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Helicobacter pylori (H. pylori) infection is the primary risk factor for the pathogenesis of gastric cancer (GC). N6‐methyladenosine (m6A) plays pivotal roles in mRNA metabolism and hnRNPA2B1 as an m6A reader is shown to exert m6A‐dependent mRNA stabilization in cancer. This study aims to explore the role of hnRNPA2B1 in H. pylori‐associated GC and its novel molecular mechanism. Multiple datasets and tissue microarray are utilized for assessing hnRNPA2B1 expression in response to H. pylori infection and its clinical prognosis in patients with GC. The roles of hnRNPA2B1 are investigated through a variety of techniques including glucose metabolism analysis, m6A‐epitranscriptomic microarray, Ribo‐seq, polysome profiling, RIP‐seq. In addition, hnRNPA2B1 interaction with poly(A) binding protein cytoplasmic 1 (PABPC1) is validated using mass spectrometry and co‐IP. These results show that hnRNPA2B1 is upregulated in GC and correlated with poor prognosis. H. pylori infection induces hnRNPA2B1 upregulation through recruiting NF‐κB to its promoter. Intriguingly, cytoplasm‐anchored hnRNPA2B1 coordinated PABPC1 to stabilize its relationship with cap‐binding eIF4F complex, which facilitated the translation of CIP2A, DLAT and GPX1 independent of m6A modification. In summary, hnRNPA2B1 facilitates the non‐m6A translation of epigenetic mRNAs in GC progression by interacting with PABPC1‐eIF4F complex and predicts poor prognosis for patients with GC. [ABSTRACT FROM AUTHOR]

The corneal epithelium is the outermost transparent barrier of the eyeball and undergoes continuous self‐renewal by limbal stem cells (LSCs) during its lifetime; however, the impact of aging on LSCs remains largely unknown. Here, we showed that the healing ability of the cornea in elderly macaques (Macaca fascicularis) was significantly decreased compared to that of younger macaques. This delayed wound closure accompanied a disordered cell arrangement and corneal opacity. A novel cytokine, Secreted and Transmembrane 1 (SECTM1), was found to facilitate corneal healing and was upregulated in young macaques upon wounding. Mechanistically, SECTM1 is essential for LSC migration and proliferation, and may partially function through Cell Division Cycle Associated 7 (CDCA7). Notably, the topical application of SECTM1 to aged wounded corneas dramatically promoted re‐epithelialization and improved corneal transparency in both mice and macaques. Our work suggests that aging may impair the expression of healing response factors and injury repair in non‐human primate corneas, and that SECTM1 application could potentially benefit corneal wound healing in clinical treatment. [ABSTRACT FROM AUTHOR]

Objectives: Scaphoid nonunion remains a challenging problem to manage with no general consensus on its treatment recommendations. We propose a novel minimally invasive (MIS) technique of arthroscopic bone grafting (ABG) with robot‐assisted fixation for the treatment of scaphoid nonunions. Methods: Patients with radiographically proven scaphoid nonunion treated by this novel surgical technique were included. Following arthroscopic debridement and iliac crest bone grafting, the scaphoid was fixed percutaneously using either multiple Kirschner (K)‐wires or a headless compression screw using a robotic navigation system. Results: Six male patients with an average age of 29.2 years were enrolled. Four patients had scaphoid waist fractures, and the other two were proximal pole fractures. During wrist arthroscopy, punctate bleeding of the proximal scaphoid fragment was observed in four out of the six patients. Half of the patients were fixed using a headless compression screw and the other half using multiple K‐wires. All the guidewires were placed with a single‐attempt using the robotic navigation system. Postoperatively, all the scaphoid fractures had complete radiographic union by 16 weeks. At a mean follow‐up of 18.3 months, there were significant improvements in wrist range of motion, grip strength, and patient‐rated outcomes. No intraoperative or early postoperative complications were encountered in any of our patients. Conclusion: Arthroscopic bone grafting with robot‐assisted fixation is a feasible and promising therapeutic option for scaphoid nonunions, regardless of the vascularity of the proximal pole fragment. This novel technique allows for anatomic restoration of the scaphoid alignment and accurate, targeted placement of implants into the scaphoid nonunion site within a single‐attempt using a robotic navigation system. [ABSTRACT FROM AUTHOR]

Background: Understanding of the early immune response in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) breakthrough infections is limited. Methods: Ninety‐eight patients with coronavirus disease 2019 (COVID‐19) breakthrough infections were divided into two groups, with intervals from receiving the second dose of inactivated vaccine to the onset of illness <60 or ≥60 days. Results: The median lymphocyte count and the median anti‐SARS‐CoV‐2 spike immunoglobulin G (IgG) and immunoglobulin M (IgM) titers were higher in the <60‐day interval group compared with the corresponding medians in the ≥60‐day interval group (p = 0.005, p = 0.001, and p = 0.001, respectively). The median interleukin‐6 (IL‐6) level in the <60‐day interval group was significantly lower than the median IL‐6 level in the ≥60‐day interval group (p < 0.001). Conclusions: Our results highlight the different anti‐SARS‐CoV‐2 spike IgG and IgM antibody titers among patients with different intervals from receiving the second dose of inactivated vaccine to the onset of illness. [ABSTRACT FROM AUTHOR]

