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Diabetic osteoporosis (DOP) belongs to secondary osteoporosis caused by diabetes; it has the characteristics of high morbidity and high disability. In the present study, we constructed a type 1 diabetic rat model and administered chondroitin sulfate (200 mg/kg) for 10 weeks to observe the preventive effect of chondroitin sulfate on the bone loss of diabetic rats. The results showed that chondroitin sulfate can reduce blood glucose and relieve symptoms of diabetic rats; in addition, it can significantly increase the bone mineral density, improve bone microstructure, and reduce bone marrow adipocyte number in diabetic rats; after 10 weeks of chondroitin sulfate administration, the SOD activity level was upregulated, as well as CAT levels, indicating that chondroitin sulfate can alleviate oxidative stress in diabetic rats. Chondroitin sulfate was also found to reduce the level of serum inflammatory cytokines (TNF-α, IL-1, IL-6, and MCP-1) and alleviate the inflammation in diabetic rats; bone metabolism marker detection results showed that chondroitin sulfate can reduce bone turnover in diabetic rats (decreased RANKL, CTX-1, ALP, and TRACP 5b levels were observed after 10 weeks of chondroitin sulfate administration). At the same time, the bone OPG and RUNX 2 expression levels were higher after chondroitin sulfate treatment, the bone RANKL expression was lowered, and the OPG/RANKL ratio was upregulated. All of the above indicated that chondroitin sulfate could prevent STZ-induced DOP and repair bone microstructure; the main mechanism was through anti-oxidation, anti-inflammatory, and regulating bone metabolism. Chondroitin sulfate could be used to develop anti-DOP functional foods and diet interventions for diabetes.

AimsChange in nitrogen (N) availability regulates phosphorus (P) acquisition and potentially alters the competition among native species and invasive weeds. This study determines how current and projected N deposition affect the growth, the intraspecific and interspecific competitive ability of native and invasive plants in calcareous soils with low P availability.MethodsA controlled greenhouse experiment was conducted using sparingly soluble hydroxyapatite (HAP) to simulate the calcareous soils with low P availability. The growth and competitive intensity between an invasive weed (Solidago canadensis) and a native weed (Pterocypsela laciniata) exposed to two levels of N addition representative of current and future N deposition in China were experimentally determined.Important FindingsP acquisition and the growth of both S. canadensis and P. laciniata growing alone significantly increased with increasing N level. However, the effect of N addition was reduced when intraspecific or interspecific competition existed. N addition altered the competitive relationship between S. canadensis and P. laciniata allowing S. canadensis to out-compete P. laciniata due to variation in P acquisition from HAP. Elevated N deposition might assist the invasion of S. canadensis in the widely distributed calcareous soils under environmental changes.

Most of the ion exchange membranes distinguished monovalent ions from the multivalent ions according to the charge difference, but scarcely had selectivity to the specific ions. In order to effectively separate potassium ions from seawater containing more than 30 times sodium ions, potassium ion-sieve composite membranes with specific selectivity to potassium ions had been synthesized in this paper. The potassium ion sieve was successfully synthesized on the flat α-Al2O3 membrane by secondary hydrothermal method to form potassium ion sieve composite membrane. Then, the results of SEM, XRD and EDS showed that the potassium ion sieve had been successfully bonded with base membrane. The results of electrodialysis experiments showed that the ionic perm-selectivity were α (K/Na) = 7.62, α (K/Mg) = 68.43 and α (K/Ca) = 162.92 respectively, which indicated that the composite membrane had special selectivity for potassium ions. The composite membrane had been evaluated under different voltages and temperatures. As the voltage increased, the ion flux and the perm-selectivity to potassium were all improved. Moreover, with the increase of temperature, the ion flux increased but the selectivity to potassium decreased. The separation performance of the composite membrane was studied by using equimolar solution (containing K+, Na+, Ca2+, Mg2+), seawater and twice concentrated seawater as the test solutions, and the results had exhibited that the composite membrane had good application performance in extracting potassium from seawater.

Over recent decades, many studies have reported that hypocrellin A (HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy (PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation (iTRAQ) 2D liquid chromatography with tandem mass spectrometric (LC–MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspase inhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation, and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species (ROS) generations. Further studies showed that PDT treatment with 0.08 µmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome c, and activation of caspase-3, -9, and -7. Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation., Graphical abstract Hypocrellin A-mediated oxidative injury induced by light emitting diode irradiation triggers mitochondrial membrane potential changes and dysfunction, then mitochondrial cytochrome c release and caspase activation, which consequently lead to apoptosis. The study demonstrated hypocrellin A may be a possible therapeutic anticancer agent directed toward mitochondria.fx1

