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In coal mines, process management is related with planning and flow of coal minerals from their mining points to journey’s end. The process is dependent on the operational decisions, which should be completed during coal production. In these systems, simulation modelling is assumed a powerful tool for decision making. The simulation modelling can further be enhanced through applying artificial intelligence (AI) and machine learning (ML) methods. The communication of water with clay minerals upholds the water adsorption on the clay surface, which makes them complex systems. Therefore, evading the water absorption from the clay turns out to be a hard job. The computational trainings of clay minerals are needed to comprehend the dynamics of water distribution. Tradition of coal slurry treatment is completed by adding medicament of its mineral flocculation sedimentation. As a result of coal, slime water contains a lot of clay minerals that are rich in kaolinite versatility and it is difficult to settle. The flotation will be one of the kaolinite recycling. In this paper, clay minerals containing a variety of minerals were taken as samples, and sodium dodecyl sulfate and sodium oleate were used as collectors to explore the flotation effect through test and molecular dynamics simulation. A machine learning based intelligent decision support system is designed to improve the outputs of the simulation model. The results show that when the pH value is 8 and the amount of collector and sec-octanol are 150 g/t and 250 g/t, respectively, the flotation rate of fine mineral can reach 63.25%. According to the molecular dynamics simulation results, the addition of the collector can reduce the hydrophilicity of the kaolinite surface, and the physical adsorption of SDS only occurs on the (001) surface.

Objective. To explore the association between infections with HIV and Schistosoma japonicum, and to determine the influences of the HIV-S. japonicum coinfections on the immune system of Yi people. Methods. A block design study was conducted in a Yi county in southwestern China, one of the endemic areas of both HIV/AIDS and S. japonicum in China. All participants were screened for HIV antibodies and S. japonicum antibodies (SjAb) and were classified into four groups: HIV(+)/S. japonicum(−), HIV(−)/S. japonicum (+), HIV(+)/S. japonicum(+), and HIV(−)/S. japonicum(−). Results. There were significant differences among the four groups in both CD4+ T lymphocytes and CD8+ T lymphocytes, but no significant difference in CD3+ T lymphocytes. Both the CD4+ T lymphocyte counts and the ratio of CD4+/CD8+ were lower in HIV-infected people compared with those uninfected. People infected with S. japonicum had increased CD4+ T lymphocyte counts but reduced CD8+ T lymphocyte counts. Similarly, the ratio of CD4+/CD8+ was higher in S. japonicum-infected people compared with those uninfected. People coinfected with HIV and S. japonicum had lower CD4+ T lymphocyte counts, lower ratio of CD4+/CD8+, and higher CD8+ T lymphocyte counts compared with those infected with HIV only or S. japonicum only. People infected with HIV only and those coinfected with HIV and S. japonicum had a higher level of IFN-γ compared with people with no infection. There were no significant differences between people infected with HIV only and with S. japonicum only in the levels of IFN-γ and IL-10. Conclusions. People coinfected with HIV and S. japonicum might have a suppressed immune function because of a decrease in CD4+ T lymphocyte counts, a lowered ratio of CD4+/CD8+, and an increase in CD8+ T lymphocyte counts. Coinfection with HIV and S. japonicum would alter the level of IFN-γ in plasma.

Few studies have focused on the epidemiology of Cryptosporidium in resource-challenged settings in China. We report a community-based cross-sectional study to investigate the prevalence of Cryptosporidium infection and its risk factors and associations with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections. The prevalence of Cryptosporidium infection was 12.6% (95% confidence interval = 11.0–14.3). Individuals living in households with ≥ 5 family members and raising domestic pigs tended to have a greater risk of Cryptosporidium infection. In addition, Cryptosporidium infection was significantly associated with HBV infection. There were no significant associations of Cryptosporidium infection with HIV viral load and HBV viral load. Further studies are needed to determine the association of Cryptosporidium infection with HBV infection.