Based on the relaxation digital‐to‐analog converter (ReDAC) architecture and the capacitor charge/discharge function under discrete time conditions, this paper proposes a new mathematical model for the output voltage of the ReDAC to implement the unconstrained relaxation DAC (Uc‐ReDAC). The system clock calibration is not required. An adaptive probabilistic binary particle swarm optimization (AP‐BPSO) algorithm is proposed for solving the binary coding configuration problem under the Uc‐ReDAC model. Simulation results show that the 8‐bit (10‐bit) Uc‐ReDAC has an average sampling rate of 7.9 MS/s (6.76 MS/s). [ABSTRACT FROM AUTHOR]

Background and Purpose: Dopamine protects the duodenal mucosa. Here we have investigated the source of dopamine in gastric juice and the mechanism underlying the effects of luminal dopamine on duodenal bicarbonate secretion (DBS) in rodents.Experimental Approach: Immunofluorescence, UPLC-MS/MS, gastric incubation and perfusion were used to detect gastric-derived dopamine. Immunofluorescence and RT-PCR were used to examine the expression of dopamine receptors in the duodenal mucosa. Real-time pH titration and pHi measurement were performed to investigate DBS.Key Results: H+ -K+ -ATPase was co-localized with tyrosine hydroxylase and dopamine transporters in gastric parietal cells. Dopamine was increased in in vivo gastric perfusate after intravenous infusion of histamine and in gastric mucosa incubated, in vitro, with bethanechol chloride or tyrosine. D2 receptors were the most abundant dopamine receptors in rat duodenum, mainly distributed on the apical membrane of epithelial cells. Luminal dopamine increased DBS in a concentration-dependent manner, an effect mimicked by a D2 receptor agonist quinpirole and inhibited by the D2 receptor antagonist L741,626, in vivo D2 receptor siRNA and in D2 receptor -/- mice. Dopamine and quinpirole raised the duodenal enterocyte pHi . Quinpirole-evoked DBS and PI3K/Akt activity were inhibited by calcium chelator BAPTA-AM or in D2 receptor-/- mice.Conclusion and Implications: Dopamine in the gastric juice is derived from parietal cells and is secreted along with gastric acid. On arrival in the duodenal lumen, dopamine increased DBS via an apical D2 receptor- and calcium-dependent pathway. Our data provide novel insights into the protective effects of dopamine on the duodenal mucosa. [ABSTRACT FROM AUTHOR]

Background: The mechanisms of vagal nerve stimulation (VNS) for the treatment of drug‐resistant epilepsy (DRE) remain unclear. This study aimed to measure spontaneous brain activity changes caused by VNS in DRE patients using resting‐state functional MRI (rs‐fMRI). Methods: The rs‐fMRI scans were performed in 16 DRE patients who underwent VNS surgery. Amplitude of low‐frequency fluctuations (ALFF) and regional homogeneity (ReHo) was generated and examined using paired sample t‐test to compare activity changes at different current intensity stage. The preoperative and postoperative ALFF/ReHo were also compared in eight responders (≥50% reduction of seizure frequency three months after surgery) and eight nonresponders using paired sample t‐test. Results: The significant ALFF and ReHo changes were shown in various cortical/subcortical structures in patients under different current intensity. After three months of stimulation, responders exhibited increased ALFF in the right middle cingulate gyrus, left parahippocampal gyrus, and left cerebellum, and increased ReHo in the right postcentral gyrus, left precuneus, left postcentral gyrus, right superior parietal gyrus, right precentral gyrus, and right superior frontal gyrus. Nonresponders exhibited decreased ALFF in the left temporal lobe and right cerebellum, increased ALFF in bilateral brainstem, decreased ReHo in bilateral lingual gyri, and increased ReHo in the right middle frontal gyrus and right anterior cingulate gyrus. Conclusions: The spontaneous neural activity changes in DRE patients caused by VNS were in an ongoing process. Increased ALFF/ReHo in frontal cortex, cingulate gyri, precentral/postcentral gyri, parahippocampal gyri, precuneus, parietal cortex, and cerebellum may implicate in VNS‐induced improvement in seizure frequency. [ABSTRACT FROM AUTHOR]

