An open GIS based 3D simulation software to predict cooling tower drift diffusion.

This paper developed XJCT-3D, a simulation software for cooling tower wet plume dispersion. By coupling it with the Open GIS component Dotspatial, we have achieved geospatial visual representation of the calculation results, which has solved the problems of low calculation efficiency and insufficient visual representation of the traditional CFD software in the calculation of cooling tower wet plume dispersion. In order to verify the validity of the XJCT-3D software simulation results, we have conducted tracer experimental data from the ChalkPoint power plant. XJCT-3D accurately models wet plume deposition during cooling tower operation. From the XJCT-3D calculation results, we have observed that the maximum value of the cooling tower thermal plume wet deposition occurs near 610 m with a maximum value of 6.9E-07 kg/m2 s. This finding suggests that the cooling tower emissions carry a significant load of particles or droplets that have settled on surfaces at this particular altitude. It provides insights into potential environmental and human health impacts and helps in identifying and assessing areas at relatively higher risk of deposition, such as nearby ecosystems, farmland, or urban areas. This information can contribute to the development of effective mitigation strategies and the implementation of appropriate measures to minimize the impact of cooling tower emissions.

SACTI model in prediction and assessment of large scale natural draft cooling tower environmental impact of nuclear power plant.

Large Scale Natural Draft Cooling Tower has become a hot topic in China because it is an important part of the nuclear power plant, and its environmental impacts include shading, solar energy loss, water deposition and salt deposition. In China, there is no built large-scale natural draft cooling tower of nuclear power plant. Therefore, model prediction becomes an effective way to solve this problem. This paper introduces the basic principles and structure of SACTI (Seasonal and Annual Cooling Tower Impact) model. SACTI is a cooling tower assessment model developed by Argonne National Laboratory, USA. A comparative case study between China's Pengze Nuclear Power Plant and the US Amos Power Plant is also presented. Calculations were carried out for the Pengze and Amos power plants, and the results showed that the maximum value of salt deposition at the Pengze plant was about 166.5 kg/(km2-month) at a distance of 800 m from the cooling tower. The maximum value of salt deposition at the Amos plant was about 92.85 kg/(km2-month) at a distance of 600 m from the cooling tower. Conclusions show that the research work can provide a useful solution in future work, the simulation results of the SACTI model have a potential mean in the absence of monitoring data. This research provides a way to generate simulation data through SACTI program in the design process of nuclear power plant cooling tower, and designers can use these data to determine how the cooling tower will affect the natural environment and manage within an appropriate range to reduce the impact on the environment.

Influence of size classifications on the crystallinity index of Albizia gummifera cellulose.

The isolation of cellulose has found considerable applications recently due to its attractive characteristics. Cellulose from Albizia gummifera of different size classifications (425 µm-599 µm and 600 µm-849 µm) was investigated using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray (EDX) analyses. The crystal plane of the preferred orientation was at (020) for the most prominent peaks. The two size classifications have a strong broad peak around 3320 cm-1 (425 µm-599 µm), and 3330 cm-1 (600 µm-849 µm), which corresponds to a different stretching mode of O-H. High percentages of carbon (C) and oxygen (O) were noticed among the elements observed in the two size classifications. The crystallinity index (CrI) obtained for the two sizes were 61.1% for 425-599 µm, and 55.8% for 600 µm-849 µm. The 425 µm-599 µm size classification had a greater crystallinity index than the 600 µm-849 µm size classification, which indicates a stronger capacity for reinforcing. These particles were also effective as fillers in composite materials. The results revealed that Albizia gummifera cellulose possessed promising potential for device applications and capable of being used in the preparation of composite materials.

Asiaticoside inhibits renal fibrosis development by regulating the miR-142-5p/ACTN4 axis.

