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Autophagy is critical to acrosome biogenesis and mitochondrial quality control, but the underlying mechanisms remain unclear. The ubiquitin ligase Nrdp1/RNF41 promotes ubiquitination of the mitophagy-associated Parkin and interacts with the pro-autophagic protein SIP/CacyBP. Here, we report that global deletion of Nrdp1 leads to formation of the round-headed sperm and male infertility by disrupting autophagy. Quantitative proteome analyses demonstrated that the expression of many proteins associated with mitochondria, lysosomes, and acrosomes was dysregulated in either spermatids or sperm of the Nrdp1-deficient mice. Deletion of Nrdp1 increased the levels of Parkin but decreased the levels of SIP, the mitochondrial fission protein Drp1 and the mitochondrial protein Tim23 in sperm, accompanied by the inhibition of autophagy, the impairment of acrosome biogenesis and the disruption of mitochondrial arrangement in sperm. Thus, our results uncover an essential role of Nrdp1 in spermiogenesis and male fertility by promoting autophagy, providing important clues to cope with the related male reproductive diseases. [ABSTRACT FROM AUTHOR]

High tumour programmed cell death-ligand 1 (PD-L1) expression is associated with poor progression-free survival (PFS) after tyrosine kinase inhibitor (TKI) therapy in ALK-rearranged non-small cell lung cancer (NSCLC). However, the characteristics of the tumour microenvironment (TME) and their prognostic values in ALK-rearranged NSCLC are unknown. Here, we collected tumour tissues from pretreated ALK-rearranged NSCLC patients, immunohistochemical staining was used to assess PD-L1 expression, and tumour-infiltrating immune cells were determined via multiplex immunofluorescence staining (mIF). Our data showed that the median values of PFS for the high PD-L1 group and low PD-L1 group who received ALK-TKI treatment were 4.4 and 16.4 months, respectively (p = 0.008). The median overall survival (OS) of the two groups was 24.0 months and not reached, respectively (p = 0.021). Via univariate and multivariate analyses, a high PD-L1 expression and a worse ECOG PS were determined to be independent prognostic factors of OS (HR = 3.35, 95% CI: 1.23–9.11, p = 0.018; HR = 6.42, 95% CI: 1.45–28.44, p = 0.014, respectively). In addition, the high PD-L1 group had increased Tregs and exhausted CD8+ T cells in both the tumour and stroma (all p < 0.05). High PD-L1 expression was an adverse predictive and prognostic biomarker for ALK-rearranged NSCLC. The characteristics of the TME in patients with high PD-L1 expression were shown to have an immunosuppressive status. [ABSTRACT FROM AUTHOR]

Mechanical responses of nanoporous Cu samples under various loading conditions are investigated by molecular dynamics simulations. Effects of loading mode, initial void size, temperature, and void distribution are analyzed. The simulations show that the collapse time under uniaxial compression is about three times that under triaxial compression, and the collapse rate increases as the temperature rises. Dislocation nucleation is found to stimulate the collapse of void. For samples with a single void, the final dislocation density under triaxial compression is lower than that under uniaxial compression, which is due to that the dislocation accumulation rate greatly slows down after the void is fully collapsed. For samples with multiple voids, the dislocation accumulation rate under triaxial compression is much faster than that under uniaxial compression, resulting in higher dislocation density under triaxial compression. Irrespective of the initial void size, the evolutions of compression stress and void volume fraction remain invariant when the initial void volume fraction is fixed; however, the dislocation density decreases as the initial void radius increases. [ABSTRACT FROM AUTHOR]

In this study, several lines of evidence showed that the BnaMPK3s-BnaARF2s module is critical for the regulation of organ size and yield in I B. napus i . Keywords: Brassica napus; BnaMPK3; BnaARF2; organ size EN Brassica napus BnaMPK3 BnaARF2 organ size 899 901 3 04/19/23 20230501 NES 230501 The larger organs have potential economic value in I Brassica napus i improvement and bioenergy production. Brassica napus, BnaMPK3, BnaARF2, organ size. [Extracted from the article]

Cardiovascular disease is the leading cause of global mortality, with anticoagulant therapy being the main prevention and treatment strategy. Recombinant hirudin (r-hirudin) is a direct thrombin inhibitor that can potentially prevent thrombosis via subcutaneous (SC) and intravenous (IV) administration, but there is a risk of haemorrhage via SC and IV. Thus, microneedle (MN) provides painless and sanitary alternatives to syringes and oral administration. However, the current technological process for the micro mould is complicated and expensive. The micro mould obtained via three-dimensional (3D) printing is expected to save time and cost, as well as provide a diverse range of MNs. Therefore, we explored a method for MNs array model production based on 3D printing and translate it to micro mould that can be used for fabrication of dissolving MNs patch. The results show that r-hirudin-loaded and hyaluronic acid (HA)-based MNs can achieve transdermal drug delivery and exhibit significant potential in the prevention of thromboembolic disease without bleeding in animal models. These results indicate that based on 3D printing technology, MNs combined with r-hirudin are expected to achieve diverse customizable MNs and thus realize personalized transdermal anticoagulant delivery for minimally invasive and long-term treatment of thrombotic disease. [ABSTRACT FROM AUTHOR]

Purpose: To examine the effect of zinc protoporphyrin IX (ZnPPIX) on the sensitivity of colorectal cancer (CRC) cells to paclitaxel. Methods: Paclitaxel-resistant CRC cells were established by incubating CRC cells with increasing concentrations of paclitaxel. Colorectal cancer cells were incubated with ZnPPIX for 1 h before treatment with paclitaxel. Cell viability, proliferation, and apoptosis were determined by MTT, colony formation, and flow cytometry assays, respectively. The effect of ZnPPIX on DNA damage response in paclitaxel-resistant cells was assessed using western blot analysis of γH2AX, p-DNA-PK, and Rad51. Results: Paclitaxel suppressed proliferation of SW480 cells at an IC50 (half-maximal inhibitory concentration) of 0.23 μM, while that of proliferation of paclitaxel-resistant SW480 cells was also suppressed by paclitaxel at an IC50 of 2.58 μM (p < 0.05). Incubation with ZnPPIX attenuated the paclitaxel-induced decrease in viability and proliferation of SW480 cells. Paclitaxel-induced apoptosis of SW480 cells was enhanced upon incubation with ZnPPIX (p < 0.05). Similarly, protein expression of γH2AX was enhanced while protein expressions of p-DNA-PK and Rad51 reduced in paclitaxel-induced SW480 cells. On incubation with ZnPPIX, protein expression of heme oxygenase-1 (HO-1) and AKT and mTOR phosphorylation decreased in SsW480 cells (p < 0.05). Conclusion: ZnPPIX enhances paclitaxel-induced chemosensitivity of CRC by suppression of HO-1-mediated AKT/mTOR activation, and could potentially be used to facilitate the management of CRC. [ABSTRACT FROM AUTHOR]

Cellular senescence is closely related to DNA damage, proteasome inactivity, histone loss, epigenetic alterations, and tumorigenesis. The mammalian proteasome activator PA200 (also referred to as PSME4) or its yeast ortholog Blm10 promotes the acetylation-dependent degradation of the core histones during transcription, DNA repair, and spermatogenesis. According to recent studies, PA200 plays an important role in senescence, probably because of its role in promoting the degradation of the core histones. Loss of PA200 or Blm10 is a major cause of the decrease in proteasome activity during senescence. In this paper, recent research progress on the association of PA200 with cellular senescence is summarized, and the potential of PA200 to serve as a therapeutic target in age-related diseases is discussed. [ABSTRACT FROM AUTHOR]