In the paper industry, chlorine is often used to treat the pulp for bleaching. After pulping, a large amount of xylan is present in the fiber. Xylanase can be used to degrade xylan in an eco‐friendly process called biobleaching, which can help minimize the usage of chlorine in the delignification process. However, a bottleneck in the adoption of biobleaching is the cost of xylanase and the requirement that xylanase be active and stable at extreme conditions. Here, we investigated whether using sodium alginate beads to immobilize an extracellular xylanase from Bacillus subtilis (Lucky9) can reduce the potential cost of enzyme usage. The optimal pH and the activity of the immobilized enzyme were increased at optimal temperature compared with the free enzyme. In addition, immobilized xylanase was shown to be more stable than free xylanase. The results of this study suggest that the immobilized xylanase has potential applications in the biobleaching industry. [ABSTRACT FROM AUTHOR]

Circular RNA (circRNA) are single‐stranded RNA with covalently closed 3′ and 5′ ends, with many recognized to be involved in human diseases as gene regulators, typically by interacting with other RNA. CircFNDC3B is a circRNA formed by back‐splicing of exons 5 and 6 of the FNDC3B gene. CircFNDC3B was recently implicated in renal carcinoma, gastric and bladder cancer. However, the expression levels of circFNDC3B and its role in colorectal cancer (CRC) remain unclear. Expression of circFNDC3B and TIMP3 levels in CRC tissues and cell lines were found to be low, whereas microRNA (miR)‐937‐5p expression was high in CRC. MicroRNA‐937‐5p downregulated TIMP3, thereby promoting tumor cell proliferation, invasion, migration and angiogenesis. Moreover, CircFNDC3B was shown to bind to miR‐937‐5p. CircFNDC3B and circFNDC3B‐enriched exosomes inhibited tumorigenic, metastatic and angiogenic properties of CRC, and miR‐937‐5p overexpression or TIMP3 knockdown could reverse these effects. In vivo CRC tumor growth, angiogenesis and liver metastasis were suppressed by circFNDC3B overexpression, circFNDC3B‐enriched exosomes or miR‐937‐5p knockdown. In conclusion, our work reports a tumor‐suppressing role for the circFNDC3B–miR‐97‐5p–TIMP3 pathway and suggests that circFNDC3B‐enriched exosomes can inhibit angiogenesis and CRC progression. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that long non‐coding RNAs (lncRNAs) are associated with carcinogenesis. LncRNA small nucleolar RNA host gene 3 (SNHG3) is up‐regulated in various cancers and positively associated with poor prognosis of these cancers. However, the precise role of lncRNA SNHG3 in bladder cancer (Bca) remains unclear. In our research, we first reported that lncRNA SNHG3 was up‐regulated in bladder cancer tissues and positively related to poor clinical prognosis. Moreover, knockdown of lncRNA SNHG3 significantly suppressed the proliferation, migration, invasion and EMT process of Bca cells in vitro and vivo. Mechanistically, we revealed that suppression of SNHG3 evidently enhanced miR‐515‐5p expression and decreased GINS2 expression at posttranscriptional levels. Moreover, SNHG3 positively regulated GINS2 expression by sponging miR‐515‐5p under a competing endogenous RNA (ceRNA) mechanism. To sum up, our study suggested lncRNA SNHG3 acted as a microRNA sponge and an oncogenic role in the progression of bladder cancer. [ABSTRACT FROM AUTHOR]

Both phototropins (phot1 and phot2) and cryptochromes (cry1 and cry2) were proven as the Arabidopsis thaliana blue light receptors. Phototropins predominately function in photomovement, and cryptochromes play a role in photomorphogenesis. Although cryptochromes have been proposed to serve as positive modulators of phototropic responses, the underlying mechanism remains unknown. Here, we report that depleting sucrose from the medium or adding gibberellic acids (GAs) can partially restore the defects in phototropic curvature of the phot1 phot2 double mutants under high‐intensity blue light; this restoration does not occur in phot1 phot2 cry1 cry2 quadruple mutants and nph3 (nonphototropic hypocotyl 3) mutants which were impaired phototropic response in sucrose‐containing medium. These results indicate that GAs and sucrose antagonistically regulate hypocotyl phototropism in a cryptochromes dependent manner, but it showed a crosstalk with phototropin signaling on NPH3. Furthermore, cryptochromes activation by blue light inhibit GAs synthesis, thus stabilizing DELLAs to block hypocotyl growth, which result in the higher GAs content in the shade side than the lit side of hypocotyl to support the asymmetric growth of hypocotyl. Through modulation of the abundance of DELLAs by sucrose depletion or added GAs, it revealed that cryptochromes have a function in mediating phototropic curvature. [ABSTRACT FROM AUTHOR]

