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Purpose: Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation. Methods: C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p

BackgroundSeveral models have been developed to predict the severity and prognosis of chronic obstructive pulmonary disease (COPD). This study aimed to identify potential predictors and construct a prediction model for COPD severity using biochemical and immunological parameters.MethodsA total of 6,274 patients with COPD were recruited between July 2010 and July 2018. COPD severity was classified into mild, moderate, severe, and very severe based on the Global Initiative for Chronic Obstructive Lung Disease guidelines. A multivariate logistic regression model was constructed to identify predictors of COPD severity. The predictive ability of the model was assessed by measuring sensitivity, specificity, accuracy, and concordance.ResultsOf 6,274 COPD patients, 2,644, 2,600, and 1,030 had mild/moderate, severe, and very severe disease, respectively. The factors that could distinguish between mild/moderate and severe cases were vascular disorders (OR: 1.44; P < 0.001), high-density lipoprotein (HDL) (OR: 1.83; P < 0.001), plasma fibrinogen (OR: 1.08; P = 0.002), fructosamine (OR: 1.12; P = 0.002), standard bicarbonate concentration (OR: 1.09; P < 0.001), partial pressure of carbon dioxide (OR: 1.09; P < 0.001), age (OR: 0.97; P < 0.001), eosinophil count (OR: 0.66; P = 0.042), lymphocyte ratio (OR: 0.97; P < 0.001), and apolipoprotein A1 (OR: 0.56; P = 0.003). The factors that could distinguish between mild/moderate and very severe cases were vascular disorders (OR: 1.59; P < 0.001), HDL (OR: 2.54; P < 0.001), plasma fibrinogen (OR: 1.10; P = 0.012), fructosamine (OR: 1.18; P = 0.001), partial pressure of oxygen (OR: 1.00; P = 0.007), plasma carbon dioxide concentration (OR: 1.01; P < 0.001), standard bicarbonate concentration (OR: 1.13; P < 0.001), partial pressure of carbon dioxide (OR: 1.16; P < 0.001), age (OR: 0.91; P < 0.001), sex (OR: 0.71; P = 0.010), allergic diseases (OR: 0.51; P = 0.009), eosinophil count (OR: 0.42; P = 0.014), lymphocyte ratio (OR: 0.93; P < 0.001), and apolipoprotein A1 (OR: 0.45; P = 0.005). The prediction model correctly predicted disease severity in 60.17% of patients, and kappa coefficient was 0.35 (95% CI: 0.33–0.37).ConclusionThis study developed a prediction model for COPD severity based on biochemical and immunological parameters, which should be validated in additional cohorts.

In the paper, the authors introduce a new class of convex functions, GT-convex functions, establish some integral inequalities for GT-convex functions and for the product of two GT-convex functions, and give some applications to classical special means.

Abstract In the paper, the authors define a new notion of “HT-convex function”, present some Hadamard-type inequalities for the new class of HT-convex functions and for the product of any two HT-convex functions, and derive some inequalities for the arithmetic mean and the p-logarithmic mean. These results generalize corresponding ones for HA-convex functions and MT-convex functions.

Background: Restless legs syndrome (RLS) is a common neurological disorder with unpleasant leg sensations and serious negative effects on mental and physical health. Many observational studies showed that people with RLS had a high risk of vascular diseases, including cerebrovascular and cardiovascular diseases (CVD), but the findings were conflicting. The Jidong RLS Cohort Study is a prospective cohort study designed to mainly examine whether or not RLS is associated with an increased risk of CVD.Methods and Design: The study recruited 8,867 healthy participants older than 18 years from October 2014 to December 2015. Participants received a physical examination in the Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation. Baseline data and blood samples were collected. Restless legs syndrome was assessed using the international RLS diagnostic criteria. All of subjects would be followed up until December 2025. Major cardiovascular/cerebrovascular events including cardiac death, myocardial infarction, ischemic heart disease, heart failure, atrial fibrillation, ischemic, and hemorrhagic stroke will be the primary outcomes. Secondary outcomes include all-cause mortality, the decline in quality of life, cognitive impairment, and depression.Discussion: This study will contribute to the scientific evidence on the association between RLS and cardiovascular risks and also provide an unprecedented opportunity for early detection and prevention of CVD.