ObjectivesHepatitis C virus (HCV) infection is a major public health problem in southwestern China. Our aim of the study was to assess the prevalence of HCV infection and its correlates in the Yi population of this region.MethodsA community-based survey was conducted to investigate sociodemographic characteristics and other associated factors for HCV infection in a rural area of southwestern China. Blood samples were collected and tested for antibodies to HCV. Anti-HCV positive samples were further assessed for HCV RNA.ResultsA total of 2558 participants aged≥14 years were included in our analysis. Of them, 2.8% (95% CI 2.2% to 3.5%) were positive for HCV antibody. Multiple logistic regression analysis revealed that sex (male vs female: adjusted OR (aOR)=3.30, 95% CI 1.80 to 6.07), marital status (unmarried vs married: aOR=0.27, 95% CI 0.09 to 0.80), ever using injection drug (aOR=28.65, 95% CI 15.9 to 51.64) and ever having blood transfusion (aOR=7.64, 95% CI 1.94 to 30.16) were significantly associated with HCV infection (indicated by positive HCV antibody). Stratified analysis by HIV infection found that in HIV-negative individuals, sex (male vs female: aOR=3.84, 95% CI 1.88 to 7.85), ever using injection drug (aOR=22.15, 95% CI 8.45 to 58.04), having multiple sexual partners (aOR=2.57, 95% CI 1.26 to 5.23), and ever having blood transfusion (aOR=16.54, 95% CI 4.44 to 61.58) were significantly associated with HCV infection and in HIV-positive individuals, ever using injection drug (aOR=8.96, 95% CI 3.16 to 25.38) was associated with HCV infection.ConclusionThe data suggested a higher risk of HCV infection in this area when compared with the rest of China and some unique associated factors. Rapid scale-up of targeted interventions are needed to prevent further transmission and consequent morbidities.

Background Schistosomiasis remains a major public health concern in China. Oncomelania hupensis (O. hupensis) is the sole intermediate host of Schistosoma japonicum, and its change in distribution and density influences the endemic S. japonicum. The Three Gorges Dam (TGD) has substantially changed the downstream water levels of the dam. This study investigated the quantitative relationship between flooding duration and the density of the snail population. Methods Two bottomlands without any control measures for snails were selected in Yueyang City, Hunan Province. Data for the density of the snail population and water level in both spring and autumn were collected for the period 2009–2015. Polynomial regression analysis was applied to explore the relationship between flooding duration and the density of the snail population. Results Data showed a convex relationship between spring snail density and flooding duration of the previous year (adjusted R 2, aR 2 = 0.61). The spring snail density remained low when the flooding duration was fewer than 50 days in the previous year, was the highest when the flooding duration was 123 days, and decreased thereafter. There was a similar convex relationship between autumn snail density and flooding duration of the current year (aR 2 = 0.77). The snail density was low when the flooding duration was fewer than 50 days and was the highest when the flooding duration was 139 days. Conclusions There was a convex relationship between flooding duration and the spring or autumn snail density. The snail density was the highest when flooding lasted about four to 5 months.

Effects of the air injection into a water-only cyclone on the separation performance of the cyclone treating coal in the 1 × 0 mm particle size range were investigated. The results showed that by using air injection the water-only cyclone had a good density separation for the +0.125 mm size fraction and minimized the effects of the particle size. When the gas-liquid ratio increased, the density cut-point decreased, as did the Ecart probable (Ep) value, which could be reduced to 0.05 for the +0.5 mm size fraction. Therefore, the density cut-point of a water-only cyclone can be adjusted in real time by changing the gas-liquid ratio to meet variable market requirements.

Although drug-eluting stents (DES) are successfully utilized for restenosis therapy, the development of local and systemic therapeutic means including nanoparticles (NP) continues. Lack of correlation between in vitro and in vivo studies is one of the major drawbacks in developing new drug delivery systems. The present study was designed to examine the applicability of the arterial explant outgrowth model, and of smooth muscle cells (SMC) cultures for prescreening of possible drugs. Elucidation of different species sensitivity (rat, rabbit, porcine and human) to diverse drugs (tyrphostins, heparin and bisphsophonates) and a delivery system (nanoparticles) could provide a valuable screening tool for further in vivo studies. The anticipated sensitivity ranking from the explant outgrowth model and SMC mitotic rates (porcine>rat>>rabbit>human) do not correlate with the observed relative sensitivity of those animals to antiproliferative therapy in restenosis models (rat≥rabbit>porcine>human). Similarly, the inhibitory profile of the various antirestenotic drugs in SMC cultures (rabbit>porcine>rat>>human) do not correlate with animal studies, the rabbit- and porcine-derived SMC being highly sensitive. The validity of in vitro culture studies for the screening of controlled release delivery systems such as nanoparticles is limited. It is suggested that prescreening studies of possible drug candidates for restenosis therapy should include both SMC cell cultures of rat and human, appropriately designed with a suitable serum.

