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Background: The purple mangosteen (Garcinia mangostana), known as the "queen of fruit," is widely consumed and unique not only because of its outstanding appearance and flavor but also its remarkable and diverse pharmacological effects. The aim of the present study is to evaluate the effect of acute mangosteen supplementation on physical fatigue during exercise. Methods: A randomized, double-blind, placebo-controlled, crossover study was carried out by 12 healthy adults. The participants were randomly assigned to receive acute oral administration of either 250 mL of the mangosteen-based juice (supplementation treatment; 305 mg of α-mangostin and 278 mg of hydroxycitric acid) or a placebo (control treatment) 1 h before cycle ergometer exercise. Time to exhaustion, heart rate, Borg Rating of Perceived Exertion score, blood biochemical markers (namely ammonia, cortisol, creatine kinase, aspartate aminotransferase, alanine aminotransferase, glucose, and lactate), muscle dynamic stiffness, and Profile of Mood States (POMS) were evaluated and recorded. Results: The results showed all parameters we examined were significantly altered by the exercise challenge, which demonstrated they directly reflected the condition of fatigue. However, there were no differences between the two treatments besides a positive impact on the POMS examination. Conclusions: The occurrence of physical fatigue depends on multiple underlying mechanisms. We concluded that acute mangosteen supplementation had no impact on alleviating physical fatigue during exercise. [ABSTRACT FROM AUTHOR]

The article discusses results of a study which examines the effectiveness of major/career planning course, focused on behavioral and adaptive components of college students through occupational engagement, career adaptability, and student career construction. The study explores the aspects of occupational engagement as integral part of a student's adaptive career decision-making. It also highlights the benefits of career exploration methods among college students.

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We fabricated Ge-on-insulator monocrystalline nanolayers with thickness H=1–18 nm using SiO2 substrate and studied their Raman spectra. The spectra display longitudinal optical (LO) phonon and confined acoustic phonon bands. For H<5 nm, additional bands due to amorphous-like inclusions appear in the spectra. With a decrease in H, the LO phonon Raman band displays enhancement and downshift. Also, as H decreases, the band homogeneously broadens proportionally to 1/H. We attribute these findings to a reduction in reflectance plus electron quantum size effect, thickness-dependent stress, and surface-disorder-induced phonon lifetime reduction. [ABSTRACT FROM AUTHOR]

The hole Hall mobility of Si1-xGex single crystal alloys grown by the traveling liquidus-zone method has been investigated. Raman analysis of the alloys with various Ge contents show excellent compositional uniformity and high crystal quality without strain. Secondary ion mass spectrometry indicates that the B concentration is homogeneous throughout the depth of the alloys. The hole Hall mobility in alloys with a low carrier concentration of ~1×1015cm-3 shows a higher mobility compared with previous results, indicating a reduction in alloy scattering effects. These results suggest that scattering processes in alloy semiconductors should be reconsidered both experimentally and theoretically. [ABSTRACT FROM AUTHOR]

Epigenetic effects are considered heritable but may also be modified by environmental factors. Arecoline (ARC), a major component of areca nut alkaloids, is an important environmental risk factor for oral cancer and hepatocellular carcinomain Taiwan. The aim of this study was to determine the influence of ARC on the epigenome. The mRNA expression of histone methyltransferases, acetyltransferases, and demethylases were assessed in K-562 cells following exposure to ARC. Results demonstrated that ARC produced changes in the expressions of several genes catalyzing histone methylation (Mll, Setdb1, and Suv39h2), acetylation (Atf2), and demethylation (JMJD6). Since H3K9 methylation is involved in maintaining the stability of heterochromatin structures and inactivating euchromatic gene expressions, data suggest that the ARC-induced epigenetic changes play a role in the mechanisms underlying chemical-mediated cytotoxicity and genotoxicity. [ABSTRACT FROM AUTHOR]

