Search

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects women of childbearing age, resulting in reproductive dysfunction, hyperinsulinemia, and obesity. While several drugs are currently approved for use in these patients, their relative effectiveness remains controversial. The purpose of this meta-analysis was to evaluate the reproductive efficacy and safety of exenatide, a glucagon-like peptide-1 receptor agonist, versus metformin, an insulin sensitizer, in the treatment of patients with PCOS. Nine randomized controlled trials (RCTs) were included, comprising 785 PCOS patients, of whom 385 received exenatide and 400 received metformin. Compared with metformin, exenatide was significantly more effective in treating these patients, as demonstrated by increased pregnancy rate (relative risk (RR) = 1.93, 95% confidence interval (CI) 1.28 to 2.92, P = 0.002), greater ovulation rate (RR = 1.41, 95% CI 1.11 to 1.80, P = 0.004), decreased body mass index (mean difference = − 1.72 kg/m2, 95% CI − 2.27 to − 1.18, P = 0.00001), and improved insulin resistance (standard mean difference = − 0.62, 95% CI − 0.91 to − 0.33, P

Triple-negative breast cancers (TNBC) frequently harbor defects in DNA double-strand break repair through homologous recombination (HR), such as BRCA1 dysfunction. However, less than 15% of TNBC patients were found to carry BRCA1 mutation, indicating that there are other mechanisms regulating BRCA1-deficient in TNBC. In the current study, we shown that overexpression of TRIM47 correlates with progression and poor prognosis in triple-negative breast cancer. Moreover, we demonstrated that TRIM47 directly interacts with BRCA1 and induces ubiquitin-ligase-mediated proteasome turnover of BRCA1, subsequently leads to a decrease of BRCA1 protein levels in TNBC. Moreover, the downstream gene expression of BRCA1, such as p53, p27, p21 was significantly reduced in the overexpression of TRIM47 cell lines but increased in TRIM47-deleted cells. Functionally, we found that overexpression of TRIM47 in TNBC cells confers an exquisite sensitivity to olaparib, an inhibitor of poly-(ADP-ribose)-polymerase (PARP), but TRIM47 inhibition significantly confers TNBC cells resistance to olaparib both in vitro and in vivo. Furthermore, we showed that overexpression of BRCA1 significant increase the olaparib resistance in TRIM47-overexpression-induced PARP inhibitions sensitivity. Taken together, our results uncover a novel mechanism for BRCA1-deficient in TNBC and targeting TRIM47/BRCA1 axis may be a promising prognostic factor and a valuable therapeutic target for TNBC.

To evaluate the diagnostic value of computer-aided diagnosis (CAD) software on ultrasound in distinguishing benign and malignant breast masses and avoiding unnecessary biopsy.This prospective, multicenter study included patients who were scheduled for pathological diagnosis of breast masses between April 2019 and November 2020. Ultrasound images, videos, CAD analysis, and BI-RADS were obtained. The AUC, accuracy, sensitivity, specificity, PPV, and NPV were calculated and compared with radiologists.Overall, 901 breast masses in 901 patients were enrolled in this study. The accuracy, sensitivity, specificity, PPV and NPV of CAD software were 89.6%, 94.2%, 87.0%, 80.4%, and 96.3, respectively, in the long-axis section; 89.0%, 91.4%, 87.7%, 80.8%, and 94.7%, respectively, in the short-axis section. With BI-RADS 4a as the cut-off value, CAD software has a higher AUC (0.906 vs 0.734 vs 0.696, all p 0.001) than both experienced and less experienced radiologists. With BI-RADS 4b as the cut-off value, CAD software showed better AUC than less experienced radiologists (0.906 vs 0.874, p 0.001), but not superior to experienced radiologists (0.906 vs 0.883, p = 0.057). After the application of CAD software, the unnecessary biopsy rate of BI-RADS categories 4 and 5 was significantly decreased (33.0% vs 11.9%, 37.8% vs 14.5%), and the malignant rate of biopsy in category 4a was significantly increased (11.6% vs 40.7%, 7.4% vs 34.9%, all p 0.001).CAD software on ultrasound can be used as an effective auxiliary diagnostic tool for differential diagnosis of benign and malignant breast masses and reducing unnecessary biopsy.ClinicalTrials.gov (NCT03887598) KEY POINTS: • Prospective multicenter study showed that computer-aided diagnosis software provides greater diagnostic confidence for differentiating benign and malignant breast masses. • Computer-aided diagnosis software can help radiologists reduce unnecessary biopsy. • The management of patients with breast masses becomes more appropriate.

Neovascularization is a prominent cause of irreversible blindness in a variety of ocular diseases. Current therapies for pathological neovascularization are concentrated on the suppression of vascular endothelial growth factors (VEGF). Despite the remarkable efficacy of anti-VEGF drugs, several problems still exist, including ocular complications and drug resistance. Thus, it is still required to design novel drugs for anti-angiogenic treatment. This study aimed to investigate the anti-angiogenic effects of a small molecule multi-target tyrosine kinase inhibitor, DCZ19931, on ocular neovascularization. The results showed that administration of DCZ19931 at the tested concentrations did not cause obvious cytotoxicity and tissue toxicity. DCZ19931 could reduce the size of choroidal neovascularization (CNV) lesions in laser-induced CNV model and suppress ocular neovascularization in oxygen-induced retinopathy (OIR) model. DCZ19931 could suppress VEGF-induced proliferation, migration, and tube formation ability of endothelial cells, exhibiting similar anti-angiogenic effects as Ranibizumab. DCZ19931 could reduce the levels of intercellular cell adhesion molecule-1 (ICAM-1) expression in vivo and in vitro. Network pharmacology prediction and western blots revealed that DCZ19931 exerted its anti-angiogenic effects through the inactivation of ERK1/2-MAPK signaling and p38-MAPK signaling. In conclusion, this study indicates that DCZ19931 is a promising drug for anti-angiogenic therapy for ocular diseases.

