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Copper is an essential trace element for the human body, and its requirement for optimistic immune functions has been recognized for decades. How copper is involved in the innate immune pathway, however, remains to be clarified. Here, we report that copper serves as a signal molecule to regulate the kinase activity of alpha-kinase 1 (ALPK1), a cytosolic pattern-recognition receptor (PRR), and therefore promotes host cell defense against bacterial infection. We show that in response to infection, host cells actively accumulate copper in the cytosol, and the accumulated cytosolic copper enhances host cell defense against evading pathogens, including intracellular and, unexpectedly, extracellular bacteria. Subsequently, we demonstrate that copper activates the innate immune pathway of host cells in an ALPK1-dependent manner. Further mechanistic studies reveal that copper binds to ALPK1 directly and is essential for the kinase activity of this cytosolic PRR. Moreover, the binding of copper to ALPK1 enhances the sensitivity of ALPK1 to the bacterial metabolite ADP-heptose and eventually prompts host cells to elicit an enhanced immune response during bacterial infection. Finally, using a zebrafish in vivo model, we show that a copper-treated host shows an increased production of proinflammatory cytokines, enhanced recruitment of phagosome cells, and promoted bacterial clearance. Our findings uncover a previously unrecognized role of copper in the modulation of host innate immune response against bacterial pathogens and advance our knowledge on the cross talk between cytosolic copper homeostasis and immune system. [ABSTRACT FROM AUTHOR]

The thermodynamic properties of one-dimensional (1-D) hydrogenic impurity in Nitride semiconductor quantum well have been investigated. Firstly, using a combination of the linear variational approach and the effective mass approximation, we obtain the eigen-energy of hydrogenic impurity states in AlN, GaN and InN quantum wells. Subsequently, we explore the quantum size effect on the thermodynamic properties of these low-dimensional semiconductor structures, revealing some novel and intriguing phenomena. It is found as the width of the quantum well is increased, the energy of hydrogenic impurity gets decreased, however, the thermodynamic parameters, such as the average energy, entropy and heat capacity of the hydrogenic impurity become increased. The physical origins of these peculiar phenomena are attributed to the competitive mechanism between the quantum confinement effect and Coulombic interaction between the electron and impurity. Finally, by conducting a comprehensive comparison of the thermodynamic parameters among GaN, InN, and AlN quantum wells, we propose an innovative strategy for modulating the thermodynamic properties of these low-dimensional semiconductor structures. This manipulation can be achieved not only through external factors such as temperature and quantum well size, but also by altering internal variables like the effective mass and relative dielectric constant of the semiconductor material. This study not only advances our understanding of the thermodynamic properties of hydrogenic impurities in semiconductor quantum wells, but also provides some theoretical guidance for practical applications in fields such as semiconductor physics, condensed matter physics, chemical physics, etc. [ABSTRACT FROM AUTHOR]

Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is a highly aggressive lymphoma with a poor response to chemotherapy, frequent relapses, low overall survival, and poor prognosis, and is the most common form of PTCL. For relapsed/ refractory(R/R) PTCLs, the efficacy of traditional chemotherapy is even worse, so clinical trials and new drugs become their therapeutic hope. The patient was a 43-year-old woman who complained of enlarged superficial lymph nodes (submandibular, neck, axillary, epitrochlear, and groin) and progressive aggravation of skin lesions, facial and limb edema, and subcutaneous masses. Histological analyses of lymph nodes and skin biopsy were suggestive of PTCL-NOS. The patient experienced failure of six lines of therapy, including multiple cycles of chemotherapy, chidamide, and BCL-2 inhibitors therapy, surprisingly, has a good response to PD-1 inhibitor combined with decitabine. We intend to provide some references for clinical practice. [ABSTRACT FROM AUTHOR]

The giant freshwater prawn (Macrobrachium rosenbergii) is a commercially cultured species in China. A sex chromosome-specific marker is crucial for sex identification and distinguishing sex chromosomes. Here, based on the results of reduced-representation genome sequencing and genome survey of M. rosenbergii, we identified steady sex-linked markers. Further nucleotide alignment analysis revealed 83.42% nucleotide similarity between the amplified W- and Z-chromosome fragments. qPCR confirmed that Z chromosome-specific fragments were present in males approximately twice as often compared to females. Similarly, the W chromosome-specific fragments were present in super females approximately twice as often compared to females. Our findings elucidate the ZW/ZZ sex determination type and contribute to exploring sex-related or sex-determining genes present on the sex chromosomes of M. rosenbergii. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the gene mutation, immune infiltration and tumor growth of primary tumor and distant tumor under different treatment modes. Materials and Methods: Twenty B16 murine melanoma cells were injected subcutaneously into the of both sides of the thigh, simulating a primary tumor and a secondary tumor impacted by the abscopal effect, respectively. They were divided into blank control group, immunotherapy group, radiotherapy group, and radiotherapy combined immunotherapy group. During this period, tumor volume was measured, and RNA sequencing was performed on tumor samples after the test. R software was used to analyze differentially expressed genes, functional enrichment, and immune infiltration. Results: We found that any treatment mode could cause changes in differentially expressed genes, especially the combination treatment. The different therapeutic effects might be caused by gene expression. In addition, the proportions of infiltrating immune cells in the irradiated and abscopal tumors were different. In the combination treatment group, T-cell infiltration in the irradiated site was the most obvious. In the immunotherapy group, CD8+ T-cell infiltration in the abscopal tumor site was obvious, but immunotherapy alone might have a poor prognosis. Whether the irradiated or abscopal tumor was evaluated, radiotherapy combined with anti-programmed cell death protein 1 (anti- PD-1) therapy produced the most obvious tumor control and might have a positive impact on prognosis. Conclusion: Combination therapy not only improves the immune microenvironment but may also have a positive impact on prognosis. [ABSTRACT FROM AUTHOR]

Shape-selective stannosilicates have been post-synthesized for the hydration of epoxide to diols. A simple acid treatment has been employed to remove extensively the interlayer double four ring units, converting the three-dimensional (3D) UTL germanosilicate into a 2D layered IPC-1P intermediate. Isomorphous incorporation of tetrahedrally coordinated Sn active centers was realized via solid-liquid treatment of IPC-1P with diammonium hexachlorostannate aqueous solution, which was accompanied by the spontaneous condensation of neighboring silica-rich cfi layers upon calcination and structural construction of a 3D PCR structure. Sn-PCR stannosilicates with tunable Sn contents were thus prepared. With Sn-derived robust Lewis acidity confined in the intersecting 10- and 8-ring channels, the Sn-PCR (Si/Sn molar ratio of 77) catalyst served as a shape-selective nanoreactor for the hydration of ethylene oxide (EO) into ethylene glycol (EG), exhibiting a remarkable EO conversion (99.5 %) as well as a steady EG selectivity (>98.4 %) at greatly reduced H2 O/EO molar ratio and near-ambient reaction temperature. [ABSTRACT FROM AUTHOR]