Renal fibrosis results in the progressive renal dysfunction and leads to chronic kidney disease (CKD) and ultimately end-stage renal disease. Asiaticoside was reported to regulate synaptopodin, desmin, nephrin, and podocin levels in adriamycin-induced nephropathy of rats. In this study, we found out that asiaticoside inhibited renal fibrosis in vitro and in vivo. Additionally, miR-142-5p was upregulated in in vitro and in vivo models of CKD. MiR-142-5p promoted the levels of collagen-I, collagen-IV, and fibronectin proteins. Additionally, miR-142-5p overexpression partly rescued the protective effect of asiaticoside on renal fibrosis. Mechanistically, miR-142-5p inhibited ACTN4 levels by binding with its 3´untranslated region, and further reduced its translation. Treatment of asiaticoside decreased miR-142-5p levels and increased ACTN4 levels. Rescue assays revealed that ACTN4 overexpression partially rescued the effect of miR-142-5p on renal fibrosis. Asiaticoside mitigated renal fibrosis by regulating the miR-142-5p/ACTN4 axis. In conclusion, asiaticoside inhibits renal fibrosis by regulating the miR-142-5p/ACTN4 axis. This novel discovery suggested that asiaticoside may serve as a potential medicine for renal fibrosis improvement.

Angiopep-conjugated nanoparticles for targeted long-term gene therapy of Parkinson's disease.

PURPOSE: To prepare an angiopep-conjugated dendrigraft poly-L-lysine (DGL)-based gene delivery system and evaluate the neuroprotective effects in the rotenone-induced chronic model of Parkinson's disease (PD). METHODS: Angiopep was applied as a ligand specifically binding to low-density lipoprotein receptor-related protein (LRP) which is overexpressed on blood-brain barrier (BBB), and conjugated to biodegradable DGL via hydrophilic polyethyleneglycol (PEG), yielding DGL-PEG-angiopep (DPA). In vitro characterization was carried out. The neuroprotective effects were evaluated in a chronic parkinsonian model induced by rotenone using a regimen of multiple dosing intravenous administrations. RESULTS: The successful synthesis of DPA was demonstrated via (1)H-NMR. After encapsulating the therapeutic gene encoding human glial cell line-derived neurotrophic factor (hGDNF), DPA/hGDNF NPs showed a sphere-like shape with the size of 119 ± 12 nm and zeta potential of 8.2 ± 0.7 mV. Angiopep-conjugated NPs exhibited higher cellular uptake and gene expression in brain cells compared to unmodified counterpart. The pharmacodynamic results showed that rats in the group with five injections of DPA/hGDNF NPs obtained best improved locomotor activity and apparent recovery of dopaminergic neurons compared to those in other groups. CONCLUSION: This work provides a practical non-viral gene vector for long-term gene therapy of chronic neurodegenerative disorders.

Gene and doxorubicin co-delivery system for targeting therapy of glioma.

The combination of gene therapy and chemotherapy is a promising treatment strategy for brain gliomas. In this paper, we designed a co-delivery system (DGDPT/pORF-hTRAIL) loading chemotherapeutic drug doxorubicin and gene agent pORF-hTRAIL, and with functions of pH-trigger and cancer targeting. Peptide HAIYPRH (T7), a transferrin receptor-specific peptide, was chosen as the ligand to target the co-delivery system to the tumor cells expressing transferrin receptors. T7-modified co-delivery system showed higher efficiency in cellular uptake and gene expression than unmodified co-delivery system in U87 MG cells, and accumulated in tumor more efficiently in vivo. DOX was covalently conjugated to carrier though pH-trigged hydrazone bond. In vitro incubation of the conjugates in buffers led to a fast DOX release at pH 5.0 (intracellular environment) while at pH 7.4 (blood) the conjugates are relatively stable. The combination treatment resulted in a synergistic growth inhibition (combination index, CI < 1) in U87 MG cells. The synergism effect of DGDPT/pORF-hTRAIL was verified in vitro and in vivo. In vivo anti-glioma efficacy study confirmed that DGDPT/pORF-hTRAIL displayed anti-glioma activity but was less toxic.

