOR]

NiCoCrAlY coatings with and without Ta were plasma-sprayed onto Ti44Al6Nb1Cr alloy to investigate their microstructure and oxidation resistance at 900 °C for 100 h. The results indicated that the oxidation resistance of the NiCoCrAlY coating was better than that of the NiCoCrAlYTa coating. The formation of Al 2 O 3 scale on the NiCoCrAlYTa coating was inhibited due to the low Al concentration and the dragging effect of Ta. Furthermore, loose NiO/CoO scale on the NiCoCrAlYTa coating promoted the inward diffusion of oxygen. As a result, an Al 2 O 3 layer was formed at the interface, suppressing interdiffusion between coating and substrate. [ABSTRACT FROM AUTHOR]

In recent years, stem cell research has continued to benefit from its crossover with chemistry, particularly the investigation of small molecular drugs modulating specific targets to regulate stem cell fate. Idebenone (IDB) is a yellow crystalline powder that is used in the treatment of chronic cerebrovascular diseases. The objective of the present study was to examine whether IDB had an influence on bone marrow‑derived mesenchymal stem cells (BMSCs) extracted from the bone marrow of Sprague‑Dawley rats. The effects of IDB on cell proliferation, cell cloning and migration were investigated. Cell cycle, apoptosis, DAPI nuclear staining and senescence‑associated β‑galactosidase (SA‑β‑gal) staining were also examined. The results revealed that IDB at suitable concentrations enhanced cell cloning capacity, promoted the proliferation of BMSCs, delayed cellular senescence, and inhibited cell apoptosis and migration. Western blot analysis indicated that IDB increased the expression of B‑cell lymphoma 2 (Bcl‑2), signal transducer and activator of transcription‑3, Nanog, octamer‑binding transcription factor 4, E‑cadherin, proliferating cell nuclear antigen, cyclinD1 and cyclinD3, and decreased the expression of Bcl‑2‑associated X protein, cleaved caspase‑3, N‑cadherin, vimentin and α‑smooth muscle actin. In conclusion, these experiments confirmed that IDB in low doses had no toxic effect and may exert protective effects on BMSCs. [ABSTRACT FROM AUTHOR]

Osteopenia, osteoporosis and bone salt metabolism disorder are common diseases in the aged and diabetics. From case reports of patients with T2DM, we have observed that metformin can decrease risk of bone fracture and promote bone formation. However, the underlying mechanism of metformin’s effect on bone metabolism remains unknown. In our research, we show that metformin can promote proliferation of murine preosteoblast by regulating AMPK-mTORC2 and AKT-mTORC1 signaling axis. Furthermore, we have observed that metformin can promote SIRT6 expression before and during differentiation of murine preosteoblast. The interaction between SIRT6 and NF-κB is highly important in osteoblast differentiation just as the relationship between OPG and RANKL in the process of bone formation. During differentiation, we show that SIRT6 inhibits phosphorylation of NF-κB and that OPG increases while RANKL decrease in HG groups. In addition, ablation of sirt6 in mice causes phosphorylation of NF-κB at high-levels and RANKL increases slightly in femur bone cells. However, other bone formation marker proteins such as RUNX2, OSTERIX and OPG appear at low-levels in sirt6 KO mice. It has been confirmed that downregulation of OCT4 is critical incident in the differentiation of embryonic stem cells. Fortunately, we observe that SIRT6 can suppress OCT4 expression in murine preosteoblast and the expression of OCT4 is at high-level in sirt6 KO mice. Taken together, this study’s results illuminate metformin’s effect on bone metabolism under HG condition and help to elucidate why metformin can promote bone fracture healing of patients with T2DM. [ABSTRACT FROM AUTHOR]

Mucin 1 (MUC1), being an oncogene, is an attractive target in tumor immunotherapy. Maltose binding protein (MBP) is a potent built-in adjuvant to enhance protein immunogenicity. Thus, a recombinant MUC1 and MBP antitumor vaccine (M-M) was constructed in our laboratory. To enhance the antitumor immune activity of M-M, CpG oligodeoxynucleotides 1826 (CpG 1826), a toll-like receptor-9 agonist, was examined in this study as an adjuvant. The combination of M-M and CpG 1826 significantly inhibited MUC1-expressing B16 cell growth and prolonged the survival of tumor-bearing mice. It induced MUC1-specific antibodies and Th1 immune responses, as well as the Cytotoxic T Lymphocytes (CTL) cytotoxicity in vivo. Further studies showed that it promoted the maturation and activation of the dendritic cell (DC) and skewed towards Th1 phenotype in vitro. Thus, our study revealed that CpG 1826 is an efficient adjuvant, laying a foundation for further M-M clinical research. [ABSTRACT FROM AUTHOR]

Our previous study demonstrated that maltose-binding protein (MBP) activated Th1 through the TLR2-mediated MyD88-dependent pathway and the TLR4-mediated TRIF-dependent pathway. The combination of MBP and BCG synergistically induced Th1 activation, and the TLR2/9-mediated MyD88-dependent pathway is involved in this process. To further explore this mechanism, we stimulated purified mouse CD4 + T cells with MBP and BCG in vitro . The results demonstrated that MBP combined with BCG synergistically increased IFN-γ production and TLR2/4/9 expression, suggesting the involvement of TLR2/4/9 in the combination-induced Th1 activation. Next, TLRs 2/4/9 were blocked to analyze the effects of TLRs on Th1 activation. The results demonstrated that MBP induced a low level of Th1 activation by upregulating TLR2-mediated MyD88-TRAF6 and TLR4-mediated TRIF-TRAF3 expression, whereas MBP combined with BCG induced synergistic Th1 activation, which was not only triggered by strong upregulation of TLR2/9-mediated MyD88-TRAF6 expression but also by shifting TLR4-mediated TRIF-TRAF3 into the TRIF-TRAF6 pathway. Moreover, we observed that a TLR4 antibody upregulated MyD88 expression and a TLR9 inhibitor downregulated TRIF expression, indicating that there was cross-talk between TLRs 2/4/9 in MBP combined with BCG-induced Th1 activation. Our findings may expand the knowledge regarding TLR cross-talk involved in regulating the Th1 response. [ABSTRACT FROM AUTHOR]

A visible-light-induced synthesis of 2,5-disubstituted 1,3,4-oxadiazoles from simple diketones and hydrazides with the assistant of the photocatalyst eosin Y catalyzed decarboxylation and cyclization under mild conditions has been discovered. The reaction tolerates a wide range of functional groups and gives a variety of valuable 1,3,4-oxadiazoles in moderate to good yields. Finally, a plausible reaction mechanism was proposed. [ABSTRACT FROM AUTHOR]

Al and Al/NiCrAlY coatings were deposited on pure titanium substrate by air plasma spraying method. Cyclic oxidation behavior and oxide scale adhesion at 800 °C for 100 cycles were investigated. For the single Al coating, a severe spalling of oxide scale and elemental interdiffusion occurred after 100 cycles. The mass loss of the single Al coating has reached to 1.39 mg/cm 2 . The oxide scale on the duplex Al/NiCrAlY coating kept a good bonding with the underlay coating. The addition of NiCrAlY layer inhibited the outward diffusion of Ti atoms and inward diffusion of Al atoms. The propagation of cracks and the formation of pores were also suppressed by NiCrAlY layer. As a result, the duplex Al/NiCrAlY coating possessed a superior cyclic oxidation resistance. [ABSTRACT FROM AUTHOR]

