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Water rights trading is an important way to solve the problem of water shortage by market mechanism. The allocation of water rights among ecological water, energy water, and grain planting water are the basis of the regional water rights trade. In this paper, the concept of coordinated development of water–ecology–energy–food is proposed. We build a water rights allocation model with fairness, efficiency, and coordinated development as the goal, to achieve water security for various industries. Taking Yinchuan city as an example, the results showed that compared with the current water rights the water rights of life increased by 1.07%, the water rights of ecology increased by 1.85%, the water rights of energy industry decreased by 1.09%, the water rights of food planting decreased by 3.27%, the water rights of other agriculture increased by 0.83%, and the water rights of the general industry increased by 0.65%. After the allocation of water rights, the cooperativity of water–ecology–energy–food increased by 7.56%, and the total value of water resources in various industries increased by 2.31 × 108 CNY. A new water rights allocation model is developed in this paper, which can provide a reference for the allocation of water rights among regional industries.

Stem cell transplantation has shown promising regenerative effects against neural injury, and photobiomodulation (PBM) can aid tissue recovery. This study aims to evaluate the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) and laser alone or combined on spinal cord injury (SCI). The animals were divided into SCI, hUCMSCs, laser treatment (LASER) and combination treatment (hUCMSCs + LASER) groups. Cell-enriched grafts of hUCMSCs (1 × 106 cells/ml) were injected at the site of antecedent trauma in SCI model rats. A 2 cm2 damaged area was irradiated with 630 nm laser at 100 mW/cm2 power for 20 min. Locomotion was evaluated using Basso-Beattie-Bresnahan (BBB) scores, and neurofilament repair were monitored by histological staining and diffusion tensor imaging (DTI). First, after SCI, the motor function of each group was restored with different degrees, the combination treatment significantly increased the BBB scores compared to either monotherapy. In addition, Nissl bodies were more numerous, and the nerve fibers were longer and thicker in the combination treatment group. Consistent with this, the in situ expression of NF-200 and glial fibrillary acidic protein in the damaged area was the highest in the combination treatment group. Finally, DTI showed that the combination therapy optimally improved neurofilament structure and arrangement. These results may show that the combination of PBM and hUCMSCs transplantation is a feasible strategy for reducing secondary damage and promoting functional recovery following SCI.

The management of ecological water conveyance (EWC) can allow riparian vegetation communities to survive the threat of degradation in hyperarid inland areas and promote the health of groundwater-recharged riparian ecosystems. However, the ultrashort-term effects of periodic EWC scheduling on riparian vegetation remain unclear. This study explored the spatiotemporal differentiation in species structure (herbs, shrubs, and trees), diversity (measured by the Simpson, Shannon-Wiener, Pielou, and Margalef indices), stability (evaluated via Godron fitting distances and abundance-biomass comparison curves), and integrity (proxied by the vegetation-based index of biotic integrity) of vegetation communities in the downstream Heihe River Basin, China. Empirical orthogonal function, Pearson correlation, canonical correspondence analysis (CCA), and partial CCA methods were used to evaluate the effects of dominant habitat environmental factors from the hydrogeographic features, soil physicochemical properties, and anthropogenic impacts. The results showed that the riparian vegetation community diversity, stability, and integrity varied moderately to slightly with hierarchical distance from near wetlands (200 m; containing mainly herbs) to far desert edges (800 m; occupied by shrubs/subshrubs). The middle transition zone (200-800 m; occupied mostly by trees/subtrees) had the best diversity and integrity but relatively poor stability. The most significant influencing factors were EWC and soil moisture. The simple diversity, fair-level integrity, and disturbed but not irreversibly damaged stability of the vegetation community were generally improved by 14.82%, 20.33%, and 30.57%, respectively, in the pre-EWC period but worsened in the post-EWC period. The difference in spatially distributed EWC quantities caused more apparent vegetation restoration in high water-supplied subareas where certain biological community instability existed. Therefore, adequate EWC management can be considered a prerequisite for the maintenance of high richness and structural stability in local communities and requires a good balance between interregional vegetation abundance and enhanced environmental tolerance.

Unclear optical parameters make photo-biomodulation (PBM) difficult to implement in diabetic foot ulcer (DFU) clinically. Here, 12 wavelengths (400–900 nm) were used to conduct PBM to heal DFU wounds in vitro and in vivo. PBM at 10 mW/cm(2) and 0.5–4 J/cm(2) with all 12 wavelengths promoted proliferation of diabetic wound cells. In a mimic DFU (mDFU) rat model, PBM (425, 630, 730, and 850 nm, and a combination light strategy) promoted mDFU healing. The positive cell proliferation, re-epithelialization, angiogenesis, collagen synthesis, and inflammation were possible mechanisms. The combination strategy had the best effect, which can be applied clinically.