Background: Intracranial artery dissection (IAD) often causes headache and cerebral vascular ischemic events. The imaging characteristics of IAD remain unclear. This study aims to characterize the appearance of culprit and non-culprit IAD using high-resolution cardiovascular magnetic resonance imaging (hrCMR) and quantify the incremental value of hrCMR in identifying higher risk lesions. Methods: Imaging data from patients who underwent intervention examination or treatment using digital subtraction angiography (DSA) and hrCMR using a 3 T CMR system within 30 days after the onset of neurological symptoms were collected. The CMR protocol included diffusion-weighted imaging (DWI), black blood T1-, T2- and contrast-enhanced T1-weighted sequences. Lesions were classified as culprit and non-culprit according to imaging findings and patient clinical presentations. Univariate and multivariate analyses were performed to assess the difference between culprit and non-culprit lesions and complementary value of hrCMR in identifying higher risk lesions. Results: In total, 75 patients were included in this study. According to the morphology, lesions could be classified into five types: Type I, classical dissection (n = 50); Type II, fusiform aneurysm (n = 1); Type III, long dissected aneurysm (n = 3); Type IV, dolichoectatic dissecting aneurysm (n = 9) and Type V, saccular aneurysm (n = 12). Regression analyses showed that age and hypertension were both associated with culprit lesions (age: OR, 0.83; 95% CI 0.75–0.92; p < 0.001 and hypertension: OR, 66.62; 95% CI 5.91–751.11; p = 0.001). Hematoma identified by hrCMR was significantly associated with culprit lesions (OR, 16.80; 95% CI 1.01–280.81; p = 0.037). Moreover, 17 cases (16 lesions were judged to be culprit) were diagnosed as IAD but not visible in DSA and 15 were Type I lesion. Conclusion: hrCMR is helpful in visualizing and characterizing IAD. It provides a significant complementary value over DSA for the diagnosis of IAD. [ABSTRACT FROM AUTHOR]

Drip irrigation is an efficient water-saving irrigation technique. However, the clogging of emitters is a major problem for drip irrigation systems that adversely affects the uniformity of water distribution and lowers the water use efficiency. The irrigation water with high sand content, if not properly treated, will cause physical clogging of emitters. To meet the requirement of drip irrigation, irrigation water of high concentration of sand particles should be filtrated in advance. In this paper, experiments on sandy water filtration by using two kinds of natural soils, sandy loam soil and sandy soil, and subsurface PVC drainage pipes were carried out. The filtration performance by using these two soils was investigated and compared. In addition, impact of sandy water filtration on physical properties of sandy loam soil and sandy soil were analyzed. Results show that both the sand content and filtration velocity of the filtered water decrease exponentially with time. The impact of sandy water filtration on physical properties of the two soils was also evaluated and the main reasons for clogging of soil pore space were analyzed. [ABSTRACT FROM AUTHOR]

Mechanical responses of nanoporous aluminum samples under shock in different crystallographic orientations (<100>, <111>, <110>, <112> and <130>) are investigated by molecular dynamics simulations. The shape evolution of void during collapse is found to have no relationship with the shock orientation. Void collapse rate and dislocation activities at the void surface are found to strongly dependent on the shock orientation. For a relatively weaker shock, void collapses fastest when shocked along the <100> orientation; while for a relatively stronger shock, void collapses fastest in the <110> orientation. The dislocation nucleation position is strongly depended on the impacting crystallographic orientation. A theory based on resolved shear stress is used to explain which slip planes the earliest-appearing dislocations prefer to nucleate on under different shock orientations. [ABSTRACT FROM AUTHOR]

Meiosis, which produces haploid progeny, is critical to ensuring both faithful genome transmission and genetic diversity. Proteasomes play critical roles at various stages of spermatogenesis, including meiosis, but the underlying mechanisms remain unclear. The atypical proteasomes, which contain the activator PA200, catalyze the acetylationdependent degradation of the core histones in elongated spermatids and DNA repair in somatic cells. We show here that the testis-specific proteasome subunit a4s/PSMA8 is essential for male fertility by promoting proper formation of spermatoproteasomes, which harbor both PA200 and constitutive catalytic subunits. Immunostaining of a spermatocyte marker, SYCP3, indicated that meiosis was halted at the stage of spermatocytes in the a4s-deficient testes. a4s stimulated the in vitro degradation of the acetylated core histones, instead of nonacetylated histones, by the PA200-proteasome. Deletion of a4s blocked degradation of the core histones at DNA damage loci in spermatocytes, leading to meiotic arrest at metaphase I. Thus, a4s is required for histone degradation at meiotic DNA damage loci, proper progression of meiosis, and fertility in males by promoting proper formation of spermatoproteasomes. These results are important for understanding male infertility and might provide potential targets for male contraception or treatment of male infertility. [ABSTRACT FROM AUTHOR]

Background: Noscapine is an opium alkaloid that has recently been shown to potentiate anti-cancer therapeutic effects by inducing apoptosis in various malignant cells without any detectable toxicity. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. Materials and Methods: In this study, we explored the anti-cancer activity of noscapine in 5-fluorouracil (5-FU)-resistant human colon cancer cell lines HT29/5-FU and LoVo/5-FU and investigated the possible underlying mechanism. The apoptosis and mitochondrial morphology of cells were detected by TUNEL assay and transmission electron microscopy (TEM). The mitochondrial membrane potential (MMP) was determined using JC-1. The mitochondrial permeability transition pore (mPTP) opening was detected by the calcein-AM/cobalt assay. The levels of glucose, lactic, and ATP in cells were evaluated by ELISA kits. Relative protein expression levels were detected by Western blot. Results: We verified that PTEN was involved in noscapine-induced apoptosis in HT29/5-FU and LoVo/5-FU cells. Noscapine greatly increased mitochondrial damage by altering mitochondrial morphology, inducing mitochondrial membrane potential depolarization, and enabling mitochondrial permeability transition pore opening in HT29/5-FU and LoVo/5-FU cells. In addition, noscapine inhibited the Warburg effect by decreasing the levels of glucose, lactic acid, and ATP and inhibiting the protein expression of glucose transporter 1, lactate dehydrogenase-B, hexokinase 2, and pyruvate kinase M2 in HT29/5-FU and LoVo/5-FU cells. However, PTEN interference counteracted the effect of noscapine on mitochondrial damage and the Warburg effect in HT29/5-FU and LoVo/5-FU cells by decreasing the activation of PI3K/mTOR signaling. Conclusion: These results indicated that noscapine induced the apoptosis of HT29/5-FU and LoVo/5-FU human colon cancer cells by regulating mitochondria damage and the Warburg effect via PTEN, and the process is closely related to the PI3K/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: Two experiments were conducted to evaluate tetrabasic zinc chloride (TBZC) on the health of weaned pigs, and to determine the optimal supplemental concentrations and whether dietary TBZC could replace the pharmacological concentrations of dietary zinc oxide (ZnO) to improve growth performance and decrease Zn excretion in weaned pigs. Methods: In Exp. 1, 180 weaned pigs (8.92±1.05 kg body weight [BW]) were randomly assigned to 1 of 5 treatments, including the basal diet containing 125 mg/kg zinc sulfate (ZnSO4), and the basal diet with 1,200, 1,800, 2,400, or 3,000 mg/kg TBZC supplementation. In Exp. 2, 240 weaned pigs (7.66±1.09 kg BW) were randomly assigned to 1 of 5 treatments, including a negative control diet without Zn supplementation, a positive control diet (2,250 mg/kg ZnO), and 3 experimental diets with different concentrations of TBZC supplementation (1,000, 1,250, and 1,500 mg/kg). Results: In Exp. 1, the average daily gain (ADG), feed efficiency (G:F) and diarrhea incidence responded quadratically (p<0.01) as the TBZC supplemental concentrations increased, and pigs fed 1,200 and 1,800 mg/kg TBZC showed the best growth performance. Moreover, 1,800 mg/kg TBZC supplementation showed the greatest (p<0.01) total antioxidant capacity and glutathione peroxidase activities in liver of pigs. Histopathological examination revealed lesions in heart, liver, lung and kidney, and mild or severe histological lesions mainly occurred with the supplementation of 2,400 and 3,000 mg/kg TBZC. In Exp. 2, 1,000 and 1,250 mg/kg TBZC supplementation in diets significantly (p<0.01) increased ADG and G:F of weaned pigs, reduced Zn excretion in feces, and had no effect on diarrheareducing compared to 2,250 mg/kg ZnO supplementation. Conclusion: The TBZC is a potential alternative to ZnO. The recommended concentration of TBZC in weaned pig diets is 1,000 to 1,250 mg/kg. [ABSTRACT FROM AUTHOR]

