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Based on the action of the mapping class group on the space of measured foliations, we construct a new boundary of the mapping class group and study the structure of this boundary. As an application, for any point in Teichmüller space, we consider the orbit of this point under the action of the mapping class group and describe the closure of this orbit in the Thurston compactification and the Gardiner–Masur compactification of Teichmüller space. We also construct some new points in the Gardiner–Masur boundary of Teichmüller space. [ABSTRACT FROM AUTHOR]

A new cocrystal of baicalein, possessing three A-ring-hydroxyl groups and without B-ring-hydroxyl groups and 4,4′-bipyridine (BE·2BPY·H2O) has been prepared and characterized. The structural analyses and Hirshfeld surfaces show that baicalein is hydrogen-bonded to co-crystallized solvent water molecules featuring for example motifs that can be described with graph set R44(8) similar to those reported for the cocrystal of myricetin with 4,4′-bipyridine. A zipper-type architecture is observed in cocrystal BE·2BPY·H2O linking a baicalein, two 4,4′-bipyridine and a solvent water molecules via classical O–H⋯N and O–H⋯O and non-classical C–H⋯O hydrogen bonds into 2D sheets. Additionally, the cocrystal shows better solubility in 0.1 M HCl in comparison to pure baicalein. Cocrystal of baicalein with zipper-type architecture shows improved solubility compared to baicalein. [ABSTRACT FROM AUTHOR]

The immunoproteasome is a multicatalytic protease complex in all eukaryotic cells, which plays a key role in regulating essential cellular processes. However, the role of immunoproteasome subunit β2i in regulation of cardiac fibrosis and inflammation in deoxycorticosterone-acetate (DOCA)/salt mice remains unknown. Wild-type (WT) and β2i knockout (KO) mice were subjected to uninephrectomy and DOCA/salt treatment for 21 days. Blood pressure was measured by the tail-cuff system. Cardiac function and remodeling were examined by echocardiography, hematoxylin-eosin (H&E) and Masson's trichrome staining. The gene and protein expressions were detected by quantitative real-time PCR, and Western blot analysis. After 21 days, DOCA/salt treatment significantly up-regulated the expression of β2i mRNA and protein in the hearts. Moreover, systolic blood pressure and heart weight/body weight (HW/BW) ratio were significantly higher in DOCA/salt mice than in sham groups, and these effects were markedly reversed in β2i knockout mice. Importantly, DOCA/salt-induced cardiac fibrosis, inflammation and the expression of collagen I, collagen III, α-SMA, IL-1β, IL-6 and TNF-α in the wild-type hearts, which were markedly attenuated by β2i knockout. These beneficial effects were due, at least in part, to the inhibition of IκBα/NF-κB and TGF-β1/Smad2/3 signaling pathways. Collectively, these findings indicate that knockout of β2i ameliorates DOCA/salt-induced cardiac fibrosis and inflammation, and may be a novel potential therapeutic target for hypertensive heart diseases. [ABSTRACT FROM AUTHOR]

We have modified the mitral repair technique in infants and small children by using autologous pericardial strips to treat mitral regurgitation resulting from a dilated mitral annulus. Our results demonstrate that this technique maintains stability and flexibility of the mitral annulus and decreases the risk of mitral stenosis. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of metformin on the proliferation, apoptosis and migration ability of human hepatocellular carcinoma cells HCCLM3. Methods HCCLM3 cells were treated with different concentrations of metformin. Cell proliferation was assessed by CCK-8 assay. The expression of related apoptosis genes, Bax and Bcl-2 were determined by RT-PCR. Cell migration was determined by scratch experiment. Results Metformin decreased the proliferation of HCCLM3 cells in a dose-dependent and time-dependent manner and the cell proliferation inhibition rate was significantly higher than the control group (P < 0.05) . The migration of HCCLM3 was inhibited when the concentration of metformin reaches 10mmol/L. The expression of Bax mRNA was up-regulated, while Bcl-2 was down-regulated after 48h treated. Conclusion Metformin can inhibit HCCLM3 cell proliferation and migration, and affect the expression of apoptosis related gene Bax and Bcl-2 in a concentration and time-dependent manner. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to investigate the role of insulin-like growth factor binding protein-related protein 1 ( IGFBP-r P1) in the development of hepatic fibrogenesis in experimental disease models and human liver samples. Methods Cellular distribution patterns of IGFBP-r P1 were assessed by immunohistochemistry in fibrotic and cirrhotic human liver specimens. Gene silencing of IGFBP-r P1 was performed on cultured hepatic stellate cells ( HSCs) by small interfering RNA (si RNA), and the silencing effect was determined by quantitative real-time polymerase chain reaction ( PCR) and Western blot. We also determined the effects of si RNA-mediated gene silencing of IGFBP-r P1 on the production of extracellular matrix ( ECM) components by Western blot. The expression of ECM components and transforming growth factor ( TGF)-β1 was studied by immunohistochemistry and Western blot in C57BL/6 wild-type mice treated with recombinant IGFBP-r P1 (r IGFBP-r P1). Results Expression of IGFBP-r P1 was significantly elevated in fibrotic and cirrhotic human liver specimens, and this increase was positively correlated with the number of collagen fibers observed. si RNA-mediated gene silencing of IGFBP-r P1 resulted in significantly decreased levels of collagen I and fibronectin in HSCs. Moreover, IGFBP-rP1 overexpression significantly increased the production of collagen, fibronectin and TGF-β1 in r IGFBP-r P1-treated mice. Conclusions IGFBP-r P1 contributes to the development of liver fibrosis and may be a novel molecule involved in the progression of hepatic fibrogenesis. [ABSTRACT FROM AUTHOR]

