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The mechanisms underlying gastrointestinal (GI) dysmotility with ulcerative colitis (UC) have not been fully elucidated. The enteric nervous system (ENS) plays an essential role in the GI motility. As a vital neurotransmitter in the ENS, the gas neurotransmitter nitric oxide (NO) may impact the colonic motility. In this study, dextran sulfate sodium (DSS)-induced UC rat model was used for investigating the effects of NO by examining the effects of rate-limiting enzyme nitric oxide synthase (NOS) changes on the colonic motility as well as the role of the ENS in the colonic motility during UC.To reveal the relationship between the effects of NOS expression changes in NOS-containing nitrergic neurons and the colonic motility in a rat UC model.Male rats (The proportion of NOS-positive neurons within the colonic myenteric plexus (MP), the relative expression of NOS, and the NOS concentration in serum and colonic tissues were significantly elevated in EG1, EG2, and EG3 compared with CG rats. In UC rats, stimulation with agonists and inhibitors led to variable degrees of increase or decrease for each indicator in the EG2 and EG3. When the rats in EGs developed UC, the mean contraction tension of the colonic smooth muscle detectedIn UC rats, an increased number of nitrergic neurons in the colonic MP leads to the attenuation of colonic motor function. To intervene NOS activity might modulate the function of nitrergic neurons in the colonic MP and prevent colonic motor dysfunction. These results might provide clues for a novel approach to alleviate diarrhea symptoms of UC patients.

The GRAS family genes encode plant-specific transcription factors that play important roles in a diverse range of developmental processes and abiotic stress responses. However, the information of GRAS gene family in the bioenergy crop Miscanthus has not been available. Here, we report the genome-wide identification of GRAS gene family in Micanthus sinensis. A total of 123 MsGRAS genes were identified, which were divided into ten subfamilies based on the phylogenetic analysis. The co-linearity analysis revealed that 59 MsGRAS genes experienced segmental duplication, forming 35 paralogous pairs. The expression of six MsGRAS genes in responding to salt, alkali, and mixed salt-alkali stresses was analyzed by transcriptome and real-time quantitative PCR (RT-qPCR) assays. Furthermore, the role of MsGRAS60 in salt and alkali stress response was characterized in transgenic Arabidopsis. The MsGRAS60 overexpression lines exhibited hyposensitivity to abscisic acid (ABA) treatment and resulted in compromised tolerance to salt and alkali stresses, suggesting that MsGRAS60 is a negative regulator of salt and alkali tolerance via an ABA-dependent signaling pathway. The salt and alkali stress-inducible MsGRAS genes identified serve as candidates for the improvement of abiotic stress tolerance in Miscanthus.

Non-small-cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) exon 20 mutant occurs in 3% of NSCLCs. Targeted agents for this population remain an unmet need. In this analysis, we pooled-analyzed the efficacy and safety of poziotinib, a novel tyrosine kinase inhibitor, in HER2 exon 20 mutant NSCLC.PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were systematically searched on March 9, 2022. The primary endpoints were objective response rate (ORR) and disease control rate. The secondary endpoint was treatment-related adverse events.Three prospective clinical trials, involving 126 patients, were identified. The pooled ORR and disease control rate of poziotinib in HER2 exon 20 mutant NSCLC were 27% (95% CI, 19-35) and 72% (95% CI, 64-80), respectively. Patients with G778_P780dupGSP had the highest ORR (88%; 95% CI, 33-100; n = 12), followed by Y772_A775dupYVMA (20%; 95% CI, 12-30; n = 88) and G776delinsVC (19%; 95% CI, 0-50; n = 13). The most common grade 3 to 4 treatment-related adverse events were skin rash (36%), diarrhea (23%), and oral mucositis (13%).Poziotinib demonstrates moderate antitumor activity in previously treated HER2 exon 20 mutant NSCLC patients with a manageable safety profile. In addition, different subgroup mutations show various benefits of poziotinib treatment. Large-scale and multiarm clinical trials are warranted to confirm a suitable population and therapeutic strategies.

The phenylpropane pathway (PPP) is one of the most extensively investigated metabolic routes. This pathway biosynthesizes many important active ingredients such as phenylpropanoids and flavonoids that affect the flavor, taste and nutrients of food. How to elucidate the metabolic phenotype of PPP is fundamental in food research and development. In this study, we designed a structural periodical table filled with 103 metabolites produced from PPP. All of them especially the 62 structural isomers were qualified and quantified with high resolution and sensitivity via multiple reaction mode in liquid chromatography tandem triple quadrupole mass spectrometry. Ginkgo biloba and soybean were used as samples for the practical application of this method: The delicate spatial-temporal metabolic balance of PPP from ginkgo biloba has been first elucidated; It is first confirmed that the salt and draught stresses could redirect the biosynthesis trend of PPP to produce more isoflavones in soybean leaves.

Taxane chemotherapy represents the standard of care in the second-line setting for non-small cell lung cancer (NSCLC) patients, but immunotherapy agents pose great challenges. Whether immunotherapy/chemotherapy alone or combination therapy has more benefits remains controversial. In this study, we provided comparisons to integrate the efficacy of immunotherapy and taxane chemotherapy as second- or later-line treatments in advanced NSCLC.PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from inception to September 1, 2020. Randomized controlled trials comparing immunotherapy and taxane chemotherapy were enrolled in the Bayesian network analysis. Overall survival (OS) and progression-free survival (PFS) with hazard ratios (HRs) were investigated.Eight trials in 13 studies with 4398 patients comparing seven treatments were identified. Pembrolizumab 10 mg/kg was associated with the best improved OS, with significant differences versus docetaxel (HR 0.81, 95% credible interval [CrI] 0.74-0.88), avelumab (HR 0.84, 95% CrI 0.75-0.95), and pembrolizumab 200 mg plus docetaxel (HR 0.75, 95% CrI 0.56-1.00). Although pembrolizumab 200 mg plus docetaxel ranked the last in terms of OS, the combination therapy showed the most favorable PFS. Additionally, the anti-programmed death-ligand 1 (PD-L1) agent, avelumab, was associated with the least improvement in PFS.As second- or later-line therapeutic strategies, pembrolizumab 10 mg/kg provided the largest OS benefits and pembrolizumab 200 mg plus docetaxel improved PFS to the greatest extent. Considering that immunotherapy has been recommended to the first-line setting of NSCLC, advanced patients who have not received immunotherapy previously might be the suitable population for our findings.