Retinal endothelial cells (RECs) are involved in many ocular diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. Salicin is the major ingredient of willow bark extract, and it has been shown to be a potent anti-inflammatory agent. We aim to explore whether salicin has a vascular protective effect in RECs. Our data indicate that the presence of salicin in RECs culture media ameliorates interleukin-1β (IL-1β)-induced cellular reactive oxygen species (ROS) production and NADPH oxidase 4 (NOX-4) expression. At the cellular level, salicin attenuates IL-1β-induced mitochondrial injury as revealed by its preservation on mitochondrial membrane potential (MMP). Furthermore, salicin inhibits IL-1β-induced production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1), vascular adhesion molecules such as intercellular cell adhesion molecule-1 (iCAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and high-mobility group protein 1 (HMGB-1). On the other hand, salicin recovers IL-1β-induced reduction of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) release. The presence of salicin significantly reduces the IL-1β-induced release of lactate dehydrogenase (LDH), indicating that it mitigates cytokine caused cytotoxicity. Mechanistically, we show that salicin suppresses IL-1β-induced activation of the nuclear factor-kappa B (NF-κB) signaling as revealed by its suppression on nuclear p65 protein and transfected NF-κB promoter. Collectively, our study demonstrates by multiple facets of its mechanisms that salicin is a protective agent in retinal endothelial cells. These results imply its potential use in therapeutic usage of retinal disease. [ABSTRACT FROM AUTHOR]

Upon cytosolic viral DNA stimulation, cGMP-AMP synthase (cGAS) catalyzes synthesis of 2'3'cGMP-AMP (cGAMP), which binds to the adaptor protein MITA (mediator of IRF3 activation, also called STING, stimulator of IFN genes) and induces innate antiviral response. How the activity of MITA/STING is regulated to avoid excessive innate immune response is not fully understood. Here we identified the tyrosine-protein phosphatase nonreceptor type (PTPN) 1 and 2 as MITA/STING-associated proteins. PTPN1 and PTPN2 are associated with MITA/STING following viral infection and dephosphorylate MITA/STING at Y245. Dephosphorylation of MITA/ STING leads to its degradation via the ubiquitin-independent 20S proteasomal pathway, which is dependent on the intrinsically disordered region (IDR) of MITA/STING. Deficiencies of PTPN1 and PTPN2 enhance viral DNA-induced transcription of downstream antiviral genes and innate antiviral response. Our findings reveal that PTPN1/2-mediated dephosphorylation of MITA/STING and its degradation by the 20S proteasomal pathway is an important regulatory mechanism of innate immune response to DNA virus. [ABSTRACT FROM AUTHOR]

BRUCE/Apollon is a membrane-associated inhibitor of apoptosis protein that is essential for viability and has ubiquitin-conjugating activity. On initiation of apoptosis, the ubiquitin ligase Nrdp1/RNF41 promotes proteasomal degradation of BRUCE. Here we demonstrate that BRUCE together with the proteasome activator PA28γ causes proteasomal degradation of LC3-I and thus inhibits autophagy. LC3-I on the phagophore membrane is conjugated to phosphatidylethanol-amine to form LC3-II, which is required for the formation of autophagosomes and selective recruitment of substrates. SIP/CacyBP is a ubiquitination-related protein that is highly expressed in neurons and various tumors. Under normal conditions, SIP inhibits the ubiquitination and degradation of BRUCE, probably by blocking the binding of Nrdp1 to BRUCE. On DNA damage by topoisomerase inhibitors, Nrdp1 causes monoubiquitination of SIP and thus promotes apoptosis. However, on starvation, SIP together with Rab8 enhances the translocation of BRUCE into the recycling endosome, formation of autophagosomes, and degradation of BRUCE by optineurin-mediated autophagy. Accordingly, deletion of SIP in cultured cells reduces the autophagic degradation of damaged mitochondria and cytosolic protein aggregates. Thus, by stimulating proteasomal degradation of LC3-I, BRUCE also inhibits autophagy. Conversely, SIP promotes autophagy by blocking BRUCE-dependent degradation of LC3-I and by enhancing autophagosome formation and autophagic destruction of BRUCE. These actions of BRUCE and SIP represent mechanisms that link the regulation of autophagy and apoptosis under different conditions. [ABSTRACT FROM AUTHOR]

Abstract Cadherin-17 (CDH17), a structurally unique member of the non-classical cadherin family, is associated with poor survival, cell proliferation, and metastasis in colorectal cancer. However, the role of CDH17 in the apoptosis and autophagy of colorectal cancer cells remains unclear. Here, we aimed to investigate the effect of CDH17 knockdown on autophagy and apoptosis in colorectal cancer cells. We inhibited CDH17 expression in KM12SM and KM12C colorectal cancer cells by RNA interference and found that silencing of CDH17 significantly inhibited cell viability and increased apoptosis in KM12SM and KM12C cells. In addition, silencing of CDH17 significantly increased the expression of cleaved caspase-3 and Bax and decreased the expression of Bcl-2. Concurrently, silencing of CDH17 significantly inhibited the conversion of LC3-I to LC3-II and decreased the formation of LC3+ autophagic vacuoles and the accumulation of acidic vesicular organelles, indicating that autophagy was significantly inhibited in KM12SM and KM12C cells. Additionally, treatment with the autophagy-specific activator rapamycin attenuated apoptosis in CDH17-knockdown cells and as indicated by decreased caspase-3 activity, decreased expression of cleaved caspase-3 and Bax, and increased expression of Bcl-2. In conclusion, CDH17 silencing induced apoptosis and inhibited autophagy in KM12SM and KM12C cells, and this autophagy protected the cells from apoptotic cell death. [ABSTRACT FROM AUTHOR]

Recently, the major challenge in treating osteosarcoma patients is the metastatic disease, most commonly in the lungs. However, the underlying mechanism of recurrence and metastasis of osteosarcoma after surgical resection of primary tumor remains unclear. This study aims to investigate whether the pulmonary metastases characteristic of osteosarcoma is associated with surgical treatment and whether surgery contributes to the formation of pre‐metastatic niche in the distant lung tissue. In the current study, the authors observe the presence of circulating tumor cells in patients undergoing surgical resection of osteosarcoma which is correlated to tumor recurrence. The pulmonary infiltrations of neutrophils and Gr‐1+ myeloid cells are characterized to form a pre‐metastatic niche upon the exposure of circulating tumor cells after surgical resection. It is found that mitochondrial damage‐associated molecular patterns released from surgical resection contribute to the formation of pre‐metastatic niche in lung through IL‐1β secretion. This study reveals that surgical management for osteosarcoma, irrespective of the primary tumor, might promote the formation of postoperative pre‐metastatic niche in lung which is with important implications for developing rational therapies during peri‐operative period. [ABSTRACT FROM AUTHOR]

