Search

Introduction: Climate change is threatening biodiversity hotspots. Notably, alpine bumblebees, which are mostly associated with a cold ecological niche, face a higher risk of extinction. Bombus formosellus is one of the alpine bumblebees endemic to Taiwan.Aims/Methods: In this study, we use ensemble ecological niche modeling for the first time to predict spatial and temporal dynamics for habitats suitable to B. formosellus under current and future climate scenarios (representative concentration pathway, RCP 2.6, 4.5, and 8.5 in the 2070s).Results: This model identified that the cool temperature with low variation, a specific range of precipitation and presence of coniferous forest and grasslands were the key factors affecting the distribution of B. formosellus. Using modeling to predict suitable habitats under various scenarios, we discovered that, compared with the current climatic conditions, the predicted suitable habitat area in the future decreased regardless of which climate change scenario was applied. In particular, RCP 8.5 appeared to be the most significant, with an area loss of nearly 87%, and fragmentation of the landscape with poor connection.Discussion: In summary, our analyses indicate that cool environments are suitable for B. formosellus. However, Taiwan’s warming is more significant in the high mountains than in the plains. The climate change trajectory may become increasingly unfavorable to B. formosellus. Consequently, this species may face the risk of extinction in the future.Implications for insect conservation: We predict that many suitable habitats of B. formosellus will disappear or become fragmented in the future. Therefore, the remaining patches have become important refuges, and protection measures in these areas should be strengthened.

The guanine nucleotide exchange factor (GEF) SOS1 catalyzes the exchange of GDP for GTP on RAS. However, regulation of the GEF activity remains elusive. Here, the authors report that PPDPF functions as an important regulator of SOS1. The expression of PPDPF is significantly increased in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and recurrence of PDAC patients. Overexpression of PPDPF promotes PDAC cell growth in vitro and in vivo, while PPDPF knockout exerts opposite effects. Pancreatic-specific deletion of PPDPF profoundly inhibits tumor development in KRAS

This study reports Ca-Fe isotope compositions of mineral separates in a set of peridotite xenoliths including ten lherzolites, one harzburgite, and one wehrlite from Hainan Island, south China. Iron isotope compositions show a small variation ( 2‰) in previous studies should be dominated by disequilibrium sub-solidus Ca redistribution between cpx and opx, which is driven by the changes of mantle temperature and chemical composition in pyroxene. The wehrlite, which was formed by reaction of peridotite with an evolved, silica-undersaturated melt, has δ44/40Ca of 3.22‰ and δ56/54Fe of 0.22‰, significantly heavier than the value of fertile mantle. Such heavy isotope signatures in the wehrlite are best explained by diffusion during the metasomatic melt percolating the refractory mantle. In summary, this study reveals that significant kinetic Ca isotope fractionations could occur in the mantle by inter-mineral Ca diffusion during re-equilibration upon cooling and Ca diffusion from melt into peridotite during melt percolation.

Objective Long noncoding RNAs (lncRNAs) are widely involved in the carcinogenesis and development of cancers. We conducted a meta-analysis to evaluate the diagnostic performance of lncRNAs in hepatocellular carcinoma (HCC). Methods After the inclusion and exclusion process, relevant information was extracted. Heterogeneity between studies was evaluated, and data synthesis was conducted by employing a bivariate random-effects model. Results In total, 20 eligible studies were enrolled. The pooled sensitivity and specificity were 0.86 (95% confidence interval [CI], 0.80–0.90) and 0.88 (95% CI, 0.82–0.92), respectively. The pooled positive likelihood ratio, pooled negative likelihood ratio, and pooled diagnostic odds ratio were 7.1 (95% CI, 4.9–10.2), 0.16 (95% CI, 0.11–0.23), and 44 (95% CI, 25–79), respectively. The results of the linear regression method and visual inspection of the Deeks funnel plot did not indicate significant publication bias. Conclusion Our meta-analysis suggested that lncRNAs have high diagnostic performance for HCC and have the potential for clinical application.

The concentration of dissolved carbon dioxide in seawater affects the formation of seabed biogenic minerals, and controls the development and evolution of marine organisms, which is one of the most important indices in the marine environment and geology survey. The concentration of free carbon dioxide in bottom seawater has important academic value for the exploration of seabed minerals, marine environment monitoring, the study of the carbon cycle in seabed sediments and even the global carbon cycle. Titration is used to determine the index, whose range is between 4 mg/L and 400 mg/L. However, the concentration of free carbon dioxide in bottom seawater in some sea areas is lower than this range, thus titration may not be suitable. A method for the determination of free carbon dioxide in artificial seawater, whose name is D.B.S/Henry’s Law, is described in this paper. D.B.S/Henry’s Law indirectly determines the content of free carbon dioxide in seawater instead of directly titrating with reagents. It is simple, fast and accurate, and it is based on the law of conservation of mass/Henry’s law and CO2 dissolution mechanisms. This discovery mainly provides a new scientific perspective for the determination of trace free carbon dioxide concentration in seawater. In addition, Henry’s law constants of carbon dioxide in artificial seawater at 3–20 degrees Celsius are determined with D.B.S/Henry’s Law. These data will be used as an important reference for the determination of free carbon dioxide in seawater in the future. D.B.S/Henry’s Law may be used as a supplement of the methods specified in national and industrial standards, which are applied to the detection of carbon dioxide Henry’s constant and free carbon dioxide content in various temperature and salinity seawater. D.B.S/Henry’s Law provides a new perspective for CO2 determination and has extensive practical application value.

