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Gallbladder cancer can be difficult to detect in its early stages and is prone to metastasize, causing bile duct obstruction, which is usually treated by stent implantation in clinic. However, the commonly used biliary stents are non-degradable, which not only prone to secondary blockage, but also need to be removed by secondary surgery. Biodegradable magnesium (Mg) is expected to one of the promising candidates for degradable biliary stents due to its excellent physicochemical property and biocompatibility. In this work, we studied the influence of high-purity Mg wires on gallbladder cancer through in vitro and in vivo experiments and revealed that the degradation products of Mg could significantly inhibit the growth of gallbladder cancer cells and promote their apoptosis. Our findings indicate that Mg biliary stent possesses the function of draining bile and treating gallbladder cancer, suggesting that Mg has good application prospects in biliary surgery. STATEMENT OF SIGNIFICANCE: Current research and development of biomedical magnesium are mainly concentrated in the cardiovascular and orthopedics field. Degradable magnesium bile duct stents have great application prospects in the treatment of bile duct blockage caused by bile duct-related cancers. At present, the effect of magnesium implants on gallbladder cancer is not clear. Our work verified the effectiveness of magnesium wire implants in inhibiting gallbladder cancer through in vivo and in vitro experiments, and studied the effect of magnesium degradation products on gallbladder cancer cells from the perspective of cell proliferation, apoptosis and cycle. This study provided new understanding for the application of magnesium in biliary surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Hyperhomocysteinemia (HHcy) causes cardiovascular diseases via regulating inflammatory responses. We investigated whether and how the epithelial sodium channel (ENaC), a recently identified ion channel in endothelial cells, plays a role in HHcy-induced endothelial dysfunction., Methods: Cell-attached patch-clamp recording in acute split-open aortic endothelial cells, western blot, confocal imaging, and wire myograph combined with pharmacological approaches were used to determine whether HHcy-mediated inflammatory signaling leads to endothelial dysfunction via stimulating ENaC., Results: The data showed that 4 weeks after L-methionine diet the levels of plasma Hcy were significantly increased and the ENaC was dramatically activated in mouse aortic endothelial cells. Administration of benzamil, a specific ENaC blocker, ameliorated L-methionine diet-induced impairment of endothelium-dependent relaxation (EDR) and reversed Hcy-induced increase in ENaC activity. Pharmacological inhibition of NADPH oxidase, reactive oxygen species (ROS), cyclooxygenase-2 (COX-2)/thromboxane B2 (TXB2), or serum/glucocorticoid regulated kinase 1 (SGK1) effectively attenuated both the Hcy-induced activation of endothelial ENaC and impairment of EDR. Our in vitro data showed that both NADPH oxidase inhibitor and an ROS scavenger reversed Hcy-induced increase in COX-2 expression in human umbilical vein endothelial cells (HUVECs). Moreover, Hcy-induced increase in expression levels of SGK-1, phosphorylated-SGK-1, and phosphorylated neural precursor cell-expressed developmentally downregulated protein 4-2 (p-Nedd4-2) in HUVECs were significantly blunted by a COX-2 inhibitor., Conclusion: We show that Hcy activates endothelial ENaC and subsequently impairs EDR of mouse aorta, via ROS/COX-2-dependent activation of SGK-1/Nedd4-2 signaling. Our study provides a rational that blockade of the endothelial ENaC could be potential method to prevent and/or to treat Hcy-induced cardiovascular disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liang, Wang, Yang, Zhu, Sun, Niu, Yao, Dong, Jiang, Tang, Lou, Yu, Shao, Wu and Zhang.)

The use of cyclosporine A (CsA) in transplant recipients is limited due to its side effects of causing severe hypertension. We have previously shown that CsA increases the activity of the epithelial sodium channel (ENaC) in cultured distal nephron cells. However, it remains unknown whether ENaC mediates CsA-induced hypertension and how we could prevent hypertension. Our data show that the open probability of ENaC in principal cells of split-open cortical collecting ducts was significantly increased after treatment of rats with CsA; the increase was attenuated by lovastatin. Moreover, CsA also elevated the levels of intracellular cholesterol (Cho), intracellular reactive oxygen species (ROS) via activation of NADPH oxidase p47 phox , serum- and glucocorticoid-induced kinase isoform 1 (Sgk1), and phosphorylated neural precursor cell-expressed developmentally downregulated protein 4-2 ( p -Nedd4-2) in the kidney cortex. Lovastatin also abolished CsA-induced elevation of α-, ß -, and γ-ENaC expressions. CsA elevated systolic blood pressure in rats; the elevation was completely reversed by lovastatin (an inhibitor of cholesterol synthesis), NaHS (a donor of H 2 S which ameliorated CsA-induced elevation of reactive oxygen species), or amiloride (a potent ENaC blocker). These results suggest that CsA elevates blood pressure by increasing ENaC activity via a signaling cascade associated with elevation of intracellular ROS, activation of Sgk1, and inactivation of Nedd4-2 in an intracellular cholesterol-dependent manner. Our data also show that NaHS ameliorates CsA-induced hypertension by inhibition of oxidative stress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Liang, Jiang, Zhu, Sun, Niu, Yang, Yang, Dong, Yao, Yu, Lou, Tang, Wu, Zhang and Ma.)

We have shown that cholesterol regulates the activity of ion channels in mouse cortical collecting duct (CCD) mpkCCD c14 cells and that the transient receptor potential melastatin 4 (TRPM4) channel is expressed in these cells. However, whether TRPM4 channel is regulated by cholesterol remains unclear. Here, we performed inside-out patch-clamp experiments and found that inhibition of cholesterol biosynthesis by lovastatin significantly decreased, whereas enrichment of cholesterol with exogenous cholesterol significantly increased, TRPM4 channel open probability ( Po ) by regulating its sensitivity to Ca 2+ in mpkCCD c14 cells. In addition, inside-out patch-clamp data show that acute depletion of cholesterol in the membrane inner leaflet by methyl-β-cyclodextrin (MβCD) significantly reduced TRPM4 Po , which was reversed by exogenous cholesterol. Moreover, immunofluorescence microscopy, Western blot, cell-surface biotinylation, and patch clamp analysis show that neither inhibition of intracellular cholesterol biosynthesis with lovastatin nor application of exogenous cholesterol had effect on TRPM4 channel protein abundance in the plasma membrane of mpkCCD c14 cells. Sucrose density gradient centrifugation studies demonstrate that TRPM4 was mainly located in cholesterol-rich lipid rafts. Lipid-protein overlay experiments show that TRPM4 directly interacted with several anionic phospholipids, including PI(4,5)P 2 . Depletion of PI(4,5)P 2 with either wortmannin or PGE2 abrogated the stimulatory effects of exogenous cholesterol on TRPM4 activity, whereas exogenous PI(4,5)P 2 (diC8-PI(4,5)P 2 , a water-soluble analog) increased the effects. These results suggest that cholesterol stimulates TRPM4 via a PI(4,5)P 2 -dependent mechanism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cai, Zhang, Yu, Yang, Ao, Zhu, Wang, Lou, Liang, Tang, Wu, Zhang and Ma.)