Purpose: Congenital muscular dystrophy (CMD) is a heterogeneous disease entity. The detailed clinical manifestation and causative gene for each subgroup of CMD are quite variable. This study aims to analyze the phenotypes and genotypes of Taiwanese patients with CMD as the epidemiology of CMD varies among populations and has been scantly described in Asia. Methods: A total of 48 patients suspected to have CMD were screened and categorized by histochemistry and immunohistochemistry studies. Different genetic analyses, including next-generation sequencing (NGS), were selected, based on the clinical and pathological findings. Results: We identified 17 patients with sarcolemma-specific collagen VI deficiency (SSCD), 6 patients with merosin deficiency, two with reduced alpha-dystroglycan staining, and two with striking lymphocyte infiltration in addition to dystrophic change on muscle pathology. Fourteen in 15 patients with SSCD, were shown to have COL6A1, COL6A2 or COL6A3 mutations by NGS analysis; all showed marked distal hyperlaxity and normal intelligence but the overall severity was less than in previously reported patients from other populations. All six patients with merosin deficiency had mutations in LAMA2. They showed relatively uniform phenotype that were compatible with previous studies, except for higher proportion of mental retardation with epilepsy. With reduced alpha-dystroglycan staining, one patient was found to carry mutations in POMT1 while another patient carried mutations in TRAPPC11. LMNA mutations were found in the two patients with inflammatory change on muscle pathology. They were clinically characterized by neck flexion limitation and early joint contracture, but no cardiac problem had developed yet. Conclusion: Muscle pathology remains helpful in guiding further molecular analyses by direct sequencing of certain genes or by target capture/NGS as a second-tier diagnostic tool, and is crucial for establishing the genotype-phenotype correlation. We also determined the frequencies of the different types of CMD in our cohort which is important for the development of a specific care system for each disease. [ABSTRACT FROM AUTHOR]

Air pollution is a severe threat to public health globally, affecting everyone in developed and developing countries alike. Among different air pollutants, particulate matter (PM), particularly combustion-produced fine PM(PM2.5) has been shown to play a major role in inducing various adverse health effects. Strong associations have been demonstrated by epidemiological and toxicological studies between increases in PM2.5 concentrations and premature mortality, cardiopulmonary diseases, asthma and allergic sensitization, and lung cancer. The mechanisms of PM-induced toxicological effects are related to their size, chemical composition, lung clearance and retention, cellular oxidative stress responses and pro-inflammatory effects locally and systemically. Particles in the ultrafine range (<100 nm), although they have the highest number counts, surface area and organic chemical content, are often overlooked due to insufficient monitoring and risk assessment. Yet, ample studies have demonstrated that ambient ultrafine particles have higher toxic potential compared with PM2.5. In addition, the rapid development of nanotechnology, bringing ever-increasing production of nanomaterials, has raised concerns about the potential human exposure and health impacts. All these add to the complexity of PM-induced health effects that largely remains to be determined, and mechanistic understanding on the toxicological effects of ambient ultrafine particles and nanomaterials will be the focus of studies in the near future. [ABSTRACT FROM AUTHOR]

Most of polypeptides containing α,β-dehydroamino acids have important biological activity, so exploration of synthetic method has practical significance. In this paper, dipeptides were prepared from l-threonine by protecting of c-terminal allyl acetate, and condensing reaction with a series of N-Boc amino acid. Then, treatment of dipeptides obtained with DMAP, (Boc)O and tetramethylguanidine in the acetonitrile occured β-elimination reaction to yield stereoselectively dehydrodipeptides. Structures of dehydrodipeptides were confirmed by H NMR, C NMR and MS. Analysis of H NMR, 2D NMR and crystal structure showed that the dehydrodipeptides were Z-configuration.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Background/Aims: Poor viability of transplanted mesenchymal stem cells (MSCs) within the ischemic heart limits their therapeutic potential for cardiac repair. Globular adiponectin (gAPN) exerts anti-apoptotic effects on several types of stem cells. Herein, we investigated the effect of gAPN on the MSCs against apoptosis induced by hypoxia and serum deprivation (H/ SD). Methods: MSCs exposed to H/SD conditions were treated with different concentrations of gAPN. To identify the main type of receptor, MSCs were transfected with siRNA targeting adiponectin receptor 1 or 2 (AdipoR1 or AdipoR2). To elucidate the downstream pathway, MSCs were pre-incubated with AMPK inhibitor Compound C. Apoptosis, caspase-3 activity and mitochondrial membrane potential were evaluated. Results: H/SD-induced MSCs apoptosis and caspase-3 activation were attenuated by gAPN in a concentration-dependent manner. gAPN increased Bcl-2 and decreased Bax expressions. The loss of mitochondrial membrane potential induced by H/SD was also abolished by gAPN. The protective effect of gAPN was significantly attenuated after the knockdown of AdipoRl rather than AdipoR2. Moreover, Compound C partly suppressed the anti-apoptotic effect of gAPN. Conclusions: gAPN inhibits H/SD-induced apoptosis in MSCs via AdipoR1-mediated pathway, possibly linked to the activation of AMPK. gAPN may be a novel survival factor for MSCs in the ischemic engraftment environment. [ABSTRACT FROM AUTHOR]

Escherichia coli that is unable to metabolize D-glucose (with knockouts in ptsG, manZ, and glk) accumulates a small amount of D-glucose (yield of about 0.01 g/g) during growth on the pentoses D-xylose or L-arabinose as a sole carbon source. Additional knockouts in the zwf and pfkA genes, encoding, respectively, D-glucose-6-phosphate 1-dehydrogenase and 6-phosphofructokinase I (E. coli MEC143), increased accumulation to greater than 1 g/liter D-glucose and 100 mg/liter D-mannose from 5 g/liter D-xylose or L-arabinose. Knockouts of other genes associated with interconversions of D-glucose-phosphates demonstrate that D-glucose is formed primarily by the dephosphorylation of D-glucose-6-phosphate. Under controlled batch conditions with 20 g/liter D-xylose, MEC143 generated 4.4 g/liter D-glucose and 0.6 g/liter D-mannose. The results establish a direct link between pentoses and hexoses and provide a novel strategy to increase carbon backbone length from five to six carbons by directing flux through the pentose phosphate pathway. [ABSTRACT FROM AUTHOR]

The article reports on the implications of the acquisition of Smithfield Foods, the largest hog producer and pork processor in the world, by Shuanghui International Holdings Ltd., the top pork producer in China. This acquisition raised concerns about domestic pork supplies and food safety in the U.S. The increase in Chinese demand for meet products is discussed.