To analyze the performance of the Prostate Health Index (phi) and its derivatives for predicting Gleason score (GS) upgrading between prostate biopsy and radical prostatectomy (RP) in the Chinese population, an observational, prospective RP cohort consisting of 351 patients from two medical centers was established from January 2017 to September 2020. Pathological reclassification was determined by the Gleason Grade Group (GG). The area under the receiver operating characteristic curve (AUC) and logistic regression (LR) models were used to evaluate the predictive performance of predictors. In clinically low-risk patients with biopsy GG ≤2, phi (odds ratio [OR] = 1.80, 95% confidence interval [95% CI]: 1.14-2.82, P = 0.01) and its derivative phi density (PHID; OR = 2.34, 95% CI: 1.30-4.20, P = 0.005) were significantly associated with upgrading to GG ≥3 after RP, and the results were confirmed by multivariable analysis. Similar results were observed in patients with biopsy GG of 1 for the prediction of upgrading to RP GG≥2. Compared to the base model (AUC = 0.59), addition of the phi or PHID could provide additional predictive value for GS upgrading in low-risk patients (AUC = 0.69 and 0.71, respectively, both P0.05). In conclusion, phi and PHID could predict GS upgrading after RP in clinically low-risk patients.

BackgroundTumor-associated macrophages (TAMs) are a significantly-poor prognostic factor for patients with triple-negative breast cancer (TNBC). The tumor microenvironment of TNBC features highly-infiltrating TAMs that contribute to tumor progression and metastasis. Therefore, TAM-targeted immunotherapies are recognized as a potential approach for treating TNBC. However, depleting TAMs alone by use of monoclonal antibodies against colony-stimulating factor 1 receptor (CSF1R) was insufficient to cause substantial tumor control. Recent studies revealed that interleukin-10 (IL-10) can directly activate terminally-exhausted CD8+ T cells to boost anti-tumor activity. We set forth to investigate whether a combination of anti-CSF1R antibody with a half-life-extended IL-10-Fc fusion protein (IL-10-Fc) may enhance anti-tumor immunity, and whether synergistic effects could be achieved with bifunctional antibody forms.MethodsAntibodies and recombinant proteins were produced in-house. In vitro CSF1R activity was evaluated by Western blot analysis of CSF1-mediated CSF1R phosphorylation and monocyte proliferation assays. In vitro IL10 activity was evaluated by MC/9 cell proliferation and CD8 T cell activation assays. 4T1 mouse breast tumor studies were performed at the National Yang Ming Chiao Tung University (Taiwan). Other tumor model studies employed the services of Crownbio (China). Methods of RNAseq analysis of 4T1 tumor masses included Cibersort, gene set enrichment analysis (GSEA) and immune gene signature score analysis.ResultsCo-treatment with a recombinant human IL-10-Fc protein significantly improved the anti-tumor efficacy of anti-mouse CSF1R antibody in a mouse CT26 colon tumor model. It was then hypothesized that a better synergistic effect could be achieved by a bifunctional anti-mouse CSF1R-IL-10 fusion protein (anti-mCSF1R-IL-10), to allow targeted-delivery of IL-10 to CSF1R-positive-TAM-rich tumor microenvironments. Indeed, anti-mCSF1R-IL-10 showed greatly increased anti-tumor efficacy in both EMT-6 and 4T1 mouse models of breast cancer. Consistent with the in vivo efficacy, gene expression profiling revealed an enhanced intratumoral interferon-gamma signature by treatment with anti-mCSF1R-IL-10 as compared to either anti-mCSF1R or IL-10-Fc alone. An anti-human CSF1R-IL-10 (hCSF1R-IL-10) was also constructed using a newly-produced anti-human CSF1R antibody and tested in cell-based functional assays, demonstrating that anti-hCSF1R-IL-10 could both inhibit CSF1-dependent cell growth and activate tumor-infiltrating T cells isolated from tumor biopsies of triple-negative breast cancer patients. Further validation of this bifunctional form will be presented.ConclusionsOur findings provide a potential strategy for simultaneously targeting TAM and exhausted T cells to potentiate anti-tumor immunity for treatment of triple-negative breast cancer.Ethics ApprovalThe studies were approved by the institutional animal care and use committee of National Yang Ming Chiao Tung University; approval numbers 1081025 and 109060.