The three-river headwater region (TRHR) supplies the Yangtze, Yellow, and Lantsang rivers, and its ecological environment is fragile, hence it is important to study the surface vegetation cover status of the TRHR to facilitate its ecological conservation. The normalized difference vegetation index (NDVI) can reflect the cover status of surface vegetation. The aims of this study are to quantify the spatial heterogeneity of the NDVI, identify the main driving factors influencing the NDVI, and explore the interaction between these factors. To this end, we used the global inventory modeling and mapping studies (GIMMS)-NDVI data from the TRHR from 1982 to 2015 and included eight natural factors (namely slope, aspect, elevation, soil type, vegetation type, landform type, annual mean temperature, and annual precipitation) and three anthropogenic factors (gross domestic product (GDP), population density, and land use type), which we subjected to linear regression analysis, the Mann-Kendall statistical test, and moving t-test to analyze the spatial and temporal variability of the NDVI in the TRHR over 34 years, using a geographical detector model. Our results showed that the NDVI distribution of the TRHR was high in the southeast and low in the northwest. The change pattern exhibited an increasing trend in the west and north and a decreasing trend in the center and south; overall, the mean NDVI value from 1982 to 2015 has increased. Annual precipitation was the most important factor influencing the NDVI changes in the TRHR, and factors, such as annual mean temperature, vegetation type, and elevation, also explained the vegetation coverage status well. The influence of natural factors was generally stronger than that of anthropogenic factors. The NDVI factors had a synergistic effect, exhibiting mutual enhancement and nonlinear enhancement relationships. The results of this study provide insights into the ecological conservation of the TRHR and the ecological security and development of the middle and lower reaches.

A water rights trading scheme in China is currently in its initial stage of development, but is without a complete pricing mechanism. This paper proposes a pricing model for transfers of water rights from agriculture to industry in water-deficient areas of China. Both the cost price and the earnings price are considered and incorporated into the model. The cost price includes construction costs, operation and maintenance costs, renewal and reconstruction costs, and economic compensation for ecological damage. The earnings price is calculated according to a reasonable return coefficient and the difference in economic value of the water resources to the buyer and seller. The value of water resources was estimated based on emergy theory in accordance with the principle of mutual benefits equilibrium. This pricing model is then applied to the transfer of surplus water rights arising from agricultural water conservation schemes to industrial uses in the Southbank Ordos Irrigation Zone of the Inner Mongolia Autonomous Region. The results indicate that this pricing model could provide technical support to the scientific and reasonable pricing of water rights transactions in water-deficient areas and that it could play an active role in promoting the healthy development of future water markets.

Background Emerging evidence suggests that the gut microbiota plays an important role in the pathological progression of Alzheimer's disease (AD). Photobiomodulation (PBM) therapy is believed to have a positive regulatory effect on the imbalance of certain body functions, including inflammation, immunity, wound healing, nerve repair, and pain. Previous studies have found that the intestinal flora of patients with AD is in an unbalanced state. Therefore, we have proposed the use of gut flora-targeted PBM (gf-targeted PBM) as a method to improve AD in an As-induced AD mouse model. Methods PBM was performed on the abdomen of the mice at the wavelengths of 630 nm, 730 nm, and 850 nm at 100 J/cm2 for 8 weeks. Morris water maze test, immunofluorescence and proteomic of hippocampus, and intestinal flora detection of fecal were used to evaluate the treatment effects of gf-targeted PBM on AD rats. Results PBM at all three wavelengths (especially 630 nm and 730 nm) significantly improved learning retention as measured by the Morris water maze. In addition, we found reduced amyloidosis and tau phosphorylation in the hippocampus by immunofluorescence in AD mice. By using a quantitative proteomic analysis of the hippocampus, we found that gf-targeted PBM significantly altered the expression levels of 509 proteins (the same differentially expressed proteins in all three wavelengths of PBM), which involved the pathways of hormone synthesis, phagocytosis, and metabolism. The 16 s rRNA gene sequencing of fecal contents showed that PBM significantly altered the diversity and abundance of intestinal flora. Specifically, PBM treatment reversed the typical increase of Helicobacter and uncultured Bacteroidales and the decrease of Rikenella seen in AD mice. Conclusions Our data indicate that gf-targeted PBM regulates the diversity of intestinal flora, which may improve damage caused by AD. Gf-targeted PBM has the potential to be a noninvasive microflora regulation method for AD patients.

Background: Emerging evidence suggests that the gut microbiota plays an important role in the pathological progression of Alzheimer’s disease (AD). Photobiomodulation (PBM) therapy is believed to have a positive regulatory effect on the imbalance of certain body functions, including inflammation, immunity, wound healing, nerve repair, and pain. Previous studies have found that the intestinal flora of patients with AD is in an unbalanced state. Therefore, we have proposed the use of gut flora-targeted PBM (gf-targeted PBM) as a method to improve AD in an Aß-induced AD mouse model. Methods: PBM was performed on the abdomen of the mice at the wavelengths of 630 nm, 730 nm, and 850 nm at 100 J/cm2 for 8 weeks. Morris water maze test, immunofluorescence and proteomic of hippocampus, and intestinal flora detection of fecal were used to evaluate the treatment effects of gf-targeted PBM on AD rats.Results: PBM at all three wavelengths (especially 630 nm and 730 nm) significantly improved learning retention as measured by the Morris water maze. In addition, we found reduced amyloidosis and tau phosphorylation in the hippocampus by immunofluorescence in AD mice. By using a quantitative proteomic analysis of the hippocampus, we found that gf-targeted PBM significantly altered the expression levels of 509 proteins (the same differentially expressed proteins in all three wavelengths of PBM), which involved the pathways of hormone synthesis, phagocytosis, and metabolism. The 16s rRNA gene sequencing of fecal contents showed that PBM significantly altered the diversity and abundance of intestinal flora. Specifically, PBM treatment reversed the typical increase of Helicobacter and uncultured Bacteroidales and the decrease of Rikenella seen in AD mice. Conclusions: Our data indicate that gf-targeted PBM regulates the diversity of intestinal flora, which may improve damage caused by AD. Gf-targeted PBM has the potential to be a noninvasive microflora regulation method for AD patients.