Dezocine, a synthetic opioid, introduced in 1970s as an analgesic, was redeveloped for relieving moderate to severe pain by Yangtze River Pharmaceutical Group in China in 2009. To date, dezocine occupies 45% of China’s opioid analgesic market. Along with dezocine being a dominated painkiller, a certain amount of research was conducted to elucidate dezocine’s action. In this review we summarize the current knowledge on the receptor, preclinical and clinical pharmacology of dezocine. Briefly, preclinical data show that dezocine is effective under varying pain conditions, particularly chronic neuropathic pain and cancer pain, through activation of opioid receptors, and inhibition of norepinephrine reuptake. Clinical data establish the effectiveness of dezocine either as a primary analgesic for postoperative pain management or a supplement for balanced analgesia. The receptor profile of dezocine is different from known pure μ agonists, and allows it to be used in combination with other opioids for additivity in efficacy or lower incidence of adverse effects.

Highly structured RNA molecules usually interact with each other, and associate with various RNA-binding proteins, to regulate critical biological processes. However, RNA structures and interactions in intact cells remain largely unknown. Here, by coupling proximity ligation mediated by RNA-binding proteins with deep sequencing, we report an RNA in situ conformation sequencing (RIC-seq) technology for the global profiling of intra- and intermolecular RNA–RNA interactions. This technique not only recapitulates known RNA secondary structures and tertiary interactions, but also facilitates the generation of three-dimensional (3D) interaction maps of RNA in human cells. Using these maps, we identify noncoding RNA targets globally, and discern RNA topological domains and trans-interacting hubs. We reveal that the functional connectivity of enhancers and promoters can be assigned using their pairwise-interacting RNAs. Furthermore, we show that CCAT1-5L—a super-enhancer hub RNA—interacts with the RNA-binding protein hnRNPK, as well as RNA derived from the MYC promoter and enhancer, to boost MYC transcription by modulating chromatin looping. Our study demonstrates the power and applicability of RIC-seq in discovering the 3D structures, interactions and regulatory roles of RNA. RNA in situ conformation sequencing (RIC-seq) enables the generation of three-dimensional interaction maps of RNA in cells, which sheds light on the interactions and regulatory functions of RNA.

To evaluate the prompt and induced dose rate in backscattering neutron hall for radiation protection and safety management. The dose rates were calculated by Monte Carlo code FLUKA, with the “multi-step” simulation method based on traditional “two-step simulation” method. Operation time of staff workers does not need to be restricted. But with the increase in beam power and irradiation time, serious consideration might need to be taken as the dose rate of samples may be higher than the limit value.

The smart grid with flexible topologies receives intensive attention recently. Transmission switching (TS) alters the power system topology during operation, and has been demonstrated for the advantage of economic and secure operation of power systems. TS includes a chain of sequential switching actions which bring disturbances to the system if the switching actions are not properly designed. Unfortunately, it is not considered or well-studied in existing works. In this paper, a new multi-period TS model that considers the transition security and a two-stage iterative method are proposed. In the TS model, we take into account the fact that only one line is permitted to switch up or down at a time and the security of each switching action is considered. The proposed iterative solution makes the TS model more tractable under AC framework. Case studies on a 6-bus system and the IEEE 57-bus test system have varified the effectiveness of the proposed model. Numerical results show that: ➀ the consideration of transition security of TS is essential; ➁ the transition path is directly related to secure and fast the transmission switching; ➂ the proposed model and solution method give an effective way to determine the switching sequence and switching timing under transition security criteria.

Composite material, tetraethylenepentamine (TEPA) incorporated UiO-66 was prepared by impregnation method to study CO2 capture in a fixed bed reactor, atmospheric pressure. All synthesized adsorbents were characterized using PXRD, N2 adsorption–desorption isotherms, FT-IR, TGA, SEM, and Elemental analysis. Characterization results have revealed that incorporated TEPA was present within pores of UiO-66. CO2 adsorption was higher on TEPA incorporated UiO-66 compared to UiO-66. It was due to the chemical interaction between –NH2 and CO2. High CO2 adsorption capacity 3.70 mmol g−1 was obtained on 30TEPA/UiO-66 at 75 °C, 1 bar. Because of more flexibility and high dispersive nature of TEPA at this temperature. The same CO2 adsorption capacity was obtained in each adsorption cycle without decomposition of the amine on 30TEPA/UiO-66. Avrami adsorption kinetic model has suggested adsorption of CO2 on composite material was chemical adsorption and deactivation model suggested an initial rate of adsorption was higher on TEPA incorporated UiO-66.

The global spread of SARS-CoV-2 is posing major public health challenges. One feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site. Here, we find that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site utilizes an endosomal entry pathway. Using Sdel as model, we perform a genome-wide CRISPR screen and identify several endosomal entry-specific regulators. Experimental validation of hits from the CRISPR screen shows that host factors regulating the surface expression of angiotensin-converting enzyme 2 (ACE2) affect entry of Sfull virus. Animal-to-animal transmission with the Sdel virus is reduced compared to Sfull in the hamster model. These findings highlight the critical role of the S1/S2 boundary of SARS-CoV-2 spike protein in modulating virus entry and transmission and provide insights into entry of coronaviruses., The SARS-CoV-2 spike protein contains a multi-basic cleavage site. Here, the authors show how this multi-basic cleavage site affects entry of SARS-CoV-2 into cells and transmission in the hamster model and identify host factors affecting entry of SARS-CoV-2 in a genome-wide CRISPR screen.