Background Intestinal helminths do not cause severe diseases in general, however, when combined with other diseases such as immunodeficiency diseases, there would be massive complications. Infections with Hepatitis B Virus (HBV) may lead to immunological disturbances and defects of cellular immunity and there is a need of clarification whether HBV infections are associated with infections with intestinal helminths. Methods A community-based cross sectional study was conducted in Tezi town, Puge County of the Liangshan Prefecture, southwestern China from October 23rd to November 3rd, 2014. Four hundred and thirty eight people (median age = 37 years, IQR = 22–49) were enrolled in this study. Modified Kato-Katz thick smear was used to detect intestinal helminths. HBV DNA was quantified to confirm HBV infection. Results Among the 438 participants, 9.1 %, 13.5 % and 30.6 % were infected with HBV, A. lumbricoides (L., 1758) and T. trichiura (L., 1771), respectively; 7.1 % (30/438) were infected with both A. lumbricoides and T. trichiura and 2.3 % (10/438) were co-infected with HBV and A. lumbricoides. The multivariate logistic regression analysis showed that age (21–30 years versus >50 years: OR = 6.66, 95 % CI = 2.15–20.68), drug abuse (OR = 6.96, 95 % CI = 1.11–43.90), A. lumbricoides infection (OR = 3.60, 95 % CI = 1.48–8.75), fertilization with faeces after disposal (OR = 0.15, 95 % CI = 0.04–0.47) and working on a farm (OR = 4.59, 95 % CI = 1.44–14.63) were significantly associated with HBV infection. Having toilets at home was negatively related to A. lumbricoides infection (OR = 0.52, 95 % CI = 0.27–0.98) and T. trichiura infection (OR = 0.48, 95 % CI = 0.28–0.80). Conclusions Ascaris lumbricoides was independently associated with HBV infection, and faeces might be the medium of HBV transmission. Improving hygiene conditions and habits are essential to reduce the risks of A. lumbricoides and T. trichiura infections.

Erratum to ‘Locally delivered nanoencapsulated tyrphostin (AGL-2043) reduces neointima formation in balloon-injured rat carotid and stented porcine coronary arteries’ [Biomaterials 26 (2005) 451–461] Shmuel Banai, Michael Chorny, S. David Gertz, Ilia Fishbein, Jianchuan Gao, Louise Perez, Galila Lazarovich, Aviv Gazit, Alexander Levitzki, Gershon Golomb Heiden Department of Cardiology, Bikur Cholim Hospital, Jerusalem, Israel Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The HebrewUniversity of Jerusalem, Ein Kerem Box 12065, Jerusalem 91120, Israel Department of Anatomy and Cell Biology, Jerusalem, Israel Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

Local delivery of antiproliferative drugs encapsulated in biodegradable nanoparticles (NP) has shown promise as an experimental strategy for preventing restenosis development. A novel PDGFRbeta-specific tyrphostin, AGL-2043, was formulated in polylactide-based nanoparticles and was administered intraluminally to the wall of balloon-injured rat carotid and stented pig coronary arteries. The disposition and elimination kinetics within the vessel wall, as well as the antirestenotic potential of the novel drug and delivery system, were evaluated. The efficacy and the local drug elimination kinetics were affected by the size of the NP and the drug-carrier binding mode. Despite similar arterial drug levels 90 min after delivery in rats, small NP were more efficacious in comparison to large NP (90 and 160 nm, respectively). AGL-2043 selectively inhibited vascular SMC in a dose-dependent manner. The antiproliferative effect of nanoencapsulated tyrphostin was considerably higher than that of surface-adsorbed drug. In the pig model, intramural delivery of AGL-2043 resulted in reduced in-stent neointima formation in the coronary arteries over control despite similar degrees of wall injury. The results of this study suggest that locally delivered tyrphostin AGL-2043 formulated in biodegradable NP may be applicable for antirestenotic therapy independent of stent design or type of injury.