During the vibration of a transmission tower, the joints will be subjected to a reciprocating load. To obtain the accurate state of the transmission tower under the load, the mechanical properties of the joints under the vibration load must be considered. In this paper, the mechanical properties of typical K-joints in transmission tower structures are studied by numerical simulation. The failure mode of the K-joint under cyclic loading is also analyzed. The mechanical properties of the K-joint are discussed from the aspects of hysteretic characteristics, stiffness degradation, energy dissipation capacity, and ductility evaluation, and the influencing factors are discussed. The results show that the failure mode of the K-joint is related to the bolt grade and steel strength. When analyzing K-joints, the moment-rotation hysteresis curve should be combined with the realistic parameters of joints to consider the hysteretic behavior of the K-joint. The results provide a theoretical reference for the accurate modeling of transmission towers.

Induced pluripotent stem cell (iPSC) line, THSJTUi001-A, was generated from a 26-year-old Chinese male patient with Wilson's disease carrying a homozygous Arg778Leu mutation in ATP7B gene, using non-integrated episomal reprogramming vectors. This cell line had normal karyotype, expressed pluripotency markers and could differentiate into the three germ layers in vivo.

Background: The sequence effect (SE), referring to step-to-step reduction in amplitude, is considered to lead to freezing of gait (FOG) in Parkinson's disease (PD). Visual cues may alleviate SE and help reduce freezing episodes. FOG patients show significant SE prior to turning or toward a doorway, but the SE toward a destination has not been clearly studied.Objectives: To examine the SE when approaching a destination in PD patients with FOG, and to further explore the effects of different types of visual cues on destination SE.Methods: Thirty-five PD patients were divided into a freezing (PD+FOG, n = 15) group and a non-freezing (PD–FOG, n = 20) group. Walking trials were tested under three conditions, including without cues (no-cue condition), with wearable laser lights (laser condition), and with transverse strips placed on the floor (strip condition). Kinematic data was recorded by a portable Inertial Measurement Unit (IMU) system. The destination SE and some key gait parameters were evaluated.Results: The PD+FOG group showed greater destination SE in the no-cue and laser conditions when compared to the PD–FOG group. There were no significant differences in the strip condition when comparing destination SE of the two groups. The destination SE was alleviated only by using the transverse strips on the floor. In contrast, transverse strips and wearable laser lights could increase the step length.Conclusions: The significant destination SE may explain why FOG patients are prone to freezing when heading toward their destination. Visual cues using transverse strips on the floor may be a more effective strategy for FOG rehabilitation in PD patients.

Most tunnel structures tend to have different degrees of structural damage such as leakage, concrete cracking, lining salinization, and falling blocks after the operation for a period. Compared with the diversity of tunnel disease detection methods, there are few studies on the methods of quantifying and evaluating the main structural diseases of the lining. Based on the regular inspection data of expressway tunnels in Liaoning Province, this paper summarizes the distribution characteristics and laws of existing structural defects of tunnel lining. In addition, based on the in-depth study of the main structural diseases of the tunnel, the extenics theory is used to extract, quantify and classify several indicators that can accurately reflect the health status of the structure, and then establish the corresponding matter-element model to determine the weight of each indicator and the tunnel structure. The comprehensive correlation degree of disease grades is combined with the qualitative evaluation and quantitative research of lining structure diseases to construct a health evaluation system for tunnel lining structures, which is convenient for managers to make reasonable decisions. At the same time, combined with the actual test data of tunnel engineering, the calculation and analysis of the extension model are carried out to verify the engineering applicability of the model.