Although deep learning models show powerful performance, they are still easily deceived by adversarial samples. Some methods for generating adversarial samples have the drawback of high time loss, which is problematic for adversarial training, and the existing adversarial training methods are difficult to adapt to the dynamic nature of the model, so it is still challenging to study an efficient adversarial training method. In this paper, we propose an adversarial training method, the core of which is the improved adversarial sample generation method AGFAT for adversarial training and the improved dynamic adversarial training method AGFAT-DAT. AGFAT uses a word frequency-based approach to identify significant words, filter replacement candidates, and use an efficient semantic constraint module as a means to reduce the time of adversarial sample generation; AGFAT-DAT is a dynamic adversarial training approach that uses a cyclic attack on the model after adversarial training and generates adversarial samples for adversarial training again. It is demonstrated that the proposed method can significantly reduce the generation time of adversarial samples, and the adversarial-trained model can also effectively defend against other types of word-level adversarial attacks. [ABSTRACT FROM AUTHOR]

With our consistent aim to further expand the solid-state landscape via molecular recognition and regulate solubility of tetrahydroberberine (THB), charge-assisted hydrogen bond (CAHB) recognitions and solubility regulation of pharmaceutical salts/cocrystals of THB are comprehensively investigated through exploring four pharmaceutical salts/cocrystals of THB. Four pharmaceutical salts/cocrystals of THB with oxalic acid, malonic acid, maleic acid and fumaric acid were obtained with solution evaporation approach. Comprehensive crystal structures and Hirshfeld surface analyses reveal CAHB recognitions between THBs and coformers are dominant intermolecular interactions to stabilize crystal packing. As expected, solubilities of four pharmaceutical salts/cocrystals of THB have been improved by dicarboxylic acids. Importantly, the dicarboxylic acid with higher solubility can modulate solubility of THB to become higher. The enthalpy of hydration for four pharmaceutical salts/cocrystals is greater than that for neutral pure THB when CAHBs (with electrostatic interactions) exist, which effectively improve solubility of THB. Solvent molecules can disrupt interactions of pharmaceutical salts/cocrystals by solvent···solute interactions when dicarboxylic acids are highly soluble thereby leading to enhancement of dissolution. Research results inspirationally enlightens that the solubility of insoluble APIs could be effectively regulated by utilizing gradient solubility coformers with simultaneously forming CAHBs between active pharmaceutical ingredients and coformers. • Designing and synthesizing four pharmaceutical salts/cocrystals of THB. • Cocrystallization of THB with dicarboxylic acids by CAHB recognitions. • Tuning solubility of THB by forming salt/cocrystals with dicarboxylic acids. [ABSTRACT FROM AUTHOR]