Dual targeting effect of Angiopep-2-modified, DNA-loaded nanoparticles for glioma.

Gene therapy offers a promising cure of brain glioma and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is able to induce cell apoptosis of glioma selectively without affecting the normal cells. In this study, the nanoscopic high-branching dendrimer, polyamidoamine (PAMAM), was selected as the principal vector. Angiopep-2, which can target to the low-density lipoprotein receptor-related protein-1 (LRP1) expressed on BCECs and glial cells, was exploited as the targeting ligand to conjugate PAMAM via bifunctional polyethyleneglycol (PEG) and then complexed with the DNA, designated as PAMAM-PEG-Angiopep/DNA nanoparticles (NPs). The cellular uptake mechanism explored in glial cells showed that the DNA of PAMAM-PEG-Angiopep/DNA NPs entered into the nuclei through the endosome/lysosome pathway. The in vivo biodistribution of PAMAM-PEG-Angiopep/DNA NPs in the brain especially the tumor site was higher than that of PAMAM-PEG/DNA NPs and PAMAM/DNA NPs. Furthermore, the TUNEL analysis showed a more wide-extended apoptosis in the PAMAM-PEG-Angiopep/pORF-TRAIL NPs treated group, compared to other groups including commercial Temozolomide-treated one. The median survival time of PAMAM-PEG-Angiopep/pORF-TRAIL NPs and Temozolomide treated on brain tumor-bearing mice was 61 and 49 days respectively, significantly longer than that of other groups. Besides, the NPs suggested low cytotoxicity after in vitro transfection. Thus, the results showed that Angiopep-2 could be exploited as a specific ligand to cross the BBB and targeted to glial cells, and PAMAM-PEG-Angiopep/DNA NPs can be a potential non-viral delivery system for gene therapy of glial tumor.

Chlorotoxin-modified macromolecular contrast agent for MRI tumor diagnosis.

Clinical diagnosis of cancers using magnetic resonance imaging (MRI) is highly dependent on contrast agents, especially for brain tumors which contain blood-brain barrier (BBB) at the early stage. However, currently mostly used low molecular weight contrast agents such as Gd-DTPA suffer from rapid renal clearance, non-specificity, and low contrast efficiency. The aim of this paper is to investigate the potential of a macromolecular MRI contrast agent based on dendrigraft poly-l-lysines (DGLs), using chlorotoxin (CTX) as a tumor-specific ligand. The contrast agent using CTX-modified conjugate as the main scaffold and Gd-DTPA as the payload was successfully synthesized. The results of fluorescent microscopy showed that the modification of CTX could markedly enhance the cellular uptake in C6 glioma and liver tumor cell lines, but not in normal cell line. Significantly increased accumulation of CTX-modified conjugate within glioma and liver tumor was further demonstrated in tumor-bearing nude mice using in vivo imaging system. The MRI results showed that the signal enhancement of mice treated with CTX-modified contrast reached peak level at 5 min for both glioma and liver tumor, 144.97% ± 19.54% and 158.69% ± 12.41%, respectively, significantly higher than that of unmodified counterpart and commercial control. And most importantly, the signal enhancement of CTX-modified contrast agent maintained much longer compared to that of controls, which might be useful for more exact diagnosis for tumors. CTX-modified dendrimer-based conjugate might be applied as an efficient MRI contrast agent for targeted and accurate tumor diagnosis. This finding is especially important for tumors such as brain glioma which is known hard to be diagnosed due to the presence of BBB.

Peptide-conjugated polyamidoamine dendrimer as a nanoscale tumor-targeted T1 magnetic resonance imaging contrast agent.