Objectives Numerous studies employ mathematical methods, such as Monte Carlo simulation, to predict the tumor killing effects of photodynamic therapy (PDT) by simulating optical propagation, photosensitizer distribution, and oxygen distribution. Whether these models faithfully reflect tumor killing is unknown, and model validation using tumor cross sections in these studies is usually insufficient to answer this question. To fill this gap in our knowledge, we employed a mouse model of breast cancer to determine the spatiotemporal effects of PDT using direct histopathological and biochemical analyses of whole tumors. Methods We prepared approximately 700 5-μm-thick serial sections of breast tumors of syngeneic mice treated with PDT employing the photosensitizer photocarcinorin (PsD-007, a second-generation photosensitizer developed in China). Three adjoining sections were subjected to hematoxylin and eosin staining to assess necrosis, the TUNEL assay to evaluate apoptosis, and CD31 staining to detect angiogenesis, respectively. We then generated a three-dimensional (3D) reconstruction of the tumor to evaluate these processes. We simultaneously used the Monte Carlo method to develop a model of light distribution throughout the tumor to evaluate the actual and simulated tumor killing effects induced by PDT. Results Tumor necrosis decreased exponentially as a function of distance from the source of illumination, while the distributions of apoptosis and neovascularization were independent of light distribution. Most apoptosis occurred in the lower layers (3000–4000 μm) of the tumor where the light intensity was too low to excite the photosensitizer. Neovascularization occurred at depths ranging from 2500 to 3500 μm. These analyses provided a 3D view of how a tumor is destroyed using PDT. Conclusions Although the optical distribution model predicted tumor necrosis caused by PDT, it was ineffective in predicting the sites of apoptosis and vascular destruction. Mathematical modeling is limited in its capabilities required to gain a comprehensive understanding of the spatiotemporal events associated with PDT. The mouse model developed here will serve as a platform for detailed direct histopathological, biochemical, and molecular genetic analyses of the effects of PDT, which will facilitate the development of optimized treatment strategies.

Ethnopharmacological relevance Byur dMar Nyer lNga Ril Bu (BdNlRB) is a classic Tibetan medicine prescription for treating " white vein disease". Alzheimer's disease (AD) is a chronic degenerative disease of the central nervous system, characterized by distinct "white vein disease". In the absence of effective drugs for AD, BdNlRB may be a possible treatment for AD. Aim of the study To verify the therapeutic effect and possible mechanism of the proved Tibetan medicine BdNlRB on Alzheimer's disease. Materials and methods 60 APP/PS1 double transgenic AD mice (Mt) and 60 As1-40 protein-induced AD mice (Mi) were divided into 3 groups according to the dose of BdNlRB: BdNlRB-100, BdNlRB-200 and BdNlRB-400, with 100, 200 and 400 mg/kg*weight, respectively. The mice were administrated by gavage for 8 weeks. The cognitive ability of mice was detected by Morris Water Maze, the expression of As protein, p-tau and microglia was detected by immunofluorescent staining, the protein expression in the hippocampus was detected by proteomics, and the abundance of fecal intestinal flora was detected by 16S RNA. Results The learning ability and memory ability of Mi mice were significantly improved after BdNlRB administration. The learning ability of Mt mice was significantly improved, while the memory ability was not improved after BdNlRB administration. After the treatment with low and medium doses of BdNlRB, the expression of p-tau decreased significantly (the rate of decrease in BdNlRB-100 and BdNlRB-200 groups was 8.05% and 12.7%, respectively), and the number of microglia increased (39.3% and 31.6%, respectively). BdNlRB significantly affected the protein expression in the hippocampus of Mt mice. 382 proteins in different expression in all three groups mainly involved in amino acid synthesis, fatty acid degradation, glutamine metabolism, synaptic vesicular cycle and oxidative phosphorylation, PPAR signaling pathway and Fc gamma-mediated phagocytosis were activated. Meanwhile, the administration of BdNlRB can regulate the intestinal flora of Mt mice, which reduces the abundance of Muribaculum and uncultured bacteroidales bacterium, and improves the abundance of Ruminococcus-1 and Ruminiclostridium-9. Conclusion The oral administration of BdNlRB significantly improved the cognitive ability of AD mice, and neuroinflammation and intestinal flora regulation were the possible mechanisms.

This paper presents a pricing model developed for the Chinese water rights trading market. The model focuses on the transfer of water rights from irrigators to industrial users in areas with limited water resources. Water rights trading is an efficient means of allocating water resources, and the price plays an important role in this market. At present, China lacks formal mechanisms in place for water rights pricing. Therefore, an integrated pricing model is built for situations when agricultural users implement water conservation measures and sell water rights to meet industrial water demand. The model accounts for project construction costs, operation and maintenance costs, renewal and reconstruction expenses, irrigation frequency compensation, and the economic cost of ecological damage. The marginal value of water rights to the industrial water user is also quantified on the basis of the production function accounting for water inputs. The pricing model is applied to an example of water rights trading between irrigators and industrial users in an agricultural area on the Yellow River near Ordos in Inner Mongolia.

