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The Functional Assessment of Chronic Illness Therapy-Palliative Care (FACIT-Pal) has been widely used in assessing the quality of life (QOL) of patients with life-limiting illness. However, the Chinese version of the FACIT-Pal has not been psychometrically validated yet. The purpose of this study was to psychometrically validate the FACIT-Pal in Chinese patients with advanced cancer. 160 patients with advanced cancer in mainland China participated in this cross-sectional study. The scalability of the instrument was determined by the item-total correlations and the reliability was tested by examining the Cronbach's alpha coefficients. The construct and concurrent validity of the FACIT-Pal were also examined. The item-total correlation coefficients ranged from 0.25 to 0.72 (P <.01). Cronbach's alpha coefficient of the Chinese version of the FACIT-Pal was 0.94, ranging from 0.78 to 0.89 for subscales. Confirmatory factor analysis (CFA) results provided support for the measurement structure of the 26-item Functional Assessment of Cancer Therapy-General (FACT-G). Exploratory factor analysis (EFA) of the 19-item palliative care subscale identified five factors accounting for 62.21% of the total variance. Total/subscale scores of the FACIT-Pal were positively correlated with that of the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 Item Scale (FACIT-Sp-12) (r = 0.338–0.811, P <.01), as well as with the Karnofsky Performance Scale (KPS) scores (r = 0.163–0.273, P <.05), except for the correlation between social/family well-being subscale score and KPS score. The Chinese version of the FACIT-Pal demonstrates desirable psychometric properties for evaluating QOL in Chinese patients with advanced cancer. [ABSTRACT FROM AUTHOR]

We investigate spalling behaviors of Ni/Al nanolaminates by molecular dynamics simulations. First, we discuss spalling damage distributions in shocked Ni/Al nanolaminates. Voids nucleate in Al layers, while no voids are located in Ni layers or along the Ni/Al interfaces. This is because the spall strength of single-crystalline Ni is higher than that of single-crystalline Al. We reveal influences of a shock-induced chemical reaction on dynamic spalling damage and fracture processes. An abnormal "decrease → increase → decrease" zigzag variation tendency of the spall strength of Ni/Al nanolaminates as the impact velocity increase is observed in our simulations, which resulted from combining effects of micro-structures, chemical reactions, and temperature softening. When the impacting intensity is relatively low, the spall strength of Ni/Al nanolaminates decreases as the impact velocity increases due to micro-structure effects. However, when the loading velocity increases to a certain magnitude (2.5 km/s), the intimate contact of liquid Al with amorphous Ni near the interface makes the chemical reaction rate increase rapidly to form a large amount of Ni/Al alloys and enhances the spall strength. [ABSTRACT FROM AUTHOR]

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]

The morphology evolution mechanism of polystyrene (PS)/poly (vinyl methyl ether) (PVME) blend thin films with different PS molecular weights (Mw) was studied. It was found that the morphology evolution was closely related to the molecular weight asymmetry between PS and PVME. In the film where Mw(PS) ≈ Mw(PVME), dewetting happened at the interface between the bottom layer and substrate after SD phase separation. While in the film where Mw(PS) >> Mw(PVME), dewetting happened at the interface between the middle PS/PVME blend layer and bottom PVME layer near the substrate prior to phase separation. The different sequences of phase separation and dewetting and different interface for dewetting occurrence were studied by regarding the competitive effects of viscoelasticity contrast between polymer components and preferential wetting between PVME and the substrate. The viscoelastic nature of the PS component played a crucial role in the sequence of phase separation and dewetting. [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]