L-Arabinose is an important component of mycobacterial cell wall. L-Arabinose is involved in the synthesis of arabinogalactan, lipoarabinomannan, and other sugar compounds, which suggests that it can modulate cell wall permeability and drug resistance. However, whether L-arabinose affects mycobacterial antibiotic resistance and the underlying regulatory mechanism remains unclear. In this study, we characterized a new transcription factor of Mycobacterium smegmatis, AraR, that responds to L-arabinose and regulates mycobacterial sensitivity to isoniazid (INH). AraR specifically recognizes two conserved 15-bp motifs within the upstream regulatory region of the arabinose (araR) operon. AraR functions as a transcriptional repressor that negatively regulates araR expression. In contrast to the effect of AraR, overexpression of the araR operon contributes to the mycobacterial INH resistance. L-arabinose acts as an effector and derepresses transcriptional inhibition by AraR. The araR-deficient strain is more resistant to INH than the wild-type strain, whereas the araR-overexpressing strain is more sensitive to INH. Addition of L-arabinose to the medium can significantly increase the resistance to INH of the wild-type strain, but not of the araR knockout strain. Therefore, we identified a new L-arabinose-responding transcription factor and revealed its effect on the bacterial antibiotic resistance. These findings can provide new insights in the regulatory mechanisms mediated by sugar molecules and their relationship with drug resistance in mycobacteria.

Background: Adjuvant trastuzumab improves survival outcomes of human epidermal receptor 2 positive early breast cancer patients. Currently, administration of 12 months adjuvant trastuzumab is the standard therapy. However, whether 6 months treatment is non-inferior to the standard 12 months treatment remains controversial. Methods: Relevant records were searched in PubMed, Cochrane Library, Web of Science, and EMBASE through Jan 14, 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were meta-analyzed. The primary endpoint was DFS with a non-inferiority hazard margin of 1.2 and the second was OS with 1.43. Results: Three randomized clinical studies met the inclusion criteria, including 3974 patients in 6 months group and 3976 in 12 months group. HR for DFS was 1.18 (95% CI 0.97–1.44, P = .09), with the non-inferiority margin comprised in the 95% CI. HR for OS was 1.14 (95% CI 0.98–1.32, P= .08), whereas the upper limit of 95% CI did not exceed the non-inferiority hazard margin. Conclusion: Our analysis failed to show that 6 months treatment was non-inferior to 12 months treatment in improving the DFS. Although the non-inferiority of the 6-month adjuvant trastuzumab treatment was found for OS, considering that breast cancer patients should receive additional systematic therapies when disease progression or relapse happens, we suggest that 12 months adjuvant trastuzumab treatment should remain the standard therapeutic strategy for patients with early human epidermal receptor 2 positive breast cancer.

Right ventricular (RV) function is considered the major determinant of prognosis in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this meta-analysis was to evaluate RV remodelling and function following balloon pulmonary angioplasty (BPA) in patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). We reviewed all studies evaluating RV function by cardiac magnetic resonance (CMR) and/or echocardiography pre- and post-BPA from PubMed/Medline prior to 15 December 2019. Ten (299 patients) of the 29 studies retrieved met the inclusion criteria: 5 CMR and 5 echocardiography studies. The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. Pooled data from CMR studies revealed BPA resulted in a significantly decreased RV end-diastolic volume index (weighted mean difference (WMD) − 28.33 ml/m2, p < 0.00001) and RV end-systolic volume index (WMD − 29.06 ml/m2, p < 0.00001) accompanied by an increased RV ejection fraction (RVEF, WMD 8.97%, p < 0.00001). Data from the echocardiography studies showed BPA resulted in decreased RV basal diameter (WMD − 0.37 cm, p = 0.0009) and an increase of RV fractional area change (WMD 5.97 %, p = 0.003), but improvements of tricuspid annular plane systolic excursion (TAPSE) and S′ were not significant. BPA improves RVEF and decreases RV volumes in patients with inoperable CTEPH or persistent/recurrent PH after PEA. • Balloon pulmonary angioplasty improves RVEF and decreases RV volumes in patients with inoperable CTEPH or persistent/recurrent PH after PEA.

A magnesium scaffold is a promising biodegradable bone repair material. However, its poor corrosion resistance limits its clinical application. In this study, we improved the corrosion resistance, biocompatibility and osteointergration ability of magnesium by alloying it with neodymium (Nd) and zinc (Zn), then fabricated a novel open-porous Mg–Nd–Zn (P-MNZ) alloy using a titanium wire space holder (TWSH) method. An in vitro corrosion experiment showed that corrosion resistance was enhanced. Both in vitro and in vivo experiments were performed to evaluate the biocompatibility and osteointergration ability of P-MNZ. The cell viability, cytoskeleton staining, ALP activity and osteogenic related gene expression confirm that the P-MNZ scaffold exhibits better biocompatibility and osteoblast differentiation properties in vitro. As for the in vivo experiment, the analysis of micro-CT scanning, Van Gieson staining and sequential polychrome labelling demonstrated that P-MNZ stimulates new bone formation and enhances the corrosion resistance of the P-MNZ scaffold. The results indicate that the P-MNZ alloy is a promising biodegradable bone repair material.