Objective To explore the role and mechanism of β1 integrin in the regulation of multicellular drug resistance in hepatocellular carcinoma (HCC). Methods This in vitro study used a liquid overlay technique to obtain multicellular spheroids of two human HCC cell lines, HepG2 and Bel-7402. The morphology of the spheroids was observed by optical and electron microscopy. The effects of exposure to 5-fluorouracil (5-FU) and cisplatin (CDDP) on cell proliferation and the induction of apoptosis were assessed in monolayer cells and multicellular spheroids. The levels of β1 integrin and the effects on the focal adhesion kinase (FAK)/protein kinase B (Akt) pathway were evaluated using Western blot analysis, immunofluorescence and flow cytometry. The role of β1 integrin was confirmed by using an inhibitory antibody. Results Cell proliferation inhibition and cell apoptosis induced by 5-FUl and CDDP were abrogated in multicellular spheroids compared with monolayer cells. There were high levels of β1 integrin in multicellular spheroids. β1 integrin inhibitory antibody prevented the formation of multicellular spheroids, coupled with a significant increase in proliferation inhibition and apoptosis induction. β1 integrin inhibitory antibody effectively suppressed activation of both FAK and Akt in multicellular spheroids. Conclusions β1 integrin mediated multicellular drug resistance through the FAK/Akt pathway in HCC spheroids.

Expression of lymphoid enhancer factor 1 (LEF1) is frequently altered in different human cancers. This study aimed to assess LEF1 expression in colon cancer tissues and to explore changed phenotypes, gene expressions, and the possible mechanism after knocked down LEF1 expression in colon cancer cell lines. A total of 106 colon cancer and matched paratumorous normal tissues were used to assess LEF1 expression using immunohistochemistry and qRT-PCR. LEF1 lentivirus was used to knockdown LEF1 expression for the assessment of cell viability, cell cycle distribution, apoptosis, and gene expressions. The nude mouse xenograft assay was performed to detect the effects of LEF1 knockdown in vivo. The data showed that the levels of LEF1 mRNA and protein were significantly increased in human colon cancer tissues compared to the matched paratumorous normal tissues and were associated with infiltration depth, lymph node and distant metastases, advanced TNM (tumor-node-metastasis) stages, and shorter overall survival. Furthermore, LEF1 knockdown reduced tumor cell viability, invasion capacity, MMP2 and MMP-9 expression, but induced apoptosis. Nude mouse xenograft assay showed that LEF1 knockdown suppressed tumor formation and growth in vivo. In addition, the expression of Notch pathway-related proteins RBP-jκ and Hes1 was reduced in LEF1 knockdown cells. Taken together, LEF1 protein was overexpressed in colon cancer tissues and knockdown of LEF1 expression inhibited colon cancer growth in vitro and in vivo. These data suggest that targeting of LEF1 expression should be further evaluated for colon cancer prevention and therapy.

The asymmetric unit of the title compound, [Ni(C2H8N2)3](C8H4O5)·H2O, contains one [Ni(en)3]2+ cation (en is ethane-1,2-diamine), one 5-hydroxyisophthalate dianion and one water molecule. In the cation, the Ni2+ ion is coordinated by six N atoms from three ethylenediamine ligands in a distorted octahedral geometry. The complex ions and water molecules are linked by weak N—H...N/O and O—H...N/O hydrogen bonds into a three-demensional structure.

In the title organic–inorganic hybrid vanadate complex, [Cu2V6O17(C10H8N2)4]n, the CuII atom is six-coordinated by two chelating 2,2′-bipyridine (bipy) ligands and two vanadate O atoms in a distorted octahedral geometry. Two [Cu(bipy)2V3O8] units are linked by a bridging O atom, which lies on an inversion center, forming a dimeric unit. The dimeric units are further connected by bridging vanadate O atoms into a two-dimensional layer parallel to (100). The layers are connected by weak C—H...O hydrogen bonds.

The title compound, C15H15NO4S, was prepared by simple condensation of methyl 2-aminobenzoate and 4-methylbenzenesulfonyl chloride. The dihedral angle between the benzene rings is 84.36 (6)°. The molecular structure is stabilized by an intramolecular N—H...O hydrogen-bonding interaction involving the carbonyl group as acceptor, generating an S(6) graph-set motif.

In the title compound, C20H22Cl3NO, the five-membered ring adopts an envelope conformation, and the two benzene rings are oriented at a dihedral angle of 40.44 (9)°. Intramolecular O—H...N and N—H...Cl hydrogen bonding is present. In the crystal, the molecules are linked via weak intermolecular C—H...O hydrogen bonds.