Wilms tumour is a renal malignancy that commonly occurs in children. LIN28A gene overexpression has been reported to be involved in various human malignancies, while its roles in Wilms tumour risk are still under investigation. Here, we genotyped four LIN28A polymorphisms in 355 Wilms tumour patients and 1070 healthy controls from four hospitals in China. The genotyped single nucleotide polymorphisms (SNPs) include the following: rs3811464 G>A, rs3811463 T>C, rs34787247 G>A and rs11247957 G>A. Overall, we found that rs3811463 T>C and rs34787247 G>A were associated with increased risk of Wilms tumour. Combination analysis of risk genotypes showed that, compared to non‐carriers, subjects with 1 risk genotype and 1‐3 risk genotypes were more likely to develop Wilms tumour, with an adjusted odds ratio (OR) of 1.58 and 1.56, respectively. Stratified analysis further demonstrated that the risk effect remained prominent in some subgroups. We also found that presence of 1‐3 risk genotypes was associated with Wilms tumour risk in subgroups > 18 months of age, females, males and those with clinical stage I + II diseases. Furthermore, expression quantitative trait locus (eQTL) analysis indicated that rs3811463 C allele was significantly associated with increased transcripts of LIN28A gene. These findings suggest that LIN28A gene polymorphisms may be associated with increased predisposition to Wilms tumour. [ABSTRACT FROM AUTHOR]

Probabilistic load flow (PLF) is an important tool in power system planning and operation. One limitation of conventional PLF is that only the probability information of random variables is obtained as a reference for related analyses. Frequency and duration information often plays an important role in power system assessment. In this study, a frequency and duration method for PLF with correlated wind power sources and loads is proposed based on Latin hypercube sampling (LHS), Nataf transformation, and Markov chains. In the proposed method, the spatial and temporal correlations among wind power sources and loads are addressed using Nataf transformation and Markov chains, which are incorporated into the LHS framework to solve the PLF problem with frequency and duration quantities. With the proposed method, not only the probability information but also the frequency and duration information of the random output variables in a PLF problem can be efficiently and accurately obtained. The performance of the proposed PLF method is verified using comparative tests on three modified test systems. [ABSTRACT FROM AUTHOR]

The present study elucidates the potential role of Trop2 in tumor invasion and the promotion of epithelial‐mesenchymal transition (EMT) when binding β‐catenin in GC. The role of Trop2 in promoting EMT in GC cells was examined by a variety of experimental assays. Moreover, the underlying molecular mechanism of Trop2 in promoting EMT was studied by in vivo and in vitro assays. The Trop2 expression in relation to tumor metastasis status was detected by IHC in 248 cases of GC tissues and 86 cases of matched adjacent tissues. Trop2 promoted the metastasis and induces EMT in GC. Meanwhile, the elevated protein levels of Trop2 and mesenchymal markers were also found in the TGF‐β1‐induced EMT model in GC cells. Importantly, Trop2 physically bound and activated β‐catenin to promote EMT; moreover, Trop2 increased the accumulation of β‐catenin in the nucleus to accelerate metastasis in GC cells. Inhibition of Trop2 expression in GC cells prevented the migration and invasion of GC cells in vivo. Trop2+/vimentin+ expression was higher in GC tissues than that in matched adjacent tissues, and Trop2+/vimentin+ expression in GC was associated with the differentiation, TNM stage, and distant metastases. These sets of data reveal a novel regulatory network of Trop2 in EMT and GC metastasis, suggesting Trop2 as a useful marker for inducing EMT and metastasis of GC, which may help to lead a better understanding of the pathogenesis of the GC. Trop2 as a useful marker for inducing EMT and metastasis of GC, which may help to lead a better understanding of the pathogenesis of the GC. [ABSTRACT FROM AUTHOR]

Abstract: Cancer cells undergo comprehensive metabolic reprogramming to meet the increased requirements of energy and building blocks for proliferation. Lipin‐1, a phosphatidic acid phosphatase converting phosphatidic acid (PA) to diacylglycerol (DAG), is upregulated in lung adenocarcinoma (LUAD) cell lines and tumor tissues. In this study, we reveal high lipin‐1 expression is correlated with poor prognosis of patients with LUAD. Knockdown of lipin‐1 decreases cell viability and proliferation in LUAD cells, whereas it has less effect on nontumorigenic lung cells. Autophagy and ER stress play important roles in tumor initiation and progression. Lipin‐1 knockdown induces the initiation of autophagy while disrupts formation of autolysosome. Lipin‐1 silencing induces the activation of ER stress through the IRE1α pathway. Furthermore, we demonstrate disrupted ER homeostasis contributes to the cell phenotype, and the elevated autophagy initiation is due to the ER stress in part. For the first time, we show lack of lipin‐1 enhances the sensitivity of LUAD cells to cisplatin treatment. Our results suggest that lipin‐1 is a potential target, alone or combined with other treatment, for lung cancer therapy. [ABSTRACT FROM AUTHOR]

The controllable polyesters with high overall performance are obtained by tuning the stereostructure of 1,4-cyclohexylene ring moieties (CHRMs) in poly(butylene adipate- co−1,4-cyclohexanedicarboxylate) (PBAC). After increasing the number of irregular cis-CHRMs in the polyester, PBAC can transform from semicrystalline polymer to amorphous one. PBAC with 58% cis-CHRMs starts to exhibit good elasticity with shape recovery of 60% at 250% deformation, indicating the transition from plastic to thermoplastic elastomer. Through blending with polylactic acid (PLA), the elastic PBAC greatly enhances the impact strength of PLA to 7.5 kJ/m2. While the tensile elongation at break is dramatically improved to 161% with the addition of plastic PBAC. The mechanism related to the stereostructure of non-planar ring of PBAC on the properties of PLA is also analyzed. Therefore, this research suggests a particular way to build non-planar ring contained polyesters to modify PLA with high toughness. POLYM. ENG. SCI., 57:1277-1284, 2017. © 2017 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