Purpose: To investigate intravoxel incoherent motion (IVIM) tensor imaging of the in vivo human heart and elucidate whether the estimation of IVIM tensors is affected by the complexity of pseudo-diffusion components in myocardium., Methods: The cardiac IVIM data of 10 healthy subjects were acquired using a diffusion weighted spin-echo echo-planar imaging sequence along 6 gradient directions with 10 b values (0~400 s/mm 2 ). The IVIM data of left ventricle myocardium were fitted to the IVIM tensor model. The complexity of myocardial pseudo-diffusion components was reduced through exclusion of low b values (0 and 5 s/mm 2 ) from the IVIM curve-fitting analysis. The fractional anisotropy, mean fraction/mean diffusivity, and Westin measurements of pseudo-diffusion tensors (f p and D*) and self-diffusion tensor (D), as well as the angle between the main eigenvector of f p (or D*) and that of D, were computed and compared before and after excluding low b values., Results: The fractional anisotropy values of f p and D* without low b value participation were significantly higher (P < .001) than those with low b value participation, but an opposite trend was found for the mean fraction/diffusivity values. Besides, after removing low b values, the angle between the main eigenvector of f p (or D*) and that of D became small, and both f p and D* tensors presented significant decrease of spherical components and significant increase of linear components., Conclusion: The presence of multiple pseudo-diffusion components in myocardium indeed influences the estimation of IVIM tensors. The IVIM tensor model needs to be further improved to account for the complexity of myocardial microcirculatory network and blood flow., (© 2020 International Society for Magnetic Resonance in Medicine.)

Previous studies have shown that high salt induces artery stiffness by causing endothelial dysfunction via increased sodium influx. We used our unique split-open artery technique combined with protein biochemistry and in vitro measurement of vascular tone to test a hypothesis that bone morphogenetic protein 4 (BMP4) mediates high salt-induced loss of vascular relaxation by stimulating the epithelial sodium channel (ENaC) in endothelial cells. The data show that high salt intake increased BMP4 both in endothelial cells and in the serum and that exogenous BMP4 stimulated ENaC in endothelial cells. The data also show that the stimulation is mediated by p38 mitogen-activated protein kinases (p38 MAPK) and serum and glucocorticoid-regulated kinase 1 (Sgk1)/neural precursor cell expressed developmentally downregulated gene 4-2 (Nedd4-2) (Sgk1/Nedd4-2). Furthermore, BMP4 decreased mesenteric artery relaxation in a benzamil-sensitive manner. These results suggest that high salt intake stimulates endothelial cells to express and release BMP4 and that the released BMP4 reduces artery relaxation by stimulating ENaC in endothelial cells. Therefore, stimulation of ENaC in endothelial cells by BMP4 may serve as another pathway to participate in the complex mechanism of salt-sensitive (SS) hypertension., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Xu Yang et al.)

Rationale: The developement of oral targeted therapeutics for obesity and obesity-related diseases is challenging, as these diseases involve multiple lesions distributed throughout the whole body. Herein, we report a successful stragety for targeted oral delivery of bindarit to multiple obesity-related lesions including inflamed adipose tissue, fatty liver and atherosclerotic plaques. Methods: The computer simulation from atomstic to mesoscale was first applied for designing bindarit-loaded nanoparticles (pBIN) and laminarin-modified bindarit-loaded nanoparticles (LApBIN). Then pBIN were suceesfully prepared using a dialysis procedure, and LApBIN were prepared though the interaction bewtween laminarin and pBIN. The physiochemical properties, in vitro and in vivo pharmacokinetics, oral targeting capability and in vivo efficacy of LApBIN in various obesity-related diseases were examined. Results: LApBIN were sucessfully designed and prepared. Following oral administration of LApBIN, the nanoparticles could be sucessully orally adsorbed and translocated to monocytes. Contributed by the recruitment of monocytes to multiple obesity-related lesions, LApBIN successfully delivered bindarit to these lesions, and effectively suppressed inflammation there, which exerted successful preventive effects on high-fat-diet-induced obesity, insulin resistance, fatty liver and atherosclerosis. Conclusions: This strategy could represent a promising approach to develop effective oral treatments for obesity and other metabolic diseases., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

We study the two-dimensional Bose-Fermi mixture on square lattice at finite temperature by using the determinant quantum Monte Carlo method within the weakly interacting regime. Here we consider the attractive Bose-Hubbard model and free spinless fermions. In the absence of boson-fermion interactions, we obtain the boundary of the collapsed state of the attractive bosons. In the presence of boson-fermion interactions, an effective p-wave interaction between fermions will be induced as far as the bosons are in a superfluid state. Moreover, we find the emergence of the composite fermion pairs at low temperatures.

Using a deterministic compartmental modeling procedure to fit prevalence from 2005-2015, we projected new HIV cases during 2016-2026 under different coverage rates ranging from 0.0001 (at baseline) to 0.15 (an optimistic assumption) with simulations on varying transmission rates, model calibration to match historical data, and sensitivity analyses for different assumptions. Compared with the baseline ( λ  = 0.0001), we found the new HIV cases would reduce with the increase of coverage rates of the voluntary medical male circumcision (VMMC) among men who have sex wtih men (MSM). The higher the coverage rate, the lower the new HIV incidence would be. As one of the first studies to model the potential impact of VMMC among MSM in China, our model suggested a modest to the significant public health impact of VMMC. Even at just 15% VMMC annual uptake rate, the reduction in new infections is substantial. Therefore, there is a strong need to determine the efficacy of VMMC among MSM, to improve the evidence base for its potential use among MSM in low circumcision settings. Only then can policymakers decide whether to incorporate VMMC into a package of HIV prevention interventions targeting MSM.

Three-dimensional(3D) Weyl semimetal(WSM) with linear energy spectra has attracted significant interest. Especially they have been observed experimentally in several solid materials with the breaking of inversion symmetry. Here we predict a new family of particle-hole([Formula: see text]) invariant 2D WSMs in the non-Abelian gauge field, which can emerge in the low energy bands being close to Fermi energy (dubbed Weyl-I) and the high energy bands being away from Fermi energy (dubbed Weyl-II), only when the time-reversal symmetry([Formula: see text]) of the 2D Dirac semimetal is broken in the presence of in-plane Zeeman fields. Moreover, a 2D Dirac node can split into a pair of Weyl nodes showing the same Berry phase, and the 2D WSM, being protected by [Formula: see text] symmetry, exhibits four Weyl-I nodes, whose energies are invariant with the variation of the magnetic field. The corresponding Fermi velocity and Berry connection have been calculated. Based on the 2D WSMs, we also examine inhomogeneous pairings of attractive Fermi gases and find a new kind of the LO states with the beat frequency. This 2D WSM provides a realistic and promising platform for exploring and manipulating exotic Weyl physics, which may increase the experimental feasibility in the context of ultracold atoms.

Voluntary medical male circumcision (VMMC) among men who have sex with men (MSM) may protect against HIV acquisition. We conducted a series of analyses to assess if expanded VMMC might reduce HIV incidence among MSM effectively and economically. We used a deterministic compartmental model to project new HIV cases (2016-2026) under annual VMMC coverage rates (λ) ranging from 0.0001 to 0.15. The 'number needed to avert' (NNA) is defined as the cumulative number of VMMCs conducted up to that year divided by the cumulative number of HIV cases averted in that specific year. Compared with the baseline circumcision coverage rate, we projected that new HIV cases would be reduced with increasing coverage. By 2026 (last year simulated), the model generated the lowest ratio (11.10) when the annual circumcision rate was the most optimistic (λ = 0.15). The breakeven point was observed at the year of 2019 with the annual VMMC coverage rate of 0.001. The total cost saved by averting HIV cases would range from 2.5 to 811 million US dollars by the end of 2026 with different hypothetical coverage rates. Our model suggests that acceleration in VMMC implementation among MSM could help stem the HIV/AIDS epidemic.

As proposed in the UNAIDSs 2014 report, to end global AIDS epidemic by 2030, 90% of people living with HIV need to be diagnosed, 90% of the diagnosed need to receive antiretroviral therapy (ART), and 90% of those on treatment need to achieve viral suppression (90-90-90 strategy). The strategies focus on the reservoir. It controls HIV spreading by reducing infectiousness of HIV infected individuals via diagnosis and treatment. In this manuscript, we compared the effects of HIV/AIDS interventions that focus on different individuals in MSM population through a dynamics model. Our results showed that, the success or not of the "90-90-90" strategies depends on a very important factor: the infectious strength among individuals taking ART. Without highly effective HIV treatment, the "90-90-90" strategies are likely to fail. Therefore, we call for the combination of both primary prevention among the susceptible with the 90-90-90 strategy among the infected to curb the HIV epidemic in Chinese MSM.