Alternative splicing involves differential exon selection of a gene transcript to generate mRNA and protein isoforms with structural and functional diversity. Abnormal alternative splicing has been shown to be associated with malignant phenotypes of cancer cells, such as chemo-resistance and invasive activity. Screening small molecules and drugs for modulating RNA splicing in human hepatocellular carcinoma cell line Huh-7, we discovered that amiloride, distinct from four pH-affecting amiloride analogues, could "normalize" the splicing of BCL-X, HIPK3 and RON/MISTR1 transcripts. Our proteomic analyses of amiloride-treated cells detected hypo-phosphorylation of splicing factor SF2/ASF, and decreased levels of SRp20 and two un-identified SR proteins. We further observed decreased phosphorylation of AKT, ERK1/2 and PP1, and increased phosphorylation of p38 and JNK, suggesting that amiloride treatment down-regulates kinases and upregulates phosphatases in the signal pathways known to affect splicing factor protein phosphorylation. These amiloride effects of "normalized" oncogenic RNA splicing and splicing factor hypo-phosphorylation were both abrogated by pretreatment with a PP1 inhibitor. Global exon array of amiloride-treated Huh-7 cells detected splicing pattern changes involving 584 exons in 551 gene transcripts, many of which encode proteins playing key roles in ion transport, cellular matrix formation, cytoskeleton remodeling, and genome maintenance. Cellular functional analyses revealed subsequent invasion and migration defects, cell cycle disruption, cytokinesis impairment, and lethal DNA degradation in amiloridetreated Huh-7 cells. Other human solid tumor and leukemic cells, but not a few normal cells, showed similar amiloridealtered RNA splicing with devitalized consequence. This study thus provides mechanistic underpinnings for exploiting small molecule modulation of RNA splicing for cancer therapeutics. [ABSTRACT FROM AUTHOR]

Background: Histone modifications in tumorigenesis are increasingly recognized as important epigenetic factors leading to cancer. Increased phosphorylation levels of histone H3 as a result of aurora B and pMSK1 overexpression were observed in various tumors. We selected aurora B and MSK1 as representatives for testing various compounds and drugs, and found that squamocin, a bis-tetrahydrofuran annonaceous acetogenin, exerted a potent effect on histone H3 phosphorylation. Methods: GBM8401, Huh-7, and SW620 cells were incubated with 15, 30, and 60 μM squamocin for 24 h. The expressions of mRNA and proteins were analyzed by qRT-PCR and Western blotting, respectively. The cell viability was determined by an MTT assay. Cell cycle distribution and apoptotic cells were analyzed by flow cytometry. Results: Our results showed that squamocin inhibited the proliferation of GBM8401, Huh-7, and SW620 cells, arrested the cell cycle at the G1 phase, and activated both intrinsic and extrinsic pathways to apoptosis. In addition, we demonstrated that squamocin had the ability to modulate the phosphorylation levels of H3S10 (H3S10p) and H3S28 (H3S28p) in association with the downregulation of aurora B and pMSK1 expressions. Conclusions: This study is the first to show that squamocin affects epigenetic alterations by modulating histone H3 phosphorylation at S10 and S28, providing a novel view of the antitumor mechanism of squamocin. [ABSTRACT FROM AUTHOR]

Background: Histone modifications in tumorigenesis are increasingly recognized as important epigenetic factors leading to cancer. Increased phosphorylation levels of histone H3 as a result of aurora B and pMSK1 overexpression were observed in various tumors. We selected aurora B and MSK1 as representatives for testing various compounds and drugs, and found that squamocin, a bis-tetrahydrofuran annonaceous acetogenin, exerted a potent effect on histone H3 phosphorylation. Methods: GBM8401, Huh-7, and SW620 cells were incubated with 15, 30, and 60 μM squamocin for 24 h. The expressions of mRNA and proteins were analyzed by qRT-PCR and Western blotting, respectively. The cell viability was determined by an MTT assay. Cell cycle distribution and apoptotic cells were analyzed by flow cytometry. Results: Our results showed that squamocin inhibited the proliferation of GBM8401, Huh-7, and SW620 cells, arrested the cell cycle at the G1 phase, and activated both intrinsic and extrinsic pathways to apoptosis. In addition, we demonstrated that squamocin had the ability to modulate the phosphorylation levels of H3S10 (H3S10p) and H3S28 (H3S28p) in association with the downregulation of aurora B and pMSK1 expressions. Conclusions: This study is the first to show that squamocin affects epigenetic alterations by modulating histone H3 phosphorylation at S10 and S28, providing a novel view of the antitumor mechanism of squamocin. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effects of purple sweet potato leaves (PSPL) consumption on oxidative stress markers in a healthy, nontrained, young male population after completing a running exercise protocol. A crossover design was applied, with 15 subjects participating in a two-step dietary intervention period. Each subject was given a high- (PSPL group) or low-polyphenol (control group) diet for 7 days with a 14-day washout period. After each dietary intervention period, all subjects performed 1 h of treadmill running at a speed corresponding to 70% of each subject's individual maximal oxygen uptake (V0307;o2max). Blood samples were taken before exercise and at 0, 1, and 3 h after exercise. Compared with the control group, PSPL consumption significantly increased plasma total polyphenols concentration and total antioxidant power (i.e., the ferric-reducing ability of plasma) in the PSPL group. The markers of oxidative damage, plasma TBARS and protein carbonyl, significantly decreased. Plasma IL-6 concentration also decreased. However, no significant difference was found in HSP72 levels between the two groups. These findings indicate that consuming a high-polyphenol diet for 7 days can modulate antioxidative status and decrease exercise-induced oxidative damage and pro-inflammatory cytokine secretion. [ABSTRACT FROM AUTHOR]

Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder, characterized by progressive microcephaly, growth retardation, immunodeficiency, and pre-disposition to tumor formation. To investigate the functions of the NBS gene product, NBS1, on neurons, PC12 cells overexpressing NBS1 and related mutants and primary cortical neuronal culture were used in the present study. Small interfering RNA (siRNA) was applied to repress the expression of endogenous Nbs1 in PC12 cells and primary cortical neurons. We demonstrated that overexpression of NBS1 increases cellular proliferation and decreases the apoptosis of PC12 cells in serum withdrawal and ionizing irradiation, through the activation of phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway. Overexpression of NBS1 also decreases neurite elongation on PC12 cells under nerve growth factor stimulation. Transfection of NBS1-overexpressing PC12 cells with a dominant negative Akt mutant attenuates the neuroprotection and cellular proliferation effects of NBS1 while having no effect on neurite elongation. PC12 cells overexpressing NBS657del5 and NBS653 mutants, in which the major NBS1 protein in cells are truncated proteins, have decreased cellular proliferation, increased cell death, and decreased neurite elongation compared with those of control PC12 cells. Repression of Nbs1 by siRNA decreases the PI 3-kinase activity and Akt phosphorylation levels, and induces neurite elongation in PC12 cells even without nerve growth factor stimulation. Repression of Nbs1 by siRNA in primary cortical neurons also increased neurite elongation, but increased neuronal death. We conclude that NBS1 can regulate neuronal proliferation and neuroprotection via PI 3-kinase/Akt pathway while regulating neuronal differentiation in a different pathway. Excessive accumulation of truncated protein secondary to 657del5 mutation may be detrimental to neurons, leading to defective neuronal proliferation and differentiation. [ABSTRACT FROM AUTHOR]

Although the introduction of nickel-titanium (NiTi) alloy into endodontic files has greatly transformed the methods of root canal instrumentation in the past decade, instrument separation is still a serious concern owing to a lack of wear resistance and improper operation. The purpose of this study was to investigate the effects of thermal nitriding surface modification of NiTi instruments on the wear resistance and cutting efficiency. In total, 25 ProFile 0.04 taper instruments were divided into 5 groups: 2 control groups and another 3 experimental groups that were subjected to thermal nitriding surface modification by treatment under 3 different conditions of 200, 250, and 300 °C. All instruments were used to make preparations in 100 acrylic endodontic training blocks. These blocks were weighed to calculate differences in weight before and after preparation. After being autoclaved, each instrument was observed under a scanning electron microscope (SEM). The results indicated that nitrogen ions were successfully introduced onto the surface of NiTi instruments. The presence of a titanium nitride (TiN) layer gave the instruments a gold appearance. Samples in the experimental groups showed increased wear resistance and cutting efficiency compared to the controls. The same results were also indicated by the SEM observations. Thermal nitriding surface treatments of NiTi rotary instruments produced higher wear resistance at a reasonable cost. It is well worth further developing this surface treatment for clinical applications. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the most common malignancy in adult kidney, and accounts for 3% of malignancies worldwide with increasing incidence. Clear cell RCC (ccRCC) is the major type in RCC. Resection by surgery is the main treatment because the response of ccRCC to traditional therapies is very poor. To identify the tumor-associated genes for better understanding the molecular mechanism of ccRCC, the full-length enriched cDNA libraries of ccRCC and normal kidney tissues were constructed by the oligo-capping method. Nucleotide sequences of the cDNA libraries of ccRCC and normal kidney tissues were sequenced. From the sequence analysis of 19,425 and 12,400 clones of ccRCC and normal kidney tissues, 4356 and 3055 genes were identified, respectively. By comparing the gene-expression patterns of ccRCC and normal tissues, the up- or down-regulated genes were identified. Among these identified genes, the differential expression of annexin A2 and argininosuccinate synthetase genes were further confirmed by quantitative real-time PCR and Western blot analysis. [ABSTRACT FROM AUTHOR]