Abstract With an aim to obtain a new supramolecular compound based on Keggin-type polyoxometalates with mixed-ligand: [Cu(I)(phen) 2 ] 2 {[Cu(II)] 2 (phen) 4 PTA}[H 3 PMoV 4 MoVI 8 O 40 ] (phen = 1,10-phenanthroline, PTA = terephthalic acid) has been synthesized under hydrothermal conditions and structurally characterized by elemental analyses, IR, X-ray single crystal diffraction, TG analyses and XPS. In the title compound, the Keggin-type phosphomolybates anions, butterfly-shaped [Cu(I)(phen) 2 ]+ subunits and dumbbell-shaped {[Cu(II)] 2 (phen) 4 PTA}2+ subunits are alternately connected to form chiral helical chains via hydrogen bonds along b axis, and the adjacent chiral helical chains are connected in the way of sharing butterfly-shaped [Cu(I)(phen) 2 ]+ subunits and dumbbell-shaped {[Cu(II)] 2 (phen) 4 PTA}2+ subunits to form 3D supramolecular reticular framework. As expected, the title compound with mixed-ligands (phen and PTA) has been successfully synthesized, inconceivably, the title compound also contains mixed-valence Cu (Cu(I) in butterfly-shaped [Cu(I)(phen) 2 ]+ subunits; Cu(II) in dumbbell-shaped {[Cu(II)] 2 (phen) 4 PTA}2+ subunits). The preliminary analyses show that mixed-valence Cu(I/II) may be due to the reduction of Cu(II) (from CuCl 2) to Cu(I) (in butterfly-shaped [Cu(I)(phen) 2 ]+ subunits) by N-containing compound. The successful results of this work provide a new idea that supramolecular materials with attractive structures and novel properties, which could be designed and synthesized by introducing of mixed-ligands into the supramolecular materials. Additionally, the electrocatalytic property of the title compound to H 2 O 2 has been studied. Graphical abstract Unlabelled Image Highlights • Compound based on Keggin POMs with mixed-ligand and Cu(I/II) was prepared. • The compound contains the right- and left-hand helical chains. • The compound exhibits good electrocatalytic activity towards H 2 O 2 reduction [ABSTRACT FROM AUTHOR]

The traditional high-temperature preparation process of polyimide can cause many problems and limits the wider application in extreme conditions. An important challenge to be solved urgently is the reduction of imidization temperature. In this work, twelve kinds of polyimide films with different chain rigidity were prepared at low temperature of 200 °C, in the absence or presence of imidazole used as the catalyst. The molecular rigidity and free volume were theoretically calculated, and relationship between structure and properties were systematically studied. The results show that imidization reaction under low temperatures is significantly affected by the rigidity of molecular chains. The rigid structure of polyimide is not conducive to the low-temperature imidization, but this adverse effect can be eliminated by adding catalyst, resulting the notably increased imidization degree. The optical and thermal properties can be improved to a certain extent for the chemically catalyzed system, resulting in relatively higher heat resistance and thermal stability. While the mechanical performance could be determined by complicating factors, greatly different from polyimide films prepared by high temperature method. To investigate aggregation structures of films, the effect of chain rigidity and catalyst on the stacking or orientation of molecular chains was further elaborated. This work can contribute to the understanding of chemically catalyzed imidization that is rarely reported in the existing research, and will provide guidance for the low-temperature preparation of high-performance polyimides. [ABSTRACT FROM AUTHOR]

The asymmetric reduction of benzoxazines with trichlorosilane gives the corresponding products (II) with mostly moderate enantioselectivity. [ABSTRACT FROM AUTHOR]

Aims Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), an intracellular pattern recognition receptor, which plays an important role in the innate immunity and inflammation. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unknown. In this study, we sought to determine the role of NOD2 on cardiac I/R injury. Main methods Mice were induced 30 min ischemia followed by 24 h of reperfusion. Histological examinations were performed on heart sections with Evans blue and triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, immunohistochemistry and immunofluorescence staining. The messenger RNA (mRNA) expression and protein levels were detected by real-time polymerase chain reaction (RT-PCR) and western blot analysis respectively. Key findings I/R injury markedly upregulated NOD2 expression in heart tissue. Treatment of WT mice with NOD2 ligand (MDP) significantly increased infarct size, the number of apoptotic cells and inflammatory cells, as compared with wild-type mice after I/R injury. Furthermore, MDP enhanced I/R-induced cardiomyocyte apoptosis and inflammation in vitro, and these effects were attenuated by NOD2-siRNA. The mechanism of NOD2 on cardiac I/R injury is partly associated with JNK, p38MAPK and NF-κB signaling pathways. Significance NOD2 aggravates myocardial I/R injury by inducing cardiomyocyte apoptosis and inflammation through JNK, p38MAPK and NF-κB signaling pathways. This study provides insight into better understanding the molecular mechanism of NOD2, which may be served as a potential target for the treatment of myocardial I/R injury. [ABSTRACT FROM AUTHOR]