A tumor-targeting carrier, peptide HAIYPRH (T7)-conjugated polyethylene glycol-modified polyamidoamine dendrimer (PAMAM-PEG-T7) was explored to deliver magnetic resonance imaging (MRI) contrast agents targeting to the tumor cells specifically. Two different types of tumors, liver cancer and early brain glioma model (involved with the blood-brain barrier), were chosen to evaluate the imaging capacity of this contrast agent. PAMAM-PEG-T7 was synthesized, conjugated with diethylene triamine pentaacetic acid (DTPA) and further chelated gadolinium (Gd), yielding GdDTPA-PAMAM-PEG-T7. The result of ICP-AES showed that about 92 Gd ions could be loaded per PAMAM molecule. The calculated longitudinal relaxivity R1 of the GdDTPA-PAMAM-PEG-T7 was 10.7 mm(-1) S(-1) per Gd (984.4 mm(-1) S(-1) per PAMAM), while that of GdDTPA was only 4.8 mm(-1) S(-1). PAMAM-PEG-T7 had better targeting capacity to the liver cancer cells in vitro and in vivo, compared with PAMAM-PEG. The accumulation of PAMAM-PEG-T7 was 162.5% times that of PAMAM-PEG. But for glioma cells, PAMAM-PEG-T7 did not show its specificity. Furthermore, GdDTPA-PAMAM-PEG-T7 could improve the diagnostic efficiency of liver cancer with the enhanced signal (187%), compared to 130% for PAMAM-PEG and 121% for GdDTPA. GdDTPA-PAMAM-PEG-T7 could selectively identify liver cancer but not early glioma. This nanoscaled MRI contrast agent GdDTPA-PAMAM-PEG-T7 might allow for selective and efficient diagnosis of tumors without the natural barrier including liver cancer.

Plasmid pORF-hTRAIL and doxorubicin co-delivery targeting to tumor using peptide-conjugated polyamidoamine dendrimer.

A combination cancer therapy was investigated via co-delivery of therapeutic gene encoding human tumor necrosis factor-related apoptosis-inducing ligand (pORF-hTRAIL) and doxorubicin (DOX) using a tumor-targeting carrier, peptide HAIYPRH (T7)-conjugated polyethylene glycol-modified polyamidoamine dendrimer (PAMAM-PEG-T7). T7, a transferrin receptor-specific peptide, was chosen as the ligand to target the co-delivery system to the tumor cells expressing transferrin receptors. The result of fluorescence scanning showed that about 375 DOX molecules were bound to one pORF-hTRAIL molecule. The co-delivery system was constructed based on the electrostatic interactions between pORF-hTRAIL-DOX complex and cationic PAMAM-PEG-T7. T7-modified co-delivery system showed higher efficiency in cellular uptake and gene expression than unmodified co-delivery system in human liver cancer Bel-7402 cells, and accumulated in tumor more efficiently in vivo. In comparison with single DOX or pORF-hTRAIL delivery system, co-delivery system induced apoptosis of tumor cells in vitro and inhibited tumor growth in vivo more efficiently. In mice bearing Bel-7402 xenografts, lower doses of co-delivery system (4 µg DOX/mouse, about 0.16 mg/kg) effectively inhibited tumor growth comparable to high doses (5 mg/kg) of free doxorubicin (77% versus 69%). These results suggested that T7-mediated co-delivery system of DOX and pORF-hTRAIL was a simply prepared, combined delivery platform which can significantly improve the anti-tumor effect. This co-delivery system might widen the therapeutic window and allow for the selective destruction of cancer cells.

Targeted delivery of chlorotoxin-modified DNA-loaded nanoparticles to glioma via intravenous administration.