InGaAs photo field-effect transistors (PhotoFETs) integrated on a half-inch Si wafer have been demonstrated by means of layer transfer technology. According to the Raman measurement and scanning transmission electron microscopy, the InGaAs layer was transferred onto the half-inch Si wafer without degradation of crystal quality or introduction of strain. The optical performance of InGaAs photoFETs on Si, operating in shortwave infrared (SWIR) region was also investigated. The photoFETs on Si wafer show a responsivity of ∼3 A W−1 at SWIR of 1550 nm with investigated range of bias. These results demonstrate InGaAs layer transfer technology is suitable for SWIR detectors on CMOS compatible platforms for monolithic integration. [ABSTRACT FROM AUTHOR]

Bilayer WSe2/MoSe2 van der Waals heterostructures have been directly grown on SiO2/Si substrates by 2-step chemical vapor deposition method. Bilayer nature with well aligned in-plane crystal orientation has been confirmed by Raman and transmission electron microscopy characterizations. Back gate transistors having bilayer WSe2/MoSe2 in the source side have been fabricated and high on/off ratio larger than 106 have been obtained. Gate-induced modulation of electron direct tunneling from source metal to the bottom MoSe2 layer and band to band tunneling from the valence band of WSe2 to the conduction band of MoSe2 can be an operation mechanism. Thanks to the drastic reduction of contact resistance due to the change of electron injection configuration, from edge to area injection at the source electrode, much higher on/off ratio with steeper switching was obtained in the WSe2/MoSe2 bilayer device as compared with the monolayer MoSe2 and WSe2 devices. [ABSTRACT FROM AUTHOR]

Ultra-thin germanium-tin on insulator (GeSnOI) structure on Si substrate has been fabricated using the direct bonding and substrate etching techniques. This process involves the growth of GeSn layer on Ge (001) substrate followed by the deposition of ALD-Al2O3 on GeSn layer, the bonding of GeSn/Ge (001) substrate to a SiO2/Si substrate, and the removal of the Ge substrate. Using the bevel substrate etching technique, we prepared different GeSnOI structures, whose thicknesses gradually varied from 50 to 0 nm, in one sample. We investigated the thickness dependence of the material quality of the fabricated structure via micro-Raman spectroscopy; the strong Ge–Ge peaks are observed in a few nm thick GeSnOI structure, suggesting high quality of the fabricated GeSnOI structure and the enhancement of Raman intensity of the Ge–Ge peak in the ultra-thin GeSnOI structure of thickness less than 10 nm is attributed to the quantum size effect. [ABSTRACT FROM AUTHOR]

Ultra-thin-body (UTB) germanium-on-insulator (GeOI) substrates with Si-passivated back interfaces have been fabricated by using advanced epitaxial-lift-off (ELO) technology. Performance of UTB GeOI p-MOSFETs with body thickness (Tbody) in the 4–16 nm range has also been characterized. Si-passivated back interfaces have been fabricated and found to be effective in mitigating the unpleasant hole-mobility degradation in the UTB GeOI regime owing to the suppression of the back interface scattering. [ABSTRACT FROM AUTHOR]