Anti-interferon (IFN)–γ autoantibodies (AIGAs) are a pathogenic factor in late-onset immunodeficiency with disseminated mycobacterial and other opportunistic infections. AIGAs block IFN-γ function, but their effects on IFN-γ signaling are unknown. Using a single-cell capture method, we isolated 19 IFN-γ–reactive monoclonal antibodies (mAbs) from patients with AIGAs. All displayed high-affinity (KD < 10−9 M) binding to IFN-γ, but only eight neutralized IFN-γ–STAT1 signaling and HLA-DR expression. Signal blockade and binding affinity were correlated and attributed to somatic hypermutations. Cross-competition assays identified three nonoverlapping binding sites (I–III) for AIGAs on IFN-γ. We found that site I mAb neutralized IFN-γ by blocking its binding to IFN-γR1. Site II and III mAbs bound the receptor-bound IFN-γ on the cell surface, abolishing IFN-γR1–IFN-γR2 heterodimerization and preventing downstream signaling. Site III mAbs mediated antibody-dependent cellular cytotoxicity, probably through antibody–IFN-γ complexes on cells. Pathogenic AIGAs underlie mycobacterial infections by the dual blockade of IFN-γ signaling and by eliminating IFN-γ–responsive cells.

The invasive alien species (IAS) Vespa bicolor is the first reported hornet that has established in Taiwan and is concerning as they prey on honeybee Apis mellifera, which leads to colony losses and public concerns. Thus, the aim of this study was to assess the current status of V. bicolor abundance, dispersal, and impact and to trace the origins of Taiwan’s V. bicolor population. Our studies took place in five areas in northern to central Taiwan. We used mtDNA in the phylogenetic analyses. Field survey and ecological niche modeling (ENM) were used to understand the origins and current range of the invasive species. Two main subgroups of V. bicolor in the phylogenetic tree were found, and a clade with short branch lengths in Southeastern China and Taiwan formed a subgroup, which shows that the Taiwan population may have invaded from a single event. Evidence shows that V. bicolor is not a severe pest to honeybees in the study area, however, using ENM, we predict the rapid dispersion of this species to the cooler and hilly mountain areas of Taiwan. The management of V. bicolor should also involve considering it a local pest to reduce loss by beekeepers and public fear in Taiwan. Our findings highlight how the government, beekeepers, and researchers alike should be aware of the implications of V. bicolor’s rapid range expansion in Taiwan, or in other countries.

Wurtzite CdS nanoparticles have been lightly deposited on Cu2O cubes, octahedra, and rhombic dodecahedra to examine facet effects on the interfacial charge transfer in a photocatalytic reaction. Instead of an expected photocatalytic activity enhancement on the basis of a favorable band alignment at the heterojunction, CdS-decorated Cu2O octahedra and rhombic dodecahedra show drastically reduced photocatalytic activities. Further increasing the CdS deposition amount leads to complete suppression of photocatalytic activity. Cu2O cubes remain inactive even after CdS deposition. Transmission electron microscopy analysis reveals epitaxial growth of the (101) planes of CdS on the (110) planes of a Cu2O rhombic dodecahedron, whereas the (110) planes of CdS align parallel to the (111) planes of a Cu2O octahedron. Because facet-dependent photocatalytic activity can be understood from different degrees of band bending at the crystal surfaces, significantly upward bending for the CdS-contacting planes can explain th...

By making Cu2O nanocubes, octahedra, and rhombic dodecahedra with tunable sizes and recording their light absorption and emission spectra, their absorption and emission bands shift steadily to longer wavelengths with increasing particle sizes from 10 nm to beyond 250 nm. Emission intensities are highest for the smallest nanocubes. Photoluminescence band shifts exceed 130 nm over this size range. For particles having the same volume, rhombic dodecahedra absorb light of shortest wavelength, while cubes show most red-shifted absorption with their band gaps differing by 0.17 eV (or 51.5 nm). They show obviously different colors. The presence of optical size and facet effects in semiconductors means that their emission wavelengths are tunable through facet control and use of nanocrystals much larger than quantum dots. A modified and general band diagram for Cu2O crystals has been constructed incorporating their optical size and facet effects with surface band bending. In addition, a more complete understanding...

The effect of specific surface area (SSA) of Fe 2 O 3 was investigated while evaluating the raw material of Y 3 Fe 5 O 12 (yttrium iron garnet (YIG)) preparation. For YIG ferrite, the specific surface area of Fe 2 O 3 , rather than average particle size ( D 50 ), was found to markedly affect the mixing homogeneity of powders in the mixing procedure and the magnetic properties. Increasing the specific surface area of Fe 2 O 3 resulted in the increase of the remanence ( B r ) and squareness ratio ( SQR ); meanwhile, it also caused an obvious reduction in coercivity ( H C ) for the sintered specimens. An upgrade in the specific surface area of raw material Fe 2 O 3 could further resulted in a decrease in slurry viscosity in the mixing procedure, which promotes slurry mixing homogeneity and further promotes reactivity in the calcination and sintering processes. Consequently, a larger B r and SQR and a smaller H C were obtained. In addition, good ferromagnetic resonance (FMR) line width (i.e., Δ H ) properties were also realized as 36.7 Oe at 3.2 GHz using the selected Fe 2 O 3 . As found in this study, the strict control of raw material Fe 2 O 3 is critical in tailoring suitable B r and H C for the YIG ferrite manufacturing process.