Betanin is a member of natural pigment betacyanins family and has extensive application in the food industry as an important natural red food colorant. Its relatively inefficient production in nature however hampers access to this phytochemicals through traditional crop-based manufacturing. Microbial bioproduction therefore represents an attractive alternative. Here, we present the construction of a Saccharomyces cerevisiae strain for betanin production. Through minimizing metabolic crosstalk, screening and modifying biosynthetic enzymes, enhancing pathway flux and optimizing fermentation conditions, a final titer of betanin of 28.7 mg/L was achieved from glucose at 25 °C in baffled shake-flask, which is the highest reported titer produced by yeast to our knowledge. This work provides a promising step towards developing synthetic yeast cell factories for de novo biosynthesis of value-added betanin and other betacyanins. [ABSTRACT FROM AUTHOR]

Based on the tumor hypoxic microenvironment and the new programmed cell death mode of combined ferroptosis, an angelica polysaccharide-based nanocarrier material was synthesized. The polymer contains hydrophilic angelica polysaccharide (ASP) that is linked by azobenzene (AZO) linker with ferrocene (Fc), and then the side chain was covalently modified with arachidonic acid (AA). It was postulated that the polymer micelles could work as an instinctive liver targeting drug delivery carrier, owing to the existence of ASP with liver targeting. Moreover, the aim was to engineer hypoxia-responsive polymer micelles which was modified by AA, for selective enhancement of ferroptosis in solid tumor, via diminishing glutathione (GSH) under hypoxia. Finally, we synthesized the amphiphilic polymer micelles AA/ASP-AZO-Fc (AAAF) by self-assembling. The structure of AAAF was confirmed by 1HNMR and FT-IR. Then, we exemplified the hydrophobic medication curcumin into polymer micelles AAAF@Cur, which has smooth and regular spheres. In vitro release test affirmed that AAAF@Cur can achieve hypoxia response to drug release. In addition, a series of cell experiments confirmed that hypoxia could enhance cell uptake and effectively improve the proliferation inhibitory activity of HepG2 cells. In conclusion, AAAF, as an effective cell carrier, is expected to develop in sensitizing ferroptosis and anti-tumor. [ABSTRACT FROM AUTHOR]

Conditional gene inactivation and restoration are powerful tools for studying gene functions in the nervous system and for modeling neuropsychiatric diseases. The combination of the two is necessary to interrogate specific cell types within defined developmental stages. However, very few methods and animal models have been developed for such purpose. Here we present a versatile method for conditional gene inactivation and in situ restoration through reversibly inverting a critical part of its endogenous genomic sequence by Cre- and Flp-mediated recombinations. Using this method, we generated a mouse model to manipulate Mecp2, an X-linked dosage-sensitive gene whose mutations cause Rett syndrome. Combined with multiple Creand Flp-expressing drivers and viral tools, we achieved efficient and reliable Mecp2 inactivation and restoration in the germline and several neuronal cell types, and demonstrated phenotypic reversal and prevention on cellular and behavioral levels in male mice. This study not only provides valuable tools and critical insights for Mecp2 and Rett syndrome, but also offers a generally applicable strategy to decipher other neurologic disorders. [ABSTRACT FROM AUTHOR]

The South American tomato pinworm, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), has invaded most Afro-Eurasian countries. Since its first detection in China in late 2017, this pest has been now present in nearly 20 provinces/prefectures in China and is threating tomato and other Solanaceous crops such as potato, eggplant, and tobacco. Here, we provide a timely review on the current distribution, damage, management, and research in China. A standard survey form was designed and 30 answered surveys from 25 provinces have been received. The data showed that the damage has been witnessed in most of the regions despite that the severities vary among the regions. The management is chemicalcontrol biased, and more efforts are needed to increase the adoption of non-chemical alternatives in the Integrated Pest Management packages. An Integrated Pest Management (IPM) package called "CAMEFA" was developed and demonstrated in Yunnan and Xinjiang, the two earliest regions for the invasion. Yet, the adoption by local growers is still limited. Besides T. absoluta, we suggest a multi-pest approach by combining IPM tactics coping with other major insect pests sharing the crop. Lastly, international projects are deemed to serve as key lever for promoting IPM of T. absoluta and other invasive insect pests. [ABSTRACT FROM AUTHOR]

Rhododendron micranthum is an evergreen shrub species widely distributed in China that has high ornamental and medicinal value. However, there is a lack of molecular and genomic data for this plant, which severely restricts the development of its relevant research. The objective of the present study was to conduct a first genomic survey of R. micranthum and determine its whole-genome sequencing scheme. Next-generation sequencing (Illumina Hi-Seq Xten) was used to measure the genome size of R. micranthum, K-mer analysis were employed to investigate its genomic profile. Finally, we conducted bioinformatics methods to performed SSR (simple sequence repeat) prediction based on the genomic data. The genome size of R. micranthum was estimated to be 554.22 Mb. The heterozygosity ratio was 0.93%, and the sequence repeat ratio was calculated to be 49.17%. The clean reads of R. micranthum were assembled into 2281551 scaffolds with a N50 value of 916 bp. A total of 479724 SSR molecular markers were identified in the R. micranthum genome, and 871656 pairs of primers designed for application. Among of them, 100 primer pairs were validated, and 71 primer pairs were successfully amplified. In summary, the R. micranthum genome is complex with high heterozygosity and low repeated sequences. In future whole-genome research in R. micranthum, higher-depth '2+3' (Illumina+PacBio) sequencing may yield better assembly results. [ABSTRACT FROM AUTHOR]

[Objectives] To investigate the mechanism of miR-23 a in the proliferation of human tongue squamous cell carcinoma cells. [Methods] Clinical tissue samples of tongue squamous cell carcinoma were collected and Tca8113 and CAL27 were cultured. Real-time quantitative PCR was performed to detect the expressions of miR-23 a and PPP2R5E in clinical tissue samples of tongue squamous cell carcinoma. MTT assay, colony formation assay and growth curve assay were used to detect the effect of miR-23 a and PPP2R5E on the proliferation of human tongue squamous carcinoma cell. Luciferase reporter assay verified the regulatory relationship between miR-23 a and PPP2R5E. [Results] The expression of miR-23 a in tongue squamous cell carcinoma was significantly up-regulated（P<0.01）. miR-23 a promoted the proliferation of tongue squamous cell carcinoma cells. Bioinformatics prediction and luciferin reporting experiments showed that PPP2R5E was a direct target gene of miR-23 a. The expression of PPP2R5E was decreased in tongue squamous cell carcinoma. PPP2R5E inhibited the proliferation of tongue squamous cell carcinoma cells. Overexpression of PPP2R5E can reverse the proliferation promoting effect of miR-23 a on tongue squamous cell carcinoma cells. [Conclusions] miR-23 a can promote the proliferation of tongue squamous cell carcinoma cells through PPP2R5E and miR-23 a plays an oncogene role in the occurrence and development of tongue squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have uncovered a progestin-only contraceptive association with an increased risk of diabetes, but limited studies have explored the relationship of endogenous progesterone and pregnenolone levels with diabetes status. A case-control study was conducted in Henan Rural Cohort (register number: ChiCTROOC- 15006699) to evaluate the dose-response independent and int eractive relationship of progesterone and pregnenolone levels with prediabetes and type 2 diabetes mellit us (T2DM) in Chinese rural population. Design: A case-control study. Methods: A total of 798 T2DM patients, 779 prediabetes patients, and 78 2 individuals with normal fasting plasma glucose were included in this study. Serum progesterone and pre gnenolone were detected by liquid chromatographytandem mass spectrometry. Logistic regression and restricted cu bic splines were used to assess the independent effects of progesterone and pregnenolone on prediabetes and T2DM. Interactive plots were employed to examine the interaction effects of progesterone and pregnenolone. Results: Progesterone in the fourth versus first quartile was positively associated with prediabetes (odds ratio (OR) (95% CI): 2.66 (1.99-3.55)) and T2DM (OR (95% CI): 6.41 (4.57-8 .98)), whereas pregnenolone in the fourth versus first quartile was inversely related to prediabetes (OR (95% CI): 0.2 3 (0.16-0.33)) and T2DM (OR (95% CI): 0.44 (0.31-0.62)). Additionally, the nonlinear dose-response associations between progesterone and pregnenolone with prediabetes and T2DM were found. Interactive effects of progesterone and pre gnenolone on prediabetes and T2DM were observed, and these significant associations remained in gender- stratified analysis. Conclusions: Prediabetes and T2DM were positively linked to serum concentra tion of progesterone and negatively related to pregnenolone in a dose-response manner in Chinese ru ral population. [ABSTRACT FROM AUTHOR]