The parasitic resistance (Rpara) of Ge p-channel metal–oxide–semiconductor field-effect transistors (p-MOSFETs) fabricated by ion implantation after germanidation (IAG) has been investigated by varying the drive-in annealing temperature. The lowest Rpara of 835 Ω µm was achieved after 450 °C drive-in annealing for 1 min. Boron segregation between NiGe and Ge induced by drive-in annealing has advantages in forming an abrupt metallic source/drain (S/D) junction and contributes to the decrease in Rpara. The appropriate process window for fabricating Ge p-MOSFETs by IAG was also given. IAG, a pathway for introducing a Ge channel into CMOS technology beyond the 10 nm node, was proved to be effective for reducing Rpara. [ABSTRACT FROM AUTHOR]

Abstract Background Myo-inositol (or inositol) and its derivatives not only function as important metabolites for multiple cellular processes but also act as co-factors and second messengers in signaling pathways. Although inositol supplementation has been widely studied in various clinical trials, little is known about its effect on idiopathic pulmonary fibrosis (IPF). Recent studies have demonstrated that IPF lung fibroblasts display arginine dependency due to loss of argininosuccinate synthase 1 (ASS1). However, the metabolic mechanisms underlying ASS1 deficiency and its functional consequence in fibrogenic processes are yet to be elucidated. Methods Metabolites extracted from primary lung fibroblasts with different ASS1 status were subjected to untargeted metabolomics analysis. An association of ASS1 deficiency with inositol and its signaling in lung fibroblasts was assessed using molecular biology assays. The therapeutic potential of inositol supplementation in fibroblast phenotypes and lung fibrosis was evaluated in cell-based studies and a bleomycin animal model, respectively. Results Our metabolomics studies showed that ASS1-deficient lung fibroblasts derived from IPF patients had significantly altered inositol phosphate metabolism. We observed that decreased inositol-4-monophosphate abundance and increased inositol abundance were associated with ASS1 expression in fibroblasts. Furthermore, genetic knockdown of ASS1 expression in primary normal lung fibroblasts led to the activation of inositol-mediated signalosomes, including EGFR and PKC signaling. Treatment with inositol significantly downregulated ASS1 deficiency-mediated signaling pathways and reduced cell invasiveness in IPF lung fibroblasts. Notably, inositol supplementation also mitigated bleomycin-induced fibrotic lesions and collagen deposition in mice. Conclusion These findings taken together demonstrate a novel function of inositol in fibrometabolism and pulmonary fibrosis. Our study provides new evidence for the antifibrotic activity of this metabolite and suggests that inositol supplementation may be a promising therapeutic strategy for IPF.

本研究針對高中科學論證教學相關實證研究進行回顧，透過內容分析方法，瞭解論證教學特徵，期能對如何在課室實施論證教學提出具體建議。為蒐集相關實證研究，本研究使用Scopus期刊數據庫搜尋國外文章，並針對臺灣教育領域三本重要的學術期刊進行國內相關文獻搜尋，且依三項篩選條件進行人工篩選：一、為實證性研究；二、研究對象為高中教師或高中學生；三、有實際教學實施。總共篩選出24篇文章。根據本研究回顧結果建議，論證教學類型大多採沉浸式論證教學，教學活動設計著重於情境布置，營造能讓學生沉浸於論證對話的學習環境中，以提高學生學習動機和學習投入，故建議沉浸式論證教學應強調營造以學生為主的學習環境來增進同儕與師生對話的機會。而結構式論證教學著重嵌入論證框架於活動、學習單或科學寫作來增進學生對論證結構的理解，建議未來研究若強調增進學生論證能力遷移可嵌入明示的論證框架於教學活動中。 This study aimed to identify the features of argumentation instruction in senior high school classrooms to formulate recommendations for researchers and curriculum developers. Therefore, we searched the Scopus database and three major Taiwan-based journals for relevant studies. In total, 24 articles were selected because they met the three filter criteria of (1) being empirical studies, (2) involving senior-high-school teacher or student participants, and (3) examining classroom teaching practices. The literature review indicates that the immersion-type argumentation instruction attracted the most attention. This type of instruction often establishes an appropriate design-based learning context to enhance students’ engagement and motivation. Several studies indicate that immersing students in a student-centered learning environment can enhance the argument discourse that they engage in with their peers and teachers. The structural-type argumentation instruction stresses the enhancement of students’ understanding of argumentation. Generally, the framework of argumentation is embedded in worksheets and scientific writing activities designed to improve students’ knowledge of the elements of argumentation. These findings highlight the potential of embedding the argumentation framework into teaching activities to improve students’ transfer of learning with respect to argumentation abilities.