Land filling is the main method to dispose municipal solid waste in China. During the decomposition of organic waste in landfills, fungi play an important role in organic carbon degradation and nitrogen cycling. However, fungal composition and potential functions in landfill have not yet been characterized. In this study, refuse and leachate samples with different areas and depths were taken from a large sanitary landfill in Beijing to identify fungal communities in landfills. In high-throughput sequencing of ITS region, 474 operational taxonomic units (OTUs) were obtained from landfill samples with a cutoff level of 3% and a sequencing depth of 19962. The results indicates that Ascomycota, with the average relative abundance of 84.9%, was the predominant phylum in landfill fungal communities. At the genus level, Family Hypocreaceae unclassified (15.7%), Fusarium (9.9%) and Aspergillus (8.3%) were the most abundant fungi found in the landfill and most of them are of saprotrophic lifestyle, which plays a big role in nutrient cycling in ecosystem. Fungi existed both in landfilled refuse and leachate while both the richness and evenness of fungal communities were higher in the former. In addition, fungal communities in landfilled refuse presented geographic variances, which could be partly attributed to physical habitat properties (pH, dissolved organic carbon, volatile solid, NH4+, NO2− and NO3−), while NO3− was considered the most significant factor (p < 0.05) in shaping fungal community.

Activation-induced cytidine deaminase (AID) mediates class switching by binding to a small fraction of single-stranded DNA (ssDNA) to diversify the antibody repertoire. The precise mechanism for highly selective AID targeting in the genome has remained elusive. Here, we report an RNA-binding protein, ROD1 (also known as PTBP3), that is both required and sufficient to define AID-binding sites genome-wide in activated B cells. ROD1 interacts with AID via an ultraconserved loop, which proves to be critical for the recruitment of AID to ssDNA using bi-directionally transcribed nascent RNAs as stepping stones. Strikingly, AID-specific mutations identified in human patients with hyper-IgM syndrome type 2 (HIGM2) completely disrupt the AID interacting surface with ROD1, thereby abolishing the recruitment of AID to immunoglobulin (Ig) loci. Together, our results suggest that bi-directionally transcribed RNA traps the RNA-binding protein ROD1, which serves as a guiding system for AID to load onto specific genomic loci to induce DNA rearrangement during immune responses.

Heterogeneous, homogeneous, and enzymatic catalysis have generally been treated and studied as three separate fields. However all three fields have many aspects that unify them, therefore it is useful to study catalysts from each field in similar manners. Heterogeneous catalysts have been studied extensively under reaction conditions to monitor dynamic changes that occur during catalytic reactions, their atomic and molecular structure, and composition and oxidation state with high spatial and time resolution. The techniques used to monitor these catalysts include sum frequency generation vibrational spectroscopy, high pressure scanning tunneling microscopy, and ambient pressure X-ray photoelectron spectroscopy. In order to use these techniques to study homogeneous catalysts and enzymes under reaction conditions, we have heterogenized homogeneous catalysts by encapsulating small metal clusters in dendrimers and immobilized enzymes through the use of DNA tethers. By studying all three fields under reaction conditions with the same techniques we aim to show that heterogeneous, homogeneous, and enzymatic catalysts all behave similarly at the molecular level.

Catalysts are generally classified into three categories: homogeneous, heterogeneous and enzyme, each evolved as an independent field. Efforts to bridge these fields are scarce but desirable. In this Perspective, we first describe how numerous classes of reactions can be achieved by all three categories of catalysts. Examples are given based on a selective survey of the literature. Next, a selection of important approaches, the benefits and challenges of constructing heterogeneous–homogeneous, heterogeneous–enzyme and homogeneous–enzyme hybrid catalysts are discussed based on published researches. Hybrid catalysts not only increase the performance, including activity, selectivity, lifetime and recyclability compared to one of the components, but also offer extra functions such as a microenvironment for different reaction pathways, and cascade catalysis for products that are challenging to produce. We expect future tailor-made hybrid catalysts will combine the advantages of the components and be optimized for industrial applications.

Urbanization and industrialization increase the concentrations of heavy metals in soils, which affect human health. A total of 127 topsoil samples were collected from the massively urbanized and industrialized district of Shanghai: Baoshan District. The sampling sites were isolated based on the land-use practice: industrial area, roadside area, residential area, and agricultural area. The absolute concentrations of heavy metals (Zn, Cr, Ni, Mn, Cu, Pb, and Cd) were determined using atomic absorption spectrometry and compared with Shanghai and the National soil background values. The geoaccumulation index (Igeo) and Nemerow pollution index were used to determine the existence and severity of the pollution of heavy metals. Enrichment factor (EF) analysis, spatial variability of pollution, and multivariate statistical analyses also were employed to determine the anthropogenic loading of heavy metals, their spatial dependency, and correlation among their sources, respectively. Moreover, potential ecological risk and human health risk [carcinogenic risk (RI) and noncarcinogenic hazard (HI)] were evaluated. The average concentration of all the metals (accounted as 229, 128, 56, 719, 55, 119, and 0.3 mg kg-1 for Zn, Cr, Ni, Mn, Cu, Pb, and Cd, respectively) was many folds higher than the background values. The indices depicted that the pollution exists in all the sites and severity decreases in the following order: industrial soils > roadside soil > residential soils > agricultural soils. However, Zn, Pb, and Cd showed high levels of pollution in all the soils. The EF values suggested that the majority of heavy metals are anthropogenically loaded; spatial variability showed that the pollution is more concentrated in Songnan town; Pearson's correlation, principal component analysis (PCA), and cluster analysis suggested different sources of origin for the majority of the heavy metals. RI of Cr and Pb ranged between 2.8E-04 and 2.7E-07. However, HI was site-specific (only for Cr, Pb, Mn), and most of the sites were in Songnan town. This study could be used as a significant piece of information for management purposes to prevent heavy metal pollution and to protect human health.