Excitation-emission matrix fluorescence spectroscopy combined with parallel factor analysis (EEM-PARAFAC) and two-dimensional correlation spectroscopy (2D-COS) were applied to evaluate the effects of anthropogenic impoundment on the characteristics of dissolved organic matter (DOM) and its heavy metal binding affinity. Three field-sampling cruises conducted in Hongze Lake from 2015 to 2016 were classified as early impoundment and late impoundment cruises according to the hydrological conditions. Five fluorescence components were derived from EEM-PARAFAC, including three humic-like components (C1 C3) and two protein-like components (C4 and C5). The results show a higher dissolved organic carbon concentration, humification degree, molecular size, and level of terrestrial humic-like substances (C1 C3) for early impoundment DOM compared with late impoundment DOM, which were derived from the relatively high inflow discharges present before impoundment. Meanwhile, the relatively high autochthonous contribution and level of protein-like substances found in late impoundment DOM suggested that anthropogenic impoundment can influence the DOM composition in Hongze Lake. Increases in the binding affinities (log K m ) of humic-like substances (C1 and C3) and decreases in the log K m of tryptophan-like substances (C4) were observed during the impoundment period. Additionally, 2D-COS results suggested that the preferential Cu(II) binding ligands in early and late impoundment DOM were tryptophan- (C4) and humic-like (C1) substances, respectively. These results indicated that impoundment-derived DOM composition alteration can decrease the bioavailability and toxicity of Cu in Hongze Lake. The results reported here will improve the understanding of DOM and heavy metal cycling in impoundment lakes. [ABSTRACT FROM AUTHOR]

As a high-hardness and anti-frictional material, titanium carbonitride (TiCN) thick coatings or thin films are increasingly being used in many industrial fields. In the present study, TiCN coatings were obtained by atmospheric plasma spray synthesis or reactive plasma spray. In order to promote the reaction between the Ti particles and reactive gases, a home-made gas tunnel was mounted on a conventional plasma gun to perform the spray process. The oxidation behavior of the TiCN coatings under different temperatures in static air was carefully investigated. As a result, when the temperature was over 700 °C, the coatings suffered from serious oxidation, and finally they were entirely oxidized to the TiO phase at 1100 °C. The principal oxidation mechanism was clarified, indicating that the oxygen can permeate into the defects and react with TiCN at high temperatures. In addition, concerning the use of a TiCN coating in high-temperature conditions, the microhardness of the oxidized coatings at different treatment temperatures was also evaluated. [ABSTRACT FROM AUTHOR]

With the deeply cognition of the micro domain, in biomedical, analytical chemistry, and integrated circuits manufacturing etc., there is an urgent need to develop some object which is micro-sized or able to be micro-operated. However, conventional micromanipulation systems are limited by space, accuracy and safety. In this work, a facile fabrication method is demonstrated to create three-dimensional (3D) electrostatic microstructures for microrobotics applications. The microstructures are developed using lamination of SU-8 photosensitive films and deposition of copper (Cu), which has potential for large-scale manufacturing. The simulation of the electrostatic microstructures movement was conducted; and the results showed the maximum deformation occurred in the waist; strain and stress concentrated at bottom edge of the microrobot. The microstructures were actuated moving on an electric substrate by varying the voltage. It was found that the microstructure step size is proportional to the square of voltage. When 1000 V, 50 Hz electric field was applied, the step size was 0.1 µm and average speed could achieve 300 µm/min, which shows great potential in microfluidics and microrobotics applications. [ABSTRACT FROM AUTHOR]

Crystalline tantalum-containing oxides are usually taken as the advanced photocatalysts for water splitting. How about the amorphous counterparts? In this work, a transformation of crystalline Na 2 Ta 2 O 6 (C Na 2 Ta 2 O 6 ) to amorphous TaO x (Am-TaO x ) was achieved by a facial hydrothermal method. We proposed a transformation mechanism based on nucleation-dissolution -recrystallization and further intensified the influence of base concentration on the composition, crystallinity, and morphology (CCM) as confirmed by XRD, TEM, EDS. N 2 -physisorption, Raman, IR, and XPS analysis. It is found that when comparing to the crystalline counterparts, amorphous samples possessed higher surface area, abundant surface hydration layers and H + adsorption, showing an unassisted photocatalytic water splitting with a rate of 70 ± 7 μmol g −1 h −1 , much larger than that of 15 ± 1 μmol g −1 h −1 of C Na 2 Ta 2 O 6 , 11 ± 1 μmol g −1 h −1 of crystalline Ta 2 O 5 (C Ta 2 O 5 ), 30±2 μmol g −1 h −1 of mixture with crystalline Ta 2 O 5 and amorphous Na x Ta y O z (C Ta 2 O 5 /Am-Na x Ta y O z ), and even 4.6 × 10 −4 μmol g −1 h −1 for commercial TiO 2 . This observation is beneficial from the short diffusion paths of amorphous state for charge carriers, amount of catalytic sites, and stronger reducing ability. These findings develop a novel and efficient pathway towards synthesizing the different CCM of tantalum-containing compounds under hydrothermal conditions and could open opportunities for further investigating the photocatalytic property of tantalum-containing materials. [ABSTRACT FROM AUTHOR]

Background: Snake-like robot is an emerging form of serial-link manipulator with the morphologic design of biological snakes. The redundant robot can be used to assist medical experts in accessing internal organs with minimal or no invasion. Several snake-like robotic designs have been proposed for minimal invasive surgery, however, the few that were developed are yet to be fully explored for clinical procedures. This is due to lack of capability for full-fledged spatial navigation. In rare cases where such snake-like designs are spatially flexible, there exists no inverse kinematics (IK) solution with both precise control and fast response.Methods: In this study, we proposed a non-iterative geometric method for solving IK of lead-module of a snake-like robot designed for therapy or ablation of abdominal tumors. The proposed method is aimed at providing accurate and fast IK solution for given target points in the robot's workspace. n-1 virtual points (VPs) were geometrically computed and set as coordinates of intermediary joints in an n-link module. Suitable joint angles that can place the end-effector at given target points were then computed by vectorizing coordinates of the VPs, in addition to coordinates of the base point, target point, and tip of the first link in its default pose. The proposed method is applied to solve IK of two-link and redundant four-link modules.Results: Both two-link and four-link modules were simulated with Robotics Toolbox in Matlab 8.3 (R2014a). Implementation result shows that the proposed method can solve IK of the spatially flexible robot with minimal error values. Furthermore, analyses of results from both modules show that the geometric method can reach 99.21 and 88.61% of points in their workspaces, respectively, with an error threshold of 1 mm. The proposed method is non-iterative and has a maximum execution time of 0.009 s.Conclusions: This paper focuses on solving IK problem of a spatially flexible robot which is part of a developmental project for abdominal surgery through minimal invasion or natural orifices. The study showed that the proposed geometric method can resolve IK of the snake-like robot with negligible error offset. Evaluation against well-known methods shows that the proposed method can reach several points in the robot's workspace with high accuracy and shorter computational time, simultaneously. [ABSTRACT FROM AUTHOR]