There is no effective treatment method for nonalcoholic fatty liver disease (NAFLD), the most common liver disease. The exact mechanism underlying the pathogenesis of NAFLD remains to be elucidated. Here, we report that tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein (TRUSS) acts as a positive regulator of NAFLD and in a variety of metabolic disorders. TRUSS expression was increased in the human liver specimens with NAFLD or nonalcoholic steatohepatitis, and in the livers of high-fat diet (HFD)-induced and genetically obese mice. Conditional knockout of TRUSS in hepatocytes significantly ameliorated hepatic steatosis, insulin resistance, glucose intolerance, and inflammatory responses in mice after HFD challenge or in spontaneous obese mice with normal chow feeding. All of these HFD-induced pathological phenotypes were exacerbated in mice overexpressing TRUSS in hepatocytes. We show that TRUSS physically interacts with the inhibitor of nuclear factor κB α (IκBα) and promotes the ubiquitination and degradation of IκBα, which leads to aberrant activation of nuclear factor κB (NF-κB). Overexpressing IκBα S32A/S36A , a phosphorylation-resistant mutant of IκBα, in the hepatocyte-specific TRUSS overexpressing mice almost abolished HFD-induced NAFLD and metabolic disorders. Conclusion: Hepatocyte TRUSS promotes pathological stimuli-induced NAFLD and metabolic disorders, through activation of NF-κB by promoting ubiquitination and degradation of IκBα. Our findings may provide a strategy for the prevention and treatment of NAFLD by targeting TRUSS., (© 2018 by the American Association for the Study of Liver Diseases.)

5-fluorouracil (5-FU) has been used in the treatment of colorectal cancer for >50 years. However, drug resistance remains an obstacle in the application of 5-FU-based chemotherapy. Bufalin, a type of steroid with anti-tumor activity, may be purified from the skin and parotid venom glands of toads. In order to improve the anti-tumor effect of 5-FU, the present study examined the combined effects of bufalin with 5-FU on human colorectal cancer HCT116 cells. Following treatment, cell proliferation was quantified using MTT assay and apoptotic cell percentage was assessed by flow cytometry. The apoptosis-associated protein expression was evaluated by western blotting. It was observed that bufalin enhanced the cytotoxicity of 5-FU in HCT116 cells via the induction of the mitochondrial apoptotic pathway. Additionally, bufalin combined with 5-FU reduced the expression levels of anti-apoptotic proteins, such as Mcl-1, XIAP and Bcl-2 and upregulated the levels of the pro-apoptotic proteins, Bax and Bad. To verify the role of Bax, RNA interference was used to knock-down Bax. It was determined that the synergistic effect between 5-FU and bufalin was diminished following the silencing of Bax. In summary, bufalin in combination with 5-FU may induce a higher level of apoptosis compared with monotherapy, and the combination mat be a potential therapeutic strategy for the treatment of colorectal cancer.

Objective: ARHGAP9 is a RhoGTPase activating protein. This study aimed to investigate the effect of ARHGAP9 on cell proliferation of gastric cancer cell., Methods: Human gastric cancer cell line SGC7901 were transfected with ARHGAP9 siRNA and the expression of epithelial to mesenchymal transition (EMT) factors, MMPs, and activated status of Akt and p38 signaling were detected. Moreover, the migration, invasion, and viability of SGC7901 cells were determined., Results: ARHGAP9 siRNA successfully inhibited cell viability, migration and invasion. The expression of E-cadherin was significantly upregulated, and expression of Snail, Vimentin, as well as MMP2 and MMP9 were obviously downregulated. Moreover, ARHGAP9 siRNA promoted inactivation of Akt and p38 signaling by inhibiting expression of p-Akt and p-p38., Conclusion: This study showed that ARHGAP9 contributed to the viability, migration, invasion as well as EMT in gastric cancer cell line SGC7901. ARHGAP9 might be used as a therapeutic target for gastric cancer., Competing Interests: None., (IJCEP Copyright © 2017.)

Silver nanoparticles (AgNPs) are increasingly used in various commercial products. This increased use raises ecological concerns because of the large release of AgNPs into the environment. Once released, the local water chemistry has the potential to influence the environmental fates and behaviors of AgNPs. The impacts of dissolved oxygen and natural organic matter (NOM) on the dissolution and stability of AgNPs were investigated in synthetic and natural freshwaters for 7 days. In synthetic freshwater, the aggregation of AgNPs occurred due to the compression of the electric double layer, accompanied by the dissolution of AgNPs. However, once oxygen was removed, the highest dissolved Ag (Ag dis ) concentration decreased from 356.5 μg/L to 272.1 μg/L, the pH of the AgNP suspensions increased from less than 7.6 to more than 8.4, and AgNPs were regenerated by the reduction of released Ag + by citrate. The addition of NOM mitigated aggregation, inhibited oxidative dissolution and induced the transformation of AgNPs into Ag 2 S due to the formation of NOM-adsorbed layers, the reduction of Ag + by NOM, and the high affinity of sulfur-enriched species in NOM for Ag. Likewise, in oxygen-depleted natural freshwaters, the inhibition of oxidative dissolution was obtained in comparison with oxygenated freshwaters, showing a decrease in the maximum Ag dis concentration from 137.6 and 57.0 μg/L to 83.3 and 42.4 μg/L from two natural freshwater sites. Our results suggested that aggregation and dissolution of AgNPs in aquatic environments depend on the chemical composition, where oxygen-depleted freshwaters more significantly increase the colloidal stability. In comparison with oxic conditions, anoxic conditions were more favorable to the regeneration of AgNPs by reducing species (e.g., citrate and NOM) and enhanced the stability of nanoparticles. This indicates that some AgNPs will be more stable for long periods in oxygen-deprived freshwaters, and pose more serious environmental risks than that in oxygenated freshwaters., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Necrotic cell death is a hallmark feature of ischemic stroke and it may facilitate inflammation by releasing intracellular components after cell-membrane rupture. Previous studies reported that β-caryophyllene (BCP) mitigates cerebral ischemia-reperfusion (I/R) injury, but the underlying mechanism remains unclear. We explored whether BCP exerts a neuroprotective effect in cerebral I/R injury through inhibiting necroptotic cell death and inflammation. Primary neurons with and without BCP (0.2, 1, 5, 25 μM) treatment were exposed to oxygen-glucose deprivation and re-oxygenation (OGD/R). Neuron damage, neuronal death type and mixed lineage kinase domain-like (MLKL) protein expression were assessed 48 h after OGD/R. Furthermore, mice underwent I/R procedures with or without BCP (8, 24, 72 mg/kg, ip.). Neurologic dysfunction, cerebral infarct volumes, cell death, cytokine levels, necroptosis core molecules, and HMGB1-TLR4 signaling were determined at 48 h after I/R. BCP (5 μM) significantly reduced necroptotic neurons and MLKL protein expression following OGD/R. BCP (24, 72 mg/kg, ip.) reduced infarct volumes, neuronal necrosis, receptor-interaction protein kinase-1 (RIPK1), receptor-interaction protein kinase-3 (RIPK3) expression, and MLKL phosphorylation after I/R injury. BCP also decreased high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels. Thus, BCP alleviates ischemic brain damage potentially by inhibiting necroptotic neuronal death and inflammatory response. This study suggests a novel application for BCP as a neuroprotective agent.