Currently, the top k query algorithms about the uncertain XML data can not deal with continuous uncertain data. The SPCProTJFast algorithm is proposed, which improves the traditional merging algorithm, combines with continuous uncertain data filtering methods, implements the top-k query algorithm over continuous uncertain XML data. In order to avoid the impact of too small probability limit on filtering effect, the HPCProTJFast algorithm is proposed, which delays the handling of continuous types of nodes and visits the continuous nodes only when the entire twig that meets the probability condition are acquired. Experimental results show that, in terms of the execution time and the filtration efficiency, these two algorithms are more efficient than the ProTJFast algorithm that deals with continuous uncertain data directly, and the HPCProTJFast algorithm is the most efficient. [ABSTRACT FROM AUTHOR]

MicroRNA-361-5p (miR-361-5p) is a tumor suppressor miRNA that is dysregulated in several types of human cancer. However, the functional significance of miR-361-5p in hepatocellular carcinoma (HCC) is unclear. This study explored the biological function of miR-361-5p in regulating the progression of HCC and the underlying molecular mechanism. RT-qPCR analysis showed that miR-361-5p was downregulated in HCC tissues and cell lines. Functional analysis revealed that miR-361-5p acted as a tumor suppressor, inhibiting cell proliferation, migration, and invasion in HCC cell lines. Bioinformatics analyses identified Twist1 as a direct target of miR-361-5p, which was validated by dual-luciferase reporter assays, RT-qPCR, and western blotting. Rescue experiments indicated that Twist1 may mediate the tumor-suppressive effect of miR-361-5p in HCC cells, and this was supported by the effect of miR-361-5p on inhibiting the epithelial-mesenchymal transition (EMT) by targeting Twist1. This study is the first to suggest that miR-361-5p inhibits tumorigenesis and EMT in HCC by targeting Twist1. These findings are valuable for the diagnosis and clinical management of HCC. [ABSTRACT FROM AUTHOR]

In order to further explore the role of Charge-assisted hydrogen bonds (CAHBs) recognition in the formation of tetrahydroberberine (THB) pharmaceutical salt/cocrystal, based on the analysis of the molecular interactions in forming unit pharmaceutical salts/cocrystal of THB and sulfophenyl acids, we speculate that hydroxyl group of sulfamic acid (SA) may cocrystallize with N atom on the quinoline ring of THB via CAHBs. Consequently, an unreported pharmaceutical salt (C 20 H 22 NO 4 ·NH 2 SO 3 , THB-SA) of the THB was designed and synthesized. The THB-SA was characterized by single crystal X-ray diffraction, XRPD and TG methods. As expected, structure analysis of the THB-SA revealed that the THB molecule binds to the SA molecule precisely through CAHBs (N+-H···O−) between the N atom on the quinoline ring and sulfonic acid group of SA in asymmetric unit of THB-SA. This successfully implemented work implies that in the preparation of THB pharmaceutical salts/cocrystals, cocrystal formers (CCFs) that can form CAHBs with THB should be selected, which will provide a facilitate way to prepare THB pharmaceutical salts/cocrystals. Image 1 • The successful preparation of THB-SA pharmaceutical salt has been verified that the formation mechanism of CAHBs in tetrahydroberberine and sulfamic acid is basically consistent with the formation mechanism of CAHBs in tetrahydroberberine and organic acids. [ABSTRACT FROM AUTHOR]

Patent ductus arteriosus is the third most common congenital heart disease and resulted from the persistence of ductal patency after birth. Ductus arteriosus closure involves functional and structural remodeling, controlled by many factors. The changes in plasma protein levels associated with PDA closure are not known. Here we for the first time demonstrate six key differential plasma proteins in human patent ductus arteriosus patients using proteomic technology and present a model to illustrate the constriction and closure of ductus arteriosus. Differentially expressed proteins were analyzed by using isobaric tags for relative and absolute quantification and validated by enzyme‐linked immunosorbent assay in new samples. The proteomic data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD008568. We found 74 upregulated and 98 downregulated proteins in the plasma of patients with PDA. Five decreased proteins (platelet factor 4, fibrinogen, von Willebrand factor, collagen, and mannose binding lectin‐associated serine protease‐2) and one increased protein (fibronectin) may increase the risk of patent ductus arteriosus. Those proteins are closely related to platelet activation and coagulation cascades, complement mannan‐binding‐lectin, and other systemic signaling pathways. Our findings for the first time indicate that the differential proteins involved in different pathways may play key roles in the nonclosure of the ductus arteriosus in humans and may be developed as biomarkers for diagnosis. All those findings may be served as the basis of understanding the etiology and pathogenesis of patent ductus arteriosus. Ductus arteriosus closure involves functional and structural remodeling, controlled by many factors and we for the first time demonstrate six key differential plasma proteins in human patent ductus arteriosus patients using proteomic technology and present a model to illustrate the constriction and closure of ductus arteriosus. Those proteins are closely related to platelet activation and coagulation cascades, complement mannan‐binding‐lectin, and other systemic signaling pathways. Our findings for the first time indicate that the differential proteins involved in different pathways may play key roles in the nonclosure of the ductus arteriosus in humans and may be developed as biomarkers for diagnosis. All those findings may be served as the basis of understanding the etiology and pathogenesis of patent ductus arteriosus. [ABSTRACT FROM AUTHOR]