Background: Myopia is a very common eye disease with an unknown etiology. Increasing evidence shows that mitochondrial dysfunction plays an active role in the pathogenesis and progression of this disease. Objectives: The purpose of this study was to analyze the relationship between mitochondrial tRNA (mt-tRNA) variants and high myopia (HM). Methods: The entire mt-tRNA genes of 150 children with HM, as well as 100 healthy subjects, were PCR-amplified and sequenced. To assess the pathogenicity, we used the phylogenetic conservation analysis and pathogenicity scoring system. Results: We identified six candidate pathogenic variants: tRNALeu (UUR)T3290C, tRNAIle A4317G, tRNAAla G5591A, tRNASer (UCN) T7501C, tRNAHis T12201C, and tRNAThr G15915A. However, these variants were not identified in controls. Further phylogenetic analysis revealed that these variants occurred at the positions, which were very evolutionarily conserved and may have structural-functional impacts on the tRNAs. Subsequently, these variantsmaylead to the impairment of mitochondrial translation and aggravated mitochondrial dysfunction, which play an active role in the phenotypic expression of HM. Conclusions: Our results suggested that variants in mt-tRNA genes were the risk factors for HM, which provided valuable information for the early detection and prevention of HM. [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]

Study Design: Observational, anatomical, radiological study.Objective: The aim of this study was to explore the incidence and type of vertebral artery (VA) variation in patients with congenital cervical scoliosis and approach their clinical importance during surgery.Summary Of Background Data: Congenital scoliosis of the cervical spine is usually sporadic and caused by a variety of bone structural anomalies. Most of the cases remain asymptomatic. Surgical intervention is the main management for patients with neurological compromise or with cosmetic demands. The operation involved more screw insertion and osteotomy than the regular degenerative cases. The incidence and pattern of VA variants in these patients have not been reported.Methods: Patients with congenital cervical scoliosis treated in our department were reviewed. We measured Cobb angle of cervical spine. We observed bilateral VAs and recorded variants. We measured their diameter in each segment through CT angiography. The bilateral diameter in each patient was then compared respectively.Result: There is a total of 44 patients enrolled. The incidence of VA variation was 41% (18/44). Fifty percent (22/44) of patients had the dominant VA with no difference between concave side and convex side. Patients with a dominant VA had a larger Cobb angle than those who had not (30.25° vs. 23.24°, P < 0.05). The courses of VA were abnormal in 18 patients. Two patients had unilateral variant in V1 segment. Twelve patients had variants in V2 segment. Eight patients had variants in V3 segment. Three patients had VA variants in multiple sites.Conclusion: In patients with congenital cervical scoliosis, the dominance of VA is not related to the convex side or concave side, but patients with a dominance of VA have a larger Cobb angle. The incidence of variant in V2 and V3 segment is higher. A thorough evaluation of bilateral VAs is required before surgery. Extra cautions must be taken during surgery.Level of Evidence: 5. [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]

The inflammatory fibroid polyp (IFP), or Vanek's tumor, is one of the least common benign lesions that originate from mesenchymal cells and may occur throughout the gastrointestinal (GI) tract. Six patients were treated by endoscopy, including endoscopic mucosal resection (EMR) in three patients and endoscopic submucosal dissection (ESD) in the other three. On the other hand, for IFP located in specific locations, such as the small intestine, and in emergency situations that causing obstruction or intussusception, a surgical operation is indispensable. 15 Fleres F, Mazzeo C, Ieni A, Rossitto M, Cucinotta E. Gastric inflammatory fibroid polyp tumor with acute intestinal obstruction - Vanek's tumor can mimick a giant gastrointestinal stromal tumor or a gastric lymphoma. [Extracted from the article]

Objectives: Evidence of the association between fine particulate (PM25, particles ≤2.5 µm in aerodynamic diameter) air pollution and fatal hemorrhagic stroke incidence is limited. This study aims to document the relationship between PM2.5 exposure and fatal hemorrhagic stroke incidence. Methods: The time-stratified case-crossover approach was applied for the analysis. Results: The mean concentration of PM2.5 is 75.33 µg/m³. Fatal hemorrhagic stroke incidence was significantly associated with PM2.5 exposure. Exposure to PM2.5 led to a 5% (2%-9%) and 5% (1%-10%) increase in fatal hemorrhagic stroke incidence in lag2 and lag03 respectively. An increased risk was observed especially in men and subjects with hypertension. Conclusions: This study provides evidence for the association between PM2.5 exposure and fatal hemorrhagic stroke incidence. Men and subjects with hypertension have increased risks, overweight may further increase their susceptibility to PM2.5 exposure related hemorrhagic stroke. [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]