In this paper, we give a new proof for the Daniel-Stone theorem for random probability measures without using the result of the classical Daniel-Stone theorem. [ABSTRACT FROM AUTHOR]

Transcriptional repression in multicellular organisms orchestrates dynamic and precise gene expression changes that enable complex developmental patterns. Here, we present phenotypic and molecular characterization of the maize (Zea mays) transcriptional corepressor RAMOSA1 ENHANCER LOCUS2 (REL2), a unique member of the highly conserved TOPLESS (TPL) family. Analysis of single recessive mutations in rel2 revealed an array of vegetative and reproductive phenotypes, many related to defects in meristem initiation and maintenance. To better understand how REL2-mediated transcriptional complexes relate to rel2 phenotypes, we performed protein interaction assays and transcriptional profiling of mutant inflorescences, leading to the identification of different maize transcription factors and regulatory pathways that employ REL2 repression to control traits directly impacting maize yields. In addition, we used our REL2 interaction data to catalog conserved repression motifs present on REL2 interactors and showed that two of these, RLFGV- and DLN-type motifs, interact with the C-terminal WD40 domain of REL2 rather than the N terminus, which is known to bind LxLxL EAR motifs. These findings establish that the WD40 domain of TPL family proteins is an independent protein interaction surface that may work together with the N-terminal domain to allow the formation of large macromolecular complexes of functionally related transcription factors. [ABSTRACT FROM AUTHOR]

In recent years, crystalline polyoxotitanium clusters (PTCs) have attracted increasing attention as a new kind of promising crystalline material. In this work, a PTC stabilized by phenylphosphonate ligands, i.e. hexa-μ-isopropanolatohexaisopropanolatodi-μ3-oxido-hexa-μ3-phenylphosphonato-heptatitanium tetrahydrate, [Ti7(μ3-O)2(O3P-Phen)6(OiPr)12]μ4H2O [PTC-54; H2O3P-Phen is phenylphosphonic acid, C6H5PO(OH)2, and HOiPr is isopropanol, C3H7OH], was obtained successfully through a facile one-step solvothermal reaction. The dumbbell-like core structure of PTC-54 can be described as two trinuclear {Ti3(μ3-O)} building units combined together by six phenylphosphonate ligands and one additional Ti atom, giving rise to a Ti7 cluster. Adjacent molecules of PTC-54 are further connected through л-л interactions between the phenyl groups to form a supramolecular one-dimensional chain. [ABSTRACT FROM AUTHOR]

A number of studies indicated that apoptosis, a specific type of programmed cell death, contributed to the loss of dopaminergic neurons during progression of Parkinson's disease (PD). Previously, the authors of the present study demonstrated that apoptosis of dopaminergic neurons was mainly achieved via the mitochondria-mediated apoptosis pathway, however, the precise molecular mechanisms remain to be elucidated. The present study aimed to determine whether mitofusin-2 (MFN2), a mitochondrial protein, participated in the apoptosis of dopaminergic neurons in a cellular model of PD induced by rotenone. The present study demonstrated that the expression of MFN2 was relatively stable following treatment with rotenone. Lentiviral knockdown and overexpression experiments for the first time, to the best of the authors knowledge, revealed that MFN2 prevented rotenone-induced cell death by amelioration of apoptosis. These results revealed a protective role of MFN2 against apoptosis in an in vitro model of PD and may be used to establish MFN2 as a potential therapeutic target for the treatment of this disease. [ABSTRACT FROM AUTHOR]

Bearings are an important part of mechanical equipment and it will cause a series of mechanical failures once the malfunction of bearing occurs. Rotor unbalance is the most common type of bearing failure; thus the assessment of bearing rotor unbalance is essential to maintain the normal operation of mechanical. In this paper, a method based on Welch power spectral density estimate (Welch-PSD) and stacked automatic encoder (SAE) is proposed to achieve state assessment of bearing rotor static unbalance by processing the two-way vibration signals collected by the acceleration sensor installed in the vertical and horizontal directions of the bearing. Firstly, the Welch-PSD method is used to decompose the vibration signal to obtain the power spectral density, and the vibration power of the working frequency is taken as the feature. Then, the Stacked Auto-Encoder method is introduced to assessment the bearing rotor unbalance state. This paper designs an experiment of rotor unbalance fault in different degree to verify the accuracy of the designed method. The experimental results show that the Welch-PSD method can accurately extract the rotor unbalance fault feature. In addition, the SAE neural network can apply the fault feature to accurately assessment the bearing rotor unbalance degree. [ABSTRACT FROM AUTHOR]

[Objectives] The research aimed to optimize extraction process of fucoidan from Sargassum fusiforme (FSF) and study its moisturizing performance. [Methods] Extracting condition of FSF by cellulase hydrolysis-ultrasonic assisted extraction method was optimized. The influences of solvent pH, enzyme dosage, extraction temperature, cellulose hydrolysis time, ultrasonication time, and the ratio of material to liquid on FSF were investigated by single factor and orthogonal experiments. [Results] The optimum extraction conditions were as followings; pH, 4.5; enzyme dosage, 1 %; extraction temperature, 40°C; cellulose hydrolysis time, 2 h; ultrasonic time, 15 min; and the ratio of material to liquid, 1:10 (g: mL). Under the optimal condition, the extraction yield of FSF was 8.50%, RSD = 2.74%. The short-time hygroscopicity (within 8 h) of crude extract of fucoidan from 5. fusiforme (CEFSF) was better than glycerin, butanediol, and sodium alginate, and the moisture retention capacity of 1% CEFSF aqueous solution was better than 1% butanediol or 1% sodium alginate, and was equal to 5% glycerin under relative humidity of 43% and 81%. The determination results of skin moisture content and transepidermal water loss rate (TEWL) showed that; 5% CEFSF solution had good moisturizing effect. [Conclusions] The research could provide certain reference for deep development of S. fusiforme. [ABSTRACT FROM AUTHOR]