Changes in resource supply ratios affect interspecific competition; however, the effects on the plant invasions are still relatively unknown. To determine the effects of phosphorus (P) availability on the competitive ability of the invasive herb Solidago canadensis in an elevated P environment, we conducted a greenhouse P addition experiment. The invasive herb S. canadensis and the native plant Pterocypsela laciniata were grown in both monoculture and mixture with P addition under an ambient N condition (P+N−) and under a high N condition (P+N+), using ambient N and P conditions (P−N−) as a control. The growth of P. laciniata was significantly inhibited by S. canadensis under the ambient conditions. The P+N− treatment promoted the growth of P. laciniata, but did not promote the growth of S. canadensis. The competition between S. canadensis and P. laciniata was alleviated under the ambient N condition after P addition. The N requirement of P. laciniata was higher than that of S. canadensis, and P. laciniata outcompeted S. canadensis under the P+N+ treatment. We concluded that P addition may reduce the competitive ability of the invasive weed S. canadensis, especially under a high N condition. The ratio of N and P might be a critical factor for determining the competitive abilities of the invasive herb S. canadensis and the native plant P. laciniata.

Diabetic osteoporosis (DOP) is one of the complications of diabetes, with high morbidity, and high disability rate. Here, we established a diabetic rat model and administered lycopene to observe its effect on DOP. Our results showed that ten weeks lycopene treatment lowered blood glucose, improved diabetic induced polydipsia, overeating and body weight loss. Lycopene treatment also enhanced bone mineral density, restored bone mechanical and bone Micro-CT parameters of diabetic rats. Subsequently, lycopene decreased serum inflammatory cytokines levels and increased serum anti-oxidant indicators levels. Moreover, lycopene reduced the number of bone marrow adipocytes, and osteoclasts numbers of diabetic rats. The serum bone turnover markers levels were down-regulated after lycopene treatment. Meanwhile, the bone and serum OPG, RUNX 2 expression levels were up-regulated by lycopene in diabetic rats, and the OPG/RANKL ratio was also up-regulated. This study showed that lycopene could ameliorate diabetic induced bone loss via anti-inflammatory, anti-oxidation, and increasing OPG/RANKL ratio in diabetic rats. Lycopene could be used for nutritional intervention in patients with diabetic osteoporosis.

Anthropogenic nitrogen (N) inputs lead to the increase of phosphorus (P) demand for plants and plant species competition in a N enriched environment may hinge on its ability to utilize soil P sources. In soils, P mostly exists as insoluble phosphate compounds with three mineral elements: iron (Fe), aluminum (Al) or calcium (Ca), and it remains largely unknown whether invasive plant species are able to access such insoluble P sources and its interaction with N enrichment to gain competitive advantage. We determined the morphological traits, growth and nutrient status of an invasive plant Canada goldenrod (Solidago canadensis L.) cultured in soluble phosphate KH2PO4 (Ortho-P), and insoluble inorganic phosphate AlPO4 (Al–P), FePO4 (Fe–P), Ca5(OH)(PO4)3 (Ca–P) at three N supply levels. Results showed that S. canadensis was able to selectively utilize P from Al–P but not from Fe–P or Ca–P by increasing root number and length under N additions. The increasing growth in S. canadensis was closely correlated with the increasing foliar P. Ability to utilize insoluble P sources under enriched N environment serves as a competitive advantage for S. canadensis in Al rich soils. Effective control of S. canadensis invasion may need to consider soil P management in the context of atmospheric N deposition as well.

Clonal integration facilitates the growth and reproduction of clonal plants by providing the ability to share resources among ramets in heterogeneous environments. The benefits of clonal integration for plant growth may depend on a contrast in resource availability and may encounter costs, especially when a young part of the clone is growing across a border between richer and poorer conditions than the old part. We studied a clonal amphibian plant growing across a border between an aquatic and a terrestrial ecosystem, which typically differ in the availability of resources. We asked whether the young part of the clone is supporting the old part with phosphorus and whether this support has costs. We performed an experiment with Alternanthera philoxeroides where plants grow from water to a terrestrial habitat. The terrestrial habitat had either a low or high phosphorus supply, and the connection between the old and young parts of the clone was either left intact or split. We determined that the young part of the clone growing in a terrestrial habitat supported the old part with phosphorus when growing on a substrate rich in phosphorus. We have found no cost of this resource translocation; on the contrary, whole clones increased not only their accumulation of phosphorus, but also of nitrogen. Our study shows how an amphibian plant may profit from heterogeneous habitats by resource sharing in a clonal network.