Background: To project the impact of partner reduction on preventing new HIV infections among men who have sex with men (MSM) under varying conditions of enhanced HIV testing and treatment (T&T) and condom use in Beijing, China., Methods and Findings: A complex network model was fitted to predict the number of new HIV infections averted from 2014 to 2023 under four scenarios of sexual behavior risk reduction (S)-S1: Male sexual partners decrease (reduced by a random value m from 1-50) while condom use increases (risk constant p is a random value between 0.2 and 1]); S2: Both sexual partners and condom use decrease (m 1, 50; p 1, 1.8); S3: Sexual partners reduce (m 1, 10) while condom use increases or decreases (p 0.2, 1.8); S4: Only MSM with ≥100 male sexual partners reduce their partners (m 1, 50) while condom use increases (p 0.2, 1). HIV prevalence will reach 23.2% by 2023 among Beijing MSM if T&T remains at the 2013 level. The three most influential factors are: T&T coverage; partner reduction (m); and the background risk (p). Under scenarios 1-4 of sexual behavioral changes with enhanced T&T interventions, the cumulative HIV new infections prevented over the 10 years will be 46.8% for S1 (interquartile range [IQR] 32.4%, 60.1%); 29.7% for S2 (IQR 18.0%, 41.4%), 23.2% for S3 (IQR 12.2%, 37.0%) and 11.6% for S4 (IQR 4.0%, 26.6%), respectively. The reproduction number R0 could drop below 1 if there were a substantial reduction of male sexual partners and/or expanded condom use., Conclusion: Partner reduction is a vital factor within HIV combination interventions to reduce HIV incidence among Beijing MSM, with substantial additional benefits derived from condom use. T&T without substantial partner reduction and increased condom use is less promising unless its implementation were extremely (and improbably) efficient.

Human Immunodeficiency Virus (HIV) is able to persist in cellular and/or anatomical viral reservoirs, despite the effective inhibition of virus replication by the antiretroviral therapy (ART). Here we develop a mathematical model to gain some insights of HIV persistence relevant to the lymphocyte recirculation network of immune system and the central nervous system (CNS). Our simulations and analyses illustrate the role of the CNS as a virus reservoir to prevent antiretroviral drugs from penetrating the blood-brain (or blood-testis) barrier, and we examine the long-term impact of this reservoir on the transmissibility of an infected individual. We observe numerically that level of HIV in peripheral blood may not accurately reflect the true mechanisms occurring within other organs.

This work was conducted to prepare β-caryophyllene-hydroxypropyl-β-cyclodextrin inclusion complex (HPβCD/BCP) and investigate its effects and mechanisms on cognitive deficits in vascular dementia (VD) rats. First, HPβCD/BCP was prepared, optimized, characterized, and evaluated. HPβCD/BCP and AM630 were then administered to VD rats to upregulate and downregulate the cannabinoid receptor type 2 (CB2). Results showed that HPβCD/BCP can significantly increase the bioavailability of BCP. Through the Morris water maze test, HPβCD/BCP can attenuate learning and memory deficits in rats. Cerebral blood flow (CBF) monitoring results indicated that HPβCD/BCP can promote the recovery of CBF. Moreover, molecular biology experiments showed that HPβCD/BCP can increase the expression levels of CB2 in brain tissues, particularly the hippocampus and white matter tissues, as well as the expression levels of PI3K and Akt. Overall, the findings demonstrated the protective effects of HPβCD/BCP against cognitive deficits induced by chronic cerebral ischemia and suggested the potential of HPβCD/BCP in the therapy of vascular dementia in the future.

Epirubicin (EPI) is one of the most widely used anticarcinogens; however, serious side effects, including cardiomyopathy and congestive heart failure, limit its long‑term administration. To overcome this problem, the HAIYPRH peptide ligand was used with EPI in the synthesis of a HAIYPRH‑EPI conjugate. The anticancer activity and cellular uptake of the conjugate were measured and evaluated. The results of the present study indicated that the cytotoxicity of HAIYPRH‑EPI was correlated with the expression of the cell surface transferrin receptor (TfR). The conjugate exerted high cytotoxicity and proapoptotic function when in an LN229 glioma cell line, which overexpresses surface TfR. It was hypothesized that transferrin (Tf) can promote cytotoxicity. Conversely, the conjugate exhibited very low cytotoxicity and proapoptotic function in a U87 glioma cell line, in which surface TfR expression was undetectable. In addition, fluorescence microscopy and flow cytometry methods were used to evaluate cellular uptake, and the results of these methods were consistent with the present hypotheses. The conjugate cellular uptake of the conjugate in LN229 cells was markedly higher compared with that in U87 cells, and it was hypothesized that Tf can enhance the uptake in LN229 cells. The cytotoxicity of HAIYPRH‑EPI was dependent upon the expression of surface TfR. Considering that the majority of cancer cells have high rates of iron uptake and surface TfR is generally overexpressed on cancer cells, it was speculated by the authors that HAIYPRH‑EPI may form part of an effective strategy for increasing the selectivity of EPI for cancer cells, as well as reducing its systemic toxicity. To confirm the hypothesis, the effects of HAIYPRH‑EPI on non‑cancerous cell lines were investigated. A future study will examine the side effects of HAIYPRH‑EPI, using a suitable delivery system in an animal model.

Versicolols A and B (1 and 2), two rare prenylated isocoumarin derivatives, along with five known isocoumarins (3-7) were isolated from the fermentation products of an endophytic fungus Aspergillus versicolor. Their structures were elucidated on the basis of extensive spectroscopic analysis, including 1D- and 2D-NMR techniques. Compounds 1 and 2 were evaluated for their cytotoxicity against five human tumor cell lines. The results showed that compounds 1 exhibited weak cytotoxicity against A549 and MCF7 cells with IC 50 values of 9.4 and 8.8 μm, and compound 2 exhibited weak cytotoxicity against SHSY5Y and MCF7 cells with IC 50 values of 8.2 and 6.8 μm, respectively.

Objective: To study subtype classification of gastric neuroendocrine neoplasm (NEN) and their clinicopathological characteristics in order to provide reference for clinical practice., Methods: Clinicopathological data of 241 gastric NEN patients (174 cases from China-Japan Friendship Hospital and 67 cases from The First Affiliated Hospital of Sun Yat-Sen University) between January 2011 and June 2016 were retrospectively summarized. According to serum gastrin, 24-hour intragastric pH monitoring and pathological grade, patients with gastric NEN were divided into 4 types: type I( (hypergastrinemia and achlorhydria, related to autoimmune chronic atrophic gastritis), type II( [hypergastrinemia and Zollinger-Ellison syndrome, related to gastrinoma or multiple endocrine neoplasia type I( (MEN-I()], type III( (sporadic disease with normal serum gastrin level), and type IIII( [poorly differentiated gastric neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC)]. Clinicopathological features, treatment and prognosis of 4 types were analyzed., Results: Of 241 gastric NEN cases, there were 86 cases (35.7%) in type I(, 7 cases (2.9%) in type II(, 61 cases (25.3%) in type III( and 87 cases(36.1%) in type IIII(. Among 86 cases of type I( gastric NEN, 73 cases (84.9%) were multiple lesions,tumor size of 66 cases (76.7%) was less than 1 cm, all the 86 cases were polypoid or granular lesions. 2 cases(2.3%)presented distant metastasis, 69 cases (80.2%) had pathological grading as NET G1; most of them received endoscopic surgery treatment and follow-up; somatostatin analogs(SSA) was used in patients with multiple lesions and repeated recurrence after endoscopic treatment. Among 7 cases of type II(, 4 cases were gastrinoma, 3 cases MEN-I(; 5 cases presented distant metastasis; treatment included surgery, SSA and proton pump inhibitor (PPI) therapy. Among 61 cases of type III( gastric NEN, 49 cases(80.3%) were single lesion,tumor size of 25 cases(41.0%) was more than 2 cm, 29 cases(47.5%) had lymph node metastasis or distant metastasis; treatment included endoscopic resection, surgery or SSA therapy according to the tumor staging. Among 87 patients of type IIII( gastric NEN, 74 cases(85.0%) had single lesion,tumor size of 51 cases (58.6%) was more than 2 cm; lesions were found in gastric cardia in 35 cases (40.2%); 65 cases (74.7%) had lymph node metastasis or distant metastasis; treatment included chemotherapy, or surgery plus chemotherapy. At the end of follow-up(June 30, 2016), 58 patients were dead, including 1 case of type I(, 12 cases of type III( and 45 cases of type IIII(. The overall survival rate of all the patients was 74.2%, and was 98.8%, 100%, 79.3%, 39.2% of types I(, II(, III(, IIII( respectively. The overall survival rate between type III( and type IIII( gastric NEN was significantly different(P = 0.000)., Conclusions: Subtype classification of gastric NEN is very significant for making therapeutic decisions and prognostic evaluation. Patients of type I( or type II( gastric NEN have good prognosis,while those of type III( and type IIII( have poor prognosis, and those of type IIII( have the worst prognosis.