Fault diagnosis for cylindrical roller bearing is of great significance for industry. In order to excavate the features of the vibration signal adequately, and to construct an effective classifier for complex vibration signals, this paper proposed a new fault diagnosis method based on Variational Mode Decomposition (VMD), Singular Value Decomposition (SVD) and Adaboost classifier. Firstly, the VMD was applied to decompose the sampled vibration signal in time-frequency domain. Subsequently, the features were extracted by using SVD. Finally, the constructed Adaboost classifier were employed to fault detection and diagnosis, which were trained by using the extracted features. Experimental data measured in a rotating machinery fault diagnosis experiment platform was used to verify the proposed method. The results demonstrate that the proposed method was effective to detect and diagnose the outer ring fault and rolling element fault in cylindrical roller bearing. [ABSTRACT FROM AUTHOR]

Background: Dof (DNA binding with one finger) proteins, a class of plant-specific transcription factors which contain a conserved C2-C2-type zinc finger domain, are involved in many fundamental processes. In the Arabidopsis photoperiod response pathway, CDF (CYCLING DOF FACTOR) proteins have a primary role as acting via transcriptional repression of the direct FLOWERING LOCUS T (FT) activator CONSTANS (CO). Our previous study indicated that one of CDF homologs, OsDOf12, was involved in photoperiodic flowering. However, the functional characterization of other rice CDF like genes is still in progress. Here, we characterized the function of OsDof4 in rice. Results: Phylogenic analysis indicated that OsDof4 is closely clustered into the same subgroup with CDFs and OsDof12. The subcellular localization experiment and transcriptional activity assay suggested that OsDof4 may function as a transcription factor. The diurnal expression pattern indicated that OsDof4 was regulated by endogenous circadian clock. Overexpression of OsDof4 led to earlier flowering under natural long-day field conditions (NLDs) and late flowering under natural short-day field conditions (NSDs), respectively. We compared the expression level of key floral genes in vector line and OsDof4-ox lines grown under long-day conditions (LDs) and short-day conditions (SDs). Real-time q-PCR results demonstrated that under LDs, Hd3a, RFT1 and Ehd1 were up-regulated whereas under SDs they were down-regulated. Hd1 was down-regulated at dusk period independent of photoperiods. Conclusions: Taken these results together, we may speculate that the abnormal flowering responses in OsDof4-ox plants under LDs and SDs might be mediated by Ehd1 and Hd1. [ABSTRACT FROM AUTHOR]

Florfenicol (FF, C12H14Cl2FNO4S), an emerging halogenated organic contaminant of concern was effectively degraded in water by sulfidized nanoscale zerovalent iron (S-nZVI). Sulfidized nZVI (62.5 m² g-1) that was prepared using a one-step method resulted in small Fe0/Fe-sulfide particles that were more stable against aggregation than unsulfidized nZVI (10.2 m² g-1). No obvious removal of FF was observed by unsulfidized nZVI. S-nZVI degraded FF, having a surface area normalized reaction rate constant of 3.1 x 10-4 L m-2 min-1. The effects of the S/Fe molar ratio, initial FF concentration, initial pH, temperature, and water composition on the removal of FF by S-nZVI, and on the formation of reaction products, were systematically investigated. Both dechlorination and defluorination were observed, resulting in four degradation products (C12H15ClFNO4S, C12H16FNO4S, C12H17NO4S, and C12H17NO5S). High removal efficiencies of FF by S-nZVI were achieved in groundwater, river water, seawater, and wastewater. The reactivity of S-nZVI was relatively unaffected by the presence of both dissolved ions and organic matter in the waters tested. [ABSTRACT FROM AUTHOR]

Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. Although EpCAM glycosylation is supposed to be associated with its function, the contribution of N-glycosylation to its function remains unclear. Here we analyzed cell adhesion ability of EpCAM in breast cancer cells. The results showed that EpCAM expression was associated with cell adhesion and N-glycosylation mutation of EpCAM decreased adhesion capacity. N-glycosylation mutation of EpCAM was correlated with lower levels of integrin β1 and fibronectin. We also found that effect of N-glycosylation of EpCAM on cell adhesion was regulated via FAK/Akt/Gsk-3β/β-catenin signaling pathway, which further adjusted MMP2/9 expression and activities. Our studies identified the characteristics and function of EpCAM glycosylation sites on breast cancer cell adhesion. These data could potentially clarify molecular regulation of EpCAM by N-glycosylation and intensify our understanding of the utility of glycosylated EpCAM as a target for breast cancer therapy. [ABSTRACT FROM AUTHOR]

The protective effects of preprocedural esmolol on myocardial injury and hemodynamics have not, to date, been investigated in patients who were scheduled for cardiac surgeries under a cardiopulmonary bypass (CPB). A pilot randomized controlled trial was performed at The First Affiliated Hospital of Dalian Medical University (Dalian, China). Patients scheduled for elective open-heart surgeries under CBP were included, and were randomized to esmolol and control groups. For patients in the esmolol groups, intravenous esmolol (70 μg/kg/min) was administered at the time of incision until CPB was performed. For patients assigned to the control group, equal volumes of 0.9% saline were administered. Markers of myocardial injury and hemodynamic parameters were observed until 12 h post surgery. A total of 24 patients were included in the present study. No significant differences in hemodynamic parameters, including the central venous pressure and heart rate, were detected between patients in the two groups during the perioperative period or within the first 12 h post-surgery (P>0.05), except for the mean arterial pressure, which was higher in the esmolol group compared with the control group at 5 and 12 h post-surgery (P<0.05). However, the serum level of cardiac troponin I was higher in patients of the control group compared with those of the esmolol group during the preoperative period (P<0.05). Although creatinine kinase was significantly different at T2 between the two groups, its MB isoenzyme was not significantly different between the groups (P>0.05). In addition, administration of esmolol was not associated with an increased risk for severe complications and adverse events in these patients. In conclusion, preoperative esmolol may be an effective and safe measure of myocardial protection for patients who undergo elective cardiac surgeries under CBP. [ABSTRACT FROM AUTHOR]

Micromechanical exfoliation of two-dimensional (2D) van der Waals materials has triggered an explosive interest in 2D material research. The extension of this idea to 1D van der Waals materials, possibly opening a new arena for 1D material research, has not yet been realized. In this paper, we demonstrate that 1D nanowire with sizes as small as six molecular ribbons, can be readily achieved in the Ta2(Pd or Pt)3Se8 system by simple micromechanical exfoliation. Exfoliated Ta2Pd3Se8 nanowires are n-type semiconductors, whereas isostructural Ta2Pt3Se8 nanowires are p-type semiconductors. Both types of nanowires show excellent electrical switching performance as the channel material for a field-effect transistor. Low-temperature transport measurement reveals a defect level inherent to Ta2Pd3Se8 nanowires, which enables the observed electrical switching behavior at high temperature (above 140 K). A functional logic gate consisting of both n-type Ta2Pd3Se8 and p-type Ta2Pt3Se8 field-effect transistors has also been successfully achieved. By taking advantage of the high crystal quality derived from the parent van der Waals bulk compound, our findings about the exfoliated Ta2(Pd or Pt)3Se8 nanowires demonstrate a new pathway to access single-crystal 1D nanostructures for the study of their fundamental properties and the exploration of their applications in electronics, optoelectronics, and energy harvesting. [ABSTRACT FROM AUTHOR]