An asymmetric synthesis of 14-methyl-1-octadecene, the sex pheromone of the peach leafminer moth, has been efficiently achieved. A key chiral intermediate, ( R)−4-(benzyloxy)−3-methylbutanal, which has been developed as the resource chemical, can be obtained in large quantities from the steroid industry. 1,11-Undecanediol is selectively masked, and then converted into a phosphonium salt derivative, thereby effectively constructing a carbon skeleton. The target molecule is synthesized in 8 linear steps, with a 42% yield. The key characteristic of our synthesis lies in its chiral-pool strategy.

Large quantities of mucilage are synthesized in seed coat epidermis cells during seed coat differentiation. This process is an ideal model system for the study of plant cell wall biosynthesis and modifications. In this study, we show that mutation in Irregular Xylem 7 (IRX7) results in a defect in mucilage adherence due to reduced xylan biosynthesis. IRX7 was expressed in the seeds from 4 days post-anthesis (DPA) to 13 DPA, with the peak of expression at 13 DPA. The seed coat epidermis cells of irx7 displayed no aberrant morphology during differentiation, and these cells synthesized and deposited the same amount of mucilage as did wild type (WT) cells. However, the distribution of the water-soluble vs. adherent mucilage layers was significantly altered in irx7 compared to the WT. Both the amount of xylose and the extent of glycosyl linkages of xylan was dramatically decreased in irx7 water-soluble and adherent mucilage compared to the WT. The polymeric structure of water-soluble mucilage was altered in irx7, with a total loss of the higher molecular weight polymer components present in the WT. Correspondingly, whole-seed immunolabeling assays and dot-immunoassays of extracted mucilage indicated dramatic changes in rhamnogalacturonan I (RG I) and xylan epitopes in irx7 mucilage. Furthermore, the crystalline cellulose content was significantly reduced in irx7 mucilage. Taken together, these results indicate that xylan synthesized by IRX7 plays an essential role in maintaining the adhesive property of seed coat mucilage, and its structural role is potentially implemented through its interaction with cellulose.

The feasibility of the anaerobic ammonium oxidation (anammox) process to treat synthetic swine wastewater containing antibiotics and heavy metals was studied in this work. Nitrogen removal performance and granule characteristics were tracked by continuous-flow monitoring to evaluate the long-term joint effects of Cu and Zn and of Cu and oxytetracycline (OTC). Cu and Zn with a joint loading rate (JLR) of 0.04 kg m(-3) day(-1) did not affect the performance, while a JLR of 0.12 kg m(-3) day(-1) caused a rapid collapse in performance. Cu and OTC addition with a JLR of 0.04 kg m(-3) day(-1) for approximately 2 weeks induced significant nitrite accumulation. Granule characteristic analysis elucidated the disparate inhibition mechanisms of heavy metals and antibiotics: the internalization of heavy metals caused metabolic disorders, whereas OTC functioned as a growth retarder. However, anammox reactors could adapt to a JLR of 0.04 kg m(-3) day(-1) via self-regulation during the acclimatization to subinhibitory concentrations, which had a stable nitrogen removal rate (>8.5 kg m(-3) day(-1)) and removal rate efficiency (>75 %) for reactors with Cu-OTC addition. Therefore, this study supports the great potential of using anammox granules to treat swine wastewater.

Octamer transcription factor 1 (OCT1) was found to influence the genesis and progression of numerous cancers except for colorectal cancer (CRC). This study tried to explore the role of OCT1 in CRC and clarify the association between its expression and patients’ clinical outcome. Transcriptional and post-transcriptional expression of OCT1 was detected in CRC cancerous tissues and paired normal mucosae by real-time PCR as well as immunohistochemistry. Moreover, the effect of OCT1 knockdown on CRC cell proliferation was investigated both in vitro and in vivo using Cell Counting Kit-8 assay, colony-forming assay, and mouse tumorigenicity assay. Expression of OCT1 was found to be elevated in CRC. Suppression of OCT1 significantly inhibited CRC cell proliferation both in vitro and in vivo. Furthermore, upregulated level of OCT1 was significantly associated with N stage, M stage, and American Joint Committee on Cancer (AJCC) stage (P = 0.027, 0.014, and 0.002, respectively) as well as differential degree (P = 0.022). By using multivariate Cox hazard model, OCT1 was also shown to be a factor independently predicting overall survival (OS; P = 0.013, hazard ratio = 2.747, 95 % confidence interval 1.125 to 3.715) and disease-free survival (DFS; P = 0.004, hazard ratio = 2.756, 95 % confidence interval 1.191 to 4.589) for CRC patients. Our data indicate that OCT1 carries weight in colorectal carcinogenesis and functions as a novel prognostic indicator and a promising target of anti-cancer therapy for CRC.

BACKGROUND The combination of durvalumab and tremelimumab results in clinical benefit, with a tolerable safety profile in patients with solid tumors. OBJECTIVE To evaluate the efficacy and safety of durvalumab in combination with tremelimumab compared with either drug alone. METHODS The online databases (PubMed, Web of Science, EMBASE, and Cochrane Library) were searched for potential clinical studies up to Nov 26, 2019. Eligible studies were prospective and registered clinical trials. Pooled odds ratios for objective response rate and disease control rate and pooled risk ratios for treatment-related adverse events were meta-analyzed. A random-effect model was used due to the synthesis of different cancer types. RESULTS Overall, 5 studies were eligible for systematic review, 3 of which were further meta-analyzed. Durvalumab plus tremelimumab was superior to tremelimumab monotherapy in improving disease control rate in head and neck squamous cell carcinoma. However, there were no significant differences between dual immunotherapy and mono-immunotherapy in pancreatic ductal adenocarcinoma and gastric and gastroesophageal junction adenocarcinoma. Additionally, pooled analyses illustrated that no significant differences in treatment-related adverse events were displayed between the 2 groups. CONCLUSION Durvalumab and tremelimumab combination therapy had a good safety profile and resulted in clinical benefit in head and neck squamous cell carcinoma. Future explorations are needed to further confirm the application of durvalumab plus tremelimumab.