Abstract Based on analyzing intermolecular interaction in building unit of cocrystal of quercetin with 4,4′-bipyridine (QUE·BPY) reported by us on before, a new cocrystal of kaempferol with 4,4′-bipyridine (KAE·BPY) has been designed and synthesized. Within the reported QUE·BPY , 3′ OH was neither involved in the formation of the building unit nor played a big role in the 2D layer. Consequently, we boldly speculate kaempferol without 3′ OH might crystallize with 4,4′-bipyridine to form similar structure to QUE·BPY. Just as expected, structural analysis shows kaempferol molecules and 4,4′-bipyridine molecules alternate connect to form the building units through 7-OH and 4′ OH hydrogen bonds, the structure of KAE·BPY is similar to QUE·BPY. This work proves that new cocrystals could be designed and synthetized by analyzing the intermolecular interaction in building unit and seeking right structure of Active Pharmaceutical Ingredients (APIs). Additionally, the cocrystal of kaempferol with 4,4′-bipyridine shows advantages in terms of hygroscopic stability in comparison to pure kaempferol. Highlights • A kaempferol-4,4′-bipyridine cocrystal was prepared by solution evaporation. • The cocrystal was prepared by analyzing intermolecular interaction of building units. • The cocrystal shows improved hygroscopic stability in comparison to pure kaempferol. [ABSTRACT FROM AUTHOR]