Arsenic hyperaccumulator Pteris vittata (PV) is efficient in taking up As and nutrients from As-contaminated soils. We evaluated the mechanisms used by PV to mobilize As and Fe by examining the impacts of As and root exudates on FeAsO4 solubilization, and As and Fe uptake in four plants: Ashyperaccumulators PV and Pteris multifida (PM), nonhyperaccumulator Pteris ensiformis (PE), and angiosperm plant tomato (Solanum lycopersicum). Phytate and oxalate were dominant in fern plants (>93%), which were 50--83, 15--42, and 0--32 mg kg-1 phytate and 10--15, 7--26, and 4--12 mg kg-1 oxalate for PV, PM, and PE respectively, with higher As inducing greater phytate exudation and no phytate being detected in tomato exudates. PV treated with phytate+FeAsO4 had higher As and Fe contents and larger biomass than phytate or FeAsO4 treatment, which were 340 vs 20 and 130 mg kg-1 As in the fronds and 7900 vs 1600 and 4100 mg kg-1 Fe in the roots. We hypothesized that As-induced phytate exudation helped PV to take up Fe and As from insoluble FeAsO4 and promoted PV growth. Our study suggests that phytate exudation may be special to fern plants, which may play an important role in enhancing As and nutrient uptake by plants, thereby increasing their efficiency in phytoremediation of As-contaminated soils. [ABSTRACT FROM AUTHOR]

The two-component system (TCS), which comprises histidine kinases (HKs), phosphotransfers (HPs), and response regulator proteins (RRs), plays pivotal roles in regulating plant growth, development, and responses to biotic and abiotic stresses. TCS genes have been comprehensively identified and investigated in various crops but poorly characterized in tomato. In this work, a total of 65 TCS genes consisting of 20 HK(L)s, six HPs, and 39 RRs were identified from tomato genome. The classification, gene structures, conserved domains, chromosome distribution, phylogenetic relationship, gene duplication events, and subcellular localization of the TCS gene family were predicted and analyzed in detail. The amino acid sequences of tomato TCS family members, except those of type-B RRs, are highly conserved. The gene duplication events of the TCS family mainly occurred in the RR family. Furthermore, the expansion of RRs was attributed to both segment and tandem duplication. The subcellular localizations of the selected green fluorescent protein (GFP) fusion proteins exhibited a diverse subcellular targeting, thereby confirming their predicted divergent functionality. The majority of TCS family members showed distinct organ- or development-specific expression patterns. In addition, most of TCS genes were induced by abiotic stresses and exogenous phytohormones. The full elucidation of TCS elements will be helpful for comprehensive analysis of the molecular biology and physiological role of the TCS superfamily. [ABSTRACT FROM AUTHOR]

Horizontal cells form the first laterally interacting network of inhibitory interneurons in the retina. Dopamine released onto horizontal cells under photic and circadian control modulates horizontal cell function. Using isolated, identified horizontal cells from a connexin-57-iCre × ROSA26-tdTomato transgenic mouse line, we investigated dopaminergic modulation of calcium channel currents (ICa) with whole cell patch-clamp techniques. Dopamine (10 μM) blocked 27% of steadystate ICa, an action blunted to 9% in the presence of the L-type Ca channel blocker verapamil (50 μM). The dopamine type 1 receptor (D1R) agonist SKF38393 (20 μM) inhibited ICa by 24%. The D1R antagonist SCH23390 (20 μM) reduced dopamine and SKF38393 inhibition. Dopamine slowed ICa activation, blocking ICa by 38% early in a voltage step. Enhanced early inhibition of ICa was eliminated by applying voltage prepulses to +120 mV for 100 ms, increasing ICa by 31% and 11% for early and steady-state currents, respectively. Voltage-dependent facilitation of ICa and block of dopamine inhibition after preincubation with a Gβγ-blocking peptide suggested involvement of Gβγ proteins in the D1R-mediated modulation. When the G protein activator guanosine 5'-O-(3-thiotriphosphate) (GTPγS) was added intracellularly, ICa was smaller and showed the same slowed kinetics seen during D1R activation. With GTPγS in the pipette, additional block of ICa by dopamine was only 6%. Strong depolarizing voltage prepulses restored the GTPγS-reduced early ICa amplitude by 36% and steady-state ICa amplitude by 3%. These results suggest that dopaminergic inhibition of ICa via D1Rs is primarily mediated through the action of Gβγ proteins in horizontal cells. [ABSTRACT FROM AUTHOR]

Aging is a critical risk factor in idiopathic pulmonary fibrosis (IPF). Dysfunction and loss of type 2 alveolar epithelial cells (AEC2s) with failed regeneration is a seminal causal event in the pathogenesis of IPF, although the precise mechanisms for their regenerative failure and demise remain unclear. To systematically examine the genomic program changes of AEC2s in aging and after lung injury, we performed unbiased single-cell RNA-seq analyses of lung epithelial cells from uninjured or bleomycin-injured young and old mice, as well as from lungs of IPF patients and healthy donors. We identified three AEC2 subsets based on their gene signatures. Subset AEC2-1 mainly exist in uninjured lungs, while subsets AEC2-2 and AEC2-3 emerged in injured lungs and increased with aging. Functionally, AEC2 subsets are correlated with progenitor cell renewal. Aging enhanced the expression of the genes related to inflammation, stress responses, senescence, and apoptosis. Interestingly, lung injury increased aging-related gene expression in AEC2s even in young mice. The synergistic effects of aging and injury contributed to impaired AEC2 recovery in aged mouse lungs after injury. In addition, we also identified three subsets of AEC2s from human lungs that formed three similar subsets to mouse AEC2s. IPF AEC2s showed a similar genomic signature to AEC2 subsets from bleomycin-injured old mouse lungs. Taken together, we identified synergistic effects of aging and AEC2 injury in transcriptomic and functional analyses that promoted fibrosis. This study provides new insights into the interactions between aging and lung injury with interesting overlap with diseased IPF AEC2 cells. [ABSTRACT FROM AUTHOR]

The discovery of photonic crystals (PCs) enables the manipulation of photons and opens an avenue to design nanostructured materials for a variety of optical devices. Due to the existence of surface plasmon polariton, metallic PCs exhibit higher efficiency and better power durability. Despite this, the costly and inefficient fabricating methods severely limit their applications. In the present work, large-area metallic glass (MG) PCs consisting of uniform rods with diameter of ~ 350 nm and height of ~ 100 nm have been prepared through the die imprinting of Pd40.5Ni40.5Si4.5P14.5 MGs with Si templates. The prepared MG PC exhibits a periodicity of 1.580 ± 0.002 µm, and possesses very low linear shrinkage of 11 nm as well as a relative linear shrinkage rate of 0.691%, which is much lower than those of the crystalline PCs under similar fabrication conditions. Uniform structural colors were observed on the surface of the MG PC under illuminating by fluorescent lamp light. Besides, polymeric PCs were successfully prepared by hot embossing from the MG PC. The die imprinting of MGs offers an inexpensive, effective and one-step approach for producing large-area and high-quality metallic PCs and may shed new insights on both scientific fundamentals and technological innovations in the PC area. [ABSTRACT FROM AUTHOR]