Objective To develop a simple and fast method for removing polyethylene glycol (PEG) and simultaneous determination of fives saponins, i.e. astragaloside IV, notoginsenoside R1, ginsenoside Rg1, ginsenoside Rb1, and ginsenoside Rd in dripping pills made from Astragali Radix and Panax notoginseng. Methods The extraction method was based on a liquid-liquid extraction using water-saturated n-butanol and the quantitative determination was based on ultra-performance liquid chromatography coupled with evaporative light scattering detection (UPLC-ELSD). The chromatographic analysis was performed on an Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 µm) with a gradient elution of acetonitrile-0.1% formic acid aqueous solution within a runtime of 15 min. Results Compared to different methods, the proposed method could remove the interference of PEG in formulation. And the calibration curves showed good linearity during the test ranges. The method was validated for limits of detection and quantification, precision, and reproducibility. The recoveries were within the range of 96.87% – 99.97%. In addition, the verified method was firstly applied to determination of the five active ingredients in Qishen Yiqi Dripping Pills (QYDP) simultaneously. Conclusion The contents of five active ingredients are stable and homogeneous in QYDP, which indicates that the method could be readily utilized as a quality evaluation method for this traditional Chinese medicine dripping pills made from Astragali Radix and Panax notoginseng.

A strategy was developed for the voltammetric determination of the antibiotic drug levofloxacin (LV) based on a glassy carbon electrode modified with a composite consisting of poly(o-aminophenol) and graphene quantum dots (PoAP/GQD) that was fabricated by electropolymerization. The PoAP/GQD composite provides a large surface area and sensing interface and strongly promotes the oxidation current of LV. Under optimal conditions, the modified GCE displays an oxidation peak current (best measured at a working voltage of 1.05 V vs. SCE) that is linearly related to the levofloxacin concentration in the range from 0.05 to 100 μM, and the detection limit is 10 nM (at an S/N of 3). The method was applied to the determination of levofloxacin in spiked milk samples where is gave recoveries between 96.0 and 101.0 %.

A Bi0.5Sb1.5Te3 thermoelectric material electroplated with a Ni barrier layer and a Ag reaction layer was bonded with a Ag-coated Cu electrode at low temperatures of 448 K (175 °C) to 523 K (250 °C) using a 4-μm-thick In interlayer under an external pressure of 3 MPa. During the bonding process, the In thin film reacted with the Ag layer to form a double layer of Ag3In and Ag2In intermetallic compounds. No reaction occurred at the Bi0.5Sb1.5Te3/Ni interface, which resulted in low bonding strengths of about 3.2 MPa. The adhesion of the Bi0.5Sb1.5Te3/Ni interface was improved by precoating a 1-μm Sn film on the surface of the thermoelectric element and preheating it at 523 K (250 °C) for 3 minutes. In this case, the bonding strengths increased to a range of 9.1 to 11.5 MPa after bonding at 473 K (200 °C) for 5 to 60 minutes, and the shear-tested specimens fractured with cleavage characteristics in the interior of the thermoelectric material. The bonding at 448 K (175 °C) led to shear strengths ranging from 7.1 to 8.5 MPa for various bonding times between 5 and 60 minutes, which were further increased to the values of 10.4 to 11.7 MPa by increasing the bonding pressure to 9.8 MPa. The shear strengths of Bi0.5Sb1.5Te3/Cu joints bonded with the optimized conditions of the modified solid–liquid interdiffusion bonding process changed only slightly after long-term exposure at 473 K (200 °C) for 1000 hours.

Tissue fibrosis is a major cause of organ dysfunction during chronic diseases and aging. A critical step in this process is transforming growth factor β1 (TGF-β1)-mediated transformation of fibroblasts into myofibroblasts, cells capable of synthesizing extracellular matrix. Here, we show that SIRT3 controls transformation of fibroblasts into myofibroblasts via suppressing the profibrotic TGF-β1 signaling. We found that Sirt3 knockout (KO) mice with age develop tissue fibrosis of multiple organs, including heart, liver, kidney, and lungs but not whole-body SIRT3-overexpressing mice. SIRT3 deficiency caused induction of TGF-β1 expression and hyperacetylation of glycogen synthase kinase 3β (GSK3β) at residue K15, which negatively regulated GSK3β activity to phosphorylate the substrates Smad3 and β-catenin. Reduced phosphorylation led to stabilization and activation of these transcription factors regulating expression of the profibrotic genes. SIRT3 deacetylated and activated GSK3β and thereby blocked TGF-β1 signaling and tissue fibrosis. These data reveal a new role of SIRT3 to negatively regulate aging-associated tissue fibrosis and discloses a novel phosphorylation-independent mechanism controlling the catalytic activity of GSK3β.