Background & Aims Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. However, the cellular defense mechanisms underlying ALD are not well understood. Recent studies highlighted the involvement of chaperone-mediated autophagy (CMA) in regulating hepatic lipid metabolism. Sorting nexin (SNX)-10 has a regulatory function in endolysosomal trafficking and stabilisation. Here, we investigated the roles of SNX10 in CMA activation and in the pathogenesis of alcohol-induced liver injury and steatosis. Methods Snx10 knockout ( Snx10 KO) mice and their wild-type (WT) littermates fed either the Lieber–DeCarli liquid alcohol diet or a control liquid diet, and primary cultured WT and Snx10 KO hepatocytes stimulated with ethanol, were used as in vivo and in vitro ALD models, respectively. Activation of CMA, liver injury parameters, inflammatory cytokines, oxidative stress and lipid metabolism were measured. Results Compared with WT littermates, Snx10 KO mice exhibited a significant amelioration in ethanol-induced liver injury and hepatic steatosis. Both in vivo and in vitro studies showed that SNX10 deficiency upregulated lysosome-associated membrane protein type 2A (LAMP-2A) expression and CMA activation, which could be reversed by SNX10 overexpression in vitro . LAMP-2A interference confirmed that the upregulation of Nrf2 and AMPK signalling pathways induced by SNX10 deficiency relied on CMA activation. Pull-down assays revealed an interaction between SNX10 and cathepsin A (CTSA), a key enzyme involved in LAMP-2A degradation. Deficiency in SNX10 inhibited CTSA maturation and increased the stability of LAMP-2A, resulting in an increase in CMA activity. Conclusions SNX10 controls CMA activity by mediating CTSA maturation, and, thus, has an essential role in alcohol-induced liver injury and steatosis. Our results provide evidence for SNX10 as a potential promising therapeutic target for preventing or ameliorating liver injury in ALD. Lay summary Alcoholic liver disease is a major cause of morbidity and mortality worldwide. Recent studies highlight the involvement of chaperone-mediated autophagy (CMA) in regulating hepatic lipid metabolism. Our study reveals that deficiency of sorting nexin (SNX) 10 increases the stability of LAMP-2A by inhibiting cathepsin A maturation, resulting in the increase of CMA activity and, thus, alleviates alcohol-induced liver injury and steatosis. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Jiang-Xian HuGan (JXHG) formulated by five natural products including Freshwater clam (Corbicula fluminea) , Curcuma longa L., Ligustrum lucidum , Eclipta prostrata (L.) L. and Paeonia lactiflora Pall. , has exhibited a great hepatoprotective effect. Aim of this study We investigated the effect of JXHG on concanavalin A (ConA)-induced acute live injury in mice, and to elucidate its underlying molecular mechanisms. Materials and methods Jiangkanling Capsule (900 mg/kg), low-dose JXHG (LJXHG, 700 mg/kg), high-dose JXHG (HJXHG, 1400 mg/kg) were administered to mice by oral gavage daily for 20 days prior to a single intravenous injection of ConA (20 mg/kg). Liver injury was evaluated by measuring the serum levels of enzymes and cytokines as well as liver histological analysis. We also measured the hepatic expression of cytokines at mRNA levels and the proteins related to NF-κB and Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathways. Result Our results showed that JXHG pretreatment significantly alleviated ConA-induced live injury as evidenced by decreased serum levels of glutamic-pyruvic transaminase (ALT) and glutamic oxalacetic transaminase (AST), and reduced hepatocyte apoptosis and mortality. Furthermore, JXHG was able to significantly reduce the serum levels of proinflammatory cytokines, down-regulate the mRNA expression of interleukin-6 (IL-6) and interferon-γ (IFN-γ), and up-regulate IL-10 as well as superoxide-dimutase-1 (SOD1), glutathione reductase (GSR) and Glutathione peroxidase 2 (GPX2) mRNA in the liver tissues after Con A injection. In addition, JXHG pretreatment dramatically suppressed the phosphorylation of NF-κB p65 (p65), increased Nrf2 expression, and decreased the expression ratio of cleaved caspase-3/caspase-3 in liver tissues. Conclusion These results suggest that JXHG protects against ConA-induced acute live injury through inhibiting NF-κB mediated inflammatory pathway and promoting Nrf2 mediated anti-oxidative stress signaling pathway. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma (ICC) is an aggressive type of cancer, and its incidence and mortality rates are increasing worldwide. Mortalin is a highly conserved chaperone protein involved in multiple pathological and physiological processes, including anti-apoptosis, carcinogenesis and metastasis. The Bcl-2 family of proteins can be divided into pro-survival and pro-apoptotic members, including B-cell lymphoma 2 (Bcl-2) and Bcl-2-like protein 4 (Bax). The aim of the present study was to investigate the association between mortalin, Bcl-2 and Bax, as well as the prognostic significance of the combined expression of mortalin, Bcl-2 and Bax in ICC. Immunohistochemistry was used to determine the expression of mortalin, Bcl-2 and Bax in 116 ICC samples and to assess the association between expression of 3 markers and clinicopathological features of ICC patients. This revealed that ICC tumor tissues overexpressed mortalin and Bcl-2 and exhibited low expression of Bax in ICC tumor tissues compared with that in corresponding peritumoral samples. According to Pearson's correlation coefficient analysis, high expression of mortalin in ICC was positively correlated with Bcl-2 expression and negatively correlated with Bax expression. Furthermore, multiple linear regression analysis demonstrated that mortalin was positively associated with Bcl-2, but not with Bax, in patients with ICC. Patients with ICC exhibiting high expression of mortalin/Bcl-2 or low expression of Bax were closely associated with a malignant ICC phenotype, a relatively low overall survival rate and a high recurrence rate. Multivariate analysis indicated that mortalin and Bcl-2 were independent prognostic indicators for ICC patients. Meanwhile, the concomitant overexpression of mortalin and Bcl-2 and the low expression of Bax were independent markers for predicting a relatively poor prognosis of ICC. The overexpression of mortalin and Bcl-2 and/or the low expression of Bax are implicated in the anti-apoptotic effect and tumor progression of ICC. Mortalin or Bcl-2, or a combination of mortalin, Bcl-2 and Bax may be used to predict the prognosis of ICC, as well as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Objective Although several statistical methods for adjusting for missing data have been developed and are widely applied in research, few studies have investigated these methods in adjusting for missingness in datasets that aim to estimate the prevalence of dementia. We attempted to develop a more feasible approach for handling missingness in a cross-sectional study among elderly. Methods Five methods of estimating prevalence, including stratified weighting (SW), inverse-probability weighting (IPW), hot deck imputation (HDI), ordinal logistic regression (OLR) and multiple imputation (MI), were applied to handle the missing data yielded by a dataset that include 2231 non-responders. Results Compared with the results of the complete case analysis, the differences in the prevalence rates of dementia and mild cognitive impairment (MCI) calculated by the prevalence-estimating methods after adjusting for non-responders were less than 7% and 6%, respectively. In contrast to the results of other methods, the estimated prevalence of dementia and MCI calculated by MI increased when more predictive factors were included, and the lowest rate of missing data was achieved using MI. Using the participants’ ages, the cognitive screening sores and activity of daily life sores as predictive variables when correcting for missingness induced relatively larger effects on the estimated dementia prevalence. Conclusions When adjusting for missingness while estimating the prevalence of dementia in cross-sectional studies, a simple method, such as SW, is recommended when limited information is available, whereas MI is the preferred method when additional information is available. Further simulation studies are needed to determine the optimal approach. [ABSTRACT FROM AUTHOR]