Background — Inflammation is critical to vascular repair after mechanical injury. Excessive inflammation enhances neointimal formation and restenosis. We examined whether transient systemic inactivation of macrophages at the time of vascular intervention could attenuate the degree of expected restenosis. Methods and Results — Liposomal clodronate (LC) inhibited the growth of cultured macrophages but had no effect on endothelial or smooth muscle cells and suppressed neointimal hyperplasia in hypercholesterolemic rabbits and rats after intravenous administration of LC, with no adverse effects. LC treatment reduced the number of blood monocytes and decreased macrophage infiltration in the injured arteries as well as smooth muscle cell proliferation, interleukin-1β transcription, and production and matrix metalloproteinase-2 activity. Conclusions — Macrophages play a pivotal role in vascular repair after mechanical arterial injury. Systemic inactivation and depletion of monocytes and macrophages by LC reduce neointimal hyperplasia and restenosis.

Arterial restenosis is responsible for the high failure rates of vascular reconstruction procedures. Local sustained drug delivery has shown promise in the prevention of restenosis. The drug release rate from mithramycin-loaded EVA matrices (0.1%) was evaluated, and their antirestenotic effect was studied in the rat carotid model and rabbit model of vascular grafts. The modulation of c-myc expression by mithramycin treatment was examined by immunohistochemistry in the rat carotid model. The proliferative response of injured rat arteries was studied by bromdeoxyuridine (BrdU) immunostaining. The impact of mithramycin treatment on vasomotor responses of the venous segments grafted into arterial circulation was studied ex vivo using vasoreactive compounds. Mithramycin was released exponentially from EVA matrices in PBS. Matrices co-formulated with PEG-4600 revealed enhanced release kinetics. The perivascular implantation of drug-loaded EVA–PEG matrices led to 50% reduction of neointimal formation, and reduced the c-myc expression and BrdU labeling in comparison to control implants. Decreased sensitivity of mithramycin-treated grafts to serotonin-induced vasoconstriction was observed. Local perivascular mithramycin treatment limits the functional alteration caused by the grafting of venous segments in high-pressure arterial environment, and potently inhibits stenosis secondary to grafting and angioplasty injury. The antirestenotic effect is associated with reduced c-myc expression and with subsequent decrease in SMC proliferation.

Poor drug residence in the arterial wall hinders clinical implementation of local drug delivery strategies for the treatment of restenosis. A rat carotid model of vascular injury and intraluminal delivery of tyrphostin-containing polylactic acid (PLA) nanoparticles (NPs) were used to determine the relationship between residence properties and biological activity of different formulations and administration modes. The effects of delivery modes (denudation and delivery time) and formulation variables (adsorbed vs encapsulated drug, and NP size) on arterial drug/NP retention were examined. Antirestenotic effects of large (160 nm) and small (90 nm) tyrphostin-containing NPs, surface-absorbed tyrphostin, and systemic treatment were compared. Fluorescent NPs were used to study the spatial distribution of the carrier in the arterial wall. The decrease in arterial tyrphostin level over time fitted a biexponential model. Delivery time and pressure, endothelium integrity, particle size, and drug-polymer association affected local pharmacokinetics and the antirestenotic results after 14 days. The PLA-based tyrphostin NP formulation ensured a prolonged drug residence at the angioplasty site after single intraluminal application. Several readily adjustable formulation and procedural factors considerably modified arterial ingress of the drug-loaded NPs and governed their subsequent redistribution, tissue binding, elimination, and ensuing antirestenotic effect.