Some long noncoding RNAs (lncRNAs) play important roles in the regulation of gene expression by acting as competing endogenous RNAs (ceRNAs). However, the roles of lncRNA associated-ceRNAs in oncogenesis are not fully understood. Here, based on lncRNA microarray data of gastric cancer, bioinformatic algorithm miRcode and microRNA (miRNA) targets database TarBase, we first constructed an lncRNA-miRNA-mRNA network. Then, we confirmed it by data of six types of other cancer including head and neck squamous cell carcinoma, prostate cancer, papillary thyroid carcinoma, pituitary gonadotrope tumors, ovarian cancer, and chronic lymphocytic leukemia. The results showed a clear cancer-associated ceRNA network. Eight lncRNAs (AC009499.1, GACAT1, GACAT3, H19, LINC00152, AP000288.2, FER1L4, and RP4-620F22.3) and nine miRNAs (miR-18a-5p, miR-18b-5p, miR-19a-3p, miR-20b-5p, miR-106a-5p, miR-106b-5p, miR-31-5p, miR-139-5p, and miR-195-5p) were involved. For instance, through its miRNA response elements (MREs) to compete for miR-106a-5p, lncRNA-FER1L4 regulates the expression of PTEN, RB1, RUNX1, VEGFA, CDKN1A, E2F1, HIPK3, IL-10, and PAK7. Furthermore, cellular experimental results indicated that FER1L4-small interfering RNA (siRNA) simultaneously suppressed FER1L4 and RB1 mRNA level. These results suggest that lncRNAs harbor MREs and play important roles in post-transcriptional regulation in cancer. [ABSTRACT FROM AUTHOR]

Abstract: The thermal boundary conductance between multilayer structures including Al film, semiconductors with high Debye temperatures (GaN, AlN, Si, diamond) and dielectric substrates (sapphire) has been measured using a two-color femtosecond laser pump-probe system (a variation of transient time-domain thermoreflectance, TDTR). The thermal boundary conductance for the combinations of semiconductors and dielectrics falls within a relatively narrow range, 10–20 MW m−2 K−1, at room temperature. The measured thermal boundary conductance between Al film and semiconductor or dielectric substrates is one order of magnitude larger than that between semiconductor and dielectric substrates. A modified diffuse mismatch model (DMM) is used to interpret the data and extract the phonon transmissivity at the interface. The predicted results of the DMM corrected by attenuation constant agree well with the experimental values. Over a wide phonon velocity, both the measured and predicted results decrease with the increasing average phonon velocity. Both the vibration mismatch and changes in the localized phonon transport near the interface contribute to the reduction in thermal boundary conductance. Other scattering mechanisms are discussed which may explain the failure of the DMM at room temperature. [Copyright &y& Elsevier]

Highlights: [•] We model 〈001〉/{100} single-crystalline Cu nanowires under bending and torsion. [•] Fivefold deformation twins (FDTs) are formed at large bending angles. [•] A reciprocal phase transformation is necessary for the formation of FDTs. [•] An orientation change of stress is also essential for the formation of FDTs. [ABSTRACT FROM AUTHOR]

[Display omitted] • N-CM particle electrode was prepared using shrimp shells via in situ hydrothermal carbonization method. • Pd catalyst was dispersed uniformly on N-CM with amorphous. • The Pd/N-CM electrode exhibited high activity and stability for electrocatalytic dechlorination DCF. Developing electrocatalysts with low cost, high abundance and high activity is the greatest challenge facing electrocatalytic hydrodechlorination technology. The Nitrogen-carbon microsphere (N-CM) material was synthesized in situ through a simple hydrothermal carbonization method using shrimp shells as C and N sources. N-CM with a rough surface was obtained at a carbonization temperature of 650 ℃, which has a large surface area of 90.14 m2/g and rich N content. Subsequently, the Pd catalyst was successfully modified on the N-CM surface by chemical reduction for electrocatalytic hydrodechlorination of Diclofenac (DCF). The successful loading of Pd and amorphous Pd structures was confirmed by a series of systematic characterizations. The amorphous Pd/N-CM-650 catalyst exhibits a fast electron transfer rate and electrocatalytic activity. Notably, at a Pd loading of 1.27 wt%, a cathode potential of −1.2 V and 20 mg of Pd/N-CM-650 particle electrodes, 25 mg/L DCF reached a dechlorination efficiency of 95% within 150 min with a current efficiency of 34.4%. Combined with the qualitative analysis and toxicity evaluation of hydrodechlorination products, the toxicity of DCF can be effectively reduced. Additionally, the cycle experiments also displayed excellent stability of the Pd/N-CM-650 electrode. [ABSTRACT FROM AUTHOR]

Background: Differences in interlaboratory research protocols contribute to the conflicting data in the literature regarding engineered nanomaterial (ENM) bioactivity. Objectives: Grantees of a National Institute of Health Sciences (NIEHS)-funded consortium program performed two phases of in vitro testing with selected ENMs in an effort to identify and minimize sources of variability. Methods: Consortium program participants (CPPs) conducted ENM bioactivity evaluations on zinc oxide (ZnO), three forms of titanium dioxide (TiO2), and three forms of multiwalled carbon nanotubes (MWCNTs). In addition, CPPs performed bioassays using three mammalian cell lines (BEAS-2B, RLE-6TN, and THP-1) selected in order to cover two different species (rat and human), two different lung epithelial cells (alveolar type II and bronchial epithelial cells), and two different cell types (epithelial cells and macrophages). CPPs also measured cytotoxicity in all cell types while measuring inflammasome activation [interleukin-1β (IL-1β) release] using only THP-1 cells. Results: The overall in vitro toxicity profiles of ENM were as follows: ZnO was cytotoxic to all cell types at ≥ 50 µg/mL, but did not induce IL-1β. TiO2 was not cytotoxic except for the nanobelt form, which was cytotoxic and induced significant IL-1β production in THP-1 cells. MWCNTs did not produce cytotoxicity, but stimulated lower levels of IL-1β production in THP-1 cells, with the original MWCNT producing the most IL-1β. Conclusions: The results provide justification for the inclusion of mechanism-linked bioactivity assays along with traditional cytotoxicity assays for in vitro screening. In addition, the results suggest that conducting studies with multiple relevant cell types to avoid false-negative outcomes is critical for accurate evaluation of ENM bioactivity. [ABSTRACT FROM AUTHOR]

Arkadia is a RING-based ubiquitin ligase that positively regulates TGF-β signaling by targeting several pathway components for ubiquitination and degradation. However, little is known about the mechanisms controlling Arkadia activity. Here we show that the LIM-only protein FHL2 binds and synergistically cooperates with Arkadia to activate Smad3/Smad4-dependent transcription. Knockdown of FHL2 by RNA interference decreases Arkadia level and restricts the amplitude of Arkadia-induced TGF-β target gene responses. We found that Arkadia is ubiquitinated via K63- and K27-linked polyubiquitination. A single mutation at the RING domain that abolishes the E3 activity diminishes Arkadia ubiquitination, indicating that this modification partly involves autocatalytic process. Mutation of seven lysines at the C-terminal region of Arkadia severely impairs ubiquitination through the K27 but not the K63 linkage and slows down the turnover of Arkadia, suggesting that K27-linked polyubiquitination might promote proteolysis-dependent regulation of Arkadia. We show that FHL2 increases the half-life of Arkadia through inhibition of ubiquitin chain assembly on the protein, which provides a molecular basis for functional cooperation between Arkadia and FHL2 in enhancing TGF-β signaling. Our study uncovers a novel regulatory mechanism of Arkadia by ubiquitination and identifies FHL2 as important regulator of Arkadia ubiquitination and TGF-β signal transduction. [ABSTRACT FROM AUTHOR]