The mechanism of exosomes derived from activated hepatic stellate cells (HSCs) involved in liver fibrosis is poorly understood. We previously reported that hypoxia-inducible factor 1 (Hif-1) regulated HSC activation, and, therefore, we investigated in current work whether Hif-1 regulates exosome secretion and the metabolic switch of HSCs, thus affecting the metabolism of liver nonparenchymal cells. In this study, the characteristics of exosomes from HSCs were assessed via electron microscopy, Western blot analysis, and acetylcholinesterase activity. Confocal microscopy was used to measure the uptake of exosomes by quiescent HSCs, Kupffer cells (KCs), and liver sinusoidal endothelial cells (LSECs). Hif-1a was inhibited via 2-ME or specific small interfering RNAs to investigate its role in exosomes derived from HSCs. It was determined that glucose transporter 1 and pyruvate kinase M2 were increasingly expressed in fibrotic liver samples, cell lysates, and exosomes derived from activated HSCs. Exosomes released from HSCs were associated with activation and glucose uptake of HSCs. Delivery of exosomes from activated HSCs induced glycolysis of quiescent HSCs, KCs, and LSECs. Disruption of Hif-1 expression suppressed the glycolysis effect delivered by exosomes. Conclusively, our results demonstrated that exosomes secreted by activated HSCs affect the metabolic switch of liver nonparenchymal cells via delivery of glycolysis-related proteins. These findings represent a novel mechanism that contributes to liver fibrosis and has significant implications for new diagnosis and treatment of liver diseases.--Wan, L., Xia, T., Du, Y., Liu, J., Xie, Y., Zhang, Y., Guan, F., Wu, J., Wang, X., Shi, C. Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exosomes in metabolic switch of liver nonparenchymal cells. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A facile quaternarization strategy to a g-C 3 N 4 ionic liquid nanostructure was developed. • Quaternarization involved a nucleophilic substitution of the tri-s-triazine subunits by n -BuBr. • The IL nanostructure improved the conductivity, dispersibility and stability of IL-CNNS dispersion. • IL-CNNS/GCE displayed a fast electron transfer and the better catalytic activity to 2,4-DCP. Abstract We have developed a facile quaternarization strategy to an ultrathin lamellar g-C 3 N 4 ionic liquid nanostructure (IL-CNNS) via a nucleophilic substitution between the tertiary amino groups in tri- s -triazine subunits and n-butyl bromide. After functionalization, the obtained IL-CNNS composite exhibits the enhanced conductivity, dispersibility and stability owing to the formation of IL structure. This composite has been characterized by several spectroscopic techniques (FT-IR, XRD, XPS, TGA and TEM). The IL-CNNS modified electrode displays the larger effective surface area and the faster electron transfer rate, hence resulting in the superior electrocatalytic activity toward 2,4-Dichlorophenol (2,4-DCP). Under the optimal conditions, the proposed 2,4-DCP sensor gives rise to the wide linear range from 0.02 to 160 μM with a low detection limit (6.21 nM, S/N = 3) by amperometric method. The developed sensor has been applied to detect 2,4-DCP in water samples with satisfactory recoveries and stability. This quaternarization strategy may open up a new avenue to fabricate the layered carbon nitride IL nanostructure for electrochemical sensing applications. [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]

ABSTRACT: Proteasomes are responsible for the turnover of most cellular proteins, and thus are critical to almost all cellular activities. A substrate entering the proteasome must first bind to a substrate receptor. Substrate receptors can be classified as ubiquitin receptors and non‐ubiquitin receptors. The intrinsic ubiquitin receptors, including proteasome regulatory particle base subunits 1, 10 and 13 (Rpn1, Rpn10, and Rpn13), determine the capability of the proteasome to recognize a ubiquitin chain, and thus provide selectivity for the 26S proteasome. However, the non‐ubiquitin receptors, including proteasome activator 200 (PA200) and PA28γ, have received great attention due to their remarkable compensatory roles relative to canonical ubiquitin‐mediated proteasomal degradation. Herein we review recent advances in understanding the contributions of these substrate receptors to proteasomal degradation, and introduce their substrates and interacting factors. We also provide insights into their biological functions related to spermatogenesis, immune responses, cellular homeostasis, and tumour development. Finally, we summarize advances in developing small‐molecule inhibitors of these substrate receptors and discuss their potential as drug targets. [ABSTRACT FROM AUTHOR]