Background and aims: The rhizosphere priming effect is caused by root carbon (C) exudation into the rhizosphere; the role of this effect in nutrient cycling and ecosystem recovery of natural grasslands as affected by different grazing intensities is still unknown. The objective of the present study was to investigate the relationships among root C exudation, rhizospheric microbial activity, and their influences on plant nutrient uptake during grazing and recovery periods . Methods: Field experiments were conducted in the Hongyuan Alpine Meadow to measure root exudation rate and nutrient cycling processes of the dominant species Elymus nutans. Three grazing intensities (an ungrazed control, moderate grazing and heavy grazing) were introduced for two months, following which all treatments received a recovery practice (no grazing for 21 days). Results: Heavy grazing significantly decreased root exudation rate, soil nitrogen (N) mineralization rate, β-1,4-glucosidase (BG) activity, and foliar C concentration, while moderate grazing had no influence on these parameters compared to the control. After the 21 days of recovery, all these parameters, except N mineralization rate and foliar C concentrations in the heavy grazing treatment, returned to similar levels as in the control, whereas root exudation rate and BG activity rose to even higher levels. Meanwhile, moderate grazing significantly promoted root exudation rate, soil inorganic N concentration, net soil N mineralization rate, and β- N-acetylglucosaminidase (NAG) activity during the recovery stage as compared to the control. Foliar quality was also improved by the recovery practice, indicating that the high availability of N and P is a consequence of the positive root-microbe feedback and will ultimately benefit grazers. Conclusions: The flush of labile C released to the rhizosphere by grazed plants stimulated extracellular enzyme activities, enhanced soil N mineralization, and increased plant nutrient uptake. These results imply that reasonable (i.e. moderate) grazing followed by a recovery practice can effectively restore and strengthen grassland vegetation, and contribute to the sustainable use of alpine meadows such as Hongyuan. [ABSTRACT FROM AUTHOR]

Background: To compare radiologic results of posterior release, internal distraction, and final pedicle subtraction osteotomy (PSO) and spinal fusionwith one-stage posterior vertebral column resection (PVCR) in treating multi-level severe congenital scoliosis.Methods: Forty-onesevere congenital scoliosis patients were used in the study. Group A comprised 24 patients who underwent one-stage PVCR. Group B comprised 17 patients who underwent posterior release with internal distraction, followed by final posterior fusion and instrumentation. The average preoperative main curve was 110.4° (95-130°) in group A and 109.4° (range 90°-126°) in group B. Postoperative follow-up time was ≥2 years (2.0-4.5 years) to analyze the radiographic and clinical outcomes.Results: A comparison of posterior release, internal distraction, and final spinal fusion with PVCR showed no significant differences in postoperative main curve and compensatory caudal curve correction, coronal and sagittal imbalance. However, significant differences were found between the 2 groups in compensatory cranial curve correction.Conclusions: Posterior release, internal distraction, and final spinal fusion produce better corrective results in compensatory cranial curve correction than PVCR in treating severe multi-level congenital scoliosis. [ABSTRACT FROM AUTHOR]

This study aimed to determine the optimal protein to energy ratio (P/E ratio) and evaluate the effect of dietary protein and lipid levels on growth performance, body composition and digestive enzymes activities in Chinese mitten-handed crab , Eriocheir sinensis. Nine practical diets containing three levels both for protein ( DP 30%, 35% and 40%) and lipid ( DL 2%, 7% and 12%) with P/E ratios ranging from 13.69 to 19.79 mg KJ−1 were fed to four replicates of crabs (3.39 ± 0.10 g) for 10 weeks. Weight gain increased significantly with the increase in DP level at each DL level. Moreover, weight gain increased in crabs fed with diets containing DL level from 2% to 12% and DP level from 30% to 35%. However, the diet containing 40% DP and 12% DL levels significantly decreased the growth performance and protein efficiency of the crabs. The whole crab and hepatopancreas lipid contents also increased as dietary lipid increased, but not dietary protein. The total protease activity increased significantly with the increase in dietary protein at each lipid level. The lipase activity was statistically comparable among different DL levels at each DP level. Taken together, the crab fed the diet containing 35% protein and 12% lipid levels with P/E 15.77 mg KJ−1 revealed optimal growth, feed utilization efficiency and digestive enzymes activities. Moreover, our study indicated that the higher dietary lipid level at a relatively lower dietary protein level could provide protein sparing effect in Eriocheir sinensis. [ABSTRACT FROM AUTHOR]

Adipocyte deposition is a key feature of age-related thymic involution, but the underlying mechanisms responsible for thymic adiposity remain to be elucidated. In the present study, we utilized rosiglitazone, a potent peroxisome proliferator-activated receptor γ agonist, to induce adipogenic differentiation of OP9-DL1 cells, and detected the metabolomics alterations during adipogenic differentiation by using liquid chromatography-mass spectrometry. The obtained metabolites were further processed by multivariate statistical analysis, including principal component analysis, partial least squares discriminant analysis, and orthogonal projection on latent-structures discriminant analysis. As a result, we identified a total of 33 significantly differential metabolites between dimethyl sulphoxide- and rosiglitazone-treated OP9-DL1 cells, which were closely related to the dysregulation of phospholipid metabolism pathway, oxidative stress, and associated amino acid metabolism. Meanwhile, two pathways including glycerophospholipid metabolism and nitrogen metabolism were significantly perturbed ( P < 0.05). Collectively, our results may provide some heuristic guidance for addressing the underlying mechanism of thymic adipogenesis, and future studies are warranted to unravel the functions of these altered metabolites in thymic adipogenesis. [ABSTRACT FROM AUTHOR]

To explore whether TLR2/TLR4 could be involved in the maturation of dendritic cells and polarization of CD4+ T cells induced by dendritic cells stimulated with MBP and BCG, in vitro and in vivo experiments using TLR2−/− or TLR4−/− mice were employed. MBP and BCG elevated CD80, CD86 and MHC class II expressed on dendritic cells and increased IL-12 protein, induced DC maturation, and indirectly promoted Th1 activation. Moreover, MBP and BCG upregulated costimulatory molecules on DCs in a TLR2- and TLR4-dependent manner. The levels of IFN-γ, IL-4, and IL-10 in CD4+ T cells cocultured with dendritic cells from different types of mice were determined with ELISPOT or ELISA method. TLR2/TLR4 is important in the maturation and activation of dendritic cells and the activation of Th1 cells induced by stimulation with MBP and BCG. In conclusion, TLR2 and TLR4 play an important role in the upregulation of costimulatory molecules and MHC class II molecules on dendritic cells and the activation of Th1 cells induced by stimulation with MBP and BCG. The results above indicate that the combination of MBP and BCG induced the maturation and activation of dendritic cells and promoted Th1 activation via TLR2/TLR4. [ABSTRACT FROM AUTHOR]