Background Focal segmental lesions (FSLs) are not uncommon in idiopathic membranous nephropathy (IMN). The reported percentage of IMN patients with focal segmental glomerulosclerosis (FSGS) lesions varies widely between studies. The objective of this study was to differentiate atypical FSL (aFSL) from typical FSGS in IMN and to analyse the clinicopathological predictors of primary outcome of IMN patients. Methods A total of 716 patients with biopsy-proven IMN between January 1, 2007 and December 31, 2017 were enrolled in the study. An atypical focal segmental lesion was defined as pure synechia, segmental hyperplasia of podocytes or thickening of the GBM accompanied by proliferation of the mesangial matrix, and absence of typical FSGS. The patients were divided into three groups: patients without FSL (FSL−), patients with typical FSGS (FSGS+), and patients with aFSL (aFSL+).The primary outcome was a 50% decline in the initial estimated glomerular filtration rate or end-stage renal disease (ESRD) incidence. Secondary outcomes included all-cause death and ESRD. Results FSGS was present in 174 patients, while aFSL was noted in 161 patients. Systolic blood pressure was higher in both aFSL+ group and FSGS+ groups compared with the FSL− group. IMN patients without FSL and with aFSL had lower serum creatinine levels than IMN patients with FSGS. Both the FSGS+ and aFSL+ groups had higher levels of proteinuria and lower albumin levels than the FSL− group. Renal tissue lesions, including tubulointerstitial fibrosis, glomerular obsolescence, and vascular sclerosis were significantly more severe in the FSGS+ group. Cox multivariate analysis showed that older age ≥ 60 years, eGFR

Background: The production of autoantibodies against tumour-associated antigens (TAAs) is believed to reflect greater immunologic reactivity in cancer patients and enhanced immune surveillance for cancer cells. Over the past few decades, a number of different TAAs and their corresponding autoantibodies have been investigated. However, positive frequency of autoantibody detection in cancer patients has been relatively low. Here we describe a novel TAA that was a fragment derived from human DNA-topoiomerase I and an autoantibody against the novel TAA with relatively high positive frequency in the sera of early-stage non-small-cell lung cancer (NSCLC), gastric cancer (GC), colorectal cancer (CRC) and oesophageal squamous cell carcinoma (ESCC). Methods: Serologic enzyme-linked immunosorbent assay (ELISA) and western blot were used to discover a novel TAA with a molecular weight of 48 kDa separated by ion exchange chromatography. Autoantibody ELISA, immnohistochemistry and immunofluorescent staining, recombinant protein cloning/expression and western blot were used to identify the novel TAA. The association of the autoantibody against the novel TAA with early-stage carcinoma was explored by screening 203 stage I/II patients and 170 stage III/IV patients with NSCLC, GC, CRC or ESCC. Results: We identified the novel TAA as a fragment derived from human DNA-topoiomerase I (TOP1). We found that the novel TAA induced specific autoantibodies with a high prevalence that ranged from 58 to 72% in some of the most common types of cancer. We observed that the immune response against the novel TAA was associated with early stage ESCC, GC, CRC and NSCLC. Conclusions: The findings in this study suggest that the autoantibody against the novel TAA may be a potential biomarker for use in the early detection and diagnosis of cancer.

A family of three-periodic nets formed from intersecting helical ladders (double helices) is described. Tilings and ring sizes are analyzed. Removal of the rungs of the ladders results in periodic patterns of linked rings (three-periodic “chain mail”). A related family of nets formed from triple helices leads similarly to interwoven threads.

5 nm Co–Rh bimetallic nanoparticles with narrow size distributions and three different atomic compositions (2, 10, and 16 % Rh) were synthesized using a colloidal method. The bimetallic nanoparticles were loaded into mesoporous silica support MCF-17 and utilized in the catalytic hydrogenation of CO (Fischer–Tropsch synthesis). As compared to the pure 5 nm Co/MCF-17 catalyst, the bimetallic Co–Rh catalysts showed a similar activity while enhancing the selectivity towards alcohols, as evidenced by an increased ratio of alcohol to hydrocarbon products. Furthermore, larger alcohols such as propanol were formed with the addition of Rh, which is not observed with the pure Co/MCF-17 catalyst. In situ synchrotron based Ambient Pressure X-ray Photoelectron Spectroscopy studies on the Co–Rh samples revealed that Rh is segregated to the surface of the nanoparticles under reaction conditions, which plays an important role in altering the selectivity towards alcohol production. An optimum surface Rh concentration exists at ~9 at.%, where a fivefold enhancement in the alcohol-to-hydrocarbon ratio was achieved.

Optical rectification is one of the most important techniques for efficient terahertz (THz) radiation generation. However, the strong THz absorption caused by the free electrons in nonlinear crystal limits the further increasing of the THz radiation generation efficiency. The interaction mechanism between the femtosecond laser and the nonlinear crystal has been analyzed and the related theoretical model has been built up. And the theoretical model of the THz radiation generation efficiency in optical rectification by tilted-pulse-front pumping has also been built. On the basis, the influence of the central wavelength, the pulse duration, and the temperature on the THz radiation generation efficiency has been analyzed quantitatively. The results show that the THz radiation generation efficiency increases first and then decreases with the increasing of the intensity of pump pulse. In addition, the maximum THz radiation generation efficiency can be achieved by cryogenic temperatures and the optimized parameters of the pump pulses and the nonlinear crystal.