The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia. The study is to investigate whether lactucin plays a key role in adipogenesis. To this end, in vivo male C57BL/6 mice fed a high-fat diet (HFD) were treated with 20 mg/kg/day of lactucin or vehicle by gavage for seven weeks. Compared with vehicle-treated controls, Lactucin-treated mice showed lower body mass and mass of adipose tissue. Consistently, in vitro 3T3-L1 cells were treated with 20 &mu, M of lactucin. Compared to controls, lactucin-treated cells showed significantly less lipid accumulation during adipocyte differentiation and lower levels of lipid synthesis markers. Mechanistically, we showed the anti-adipogenic property of lactucin was largely limited to the early stage of adipogenesis. Lactucin-treated cells fail to undergo mitotic clonal expansion (MCE). Further studies demonstrate that lactucin-induced MCE arrests might result from reduced phosphorylation of JAK2 and STAT3. We then asked whether activation of JAK2/STAT3 would restore the inhibitory effect of lactucin on adipogenesis with pharmacological STAT3 activator colivelin. Our results revealed similar levels of lipid accumulation between lactucin-treated cells and controls in the presence of colivelin, indicating that inactivation of STAT3 is the limiting factor for the anti-adipogenesis of lactucin in these cells. Together, our results provide the indication that lactucin exerts an anti-adipogenesis effect, which may open new therapeutic options for obesity.

OBJECTIVES: Cerebral ischemia seriously threatens human health and is characterized by high rates of incidence, disability and death. Developing an ideal animal model of cerebral ischemia that reflects the human clinical features is critical for pathological studies and clinical research. The goal of this study is to establish a local cerebral ischemia model in rhesus macaque, thereby providing an optimal animal model to study cerebral ischemia. METHODS: Eight healthy rhesus monkeys were selected for this study. CT scans were performed before the operation to exclude cerebral vascular and intracranial lesions. Under guidance and monitoring with digital subtraction angiography (DSA), a microcatheter was inserted into the M1 segment of the middle cerebral artery (MCA) via the femoral artery. Then, autologous white thrombi were introduced to block blood flow. Immediately following embolization, multisequence MRI was used to monitor cerebrovascular and brain parenchymal conditions. Twenty-four hours after embolization, 2 monkeys were sacrificed and subjected to perfusion, fixation and pathological examination. RESULTS: The cerebral ischemia model was established in 7 rhesus monkeys; one animal died during intubation. DSA and magnetic resonance angiography (MRA) indicated the presence of an arterial occlusion. MRI showed acute local cerebral ischemia. HE staining revealed infarct lesions formed in the brain tissues, and thrombi were present in the cerebral artery. CONCLUSION: We established a rhesus macaque model of local cerebral ischemia by autologous thrombus placement. This model has important implications for basic and clinical research on cerebral ischemia. MRI and DSA can evaluate the models to ensure accuracy and effectiveness.

This study was conducted to investigate the effects of different levels of dietary partial MEs and coated cysteamine (CC) supplementation on gut microbiota in finishing pigs. Results showed that whittling down dietary partial MEs (Cu, Fe, Zn, Mn) by 20% and 40% had little effect on the microbial diversity, community structure, and bacterial relative abundance in the ileum of finishing pigs. Supplementation with 1,600 mg/kg CC also had no obvious effect on the microbial diversity, community structure, and bacterial relative abundance in the finishing pig ileum when fed diets with a normal MEs level. However, the abundance of Peptostreptococcaceae, Pasteurella, and Pasteurella_aerogenes was higher, and the abundance of Actinobacillus_minor was lower in the 20% ME reduction diet treatment than that in the 20% ME reduction with 1,600 mg/kg CC diet group (p

In congenital heart disease (CHD), the presence of pulmonary arterial hypertension (PAH) is associated with a poor prognosis. In this study, we aim to investigate the role of pulmonary artery compliance (Cp) in predicting the mortality of PAH associated with adult congenital heart disease (APAH-CHD). One-hundred and seventy-five patients of APAH-CHD who underwent a comprehensive clinical evaluation were included in this study. All patients were followed up in a 6-month interval and the primary end point was all cause of death. The duration of mean follow-up was 67±26 months, of which there were twenty-three death. Cp had an inverse correlation with pulmonary artery resistance (PVR), regardless of the clinical phenotype (Eisenmenger syndrome, PAH with small defect and PAH after defect correction). Patients in the lowest Cp group (Cp ≤ 0.84 mL/mmHg) had advanced WHO function class, worse exercise tolerance, liver function, and status of oxygen saturation. In univariate cox regression analysis, Cp (HR = 1.359, P < 0.001), PVR (HR = 0.972, P = 0.001), pulmonary blood flow (HR = 1.092, P = 0.001), heart rate (HR = 1.038, P = 0.028) and 6-minute walking distance (HR = 1.003, P = 0.037) were predictors of survival. After adjustment by bivariate analysis, Cp was the independent predictor. Kaplan-Meier survival curves showed that patients with Cp < 1.04 mL/mmHg had worse prognosis. In conclusion, Cp possibly reflects disease severity and decreased Cp was associated with poor prognosis in patients with APAH-CHD.