In the title compound, C28H30ClNO2, the cyclopentane ring adopts an envelope conformation. In the crystal structure, molecules are linked by intermolecular O—H...O hydrogen bonds, forming chains running along the a axis.

In this paper, operator m-convex and (α,m)-convex function on the co-ordinates are defined, and some new integral inequalities of Hermite-Hadamard type for operator mconvex and (α,m)-convex on the co-ordinates are established. [ABSTRACT FROM AUTHOR]

Delisheng is a widely used antineoplastic agent in China. Although previous studies revealed that Delisheng exhibits numerous pharmacological effects including the inhibition of cancer cell differentiation and enhancement of immune function with the lowest toxicity, the precise anticancer mechanisms of Delisheng in human hepatocellular carcinoma (HCC) cells remains largely unknown. The present study investigated the potential mechanisms underlying the anticancer properties of Delisheng on Hep3B cells. Delisheng demonstrated a strong anti‑proliferation effect on Hep3B cells compared with normal liver HL‑7702 cells, as detected by MTT assays. In addition, Delisheng arrested the cells in G/G1 phase. Furthermore, it exhibited a pro‑apoptotic effect on Hep3B cells, as detected by flow cytometry. When exposed to Delisheng, Hep3B cells demonstrated decreased vascular endothelial growth factor (VEGF) and osteopontin (OPN) and increased endostatin (ES) protein expressions, as detected using immunocytochemistry staining and western blotting. These data suggest that Delisheng induces antiproliferation and apoptosis of Hep3B cells via modulation of VEGF, OPN and ES protein expression. It is hypothesized that Delisheng may be used as a novel anticancer therapeutic in HCC. [ABSTRACT FROM AUTHOR]

In the paper, by establishing a Riemann-Liouville fractional integral identity involving an n-times differentiable function, the authors present some Hermite-Hadamard type inequalities involving Riemann-Liouville fractional integrals for s-convex functions. [ABSTRACT FROM AUTHOR]

In the paper, by creating an integral identity involving an n-times differentiable function, the authors establish some new Hermite-Hadamard type inequalities for preinvex functions and generalize some known results. [ABSTRACT FROM AUTHOR]

As the population of transformers in service increases and their operating time extends, much attention has been focused on their availability and reliability. However, insufficient research work concentrates on how to evaluate transformer's aging condition, although huge progress has been made on the techniques of fault diagnosis and condition assessment of transformer in past decades. This paper presents the concept of Aging Index (AI), which is a practical tool that combines the results of routine inspections, and site and laboratory testing to estimate the aging condition of oil-immersed transformers. Further, frequency domain spectroscopy (FDS) as a novel non-destructive testing technique to estimate remained life expectancy is included in aging evaluation system. Moreover, a software system based on transformer's electrical and thermal parameters is developed correspondingly, by using a multi-parameters analytic approach. This system would dedicate to decision-making and replacement planning and has good application prospects. [ABSTRACT FROM AUTHOR]

Clinical diagnosis of acute graft-versus-host disease (aGVHD) mainly depends on clinical manifestation and tissue biopsies, leading to a delayed diagnosis and treatment for aGVHD patients when the early symptom is insignificant. Our objective was to investigate the possibility of prewarning the risk of aGVHD before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) by serum protein profiling combined with serum ferritin. The difference in polypeptide expression before and after transplantation had been compared by using CLINPROT technology, and serum ferritin levels have been analyzed simultaneously. Through combining serum ferritin and MS spectral data, the diagnosis sensitivity and specificity of our model for prewarning severe aGVHD (III~ IV°aGVHD) before transplant all increased to 90.0%, while after transplant, the sensitivity and specificity are 78.3% and 86.4%. Our joint prewarning model could predict the risk of aGVHD, especially severe aGVHD before and after transplant, which also provides a reliable method to the continuous monitoring of the condition of patients. [ABSTRACT FROM AUTHOR]