Sanguinarine, a bioactive benzophenanthridine alkaloid extracted from plants of the Papaveraceae family, has shown antitumour effects in multiple cancer cells. But the therapeutic effects and regulatory mechanisms of sanguinatine in gastric cancer (GC) remain elusive. This study was aimed to investigate the correlation of dual-specificity phosphatase 4 (DUSP4) expression with clinicopathologic features and overall survival in patients with GC and explore the effects of sanguinarine on tumour growth and invasion in GC cells (SGC-7901 and HGC-27) and underlying molecular mechanisms. Immunohistochemical analysis showed that decreased DUSP4 expression was associated with the sex, tumour size, depth of invasion and distant metastasis in patients with GC. Functional experiments including CCK-8, Transwell and flow cytometry analysis indicated that sanguinarine or DUSP4 overexpression inhibited GC cell viability and invasive potential, and induced cell apoptosis and cycle arrest in S phase, but DUSP4 knockdown attenuated the antitumour activity of sanguinarine. Further observation demonstrated that sanguinarine up-regulated the expression of DUSP4 and Bcl-2-associated X protein (Bax), but down-regulated phosphorylated extracellular signal-regulated kinase (p-ERK), proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP-2) and B-cell lymphoma 2 (Bcl-2) expression. Taken together, our findings indicate that sanguinarine inhibits growth and invasion of GC cells through regulation of the DUSP4/ERK pathway, suggesting that sanguinarine may have potential for use in GC treatment. [ABSTRACT FROM AUTHOR]

Gastric cancer ( GC) is a multistep and multistage disease and the majority of GC cells could overexpressed one or more oncogenes. Trop2 and amphiregulin ( AREG) are both overexpressed in various epithelial cell cancers and have the role in the increases tumor cells division and metastasis. However, little is known about the function and correlation of two oncogenes coexpressed in GC. The expression level of these two genes in 791 cases of GC tissues were tested, the correlations between two genes expression and clinical pathological characteristics and overall survival in GC patients through immunohistochemistry ( IHC) were analyzed. This study also explored the mRNA expression level of two genes in 26 cases of freshly GC tissues by qRT- PCR. The results indicated that Trop2+/ AREG+ coexpression was higher in GC tissues than in adjacent tissues. Trop2+/ AREG+ protein coexpression were associated with Tumor Node Metastasis ( TNM) stage ( χ2 = 50.345, P < 0.001), tumor size ( χ2 = 40.349, P < 0.001), lymph node metastases ( χ2 = 26.481, P < 0.001), and distant metastases ( χ2 = 8.387, P = 0.039). GC patients with Trop2+ and AREG+ protein coexpression had poor overall survival rates ( HR = 3.682, 95% CI = 2.038-6.654, P < 0.001). The expression level of Trop2/ AREG were positively correlated ( r 0.254 and P < 0.001). The result of the mRNA expression was similar to that of the protein expression. Overall, Trop2 and AREG could be seen as prognostic cobiomarker in GC and combined detection of Trop2 and AREG could be viewed as helpful in predicting the prognosis of the GC patients. [ABSTRACT FROM AUTHOR]

In this Letter, three types of bearingless switched reluctance machines (BSRMs) with different hybrid stator structures are designed and analysed. First of all, topologies of three BSRMs, the conventional 8/10 pole, 12/14 pole BSRMs and a novel 12/12 pole BSRM with axial split phase inner stator permanent magnet structure, are given. Then, the electromagnetic performances, including the distribution of magnetic fields, suspension force and electromagnetic torque are comprehensively compared by means of 2D and 3D finite‐element method (FEM). The results based on theoretical analysis and FEM reveal that the proposed 12/12 pole BSRM would exhibit complete decoupling, shorter magnetic circuit, higher torque (power) density and suspension force than the conventional ones. Further, it is found that four degree‐of‐freedom suspension of the rotor can be realised by two‐phase suspension windings in the proposed 12/12 pole BSRM. Finally, a prototype machine is designed and manufactured to verify the validity of the topology design and electromagnetic performance. [ABSTRACT FROM AUTHOR]