Na+/Ca2+ exchanger (NCX) is one of the major mechanisms for removing Ca2+ from the cytosol especially in cardiac myocytes and neurons, where their physiological activities are triggered by an influx of Ca2+. NCX contains a large intracellular loop (NCXIL) that is responsible for regulating NCX activity. Recent evidence has shown that proteins, including kinases and phosphatases, associate with NCX1IL to form a NCX1 macromolecular complex. To search for the molecules that interact with NCX1IL and regulate NCX1 activity, we used the yeast two-hybrid method to screen a human heart cDNA library and found that the C-terminal region of sarcomeric mitochondrial creatine kinase (sMiCK) interacted with NCX1IL. Moreover, both sMiCK and the muscle-type creatine kinase (CKM) coimmuno-precipitated with NCX1 using lysates of cardiacmyocytes and HEK293T cells that transiently expressed NCX1 and various creatine kinases. Both sMiCK and CKM were able to produce a recovery in the decreased NCX1 activity that was lost under energy-compromised conditions. This regulation is mediated through a putative PKC phosphorylation site of sMiCK and CKM. The autophosphorylation and the catalytic activity of sMiCK and CKM are not required for their regulation of NCX1 activity. Our results suggest a novel mechanism for the regulation of NCX1 activity. [ABSTRACT FROM AUTHOR]

Alternative splicing (AS) is a process that enables the generation of multiple protein isoforms with different biological properties from a single mRNA. Cancer cells often use the maneuverability conferred by AS to produce proteins that contribute to growth and survival. In our previous studies, we identified that amiloride modulates AS in cancer cells. However, the effective concentration of amiloride required to modulate AS is too high for use in cancer treatment. In this study, we used computational algorithms to screen potential amiloride derivatives for their ability to regulate AS in cancer cells. We found that 3,5‐diamino‐6‐chloro‐N‐(N‐(2,6‐dichlorobenzoyl)carbamimidoyl)pyrazine‐2‐carboxamide (BS008) can regulate AS of apoptotic gene transcripts, including HIPK3, SMAC, and BCL‐X, at a lower concentration than amiloride. This splicing regulation involved various splicing factors, and it was accompanied by a change in the phosphorylation state of serine/arginine‐rich proteins (SR proteins). RNA sequencing was performed to reveal that AS of many other apoptotic gene transcripts, such as AATF, ATM, AIFM1, NFKB1, and API5, was also modulated by BS008. In vivo experiments further indicated that treatment of tumor‐bearing mice with BS008 resulted in a marked decrease in tumor size. BS008 also had inhibitory effects in vitro, either alone or in a synergistic combination with the cytotoxic chemotherapeutic agents sorafenib and nilotinib. BS008 enabled sorafenib dose reduction without compromising antitumor activity. These findings suggest that BS008 may possess therapeutic potential for cancer treatment.

Abstract Alternative splicing is a mechanism for increasing protein diversity from a limited number of genes. Studies have demonstrated that aberrant regulation in the alternative splicing of apoptotic gene transcripts may contribute to the development of cancer. In this study, we isolated 4β-Hydroxywithanolide E (4bHWE) from the traditional herb Physalis peruviana and investigated its biological effect in cancer cells. The results demonstrated that 4bHWE modulates the alternative splicing of various apoptotic genes, including HIPK3, SMAC/DIABLO, and SURVIVIN. We also discovered that the levels of SRSF1 phospho-isoform were decreased and the levels of H3K36me3 were increased in 4bHWE treatment. Knockdown experiments revealed that the splicing site selection of SMAC/DIABLO could be mediated by changes in the level of H3K36me3 in 4bHWE-treated cells. Furthermore, we extended our study to apoptosis-associated molecules, and detected increased levels of poly ADP-ribose polymerase cleavage and the active form of CASPASE-3 in 4bHWE-induced apoptosis. In vivo experiments indicated that the treatment of tumor-bearing mice with 4bHWE resulted in a marked decrease in tumor size. This study is the first to demonstrate that 4bHWE affects alternative splicing by modulating splicing factors and histone modifications, and provides a novel view of the antitumor mechanism of 4bHWE.