The easily accessible mesenchymal stem cells in the Wharton's jelly of human umbilical cord tissue (hUCMSCs) have excellent proliferation and differentiation potential, but it remains unclear whether hUCMSCs can differentiate into odontoblasts. In this study, mesenchymal stem cells were isolated from the Wharton's jelly of human umbilical cord tissue using the simple method of tissue blocks culture attachment. UCMSC surface marker expression was then evaluated for the isolated cells using flow cytometry. The third-passage hUCMSCs induced by conditioned medium from developing tooth germ cells (TGC-CM) displayed high alkaline phosphatase (ALP) levels (P < 0.001), an enhanced ability to proliferate (P < 0.05), and the presence of mineralized nodules. These effects were not observed in cells treated with regular medium. After induction of hUCMSCs, the results of reverse transcriptional polymerase chain reaction (PCR) indicated that the dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP1) genes were significantly tested. Additionally, dentin sialoprotein (DSP) and DMP1 demonstrated significant levels of staining in an immunofluorescence analysis. In contrast, the control cells failed to display the characteristics of odontoblasts. Taken together, these results suggest that hUCMSCs can be induced to differentiate into odontoblast-like cells with TGC-CM and provide a novel strategy for tooth regeneration research. [ABSTRACT FROM AUTHOR]

Abstract: We examined the protective effect of l-citrulline on ethanol-induced gastric ulcer in rats. Administration of l-citrulline at doses of 300, 600 and 900mg/kg body weight prior to ethanol ingestion protected the stomach from ulceration. The gastric lesions were significantly attenuated by all doses of l-citrulline as compared to the ethanol group. Pre-treatment with l-citrulline prevented the oxidative damage and the decrease of nitric oxide content as well as the increase of the myeloperoxidase activity. Consequently, significant changes observed included the attenuation in the elevation in total nitric oxide synthase activity and inducible nitric oxide synthase activity as well as the decrease in constitutive nitric oxide synthase activity in the gastric mucosa induced by ethanol. Analysis of serum cytokines of ethanol-induced rats showed a moderate decrease in interleukin-10 with considerable increase of interleukin-6 while l-citrulline inhibited the acute alteration of cytokines. These results suggested the gastroprotective effect of l-citrulline. [Copyright &y& Elsevier]

Background: The efficient microbial utilization of lignocellulosic hydrolysates has remained challenging because this material is composed of multiple sugars and also contains growth inhibitors such as acetic acid (acetate). Using an engineered consortium of strains derived from Escherichia coli C and a synthetic medium containing acetate, glucose, xylose and arabinose, we report on both the microbial removal of acetate and the subsequent simultaneous utilization of the sugars. Results: In a first stage, a strain unable to utilize glucose, xylose and arabinose (ALS1392, strain E. coli C ptsG manZ glk crr xylA araA) removed 3 g/L acetate within 30 hours. In a subsequent second stage, three E. coli strains (ALS1370, ALS1371, ALS1391), which are each engineered to utilize only one sugar, together simultaneously utilized glucose, xylose and arabinose. The effect of non-metabolizable sugars on the metabolism of the target sugar was minimal. Additionally the deletions necessary to prevent the consumption of one sugar only minimally affected the consumption of a desired sugar. For example, the crr deletion necessary to prevent glucose consumption reduced xylose and arabinose utilization by less than 15% compared to the wild-type. Similarly, the araA deletion used to exclude arabinose consumption did not affect xylose- and glucose-consumption. Conclusions: Despite the modest reduction in the overall rate of sugar consumption due to the various deletions that were required to generate the consortium of strains, the approach constitutes a significant improvement in any single-organism approach to utilize sugars found in lignocellulosic hydrolysate in the presence of acetate. [ABSTRACT FROM AUTHOR]

Cancer remains a major public health problem in many countries. It was found to contain a subset of cancer stem cells (CSCs) that are capable of proliferation and self-renewal, and differentiation into various types of cancer cells. CSCs often display characteristics of chemotherapy resistance and radiotherapy resistance. Numerous putative biomarkers of CSCs are currently identified including CD133, CD44, CD24, ALDH (aldehyde dehydrogenase), and ABCG2. Interestingly, no single marker is exclusively expressed by CSCs. Thus, the various combinations of different biomarkers will be possible to identify CSCs, and considerable work is being done to recognize new ones. In order to demonstrate the mechanisms of resistance and response to therapy and predict the outcome as well as prognosis, the ways to track and identify CSCs will be extremely important. The technologies of molecular imaging will reveal mechanisms of cancer progression and provide visual targets for novel therapeutics. Limited studies were investigated on the detection of various types of CSCs by molecular imaging. Although the tracking of circulating CSCs is still hampered by technological challenges, personalized diagnosis and therapies of cancers are expected to be established based on increased understanding of molecular imaging of cancer stem-like cells biomarkers. [ABSTRACT FROM AUTHOR]

Cancer remains a major public health problem in many countries. It was found to contain a subset of cancer stem cells (CSCs) that are capable of proliferation and self-renewal, and differentiation into various types of cancer cells. CSCs often display characteristics of chemotherapy resistance and radiotherapy resistance. Numerous putative biomarkers of CSCs are currently identified including CD133, CD44, CD24, ALDH (aldehyde dehydrogenase), and ABCG2. Interestingly, no single marker is exclusively expressed by CSCs. Thus, the various combinations of different biomarkers will be possible to identify CSCs, and considerable work is being done to recognize new ones. In order to demonstrate the mechanisms of resistance and response to therapy and predict the outcome as well as prognosis, the ways to track and identify CSCs will be extremely important. The technologies of molecular imaging will reveal mechanisms of cancer progression and provide visual targets for novel therapeutics. Limited studies were investigated on the detection of various types of CSCs by molecular imaging. Although the tracking of circulating CSCs is still hampered by technological challenges, personalized diagnosis and therapies of cancers are expected to be established based on increased understanding of molecular imaging of cancer stem-like cells biomarkers. [ABSTRACT FROM AUTHOR]

Sac family phosphoinositide (PI) phosphatases are an essential family of CX5R(T/S)-based enzymes, involved in numerous aspects of cellular function such as PI homeostasis, cellular signalling, and membrane trafficking. Genetic deletions of several Sac family members result in lethality in animal models and mutations of the Sac3 gene have been found in human hereditary diseases. In this study, we report the crystal structure of a founding member of this family, the Sac phosphatase domain of yeast Sac1. The 2.0 Å resolution structure shows that the Sac domain comprises of two closely packed sub-domains, a novel N-terminal sub-domain and the PI phosphatase catalytic sub-domain. The structure further shows a striking conformation of the catalytic P-loop and a large positively charged groove at the catalytic site. These findings suggest an unusual mechanism for its dephosphorylation function. Homology structural modeling of human Fig4/Sac3 allows the mapping of several disease-related mutations and provides a framework for the understanding of the molecular mechanisms of human diseases. [ABSTRACT FROM AUTHOR]

We present a new method of performing high-resolution path delay testing on designs targeted to field- programmable gate arrays. Our built-in self-test (BIST) architecture uses an on-chip delay line element to set the launch time of each test pattern generator to its optimum point for stressing paths in the routed chip. The rising and falling edges of each test pattern are controllable with high precision, and consequently, our test architecture catches very small timing faults that exist in the path. For example, on Xilinx Virtex-4, we catch defects as small as 78 ps using the IDELAY delay line circuit that is available on that device. Our approach was validated on Virtex-4, and the same method can be applied to any device that supports on-chip delay lines that are adjustable at runtime. Furthermore, our architecture simultaneously tests multiple paths to reduce the overall test time. [ABSTRACT FROM AUTHOR]