While adverse effects of nanoparticles on lung health have previously been proposed, few studies have addressed the direct effects of nanoparticle exposure on the airway epithelium. In this work, we examine the response of the pulmonary airway to nanoparticles by measuring intracellular Ca2+ concentration ([Ca2+]i) in the Calu-3 epithelial layer stimulated by 3-mercaptopropionic-acid (3MPA) coated CdSe-CdS/ZnS core-multishell quantum dots (QDs). Simultaneous transient transepithelial electrical resistance (TEER) decrease and global [Ca2+]i increase in Calu-3 epithelial layer, accompanied by cell displacements, contraction, and expansion, were observed under QD deposition. This suggests that a QD-induced global [Ca2+]i increase in the Calu-3 epithelial layer caused the transient TEER decrease. The [Ca2+]i increase was marked and rapid in the apical region, while [Ca2+]i decreased in the basolateral region of the epithelial layer. TEER transient response and extracellular Ca2+ entry induced by QD deposition were completely inhibited in cells treated with stretched-activated (SA) inhibitor GdCl3 and store-operated calcium entry (SOCE) inhibitor BTP2 and in cells immersed in Ca2+-free medium. The voltage-gated calcium channel (VGCC) inhibitor nifedipine decreased, stabilized, and suppressed the TEER response, but did not affect the [Ca2+]i increase, due to QD deposition. This demonstrates that the Ca2+ influx activated by QDs' mechanical stretch occurs through activation of both SA and SOCE channels. QD-induced [Ca2+]i increase occurred in the Calu-3 epithelial layer after culturing for 15 days, while significant TEER drop only occurred after 23 days. This work provides a new perspective from which to study direct interactions between airway epithelium and nanoparticles and may help to reveal the pathologies of pulmonary disease.

With increasing knowledge of the relevance of vascular cell adhesion molecule 1 (VCAM-1) for tumor growth, metastasis, angiogenesis, and related processes, it has become an attractive anti-tumor strategy to target VCAM-1 expression on the tumor vasculature. We designed a new targeted nanodrug, denoted PVQ, based on a photosensitizer (for the photodynamic effect), VCAM-1 target and quantum dot (QD) carrier, using conjugated water-dispersible colloidal CdSe–CdS/ZnS QDs, protoporphyrin IX (PpIX) photosensitizers, and VCAM-1 binding peptides. Its targeting ability and photodynamic therapy (PDT) efficiency against VCAM-1 expression in human umbilical vein endothelial cells (HUVECs) were then investigated. Conjugates of QD–VCAM-1 binding peptide (VQ), PpIX–VCAM-1 binding peptide (PV), and PVQ prepared using amide coupling were verified by agarose gel electrophoresis, Fourier transform infrared spectroscopy, and fluorescence spectrometry. VCAM-1 expression in HUVECs was induced by TNF-α treatment. PVQ conjugates were co-cultured with VCAM-1 expressing (VCAM-1(+)) and non-expressing (VCAM-1(−)) HUVECs, and target imaging, ROS generation, cell death, and apoptosis were analyzed using confocal fluorescence microscopy. VCAM-1 target imaging could not distinguish between VCAM-1(+) and VCAM-1(−) HUVECs after only 6 h of incubation; however it could distinguish between the cells after incubation for 24 h. After incubation for ca. 30 min, PVQ generated a significantly higher yield of ROS (3.6 fold) in VCAM-1(+) HUVECs compared with VCAM-1(−) cells, during 10 min of irradiation at a wavelength of 405 nm, and this was followed by a second rise in ROS at 30 min after irradiation. Moreover, cell destruction was observed clearly in VCAM-1(+) cells treated with PVQ and almost all cells became round after 30 min of irradiation at 405 nm. PVQ-induced PDT effects caused a significant apoptosis (onset and late apoptosis) in VCAM-1(+) HUVECs at 6 h after PDT treatment. In conclusion, PVQ shows a great potential for targeted PDT in cancer therapy.

Apoptosis is one of the major mechanisms of photodynamic therapy (PDT) that leads to tumor degradation. Apoptosis-related genes and proteins function in a certain order and timing in the complex network of apoptosis. To further understanding of the apoptotic mechanism of PDT, this research examined the time course of apoptosis from PsD007 (a second-generation photosensitizer developed in China) induced PDT on the rat acute myeloid leukemia cell line LT12. MTT was used to detect the temporal dynamic of PDT killing effects and identified the "apoptotic window" of 2-24 h. Apoptosis showed a basal peak at 2 h, and the duration of apoptosis depended on PDT dose, which disappeared quickly at low concentrations but lasted to higher levels to 6 or 12 h at high concentrations as detected by flow cytometry. High-content imaging confirmed these results. An 84-gene apoptosis PCR array identified 15 genes with an expression level change of over twofold at 6 h post-PDT. Nine apoptosis-related genes showed changes in expression at 2-12 h after PDT. TNF family genes TNF and FASLG showed a maximal change of 3.47- and 4.42-fold from baseline. Key apoptosis proteins such as activated caspases showed strong up-regulation after PDT, with the expression peaks of cleaved caspase-7, caspase-9 and PARP at 4-6 h, and cleaved caspase-3 delayed to 6-12 h. Our findings help clarify the time course of apoptosis events in response to PDT treatment in a leukemia cell line and may help contribute to the clinical application of PDT in leukemia treatment.