A ratiometric thermometer based on a mixed-metal LnIII metal-organic framework is reported that has good sensitivity in a wide temperature range from 4 to 290 K and a quantum yield of 22% at room temperature. The sensing mechanism in the europium-doped compound Tb0.95Eu0.05HL (H4L = 5-hydroxy-1,2,4-benzenetricarboxylic acid) is based not only on phonon-assisted energy transfer from TbIII to EuIII centers, but also on phonon-assisted energy migration between neighboring TbIII ions. It shows good performance in a wide temperature range, especially in the range 4-50 K, reaching a sensitivity up to 31% K-1 at 4 K. [ABSTRACT FROM AUTHOR]

Synthesis of 5-vinyl-2-norbornenebased on the Diels–Alderreactions of cyclopentadiene (CPD) generated from dicyclopentadiene(DCPD) and 1,3-Butadiene (BD) have been investigated in a continuoustube reactor under high temperature and high pressure. The experimentalresults show that the concentration of main product 5-vinyl-2-norbornene(VNB) increases with the increasing of reaction time at low reactiontemperature. The elevated temperature greatly promotes the synthesisrate of both product VNB and its isomer cis-3a,4,7,7a-tetrahydroindene(THI) and tricyclopentadiene, resulting in a mountain-shaped curveof VNB concentration versus the reaction time. Particularly, it hasbeen confirmed that the trimer (4,4a,4b,5,8,8a,9,9a-octahydro-1H-1,4-methanofluoreneshould be prepared by direct reaction of BD with DCPD rather thanby the reaction of CPD with VNB or THI. This comprehensive study canlay a solid foundation for the process optimization of VNB synthesis. [ABSTRACT FROM AUTHOR]

Megawatt-scale datacenters have emerged to meet the increasing demand for IT applications and services. The hunger for power brings large electricity bills to datacenter operators and causes significant impacts to the environment. To reduce costs and environmental impacts, modern datacenters, such as those of Google and Apple, are beginning to integrate renewable or green energy sources into their power supply. This article investigates the green-energy-aware power management problem for these datacenters and surveys and classifies works that explicitly consider renewable energy and/or carbon emission. Our aim is to give a full view of this problem. Hence, we first provide some basic knowledge on datacenters (including datacenter components, power infrastructure, power load estimation, and energy sources' operations), the electrical grid (including dynamic pricing, power outages, and emission factor), and the carbon market (including cap-andtrade and carbon tax). Then, we categorize existing research works according to their basic approaches used, including workload scheduling, virtual machine management, and energy capacity planning. Each category's discussion includes the description of the shared core idea, qualitative analysis, and quantitative analysis among works of this category. [ABSTRACT FROM AUTHOR]

PPP2R5E belongs to the phosphatase 2A regulatory subunit B family and acts as a tumor suppressor in human cancer. However, the role of PPP2R5E in the tumorigenesis of gastric cancer is unclear. Here, we declare that PPP2R5E is downregulated by miR-23a and induces cell growth inhibition and apoptosis in gastric cancer cells. Furthermore, ASO-miR-23a suppresses tumor growth derived from MGC803 cells in vivo. PPP2R5E is identified as a new target of miR-23a. Moreover, overexpression of PPP2R5E reversed the negative effects of miR-23a. We highlight the significance of miR-23a and PPP2R5E in the proliferation and apoptosis of gastric cancer cells. [ABSTRACT FROM AUTHOR]

Background B-cell lymphoma 6 (BCL6) protein, an evolutionarily conserved zinc finger transcription factor, showed to be highly expressed in various human cancers in addition to malignancies in the lymphoid system. This study investigated the role of BCL6 expression in breast cancer and its clinical significance in breast cancer patients. Methods Expression of BCL6 protein was assessed using in situ hybridization and immunohistochemistry in 127 breast cancer patients and 50 patients with breast benign disease as well as in breast cell lines. Expression of BCL6 was restored or knocked down in two breast cancer cell lines (MCF-7 and T47D) using BCL6 cDNA and siRNA, respectively. The phenotypic change of these breast cancer cell lines was assessed using cell viability MTT, Transwell invasion, colony formation, and flow cytometry assays and in a xenograft mice model. Luciferase reporter gene, immunoblot, and qRT-PCR were used to investigate the molecular events after manipulated BCL6 expression in breast cancer cells. Results BCL6 protein was highly expressed in breast cancer cell lines and tissue specimens and expression of BCL6 protein was associated with disease progression and poor survival of breast cancer patients. In vitro, the forced expression of BCL6 results in increased proliferation, anchorage-independent growth, migration, invasion and survival of breast cancer cell lines, whereas knockdown of BCL6 expression reduced these oncogenic properties of breast cancer cells. Moreover, forced expression of BCL6 increased tumor growth and invasiveness in a nude mouse xenograft model. At the gene level, BCL6 was a target gene of miR-339-5p. Expression of BCL6 induced expression of CXCR4 and cyclinD1 proteins. Conclusions The current study demonstrated the oncogenic property of BCL6 in breast cancer and further study could target BCL6 as a novel potential therapeutic strategy for breast cancer. [ABSTRACT FROM AUTHOR]

Background: B-cell lymphoma 6 (BCL6) protein, an evolutionarily conserved zinc finger transcription factor, showed to be highly expressed in various human cancers in addition to malignancies in the lymphoid system. This study investigated the role of BCL6 expression in breast cancer and its clinical significance in breast cancer patients. Methods: Expression of BCL6 protein was assessed using in situ hybridization and immunohistochemistry in 127 breast cancer patients and 50 patients with breast benign disease as well as in breast cell lines. Expression of BCL6 was restored or knocked down in two breast cancer cell lines (MCF-7 and T47D) using BCL6 cDNA and siRNA, respectively. The phenotypic change of these breast cancer cell lines was assessed using cell viability MTT, Transwell invasion, colony formation, and flow cytometry assays and in a xenograft mice model. Luciferase reporter gene, immunoblot, and qRT-PCR were used to investigate the molecular events after manipulated BCL6 expression in breast cancer cells. Results: BCL6 protein was highly expressed in breast cancer cell lines and tissue specimens and expression of BCL6 protein was associated with disease progression and poor survival of breast cancer patients. In vitro, the forced expression of BCL6 results in increased proliferation, anchorage-independent growth, migration, invasion and survival of breast cancer cell lines, whereas knockdown of BCL6 expression reduced these oncogenic properties of breast cancer cells. Moreover, forced expression of BCL6 increased tumor growth and invasiveness in a nude mouse xenograft model. At the gene level, BCL6 was a target gene of miR-339-5p. Expression of BCL6 induced expression of CXCR4 and cyclinD1 proteins. Conclusions: The current study demonstrated the oncogenic property of BCL6 in breast cancer and further study could target BCL6 as a novel potential therapeutic strategy for breast cancer. [ABSTRACT FROM AUTHOR]