The searching for Y3Fe5O12 (YIG) ferrite base material is a difficult challenge for microwave phase shifter. Although YIG ferrite is promising for its good microwave characteristics, the adjustment of its corresponding magnetic properties for applied frequency is always a tough challenge. In this work, a study was made to evaluate the impacts of stoichiometry and sintering temperature on hysteresis properties of Mn, Al and Gd substituted YIG ferrites. The Mn, Al substituted YIG ferrite, (Y3)(MnxAl0.83−xFe4.17)O12 showed its best properties for application in 2–4 GHz frequency range (i.e. S-band) latching phase shifter at x = 0.13. Magnetic properties were further improved by sintering optimization. The increasing sintering temperature increases saturation magnetization (4πMs), remanence (Br) and squareness ratio (SQR), while decreasing the coercivity (Hc). To further investigate the impact to sintering process, Gd substituted YIG ferrites are also discussed. (Y3−yGdy)(Mn0.13Al0.7−0.5yFe4.17)O12 with y = 0.6 demonstrated its best magnetic properties at 1450 °C sintering. Although the 4πMs, Br and SQR are comparable to that of previous results, its Hc cannot meet the requirement. (Y3)(MnxAl0.83−xFe4.17)O12 ferrites with x = 0.13 sintered at 1430 °C shows the optimum magnetic properties: 4πMs = 675 G, Br = 575 G, Hc = 0.45 Oe, SQR = 0.86. Good ferromagnetic resonance (FMR) linewidth (i.e. ΔH) were also realized as 38.6 Oe at 3.2 GHz. Base on above results, we reveal Mn, Al substituted YIG ferrite is a good candidate for practical latch phase shifter applications at S-band.

In this paper, we analyzed near-threshold-voltage (NTV) CMOS circuits with various body bias and proposed an NTV adder design with dual body bias. By adopting different body bias in the same time, adder delay and leakage power can be reduced. Also, the critical path is optimized to achieve better energy efficiency. The performance analysis are all performed under TSMC 90nm CMOS process with Monte Carlo simulation.

In this work, we have developed an electrochemical aptasensor for high-sensitivity determination of carcinoembryonic antigen (CEA) based on lead ion (Pb2+)-dependent DNAzyme-assisted signal amplification and graphene quantum dot-ionic liquid-nafion (GQDs-IL-NF) composite film. We designed hairpin DNA containing CEA-specific aptamers and DNAzyme chains. In the presence of CEA, hairpin DNA recognized the target and performed a DNAzyme-assisted signal amplification reaction to yield a large number of single-stranded DNA. The GQDs-IL-NF composite film was immobilized on the glassy carbon electrode for the interaction with single-stranded DNA through noncovalent π-π stacking interaction. Therefore, the methylene blue-labeled substrate DNA (MB-substrate) was fixed on the electrode and exhibited an initial electrochemical signal. Under optimal conditions, the response current change was proportional to the concentration of CEA, demonstrating a wide linear range from 0.5 fg mL−1 to 0.5 ng mL−1, with a low detection limit of 0.34 fg mL−1. Furthermore, the proposed aptasensor was successfully applied in determining CEA in serum samples, showing its superior prospects in clinical diagnosis.

Intense noise exposure causes hearing loss by inducing degeneration of spiral ganglia neurites that innervate cochlear hair cells. Nicotinamide adenine dinucleotide (NAD(+)) exhibits axon-protective effects in cultured neurons; however, its ability to block degeneration in vivo has been difficult to establish due to its poor cell permeability and serum instability. Here, we describe a strategy to increase cochlear NAD(+) levels in mice by administering nicotinamide riboside (NR), a recently described NAD(+) precursor. We find that administration of NR, even after noise exposure, prevents noise-induced hearing loss (NIHL) and spiral ganglia neurite degeneration. These effects are mediated by the NAD(+)-dependent mitochondrial sirtuin, SIRT3, since SIRT3-overexpressing mice are resistant to NIHL and SIRT3 deletion abrogates the protective effects of NR and expression of NAD(+) biosynthetic enzymes. These findings reveal that administration of NR activates a NAD(+)-SIRT3 pathway that reduces neurite degeneration caused by noise exposure.

Two types of Bi0.4Sb1.6Te3 powder exhibiting particle and grain-size differences were fabricated using a high-energy ball milling process. The mixtures at different ratios were consolidated by vacuum hot pressing to produce nano-/micro-structured composites with the same chemical compositions. Measurements of the Seebeck coefficient, electrical resistivity, and thermal conductivity provided a ZT value as high as 1.19 at 373 K for a sample containing 40% nanograin powders. This ZT value is higher than that of the monolithic nanostructured Bi0.4Sb1.6Te3 sample. The ZT values of this sample at a temperature ranging between 400 and 495 K are between 1.0 and 1.1. Such ZT characteristics make the ZT value suitable for power generation applications because no other materials with a similarly high ZT value have been observed in this temperature range. The achieved higher ZT value is potentially attributed to the unique nano-/micro-structures, in which the dispersed nanograin powders can increase phonon scattering sites and reduce thermal conductivity. Furthermore, the existence of micropowders can provide fast carrier transportation network that enhances electrical conductivity. The results indicated that the nano-/micro-structured Bi0.4Sb1.6Te3 alloy can serve as a high-performance material for application in thermoelectric (TE) devices.