Abstract In this study, a new type of field-effect transistor (FET)-based biosensor is demonstrated to be able to overcome the problem of severe charge-screening effect caused by high ionic strength in solution and detect proteins in physiological environment. Antibody or aptamer-immobilized AlGaN/GaN high electron mobility transistors (HEMTs) are used to directly detect proteins, including HIV-1 RT, CEA, NT-proBNP and CRP, in 1X PBS (with 1%BSA) or human sera. The samples do not need any dilution or washing process to reduce the ionic strength. The sensor shows high sensitivity and the detection takes only 5 minutes. The designs of the sensor, the methodology of the measurement, and the working mechanism of the sensor are discussed and investigated. A theoretical model is proposed based on the finding of the experiments. This sensor is promising for point-of-care, home healthcare, and mobile diagnostic device.

Graphene (Gr)/gold (Au) and graphene-oxide (GO)/Au nanocomposites (NCPs) were synthesized by performing pulsed-laser-induced photolysis (PLIP) on hydrogen peroxide and chloroauric acid (HAuCl4) that coexisted with Gr or GO in an aqueous solution. A 3-month-long aqueous solution stability was observed in the NCPs synthesized without using surfactants and additional processing. The synthesized NCPs were characterized using absorption spectroscopy, transmission electron microscopy, Raman spectroscopy, energy dispersive spectroscopy, and X-ray diffraction to prove the existence of hybrid Gr/Au or GO/Au NCPs. The synthesized NCPs were further evaluated using the photocatalytic reaction of methylene blue (MB), a synthetic dye, under UV radiation, visible light (central wavelength of 470 nm), and full spectrum of solar light. Both Gr/Au and GO/Au NCPs exhibited photocatalytic degradation of MB under solar light illumination with removal efficiencies of 92.1% and 94.5%, respectively.

Among the different Science, Technology, Engineering, and Math fields, engineering continues to have one of the highest rates of attrition (Hewlett et al., 2008). The turnover rate for women engineers from engineering fields is even higher than for men (Frehill, 2010). Despite increased efforts from researchers, there are still large gaps in our understanding of the reasons that women leave engineering. This study aims to address this gap by examining the reasons why women leave engineering. Specifically, we analyze the reasons for departure given by national sample of 1,464 women engineers who left the profession after having worked in the engineering field. We applied a person-environment fit theoretical lens, in particular, the Theory of Work Adjustment (TWA) (Dawis and Lofquist, 1984) to understand and categorize the reasons for leaving the engineering field. According to the TWA, occupations have different “reinforcer patterns,” reflected in six occupational values, and a mismatch between the reinforcers provided by the work environment and individuals’ needs may trigger departure from the environment. Given the paucity of literature in this area, we posed research questions to explore the reinforcer pattern of values implicated in women’s decisions to leave the engineering field. We used qualitative analyses to understand, categorize, and code the 1,863 statements that offered a glimpse into the myriad reasons that women offered in describing their decisions to leave the engineering profession. Our results revealed the top three sets of reasons underlying women’s decision to leave the jobs and engineering field were related to: first, poor and/or inequitable compensation, poor working conditions, inflexible and demanding work environment that made work-family balance difficult; second, unmet achievement needs that reflected a dissatisfaction with effective utilization of their math and science skills, and third, unmet needs with regard to lack of recognition at work and adequate opportunities for advancement. Implications of these results for future research as well as the design of effective intervention programs aimed at women engineers’ retention and engagement in engineering are discussed.

While a base substitution in intron 4 of GLA (IVS4+919G>A) that causes aberrant alternative splicing resulting in Fabry disease has been reported, its molecular mechanism remains unclear. Here we reported that upon IVS4+919G>A transversion, H3K36me3 was enriched across the alternatively spliced region. PSIP1, an adapter of H3K36me3, together with Hsp70 and NONO were recruited and formed a complex with SF2/ASF and SRp20, which further promoted GLA splicing. Amiloride, a splicing regulator in cancer cells, could reverse aberrant histone modification patterns and disrupt the association of splicing complex with GLA. It could also reverse aberrant GLA splicing in a PP1-dependant manner. Our findings revealed the alternative splicing mechanism of GLA (IVS4+919G>A), and a potential treatment for this specific genetic type of Fabry disease by amiloride in the future.