Two 2-phenylethanol biosynthetic pathways were constructed into Arabidopsis ; 2-phenylethanol biosynthesis led to reduced rate of lignin biosynthesis and increased cellulose-to-glucose conversion in the transgenic plants. Lignin is the second most abundant biopolymer on the planet with importance for various agro-industrial activities. The presence of lignin in cell walls, however, impedes biofuel production from lignocellulosic biomass. The phenylpropanoid pathway is responsible for the biosynthesis of lignin and other phenolic metabolites such as 2-phenylethanol. As one of the most used fragrance chemicals, 2-phenylethanol is synthesized in plants from l-phenylalanine which is the first specific intermediate towards lignin biosynthesis. Thus, it is interesting to prove the concept that the phenylpropanoid pathway can be modulated for reduction of lignin as well as production of natural value-added compounds. Here we conferred two 2-phenylethanol biosynthetic pathways constructed from plants and Saccharomyces cerevisiae into Arabidopsis. As anticipated, 2-phenylethanol was accumulated in transgenic plants. Moreover, the transformants showed 12–14 % reduction in lignin content and 9–13 % increase in cellulose content. Consequently, the glucose yield from cell wall hydrolysis was increased from 37.4 % in wild type to 49.9–52.1 % in transgenic plants with hot water pretreatment. The transgenic plants had normal development and even enhanced growth relative to the wild type. Our results indicate that the shunt of l-phenylalanine flux to the artificially constructed 2-phenylethanol biosynthetic pathway most likely reduced the rate of lignin biosynthesis in Arabidopsis.

Liver dysfunction reflects the status of heart failure, and previous studies have demonstrated that serum lactate dehydrogenase (S-LDH) levels are increased in patients exhibiting heart failure and liver dysfunction. Right heart failure is a main characteristic of idiopathic pulmonary arterial hypertension (IPAH). The aim of the present study was to assess the prognostic significance of S-LDH levels in patients with IPAH. S-LDH levels were determined in 173 patients with IPAH, and these patients were subclassified into two groups according to a defined upper reference limit of S-LDH (250 IU/l). Right heart catheterization was performed in all patients. A total of 53 patients were found to have elevated S-LDH to ≥250 IU/l. In a mean follow-up period of 31.2±17.9 months, 57 patients succumbed. In the group with lower S-LDH levels (S-LDH

Pseudomonas aeruginosa is a common pathogenic bacterium in urinary tract infections (UTIs), particularly catheter-associated UTIs. The aim of this study was to investigate the effect of azithromycin (AZM) on P. aeruginosa isolated from UTIs. Isolates were identified by biochemical assays and the Vitek system. Antimicrobial susceptibility was determined using the disk diffusion assay. Biofilm formation and adhesion were assayed using a crystal violet staining method. The swimming motility was assayed on agar plates. The elastase activity and rhamnolipid production were determined by the elastin-Congo red method and orcinol reaction, respectively. A total of 32 bacterial isolates were collected from 159 urinary catheters and eight of them were P. aeruginosa isolates. The results showed that the P. aeruginosa isolates had stronger biofilm formation capability and the biofilms were thicker than those of P. aeruginosa PAO1. AZM inhibited biofilm formation and adhesion on urinary catheters, and also decreased swimming motility and the production of virulence factors. The results of this study indicated that AZM is potentially a good choice for use in the treatment of UTIs.

The scheduling optimization of the flow line is a core of modern managing technology and Data Processing. The goal of the problem is to minimize the sum of the total flow time. Aiming at machine scheduling of production process, this paper presents a genetic algorithm based heuristic for the problem. An encoding method based working procedure and parthenogenetic operations are applied to solve the flow line scheduling problem. The computational results indicate that the proposed approach is effective in terms of reduced makespan for the attempted problems.

In this letter, a digital watermarking method which combines the singular value decomposition (SVD) and the discrete cosine transform (DCT) is presented. First of all, The Arnold scrambling and the DCT are performed on the watermark and the original image, respectively. The SVD transform is performed on the image when scrambled watermark is embedded, then the watermarked image is formed. Finally, we extract watermark from the image which is handled by halftone screens. The experimental results show that this method can achieve the highest possible robustness without losing the transparency. Also it can anti printing and scanning. All the processes do not require any additional equipment. It will bring new hope to the field of anti-counterfeiting printing with singular value decomposition is applied to the half-tone image area.

The diaphragm capsule, one of the most important components of the vacuum pressure sensor, should have linear elastic characteristic. Make research on simulation of the diaphragm capsule packaged in vacuum pressure sensor by finite elements Analysis to obtain its elastic characteristic, and get its elastic characteristic by experiment. Compare the displacements between simulation and experiment at each load, the maximum error is smaller than 5%. The analysis results can be used for the structure design of the diaphragm capsule.

Background Soluble suppression of tumorigenicity (sST2) has been proposed to be a marker for biomechanical strain and a possible predictor of mortality in patients with chronic heart failure. The use of sST2 in pulmonary arterial hypertension (PAH) has not been well defined. Hypothesis Plasma sST2 levels may correlate with the disease severity and predict clinical worsening in PAH. Methods We performed a cohort study of 40 idiopathic PAH patients with data on demographics, exercise capacity, echocardiographic parameters, laboratory tests, hemodynamics, and medications. Plasma sST2 was assessed with the high-sensitivity ST2 ELISA kit at diagnostic catheterization. All patients were followed up from the date of blood sampling. The endpoint was clinical worsening. Results sST2 was significantly elevated in patients with idiopathic PAH compared with control subjects (28.9 ± 13.9 vs 20.7 ± 7.5 ng/mL, P = 0.003). Pearson correlation analysis revealed that sST2 levels correlated with cardiac index (r = −0.534, P = 0.000) and pulmonary vascular resistance (r = 0.350, P = 0.027), and could reflect disease severity of PAH. After a mean follow-up of 14 ± 5 months, 12 patients showed clinical worsening. Receiver operating characteristic analysis suggested that sST2 levels >31.4 ng/mL discriminated clinical worsening with a sensitivity and specificity of 83.3% and 78.6%, respectively. Kaplan-Meier analysis showed that higher sST2 levels (>31.4 ng/mL) were associated with poor clinical outcomes (P = 0.008). Multivariate Cox regression analysis showed that sST2 was an independent predictor of clinical worsening (hazard ratio: 6.067, 95% confidence interval: 1.317–27.948, P = 0.021). Conclusions sST2 correlates with disease severity and is a significant predictor of clinical worsening in patients with PAH.