Arsenic is frequently found in poultry waste, most of which is transformed from feed additive organoarsenicals, resulting in arsenic pollution of soils and water around poultry farms. The North China Plain, an important area for livestock breeding of China, was chosen to investigate the pollution characteristics and assess the health risk of arsenic around chicken farms. Among the 138 chicken farms sampled, almost no roxarsone, a common organoarsenical, was detected in chicken feeds, manure, and surface soils, while the detectable rate of other arsenic species was high. Because of long-term enrichment, the concentrations of arsenic species in manure were generally higher than that in feed. As(III) was the main inorganic arsenic species in the manure, where is reducing environment. In surface soils beneath the accumulated manure, As(V) was the predominant arsenic species with 100% detectable rate. The detectable rate and average concentrations at 0 cm were generally higher than those at 25 cm depth, indicating that arsenic accumulated in the surface soils. In addition, a typical conceptual diagram of arsenic was developed to clarify the pollution process from feed to soil. Through health risk assessment of inorganic arsenic, the carcinogenic risk (CR) and non-carcinogenic risk (non-CR) were both negligible. The city of Jiaozuo had the highest CR and non-CR, which was 11 times higher than that of the city with the lowest risks. This study presents a clear picture and evaluation of arsenic pollution on chicken farms, inspiring future studies assessing arsenic pollution after the ban of organoarsenicals. • Arsenic is widely present in chicken feed, manure, and surface soil with different species. • Arsenic accumulated in chicken manure and surface soils. • A typical pollution pattern of arsenic was developed to clarify the pollution process from feed to soil. [ABSTRACT FROM AUTHOR]

The nitric oxide receptor soluble guanylyl cyclase (sGC) exists in multimeric protein complexes, including heat shock protein (HSP) 90 and endothelial nitric oxide synthase. Inhibition of HSP90 by geldanamycin causes proteasomal degradation of sGC protein. In this study, we have investigated whether COOH terminus of heat shock protein 70-interacting protein (CHIP), a co-chaperone molecule that is involved in protein folding but is also a chaperone-dependent ubiquitin E3 ligase, could play a role in the process of degradation of sGC. Transient overexpression of CHIP in COS-7 cells degraded heterologous sGC in a concentration-related manner; this downregulation of sGC was abrogated by the proteasome inhibitor MG-132. Transfection of tetratricopeptide repeats and U-box domain CHIP mutants attenuated sGC degradation, suggesting that both domains are indispensable for CHIP function. Results from immunoprecipitation and indirect immunofluorescent microscopy experiments demonstrated that CHIP is associated with sGC, HSP90, and HSP70 in COS-7 cells. Furthermore, CHIP increased the association of HSP70 with sGC. In in vitro ubiquitination assays using purified proteins and ubiquitin enzymes, E3 ligase CHIP directly ubiquitinated sGC; this ubiquitination was potentiated by geldanamycin in COS-7 cells., followed by proteasomal degradation. In rat aortic smooth muscle cells, endogenous sGC was also degraded by adenovirus-infected wild-type CHIP but not by the chaperone interaction-deficient K30A CHIP, whereas CHIP, but not K30A, attenuated sGC expression in, and nitric oxide donor-induced relaxation of, rat aortic rings, suggesting that CHIP plays a regulatory role under physiological conditions. This study reveals a new mechanism for the regulation of sGC, an important mediator of cellular and vascular function. [ABSTRACT FROM AUTHOR]

In this paper, a jitter measurement circuit for mixed-signal production test based on the interpolation algorithm is presented. By utilizing the limited sampling points per cycle, the original signal under test is reconstructed with a high accuracy. From the reconstructed signal, most timing jitter features can be characterized. To validate the design effectiveness, comparative studies have been performed between this jitter measurement method and other standard jitter characterization instruments. [ABSTRACT FROM AUTHOR]

Vascular soluble guanylate cyclase (sGC) exists in multimeric complexes with endothelial nitric oxide (NO) synthase (eNOS) and heat shock protein 90 (hsp90). Whereas disruption of hsp90-eNOS complexes clearly attenuates eNOS-dependent vascular relaxation, the contribution of sGC-hsp90 complexes to eNOS- or NO donor-dependent relaxations remains unclear. Isolated rat thoracic aortic rings were preincubated with structurally diverse hsp90 binding inhibitors, radicicol (RA) or geldanamycin (GA), or vehicle for 0.5, 1, or 15 h. Preconstricted vessels were exposed to ACh, 8-bromo-cGMP (8-BrcGMP), forskolin, or one of three NO donors: nitroglycerin (NTG), sodium nitroprusside, or spermine NONOate (SNN). Both RA and GA inhibited endothelium-dependent relaxations dose dependently. Indomethacin or the antioxidant tiron did not affect the inhibition of ACh-induced relaxations by GA. Long-term (15 h) exposure to RA inhibited all NO donor-induced relaxations; however, GA inhibited SNN-induced relaxation only. The effects of GA and RA appeared to be selective because 15-h treatment with either agent did not affect forskolin-induced relaxations and only slightly decreased 8-BrcGMP-induced relaxations. Similarly to their effects on NO-donor-induced relaxation, 15-h exposure to RA, but not to GA, decreased hsp90-bound sGC protein expression and NTG-stimulated cGMP formation in aortic rings, whereas RA more than GA reduced SNN-stimulated cGMP formation. We conclude that RA, much more so than GA, selectively inhibits sGC-dependent relaxations of aortic rings by reducing sGC expression, disrupting sGC-hsp90 complex formation and decreasing cGMP formation. These studies suggest that hsp90 regulates both eNOS- and sGC-dependent relaxations. [ABSTRACT FROM AUTHOR]

Molybdenum trioxide nanobelts and prism-like particles with good crystallinity and high surface areas have been prepared by a facile hydrothermal method, and the morphology could be controlled by using different inorganic salts, such as KNO3, Ca(NO3)2, La(NO3)3, etc. The possible growth mechanism of molybdenum trioxide prism-like particles is discussed on the basis of the presence of H+ and the modification of metal cations. The as-prepared nanomaterials are characterized by means of powder X-ray diffraction (PXRD), field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), Fourier transformation infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and ultraviolet and visible spectroscopy (UV−vis). TEM and HRTEM micrographs show that the molybdenum trioxide nanobelts and prism-like particles have a relatively high degree of crystallinity and uniformity. BET specific surface areas of the as-prepared molybdenum trioxide nanocrystals are 67−79 m2 g-1. XPS analysis indicates that the hexavalent molybdenum is predominant in the nanocrystals. UV−vis spectra reveal that the direct band gap energy of the annealed molybdenum trioxide prism-like particles shows a pronounced blue shift compared to that of bulk MoO3 powder. Interestingly, molybdenum trioxide nanobelts exhibit a red shift under this condition. [ABSTRACT FROM AUTHOR]

Summary: This paper reports a computational method for folding small helical proteins. The goal was to determine the overall topology of proteins given secondary structure assignment on sequence. In doing so, a Monte Carlo protocol, which combines coarse-grained normal modes and a Hamiltonian at a different scale, was developed to enhance sampling. In addition to the knowledge-based potential functions, a small-angle X-ray scattering (SAXS) profile was also used as a weak constraint for guiding the folding. The algorithm can deliver structural models with overall correct topology, which makes them similar to those of 5∼6 Å cryo-EM density maps. The success could contribute to make the SAXS technique a fast and inexpensive solution-phase experimental method for determining the overall topology of small, soluble, but noncrystallizable, helical proteins. [Copyright &y& Elsevier]