Bio-sensing techniques utilizing metallic nanoparticles as a probe have gained more and more attention and play today an important role in the detection of bacteria. To date, although several sensing materials have been tested, there is still a long way to go to achieve a fast, low-cost, ultrasensitive and multifunctional substrate suitable for a universal biosensor for detection of bacterial cells. Here, we report a novel probe design based on anisotropic plasmonic nanoparticles organized to a biocompatible 3D bio-inorganic scaffold, i.e. , nanoplate-bacteria-nanorod supercrystals (NBNS) with extremely high surface-enhanced Raman spectroscopic (SERS) activity as a model of synergistic plasmonic enhancement from nanoparticles and assembly. This unique structure of nanoparticles incorporated into supercrystal assembly allows efficient detection, identification and classification of cells and bacteria. In this design, the NBNS ensures that the target cells take advantage of the superior multifold increase in Raman scattering signals (electromagnetic enhancement from both types of nanoparticles), due to the geometry of the 3D scaffold. The excellent reproducibility and stability of NBNS substrates were confirmed by comparing the SERS activities of different substrates and analytes. Principal component analysis (PCA) applied to the SERS spectra clearly discriminated the homogeneous bacterial samples and their mixtures. Successful detection and identification of bacteria in model samples consisting of two representative bacteria blends in Fanta soft-drink were demonstrated via plasmonic bio-inorganic scaffold combined with PCA analysis. We believe that this work will greatly facilitate the development of ultrasensitive SERS probes for highly advanced biosensor, pioneering the use of SERS for controlling food safety. [ABSTRACT FROM AUTHOR]

As a result of global climate change, frequent and intensive extreme climate events are observed and predicted. These extreme climate events can change ecosystem functions through driving plant growth and mortality, as well as ecological and evolutionary processes into different directions. We simulated a 1-in-100-year extreme precipitation event in different plant growth seasons (i.e. spring, summer, or autumn) to investigate the functional responses of a mesophytic alpine grassland ecosystem to climate change in the Tibetan plateau. The results demonstrated that the seasonal distribution of extreme precipitation is a critical factor in determining soil microbial- and plant-productivity. The response of vegetation net primary productivity (NPP) to extreme precipitation depends on the growth seasons and plant types. Total NPP in the treatments experienced extreme precipitation in the early (spring), mid- (summer) and late- (autumn) plant growth seasons were significant lower, higher, and no difference, respectively, compared with the control. Soil temperature and moisture were the key abiotic factors that affected ecosystem functions. For example, in the early plant growth season, no changes of soil moisture and the decreased temperature in response to the extreme precipitation resulted in a substantial decline in NPP. By contrast, in the mid-plant growth season, higher temperature and soil moisture elicited positive synergistic effects on plant growth and soil microbial processes. The increased sensitivity of above-ground NPP and the shift of dominant species from sedges to less palatable forbs might inevitably exaggerate the degradation of this grassland. Nevertheless, a high resilience index in the related ecological processes could potentially contribute to the grassland acclimation and stability, as most parameters returned to the similar levels as in the control after the extreme events ceased. Therefore, several synergistic or antagonistic mechanisms are hypothesized to operate in parallel or at different levels of organization and timescales. Further studies involving a range of different potential scenarios and longer periods are needed to predict the future climate change impacts on mesophytic grassland. [ABSTRACT FROM AUTHOR]

Our previous study demonstrated that maltose-binding protein (MBP) combined with BCG induced synergistic mouse Th1 activation in viv o. Here, to explore the mechanism of MBP combined with BCG on Th1 activation, mouse purified CD4 + T cells were stimulated with MBP and BCG in vitro . The results showed that MBP combined with BCG synergistically increased IFN-γ production, accompanied with the upregulation of TLR2/9 expressions, suggesting that TLR2/9 were involved in the combination-induced Th1 activation. Next, TLR2 antibodies and TLR9 inhibitor were used to further analyze the effects of TLRs in Th1 activation. Results showed TLR2 antibody partly decreased MBP combined with BCG-induced IFN-γ production, MyD88 expression and IκB phosphorylation, indicating that TLR2-mediated MyD88-dependent pathway was involved in the MBP combined with BCG-induced Th1 activation. Moreover, MBP combined with BCG-induced Th1 activation was completely abrogated by TLR9 inhibitor, suggesting that TLR9-mediated MyD88-dependent pathway played a more important role than TLR2 in the combination-induced Th1 activation. Further study showed that TLR9 inhibitor downregulated TLR2 expression, suggesting that TLR9 signaling regulated TLR2 activation to favor Th1 resonse induced by MBP combined with BCG. Collectively, we demonstrated for the first time that the cross-talk of TLR2 and TLR9 triggered Th1 activation collaboratively and our findings provided valuable information about designing more effective adjuvant for cancer therapy. [ABSTRACT FROM AUTHOR]

YVO 4 nano/microcrystals with multiform morphologies were successfully synthesized via a facile hydrothermal method using NH 4 VO 3 as vanadium source. The samples were characterized by XRD, FT-IR, SEM, EDX and photoluminescence (PL) spectroscopies. The experimental results indicate that the shape and size of as-prepared architectures can be rationally modified by controlling the reaction conditions, such as reaction time, different organic additives and the pH value of solution. Multiform morphologies YVO 4 :Eu 3+ sample have been obtained with the sodium citrate reagent (Cit 3− ), macrogol (PEG), polyvinylpyrrolidone (PVP) and cetyl trimethyl ammonium bromide (CTAB) were employed as surfactant. When Cit 3− added to solution, YVO 4 :Eu 3+ has the highest PL intensity. In addition, the luminescent properties of the YVO 4 :Ln 3+ (Ln = Eu, Dy and Sm) have been systematically investigate. Upon ultraviolet excitation, the obtained YVO 4 :Ln 3+ exhibit red, light blue, orange red, emission, respectively. [ABSTRACT FROM AUTHOR]

Ischemic stroke can activate multiple transcription factors and cause inflammatory reactions, which involve pattern recognition receptors with immunostimulatory effects. Toll-like receptor 4 (TLR4) is one of the receptors related to innate immunity and several inflammatory reactions. The promising anti- inflammatory activity of salvianolic acid B (SAB) had been previously reported, but its effect on ischemic stroke remains unknown. An oxygen-glucose deprivation and reoxygenation (OGD/R) model in vitro and a middle cerebral artery occlusion (MCAO) model in vivo were used in this paper, and the results showned that SAB remarkably increased the viabilities of PC12 cells and primary cortical neurons after OGD/R injury and notably prevented cerebral ischemia/reperfusion (I/R) injury. SAB also significantly ameliorated NeuN release from primary cortical neurons. Further research indicated that the neuroprotection of SAB was completed through inhibiting the TLR4/MyD88/TRAF6 signaling pathway. The blocking of TLR4 by SAB also restrained NF-kB transcriptional activity and pro-inflammatory cytokine responses (IL-1β, IL-6, and TNF-α). These findings supply a new insight that will aid in clarifying the effect of SAB against cerebral I/R injury and provide the development of SAB as a potential candidate for treating ischemic stroke. [ABSTRACT FROM AUTHOR]