This study aims to explore the use of postoperative autogenous shed blood reinfusion using Orthopedic Perioperative Autotransfusion System (OrthoPAT) system in treating patients undergoing unilateral total knee arthroplasty (TKA). Fifty patients undergoing unilateral TKA were enrolled as the experimental group A and were treated with reinfusion of autologous shed blood within 6 hours after unilateral TKA using OrthoPAT. Accordingly, 50 patients undergoing unilateral TKA were selected as the experimental group B and were treated with allogeneic blood transfusion. Different indexes were observed at different times. Patients in both groups had relatively stable hemodynamics, and there was no postoperative coagulopathy. Prothrombin time, thrombin time, and activated partial thromboplastin time were lower, and fibrinogen was higher in group A than that in group B 24 hours after surgery (all P < 0.05). White blood cell, red blood cell, hemoglobin, hematocrit (Hct), and platelet count levels in group A were lower than those in group B 12 hours after surgery (all P < 0.05). The postoperative complications of the 2 groups have significant difference (P < 0.05). Postoperative autogenous shed blood reinfusion using OrthoPAT system in the treatment of patients undergoing unilateral TKA may improve the coagulation function of patients and reduce the rejection caused by standard allogeneic blood transfusion.

The role of type III transforming growth factor-β receptor (TβRIII) in the pathogenesis of heart diseases remains largely unclear. Here, we investigated the functional role and molecular mechanisms of TβRIII in the development of myocardial hypertrophy. Western blot and quantitative real time-polymerase chain reaction analyses revealed that the expression of TβRIII was significantly elevated in human cardiac hypertrophic samples. Consistently, TβRIII expression was substantially increased in transverse aortic constriction (TAC)- and isoproterenol-induced mouse cardiac hypertrophy in vivo and in isoproterenol-induced cardiomyocyte hypertrophy in vitro. Overexpression of TβRIII resulted in cardiomyocyte hypertrophy, whereas isoproterenol-induced cardiomyocyte hypertrophy was greatly attenuated by knockdown of TβRIII in vitro. Cardiac-specific transgenic expression of TβRIII independently led to cardiac hypertrophy in mice, which was further aggravated by isoproterenol and TAC treatment. Cardiac contractile function of the mice was not altered in TβRIII transgenic mice; however, TAC led to significantly decreased cardiac contractile function in TβRIII transgenic mice compared with control mice. Conversely, isoproterenol- and TAC-induced cardiac hypertrophy and TAC-induced cardiac contractile function impairment were partially reversed by suppression of TβRIII in vivo. Our data suggest that TβRIII mediates stress-induced cardiac hypertrophy through activation of Ca(2+)/calmodulin-dependent protein kinase II, which requires a physical interaction of β-arrestin2 with both TβRIII and calmodulin-dependent protein kinase II. Our findings indicate that stress-induced increase in TβRIII expression results in cardiac hypertrophy through β-arrestin2-dependent activation of calmodulin-dependent protein kinase II and that transforming growth factor-β and β-adrenergic receptor signaling are not involved in spontaneous cardiac hypertrophy in cardiac-specific transgenic expression of TβRIII mice. Our findings may provide a novel target for control of myocardial hypertrophy., (© 2016 American Heart Association, Inc.)

This study aimed to identify the effect of β-caryophyllene (BCP) pretreatment and elucidate the Nrf2/HO-1 signaling mechanism after focal cerebral ischemia-reperfusion (I-R) injury in rats. Adult male Sprague-Dawley rats were randomly assigned to the sham-operated group, I-R group and BCP pretreated I-R group. At 24 h after reperfusion, neurological deficits and infarct volume were evaluated. Pathological changes of neuron in hippocampuses were observed by Nissil staining and transmission electron microscopy (TEM). Oxidative stress was assessed by malondialdehyde (MDA) level, lipid peroxidation (LPO), nitric oxide (NO), superoxide dismutase (SOD) and Catalase (CAT) activity. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were analysed by Western blotting and real-time quantitative polymerase chain reaction (Q-PCR). The protein expression of Bcl-2 and Bax was determined by immunohistochemistry. Apoptotic cells were detected using TUNEL staining. In I-R group, neurological deficit scores, cerebral infarct volume, MDA levels, LPO content, NO level, expression of Bax and TUNEL-positive cells were found to be increased at 24 h after I-R injury, while SOD activity, CAT activity and expression of Bcl-2 were decreased. However, results in the BCP pretreatment groups were reversed. And the protein and mRNA expressions of Nrf2 and HO-1 were significantly up-regulated in the BCP pretreated I-R group. Results of Nissil staining and TEM scan manifested that BCP remarkablely improved neuronal injury after I-R in rats. All the above suggested that BCP pretreatment played a neuroprotective role in cerebral I-R injury, which might be exerted by upregulating the expression of Nrf2 and HO-1 to ameliorate oxidative damage and neuronal apoptosis.

Recent studies suggest that the epithelial sodium channel (ENaC) is expressed in the endothelial cells. To test whether high salt affects the NO production via regulation of endothelial ENaC, human umbilical vein endothelial cells (HUVECs) were incubated in solutions containing either normal or high sodium (additional 20 mM NaCl). Our data showed that high sodium treatment significantly increased α-, β-, and γ-ENaC expression levels in HUVECs. Using the cell-attached patch-clamp technique, we demonstrated that high sodium treatment significantly increased ENaC open probability (P O ). Moreover, nitric oxide synthase (eNOS) phosphorylation (Ser 1177) levels and NO production were significantly decreased by high sodium in HUVECs; the effects of high sodium on eNOS phosphorylation and NO production were inhibited by a specific ENaC blocker, amiloride. Our results showed that high sodium decreased AMP-activated kinase (AMPK) phosphorylation in endothelial cells. On the other hand, metformin, an AMPK activator, prevented high sodium-induced upregulation of ENaC expression and P O . Moreover, metformin prevented high salt-induced decrease in NO production and eNOS phosphorylation. These results suggest that high sodium stimulates ENaC activation by negatively modulating AMPK activity, thereby leading to reduction in eNOS activity and NO production in endothelial cells.