The predictive value of excision repair cross-complementation group 1 (ERCC1) gene for survival and response to platinum-based chemotherapy in gastric cancer (GC) remains controversial. We performed a meta-analysis to clarify the precise estimation of the prognostic and predictive effect of ERCC1. A systematic literature search was conducted using PubMed, ScienceDirect, Wiley and American Society of Clinical Oncology (ASCO) before March 2014. Studies analyzing survival data and/or chemotherapy response in GC by ERCC1 status were identified. The principal outcome measures were hazard ratios (HRs) for survival and relative risks (RRs) for chemotherapy response. Pooled HRs and RRs were calculated using fixed- or random-effects models according to the heterogeneity. Twenty-one studies involving 1,628 patients met our inclusion criteria. High ERCC1 expression was significantly associated with shorter overall survival (OS) and lower response to chemotherapy in advanced GC patients receiving palliative chemotherapy (HR 1.83; 95 % CI 1.45–2.31; P

The aim of this study was to investigate incidence trend of childhood type 1 diabetes in Shanghai, a megalopolis in east China. We established a population-based retrospective registry for the disease in the city's registered population during 1997-2011 and collected 622 incident type 1 diabetes in children aged 0-14 years. Standardized incidence rates and 95 % CI were estimated by applying the capture-recapture method and assuming Poisson distribution. Incidence trend was analyzed using the Poisson regression model. The mean annual incidence of childhood type 1 diabetes was 3.1 per 100,000 person-years. We did not observe significant difference in incidence between boys and girls. The incidence is unstable and had a mean annual increase 14.2 % per year during the studied period. A faster annual increase was observed in boys, warmer seasons, and in the outer regions of the city. If present trends continue, the number of new type 1 diabetes cases will double from 2016 to 2020, and prevalent cases will sextuple by 2025. Our results showed the incidence of childhood type 1 diabetes was rising rapidly in Shanghai. More studies are needed to analyze incidence changes in other regions of China for appropriate allocation of healthcare resources.

Organometallic iridium complexes are potent anticancer candidates which act through different mechanisms from cisplatin-based chemotherapy regimens. Here, ten phosphorescent cyclometalated iridium(III) complexes containing 2,2′-bipyridine-4,4′-dicarboxylic acid and its diester derivatives as ligands are designed and synthesized. The modification by ester group, which can be hydrolysed by esterase, facilitates the adjustment of drug-like properties. The quantum yields and emission lifetimes are influenced by variation of the ester substituents on the Ir(III) complexes. The cytotoxicity of these Ir(III) complexes is correlated with the length of their ester groups. Among them, 4a and 4b are found to be highly active against a panel of cancer cells screened, including cisplatin-resistant cancer cells. Mechanism studies in vitro indicate that they undergo hydrolysis of ester bonds, accumulate in mitochondria, and induce a series of cell-death related events mediated by mitochondria. Furthermore, 4a and 4b can induce pro-death autophagy and apoptosis simultaneously. Our study indicates that ester modification is a simple and feasible strategy to enhance the anticancer potency of Ir(III) complexes.

The aim of our study was to analyze hepatic dysfunction and failure after hepatocellular carcinoma (HCC) resection and relationship of clinical and pathological factors. Clinical and pathological data of 467 HCC patients was retrospectively reviewed, who underwent liver resection from January 2002 to December 2008 in the Affiliated Hospital of Medical College, Qingdao University, and the post-resectional liver dysfunction and failure risk factors were analyzed by univariate and multivariate analysis. The morbidity of post-resectional liver dysfunction and failure was 1.7% and 2.1%. The post-resectional liver dysfunction and failure after HCC hepatectomy into the statistical analysis: univariate analysis revealed preoperative platelet level ( 64 U/L), Child-Pugh classification (B), MELD score (≥ 9), intraoperative bleeding (≥ 1000 mL), blood transfusion were positive factors, multivariate analysis (Logistic) revealed that preoperative platelet level (0.983, 95% CI = 0.971–0.995) and intraoperative blood transfusion (3.145, 95% CI = 1.027–12.028) were independent risk factors for post-resectional liver dysfunction and failure. Prevented liver failure and liver dysfunction occurring after liver resection, it is the key to accurate preoperative assessment of liver function and the patient’s reserved liver functional, precise hepatectomy and reasonable blockage of hepatic inflow.

Directly starting from lactic acid (LA) and trimesic acid (TMA), novel biodegradable material poly(lactic acid-trimesic acid) (PLT), a modified polylactic acid (PLA) with terminal carboxyl, was synthesized via melt copolycondensation. The optimal synthetic conditions, including catalyst kinds and dosage, prepolymerization time, copolymerization temperature and time, were discussed. When L-lactic acid (L-LA) and TMA as molar feed ratio n(L-LA)/n(TMA) 120/1 was prepolymerized for 8 h at 140 °C, the copolycondensation catalyzed by 0.9 wt % SnCl2 at 190 °C for 8 h gave PLT with the biggest intrinsic viscosity ([η]) 1.91 dL∙g−1, and the corresponding weight-average molecular weight (Mw) was 14,100 Da. Serial L-PLTs at different molar feed ratios were synthesized and characterized with FTIR, 1H NMR, GPC, DSC, and XRD. Increasing n(L-LA), Mw increased first, and the biggest Mw was 17500 Da at n(L-LA)/ n(TMA) 240/1, then decreased. Using D,L-lactic acid (D,L-LA) instead of L-LA, the influences of LA stereochemical configuration were investigated. The peak phenomenon of Mw was similar, but the biggest Mw was 23,100 Da at n(D,L-LA)/n(TMA) 320/1. The serial L-PLTs had a certain crystallinity (10.2%∼23.0%), while all D,L-PLTs were amorphous. These differences may be in touch with the reaction mechanism of direct melt copolycondensation. The method was simple and practical for the synthesis of PLA biomedical materials applied in drug delivery carrier, and vessel substitution material.