Abstract: Graphene oxide (GO) was chemically grafted by ionic liquid (IL) containing amino groups for preparation of IL covalently functionalized GO (IL–CFGO). SEM, FTIR and XRD results confirmed that IL had been successfully anchored on GO surface, resulting in more active sites and higher conductivity. The IL–CFGO composite was coated on the surface of carbon IL electrode (CILE) to construct electrochemical sensor for simultaneous detection of Cu(II) and Sb(III). The experimental factors including pH, deposition time and potential were optimized. Differential pulse voltammetry was employed for the simultaneous determination of Cu(II) and Sb(III) under the optimal conditions. The IL–CFGO/CILE exhibited the wide linear ranges of 0.1∼28 μM for Cu(II) and 0.1∼20 μM for Sb(III) with detection limits of 0.04 and 0.06 μM, respectively. The proposed sensor displayed good reproducibility, selectivity and acceptable stability owing to the contributions of the more active sites and the enhanced conductivity. [ABSTRACT FROM AUTHOR]

Hydroxyl radical (•OH), as the most deleterious reactive oxygen species, is believed to be the etiological agent for many diseases and aging. An altered •OH level has been confirmed in certain types of superoxide dismutase (SOD) mutation, but the regulation of •OH by SOD in situ is still controversial or unclear because of the lack of effective tools to detect •OH in the biological environment. Herein we report the first two-photon excitable molecular probe (P2) for •OH, which is able to track the subtle fluctuation of •OH level both in vitro and in vivo with high sensitivity and specificity. The probe was successfully applied to visualize •OH variations in a variety of SOD1-involved biological processes, confirming that the inhibited enzymatic activity and down-regulated expression of SOD1 both lead to elevated intracellular •OH level. This is the first report to visually reveal the relationship between SOD1 and •OH level with a molecular tool. [ABSTRACT FROM AUTHOR]

20 to explain the plastic deformation mechanism; the explanation of why the twin boundary can serve as an obstacle of dislocation movement on one side and also serve as dislocation nucleation sites is presented in Figs. 22 and 23; and the energy of grain boundary, twin boundary, and stacking faults are listed in Table I to explain why grain boundary only plays one role as dislocation nucleation sites, but the twin boundary can play two roles. The nanowires in both our paper and Ref. [3] were constructed according to the previous experimental observation.[4] In Ref. [3], the plastic deformation mechanism of polycrystalline nanowires was studied. [Extracted from the article]

Biological removal of nitrate, a highly concerning contaminant, is limited when the aqueous environment lacks bioavailable electron donors. In this study, we demonstrated, for the first time, that bacteria can directly use the electrons originated from the photoelectrochemical process to carry out the denitrification. Ln such photoelectrotrophic denitrification (PEDeN) systems (denitrification biocathode coupling with TiO2 photoanode), nitrogen removal was verified solely relying on the illumination dosing without consuming additional chemical reductant or electric power. Under the UV illumination (30 mW-cm-2, wavelength at 380 ± 20 nm), nitrate reduction in PEDeN apparently followed the first-order kinetics with a constant of 0.13 ± 0.023 IT1. Nitrate was found to be almost completely converted to nitrogen gas at the end of batch test Compared to the electrotrophic denitrification systems driven by organics (OEDeN, biocathode/acetate consuming bioanode) or electricity (EEDeN, biocathode/abiotic anode), the denitrification rate in PEDeN equaled that in OEDeN with a COD/N ratio of 9.0 or that in EEDeN with an applied voltage at 2.0 V. This study provides a sustainable technical approach for eliminating nitrate from water. PEDeN as a novel microbial metabolism may shed further light onto the role of sunlight played in the nitrogen cycling in certain semiconductive and conductive minerals-enriched aqueous environment [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]