The objective of this study was to investigate the formation of different nitrosamines during chlorination or chloramination (chlor(am)ination) of five phenylurea herbicides (fluometuron, diuron, linuron, metobromuron, and propanil), with the effects of disinfection approaches, additional inorganic nitrogen, and reaction pH being studied. By analyzing six nitrosamines, N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR) formation was observed. The dimethylamine functional group was the key to determining whether a particular phenylurea herbicide was an important nitrosamine precursor, as the NDMA conversion ratio was much higher. Chlorination with ammonium or dichloramination enhanced the NDMA formation. NPYR formation from the herbicides that did not form NDMA was detected and was more vigorous during dichloramination or in the presence of either ammonium or nitrite. The NPYR formation was possibly related to the aniline molecular fragment from the phenylurea herbicides. Both NDMA and NPYR formation were higher at pH 8. Overall, the maximum nitrosamine conversions decreased in the order: fluometuron > diuron > propanil > metobromuron > linuron (up to 0.99%, 0.46%, 0.005%, 0.004%, and 0.003% molar conversion rates, respectively) during chlorination or chloramination and dichloramine > free chlorine > monochloramine (up to 0.99%, 0.41%, and 0.005% molar conversion rates, respectively) for given herbicide, chlorine, and nitrogen doses. Applying the results of this study, phenylurea herbicide concentrations ranging from several to tens of μg L(-1) will yield a NDMA concentration in drinking water above the level for a theoretical 10(-6) lifetime cancer risk. NPYR formation will increase the risk of these phenylurea herbicide concentrations to downstream water users. The true adverse environmental impacts of these phenylurea herbicides are important to emphasize given their high loadings as non-point source pollutants and their typical environmental scenarios (e.g., at neutral pH or with the co-occurrence of inorganic nitrogen), likely resulting in more efficient nitrosamine formation.

A phytochemical investigation on the stems of Garcinia bracteata collected from Xishuangbanna resulted in the isolation of a new flavone. By analysis of the HRESIMS, IR, UV, 1D and 2D NMR spectra, the structure of the new compound was determined as 7-methoxy-4',6-dihydroxy-8-isobutyryl-flavone(1). Compound 1 was also tested for its anti-tobacco mosaic virus(TMV) activity. Results suggested the 1 possessed remarkable anti-TMV activity, with an inhibition rate of 28.2%.

A rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of ribavirin, sofosbuvir and its metabolite GS-331007 in rat plasma was established. The analytes and the internal standard (midazolam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1mm×50mm, 1.7μm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 245.1→113.1 for ribavirin, m/z 530.3→243.1 for sofosbuvir, m/z 261.5→113.1 for GS-331007 and m/z 326.2→291.1 for midazolam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 5-1000ng/mL for ribavirin, 10-2000ng/mL for sofosbuvir and 10-2000ng/mL for GS-331007. Total time for each chromatograph was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD) <10.0% and the accuracy values ranged from -10.6% to 11.6%. The method was successfully applied to a pharmacokinetic study of ribavirin, sofosbuvir and GS-331007 in rats., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A new phenylpropanoid (1), together with seven known ones (2-8), has been isolated from the flowers of Rosa rugosa collected from Shanxi province by using various chromatographic techniques. Compound 1 is a new compound, and it displayed cytotoxicity against NB4, SH-SY5Y, PC3, A549 and MCF7 cell lines with IC₅₀ values of 8.2, 6.2, 4.3, 2.8, and 9.6 µmol · L⁻¹ respectively.

Background and Purpose: The molecular identity of calcium-activated chloride channels (CaCCs) in vascular endothelial cells remains unknown. This study sought to identify whether anoctamin-1 (Ano1, also known as TMEM16A) functions as a CaCC and whether hypoxia alters the biophysical properties of Ano1 in mouse cardiac vascular endothelial cells (CVECs)., Experimental Approach: Western blot, quantitative real-time PCR, confocal imaging analysis and patch-clamp analysis combined with pharmacological approaches were used to determine whether Ano1 was expressed and functioned as CaCC in CVECs., Key Results: Ano1 was expressed in CVECs. The biophysical properties of the current generated in the CVECs, including the Ca(2+) and voltage dependence, outward rectification, anion selectivity and the pharmacological profile, are similar to those described for CaCCs. The density of ICl ( C a) detected in CVECs was significantly inhibited by T16Ainh -A01, an Ano1 inhibitor, and a pore-targeting, specific anti-Ano1 antibody, and was markedly decreased in Ano1 gene knockdown CVECs. The density of ICl ( C a) was significantly potentiated in CVECs exposed to hypoxia, and this hypoxia-induced increase in the density of ICl ( C a) was inhibited by T16Ainh -A01 or anti-Ano1 antibody. Hypoxia also increased the current density of ICl ( C a) in Ano1 gene knockdown CVECs., Conclusions and Implications: Ano1 formed CaCC in CVECs of neonatal mice. Hypoxia enhances Ano1-mediated ICl ( C a) density via increasing its expression, altering the ratio of its splicing variants, sensitivity to membrane voltage and to Ca(2+) . Ano1 may play a role in the pathophysiological processes during ischaemia in heart, and therefore, Ano1 might be a potential therapeutic target to prevent ischaemic damage., (© 2014 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.)

This study aimed to optimize and evaluate a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles (Cur-BSA-NPs-Gel). Albumin nanoparticles were prepared via a desolvation method, and the gels were prepared via a cold method. The central composite design and response surface method was used to evaluate the effects of varying Pluronic F127 and Pluronic F68 concentrations on the sol-gel transition temperature, which is an indicator of optimum formulations. The optimized formulation was a free-flowing liquid below 30.9°C that transformed into a semi-solid gel above 34.2°C after dilution with simulated tear fluid. Results of the in vitro release and erosion behavior study indicated that Cur-BSA-NPs-Gel achieved superior sustained-release effects and that incorporation of albumin nanoparticles exerted minimal effects on the gel structure. In addition, in vivo ophthalmic experiments employing Cur-BSA-NPs-Gel were subsequently performed in rabbits. In vivo eye irritation results showed that Cur-BSA-NPs-Gel might be considered safe for ophthalmic drug delivery. The in vivo study also revealed that the formulation could significantly increase curcumin bioavailability in the aqueous humor. In conclusion, the optimized in situ gel formulation developed in this work has significant potential for ocular application.

Objective: To project the HIV/AIDS epidemics among men who have sex with men (MSM) under different combinations of HIV testing and linkage to care (TLC) interventions including antiretroviral therapy (ART) in Beijing, China., Design: Mathematical modeling., Methods: Using a mathematical model to fit prevalence estimates from 2000-2010, we projected trends in HIV prevalence and incidence during 2011-2020 under five scenarios: (S1) current intervention levels by averaging 2000-2010 coverage; (S2) increased ART coverage with current TLC; (S3) increased TLC/ART coverage; (S4) increased condom use; and (S5) increased TLC/ART plus increased condom use., Results: The basic reproduction number based upon the current level of interventions is significantly higher than 1 (R0 = 2.09; 95% confidence interval (CI), 1.83-2.35), suggesting that the HIV epidemic will continue to increase to 2020. Compared to the 2010 prevalence of 7.8%, the projected HIV prevalence in 2020 for the five prevention scenarios will be: (S1) Current coverage: 21.4% (95% CI, 9.9-31.7%); (S2) Increased ART: 19.9% (95% CI, 9.9-28.4%); (S3) Increased TLC/ART: 14.5% (95% CI, 7.0-23.8%); (S4) Increased condom use: 13.0% (95% CI, 9.8-28.4%); and (S5) Increased TLC/ART and condom use: 8.7% (95% CI, 5.4-11.5%). HIV epidemic will continue to rise (R0 > 1) for S1-S4 even with hyperbolic coverage in the sensitivity analysis, and is expected to decline (R0 = 0.93) for S5., Conclusion: Our transmission model suggests that Beijing MSM will have a rapidly rising HIV epidemic. Even enhanced levels of TLC/ART will not interrupt epidemic expansion, despite optimistic assumptions for coverage. Promoting condom use is a crucial component of combination interventions.