Background and Aims: An immune imbalance in the cytokine profile exerts a profound influence on the progression of hepatitis B virus (HBV) infections and hepatocellular carcinoma (HCC). The present study evaluated the immune status of T helper (Th) 17 and Th1 cells in patients with HBV-related and non-HBV-related HCC. Methods: We randomly enrolled 150 patients with HCC. Blood samples and tissue samples were obtained. The distributions and phenotypic features of Th17 and Th1 cells were determined by flow cytometry and/or immunohistochemistry. Results: Compared to corresponding non-tumor regions, the levels of Th17 and Th1 cells were significantly increased in tumors of patients with HCC (P<0.001). The intratumoral densities of IL-17-producing cells and IFN-γ-producing cells were associated with overall survival (OS, P = 0.001) and disease-free survival (DFS, P = 0.001) of patients with HCC. The ratio of Th17 to Th1 in HBV-related HCC was higher than in non-HBV-related HCC. A multivariate Cox analysis revealed that the Th17 to Th1 ratio was an independent prognostic factor for OS (HR = 2.651, P = 0.007) and DFS (HR = 2.456, P = 0.002). Conclusions: HBV infections can lead to an imbalance in immune status in patients with HCC. An elevated Th17 to Th1 ratio may promote tumor progression. The Th17 to Th1 ratio could serve as a potential prognostic marker for scoring the severity of HCC. [ABSTRACT FROM AUTHOR]

Abstract: Chinese grasslands have undergone great changes in land use in recent decades. Approximately 18.2% of the present arable land in China originated from the cultivation of grassland, but its impact on the carbon cycle has not been fully understood. This study was conducted in situ for 3 years to assess the comprehensive effects of cultivation of temperate steppe on soil organic carbon (SOC) and soil respiration rates as well as ecosystem respiration. As compared with those in the Stipa baicalensis steppe, the SOC concentrations at depths of 0–10 and 10–20cm in the spring wheat field were found to have decreased by 38.3 and 17.4% respectively from 29.5 and 21.9gkg−1 to 18.2 and 18.1gkg−1 after a cultivation period of 30 years. Accordingly, the total amounts of soil respiration through the growing season (from April to September) in 2002, 2003 and 2004 were 265.2, 282.2 and 237.4gCm−2 respectively in the spring wheat field, which were slightly lower than the values of 342.2, 412.0 and 312.1gCm−2 in the S. baicalensis steppe, while ecosystem respiration of 690.9, 991.2 and 569.6gCm−2 respectively in the spring wheat field were markedly higher than those of 447.0, 470.9 and 429.7gCm−2 in the steppe plot. Similar seasonal variations of ecosystem respiration and soil respiration existed in both sample sites. Respiration rates were higher and greater differences existed in both ecosystem respiration and soil respiration during the exuberant growth stage of plants (from mid-June to mid-August). However, in the slower-growth period of the growing season (before late May and after late August), the CO2 effluxes of the two sample sites were similar and remained at a relatively low level. The results also showed that ecosystem respiration and soil respiration were under similar environmental controls in both sample sites. Soil water content at a depth of 0–10cm and soil temperatures at 5 and 10cm were the main factors affecting the variations in ecosystem respiration and soil respiration rates in droughty years of 2002 and 2004 and in the rainy 2003, respectively. This study suggests that the conversion of the grassland to the spring wheat field has increased the carbon loss of the whole ecosystem due to the change of vegetation cover type and significantly reduced the carbon storage of surface soil. In addition, the tillage of grassland had different effects on ecosystem respiration and soil respiration. The effects were also dissimilar in different growth stages, which should be fully considered when assessing and predicting the effects of cultivation on the net CO2 balance of grassland ecosystems. [Copyright &y& Elsevier]