The aim of this study is to investigate clinical implications of human leukocyte antigen-G (HLA-G) expression in breast cancer.HLA-G expression in 235 primary breast cancer tissues was investigated using immunohistochemistry, and plasma soluble HLA-G (sHLA-G) was measured in 44 breast cancer patients using a specific HLA-G enzyme-linked immunosorbent assay (ELISA). Effects of estradiol/progesterone and their antagonists tamoxifen/RU486 on HLA-G expression in cultured breast cancer MCF-7 cells were determined by real-time polymerase chain reaction (PCR) and the ELISA. Alterations of HLA-G expression by the hormone treatments on subsequent allocytotoxic lymphocyte (allo-CTL) response were also examined.In the study, approximately 66% of neoplasm lesions were identified to have positive HLA-G expression. This expression was significantly correlated with tumor size, nodal status, and clinical disease stage (P = 0.0001, 0.012, and 0.0001, respectively). Patients with positive HLA-G expression had a lower survival rate than those with negative expression (P0.028). Plasma sHLA-G levels were significantly higher in breast cancer patients than in healthy controls (P0.001), with the area under the receiver-operating characteristic (ROC) curve being 0.95. HLA-G expression in breast cancer MCF-7 cells was enhanced by estradiol/progesterone but reduced by their antagonists. Cytotoxicity studies showed that allo-CTL response in MCF-7 cells was inhibited by prior treatment with estradiol/progesterone, but was amplified by their antagonists. The effects could be restored or further strengthened by the addition of anti-HLA-G antibodies.Our findings suggest that HLA-G may have potential clinical implications in diagnosis, prognosis, and immunotherapy of patients with breast cancer.

A murine primary mammary tumor model was established to investigate the treatment with ginsenosides Rg3. The relationship between ginsenosides Rg3 and primary mammary tumor was explored. Mammary tumor was induced by using the 7,12-dimethybenz(a)anthracene (DMBA). Ginsenoside Rg3 was employed for treatment. The incidence of mammary tumor in every group was compared, and the expressions of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were detected by immunohistochemical method. The cell cycle and apoptosis percentage were determined by means of flow cytometry. The incidence of tumor in treatment group was significantly lower than that in control group (60.00% vs 33.33%, P < 0.05). The average diameter of mammary tumor was (0.86±0.27) cm in control group and (0.39±0.09) cm in treatment group, with the difference being significant between control and treatment groups (P < 0.01). The MVD value was (31.9±5.3) in control group and (20.1±4.9) in treatment group, respectively. There was a significant difference between the two groups (P < 0.05). The apoptosis percentage in control group was significant lower than that in treatment group [(2.47±0.69)% vs (5.67±0.99)%, P < 0.05]. Ginsenoside Rg3 can play an antitumor role in primary mammary tumor model by inhibiting angiogenesis, cell cycle progression, and promoting cell apoptosis.

The present study aimed to explore the role of P2Y(1) receptor in glial fibrillary acidic protein (GFAP) production and glial cell line-derived neurotrophic factor (GDNF) secretion of astrocytes under ischemic insult and the related signaling pathways.Using transient right middle cerebral artery occlusion (tMCAO) and oxygen-glucose-serum deprivation for 2 h as the model of ischemic injury in vivo and in vitro, immunofluorescence, quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, enzyme linked immunosorbent assay (ELISA) were used to investigate location of P2Y(1) receptor and GDNF, the expression of GFAP and GDNF, and the changes of signaling molecules.Blockage of P2Y(1) receptor with the selective antagonist N(6)-methyl-2'-deoxyadenosine 3',5'-bisphosphate diammonium (MRS2179) reduced GFAP production and increased GDNF production in the antagonist group as compared with simple ischemic group both in vivo and in vitro. Oxygen-glucose-serum deprivation and blockage of P2Y(1) receptor caused elevation of phosphorylated Akt and cAMP response element binding protein (CREB), and reduction of phosphorylated Janus kinase2 (JAK2) and signal transducer and activator of transcription3 (STAT3, Ser727). After blockage of P2Y(1) receptor and deprivation of oxygen-glucose-serum, AG490 (inhibitor of JAK2) reduced phosphorylation of STAT3 (Ser727) as well as expression of GFAP; LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3-K), decreased phosphorylation of Akt and CREB; the inhibitor of mitogen-activated protein kinase kinase1/2 (MEK1/2) U0126, an important molecule of Ras/extracellular signal-regulated kinase (ERK) signaling pathway, decreased the phosphorylation of JAK2, STAT3 (Ser727), Akt and CREB.These results suggest that P2Y(1) receptor plays a role in the production of GFAP and GDNF in astrocytes under transient ischemic condition and the related signaling pathways may be JAK2/STAT3 and PI3-K/Akt/CREB, respectively, and that crosstalk probably exists between them.