Most patients with epithelial ovarian cancer ( EOC) are diagnosed at an advanced stage, and therapeutic options for these patients are limited. The identification of suitable biomarkers could be helpful for patients with EOC, who might benefit from targeted therapies even in advanced stages of the disease. Trophoblast cell surface antigen 2 ( TROP2) is highly expressed in various human malignant tumours; however, this has not been demonstrated clearly in EOC. In this study, we further evaluated whether TROP2 is a promising marker for EOC, and thus also a potential target for EOC immunotherapy. Quantitative real-time polymerase chain reaction (qPCR) and fluorescence-activated cell sorting (FACS) analysis were employed to determine TROP2 mRNA and protein expression in both human EOC and normal ovarian cell lines. Additionally, TROP2 protein expression was measured by immunohistochemistry in 128 EOC tissue samples, 21 normal ovarian tissues and 18 normal fallopian tubes. The correlations between TROP2 protein expression and patients' clinicopathological features were investigated, and survival outcomes were analysed. TROP2 mRNA and protein levels were upregulated significantly in EOC cell lines compared with normal cell lines. The protein of TROP2 was expressed in the majority of EOC tissue samples (90.6%) and overexpressed in 75 (58.6%) of the 128 tumour samples. TROP2 overexpression was correlated with relevant clinicopathological characteristics and was associated with significantly shortened overall survival and disease-free survival. Furthermore, TROP2 was an independent prognostic marker for EOCs as analysed by Cox regression. TROP2 was a potential biomarker for targeted therapy in patients with TROP2-overexpressing EOC. [ABSTRACT FROM AUTHOR]

Objective To evaluate safety, tolerability, seizure frequency, and regional variations in treatment responses with the AMPA antagonist, perampanel, in a large extension study during up to 3 years of treatment. Methods Patients ≥12 years old with partial-onset seizures despite treatment with 1-3 antiepileptic drugs at baseline completed a perampanel phase III trial and entered extension study 307 ( NCT00735397). Patients were titrated to 12 mg/day (or their individual maximum tolerated dose) during the blinded conversion period, followed by open-label maintenance. Exposure, safety (adverse events [AEs], vital signs, weight, electrocardiography [ ECG], laboratory values) and seizure outcomes were analyzed; key measures were assessed by geographic regions. Results Among 1,216 patients, median exposure was 1.5 years (range 1 week to 3.3 years), with >300 patients treated for >2 years. Treatment retention was 58.5% at cutoff. AEs reported in ≥10% of patients were dizziness, somnolence, headache, fatigue, irritability, and weight increase. Only dizziness and irritability caused discontinuation in >1% of patients (3.9% and 1.3%, respectively). The only serious AEs reported in >1% of patients were epilepsy-related (convulsion, 3.0%; status epilepticus, 1.1%). No clinically relevant changes in vital signs, ECG or laboratory parameters were seen. After titration/conversion, responder rate and median percentage change from baseline in seizure frequency were stable: 46% for both measures at 9 months (in 980 patients with ≥9 months' exposure) and 58% and 60%, respectively, at 2 years (in the 337 patients with 2 years' exposure). Median percentage reduction in frequency of secondarily generalized ( SG) seizures ranged from 77% at 9 months (N = 422) to 90% at 2 years (N = 141). Among the 694 patients with maintenance data ≥1 year, 5.3% were seizure-free for the entire year. Significance No new safety signals emerged during up to 3 years of perampanel exposure in 39 countries. Seizure responses remained stable, with marked reductions, particularly in SG seizures. A PowerPoint slide summarizing this article is available for download in the Supporting Information section . [ABSTRACT FROM AUTHOR]

Objective To better understand the relationship between efficacy and perampanel dose, integrated actual (last) dose data from three phase III trials and an extension study (blinded Conversion Period; open-label Maintenance Period) were analyzed. Methods Seizure frequency data were analyzed in patients who were randomized to and completed the 13-week Maintenance Period of the phase III studies on perampanel 8 mg, and who received an actual (last) dose of 12 mg during (1) the extension 16-week blinded Conversion Period or (2) weeks 1-13 of the extension Maintenance Period. Due to a treatment-by-region interaction (p = 0.042), analyses excluded patients from the Latin America region (n = 162/1,480; 10.9% of the treated cohort). Results Of 372 patients randomized to 8 mg in the phase III studies, 273 completed the Maintenance Period at 8 mg and 267 entered the extension study. In patients who then had an actual (last) dose of 12 mg during the extension blinded Conversion Period (n = 217), median percent change in seizure frequency per 28 days improved from −32.4% (8 mg, phase III Maintenance Period) to −44.2% (12 mg, extension blinded Conversion Period); 50% responder rates increased slightly from 37.3% to 42.9%. In patients who completed the phase III studies on 8 mg and had an actual (last) dose of 12 mg during weeks 1-13 of the extension Maintenance Period (n = 181), median percent change in seizure frequency per 28 days improved from −34.1% (phase III Maintenance Period) to −46.0% (weeks 1-13 extension Maintenance Period); 50% responder rates were 39.2% and 46.4%. Seizure control remained substantially unchanged in patients who completed the phase III studies at 12 mg and continued on that dose during the extension. Significance Increasing perampanel dose from 8 to 12 mg can produce additional benefits in seizure control in at least some patients who tolerate the higher dose. [ABSTRACT FROM AUTHOR]