Actinomorphic flowers usually orient vertically (relative to the horizon) and possess symmetric nectar guides, while zygomorphic flowers often face horizontally and have asymmetric nectar guides, indicating that floral symmetry, floral orientation, and nectar guide patterning are correlated. The origin of floral zygomorphy is dependent on the dorsoventrally asymmetric expression of CYCLOIDEA (CYC)-like genes. However, how horizontal orientation and asymmetric nectar guides are achieved remains poorly understood. Here, we selected Chirita pumila (Gesneriaceae) as a model plant to explore the molecular bases for these traits. By analyzing gene expression patterns, protein–DNA and protein–protein interactions, and encoded protein functions, we identified multiple roles and functional divergence of 2 CYC-like genes, i.e. CpCYC1 and CpCYC2, in controlling floral symmetry, floral orientation, and nectar guide patterning. CpCYC1 positively regulates its own expression, whereas CpCYC2 does not regulate itself. In addition, CpCYC2 upregulates CpCYC1, while CpCYC1 downregulates CpCYC2. This asymmetric auto-regulation and cross-regulation mechanism might explain the high expression levels of only 1 of these genes. We show that CpCYC1 and CpCYC2 determine asymmetric nectar guide formation, likely by directly repressing the flavonoid synthesis-related gene CpF3′5′H. We further suggest that CYC-like genes play multiple conserved roles in Gesneriaceae. These findings shed light on the repeated origins of zygomorphic flowers in angiosperms. CYCLOIDEA-like genes play multiple roles in determining floral symmetry, floral orientation, and nectar guide patterning in the model plant Chirita pumila and likely other Gesneriaceae species. [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]

A series of arylidene N -alkoxydiketopiperazines was designed and stereoselectively synthesized via oxime-ether formation and intramolecular acylation. Possible cyclization and acid-catalyzed rearrangement-fragmentation mechanisms were discussed. The crystal structure of the novel diketopiperazine further confirmed the rearrangement mechanism. Most compounds exhibited antitumor activity. Several compounds were more potent against caspase-3. Specifically, compounds 6e , 6g , and 6f inhibited caspase-3 at IC 50 values lying within the low micromolar range and demonstrated good selectivity. The binding modes of alkoxydiketopiperazines in the active center of caspase-3 were also discussed based on the molecular docking results. [ABSTRACT FROM AUTHOR]

Many patients with diabetes are at increased risk of cognitive dysfunction and dementia. Resveratrol, a polyphenol found mainly in grapes and red wine, has antioxidant, anti-inflammatory, and neuroprotective activities. Studies demonstrated that resveratrol could prevent memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats. However, whether administration of resveratrol could modulate the structural synaptic plasticity in diabetic rats remains unknown. Therefore, we tested its influence against cognitive dysfunction as well as on hippocampal structural synaptic plasticity in streptozotocin-induced diabetic rats. Our results showed that the cognitive performances in diabetic group were markedly deteriorated, accompanied by noticeable alterations in oxidative as well as inflammation parameters, SYN and GAP-43 expression were reduced in the hippocampus. In contrast, chronic treatment with resveratrol (10, 20 mg/kg) improved neuronal injury and cognitive performance by attenuating oxidative stress and inflammation as well as inhibiting synapse loss in diabetic rats. In conclusion, the present study suggested that oral supplementation of resveratrol might be a potential therapeutic strategy for the treatment and/or prevention of diabetic encephalopathy. [ABSTRACT FROM AUTHOR]

Given three eigenvalues and their corresponding eigenfunctions of the beam. It is assumed that the total mass of a beam is known. The problem of constructing the physical elements of the system from the known data is considered. The sufficient conditions for the construction of a physical realizable system with positive continuous variable: bending rigidity function and density function are established. If these conditions are satisfied, the system may be constructed uniquely. [ABSTRACT FROM PUBLISHER]