Aim Metronomic photodynamic therapy (mPDT) with a longer irradiation time and lower energy compared with acute (or classic) photodynamic therapy (aPDT) is a more effective treatment than aPDT for tumor cells, especially colorectal cancer. However, the underlying mechanisms of the superior effects of mPDT are unknown. Methods we used SWATH-MS (sequential window acquisition of all theoretical mass spectra) to identify differentially expressed proteins (DEPs) specific to aPDT (conventional fluence rate, 20 mW/cm2, 4 min 10 s), mPDT (metronomic fluence rate, 0.4 mW/cm2, 3.5 h), and control groups of SW837 cells. The photosensitizer used in both PDT methods was aminolevulinic acid which were incubated with the cells before irradiation. Results A total of 6805 proteins were identified in the three groups of SW837 cells. aPDT induced 333 DEPs and mPDT induced 1716 DEPs compared with the control. We identified 185 common DEPs in the two PDT groups, 148 different DEPs in the aPDT group, and 1531 different DEPs in the mPDT group. Most of the 185 common DEPs were involved in the extracellular component, participated in the processes of vesicle transport and secretion, binding, and hydrolase/catalytic activity. They were also involved in PI3K-Akt, cGMP-PKG, RAS, and aAMP signaling pathways. In addition, the 1531 different DEPs in the mPDT group participated in similar processes and molecular functions, but in a more complex manner than those in the aPDT group. Conclusion our proteome data suggest that mPDT has a complex tumor destruction mechanism with more involved proteins compared with aPDT, which may explain the better tumor killing effect of mPDT.

As the second longest river in China, the Yellow River is noted for its relatively low water discharge as compared with its huge sediment load. The Xiliu Gully and Heilai Gully, two typical watersheds located in the Inner-Mongolia reach of the upper Yellow River and China Loess Plateau area, is a serious soil erosion and water-deficient region, which belongs to the arid and semi-arid inland basin. In the region, water-consumption mainly depends on rainfall, where there contains grassland, cropland and desert and so on. With the development of economy and society of Eerduosi, the problem of water shortage has become a bottle neck of further development. Based on the hydrogeology features in the Loess Plateau Area, the study proposed the concept of rainfall resource potential, which was composed of surface runoff and soil water. A water yield model based on InVEST (the Integrated Valuation of Ecosystem Services and Tradeoffs) was employed to estimate rainfall resource potential of the two typical watersheds. Based on extensive field research and literature analysis, the process of runoff generation, water enriching and transport was concluded. The highly efficient utilization of rainfall resource in different regions was integrated, which were made of silt trap dams, shallow shaft and ponds. The study provided scientific basis for Spatial Distribution of silt trap dams and high efficient utilization mode of rainfall resource resources.

Systemic PDT (SPDT) approach is developed to treat a variety of hematological diseases, including cancers and blood-borne infections. We evaluated the efficacy of an SPDT method for treating leukemia using a Brown Norway myeloid leukemia (BNML) rat model with the LT12 cells engineered to express GFP. The survival times of animals receiving SPDT at 5 (early-SPDT) and 10 (mid-SPDT) days post-LT12 injection were prolonged by 2 days, the rats in the late-SPDT group (15 days) exhibited a 6-day increase in life span (p

Breath acetone has long been a known biomarker for diabetes. However whether breath acetone analysis can be used for clinical applications ultimately depends on how breath acetone concentration is quantitatively and accurately related to an established clinical diagnostic parameter(s). Numerous studies of breath acetone using human subjects have been done, yet this fundamental question remains unaddressed because complex physiological processes and various conditions of humans are relevant to change of breath acetone. We report for the first time on the study of breath acetone and its correlations with blood glucose (BG) and blood β-hydroxybutyrate (BHB) using an animal model of rats. 18 non-diabetic healthy rats and 20 lab-developed type 1 diabetic (T1D) rats were used as two subject groups. Breath gas samples from the rats were collected using a noninvasive oral intubation method that was compared with the intrusive and time-consuming method of tracheostomy. Breath acetone concentrations were measured using a cavity ringdown spectroscopy based breath analyzer without using additional sample preparation, sample pre-concentration, or calibration. The measured breath acetone concentrations were in the ranges of 1.9–4.3 ppm (part per million by volume) for the 20 T1D rats and 1.4–2.8 ppm for the 18 non-diabetic healthy rats. Simultaneous BG and blood BHB levels were also obtained. Results show that breath acetone, BG, and blood BHB in the T1D rat group all have significant difference from the one in the healthy rat group (P < 0.05). A significant positive relationship (Pearson’s r = 0.644, P < 0.05) between breath acetone and blood BHB was found to exist in both subject groups. A significant negative relationship (Pearson’s r = −0.678, P < 0.05) between breath acetone and BG was found in the T1D rats only. However, the relationship between breath acetone and BG shifts from negative to weakly positive when T1D rats were treated with insulin. Furthermore, results from a multiple linear regression model analysis reveal that breath acetone has a predictive nature for blood BHB in T1D rats, which confirms the sole report in T1D human subjects. This result suggests that the animal model can be used for large scale clinical study to help address fundamentals in human breath analysis in some cases.