This study focused on reducing the haloacetic acid (HAA) concentrations in treated drinking water. HAA has been thought to be one possible nutrient supporting heterotrophic bacteria regrowth in drinking water. In this study, experiments were conducted using a pilot-scale system to evaluate the efficiency of biological filters (BF) for reducing excess HAA concentrations in water. The BF system reduced the total HAA concentration and the concentrations of five HAA species in the water. Dichloroacetic acid (DCAA), monobromoacetic acid (MBAA) and dibromoacetic acid (DBAA) were the three main HAA5 species that were present in the treated drinking water in this investigation. Combined, these three species represent approximately 77% of the HAA5 in the finished water after BF. The verification of the empirical HAA equation for the outlet in the BF system indicated linear relationships with high correlation coefficients. The empirical equation for the HAA5 concentrations in the finished water was established by examining other nutrients (e.g., dissolved organic carbon (DOC), ultraviolet absorbance at 254 nm wavelength (UV254), and ammonia nitrogen) that can reduce pathogenic contamination. These findings may be useful for designing advanced processes for conventional water treatment plants or for managing water treatment and distribution systems for providing high-quality drinking water.

Aim: To investigate H2B monoubiquitination (uH2B) and H3K4 di- and tri-methylation (H3K4-2me, H3K4-3me) levels and their clinical significance in gastric cancer (GC)., Methods: Immunohistochemistry (IGC) was used to detect the differential levels of uH2B, H3K4-2me and H3K4-3me modifications in GC specimens from chemo/radiotherapy-naïve patients who underwent potentially curative surgical resection (n = 159) and in a random sampling of non-tumor gastric epithelium specimens (normal controls, n = 20). The immunohistochemistry (IHC)-detected modifications were classified as negative, low-level, or high-level using a dual-rated (staining intensity and percentage of positively-stained cells) semi-quantitative method. The relationships between uH2B modification levels and clinicopathological parameters of GC were assessed by a Wilcoxon rank sum test (pairwise comparisons) and the Kruskal-Wallis H test (multiple comparisons). The correlation between uH2B modification and survival was estimated by Kaplan-Meier analysis, and the role of uH2B as an independent prognostic factor for survival was assessed by multivariate Cox regression analysis., Results: The presence and level of H3K4-2me and H3K4-3me IHC staining was similar between the normal controls and GC specimens. In contrast, the level of uH2B was significantly lower in the malignant gastric tissues (vs normal control tissues) and decreased along with increases in dedifferentiation (well differentiated > moderately differentiated > poorly differentiated). The level of uH2B correlated with tumor differentiation (P < 0.001), Lauren's diffuse- and intestinal-type classification (P < 0.001), lymph node metastasis (P = 0.049) and tumor-node-metastasis stage (P = 0.005). Patients with uH2B+ staining had higher 5-year survival rates than patients with uH2B-staining (52.692 ± 2.452 vs 23.739 ± 5.207, P < 0.001). The uH2B level was an independent prognostic factor for cancer-specific survival (95%CI: 0.237-0.677, P = 0.001)., Conclusion: uH2B displays differential IHC staining patterns corresponding to progressive stages of GC. uH2B may contribute to tumorigenesis and could be a potential therapeutic target.

A set of deterministic SIS models with density-dependent treatments are studied to understand the disease dynamics when different treatment strategies are applied. Qualitative analyses are carried out in terms of general treatment functions. It has become customary that a backward bifurcation leads to bistable dynamics. However, this study finds that finds that bistability may not be an option at all; the disease-free equilibrium could be globally stable when there is a backward bifurcation. Furthermore, when a backward bifurcation occurs, the fashion of bistability could be the coexistence of either dual stable equilibria or the disease-free equilibrium and a stable limit cycle. We also extend the formula for mean infection period from density-independent treatments to density-dependent ones. Finally, the modeling results are applied to the transmission of gonorrhea in China, suggesting that these gonorrhea patients may not seek medical treatments in a timely manner.

In this paper, two mathematical models, the baseline model and the intervention model, are proposed to study the transmission dynamics of echinococcus. A global forward bifurcation completely characterizes the dynamical behavior of the baseline model. That is, when the basic reproductive number is less than one, the disease-free equilibrium is asymptotically globally stable; when the number is greater than one, the endemic equilibrium is asymptotically globally stable. For the intervention model, however, the basic reproduction number alone is not enough to describe the dynamics, particularly for the case where the basic reproductive number is less then one. The emergence of a backward bifurcation enriches the dynamical behavior of the model. Applying these mathematical models to Qinghai Province, China, we found that the infection of echinococcus is in an endemic state. Furthermore, the model appears to be supportive of human interventions in order to change the landscape of echinococcus infection in this region.

The purposes of this paper are twofold: to develop a rigorous approach to analyze the threshold behaviors of nonlinear virus dynamics models with impulsive drug effects and to examine the feasibility of virus clearance following the Manuals of National AIDS Free Antiviral Treatment in China. An impulsive system of differential equations is developed to describe the within-host virus dynamics of both wild-type and drug-resistant strains when a combination of antiretroviral drugs is used to induce instantaneous drug effects at a sequence of dosing times equally spaced while drug concentrations decay exponentially after the dosing time. Threshold parameters are derived using the basic reproduction number of periodic epidemic models, and are used to depict virus clearance/persistence scenarios using the theory of asymptotic periodic systems and the persistence theory of discrete dynamical systems. Numerical simulations using model systems parametrized in terms of the antiretroviral therapy recommended in the aforementioned Manuals illustrate the theoretical threshold virus dynamics, and examine conditions under which the impulsive antiretroviral therapy leads to treatment success. In particular, our results show that only the drug-resistant strain can dominate (the first-line treatment program guided by the Manuals) or both strains may be rapidly eliminated (the second-line treatment program), thus the work indicates the importance of implementing the second-line treatment program as soon as possible.

Stability of drinking water can be indicated by the assimilable organic carbon (AOC). This AOC value represents the regrowth capacity of microorganisms and has large impacts on the quality of drinking water in a distribution system. With respect to the effectiveness of traditional and advanced processing methods in removing trace organic compounds (including TOC, DOC, UV(254), and AOC) from water, experimental results indicate that the removal rate of AOC at the Cheng Ching Lake water treatment plant (which utilizes advanced water treatment processes, and is hereinafter referred to as CCLWTP) is 54%, while the removal rate of AOC at the Gong Yuan water treatment plant (which uses traditional water treatment processes, and is hereinafter referred to as GYWTP) is 36%. In advanced water treatment units, new coagulation-sedimentation processes, rapid filters, and biological activated carbon filters can effectively remove AOC, total organic carbon (TOC), and dissolved organic carbon (DOC). In traditional water treatment units, coagulation-sedimentation processes are most effective in removing AOC. Simulation results and calculations made using the AutoNet method indicate that TOC, TDS, NH(3)-N, and NO(3)-N should be regularly monitored in the CCLWTP, and that TOC, temperature, and NH(3)-N should be regularly monitored in the GYWTP.

This study investigates the microorganism growth indicator and determines the assimilable organic carbon (AOC) content at the Cheng-Ching Lake Advanced Water Treatment Plant (CCLAWTP) in Kaohsiung, Taiwan. Notably, AOC is associated with the biological stability within the water distribution network and has garnered considerable attention in the environmental engineering field in recent years. Water samples were collected from the effluent of each unit in CCLAWTP once monthly during December 2008 to November 2009. Items of water quality related to carbon concentration levels, including AOC, total organic carbon, dissolved organic carbon, UV(254), and specific ultraviolent absorbance were analyzed. Analytical results demonstrate that the average AOC concentration in raw water was 83.61 μg/L and reduced in freshwater was controlled at an average of 50 μg/L after an advanced treatment system of roughly 54% of AOC was removed in compliance with treatment plant standards. If AOC concentrations in freshwater can be reduced, study results can provide a direction for improving water treatment capabilities.