Marine siliceous rocks are widely distributed in the central orogenic belt (COB) of China and have a close connection to the geological evolution and metallogenesis. They display periodic distributions from Mesoproterozoic to Jurassic with positive peaks in the Mesoproterozoic, Cambrian—Ordovician, and Carboniferous—Permian and their deposition is enhanced by the tensional geological settings. The compressional regimes during the Jinning, Caledonian, Hercynian, Indosinian, and Yanshanian orogenies resulted in sudden descent in their distribution. The siliceous rocks of the Bafangshan-Erlihe ore deposit include authigenic quartz, syn-depositional metal sulphides, and scattered carbonate minerals. Their SiO2content (71.08–95.30%), Ba (42.45–503.0 ppm), and ΣREE (3.28–19.75 ppm) suggest a hydrothermal sedimentation origin. As evidenced by the Al/(Al + Fe + Mn), Sc/Th,(La/Yb)N, and(La/Ce)Nratios andδCe values, the studied siliceous rocks were deposited in a marginal sea basin of a limited ocean. We suggest that the Bafangshan-Erlihe area experienced high- and low-temperature stages of hydrothermal activities. The hydrothermal sediments of the former stage include metal sulphides and silica, while the latter was mainly composed of silica. Despite the hydrothermal sedimentation of the siliceous rocks, minor terrigenous input, magmatism, and biological activity partly contributed to geochemical features deviating from the typical hydrothermal characteristics.

This paper extends our previous algorithm for clustering. This previous algorithm works fine on simulated data. It can acquire satisfactory clustering results even with annular or zonal simulated data by causing the data to shrink within a cluster. To make use of the advantages of the previous algorithm, a one-dimensional (1D) histogram is mapped to a two-dimensional (2D) image and can be clustered by the previous algorithm, thus leading to stable results of histogram thresholds. The shrinking procedures of the 2D image or the 1D histogram are given, and a new parameter strategy is discussed.

G protein-coupled receptors (GPCRs) are signaling molecules with a wide variety of skills. Members of this large family of membrane protein have been shown to regulate the activities of the different signaling pathways of the ligand specific manner. α2–adrenoceptors (α2-ARs) are one of the GPCRs and the stimulation of them could modulate many classical effects such as hypotension, bradycardia, etc.. Recently, α2A-AR is more and more important for its role in the therapeutic applications in central nervous system (CNS) diseases. High throughput screening of α2A-AR agonists was established by LANCETM cAMP assay from a compound library of 80,000 small-molecule compounds to find out potential human α2A-adrenoceptor (α2A-AR) agonists that might have therapeutic effect in CNS diseases. From the preliminary and secondary screening, 37 compounds were identified as α2AAR agonists, and six compounds among them presented more pronounced α2A-AR stimulating activity than guanfacine, a selective α2A-AR agonist. The study provided referred data for the development of potent α2A-AR agonists and suggested that the existence of the parent structure (1, 2, 4-benzothiadiazine 1, 1-dioxide) bodes well for pharmaceutical development of α2A-AR agonists.

Gold nanoparticles/carbon nanotubes (Au-NPs/CNTs) composites synthesized by microwave-assisted method was modified on the gold coated quartz crystal by chitosan (CHIT) to immobilize anti-HbsAg antibody (HBsAb). Thus a HBsAb/(Au-NPs/CNTs)/CHIT/gold electrode was constructed and applied to the quantitative determination of Hepatitis B surface antigen (HBsAg) by quartz crystal microbalance (QCM). The obtained results show that Au-NPs/CNTs composites possessing high specific surface area is superior to gold nanoparticles (Au-NPs) in improving the detection sensitivity of HBsAg, and the detection sensitivity is 25.571 Hz/(μg/mL) and the linear range is 0.01 μg/mL ~ 5.0 μg/mL. The QCM immunosensor has good regenerability and not significant difference with ELISA in sample detection.

The entangled materials with spiral wire structure have been investigated in terms of the stretching behavior, mechanical properties, and stress–strain hysteresis effect. The results indicate that these materials are much more flexible than that with non-woven wire structure. They exhibit 1.05 MPa yielding strength and 5.7 MPa Young’s modulus in average at the porosity of 60%, and 2.47 MPa yielding strength and 12.3 MPa Young’s modulus in average at the porosity of 45%. Under tensile loading the materials exhibit a unique stress–strain behavior that goes through a long strain period after yielding and follows a quick stress increase on the stress–strain curve due to the ‘unclosing’ and ‘straightening’ mechanism of the spiral wire structure. In addition, these materials exhibit obvious stress–strain hysteresis effect. Their energy dissipation values determined according to the stress–strain hysteresis loops are 28.6 mJ/cm 3 at the porosity of 60% and 102.3 mJ/cm 3 at the porosity of 45%, which are much larger than that of the polymer foam, implying their promising applications for the energy absorption.

We present the fabrication of submicron polyimide film sandwiched by Al film. The preparation in two-step method and spin-coating parameters of submicron polyimide film are described. To achieve self-supported structure, thick nickel mesh (ca. 200 μm) was introduced by micro-electroforming. Using negative tone photoresist SU-8 2150, the nickel grid width was demonstrated in good agreement with its original design value with optical microscopy.