Mg-7.8Gd-2.7Y-2.0Ag-0.4Zr (wt.%) alloy was prepared by traditional metal mold gravity casting, and then was solutionized and aged. The solution and aging processing were optimized, the microstructure evolution during solution and aging of the alloys was investigated, the isothermal aging hardening process was studied, and the room temperature tensile properties and strengthening mechanism of the alloys were studied. The results show that alloys exhibit obvious double peak aging characteristics during the isothermal aging process due to the precipitation process difference of β′ and γ″, and a higher aging temperature is beneficial to shorten the time to peak hardness. The optimal solution and aging parameters were 510 °C for 6 h and 200 °C for 32 h, respectively. The lattice distortion of α-Mg caused by Ag is much greater than that of Gd and Y, so the strengthening effect of Ag is the most significant. The yield strength, ultimate tensile strength, and elongation of the alloy after the optimized solution and aging process reach 273.1 MPa, 410.7 MPa, and 4.85%, respectively. The contribution of precipitation strengthening to the yield strength of alloy after aging at 200 °C and 225 °C is about 51%. • A super high strength Mg-7.8Gd-2.7Y-2.0Ag-0.4Zr alloy prepared by traditional metal mold casting was developed. • The difference of precipitation process of precipitates during aging leads to double peak aging characteristics. • Ag element has higher solid solution strengthening effect from the perspective of lattice distortion. [ABSTRACT FROM AUTHOR]

Dy 3+ and Eu 3+ codoped KSr 4 (BO 3 ) 3 phosphors were successfully synthesized by solid-state reaction process. Under near-ultraviolet (near-UV) excitation, individual Dy 3+ or Eu 3+ ion activated sample exhibits characteristic emissions in their respective regions. In KSr 4 (BO 3 ) 3 :Dy 3+ , x Eu 3+ phosphors, the energy transfer from Dy 3+ to Eu 3+ was revealed to be resonant type by dipole–dipole mechanism. And the critical distance R Dy–Eu was calculated to be 13.95 Å. The energy transfer efficiency of KSr 4 (BO 3 ) 3 :Dy 3+ , x Eu 3+ reached about 20% when the concentration of Eu 3+ was 0.035. Moreover, the emitting colors of Dy 3+ and Eu 3+ codoped samples can be adjusted from the edge of white area to warm white via tuning the activator (Eu 3+ ) doped concentration. More significantly, the chromaticity coordinates (0.334, 0.351) of KSr 4 (BO 3 ) 3 :0.005Dy 3+ , 0.015Eu 3+ sample are extremely adjacent to standard white light (0.33, 0.33). The quantum efficiency of the KSr 4 (BO 3 ) 3 :0.005Dy 3+ , 0.015Eu 3+ phosphor with 389 nm excitation is found to be 42%, demonstrating that the obtained single-component white-emitting phosphor exhibits potential applications for solid state lighting. [ABSTRACT FROM AUTHOR]

Mucin 1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas and is an attractive target in tumor immunotherapy. Our previous study showed that the MUC1–MBP/BCG anti-tumor vaccine induced a MUC1-specific Th1-dominant immune response, simulated MUC1-specific cytotoxic T lymphocyte killing activity, and could significantly inhibit MUC1-expression B16 cells' growth in mice. To help move the vaccine into a Phase I clinical trial, in the current study, a pre-clinical toxicity and immunogenicity evaluation of the vaccine was conducted. The evaluation was comprised of a single-dose acute toxicity study in mice, repeat-dose chronic toxicity and immunogenicity studies in rats, and pilot toxicity and immunogenicity studies in cynomolgus monkeys. The results showed that treatment with the MUC1–MBP/BCG anti-tumor vaccine did not cause any organ toxicity, except for arthritis or local nodules induced by BCG in several rats. Furthermore, the vaccine significantly increased the levels of IFN-γ in rats, indicating that Th1 cells were activated. In addition, the results showed that the MUC1–MBP/BCG anti-tumor vaccine induced a MUC1-specific IgG antibody response both in rats and cynomolgus monkeys. Collectively, these data are beneficial to move the MUC1–MBP/BCG anti-tumor vaccine into a Phase I clinical trial. [ABSTRACT FROM AUTHOR]

In this paper, GdOF crystals with high uniformity, monodispersity and a variety of well-defined morphologies, such as spheres, nanorods, and nanorod bundles have been successfully synthesized via the urea based homogeneous precipitation method followed by a heat treatment. The influence of pH values, fluoride sources and reaction time on the sizes and morphologies was systematically investigated and discussed. The possible formation mechanism for the precursor has been presented. Under ultraviolet excitation, the GdOF:Ln3+ (Ln = Eu, Tb) submicron spheres show their characteristic f–f emissions and give red, and green emissions, respectively. Moreover, for Tb3+/Eu3+ co-doped GdOF phosphors, tunable emissions have been obtained and the color tones can be tuned from green, through yellow, and then to red by simply adjusting the doping Eu3+ concentrations. This merit of multicolor emissions in the visible region makes these materials hold great promise for applications in field-emission displays. [ABSTRACT FROM AUTHOR]

In this paper, well defined LaOF crystals with multiform morphologies were first prepared via the urea-based precipitation method followed by a heat treatment. The morphologies of the LaOF samples, including nanospheres and nanorods, can be easily modulated by changing the fluorine sources. XRD, FT-IR, SEM, TEM, and emission spectra were used to characterize the prepared samples. Under ultraviolet excitation, the LaOF:Ln 3+ nanospheres display the characteristic f–f transitions of Ln 3+ (Ln = Eu, Tb) ions and give bright red, and green emissions, respectively. Furthermore, by codoping the Tb 3+ and Eu 3+ ions into LaOF host and varying the doping concentration of the Eu 3+ ions, multicolor tunable emissions have been obtained under the irradiation of 379 nm. These results show this material may have potential applications in field-emission displays. [ABSTRACT FROM AUTHOR]

With K + as charge compensator, a series of KSr 4 (BO 3 ) 3 :Dy 3+ , Tb 3+ phosphors were successfully synthesized by solid–state reaction process. Under near-ultraviolet excitation (389 nm), the green emission of Tb 3+ is observed in Dy 3+ /Tb 3+ codoped samples due to the efficient energy transfer from Dy 3+ to Tb 3+ . The energy transfer efficiency, average donor-acceptor distance, as well as transfer mechanism were also studied. The energy transfer efficiency of KSr 4 (BO 3 ) 3 :Dy 3+ , xTb 3+ increased gradually and reached about 60% when the concentration of Tb 3+ was 0.030. And the critical distance R Dy-Tb was calculated to be 15.36 Å. Moreover, the energy transfer mechanism from Dy 3+ to Tb 3+ in KSr 4 (BO 3 ) 3 host was demonstrated to be dipole–dipole interaction. In addition, the emitting colors of Dy 3+ /Tb 3+ codoped samples can be adjusted from the edge of white area to green via tuning the Tb 3+ doped concentration. [ABSTRACT FROM AUTHOR]