The separate content of six types of heavy metals (Cd, Hg, Pb, As, Cu and Cr) in soil for Yanjiao area was evaluated in this article. Hakanson Potential ecological risk index was applied to analyze single factor potential ecological risk possibility and comprehensive ecological risk index regarding six types of pollution element in the soil. The result shows that the average value of potential ecological risk index sequences as Cd>Hg>Pb>Cu>As>Cr. The average ecological risk index of Cd is 44.90, which indicates that the soil ecological risk of the area is moderate. The average ecological risk index of other 5 types of heavy metals belongs to mild ecological risk grade. Based on the analysis of comprehensive ecological risk index, 15% of the sample points belong to the moderately ecological risk grade, and the rest 85% sample points belong to the lightly ecological risk grade. Among these elements, Cd and Hg contribute most to the ecological risk, and they are the major risk elements of the ecological risk.

The thermoelectric conversion efficiency of the thermoelectric material Bi 2 Te 3 is significantly affected by its microstructure because of its anisotropy. In this study, the zone-melting technique is used to grow Bi 2 Te 3 columnar crystals. The zone-melting process directionally solidifies and purifies an ingot by a moving a heater along the ingot. For predicting the temperature variation and distribution in the crystallization process and the microstructures of Bi 2 Te 3 , a zone-melting model is developed and numerical simulation techniques are used. The simulation results are compared with experimental measurements to verify the numerical model. The verified numerical model is used to investigate the optimal process parameters. The process parameters, namely the temperature of the heater and the movement speed of the heater and the cooling devices, are adjusted in order to obtain good-quality columnar crystals. The shapes of the solidification interface, which greatly affect the direction of grain growth and the grain size, are compared.

A study was made to evaluate the impacts of stoichiometry and sintering temperature on hysteresis properties of an Mn, Al substituted Y 3 Fe 5 O 12 (YIG) ferrite. The Mn, Al substituted YIG ferrite, (Y 3 )(Mn x Al 0.83-x Fe 4.17 )O 12 showed the best properties for application in 2-4 GHz frequency range (i.e., S-band) latching phase shifter at x =0.13 . Magnetic characteristics were further improved by sintering process. The increasing sintering temperature increases saturation magnetization (4π M s ), remanence (B r ), and squareness ratio, while decreasing the coercivity (H c ). In addition, good ferromagnetic resonance linewidth (i.e., ΔH) properties were also realized as 38.6 Oe at 3.2 GHz. Based on above magnetic characteristics, (Y 3 )(Mn x Al 0.83-x Fe 4.17 )O 12 is a good candidate for practical latch phase shifter applications at S-band.

A new tetranuclear dinitrosyliron complex [(μ-SC3H4SN)Fe(NO)2]4 (2), each of a Fe center coordinated with two S or two N, was prepared by CO replacement from the reduced precursor (CO)2Fe(NO)2 with 1 equiv of HSC3H4SN (2-mercaptothiazoline) in the presence of O2(g). The structure of 2 is similar to [(Imid-iPr)Fe(NO)2]4 (Imid-iPr = 2-isopropylimidazole) (Hess et al. J Am Chem Soc 133:20426–20434, 2011), and both complexes comprise a quadrilateral plane of irons with corresponding ligands, SC3H4SN− or Imid-iPr−, bridging the edges and two nitrosyl ligands capping the irons at the corners. An additional equiv of SC3H4SN− was added to 2, which results in the mononuclear {Fe(NO)2}9 (SC3H4SN)2Fe(NO) 2 − (3), in the manner of N bound-[SC3H4SN]. Reaction of (TMEDA)IFe(NO)2 (TMEDA = tetramethylethylenediamine) and complex 3 leads to the formation of complex 2. Dinuclear complex [(μ-C5H7N2)Fe(NO)2]2 (4) can be synthesized by the ligand displacement of SC3H4SN− to C5H7N2 − (3,5-dimethylpyrazolate) of 2 (Chong et al. Can J Chem 57:3119–3125, 1979). Complexes 2–4 were characterized by IR and UV–Vis. The molecular structures of 2 and 3 were determined by X-ray single crystal diffraction.