Recently, the first drug in a new class of antiretroviral HIV drugs was approved, the fusion inhibitor enfuvirtide. We develop a mathematical model that describes the binding of the virus to T cells. We model the effect of enfuvirtide upon this process using impulsive differential equations. We find equilibria and determine stability in the case of no therapy and then when therapy is taken with perfect adherence. We determine analytical thresholds for the dosage and dosing intervals to ensure the disease-free equilibrium remains stable. We also explore the effects of partial adherence. Our theoretical results suggest that partial adherence may, at times, be worse than no therapy at all, but at other times may in fact as good as perfect adherence. It follows that patients should be counselled on the importance of adherence to this new antiretroviral drug., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

This work prepares molecular sieve catalysts with various metal species and various metal weight loadings by impregnation, and then screens them in a catalytic combustion system. The current study further investigates the molecular sieve catalyst in an RCO system after it performed well in combustion efficiency. This work tests its performances in terms of CO(2) yield, pressure drop, the difference between temperatures of the inlet and outlet gases (T(d)), and thermal recovery efficiency (TRE), with various operational conditions. Experimental results demonstrate that the 10 wt% Cu/(MS) catalyst was the most active because it has the greatest combustion efficiency to treat volatile organic compounds (VOCs) than Co/(MS) catalysts and Mn/(MS) catalysts. The 10 wt% Cu/(MS) catalyst used in an RCO system reaches over 95% CO(2) yields under the heating zone temperature (T(set))=400°C, gas velocity (U(g))=0.37 m/s, isopropyl alcohol (IPA) concentration=200-400 ppm conditions. Moreover, the RCO system performed well in economic efficiency with the RCO with in terms of TRE, T(d) and pressure drop. The TRE ranged from 90.4% to 94.6% and T(d) ranged from 14.0 to 34.2°C under various conditions at T(set)=300-450°C. Finally, the results of the stability test demonstrated that the catalyst was very stable at various U(g) values and various T(set) values., (Copyright © 2010 Elsevier B.V. All rights reserved.)

A sampling program was conducted to investigate the formation of disinfection by-products (DBPs) and dissolved organic carbon (DOC) at two advanced water treatment plants in Kaohsiung City, Taiwan. The results in this study can be used as a reference for the operational control of water treatment plants and the setting of regulations in Taiwan. Samples of drinking water were collected from two advanced water treatment plants from June 2007 to April 2008. Changes in the concentration of dissolved organic carbon, the trihalomethane formation potential, and the haloacetic acids formation potential were measured in raw water samples. Variations in the concentrations of trihalomethanes (THMs) and haloacetic acids (HAA(5)) in finished drinking water were evaluated. The major species of HAA(5) were in the order of dichloroacetic acid and trichloroacetic acid and the THM was of trichloromethane. DOC was strongly related to DBPs in raw water. In this investigation, the removal efficiency of DBPs in Plant A (ultrafiltration/reverse osmosis system) exceeded that in Plant B (ozonation/biological activated carbon system). Both advanced water treatment plants greatly improved the quality of drinking water.

The purpose of this work is to investigate an advanced water treatment system changes on disinfects by-products (DBPs) precursors removal efficiencies of treatment plant and associated trihalomethanes (THMs) and haloacetic acids (HAA(5)) formation and assimilable organic carbon (AOC) in reduction from raw water through finished water of Fong-shan Water Treatment Plant (FSWTP) in Kaohsiung City, Taiwan. Drinking water samples were collected from an advanced water treatment plant during March-October 2008. In the formation of DBPs, advanced water treatment processes efficiently removed THMs and HAA(5). The concentrations of THMs and HAA(5) in finished water were reduced to 13.97 microg/L and 17.67 microg/L, respectively. In this investigation, the AOC was reduced effectively by ozonation and biological activated carbon (BAC) processes. Experimental results of this 6-month investigation indicate that AOC concentrations in the finished water can meet the WTP criterion of 50 microg acetate-C/L in the world. Results of this study provide a valuable reference for solving DBPs and AOC control of water treatment plants and the setting of regulations in Taiwan.

Printed circuit board wastewater typically contains organics and metal ions. The study explored the feasibility of a sequential procedure, FFP (the combination of the Fenton method and the Ferrite process), for treating printed circuit board wastewater, and established the optimum parameters for it. The analytical results showed that the proper pH level was 2 for Fenton oxidation, and the appropriate H2O2 dosing type was batch dosing. For the Ferrite process, the suitable Fe/M (Fe is the total dose of Fe2+ added to a solution and M is the initial total moles of various metal ions in untreated wastewater) molar ratio was 10 and the sludge met the toxicity characteristic leaching procedure (TCLP) standards. Following FFP treatment, effluent water or sludge easily met Taiwan's standards. Finally, the SEM/EDS test demonstrated that particle sizes of the sludge were approximately 50-80 nm, and the saturation magnetization was 67.5 emu/g.

Industrial wastewater typically contains various metal ions. Traditional metal ion treatment processes such as chemical precipitation generate large volumes of toxic sludge which needs to be further solidified or disposed of. The ferrite process (FP), which is another effective approach of treating metal ion-containing wastewater, can crystallize metal ions into ferrites; the sludge easily precipitates, is stable and can be recycling. This investigation explores the feasibility of the Fenton process and the FP (FFP) for treating wastewater that contains metal ions. It considers one factor that adds noise to the FP, ethylenediaminetetraacetic acid, and establishes the optimum parameters of each procedure. The analytical results demonstrate that the proper conditions for Fenton process were pH = 2, [Fe(2+)] = 10(-2) M, H(2)O(2) dosing rate = 5 x 10(-4) mol min(-1), reaction time = 12 min. For the proposed multi-stage FP, the preferred Fe(2+) dosage was 0.098 mol in each stage and the sludge met the toxicity characteristic leaching procedure standards. Following the FFP, the effluent water or the sludge easily met Taiwan's standards. Finally, the SEM test demonstrated that size of the sludge particles was 50-110 nm.

Wastewater reuse can significantly reduce environmental pollution and save the water sources. The study selected Cheng-Ching Lake water treatment plant in southern Taiwan to discuss the feasibility of wastewater recycling and treatment efficiency of wastewater treatment units. The treatment units of this plant include wastewater basin, sedimentation basin, sludge thickener and sludge dewatering facility. In this study, the treatment efficiency of SS and turbidity were 48.35-99.68% and 24.15-99.36%, respectively, showing the significant removal efficiency of the wastewater process. However, the removal efficiencies of NH(3)-N, total organic carbon (TOC) and chemical oxygen demand (COD) are limited by wastewater treatment processes. Because NH(3)-N, TOC and COD of the mixing supernatant and raw water are regulated raw water quality standards, supernatant reuse is feasible and workable during wastewater processes at this plant. Overall, analytical results indicated that supernatant reuse is feasible.

We study the three-dimensional XY model with a Zq anisotropic term. At temperatures T

This investigation conducted a full-scale survey the drinking water distribution system in Kaohsiung city, Taiwan. The aim was to investigate whether the distribution system was capable of maintaining high water quality from the water treatment facilities through to the end user. The results showed that the distribution system can maintain high water quality, except for suitable chlorine residuals. The authors plotted chlorine residual contour maps to identify areas with low chlorine residuals, helping them prioritize sections that must be flushed or renewal. The contour maps also provide sufficient and clear information for locating booster chlorination stations. Contour maps enable water facilities to identify how water quality decays in the distribution systems and the locations of such decay. Water quality decay can be caused by properties of pipeline materials, hydraulic conditions, and/or biofilm thickness. However, understanding the exact reasons is unnecessary because the contour maps provide sufficient information for trouble-shooting the distribution systems.