Long-range ordered three-dimensional (3D) nanoassembly of bimetallic nanorods has been fabricated on coffee ring formed on the silicon substrate. Two kinds of arrangements, i.e., axial alignment of the nanorods perpendicular and parallel to the substrate, can be observed in the nanoassembly. Moreover, facet blocking of the nanorods can efficiently yield 3D nanoassembly with edge-on substrate. The long-range ordered 3D nanoassembly with edge-on substrate can provide highly reproducible and significant Raman-enhanced signal in contrast with random aggregated substrate. The representative vibrational band of Escherichia coli bacteria could be efficiently amplified by aid of the substrate due to strong field enhancement effects arising from the superstructure. Furthermore, vancomycin-coated nanoassembly with edge-on substrate as a robust nanosensor can efficiently capture E. coli bacteria and improve stability of the nanosensor for assay of E. coli bacteria. [ABSTRACT FROM AUTHOR]

Sphere-like and cauliflower-like hexagonal-vaterite LuBO 3 have been successfully synthesized for the first time via a chemical conversion route using Lu(OH)CO 3 colloid spheres as sacrificial precursor and H 3 BO 3 as boron source without any additional surfactant. FTIR analysis provides an additional evidence of the formation of vaterite-type LuBO 3 in this method. It was found that, an appropriate amount ethanol in the hydrothermal process has a great effect on the products' morphology and crystallinity. Time-dependent experiments indicate that the formation of LuBO 3 crystals went through a two-stage growth process, which involves a fast nucleation of primary particles followed by a slow aggregation and crystallization of primary particles. An investigation on the photoluminescence (PL) properties of LuBO 3 :Eu 3+ phosphors with different morphologies indicates that their PL intensity are dependent on their crystallinity. The effect of Eu 3+ and Tb 3+ doping concentration on PL intensity were also investigated and the quenching concentration of LuBO 3 :Eu 3+ and LuBO 3 :Tb 3+ is 0.25 and 0.20, respectively. Moreover, for Eu 3+ /Tb 3+ doped LuBO 3 phosphors, the color tones can be tuned from green, through green–yellow and yellow, and then to red by simply adjusting the relative doping concentrations of the Tb 3+ and Eu 3+ ions. [ABSTRACT FROM AUTHOR]

Grain shape and orientation control on Cu 2 O films were achieved on ITO substrates via the electrochemical route by changing the solution pH. The film orientation was delicately tuned in sequence from the [1 0 0] direction to [1 1 0] and [1 1 1] direction with the solution pH rising from 9.0 to 10.5 and 12.3. The surface grains of the Cu 2 O film showed shape evolution associated with the solution pH and the orientation. Measurements on the as-prepared Cu 2 O films demonstrated that the flat band potential and the band gap energy depend on the grain shapes and the orientation. The evolution mechanisms of the grain shape and the orientation as well as their relationship to the semiconductor properties were elucidated based on the crystal structure and the coordination chemistry. [ABSTRACT FROM AUTHOR]

A glycoside hydrolase family protein, designated AmyASS, from the marine fish pathogen Aeromonas salmonicida ssp. salmonicida A449 was expressed in Escherichia coli as inclusion bodies, which was renatured by a simple stepwise dialysis. AmyASS has more than 50% identity with many putative glycosidases. Based on the mode of hydrolytic action and the type of substrates, AmyASS was clearly defined as a saccharifying-type α-amylase, which is the third extracellular α-amylase of A. salmonicida ssp. s almonicida . AmyASS showed a raw starch digesting ability, and the specific activity toward raw rice starch (23.5 ± 1.6 U mg −1 ) was much higher than that toward raw wheat starch and raw mung starch. The catalytic region of AmyASS has 50% identity with the raw starch-degrading α-amylase AmyP, whereas AmyASS does not possess a starch-binding domain (SBD). AmyASS was optimally active at pH 6.0 and 40 °C toward soluble starch and at pH 7.0 and 40 °C toward raw starch. The enzyme exhibited stability under acidic (pH 6.0) conditions, while the activity decreased rapidly under neutral (pH 7.0) conditions. The AmyASS activity was stimulated by Ca 2+ , Co 2+ and Cu 2+ . [ABSTRACT FROM AUTHOR]

The growing demand for wearable electronics boosts researches on flexible fibrous energy storage devices, such as fibrous Zn-MnO 2 battery. One bottleneck for the capacity of fibrous MnO 2 electrode, especially at high discharge rate, is the inefficient interfacial charge transfer between nano particles within mechanical-mixed MnO 2 aggregates. Herein, nano γ-MnO 2 has been in-situ grafted on nano carbon branches via a mild interfacial oxidation reaction using KMnO 4 -doped MnO 2 sol precursor, to form nano composites of MnO 2 @ hierarchical carbon networks. The grafting reaction selectively takes place at defective sites with a mixed bonding state on the surface of the carbon branches, during which a rapid δ-to-γ crystal transformation is largely boosted, instead of traditional slow δ-to-α crystal transformation. An efficient fibrous MnO 2 electrode based on the composites of MnO 2 @ hierarchical carbon networks is successfully applied to fibrous Zn-MnO 2 battery, by giving a 2.5 times of capacitance promotion and a better charging-discharging cycling stability. [Display omitted] • A rapid δ-to-γ crystal transformation of MnO 2 have been boosted at hierarchical carbon interface. • The rapid crystal transformation takes place by using Mn(VII)-doped MnO 2 precursor as a mild oxidant. • Highly capacitive MnO 2 @HCNW materials have been synthesized via the crystal-transformation reaction. • Efficient fibrous Zn-MnO 2 battery was assembled, and gives a 2.5-times capacitance promotion. [ABSTRACT FROM AUTHOR]

Lipid oxidation of tea seed oil (TSO) limits its development in food industry. Microencapsulation is an effective solution, and nano-size may provide more biological activities for hydrophobic core than micron-size. In this study, by applying two novel types of wall materials, namely ethanol extract of propolis (EEP) and phosphatidylcholine (PC), a modified complex coacervation was proposed to construct EEP-PC-TSO (tea seed oil) nano-microcapsules. The influence of the pH of electrostatic adsorption, homogeneous pressure, and core/wall ratio on the physicochemical properties of the TSO nano-microcapsules, the effect of EEP as bioactive wall material on the oxidative stability of TSO, and the nano particle size on the antioxidant activity of EEP-PC-TSO nano-microcapsules were investigated. The results showed that, due to electrostatic adsorption, EEP-PC-TSO nano-microcapsules (445.23 nm–95.30 nm) were successfully prepared via the modified complex coacervation. The characterization results represented that the nano-microcapsules hold well nano-structure, morphology and interface characteristics. The EEP-PC cross-linked wall provided multifaceted protective effects on the oxidation of TSO in EEP-PC-TSO nano-microcapsules, and the nano-microencapsulation can synergistically improve the antioxidant activity of microcapsules. This nano-microcapsules will provide a potential significance for high-value applications of edible oil in food industry. [Display omitted] • EEP-PC-TSO nano-microcapsules was constructed via modified complex coacervation. • Higher homogenous pressures slightly improved the encapsulation efficiency. • EEP improved the protection effect for oxidation of TSO as a novel wall material. • The nano-microencapsulation synergistically improved the antioxidant activity. [ABSTRACT FROM AUTHOR]