JAG1 is a Notch ligand that plays a critical role in multiple signaling pathways. However, the functionality of JAG1 in non-small cell lung cancer (NSCLC) has not been investigated thoroughly. By comparison of gene transcripted RNA profiles in the cell line pair with differential invasion ability, we identified JAG1 as a potential metastasis enhancer in lung cancer. Ectopic expression of JAG1 on lung cancer cells enhanced cell migration and invasion as well as metastasis in vitro and in vivo. Conversely, knockdown of JAG1 with siRNA in highly invasive cancer cells led to the reduction of migration and invasion. In clinical analysis, JAG1 mRNA expression was higher in tumors than in adjacent normal tissues in 14 of 20 patients with squamous cell carcinoma (SCC). SCC patients with higher JAG1 transcription had poor overall survival than those with low-transcripted JAG1. Microarray analysis indicated that the enforced JAG1 transcription was associated with an elevated HSPA2 RNA transcription, which played a role in promoting cancer cell migration and invasion. In conclusion, this is the first study that demonstrated that JAG1 might act as a potential prognostic marker and JAG1/HSPA2 axis mediates lung cancer malignancy at least partly.

α-parvin (PARVA) is known to be involved in the linkage of integrins, regulation of actin cytoskeleton dynamics and cell survival. However, the role that PARVA plays in cancer progression remains unclear. Here, using a lung cancer invasion cell line model and expression microarrays, we identify PARVA as a potential oncogene. The overexpression of PARVA increased cell invasion, colony-forming ability and endothelial cell tube formation. By contrast, knockdown of PARVA inhibited invasion and tube formation in vitro. Overexpression of PARVA also promoted tumorigenicity, angiogenesis and metastasis in in vivo mouse models. To explore the underlying mechanism, we compared the expression microarray profiles of PARVA-overexpressing cells with those of control cells to identify the PARVA-regulated signalling pathways. Pathway analysis showed that eight of the top 10 pathways are involved in invasion, angiogenesis and cell death. Next, to identify the direct downstream signalling pathway of PARVA, 371 significantly PARVA-altered genes were analysed further using a transcription factor target model. Seven of the top 10 PARVA-altered transcription factors shared a common upstream mediator, ILK. Lastly, we found that PARVA forms a complex with SGK1 and ILK to enhance the phosphorylation of ILK, which led to the phosphorylation of Akt and GSK3β. Notably, the inactivation of ILK reversed PARVA-induced invasion. Taken together, our findings imply that PARVA acts as an oncogene by activating ILK, and that this activation is followed by the activation of Akt and inhibition of GSK3β. To our knowledge, this is the first study to characterize the role of PARVA in lung cancer progression.

The diagnosis of periprosthetic joint infection is sometimes straightforward with purulent discharge from the fistula tract communicating to the joint prosthesis. However it is often difficult to differentiate septic from aseptic loosening of prosthesis because of the high culture-negative rates in conventional microbiologic culture. This study used quantitative reverse transcription polymerase chain reaction (RT-qPCR) to amplify bacterial 16S ribosomal RNA in vitro and in 11 clinical samples. The in vitro analysis demonstrated that the RT-qPCR method was highly sensitive with the detection limit of bacterial 16S rRNA being 0.148 pg/μl. Clinical specimens were analyzed using the same protocol. The RT-qPCR was positive for bacterial detection in 8 culture-positive cases (including aerobic, anaerobic, and mycobacteria) and 2 culture-negative cases. It was negative in one case that the final diagnosis was confirmed without infection. The molecular diagnosis of bacterial infection using RT-qPCR to detect bacterial 16S rRNA around a prosthesis correlated well with the clinical findings. Based on the promising clinical results, we were attempting to differentiate bacterial species or drug-resistant strains by using species-specific primers and to detect the persistence of bacteria during the interim period before the second stage reimplantation in a larger scale of clinical subjects.