A finite element model of floating raft vibration isolation system are established in this paper. The stress cloud and the natural frequencies are given based on the analysis of the static response and modes of this floating raft vibration isolation system. The calculation and analysis above may be helpful for preventing the floating raft system from working on resonant area and for keeping the oversize dynamic deformation. On this basis, vibration isolation effect has been assessed by vibration level difference

There are a lot of developments focused on 3D surface reconstruction based on 2D contours in recent decades, mostly based on closed contours. Due to the limitation of imperfect technology on material classification and edge extraction, it’s difficult to extract closed contours automatically, and this situation limits the application of 3D surface reconstruction based on contour. This paper designs a reconstruction algorithm based on non-closed contour, which not only provides a new viewpoint for research on 3D reconstruction, but also make 3D reconstruction based on contour more applicable.

As the substrates of biosensor or biomicroarray, silicon, silica and gold matrixes are usually used as the surfaces of bio-recognition. In this research, designed micro-patterned silicon/silica slide and gold/silica slide were utilized respectively as the substrates of DNA and protein detection. The results suggested the detection limit of protein and DNA on silicon/silica slide were 10 μg/L and 10 pM respectively, and those on gold/silica slide were 10 μg/L and 100 pM respectively. The patterned silicon/silica and gold/silica slide could be used as the support of bio-microarray in high-sensitive biorecognition.

Montmorillonite/SBS composite modifed asphalts were prepared by mixing montmorillonite with SBS-modified asphalt, further the corresponding asphalt mixtures were obtained. The paving technical indexes of the mixture such as physical properties, moisture suscepyibility, and high temperature stability were tested, and compared with that of the corresponding SBS-modifed asphalt mixture and base asphalt mixture. The results demonstrate that the montmorillonite/SBS composite modifed asphalt mixture exhibites enhanced stability, improved flow value and moisture susceptibility, and increased high temperature stability.

The two cooling styles of spraying cooling and water jacket cooling were studied for exhaust gas of engine within water-collecting box (WCB). Based on Eulerian-Lagrangian method, the heat and mass transfer between exhaust gas and water droplets were solved. By comparing the general characteristic index K/ΔP of six models with different tubes, the model with bended tubes is defined as the best model in which the length of outer tube is less than inner one. With the increase of water spraying flux, the gas temperature and the evaporation rate of water droplets tend to decrease. The decrease of gas temperature can be restrained by the phenomenon of “water assembled”, after the spraying flux rise to a certain value with continued increase. Compared with the water jacket cooling, the spraying cooling has a high heat transfer coefficient and a low cooling water cost, as well as reduces the resistance lost of exhaust gas.

A framework of modeling and simulating a typical artificial system is proposed based on discrete event system and Petri net. Firstly, the system model is constructed based on discrete event system theory. Secondly, the model is described and analyzed by using Petri net. Then, the simulation procedures on Matlab platform are presented in detail. The proposed framework is applied to modeling and simulating a logical control system of a marine diesel engine. The simulation results indicate that this logical control system model can be constructed by the given framework and the proposed method is effective in simulating and analyzing this kind of artificial system.

The correct and prompt diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) plays a pivotal role in determining appropriate therapy. This study aimed to compare the diagnostic efficacy of pulmonary ventilation/perfusion (V/Q) scanning and computed tomography pulmonary angiography (CTPA) using pulmonary angiography as the golden standard.A total of 114 consecutive patients (49 men and 65 women, age 43.3 ± 15.3 years) suspected of having CTEPH were prospectively enrolled. All patients underwent V/Q scanning, CTPA, and pulmonary angiography within an interval of 7 days from one another. Interpretation of V/Q images was based on the refined Pulmonary Embolism Diagnosis criteria. For threshold 1, high-probability and intermediate-probability V/Q scan findings were considered to be positive, and low-probability/normal V/Q scan findings were negative. For threshold 2, only a high-probability V/Q scan finding was considered to be positive, and intermediate-probability and low-probability/normal V/Q scan findings were considered to be negative.Fifty-one patients (44.7%) had a final diagnosis of CTEPH. V/Q scan showed high probability, intermediate probability, and low probability/normal scan in 52, three, and 59 patients, respectively. CTPA revealed 50 patients with CTEPH and 64 patients without CTEPH. The sensitivity, specificity, and accuracy of the V/Q scan were 100, 93.7, and 96.5%, respectively, with threshold 1, and 96.1, 95.2, and 95.6%, respectively, with threshold 2; similarly, the sensitivity, specificity, and accuracy of CTPA were 92.2, 95.2, and 93.9%, respectively.In conclusion, both V/Q scanning and CTPA are accurate methods for the detection of CTEPH with excellent diagnostic efficacy.

Background: Inhaled iloprost (average >30 µg/d) has been considered an effective treatment for severe pulmonary hypertension (PH). Further evidence also showed that low-dose iloprost given intravenously was equally effective as high-dose iloprost in the therapy of systemic sclerosis. Hypothesis: Patients with pulmonary hypertension will benefit from inhalation of low-dose iloprost. Methods: Sixty-two patients with PH were enrolled and initiated with neubulizedlow-dose iloprost (2.5 µg per inhalation, 6× daily) for 24 weeks in 13 medical centers in China. Efficacy endpoints included changes in 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC), and hemodynamic parameters. Results: Fourteen patients (22.6%) prematurely discontinued the study: 8 due to clinical worsening (6 in WHO-FCIII–IV at baseline), 4 because of protocol change, and 2 patients lost during follow-up. In the remaining 48 patients, 6MWD was increased from 356 ± 98 meters to 414 ± 99 meters (P < 0.001) and WHO-FC improved significantly (P = 0.006) after 24-week inhalation therapy. Cardiac output, cardiac index, and mixed venous oxygen saturation improved significantly compared with baseline (n = 34, P < 0.05). Most of the hemodynamic parameters improved significantly in patients in WHO-FC II (P < 0.05) but not in patients in WHO-FCIII–IV. Conclusions: Low-dose iloprost inhalation significantly improved exercise capacity and functional status in patients with PH. It was well tolerated. The improvement of hemodynamics was confirmed in patients with WHO-FCI–II but not in patients with WHO-FCIII–IV, suggesting the importance of early treatment in patients with advanced disease stages. Clin. Cardiol. 2012 DOI: 10.1002/clc.21987 This study was supported by National Grant from the Ministry of Science and Technology (Beijing, China, project number 2006BAI01A07) and the Capital Development Scientific Fund (Beijing, China, project number 2005-1018). The authors have no other funding, financial relationships, or conflicts of interest to disclose.