Anisotropy, chemical vapor deposition, KNb 3O 8 nanobelts, solar-blind ultraviolet photodetectors, ultrawide bandgap Keywords: anisotropy; chemical vapor deposition; KNb 3O 8 nanobelts; solar-blind ultraviolet photodetectors; ultrawide bandgap EN anisotropy chemical vapor deposition KNb 3O 8 nanobelts solar-blind ultraviolet photodetectors ultrawide bandgap 1 1 1 06/10/22 20220610 NES 220610 B Solar-Blind Ultraviolet Photodetectors b In article number 2111673, Xiaosheng Fang, Zhongming Wei, Hua Xu, and co-workers fabricate a polarization sensitive solar-blind ultraviolet photodetector based on ultrathin KNb SB 3 sb O SB 8 sb nanobelts synthesized via chemical vapor deposition growth. Polarization Sensitive Solar-Blind Ultraviolet Photodetectors Based on Ultrawide Bandgap KNb3O8 Nanobelt with Fringe-Like Atomic Lattice (Adv. Funct. [Extracted from the article]

In recent years, circular RNAs (circRNAs/circs) have attracted significant attention due to their potentially important functions in a variety of human cancer types. circ_0067934 is a newly identified circRNA, the role of which in gastric cancer (GC) has yet to be reported, to the best of our knowledge. In the present study, the expression levels of circ_0067934, microRNA (miR)-1301-3p and kinesin family member 23 (KIF23) in GC cells were detected via reverse transcription-quantitative PCR. Cell proliferation was measured using Cell Counting Kit-8 assays and EdU staining. Wound healing and Transwell assays were performed to assess cell migration and invasion, respectively. Western blotting was performed to measure the protein expression levels of Ki67, proliferating cell nuclear antigen, MMP2, MMP9 and KIF23. The starBase database and luciferase reporter assays were used to predict and verify the binding between circ_0067934 and miR-1301-3p, as well as KIF23, in GC cells. The results demonstrated that circ_0067934 expression was upregulated in GC cells, and circ_0067934 silencing significantly inhibited GC cell proliferation, migration and invasion. In addition, miR-1301-3p was regulated by circ_0067934, and miR-1301-3p overexpression suppressed GC cell migration, invasion and proliferation. miR-1301-3p was found to target KIF23, and KIF23 overexpression reversed the effects of circ_0067934 silencing and miR-1301-3p overexpression on cell proliferation, migration and invasion. In conclusion, circ_0067934 may regulate the proliferation, invasion and migration of GC cells via the miR-1301-3p/KIF23 signaling axis, which may represent a novel therapeutic target for GC metastasis. [ABSTRACT FROM AUTHOR]

• TRAF6-overexpressing DCs are more mature. • TRAF6-overexpressing DCs have anti-tumor properties in vivo. • TRAF6-overexpressing DCs have a stronger Th1 and Tc1 immune response in vivo. Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) signaling is a critical positive mechanism for the development, homeostasis and activation of immune cells. We investigated the effect of TRAF6 overexpression on dendritic cells (DCs) maturation. TRAF6-overexpressing DCs had increased expression of costimulatory molecules, major histocompatibility complex (MHC) molecules and IL-12 expression. This indicated that TRAF6 promoted the maturation of DCs and indirectly promoted Th1 activation. The antitumor activities between TRAF6-overexpressing DCs and control DCs were compared by administering DCs pulsed with mucin 1 (MUC1) Ag peptide in a therapeutic human MUC1-overexpressing mouse B16 melanoma cells (B16-MUC1) model. Administration of TRAF6-overexpressing DCs significantly inhibited the growth of B16-MUC1 tumors, accompanied by an increase in MUC1-specific Th1 responses and Tc1 responses, as well as a decrease in Tregs levels. TRAF6 signaling has been found to be involved in DCs maturation and Th1 activation in vitro , as well as therapeutic tumor models in vivo , indicating that TRAF6-overexpressing DCs may be a promising approach for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Transcatheter arterial chemoembolization (TACE) is widely used for the treatment of advanced hepatocellular carcinoma (HCC). However, the long-term hypoxic microenvironment caused by TACE seriously affects the therapeutic effect of TACE. HIF-2α plays a crucial role on the chronic hypoxia process, which might be an ideal target for TACE therapy. Herein, a multifunctional polyvinyl alcohol (PVA)/hyaluronic acid (HA)-based microsphere (PT/DOX-MS) co-loaded with doxorubicin (DOX) and PT-2385, an effective HIF-2α inhibitor, was developed for enhanced TACE treatment efficacy. In vitro and in vivo studies revealed that PT/DOX-MS had a superior ability to treat HCC by blocking the tumor cells in G2/M phase, prompting cell apoptosis, and inhibiting tumor angiogenesis. The antitumor mechanisms of PT/DOX-MS were possibly due to that the introduction of PT-2385 could effectively inhibit the expression level of HIF-2α in hypoxic HCC cells, thereby down-regulating the expression levels of Cyclin D1, VEGF and TGF-α. In addition, the combination of DOX and PT-2385 could jointly inhibit VEGF expression, which was another reason accounting for the combined anti-cancer effect of PT/DOX-MS. Overall, our study demonstrated that PT/DOX-MS is a promising embolic agent for enhanced HCC treatment via the combined effect of hypoxia microenvironment improvement, chemotherapy, and embolization. [ABSTRACT FROM AUTHOR]

Autophagy is an essential eukaryotic pathway requiring tight regulation to maintain homeostasis and preclude disease. Using yeast and mammalian cells, we report a conserved mechanism of autophagy regulation by RNA helicase RCK family members in association with the decapping enzyme Dcp2. Under nutrient-replete conditions, Dcp2 undergoes TOR-dependent phosphorylation and associates with RCK members to form a complex with autophagy-related (ATG) mRNA transcripts, leading to decapping, degradation and autophagy suppression. Simultaneous with the induction of ATG mRNA synthesis, starvation reverses the process, facilitating ATG mRNA accumulation and autophagy induction. This conserved post-transcriptional mechanism modulates fungal virulence and the mammalian inflammasome, the latter providing mechanistic insight into autoimmunity reported in a patient with a PIK3CD/p110δ gain-of-function mutation. We propose a dynamic model wherein RCK family members, in conjunction with Dcp2, function in controlling ATG mRNA stability to govern autophagy, which in turn modulates vital cellular processes affecting inflammation and microbial pathogenesis. [ABSTRACT FROM AUTHOR]