In this work, carbon dots (C-dots) with amino groups are synthesized by one-pot hydrothermal method, which could be treated in aqueous solution. The new material is used as cathode interlayer in organic solar cells (OSCs) for the first time. The C-dots cathode interlayer reduces the work function, improves the extraction and transportation of charge carriers, and reduces the recombination of charge carriers in device. As a result, the champion power conversion efficiency (PCE) of the C-dots based device is 15.41% when using PM6:Y6 as active layer. In addition, after 1 h of continuous UV illumination, 97.5% of the original PCE for C-dots based device could be maintained while devices based on ZnO cathode interlayer only remained 80.9%, indicating that C-dots are potential candidates as stable and efficient cathode interlayer to overcome the inherent poor photostability drawback of ZnO. [Display omitted] • An aqueous solution treated and inexpensive C-dots was synthesized. • The PCE reached 15.41% with the C-dots cathode interlayer. • 97.5% initial efficiency was maintained under 1 h continuous UV illumination. [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]

Next generation sequencing (NGS) based gene panel testing is increasingly available as a molecular diagnostic approach for inborn errors of metabolism. Over the past 40 years patients have been referred to the Vitamin B 12 Clinical Research Laboratory at McGill University for diagnosis of inborn errors of cobalamin metabolism by functional studies in cultured fibroblasts. DNA samples from patients in which no diagnosis was made by these studies were tested by a NGS gene panel to determine whether any molecular diagnoses could be made. 131 DNA samples from patients with elevated methylmalonic acid and no diagnosis following functional studies of cobalamin metabolism were analyzed using the 24 gene extended cobalamin metabolism NGS based panel developed by Baylor Miraca Genetics Laboratories. Gene panel testing identified two or more variants in a single gene in 16/131 patients. Eight patients had pathogenic findings, one had a finding of uncertain significance, and seven had benign findings. Of the patients with pathogenic findings, five had mutations in ACSF3 , two in SUCLG1 and one in TCN2 . Thus, the NGS gene panel allowed for the presumptive diagnosis of 8 additional patients for which a diagnosis was not made by the functional assays. [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]

Recurrent rhabdomyolysis warrants comprehensive evaluations to search for underlying muscle diseases, including metabolic myopathies, LPIN1 -myopathy, RYR1 -myopathy, and less commonly muscular dystrophies. The absence of weakness and the normal or minimally elevated creatine kinase levels between attacks are typical of metabolic myopathies, LPIN1 -myopathy, and RYR1 -myopathy, while the presence of weakness and the highly elevated creatine kinase levels between attacks point toward muscular dystrophies. Here we report a 32-year-old man with a one-year history of recurrent rhabdomyolysis, who had normal strength, slightly elevated baseline creatine kinase level, and normal muscle histopathology. All workups for metabolic myopathies, LPIN1 -myopathy and RYR1 -myopathy were unrevealing. Next generation sequencing of muscular dystrophy-related genes revealed a hemizygous deletion of exons 17–34 of the dystrophin-encoding gene. Immunohistochemical study revealed absent staining for the rod domain of dystrophin. Dystrophinopathy should be considered in patients with recurrent rhabdomyolysis despite the absence of fixed weakness or highly elevated resting creatine kinase level. [ABSTRACT FROM AUTHOR]

Exfoliated poly(ethylene terephthalate)(PET)/organoclay nanocompositeswere prepared by extrusion blending method with different clay contentsand molecular weights of raw PET. Pyromellitic dianhydride (PMDA)was extruded, together with PET and clay, to introduce long-chainbranching to PET backbone and delaminate the clay layers. Althoughthe molecular weights and viscoelastic properties of nanocompositeswere much lower than those of foamable PMDA-modified PET, the meltfoamability of nanocomposites was significantly improved by the well-dispersedclays due to the heterogeneous nucleation effect, enhanced nonisothermalcrystallization rate, and so on. Foaming temperature windows witha width of 20–60 °C were explored for PET/clay nanocompositeswith intrinsic viscosities of 0.67–0.94 dL/g, in which nanocompositesfoams with cell diameters of 29–53 μm, cell densitiesof 6.5 × 107–6.9 × 108cells/cm3, and expansion ratio of 10–50 could be controllablyproduced using supercritical CO2as a blowing agent. [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.