Jacopo M Fontana,1 Huijuan Yin,1 Yun Chen,2 Ricardo Florez,1 Hjalmar Brismar,1 Ying Fu1 1Section of Cellular Biophysics, Department of Applied Physics, Royal Institute of Technology, Science for Life Laboratory, Solna, 2Department of Molecular and Clinical Medicine/Clinical Physiology, The Sahlgrenska Academy and University Hospital, University of Gothenburg, Gothenburg, Sweden Abstract: Colloidal semiconductor quantum dots (QDs) have been extensively researched and developed for biomedical applications, including drug delivery and biosensing assays. Hence, it is pivotal to understand their behavior in terms of intracellular transport and toxicological effects. In this study, we focused on 3-mercaptopropionic acid-coated CdSe-CdS/ZnS core-multishell quantum dots (3MPA-QDs) converted from the as-grown octadecylamine-coated quantum dots (ODA-QDs) and their direct and dynamic interactions with human umbilical vein endothelial cells (HUVECs). Live cell imaging using confocal fluorescence microscopy showed that 3MPA-QDs first attached to and subsequently aggregated on HUVEC plasma membrane~25min after QD deposition. The aggregated QDs started being internalized at ~2hand reached their highestinternalization degree at ~24h. They were released from HUVECs after ~48h. During the 48 h period, the HUVECs responded normally to external stimulations, grew, proliferated and wound healed without any perceptible apoptosis. Furthermore, 1) 3MPA-QDs were internalized in newly formed LysoTracker-stained early endosomes; 2) adenosine 5'-triphosphate-induced [Ca2+]i modulation caused a transient decrease in the fluorescence of 3MPA-QDs that were attached to the plasma membrane but a transient increase in the internalized 3MPA-QDs; and 3) fluorescence signal modulations of co-stained LysoTracker and QDs induced by the lysosomotropic agent Gly-Phe-β-naphthylamide were spatially co-localized and temporally synchronized. Our findings suggest that 3MPA-QDs converted from ODA-QDs are a potential nontoxic fluorescent probe for future use in clinical applications. Moreover, the photophysical strategy and techniques reported in this work are easily applicable to study ofdirect interactions between other nanoparticles and live cells; contributing to awareness and implementation of the safe applications of nanoparticles. Keywords: colloidal semiconductor quantum dots, human umbilical vein endothelial cell, intracellular labeling, nanotoxicity, adenosine 5'-triphosphate, endosome

Metronomic photodynamic therapy (mPDT) was developed to improve tumor-specific responses through cell death by apoptosis. We developed an mPDT suppository kit including ALA and LED suppositories and analyzed its killing effect on rectal tumors in rabbits. Methods: The ALA (10 wt%) suppository was prepared using ALA powder, type 36 semi-synthetic fatty acid glyceride, and azone. The LED suppository was constructed by encapsulating LED units and a circuit in transparent epoxy resin. VX2 cells were injected into the rectal submucosa of rabbits to establish a carcinoma model in situ. The ALA suppository was inserted into the rectal cavity for 30 min of uptake and activated for 1 h by the LED suppository at a power density of 20 mW/cm2. The mPDT process was repeated three times once a day. MRI was used to monitor tumor growth, histopathology and TUNEL staining were performed at 14 days after mPDT. Results: The overall response rate was 60% in the mPDT group using the kit in which the tumor size was decreased up to about 50% at 7 days post-mPDT and almost eliminated at 14 days. HE staining showed that only 6.16% of the tumor tissue remained after mPDT treatment. TUNEL detection showed that the apoptosis rate was 18.9%. Conclusion: We verified the killing effect of the mPDT suppository kit on rectal tumors in rabbits based on mPDT that induced tumor cell apoptosis.

This study evaluated the effects and mechanism of action of combining irreversible electroporation (IRE) and photodynamic therapy (PDT) in breast cancer cells in vitro and in vivo. Jin’s formula was used to assess killing efficacy of different IRE+PDT dosing combinations in breast cancer MCF-7 cells. Flow cytometry, high-content imaging, and confocal laser scanning microscopy were used to detect apoptosis. qRT-PCR and western blotting were used to evaluate expression of apoptosis-related genes and proteins. IRE+PDT combination therapy was administered to BALB/C mice with breast cancer tumors in vivo; tumor size was used to assess treatment efficacy. Killing mechanisms were examined using transmission electron microscopy and immunohistochemistry. We found that IRE+PDT combination therapy produced significant synergistic killing effects in breast cancer cells (highest Jin q value of 1.32). Early apoptosis rates were significantly higher in the IRE+PDT group (16.0%) than in IRE-alone (7.6%) and PDT-alone (4.6%) groups (P