We have found that tumor-associated macrophages (TAMs) isolated from metastatic tumors displayed a predominant M2 phenotype. Preclinical studies show that M2-polarized TAMs forge an immunosuppressive microenvironment at metastatic niches to facilitate colonization. Colony-stimulating factor 1 receptor (CSF-1R) signaling is known to regulate the survival and maintenance of M2 TAMs, suggesting targeting CSF-1R might have therapeutic potential in halting cancer progression. To this end, we developed an orally active and selective small-molecule CSF-1R inhibitor EI-1071. Experimental procedures: EI-1071 was evaluated in kinase and cell-based bioassays, including macrophage proliferation and osteoclast differentiation. In vivo activity was verified using murine syngeneic models of colorectal cancer and breast cancer. EI-1071 was administered individually or in combination with an anti-PD1 antibody. Tumor infiltrating leucocytes were profiled using flow cytometric analysis. Results: EI-1071 exhibited nanomolar potency for inhibition of CSF-1R but not other 453 kinases tested. In cell-based bioassays, EI-1071 inhibited CSF-1R activity in human monocytes/macrophages, AML-5 leukemia, MNFS-60 leukemia, and human osteoclasts. In preclinical studies, EI-1071 displayed a favorable ADME properties, including hepatocyte stability, high Caco-2 permeability, and pharmacokinetic profiles. Oral administration of EI-1071 reduced TAM infiltration in the MC38 colorectal cancer and EMT6 breast cancer models. Moreover, EI-1071 dosed with an anti-PD-1 antibody showed further enhanced antitumor activity in vivo . Conclusions: Preclinical characterization of EI-1071 demonstrated that it is a potent and selective CSF-1R inhibitor and has a favorable drug like properties for further clinical evaluation. Therefore, EI-1071 is undergoing IND-enabling activities for the First-In-Human (FIH) Phase 1 study. Citation Format: Hung-Kai Chen, Huey-Wen Hsiao, Li-Ming Lu, Chih-Lun Hsiao, Yin-Ping Wang, Jing-Yi Huang, Chu-Bin Liao, Shao-Zheng Peng, Daw-Tsun Shih. A potent and selective cfms inhibitor EI-1071 inhibits CSF1R signaling and regulates the tumor-associated macrophages [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 343.

Two kinds of Bi0.4Sb1.6Te3 powder with different particle and grain sizes were fabricated by high-energy ball milling. Powder mixtures with varied weight ratios were consolidated by vacuum hot pressing (HP) to produce nano/ microstructured composites of identical chemical composition. From measurements of the Seebeck coefficient, electrical resistivity, and thermal conductivity of these composites, a figure of merit (ZT) value of up to 1.19 was achieved at 373 K for the sample containing 40% nanograin powder. This ZT value is higher than that of monolithic nanostructured Bi0.4Sb1.6Te3. It is further noted that the ZT value of this sample in the temperature range of 450 K to 575 K is in the range of 0.7 to 1.1. Such ZT characteristics are suitable for power generation applications as no other material with a similar high ZT value in this temperature range has been observed until now. The achieved high ZT value can probably be attributed to the unique nano/microstructure, in which the dispersed nanograin powder increases the number of phonon scattering sites, which in turn results in a decrease of the thermal conductivity while simultaneously increasing the electrical conductivity, owing to the existence of the microsized powder that can provide a fast carrier transportation network. These results indicate that the nano/microstructured Bi0.4Sb1.6Te3 alloy can serve as a high-performance material for application in thermoelectric devices.

Salt-inducible kinase 2 (SIK2) is an important regulator of cAMP response element-binding protein-mediated gene expression in various cell types and is the only AMP-activated protein kinase family member known to interact with the p97/valosin-containing protein (VCP) ATPase. Previously, we have demonstrated that SIK2 can regulate autophagy when proteasomal function is compromised. Here we report that physical and functional interactions between SIK2 and p97/VCP underlie the regulation of endoplasmic reticulum (ER)-associated protein degradation (ERAD). SIK2 co-localizes with p97/VCP in the ER membrane and stimulates its ATPase activity through direct phosphorylation. Although the expression of wild-type recombinant SIK2 accelerated the degradation and removal of ERAD substrates, the kinase-deficient variant conversely had no effect. Furthermore, down-regulation of endogenous SIK2 or mutation of the SIK2 target site on p97/VCP led to impaired degradation of ERAD substrates and disruption of ER homeostasis. Collectively, these findings highlight a mechanism by which the interplay between SIK2 and p97/VCP contributes to the regulation of ERAD in mammalian cells.

Ca3Co4O9+δ and Ca3−xPrxCo3.95Ga0.05O9+δ (x = 0.02, 0.05 and 0.10) samples were prepared by conventional solid-state synthesis. The thermoelectric (TE) properties were measured at 300–750 K. The XRD patterns revealed that all the samples are single phase. The thermopower of all the samples was positive, indicating that the predominant carriers are holes over the entire temperature range. The power factor of Ca2.9Pr0.10Co3.95Ga0.05O9+δ was improved about 52.6 % compared to Ca3Co4O9+δ at 300 K. Ca2.9Pr0.10Co3.95Ga0.05O9+δ had the highest dimensionless figure of merit of 0.030 at 300 K, representing an improvement of about 50 % compared to Ca3Co4O9+δ. These results indicate that partial substitution of Pr3+ ion improves the TE properties of Ca3Co4O9+δ.

Assessing the progress of alien plant invasion is pivotal for weed management. In this study, we develop a spatially explicit logistic regression imbedded cellular automaton (CA)-based species expansion model to estimate the invasion of a Central American Mimosoid tree Leucaena leucocephala (LELE) in a tropical coastal region of Taiwan. We delineated the LELE infested areas in 1988, 1997 and 2007 using the Satellite Pour L'observation de la Terre (SPOT), and refined the classifications using high spatial resolution aerial photographs or Formosat-2 satellite images (Center for Space and Remote Sensing Research, Taiwan). Dynamics of LELE by referring to 1988–1997 LELE spatial distributions were ingested into a logistic model to build transition rules for CA simulation. The results showed that the enhanced CA model can precisely (95% overall accuracy by comparing with the 2007 LELE distribution) model the population expansion of LELE. This study highlights the strength of this spatially explicit predictive m...