In the paper, some new inequalities of Hermite-Hadamard type for (α, m)-convex functions are obtained. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a typical hypervascular tumor, and increased levels of vascular endothelial growth factor (VEGF) are associated with progression of HCC. Tumor suppression gene PTEN (phosphatase and tensin homolog deleted on chromosome 10), an important antagonist of the phosphoinositide-3-kinase (PI3K)/adenosine triphosphate-dependent tyrosine kinase (Akt) pathway, is also commonly lost or mutated in HCC. However, the effect of PTEN on VEGF-mediated angiogenesis in HCC remains unknown. To explore this relationship, we expressed a panel of PTEN mutants in human HCC cells with low expression of PTEN (HepG2 cells). Overexpression of PTEN in HepG2 cells resulted in the downregulation of proliferation and migration of cocultured endothelial cells and decreased expression of hypoxia-inducible factor 1 (HIF-1) and VEGF. Similarly, using a nude mouse model, we demonstrated that PTEN decreased expression of HIF-1 and VEGF and suppressed HepG2-induced angiogenesis. This inhibitory effect was not observed in cells expressing a phosphatase-deficient PTEN mutant, suggesting that PTEN inhibits angiogenesis and VEGF through a phosphatase-dependent pathway. Strikingly, reintroducing the C2 domain of PTEN also resulted in a significant decrease in angiogenesis and VEGF expression, although it did not affect Akt phosphorylation or HIF-1 expression. In summary, this study suggests the novel viewpoint that PTEN suppresses angiogenesis and VEGF expression in HCC through both phosphatase-dependent and -independent mechanisms. [ABSTRACT FROM PUBLISHER]

In order to investigate the neuroprotection of insulin in retinal neurons, we used retinal neuronal culture as a model system to study the protective effects of insulin against H2O2-induced cytotoxicity and apoptotic death. Primary retinal neuronal cultures were grown from retinas of 0–2-day old Sprague-Dawley rats. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Apoptotic cell death was evaluated by the TdT-mediated digoxigenin-dUTP nick-end labeling assay, and by DNA laddering analysis. Phosphoinositide 3-kinase (PI3K) activity was measured using phosphoinositide 4,5-bisphophate and [γ-32P]ATP as substrate. Western blot analysis with anti-phospho-Akt (pS473) antibody was performed to examine the level of phosphorylated Akt. We observed that treatment with 100 μM H2O2 for 24 h significantly decreased cell viability and induced apoptotic death of retinal neurons, and that pretreatment with 10 nM insulin significantly inhibited or attenuated H2O2-induced cytotoxicity and apoptosis. Pretreatment with LY294002, a specific PI3K inhibitor, abolished the cytoprotective effect of insulin. Insulin also strongly activated both PI3K and the downstream effector Akt. These results suggest that insulin protects retinal neurons from oxidative stress-induced apoptosis and that the PI3K/Akt signal pathway is involved in insulin-mediated retinal neuroprotection. Edited by Ming-Hua XU [ABSTRACT FROM AUTHOR]

Background/Objective. We aimed to examine the expression of lymphoid enhancer factor 1 (LEF1) and Notch2 in colorectal cancer (CRC) and their association with clinicopathologic variables and CRC patients' prognosis. Methods. Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot analysis were performed to assess the expression of LEF1 and Notch2 in 184 patients with CRC. Results. We observed a strong negative correlation between LEF1 expression and Notch2 expression (P < 0.001). Both LEF1 mRNA and protein expression increased while the Notch2 mRNA and protein expression decreased in tumor specimens compared with the matched paratumorous normal tissue (P < 0.001). An increase in LEF1 protein expression was significantly associated with lymph node metastases, distant metastasis, advanced TNM (tumor-node-metastasis) stage, and shorter overall survival. A decrease in Notch2 protein expression was associated with poorly differentiated tumors, lymph node metastases, distant metastasis, advanced TNM stage, and shorter overall survival of patients. In the multivariate Cox regression analysis, the LEF1 protein expression (P < 0.001), Notch2 protein expression (P < 0.001), TNM stage (P < 0.001), and the combination of increased LEF1 protein coexpression and decreased Notch2 protein coexpression (P < 0.001) were found to be independent prognostic indicators in CRC. Conclusion. Our results suggest that increased LEF1 coexpression and decreased Notch2 coexpression represent a risk factor for poor overall survival of CRC patients. [ABSTRACT FROM AUTHOR]