This paper introduces a feature optimization method for robot long-range feature-based visual homing in changing environments. To cope with the changing environmental appearance, the optimization procedure is introduced to distinguish the most relevant features for feature-based visual homing, including the spatial distribution, selection and updating. In the previous research on feature-based visual homing, less effort has been spent on the way to improve the feature distribution to get uniformly distributed features, which are closely related to homing performance. This paper presents a modified feature extraction algorithm to decrease the influence of anisotropic feature distribution. In addition, the feature selection and updating mechanisms, which have hardly drawn any attention in the domain of feature-based visual homing, are crucial in improving homing accuracy and in maintaining the representation of changing environments. To verify the feasibility of the proposal, several comprehensive evaluations are conducted. The results indicate that the feature optimization method can find optimal feature sets for feature-based visual homing, and adapt the appearance representation to the changing environments as well. [ABSTRACT FROM AUTHOR]

Classifier fusion is used to combine multiple classification decisions and improve classification performance. While various classifier fusion algorithms have been proposed in literature, average fusion is almost always selected as the baseline for comparison. Little is done on exploring the potential of average fusion and proposing a better baseline. In this paper we empirically investigate the behavior of soft labels and classifiers in average fusion. As a result, we find that; by proper sampling of soft labels and classifiers, the average fusion performance can be evidently improved. This result presents sampling based average fusion as a better baseline; that is, a newly proposed classifier fusion algorithm should at least perform better than this baseline in order to demonstrate its effectiveness. [ABSTRACT FROM AUTHOR]

Codebook is an effective image representation method. By clustering in local image descriptors, a codebook is shown to be a distinctive image feature and widely applied in object classification. In almost all existing works on codebooks, the building of the visual vocabulary follows a basic routine, that is, extracting local image descriptors and clustering with a user-designated number of clusters. The problem with this routine lies in that building a codebook for each single dataset is not efficient. In order to deal with this problem, we investigate the influence of vocabulary sizes on classification performance and vocabulary universality with the kNN classifier. Experimental results indicate that, under the condition that the vocabulary size is large enough, the vocabularies built from different datasets are exchangeable and universal. [ABSTRACT FROM AUTHOR]

Feature combination is a powerful approach to improve object classification performance. While various combination algorithms have been proposed, average combination is almost always selected as the baseline algorithm to be compared with. In previous work we have found that it is better to use only a sample of the most powerful features in average combination than using all. In this paper, we continue this work and further show that the behaviors of features in average combination can be integrated into the k-Nearest-Neighbor (kNN) framework. Based on the kNN framework, we then propose to use a selection based average combination algorithm to obtain the best classification performance from average combination. Our experiments on four diverse datasets indicate that this selection based average combination performs evidently better than the ordinary average combination, and thus serves as a better baseline. Comparing with this new and better baseline makes the claimed superiority of newly proposed combination algorithms more convincing. Furthermore, the kNN framework is helpful in understanding the underlying mechanism of feature combination and motivating novel feature combination algorithms. [ABSTRACT FROM AUTHOR]

A novel quinic acid derivative, 5-O-trans-o-coumaroylquinic acid methyl ester (1), together with three known ones, chlorogenic acid methyl ester (2), macranthoin F (3) and macranthoin G (4), were isolated from the aerial parts of the invasive plant Ageratina adenophora (Spreng.). The structure of new compound 1 was elucidated on the basis of extensive spectroscopic analysis, including 1D- and 2D-NMR techniques. Compounds 2-4 were isolated from plant A. adenophora for the first time. All the compounds showed in vitro antibacterial activity toward five assayed bacterial strains, especially 3 and 4, which showed in vitro antibacterial activity against Salmonella enterica with MIC values of 7.4 and 14.7 μM, respectively. Compound 1 was further found to display in vitro anti-fungal activity against spore germination of Magnaporthe grisea with an IC50 value 542.3 μM. These four compounds were also tested for their antioxidant activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radical. [ABSTRACT FROM AUTHOR]

It can be argued that an ideal anti-cocaine medication would be one that accelerates cocaine metabolism producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway, i.e., hydrolysis catalyzed by butyrylcholinesterase (BChE) in plasma. However, wild-type BChE has a low catalytic efficiency against naturally occurring (−)-cocaine. Interestingly, wild-type BChE has a much higher catalytic activity against unnatural (+)-cocaine. According to available positron emission tomography (PET) imaging analysis using [11C](−)-cocaine and [11C](+)-cocaine tracers in human subjects, only [11C](−)-cocaine was observed in the brain, whereas no significant [11C](+)-cocaine signal was observed in the brain. The available PET data imply that an effective therapeutic enzyme for treatment of cocaine abuse could be an exogenous cocaine-metabolizing enzyme with a catalytic activity against (−)-cocaine comparable to that of wild-type BChE against (+)-cocaine. Our recently designed A199S/F227A/S287G/A328 W/Y332G mutant of human BChE has a considerably improved catalytic efficiency against (−)-cocaine and has been proven active in vivo. In the present study, we have characterized the catalytic activities of wild-type BChE and the A199S/F227A/S287G/A328 W/Y332G mutant against both (+)- and (−)-cocaine at the same time under the same experimental conditions. Based on the obtained kinetic data, the A199S/F227A/S287G/A328 W/Y332G mutant has a similarly high catalytic efficiency (k cat/K M) against (+)- and (−)-cocaine, and indeed has a catalytic efficiency (k cat/K M =1.84×109 M−1 min−1) against (−)-cocaine comparable to that (k cat/K M =1.37×109 M−1 min−1) of wild-type BChE against (+)-cocaine. Thus, the mutant may be used to effectively prevent (−)-cocaine from entering brain and producing physiological effects in the enzyme-based treatment of cocaine abuse. [ABSTRACT FROM AUTHOR]

Bag-of-visual-words has been shown to be a powerful image representation and attained great success in many computer vision and pattern recognition applications. Usually, for a given dataset, researchers choose to build a specific visual vocabulary from the dataset, and the problem of deriving a universal visual vocabulary is rarely addressed. Based on previous work on the classification performance with respect to visual vocabulary sizes, we arrive at a hypothesis that a universal visual vocabulary can be obtained by taking-into account the similarity extent of keypoints represented by one visual word. We then propose to use a similarity threshold-based clusterng method tocalculate the optimal vocabulary size, where the universal similarity threshold can be obtained empirically. With the optimal vocabulary size, the optimal visual vocabularies of limited sizes from three datasets are shown to be exchangeable and therefore universal. This result indicates that a universal and compact visual vocabulary can be built from a not too small dataset. Our work narrows the gab between bag-of-visual-words and bag-of-words, where a relatively fixed vocabulary can be used with different text datasets. [ABSTRACT FROM AUTHOR]