This work presents flexible tactile sensor using piezoresistive nanocomposite rubber elastomers (C-PDMS): Carbon-black (C) powders filled into polymethylsiloxane (PDMS) using solvent-wetting methods with n-Hexane to produce well-dispersed conductive polymeric nanocomposites. The C-PDMS nanocomposites are utilized to measure resistance changes. In application, the C-PDMS is casted and stacked into PDMS substrate and gold films deposited with 3-mercaptopropyltrimethoxysilane (MPTMS) adhesion layers as bond pads to implement the flexible polymer-based devices. Typical normal load tests show resistance changes of C-PDMS piezoresistors on flat surface are ranging 2.92%∼4.45% (ΔR/R 0 /mN). Moreover, resistance changes of C-PDMS piezoresistors on curved surface are ranging 0.92%∼0.98% (ΔR/R 0 /mN).

This study based on piezo-electric sensing principle to develop a high S/N ratio MEMS microphone. The patterned PZT and electrodes designed implemented above the clamped diaphragm to generate high stress concentration on PZT and Si bimorph diaphragm. The proposed central-circle electrode design can induce more charge than the edge-surrounded electrode design (served as the reference design). The proposed design also provides a smooth stress distribution across electrode to tolerate more process variation such as offset from double-side alignment and boundary change by DRIE undercut. The measured results demonstrate the S/N is about 64dB (reference design: 53dB) for the piezo-electric microphone.

Owing to energy conservation of waste heat, Lead telluride, PbTe, based materials have promising good thermoelectric properties around a range of middle temperature (Fig. 1, from 300 to 600°C), due to their high melting point, fine chemical stability, and the high figure of merit Z. The general physical properties and factors affecting the figure of merit have been reviewed. This research is focused on the n-type of PbTe materials and collocated with analysis of densities, hardness, elastic modulus, and thermoelectric properties thermoelectric figure of merit ZT=GS2T/κ (where G is electrical conductivity, S is Seebeck coefficient , T is absolute temperature, and κ is thermal conductivity). Room temperature hardness and Young’s modulus are measured by nano-indentation. In this study, the hot-press compacts under the pressure of 4 ton/cm2 can reach the maximum density about 8.2 g/cm3, and hardness and elastic modulus are 0.6 GPa and 70 GPa, respectively. The figure of merit value (ZT) of PbTe in low temperature (around 340°C) was found about 1 with carrier concentration above 1019 cm−3. These results also indicate that the powder metallurgy parameters provide potentialities for further increase of the high efficiency of energy conversion in PbTe materials.

To analyze the medication features and the regularity of prescriptions of traditional Chinese medicine in treating patients with Qi-deficiency and blood-stasis syndrome of chronic heart failure based on modern literature. In this article, CNKI Chinese academic journal database, Wanfang Chinese academic journal database and VIP Chinese periodical database were all searched from January 2000 to December 2015 for the relevant literature on traditional Chinese medicine treatment for Qi-deficiency and blood-stasis syndrome of chronic heart failure. Then a normalized database was established for further data mining and analysis. Subsequently, the medication features and the regularity of prescriptions were mined by using traditional Chinese medicine inheritance support system(V2.5), association rules, improved mutual information algorithm, complex system entropy clustering and other mining methods. Finally, a total of 171 articles were included, involving 171 prescriptions, 140 kinds of herbs, with a total frequency of 1 772 for the herbs. As a result, 19 core prescriptions and 7 new prescriptions were mined. The most frequently used herbs included Huangqi(Astragali Radix), Danshen(Salviae Miltiorrhizae Radix et Rhizoma), Fuling(Poria), Renshen(Ginseng Radix et Rhizoma), Tinglizi(Semen Lepidii), Baizhu(Atractylodis Macrocephalae Rhizoma), and Guizhi(Cinnamomum Ramulus). The core prescriptions were composed of Huangqi(Astragali Radix), Danshen(Salviae Miltiorrhizae Radix et Rhizoma) and Fuling(Poria), etc. The high frequent herbs and core prescriptions not only highlight the medication features of Qi-invigorating and blood-circulating therapy, but also reflect the regularity of prescriptions of blood-circulating, Yang-warming, and urination-promoting therapy based on syndrome differentiation. Moreover, the mining of the new prescriptions provide new reference and inspiration for clinical treatment of various accompanying symptoms of chronic heart failure. In conclusion, this article provides new reference for traditional Chinese medicine in the treatment of chronic heart failure.

Cd in soil samples at 12 sites from Dabizhuang, Tianjin, was analyzed with the sequential extraction. According to its area types, the Ssites are divided into 5 groups. The test of Cd in soil was carried out by using atomic absorption spectrometry. The analyzed results showed that the area around the factory was seriously polluted, and sewage irrigation was moderately polluted. Cd is mainly existed as Carbonate and ionic form in soil which are the non-stable species.