Poly(trimethylene terepthalate) (PTT) has in recent years, attracted much interest for its application in fibers and engineering thermoplastics, due to its outstanding properties such as good resilience and elastic recovery [1, 2]. As a typical semicrystalline polymer, the crystallization behavior of PTT is the primary property that affects its physical properties and processing conditions, and thus many articles have appeared describing this topic [3–10]. In previous works, we reported the crystallization kinetics of PTT including the secondary crystallization process, and the crystallization behavior of PTT at high undercoolings was also explored [6, 7]. A series of copolyesters based on PTT with modified thermal properties have been prepared and their composition dependence of thermal properties was also presented [8–10]. Moreover, recently increasing attention has been given to the fabrication and the property studies of polymer/carbon nanotubes (CNTs) composites due to the high aspect ratio, nanosize in diameter, very low density, excellent physical properties of CNTs, and the remarkably enhanced physical properties of the composites [11–15]. However, so far there is a little research on the crystallization behavior of such polymer nanocomposites, especially in the nucleation effect of CNTs on the polymer matrix despite of its potential, academic, and technological values. In this communication, PTT composites with multiwalled carbon nanotubes (MWNTs), in which the nanotube consists of several layers of coaxial carbon tubes [16, 17], were prepared, and the influence of MWNT on crystallization of PTT matrix was discussed. To our knowledge, it is the first time that poly(trimethylene terephthalate)/multiwalled carbon nanotube composites were prepared and their crystallization behavior was presented. PTT ([g] = 0.0795 m/kg at 298 K) used in this study is the same polymer which has been described in one of our previous articles [6]. MWNTs were purchased from Bill Nanotech Co., Ltd (Shenzhen, China). These MWNTs were produced via the chemical vapor deposition (CVD) method and have lengths up to a few microns and diameters between 70 and 100 nm. The purchased MWNTs were purified to remove amorphous carbon and iron impurities [18]. In a typical experiment, an MWNT sample was heated and refluxed in an aqueous HNO3 solution (2.6 M) for 13 h. After filtering through a Teflon-PTFE membrane, the remaining solid was washed with deionized water until the pH was neutral. The purified MWNTs were then functionalized by tetrabutyl titanate to enhance the compatibility of MWNT with PTT. To fabricate PTT–MWNT composites, weighed PTT sample was dissolved in the solution of 1:1 (w/w) 1,1,2,2-tetrachloroethane/phenol at 353 K to form a clear solution. Appropriate amount of functionalized MWNT was weighed according to the required percentage, and was added to the solution. The mixture was refluxed with stir for 4 h to form a homogeneous suspension and then sonicated for 1 h. Finally, the mixture was cast into an aluminum mold in the form of a film. The mold with the suspension was vacuum dried in an oven at 373 K for 48 h. The resultant composite was denoted according to the weight percentage of MWNT in Y. Xu (&) H.-B. Jia J.-N. Piao Department of Polymer Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, P.R. China e-mail: xuyong@zuaa.zju.edu.cn

After successfully being commercialized in the 1990s, poly(trimethylene terephthalate) (PTT) has drawn more and more attention due to its superior characteristics, such as elastic recovery, chemical resistance and resilience in comparison with poly (ethylene terephthalate) (PET) and poly (butylene terephthalate) (PBT) [1, 2]. PTT is a typical semicrystalline polymer material and many reports were focused on its crystallization behaviors recently. Huang and Chang [3] investigated the crystallization behavior for PTT from the melt and analyzed the kinetics in the temperature range from 451 K to 483 K, some important parameters for crystallization such as equilibrium melting temperature(Tm 0 = 521 K), lateral surface-free energy (r),work of chain folding (q) were also reported. Crystallization kinetics parameters of PET, PTT and PBT were compared by Chuah [4], it could be concluded that PTT crystallized faster than PET but slower than PBT at the same degree of undercooling. Hong and his coworkers [5] took note of the inaccuracy of Chang and Huang in determining the work of chain folding (q) and gave a more reasonable value of 27.2 kJ mol, they also investigated the regime behaviors of PTT crystallization using the secondary crystallization theory [6] and found the boundaries between the classical regime I fi II and regime II fi III are located at 488 and 468 K, respectively. We also carried out the kinetics analysis of PTT crystallization including the secondary crystallization process using a new mathematical model constructed by us [7]. Much of the above work has concentrated on the measurement of overall rate of crystallization or the measurement of spherulitic growth rate of PTT crystallization from melt at low and moderate degrees of undercooling (DT = Tm –Tc, Tc is crystallization temperature), yet a detailed overall kinetics analysis at high undercoolings (DT > 70 K), especially in the temperature range where the fastest crystallization rate would occur is still lacking. However, study of the behavior of a semicrystalline polymer crystallizing in this temperature range is of great importance from both theoretical and practical view points. Of theoretical importance is the mechanism of nucleation, the growth geometry of crystals and the formation of polymer fine structure during crystallization. The practical importance is that such crystallization data may be very useful to polymer processing such as fiber spinning and injection molding, because most polymer shaping processes need a very fast crystallization rate to shorten the solidifying time. The importance also arises from the effect of final crystallinity on the physical and chemical properties of polymers. In this study, we present the isothermal crystallization behavior of PTT from 356 K to 465 K, the overall crystallization kinetics data in the temperature range 356–450 K was reported for the first time. Poly(trimethylene terephthalate) samples with different molecular weights were obtained by the polycondensation of terephthalic acid in the melt phase with 1,3-propandediol using different reaction time Y. Xu (&) H.-b. Jia Department of Polymer Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, P. R. China e-mail: njust_xuy@hotmail.com

Using the mechanical principle, the theory of modern geometry and advanced calculus, Hamiltonian mechanics was generalized to Kahler manifolds, and the Hamiltonian mechanics on Kahler manifolds was established. Then the complex mathematical aspect of Hamiltonian vector field and Hamilton’s equations was obtained, and so on.

This paper presents scheduling models for dispatching vehicles to accomplish a sequence of container jobs at the container terminal, in which the starting times as well as the order of vehicles for carrying out these jobs need to be determined. To deal with this scheduling problem, three mixed 0–1 integer programming models, Model I, Model II and Model III are provided. We present interesting techniques to reformulate the two mixed integer programming models, Model I and Model II, as pure 0–1 integer programming problems with simple constraint sets and present a lower bound for the optimal value of Model I. Model III is a complicated mixed integer programming model because it involves a set of non-smooth constraints, but it can be proved that its solutions may be obtained by the so-called greedy algorithm. We present numerical results showing that Model III is the best among these three models and the greedy algorithm is capable of solving large scale problems.