Particulate pollutants cause adverse health effects through the generation of oxidative stress. A key question is whether these effects are mediated by the particles or their chemical compounds. In this article we show that aliphatic, aromatic, and polar organic compounds, fractionate from diesel exhaust particles (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses showed that the quinone-enriched polar fraction was more potent than the polycyclic aromatic hydrocarbon (PAI-I)-enriched aromatic fraction in O2- generation, decrease of membrane potential (δψm), loss of mitochondrial membrane mass, and induction of apoptosis. A major effect of the polar fraction was to promote cyclosporin A (CsA)-sensitive permeability transition pore (PTP) opening in isolated liver mitochondria. This opening effect is dependent on a direct effect on the PTP at low doses as well as on an effect on δψm at high doses in calcium (Ca2+-loaded mitochondria. The direct PTP effect was mimicked by redox-cycling DEP quinones. Although the aliphatic fraction fiuiled to pertur mitochondrial function, the aromatic fraction increased the Ca2+ retention capacity at low doses and induced mitochondrial swelling and a decrease in δψm at high doses. This swelling effect was mostly GA insensitive and could be reproduced by a mix- ture of PAl-Is present in DEPs. These chemical effects on isolated mitochondria could be reproduced by intact DEPs as well as ambient ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles failed to exert mitochondrial effects. These results suggest that DEP and UFP effects on the PTP and δψm are mediated by adsorbed chemicals rather than the particles themselves. [ABSTRACT FROM AUTHOR]

In this paper, we present the concept and design of a time-to-voltage converter (TVC), and demonstrate its application to on-chip phase-locked loop (PLL) jitter measurement The TVC operates in an analog, continuous mode without using a sampling clock. It compares the signal under measurement with a reference signal by charging and discharging a capacitor. First, the low-frequency reference signal charges the capacitor in one cycle. Then, the jitter signal discharges the same capacitor repeatedly until the voltage on the capacitor falls below a threshold. The number of times the jitter signal needs to discharge the capacitor is recorded on a binary counter. We demonstrated that a 160-ps injected jitter is successfully measured by the proposed TVC with a 2-MHz reference signal. We also demonstrated the successful measurement of a 14-ps average PLL jitter, without jitter injection. An 8% measurement error is found in both experiments, using four-bit counters. Finally, we analyze the relations between design parameters and show trade-offs between measurement resolution and measurement time. [ABSTRACT FROM AUTHOR]

Analyzes the regulation of p21, a well characterized p53 target gene, by various p53 mutants deficient in one or more of the activation domains. Use of stable cell lines to analyze differential regulation of p21 by wild-type p53 or various mutants; Protein extraction and immunoblotting; Generation of short interference RNA expression plasmids under the control of the U6 promoter.

Nd 0.9 Ln 0.1 BaCo 2 O 6- δ (NLnBCO, Ln = La, Sm, Gd) materials are synthesized by EDTA-citrate method. The effects of rare earth element doping on crystal structure, thermal expansion behavior, electrical conductivity and electrochemical properties are investigated. Nd 0.9 Ln 0.1 BaCo 2 O 6- δ crystallizes in tetragonal symmetry with the space group P4/mmm. It is found that both the unit cell volume and the average valence of cobalt in NLnBCO increase, whereas the oxygen vacancy content (δ value) decreases with the gradual enlargement of the radius of the doped rare earth elements. XPS and O 2 -TPD results prove that the surface oxygen adsorption ability of NLnBCO improves gradually with the steady increase of Co4+ concentration in the material. The electrochemical impedance spectroscopy measurement results indicate that among the doped materials, Nd 0.9 La 0.1 BaCo 2 O 6- δ exhibits the lowest polarization resistance of 0.083 Ω cm2 at 700 °C in air. The anode-supported fuel cell constructed with this cathode shows a power output of 1.045 W cm−2 at 700 °C, and stable current density of 1.7 A cm−2 has been obtained with the load of 0.6 V for prolonged 100 h consecutive measurement. The rate limiting step of the oxygen reduction reaction (ORR) is the charge transfer process on Nd 0.9 La 0.1 BaCo 2 O 6- δ cathode. Our studies prove that doping La3+ with larger radius than Nd3+ is an effective way to promote the ORR reaction on NdBaCo 2 O 6- δ cathode. • The effects of rare earth element doping on the electrochemical properties of Nd 0.9 Ln 0.1 BaCo 2 O 6- δ are investigated. • La3+ doping improves the surface oxygen adsorption ability of Nd 0.9 Lan 0.1 BaCo 2 O 6- δ. • The anode-supported fuel cell constructed with Nd 0.9 Lan 0.1 BaCo 2 O 6- δ cathode shows a power output of 1.045 W cm−2 at 700 °C. [ABSTRACT FROM AUTHOR]

• Temperature effects on shock wave propagation properties are studied. • Temperature effects on shock-induced micro-plasticity behaviors are studied. • Melting and re-crystallization under shock loading is analyzed. • Spalling under elevated temperature is investigated and compared with experiments. Initial temperature effects on shock responses, including shock-induced plasticity and spalling damage behaviors of single-crystalline Cu are investigated by molecular dynamics simulations. Firstly, initial temperature effects on stress wave profiles are investigated. The simulations show that shock Hugoniot stress deceases as initial temperature increases, which can be explained by the Rakine-Hugoniot conservation theory. Initial temperature effects on dislocation density are studied. It is found that the dislocation density decreases as initial temperature increases. Shock-induced spalling is dominated by cavitation, i.e., void nucleation, growth and coalescence. Initial temperature effects on cavitation are discussed. In cases of relatively low shock intensity, the total number of voids increases as initial temperature rises; for strong shock intensities that induce melting and micro-spalling, initial temperature effects on the total number of voids are not obvious. Furthermore, initial temperature effects on spall strength are found to be dependent on shock intensity. For relatively weak shock intensity, the simulations show that spall strength starts to drop when initial temperature exceeds 900 K, far below the melting temperature, this result is well consistent with previous experimental measurements; however, for high shock intensity, our simulations predict that spall strength decreases monotonically as initial temperature increases. [ABSTRACT FROM AUTHOR]

• Features of stress wave evolutions in multilayers are investigated by atomistic simulations. • Strong discontinuities of stress components at the interfaces are revealed. • Slip transmission of lattice dislocations across semi-coherent interfaces is direction-dependent. • Thermal dissipation process during cavitation is analyzed. • More clear explanation of spallation process is shown by contour plots and profiles of stress. Shock response and spalling behaviors of semi-coherent {111} Cu-Al multilayer are investigated by molecular dynamics simulations. Firstly, the influences of interfaces on shock wave propagation are studied. The simulations show that reflection-unloading happens when the shock wave propagates from Cu to Al and reflection-loading occurs when the shock wave propagates from Al to Cu. Strong discontinuities of stress components at the interfaces are revealed as well, the discontinuities are correlated to mismatches of Hugoniot curves and elastic-plastic properties of the two materials adjacent to the interfaces. Secondly, shock induced dislocation activities are studied. It is found that the stress barrier offered by the interface Cu-Al is smaller than that offered by Al-Cu. In fact, the resistance for dislocations to transmit through interfaces is determined by the coherency stresses, Koehler stresses and misfit dislocations at the interface. In addition, spalling fracture of Cu-Al multilayers after stress wave reflection at the free surface is studied. It is observed that ductile damage only nucleates in Al layer, rather than in Cu layers. This observation agrees well with the experimental results of Han (Acta Mater., 2014 (63) 150–161). Due to complex reflection and transmission of the stress waves at the interfaces, the profile of the free surface velocity histories of the multilayer target is quite different from that of the single-crystalline counterpart. In order to study thermal dissipation process during cavitation, analysis on thermal dissipation in the spalling damage zones is also provided in this paper. Moreover, contour plots and profiles of stress are illustrated to understand the spallation process of the multilayer target deeply. Tensile stress emerges in Al 1 layer first, causing voids to nucleate; then the tensile stress wave attenuates rapidly and propagates to Cu 1 and Cu 2 layers. With the dissipation effect of damage and plastic deformation in the target, the tensile stress wave dissipates ultimately. [ABSTRACT FROM AUTHOR]