DNA glycosylases play important roles in DNA repair in a variety of organisms, including humans. However, the function and regulation of these enzymes in the pathogenic bacterium Mycobacterium tuberculosis and related species are poorly understood. In the present study, the physical and functional interactions between 3-methyladenine DNA glycosylase (MAG) and topoisomerase I (TopA) in M. tuberculosis and M. smegmatis were characterized. MAG was found to inhibit the function of TopA in relaxing supercoiled DNA. In contrast, TopA stimulated the cleavage function of MAG on a damaged DNA substrate that contains hypoxanthine. The interaction between the two proteins was conserved between the two mycobacterial species. Several mutations in MAG that led to the loss of its interaction with and activity regulation of TopA were also characterized. The results of this study further elucidate glycosylase regulation in both M. smegmatis and M. tuberculosis.

A method using principal component analysis (PCA) of dynamic power supply current was proposed for testing of analog circuits in this paper. The basic model of the proposed method and the general rule for analog fault detection were described in detail. At first, the principal component model of fault-free circuits was constructed. Then the circuits-under-test was compared with the principal component model to calculate the statistic for fault detection. The features of power supply current in both time and frequency domain were combined by PCA, and it could overcome the difficulty to determine threshold by empirical knowledge. The proposed method was applied to detect faults of the signal filtering and amplifying circuit, which is used in the ultrasonic liquid-level sensor. The results show that the power supply current contains information about the circuit’s faults, and can be used for fault detection of analog circuits by analyzing this signal.

For the stereo matching problem in the non-texture, occluded and depth discontinuity regions, a new stereo matching algorithm that based on the adaptive support-weight of Graph Cuts is proposed. It can reduce the matching error in the depth discontinuity and non-texture regions by the single adaptive support-weight matching methods. The occlusion and smoothness penalty is considered by building the energy function. The experimental results show that the proposed algorithm can achieve more precise and reliability matching.

This paper has done CAE analysis of hot stamping, and optimized the water-cooled system which takes the degree of uniform temperature of blank as the objective function of optimization. The aim is to find a method of optimizing hot stamping mold cooling system based on ANSYS Parametric Design Language (APDL) with ANSYS Mechanical/LS-DYNA software and lay the foundation for designing hot stamping mold. And the work mainly consists of three sections, building parametric finite element model, simulating the process of quenching and optimizing the location parameters and radiuses of each coolant duct. Finally, contrast the optimal result with the initial result and get the conclusion, and moreover, point out the future work.

The apparent features of p75 neurotrophin receptor (p75(NTR)) expression indicated that p75(NTR) would serve as a potential stem cell marker for normal human laryngeal squamous epithelia. In human laryngeal squamous cell carcinoma (LSCC) p75(NTR) is differentially expressed. The abnormal expression and distribution of p75(NTR) may indicate malignant transformation.To investigate the expression of p75(NTR) and its possible roles in normal laryngeal squamous epithelia and LSCC.We used immunohistochemistry methods to examine normal laryngeal epithelia, para-cancer mucosa with dysplasia, laryngeal papilloma, and LSCC specimens for the expression of p75(NTR), nerve growth factor (NGF), -tyrosine kinase receptor (TrkA), p63, and Ki67. Immunocytochemistry and flow cytometry were used to examine the expression of p75(NTR) in Hep-2 cells.The expression of p75(NTR) was only located in basal cells of normal laryngeal epithelia, consistent with the staining features of epithelial stem cells as evidenced by parallel staining of p63, a putative keratinocyte stem cell marker. p75(NTR) is differentially expressed in LSCC, although no significant relationship was found with many clinicopathologic factors, this expression and distribution may correlate to malignant transformation and tumor proliferation. Co-expression of p75(NTR) and CD133 was confirmed, showing the association of p75(NTR)-positive cells with cancer stem cells in Hep-2 cells.

Confident protein-DNA interaction (PDI) data could significantly improve our understanding of transcriptional regulation network in both prokaryotes and eukaryotes. New methods need to be established for validating and mining the protein-DNA interaction data produced by bioinformatic tools and large-scale screening assays. In this study, we integrated bacterial one-hybrid technique (B1H) with classical chromatin immunoprecipitation (ChIP) assay to develop an innovative B1H-ChIP method, which has the advantages of being high-throughput, low cost, and easy-to-perform. Using this method, we validated two pairs of previously reported PDIs and further successfully discovered five novel target genes for Mce2R and four novel regulators of the gene dnaA in the human pathogen Mycobacterium tuberculosis. New PDI data suggest that Mce2R may play novel roles in the regulation of multi-drug resistance, cell wall synthesis, and intracellular growth of M. tuberculosis, and there exists a probable selective regulation of dnaA under different host conditions. Our findings provide important new information for understanding unique regulatory mechanisms in the pathogen. The B1H-ChIP approach has wide applications both in validating and discovering PDIs and in unraveling transcriptional regulatory network in prokaryotes and eukaryotes.