Gene therapy offers great potential for brain glioma. However, therapeutic genes could not reach glioma spontaneously. A glioma-targeting gene delivery system is highly desired to transfer exogenous genes throughout the tumor focus. In this study, the nanoscopic high-branching dendrimer, polyamidoamine (PAMAM), was selected as the main vector. Chlorotoxin (CTX), which has been demonstrated to bind specifically to receptor expressed in glioma, was exploited as the targeting ligand to conjugate PAMAM via bifunctional polyethyleneglycol (PEG), yielding PAMAM-PEG-CTX. The cellular uptake of CTX itself was observed apparently in C6 glioma cells, almost not in 293 cells. The modification of CTX could significantly increase the cellular uptake of vectors and the DNA-loaded nanoparticles (NPs) in C6 cells. The in vivo distribution of PAMAM-PEG-CTX/DNA NPs in the brain was higher than that of PAMAM/DNA NPs and PAMAM-PEG/DNA NPs. Furthermore, the gene expression of PAMAM-PEG-CTX/DNA NPs was higher and broader in glioma than that of unmodified and PEG-modified counterparts. The TUNEL analysis showed a more wide-extended apoptosis in the CTX-modified group, compared to other groups including commercial temozolomide group. The median survival time of CTX-modified group and temozolomide group was 59.5 and 49 days, respectively, significantly longer than that of other groups. The results suggested that CTX could be exploited as a special glioma-targeting ligand, and PAMAM-PEG-CTX/DNA NPs is a potential non-viral delivery system for gene therapy of glioma via intravenous administration.

Peptide-conjugated PAMAM for targeted doxorubicin delivery to transferrin receptor overexpressed tumors.

The purpose of this work was to evaluate the potential of HAIYPRH (T7) peptide as a ligand for constructing tumor-targeting drug delivery systems. T7 could target to transferrin-receptor (TfR) through a cavity on the surface of TfR and then transport into cells via endocytosis with the help of transferrin (Tf). In this study, T7-conjugated poly(ethylene glycol) (PEG)-modified polyamidoamine dendrimer (PAMAM) (PAMAM-PEG-T7) was successfully synthesized and further loaded with doxorubicin (DOX), formulating PAMAM-PEG-T7/DOX nanoparticles (NPs). In vitro, almost 100% of DOX was released during 2 h in pH 5.5, while only 55% of DOX was released over 48 h in pH 7.4. The cellular uptake of DOX could be significantly enhanced when treated with T7-modified NPs in the presence of Tf. Also, the in vitro antitumor effect was enhanced markedly. The IC(50) of PAMAM-PEG-T7/DOX NPs with Tf was 231.5 nM, while that of NPs without Tf was 676.7 nM. T7-modified NPs could significantly enhance DOX accumulation in the tumor by approximately 1.7-fold compared to that of unmodified ones and by approximately 5.3-fold compared to that of free DOX. For in vivo antitumor studies, tumor growth of mice treated with PAMAM-PEG-T7/DOX NPs was significantly inhibited compared to that of mice treated with PAMAM-PEG/DOX NPs and saline. The study provides evidence that PAMAM-PEG-T7 can be applied as a potential tumor-targeting drug delivery system. T7 may be a promising ligand for targeted drug delivery to the tumor.

Evaluation and mechanism studies of PEGylated dendrigraft poly-L-lysines as novel gene delivery vectors.

Dendrimers have attracted great interest in the field of gene delivery due to their synthetic controllability and excellent gene transfection efficiency. In this work, dendrigraft poly-L-lysines (DGLs) were evaluated as a novel gene vector for the first time. Derivatives of DGLs (generation 2 and 3) with different extents of PEGylation were successfully synthesized and used to compact pDNA as complexes. The result of gel retardation assay showed that pDNA could be effectively packed by all the vectors at a DGLs to pDNA weight ratio greater than 2. An increase in the PEGylation extent of vectors resulted in a decrease in the incorporation efficiency and cytotoxicity of complexes in 293 cells, which also decreased the zeta potential a little but did not affect the mean diameter of complexes. Higher generation of DGLs could mediate higher gene transfection in vitro. Confocal microscopy and cellular uptake inhibition studies demonstrated that caveolae-mediated process and macropinocytosis were involved in the cellular uptake of DGLs-based complexes. Also the results indicate that proper PEGylated DGLs could mediate efficient gene transfection, showing their potential as an alternate biodegradable vector in the field of nonviral gene delivery.