The present study explored a novel strategy for attenuation of restenosis after arterial injury by a bisphosphonate encapsulated in polymeric nanoparticles (NP) for transient selective depletion of macrophages. A bisphosphonate (BP), 2-(2-Aminopyrimidino) ethyldiene-1,1-bisphosphonic acid betaine (ISA), was successfully formulated in 400 nm sized polylactide/glycolide-based NP with high yield (69%) and entrapment efficiency (60% w/w). ISA NP, but not blank NP or free ISA, exhibited specific and significant cytotoxic effect on macrophages-like RAW 264 cells, in a dose-dependent manner, with no inhibitory effect on the growth of smooth muscle cells (SMCs). Fluorescent pyrene-labeled NP were shown to be taken up by RAW 264 cells, but not by SMCs. Intravenously (IV) administered ISA NP (15 mg/kg, single dose on day-1) resulted in a significant attenuation of neointima to media area ratio (N/M) by 40% and stenosis by 45% 14 days after rat carotid injury, in comparison to animals treated with free ISA, buffer or blank NP. However, the effect was not preserved 30 days post injury, and an insignificant reduction of neointimal formation was observed. Neointimal hyperplasia was also significantly suppressed after subcutaneous (SC) injection of ISA NP (15 mg/kg, single dose on day-1), reducing both N/M and stenosis. Intraperitoneal (IP) injection of silica, a known selective toxin for macrophages, (1000 mg/kg), also resulted in a significant inhibition of N/M and stenosis, which further reinforces the cause-effect relationship of macrophage-inactivation and the prevention of neointima formation. Biocompatible and biodegradable NP loaded with ISA characterized by high colloidal stability, reproducible activity, and high drug entrapment warrant further consideration for restenosis therapy, and may be useful in other disease processes involving monocytes/macrophages.

Monocytes/macrophages play a pivotal role in the formation of neointinal hyperplasia following vascular injury. Transient depletion of circulating monocytes by particulate delivery systems containing bisphosphonates, such as alendronate, results in restenosis inhibition. We hypothesized that a self-suspendable nanoparticulate dosage form, with a minimum amount of expients, could be formulated by complexing the negatively charged alendronate with gallium or gadolinium. We further hypothesized that a synergistic biological effect could be obtained by nanosuspensions of alendronate with these counter ions. Nanosuspensions (150-250 nm) of alendronate-gallium and alendronate-gadolinium were successfully formulated with no additives except for the active agents and HCl for pH adjustment. Both nanosuspensions exhibited macrophage cell line growth inhibition in a dose-response relationship in comparison to the various agents in solution and in liposomes. A synergistic effect of the nanosuspensions was observed in the inhibition of raw264 macrophages, and in reducing IL-1beta and TNF-alpha secretion in cell culture. Single IV administration at the time of injury, of alendronate-gallium or alendronate-gadolinium nanosuspensions resulted in inhibition of neointimal hyperplasia and stenosis in the rat model of vascular injury. The results correlated with the significant reduction of circulating monocytes. The nanosuspensions possess the advantages of no additives for minimal provocation of side effects, and the potential of immunomodulating inflammatory disorders.

Systemic transient depletion of monocytes and macrophages by liposome-encapsulated bisphosphonates (BPs), reduces neointimal formation in experimental restenosis. The aim of this study was to examine the antirestenotic effect of a polymeric nanoparticulate formulation containing the BP alendronate (ALN). The BP was successfully formulated in polylactide-co-glycolide (PLGA) nanoparticles (NP). ALN NP with negative charge, size of 223 ± 64 nm, and high entrapment efficiency (55.1%) have been formulated. ALN NP exhibited a significant cytotoxic effect, in a dose–response relationship, on macrophage-like RAW264 cells in cell culture. Subcutaneously (SC) administrated ALN NP (1.5 mg/kg on days − 1 and + 6) resulted in a significant attenuation of neointima to media ratio (N/M) by 52.7% and stenosis by 39.7% 28 days after balloon injury in the hypercholesterolemic rabbit model. Moreover, a good correlation was found between macrophage abundance in the injured arteries and the extent of stenosis. ALN NP treatment resulted in the reduction of both interleukin-1β and matrix metalloproteinases (2 and 9). It is concluded that a particulated dosage form of polymeric NP loaded with ALN reduce neointimal formation in vivo by systemic transient depletion of monocytes.