The major acid phosphatase from Legionella pneumophila ( LpMAP) belongs to the histidine acid phosphatase superfamily. It contains the characteristic histidine acid phosphatase (HAP) sequence motif RHG XR XP responsible for the hydrolysis of a phosphoryl group from phosphate monoesters under acidic conditions. Here, the crystallization and preliminary X-ray analysis of crystals of LpMAP in the apo form and in complex with L-(+)-tartrate are described. By using the hanging-drop vapour-diffusion method, apo LpMAP and LpMAP-tartrate were crystallized in space group P21, with unit-cell parameters a = 91.50, b = 56.48, c = 146.35 Å, β = 110.01°, and in space group P1, with unit-cell parameters a = 55.51, b = 73.51 , c = 98.78 Å, α = 78.82, β = 77.65, γ = 67.73°, respectively. Diffraction data were collected at 100 K and the phases were determined using the molecular-replacement method. [ABSTRACT FROM AUTHOR]

The fungus Cryptococcus is a major cause of meningoencephalitis in HIV-infected as well as HIV-uninfected individuals with mortalities in developed countries of 20% and 30%, respectively. In HIV-related disease, defects in T-cell immunity are paramount, whereas there is little understanding of mechanisms of susceptibility in non-HIV related disease, especially that occurring in previously healthy adults. The present description is the first detailed immunological study of non-HIV-infected patients including those with severe central nervous system (s-CNS) disease to 1) identify mechanisms of susceptibility as well as 2) understand mechanisms underlying severe disease. Despite the expectation that, as in HIV, T-cell immunity would be deficient in such patients, cerebrospinal fluid (CSF) immunophenotyping, T-cell activation studies, soluble cytokine mapping and tissue cellular phenotyping demonstrated that patients with s-CNS disease had effective microbiological control, but displayed strong intrathecal expansion and activation of cells of both the innate and adaptive immunity including HLA-DR+ CD4+ and CD8+ cells and NK cells. These expanded CSF T cells were enriched for cryptococcal-antigen specific CD4+ cells and expressed high levels of IFN-γ as well as a lack of elevated CSF levels of typical T-cell specific Th2 cytokines -- IL-4 and IL-13. This inflammatory response was accompanied by elevated levels of CSF NFL, a marker of axonal damage, consistent with ongoing neurological damage. However, while tissue macrophage recruitment to the site of infection was intact, polarization studies of brain biopsy and autopsy specimens demonstrated an M2 macrophage polarization and poor phagocytosis of fungal cells. These studies thus expand the paradigm for cryptococcal disease susceptibility to include a prominent role for macrophage activation defects and suggest a spectrum of disease whereby severe neurological disease is characterized by immune-mediated host cell damage. [ABSTRACT FROM AUTHOR]

Because of the influence of the environment and the characteristics of the locust slices, locust slices obtained from experiments are always incomplete or folded. To match and reconstruct this folded area, the slice in the sequences adjacent to the slice which needs to be repaired is used as the reference image, and in this way, the slice is repaired successfully. The image mosaic and repair algorithm used in the article has the following steps: image preprocessing, feature extraction, feature matching, coordinate transformation and image mosaic and repair. Firstly, as there is some noise in the slice image that can influence the repairing effect, we use wavelet denoising on images to reduce the effect of noise on feature extraction before searching the feature points; secondly, as there are no related materials about how to match or repair locust slices, in order to find more suitable feature extraction methods for locust slices, we compare the scale-invariant feature transform (SIFT) with speed-up robust features (SURF) algorithm which are already widely used in computer vision and image registration, and then generate the image feature vectors to complete the feature extraction from the initial slice image, record the scale, position and direction of the feature points at the same time, and finish the preliminary matching between the two slices; thirdly, as the preliminary matching can not completely remove the error matching points, random sample consensus (RANSAC) algorithm is used to correct the matching errors and eliminate the error matching points by repeatedly choosing a group of random subsets of the data, finally leaving the correct matching points; fourthly, the homography matrix is calculated by using the least square method based on all the correct matching points, which makes full use of existing points to calculate and therefore makes the results have more universal adaptability; finally, the locust slices mosaic is finished using the correct matching points and the homography matrix, the corresponding matching block for the folded part is found out using space mapping model and the slice repair is completed. The experiment adopts two groups of positive images of locust slice obtained from the experimental environment under the microscope. What's more, statistical results of contrast experiment with SIFT and SURF algorithm are obtained, each of which shows the running time, the number of matching points and matching rate. The experimental results show that: the matching rates reach 72.2% and 34.0% using SIFT algorithm and SURF algorithm, respectively, which means that SIFT algorithm can meet the requirements of image mosaic more precisely compared with SURF algorithm. As the matching rate doesn't perform as well as expected, the error sources such as the change of content or the effect from the fold are briefly analyzed. The registration algorithm provides the reference for the later work of the folded area's opening on the slice image and the three-dimensional reconstruction of locust. [ABSTRACT FROM AUTHOR]

Dephospho-CoA kinase (DPCK; EC 2.7.1.24) catalyzes the final step in the coenzyme A biosynthetic pathway. DPCK transfers a phosphate group from ATP to the 3-hydroxyl group of the ribose of dephosphocoenzyme A (dCoA) to yield CoA and ADP. Upon the binding of ligands, large conformational changes is induced in DPCKs, as well as in many other kinases, to shield the bound ATP in their catalytic site from the futile hydrolysis by bulk water molecules. To investigate the molecular mechanisms underlying the phosphoryl transfer during DPCK catalytic cycle, we determined the crystal structures of the Legionella pneumophila DPCK (LpDPCK) both in its apo-form and in complex with ATP. The structures reveal that LpDPCK comprises of three domains, the classical core domain, the CoA domain, and the LID domain, which are packed together to create a central cavity for substrate-binding and enzymatic catalysis. The binding of ATP induces large conformational changes, including a hinge-bending motion of the CoA binding domain and the “helix to loop” conformational change of the P-loop. Finally, modeling of a dCoA molecule to the enzyme provides insights into the catalytic mechanism of DPCK. [ABSTRACT FROM AUTHOR]

Aim: This study aimed at predicting how sub-alpine coniferous ecosystems respond to global changes in the Eastern Tibetan Plateau by understanding soil microbial communities and activities, as well as variation in the quality and quantity of soil organic matter. Methods: An experiment was conducted to examine soil microbial communities and their related soil processes in rhizospheric soil of two coniferous species that were exposed to two levels of temperature (unwarmed and infrared heater warming) and two levels of nitrogen (unfertilized and 25 g N m a) from April 2007. Results: Four-year night warming alone slightly affected the phospholipid fatty acid contents of the microbial community. However, the combination of nitrogen addition and soil warming significantly affected soil microbial composition while reducing the biomass of major microbial groups and the activities of most enzymes, especially in Abies faxoniana plots. The combination of warming and nitrogen addition increased soil labile C and N pools in Picea asperata plots and was beneficial for soil recalcitrant C, as well as for labile and total C and N pools in A. faxoniana plots. Conclusion: Results indicated that future warming will slightly affect soil microbial communities and their related soil processes. However, warming combined with high nitrogen deposition will significantly constrain soil microbial biomass and enzyme activities, consequently increasing soil C and N pools in sub-alpine coniferous forests of this region. [ABSTRACT FROM AUTHOR]