While adverse effects of nanoparticles on lung health have previously been proposed, few studies have addressed the direct effects of nanoparticle exposure on the airway epithelium. In this work, we examine the response of the pulmonary airway to nanoparticles by measuring intracellular Ca2+ concentration ([Ca2+]i) in the Calu-3 epithelial layer stimulated by 3-mercaptopropionic-acid (3MPA) coated CdSe-CdS/ZnS core-multishell quantum dots (QDs). Simultaneous transient transepithelial electrical resistance (TEER) decrease and global [Ca2+]i increase in Calu-3 epithelial layer, accompanied by cell displacements, contraction, and expansion, were observed under QD deposition. This suggests that a QD-induced global [Ca2+]i increase in the Calu-3 epithelial layer caused the transient TEER decrease. The [Ca2+]i increase was marked and rapid in the apical region, while [Ca2+]i decreased in the basolateral region of the epithelial layer. TEER transient response and extracellular Ca2+ entry induced by QD deposition were completely inhibited in cells treated with stretched-activated (SA) inhibitor GdCl3 and store-operated calcium entry (SOCE) inhibitor BTP2 and in cells immersed in Ca2+-free medium. The voltage-gated calcium channel (VGCC) inhibitor nifedipine decreased, stabilized, and suppressed the TEER response, but did not affect the [Ca2+]i increase, due to QD deposition. This demonstrates that the Ca2+ influx activated by QDs’ mechanical stretch occurs through activation of both SA and SOCE channels. QD-induced [Ca2+]i increase occurred in the Calu-3 epithelial layer after culturing for 15 days, while significant TEER drop only occurred after 23 days. This work provides a new perspective from which to study direct interactions between airway epithelium and nanoparticles and may help to reveal the pathologies of pulmonary disease.

Photodynamic therapy (PDT) using photosensitized reaction to produce cytotoxicity was used for cancer therapy in recent years. To study the effectiveness of PDT mediated by a novel photosensitizer (PS), DTPP 5-(4'-(2″-dicarboxymethylamino)acetamidophenyl)-10, 15, 20-triphenylporphyrin, on lung cancer A549 cell lines in vitro, DTPP was employed in different concentrations (2, 4, 6, 8, 10, 12, 15, 20, 25, and 30 μg/ml) and combined with 650 nm laser of different power densities (0.6, 1.2, 2.4, 4.8, 7.2, and 9.6 J/cm(2)) that resulted in obvious inhibition of cell proliferation and apoptosis. Results showed that cell survival rates have a dependent relationship with time and PS concentrations and no significant cytotoxicity was induced by DTPP itself. Apoptosis and cell cycle S arrest were observed; cytoskeleton morphologic observation revealed collapse, sparkling, and shrunken shapes. Apoptosis-related protein caspase-3 overexpression was detected while caspase-9, bcl-2, and cytoskeleton protein beta-catenin were in low levels of expression than the control. Cleavage of beta-catenin by caspase-3 or other proteases from the lysosome might be the main reason for the cytoskeleton collapse as beta-tubulin and actin were at a stable level 12 h after PDT. This paper gives a better understanding of the effectiveness of DTPP-mediated PDT in lung cancer A549 cells both with regard to dosimetry and apoptosis changes.

Photodynamic therapy (PDT) has been shown to inactivate blood-borne pathogenic microorganisms in vitro. The method may be used to purify blood in the body, kill pathogenic microorganisms, and treat difficult diseases. Our aim was to investigate the safety of photodynamic blood purification (PBP) therapy using an in vivo blood circulation experiment in an animal model. Twenty-four New Zealand rabbits were used as experimental subjects; 12 received PDT and 12 served as negative controls. Extracorporeal blood bypass was established using the femoral artery and vein. A sterile disposable irradiation chamber was connected in the bypass pathway. Hematoporphyrin monomethyl ether was injected intravenously as a photosensitizer with an initial bolus of 3.7 mg, followed by a continuous infusion at 24 mg/h during PDT administration. Five minutes after initial injection, a laser beam was vertically focused on the irradiation chamber side wall, with a 9.5 cm(2) spot area, 1 h exposure time, and 20 mW/cm(2) power density. Six animals received a single PDT application, and six received PDT every other day for three applications. The 12 control group animals underwent extracorporeal blood circulation but did not receive the photosensitizer or light treatment. Blood samples were taken 20 min, 1 day, 4 days, and 7 days after PDT treatment for analysis of cell counts, coagulation, liver and renal function, and other biochemical changes. On the 7th day, animals were sacrificed, and parenchymal organs were evaluated for morphological changes. There were no significant differences in white blood cells, red blood cells, or destroyingplatelets after PDT compared with the control group. There was a little significant difference in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, uric acid, blood urea nitrogen, and creatinine in the PDT group compared with the control group, except at individual time points. We found no significant damage in the heart, liver, spleen, lungs, kidneys, or other organs after PDT. This short-duration, fixed-strength PBP method did not cause changes in blood parameters or in the structure or function of major organs in an animal model. These findings suggest that PBP is safe in vivo and has potential as a new therapy for inactivating blood-borne microorganisms.