OBJECTIVES Macrophage depletion by liposomal clodronate inhibits neointimal formation after balloon-injury. The present study examined bisphosphonates (BPs) potency-effect relationship and the role of systemic versus local monocytes in vascular repair. METHODS AND RESULTS Liposomal preparations of clodronate, pamidronate, alendronate, and ISA-13-1 inhibited RAW-264 macrophages growth in a dose-response manner. Administration to balloon-injured rats suppressed neointimal growth. Neointima to media ratio (N/M) at 14 days was reduced from 1.35 +/- 0.22 (control) to 0.4 +/- 0.1 and 0.9 +/- 0.17 by liposomal alendronate (1.5 mg/kg, i.v.) and liposomal ISA-13-1 (15 mg/kg), respectively (n = 8-10, P < 0.05). Suppression of neointimal formation was preserved at 30 days. Subcutaneous administration of liposomal BP (LBP) was also effective in suppressing neointimal formation, while short local intraluminal application had no effect. Immunostaining for ED-1 and ED-2 revealed no resident macrophages in the arterial wall, and reduced macrophage infiltration in LBP-treated animals. Arterial PDGF-B chain and PDGF-beta receptor activation were reduced in LBP-treated animals and up-regulation of the PDGF receptor was noted. CONCLUSIONS Systemic transient inactivation of monocytes and macrophages by LBPs reduced macrophage infiltration and neointimal formation in the rat carotid injury model. The findings demonstrate a BP potency-effect relationship, and highlight the role of circulating monocytes in vascular injury and repair.

Collagen matrices can be used as non-viral biocompatible gene carriers for localized implantable gene therapy. Collagen matrices embedding pDNA with enhanced binding through condensing agent linkage to the matrix or to the pDNA have been formulated, and characterized in various systems. pDNA and condensed pDNA were released intact from the matrices within 1-2 days. In vitro transfection with collagen matrices containing pDNA (luciferase encoding), pDNA in liposome (LIP), and pDNA with polyethylenimine (PEI) resulted in significantly higher expression levels in comparison to naked pDNA. pDNA-LIP matrices exhibited a dose response transfection of NIH 3T3, 293, MDA-MB-231 and smooth muscle cells (SMCs) in cell cultures. Subdermal implantations of collagen-polylysine-pDNA matrices in rats resulted in significantly higher gene expression levels in comparison to non-condensed pDNA matrices. Perivascular treatment with pDNA matrix and of naked pDNA solution in balloon-injured rat carotid arteries resulted in significant expression. In conclusion, a facile method for embedding cationic formulations of pDNA in collagen matrices was developed. These bioactive matrices seem to be suitable for tissue engineering and local gene therapy strategies.

Sustained release polymeric gene delivery systems offer increased resistance to nuclease degradation, increased amounts of plasmid DNA (pDNA) uptake, and the possibility of control in dosing and sustained duration of pDNA administration. Furthermore, such a system lacks the inherent problems associated with viral vectors. Biodegradable and biocompatible poly(DL-lactide-co-glycolide) polymer was used to enacapsulate pDNA (alkaline phosphatase, AP, a reporter gene) in submicron size particles. Gene expression mediated by the nanoparticles (NP) was evaluated in vitro and in vivo in comparison to cationic-liposome delivery. Nano size range (600 nm) pDNA-loaded in poly(DL-lactide-co-glycolide) polymer particles with high encapsulation efficiency (70%) were formulated, exhibiting sustained release of pDNA of over a month. The entrapped plasmid maintained its structural and functional integrity. In vitro transfection by pDNA-NP resulted in significantly higher expression levels in comparison to naked pDNA. Furthermore, AP levels increased when the transfection time was extended, indicating sustained activity of pDNA. However, gene expression was significantly lower in comparison with standard liposomal transfection. Seven days after i.m. injections in rats, naked pDNA and pDNA-NP were found to be significantly more potent (1-2 orders of magnitude) than liposomal pDNA. Plasmid DNA-NP treatment exhibited increased AP expression after 7 and 28 days indicating sustained activity of the NP.