We report the design and implementation of a high-speed, automated laser radar (ladar) system with sensitivity enhanced by a polarimetric imaging technique. This ladar is able to analyze the Stokes vector of the reflected light from a target at video-rate. With a polarization state generator and a polarization state analyzer, the system is capable of performing a complete Mueller matrix imaging of the scene under observation. This polarization-sensitive ladar (pladar) is applied to various scenes and found to yield the ability to detect information that is indiscernible to a conventional, intensity-based ladar. [ABSTRACT FROM AUTHOR]

Empirical-likelihood-based inference for the parameters in a partially linear single-index model with randomly censored data is investigated. We introduce an estimated empirical likelihood for the parameters using a synthetic data approach and show that its limiting distribution is a mixture of central chi-squared distribution. To attack this difficulty we propose an adjusted empirical likelihood to achieve the standard χ-limit. Furthermore, since the index is of norm 1, we use this constraint to reduce the dimension of parameters, which increases the accuracy of the confidence regions. A simulation study is carried out to compare its finite-sample properties with the existing method. An application to a real data set is illustrated. [ABSTRACT FROM AUTHOR]

In this paper, we present a variable selection procedure by combining basis function approximations with penalized estimating equations for semiparametric varying-coefficient partially linear models with missing response at random. The proposed procedure simultaneously selects significant variables in parametric components and nonparametric components. With appropriate selection of the tuning parameters, we establish the consistency of the variable selection procedure and the convergence rate of the regularized estimators. A simulation study is undertaken to assess the finite sample performance of the proposed variable selection procedure. [ABSTRACT FROM AUTHOR]

Abstract: Cocaine addiction and overdose are a well-known public health problem. There is no approved medication available for cocaine abuse treatment. Our recently designed and discovered high-activity mutant (A199S/S287G/A328W/Y332G) of human butyrylcholinesterase (BChE) has been recognized to be worth exploring for clinical application in humans as a potential anti-cocaine medication. The catalytic rate constant (k cat) and Michaelis–Menten constant (K M) for (−)-cocaine hydrolysis catalyzed by A199S/S287G/A328W/Y332G BChE (without fusion with any other peptide) have been determined to be 3060min−1 and 3.1μM, respectively, in the present study. The determined kinetic parameters reveal that the un-fused A199S/S287G/A328W/Y332G mutant has a ∼1080-fold improved catalytic efficiency (k cat/K M) against (−)-cocaine compared to the wild-type BChE. The ∼1080-fold improvement in the catalytic efficiency of the un-fused A199S/S287G/A328W/Y332G mutant is very close to the previously reported the ∼1000-fold improvement in the catalytic efficiency of the A199S/S287G/A328W/Y332G mutant fused with human serum albumin. These results suggest that the albumin fusion did not significantly change the catalytic efficiency of the BChE mutant while extending the plasma half-life. In addition, we have also examined the catalytic activities of the A199S/S287G/A328W/Y332G mutant against two other substrates, acetylthiocholine (ATC) and butyrylthiocholine (BTC). It has been shown that the A199S/S287G/A328W/Y332G mutations actually decreased the catalytic efficiencies of BChE against ATC and BTC, while considerably improving the catalytic efficiency of BChE against (−)-cocaine. [ABSTRACT FROM AUTHOR]

The stomach is the most common site of gastrointestinal stromal tumors (GISTs), but the clinical behavior of gastric GISTs at different sites is unclear. This study was designed to evaluate the clinicopathological (CP) parameters and influence of different gastric sites on outcome in patients with GIST. The CP and follow-up records of 187 patients with GIST who were treated at TianJin Medical University Cancer Institute & Hospital between January 1985 and December 2006 were reviewed. There were 97 men and 90 women (aged 17–88 (median, 56.5) years). CP factors were assessed for overall survival (OS) by using univariate and multivariate analysis. The numbers of cases of upper, middle, and lower third gastric GISTs were 69 (36.9%), 103 (55.1%), and 15 (8%), respectively. Sites of GISTs in the middle or upper stomach, tumor size, intermediate- or high-risk groups, high mitotic count, and low resection status were associated with poor OS ( p = 0.041, 0.046, 0.006, 0.000, 0.000, respectively) in a univariate analysis. In a multivariate analysis, tumor location in the upper and middle third of the stomach ( p = 0.035), an intermediate or high risk ( p = 0.01), and incomplete resection status ( p = 0.006) were predictive of poor OS. Patients in intermediate- and high-risk groups had an unfavorable outcome. A complete resection is the most important treatment for survival. The location of GIST in the lower third of the stomach may be a favorable factor, and the significance of different tumor sites for prognosis of gastric GISTs needs to be further clarified. [ABSTRACT FROM AUTHOR]

The Bowman–Birk protease inhibitors have recently attracted attention for their potential as cancer preventive and suppressing agents. They contain two canonical binding loops, both consisting of nine highly conserved residues capable of inhibiting corresponding serine proteases. In this study, we cloned the cDNA of the mung bean trypsin inhibitor, one of the most studied Bowman–Birk protease inhibitors. A modified peptide, Lys33GP, with 33 residues derived from the long chain of the Lys active fragment of mung bean trypsin inhibitor, was successfully expressed in Escherichia coli as a glutathione- S-transferase fusion protein. The recombinant product was obtained with a high yield, and exhibited potent inhibitory activity. Meanwhile, a shorter peptide composed of only 16 residues (the Lys16 peptide), corresponding to the active core of the fragment, was synthesized. Both the recombinant and the synthesized peptides had the same inhibitory activity toward trypsin at a molar ratio of 1 : 1, implying that the Lys16 peptide with two disulfide bonds is possibly the essential structural unit for inhibitory activity. Using site-directed mutagenesis, the P1 position Lys was replaced by Phe, and the resulting mutant, Lys33K/F, was determined to have potent chymotrypsin inhibitory activity. Both Lys33GP and the Lys33K/F mutant may be potential pharmaceutical agents for the prevention of oncogenesis. [ABSTRACT FROM AUTHOR]

Bioactive SiO2-CAO-P2O5 gel (BAG) nanoparticles with 40 nm in diameter were synthesized by the sol-gel route and further modified via the ring-opening polymerization of lactide on the surface of particles. Surface modified BAG (mBAG) was introduced in poly(L-lactide) (PLLA) matrix as bioactive filler. The dispersibility of mBAG in PLLA matrix was much higher than that of rough BAG particles. Tensile strength of the mBAG/PLLA composite could be increased to 61.2 MPa at 2 wt% filler content from 53.4 MPa for pure PLLA. The variation of moduli of the BAG/PLLA and mBAG/PLLA composites always showed an enhancement tendency with the increasing content of filler loading. The SEM photographs of the fracture surfaces showed that mBAG could be homogeneously dispersed in the PLLA matrix, and the corrugated deformation could absorb the rupture energy effectively during the breaking of materials. In vitro bioactivity tests showed that both BAG and mBAG particles could endow the composites with ability of the calcium sediment in SBF, but the surface modification of BAG particles could weaken this capability to some extent. Biocompatibility tests showed that both BAG and mBAG particles could facilitate the attachment and proliferation of the marrow cells on the surface of the composite. All these results showed that the mBAG/PLLA composite would be a promising material for bone tissues regeneration. [ABSTRACT FROM AUTHOR]