Since its development for fibers and engineering thermoplastics in the 1990s [1–3], poly(trimethylene terephthalate) (PTT) has attracted much attention due to its outstanding characteristics, such as high elastic recovery, chemical resistance, and resilience [4, 5]. Like poly (ethylene terephthalate) (PET) and poly(butylene terephthalate) (PBT), PTT is a typical semicrystalline polymer and the investigation of its crystallization kinetics has significant importance both from scientific and technological points of view. PTT crystallizes faster than PET but slower than PBT [6]. Its maximum crystallization rate occurs at 415 K. It has clearly been observed that a primary crystallization process and a secondary crystallization process consecutively occur during isothermal annealing of PTT [7], nevertheless no detailed kinetics analyses of the latter have been reported so far. Although the nature of the secondary crystallization of polymers is still unclear, several models have been proposed to modify the original Avrami theory to include this process [8–11]. Hillier [8] has proposed a model, which considered that the secondary crystallization of polymers is a first-order process with an Avrami form (i.e., the Avrami exponent is a constant and always equals to 1). Despite this model being a better fit than the Avrami equation to some isotherms analyzed, the imposed invariable Avrami exponent seems quite arbitrary. Velisaris and Seferis [10] have found another way to consider secondary crystallization by describing the time dependence of crystallization degree as a linear combination of two Avrami expressions

Objective: To evaluate the clinical efficacy of Shengmai Powder (SMP) in treating acute viral myocarditis objectively.Methods: One hundred and twenty-four patients with acute viral myocarditis were randomized into the treated group (SMG,n = 64) and the control group (CG,n = 60). Such myocardial nutrient medicine as ATP, CoA, Vit-C, were given to both groups. And to the treated group, 40 ml of Shengmai Injection per day was given intravenously for 2 weeks, which was followed by oral intake of Shengmai granule, one package three times daily for another 2 weeks in total. The same anti-arrhythmia agents were applied to both groups, and no fructose-1, 6-diphosphate (FDP) for either. Semi-quantitative scoring method was adopted to observe such symptoms as chest stuffiness, palpitation and chest pain before treatment and four weeks after treatment. Meanwhile, ECG, dynamic ECG by Holter monitor, left ventricular enddiastolic dimension (LVEDD), left ventricular ejection fraction (LVEF), serum neutralizing antibody of virus Coxsackie B, cardiac troponin I (cTnl) and cardiac troponin T (cTnT) were examined.Results: (1) Compared with the control group, more significant improvement was got in SMG in respects of chest stuffiness, palpitation, chest pain and arrhythmia (P

The 5′-terminal (RTn) and 3′-terminal (RTc) halves of the coat protein readthrough domain and the 19 ku cysteine-rich protein of Chinese wheat mosaic virus (CWMV) were amplified by RT-PCR, cloned and expressed inE. coli. Antisera and monoclonal antibodies against these proteins were prepared by immunising these purified proteins to mice. Detection of RTn, RTc and 19 ku proteins in CWMV infected wheat sap and leaf tissue indicated that the RTn and RTc proteins were distributed on the surface of virus particles whereas the 19 ku protein was in the cytoplasm of the infected wheat cells.

Insoluble Mo(W)–S–Cu cluster compound films with a metallic lustre of various shades and colours have been applied to copper surface to provide attractive finishes. The anticorrosive characteristics of the Mo(W)–S–Cu cluster compound films with and without various passivation treatments are investigated by using accelerated chemical corrosion tests, LSV, XPS and AES determination. The results indicate that the films are liable to be oxidized gradually when exposed to air and they provide poor protective effect against Cl− or H2S erosion to copper. Colour loss or change as well as film degradation will occur. After PMTA passivation, not only are the colours of the films stabilized, but film degradation is also prevented. The protection effect of PMTA on the films can be attributed to the formation of a layer of dense, insoluble and transient polymeric coordination compound film via reaction of PMTA with Cu(i) in the coloured films.

Background Hepatitis B virus (HBV) is a major cause of liver infection in human. Because of the lack of an appropriate cell culture system for supporting HBV infection efficiently, the cellular and molecular mechanisms of hepadnavirus infection remain incompletely understood. Duck heptatitis B virus (DHBV) can naturally infect primary duck hepatocytes (PDHs) that provide valuable model systems for studying hepadnavirus infection in vitro. In this report, we explored global changes in cellular protein expression in DHBV infected PDHs by two-dimension gel electrophoresis (2-DE) combined with MALDI-TOF/TOF tandem mass spectrometry (MS/MS). Results The effects of hepadnavirus infection on hepatocytes were investigated in DHBV infected PDHs by the 2-DE analysis. Proteomic profile of PDHs infected with DHBV were analyzed at 24, 72 and 120 h post-infection by comparing with uninfected PDHs, and 75 differentially expressed protein spots were revealed by 2-DE analysis. Among the selected protein spots, 51 spots were identified corresponding to 42 proteins by MS/MS analysis; most of them were matched to orthologous proteins of Gallus gallus, Anas platyrhynchos or other avian species, including alpha-enolase, lamin A, aconitase 2, cofilin-2 and annexin A2, etc. The down-regulated expression of beta-actin and annexin A2 was confirmed by Western blot analysis, and potential roles of some differentially expressed proteins in the virus-infected cells have been discussed. Conclusions Differentially expressed proteins of DHBV infected PDHs revealed by 2-DE, are involved in carbohydrate metabolism, amino acid metabolism, stress responses and cytoskeleton processes etc, providing the insight to understanding of interactions between hepadnavirus and hepatocytes and molecular mechanisms of hepadnavirus pathogenesis.

A careful scanning tunneling microscope (STM) observation has been made on the micromorphology structure of the crystal faces for a group of pyrites which include two types of pyrite specimens: natural pyrites, from the different stage of hydrothermal ore deposits and artificial crystal of pyrite. It has been discovered that there is a set of micromorphological structures on the surfaces of pyrite crystals, including pisolitic hillocks, lotus root-like hillocks and spiral steps. This study reveals that the micromorphology of pyrite crystals, which are closely related to thermodynamic conditions and dynamic environment of the ore-forming systems, carries a lot of genetic information.