Proper water use requires its monitoring and evaluation. An indexes system of overall water use efficiency is constructed here that covers water consumption per 10,000 yuan GDP, the coefficient of effective utilization of irrigation water, the water consumption per 10,000 yuan of industrial value added, domestic water consumption per capita of residents, and the proportion of water function zone in key rivers and lakes complying with water-quality standards and is applied to 31 provinces in China. Efficiency is first evaluated by a projection pursuit cluster model. Multidimensional efficiency data are transformed into a low-dimensional subspace, and the accelerating genetic algorithm then optimizes the projection direction, which determines the overall efficiency index. The index reveals great variety in regional water use, with Tianjin, Beijing, Hebei, and Shandong showing highest efficiency. Shanxi, Liaoning, Shanghai, Zhejiang, Henan, Shanxi, and Gansu also use water with high efficiency. Medium efficiency occurs in Inner Mongolia, Jilin, Heilongjiang, Jiangsu, Hainan, Qinghai, Ningxia, and Low efficiency is found for Anhui, Fujian, Jiangxi, Hubei, Hunan, Guangdong, Guangxi, Chongqing, Sichuan, Guizhou, Yunnan, and Xinjiang. Tibet is the least efficient. The optimal projection direction is a* = (0.3533, 0.7014, 0.4538, 0.3315, 0.1217), and the degree of influence of agricultural irrigation efficiency, water consumption per industrial profit, water used per gross domestic product (GDP), domestic water consumption per capita of residents, and environmental water quality on the result has decreased in turn. This may aid decision making to improve overall water use efficiency across China.

Metronomic photodynamic therapy (mPDT) has emerged as an attractive treatment for the selective destruction of tumor cells by induction of apoptosis. Here, we compared the effects of mPDT and acute photodynamic therapy (aPDT) on human SW837 colorectal cancer (CRC) cells. CRC cells were subjected to mPDT using various exposure durations, concentrations of 5-aminolevulinic acid (ALA), fluence rates and energy densities. The effects were compared with those induced by aPDT. We found that apoptosis and autophagy were earlier induced to a greater extent by mPDT than by the same dose applied as aPDT. The survival rates for mPDT vs. aPDT were 35.2%, 32.4%,27.6%,31.6% vs. 85.7%, 71.1%, 67.8%, 42.1% after 3, 6, 12, and 24 h PDT, respectively. For the same time points, the apoptotic rates for mPDT vs. aPDT were 43.2%, 47.3%, 54.7%, and 50.3% vs. 14.6%, 17.6%, 27.1%, and 53.2%, respectively. mPDT induced a peak rate of autophagy of 20.0% at 3 h, whereas aPDT induced two smaller peaks at 3 h (14.1%) and 12 h (15.8%). Advanced autophagosomes were more abundant in mPDT- than aPDT-treated cells and appeared earlier after mPDT (3 h) than after aPDT (3−12 h). Western Bloting results showed that the ratio of LC3B-II/β − actin at 3 h was higher (1.04 times) after mPDT than aPDT. Collectively, these datas indicated that ALA-mPDT was more effective than the same dose of ALA-aPDT at inducing SW837 CRC cell death via apoptosis and autophagy. Thus, mPDT may be a superior choice than aPDT for the treatment of human CRC.

Based on the annual maximum flood discharge sequence of the Longtouguai hydrological station in the Xiliugou River Basin from 1960 to 2015, the statistical probability characteristics of extreme flood discharge were analyzed by using generalized extreme value (GEV) distribution, generalized Pareto (GP) distribution, Pearson type III (P-III) distribution, general logistic (GLO), and Burr distribution. The parameters were estimated by the L-moments method, and the optimal distributions were selected by some of goodness-of-fit method. The results showed that the annual maximum flood discharge series decreased significantly with an abrupt change point around 2005. From the L-moments and goodness-of-fit test method, Burr distribution can better fit the annual maximum flood discharge before and after the abrupt change. Compared with the sequence before the change, the return period becomes larger and the probability of severe flood is smaller. The designed maximum flood peak discharge for the same return period of the entire sequence is smaller than that of the sequence before the change.

The objective of this study was to generate an effective vaccine against lung cancer using photosensitizing drug-mediated photodynamic therapy (PDT) and to study the mechanism. The efficiency of a photosensitizing drug (DTPP) was investigated by singlet oxygen yield determination, killing effect analysis, and cell apoptosis induction effect assessment. DTPP-based PDT tumor cell lysates and cell surface antigens obtained from acid-eluted adherent cells were then used as vaccines to prevent lung cancer using LA795 murine lung cells. The optimal protocol for PDT vaccine preparation was selected based on the tumor growth retardation effect of the vaccines, DTPP concentration, illumination dose, and numbers of DTPP-based PDT cells. To study the mechanism of the anti-tumor effect of vaccines, host anti-tumor immune responses were studied, including CD4(+)/CD8(+) ratios and percentage of NK cells and serum cytokine levels. A comparison of cytokine (IFN-γ and IL-1) secretion from splenocytes and tumor pathologic features from mice immunized with vaccines were compared with controls and showed that the optimal protocol for PDT vaccine preparation was LA795 cells exposed to 10 μg/ml DTPP photosensitizer for 24 h, illuminated with 7.2 J/cm(2) at 20 mW/cm(2) (630 nm) and 2 × 10(7) PDT cell lysates injected per mouse. DTPP-based PDT cell lysate vaccination had a significant inhibitory effect on tumor growth based on increased CD4(+)/CD8(+) ratios, NK cell percentages, elevated serum IFN-γ and IL-1 levels, and lymphocyte aggregation at the edge of tumors. Thus, DTPP-based PDT can induce LA795 cell apoptosis that can generate anti-tumor effects without use of an adjuvant.