Purpose Three phase III studies (304 [ClinicalTrials.gov identifier: NCT00699972], 305 [ NCT00699582], 306 [ NCT00700310]) evaluated perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ( AMPA) receptor antagonist, as adjunctive therapy for refractory partial seizures. We report post hoc analyses of pooled study data by randomized dose. Methods Patients with partial seizures despite receiving 1-3 antiepileptic drugs were randomized to once-daily placebo, perampanel 8 or 12 mg (studies 304, 305), or placebo, perampanel 2, 4, or 8 mg (study 306). Studies included a 6-week baseline period and double-blind treatment phase (6-week titration; 13-week maintenance). Primary end points were median change in partial seizure frequency (baseline vs. double-blind phase) and percentage of patients achieving ≥50% reduction in seizure frequency (baseline vs. maintenance). Here, these end points, together with secondary, exploratory, and safety end points, were assessed using pooled study data. Key Findings The pooled intent-to-treat analysis set (randomized, treated patients with any seizure data) included 1,478 patients. Median changes in partial seizure frequency were greater with perampanel than placebo (perampanel 4 mg, −23.3%; 8 mg, −28.8%; 12 mg, −27.2%; placebo, −12.8%; p < 0.01, each dose vs. placebo), as were 50% responder rates (perampanel 4 mg, 28.5%; 8 mg, 35.3%; 12 mg, 35.0%; placebo, 19.3%; p < 0.05, each dose vs. placebo). In addition, median changes in complex partial plus secondary generalized seizure frequency were also greater with perampanel than placebo (perampanel 4 mg, −31.2%; 8 mg, −35.6%; 12 mg, −28.6%; placebo, −13.9%). Perampanel was generally well tolerated. The most frequent treatment-emergent adverse events ( TEAEs) were dizziness, somnolence, and headache. Most TEAEs were mild/moderate; relatively few patients experienced severe TEAEs (placebo, 5.4%; perampanel, 8.9%) or serious TEAEs (placebo, 5.0%; perampanel, 5.5%). There were no deaths and no clinically important mean changes in laboratory values, electrocardiography ( ECG) findings, or vital signs. Significance Perampanel reduced partial seizure frequency and improved responder rates compared with placebo, with an acceptable tolerability profile. [ABSTRACT FROM AUTHOR]

The most commonly used curing agents for soy-based adhesives are polyamines, which have the problem of low solid content and/or high viscosity. To overcome this problem, a new type of polyamidoamine (PADA) resin was synthesized and applied to soy flour-based adhesives to improve their water resistance. The PADA solution obtained had a high solid content of 50 wt% and low viscosity of 270 cP. The optimum weight ratio of soy flour/PADA/maleic anhydride to prepare adhesive was 40/7/1.68. The wet strength of plywood prepared at the optimum weight ratio was 0.82 MPa, which meant the plywood could be used as type II plywood according to the Chinese National Standard GB/T 9846.7-2004. The results of water-insoluble solid content measurement and SEM observation demonstrated that cured soy flour-PADA-maleic anhydride adhesive had a 16 % greater water-insoluble solid content than soy flour-NaOH adhesive. The cross-linking network formed by the reactions of PADA and MA would increase the water-insoluble solid contents and improve water resistance of cured soy flour-based adhesives. [ABSTRACT FROM AUTHOR]

The article reports a study which examined whether the onset of rheumatoid arthritis (RA) in women before conception affects the time to pregnancy (TTP). It mentions that the study evaluated pregnant women who enrolled in the Danish National Birth Cohort between 1996 and 2002, and used the Danish National Hospital Discharge Registry to identify women with RA. Details pertaining to the methods, data analysis and study results are also presented.

Melamine-modified montmorillonite (MA-MMT) was prepared via cation exchange. The intercalation behavior was investigated by Fourier transform infrared spectrometer (FT-IR), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The results showed that the d-spacing value increased from 1.25 nm for Na-montmorillonite (Na+MMT) to 1.53 nm for MA-MMT. Different kinds of montmorillonite combined with melamine pyrophosphate (MPP) were used to prepare flame-retardant polyamide 6 (FR-PA6). Flame retardance of FR-PA6 samples was investigated by limiting oxygen index (LOI), UL-94 vertical burning method, and cone calorimeter test. Morphology and component of char residues for FR-PA6 were investigated by scanning electron microscope (SEM) and XPS. It was found that MA-MMT/MPP system contributed both excellent flame retardance and anti-dripping ability for PA6. MA-MMT particles can fill flaws of char residues and strengthen the char layer, leading to form more intumescent char layer. POLYM. ENG. SCI., 2011. © 2010 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