• Mechanism between IGFBPrP1 and autophagy in liver fibrogenesis is poorly understood. • IGFBPrP1 promoted autophagy and contributed to hepatic stellate cell activation. • H19 is an autophagy promoter to accelerate IGFBPrP1-induced autophagy. • Mutual regulation occurred between H19 and PI3K/AKT/mTOR pathway in IGFBPrP1-induced hepatic stellate cells activation. • New insights for further studies on the prevention and treatment of liver fibrosis. Our previous study found that insulin-like growth factor binding protein-associated protein (IGFBPrP1) drives hepatic stellate cells (HSCs) activation, and IGFBPrP1 and transforming growth factor β1 (TGFβ1) likely interact with each other to promote HSCs activation. TGFβ1 reportedly promotes autophagy and contributes to HSCs activation; however, the mechanism between IGFBPrP1 and autophagy in liver fibrogenesis is yet unknown. Moreover, long noncoding RNA (lncRNA) H19 participates in autophagy regulation and plays a crucial function in liver fibrosis. To define the relationship between IGFBPrP1 and autophagy and the role of H19 in IGFBPrP1-induced hepatic fibrosis. IGFBPrP1 and autophagy were detected in bile duct ligation (BDL)-induced hepatic fibrosis. Adenovirus-mediated IGFBPrP1 was transfected into mouse liver and JS-1 cells with or without LY294002 or rapamycin to examine the effects of IGFBPrP1 on HSCs activation and autophagy as well as the PI3K/AKT/mTOR pathway. lncRNA H19 in liver fibrosis tissues and JS-1 cells induced by IGFBPrP1 were detected, then autophagy and HSCs activation level were detected in JS-1 cells by IGFBPrP1 with H19 overexpression or knowdown. IGFBPrP1 expression and autophagy level were concomitantly increased in liver tissue with BDL-induced hepatic fibrosis. Furthermore, we found that IGFBPrP1 stimulated autophagy and HSCs activation in vivo and in vitro , and PI3K/AKT/mTOR signaling pathway was involved in the regulation of autophagy by IGFBPrP1. In addition, H19 promoted autophagy by interacting with the PI3K/AKT/mTOR pathway in IGFBPrP1-induced HSCs activation. IGFBPrP1 promoted autophagy and contributed to HSCs activation via mutual regulation between H19 and the PI3K/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

Wang-bi tablet (WB) consists of 17 traditional Chinese medicines and has been used for treating rheumatoid arthritis (RA) in China for many years, however, its pharmacologic mechanism is not clear. The aim of this study was to investigate the therapeutic effect of WB on collagen-induced mouse arthritis and explored the underlying mechanism. DBA/1 mice were used to establish a type II collagen-induced arthritis (CIA) model. From the day of arthritis onset, mice were treated daily by gavage with either total glucosides of paeony (TGP, 0.37 g/kg/d) or WB at a lower (1.11 g/kg/d, WBL) or higher dose of (3.33 g/kg/d, WBH) for 8 weeks. The severity of arthritis, levels of cytokines and the activation of signaling pathways were determined. Our results revealed that WB treatment effectively alleviated inflammatory symptoms and prevented bone erosions and joint destructions. It obviously decreased the serum concentration of pro-inflammatory cytokines TNF-α, IL-6 and IL-17α, while increased the concentration of anti-inflammatory cytokine IL-10. Interestingly, the proportion of splenic Treg cells were increased significantly. In vitro experiments showed that WB inhibited the differentiation of osteoclasts. Consistently, the mRNA levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CtsK), and the activation of NF-κB and JAK-STAT3 signaling pathways in the paws of CIA mice were inhibited by WB treatment. On the other hand, up-regulation of osteogenic genes Runx2, Osterix mRNA, and activation of Wnt/β-catenin signaling pathway along with a decreased receptor activator of nuclear factor κB ligand (RANKL) expression were found in WB treated mice. Our results suggest that the therapeutic effect of Wang-bi tablet could be attributed to its inhibitory activity on NF-κB and STAT3 signaling pathway-mediated osteoclast differentiation, and its enhancement on Wnt/β-catenin signaling pathway-mediated osteoblast functions. Image 1 [ABSTRACT FROM AUTHOR]

The title compound, [CuCl(C12H8N2)2][SbF6], was synthesized as green block-shaped crystals by the hydro­thermal method. The crystal structure consists of discrete [CuCl(phen)2]+ (phen is 1,10-phenanthroline) and [SbF6]− ions. The Cu atom is coordinated by four N atoms of two 1,10-phenanthroline ligands and by a Cl atom, with a slightly distorted trigonal–bipyramidal stereochemistry. [ABSTRACT FROM AUTHOR]