Purpose: To evaluate safety, tolerability, and seizure outcome data during long-term treatment with once-daily adjunctive perampanel (up to 12 mg/day) in patients with refractory partial-onset seizures. Methods: Study 307 was an extension study for patients completing the double-blind phase of three pivotal phase III trials (studies 304, 305, and 306). The study consisted of two phases: an open-label treatment phase (including a 16-week blinded conversion period and a planned 256-week maintenance period) and a 4-week follow-up phase. Patients were blindly titrated during the conversion period to their individual maximum tolerated dose (maximum 12 mg/day). Adverse events (AEs) were monitored throughout the study and seizure frequency recorded. The interim data cutoff date for analyses was December 1, 2010. Key Findings: In total, 1,218 patients were enrolled in the study. At the interim cutoff date, 1,186 patients were in the safety analysis set; 1,089 (91.8%) patients had >16 weeks of exposure to perampanel, 580 (48.9%) patients had >1 year of exposure, and 19 (1.6%) patients had >2 years of exposure. At the interim analysis, 840 (70.8%) patients remained on perampanel treatment. The large majority of patients (n = 1,084 [91%]) were titrated to 10 mg or 12 mg/day. Median (range) duration of exposure was 51.4 (1.1-128.1) weeks. Treatment-emergent AEs were reported in 87.4% of patients. The most frequent were dizziness (43.9%), somnolence (20.2%), headache (16.7%), and fatigue (12.1%). Serious AEs were reported in 13.2% of patients. In the intent-to-treat analysis set (n = 1,207), the frequency of all seizures decreased over the first 26 weeks of perampanel treatment in patients with at least 26 weeks of exposure to perampanel (n = 1,006 [83.3%]); this reduction was maintained in patients with at least 1 year of exposure (n = 588 [48.7%]). The overall median percent changes in seizure frequency in patients included in each 13-week interval of perampanel treatment were −39.2% for weeks 14-26 (n = 1,114), −46.5% for weeks 40-52 (n = 731), and −58.1% for weeks 92-104 (n = 59). Overall responder rates in patients included in each 13-week interval of perampanel treatment were 41.4% for weeks 14-26 (n = 1,114), 46.9% for weeks 40-52 (n = 731), and 62.7% for weeks 92-104 (n = 59). During the blinded conversion period, the reduction in seizure frequency in patients previously randomized to placebo (−42.4%, n = 369) was similar to that in patients previously randomized to perampanel (−41.5%, n = 817). Significance: Consistent with pivotal phase III trials, these interim results demonstrated that perampanel had a favorable tolerability profile in patients with refractory partial-onset seizures over the longer term. The decrease in seizure frequency was consistent and maintained in those patients over at least 1 year of perampanel exposure. [ABSTRACT FROM AUTHOR]

The title compound, [Fe(2)(C(9)H(11)NS(2)){Fe(C(5)H(5))(C(17)H(14)P)}(CO)(5)], was prepared as an aza-dithiol-ato-iron model for the iron-only hydrogenase active site. The Fe(2)S(2) unit exhibits a butterfly conformation and the ferrocenyldiphenyl-phosphine ligand is trans to the Fe-Fe bond. The Fe-Fe distance of 2.5160 (8) Å is longer than found in related model structures. Intra-molecular C-H⋯S and inter-molecular C-H⋯O hydrogen bonds are observed.

The asymmetric unit of the title compound, C(12)H(8)N(2)O(6)S, an important diphenyl sulfone derivative, contains one half-mol-ecule; a mirror plane passes through the SO(2) group. The dihedral angle between the two symmetry-related benzene rings is 40.10 (13)°. An intra-molecular C-H⋯O hydrogen bond results in the formation of a five-membered ring, which adopts an envelope conformation.

In the sulfone mol-ecule of the title compound, C(12)H(12)N(2)O(2)S·C(2)H(3)N, the two benzene rings are oriented at a dihedral angle of 80.69 (3)°. Weak intra-molecular C-H⋯O hydrogen bonds result in the formation of two five-membered rings, which both have envelope conformations. In the crystal structure, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules.

In the crystal structure of the title compound, C(26)H(33)N(3)O(4), there are two crystallographically independent mol-ecules. The two cyclohexane rings are trans-fused; the ring neighboring the phenyl group is in a half-chair conformation and the other is in a chair conformation. The two nitro groups and the benzene ring of the dinitro-phenyl group are almost coplanar. Intra-molecular N-H⋯O hydrogen bonds and weak inter-molecular C-H⋯O hydrogen bonds are observed.

The title complex, [Cu(2)(C(22)H(20)Br(2)N(4)O(2))(ClO(4))(2)], was prepared by the condensation of 2,6-diformyl-4-bromo-phenol with 1,3-diamino-propane in the presence of copper(II) ions. The macrocyclic ligand shows an approximately planar structure except for the two propene groups in the macrocycle. The coordination polyhedron of each Cu atom can be described as distorted square pyramidal. The two Cu atoms are bridged by two phenolate O atoms of the macrocycle, with a Cu⋯Cu distance of 3.109 (2) Å.