Hypocrellin A (HA), a perihydroxylated polycyclic quinone isolated from the fungus of Shiraia bambusicola, exhibits a wide spectrum of biological activities in pre-clinical studies. However, poor water solubility is a major clinical constraint factor of HA, leading to unpredictable bioavailability. In this study, HA-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA/HA NPs) were prepared by the single-emulsion solvent-evaporation technique. Characterization of PLGA/HA NPs showed that HA was successfully encapsulated on the PLGA. The drug-loading content and encapsulation efficiency (EE) were 7.0% and 57.5%, respectively. The in vitro release profile demonstrated that HA was released more slowly from nanoparticles in pH 1.5 and pH 6.8 than in pH 7.4. Furthermore, the highest solubility of PLGA/HA NPs in aqueous solution was approximately 35.67-fold that of native HA (n-HA). PLGA/HA NPs had more superior stability compared with n-HA in physiological conditions. In this paper, a sample and sensitive LC-MS/MS method was validated for the first time to quantify HA in rat plasma. The pharmacokinetic parameters and bioavailability of HA between PLGA/HA NPs and n-HA were compared after oral administration in rat. The results implied that the relative bioavailability of PLGA/HA NPs was 2.67-fold that of n-HA, and PLGA/HA NPs had a longer half-life. Therefore, these results suggested that PLGA-blend nanoparticles improved the solubility, stability and bioavailability of HA, and could become a potential and promising carrier for the oral delivery of HA.

Salidroside from Rhodiola rosea L. has hypoglycemic effects, and has anti-osteoporosis effect in diabetic rats. Whether it has beneficial effects on diabetic nephropathy (DN) has not been fully reported. Here, a DN rat model was established by streptozotocin (STZ). Salidroside (10, and 20 mg kg−1 d−1) were orally giving for eight weeks. The purity of salidroside was 99%. The results showed that eight weeks salidroside supplementation dose-dependently decreased blood glucose, serum insulin, serum creatinine, blood urea nitrogen (BUN), as well as urinary albumin of DN rats, repaired the pathological changes of kidney tissue, the renal sclerosis and fibrosis in the kidney of DN rats were improved, and the activities of oxidative defense system associated enzyme such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were also improved. Serum inflammatory cytokines (including tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1β, and interleukin-6) were decreased significantly in DN rats after eight weeks salidroside supplementation. Immunohistochemical results showed that fibrosis related proteins such as transforming growth factor-β1 (TGF-β1), phospho-Smad2 (p-Smad2), and phospho-Smad3 (p-Smad3) expression levels were decreased significantly in the kidney of salidroside treated group. Our results indicate that daily salidroside consumption could alleviate DN in rats, the main mechanisms are anti-inflammatory, anti-oxidative stress, and inhibition of the TGF-β1/Smad2/3 pathway. This study suggested that salidroside could be used as a nutrient against DN, as well as diabetes.

Invasive plants readily invade metal-contaminated areas. The hyperaccumulation of toxic heavy metals is not an uncommon feature among plant species. Although several hypotheses were proposed to explain this phenomenon, it is currently unclear how hyperaccumulation may benefit plants. The invasive Crofton weed (Ageratina adenophora) is a known hyperaccumulator of chromium and lead. We previously found that the species can also hyperaccumulate cadmium. The role of phytoaccumulation in defense to pathogen attack is unclear. We inoculated A. adenophora plants with a common generalist pathogen (Rhizoctonia solani) to test its resistance under cadmium treatment. We found evidence that cadmium hyperaccumulation reduced pathogen infection in A. adenophora. Our findings indicate elemental defense is highly cost efficient for hyperaccumulators inhabiting metal-contaminated sites, where plants were only modestly affected by cadmium. The reduction in pathogen damage conferred by cadmium was relatively high, particularly under lower cadmium levels. However, the benefits at higher levels may be capped. Elemental defense may be a key mechanism for plant invasion into polluted sites, especially in regions with widespread industrial activity. Our study highlights the importance of testing different metal concentrations when testing plant resistance and the importance of considering enemy attack when selecting plants for phytoremediation.

Chondroitin sulfate (CS) has antioxidative, anti-inflammatory, anti-osteoarthritic and hypoglycemic effects. However, whether it has antidiabetic osteoporosis effects has not been reported. Therefore, in this study, we established a STZ-induced diabetic rat model, CS (500 mg kg&minus, 1 d&minus, 1) was orally administrated for eight weeks to study its preventive effects on diabetic osteoporosis. The results showed that eight weeks of CS treatment improved the symptoms of diabetes, the CS-treated group has increased body weight, decreased water or food intake, decreased blood glucose, increased bone-mineral density, repaired bone morphology and decreased femoral osteoclasts and tibia adipocytes numbers. After CS treatment, bone histomorphometric parameters returned to normal, the levels of serum inflammatory cytokines (IL-1&beta, IL-6 and TNF-&alpha, ) decreased significantly, serum SOD, GPX and CAT activities increased and MDA level increased. In the CS-treated group, the levels of serum ALP, CTX-1, TRACP 5b, osteocalcin and RANKL decreased and the serum RUNX 2 and OPG levels increased. Bone immunohistochemistry results showed that CS can effectively increase the expression of OPG and RUNX2 and reduce the expression of RANKL in diabetic rats. All of these indicate that CS could prevent STZ induced diabetic osteoporosis&mdash, mainly through decreasing blood glucose, antioxidative stress, anti-inflammation and regulation of OPG/RANKL expression. CS can therefore effectively prevent bone loss caused by diabetes.

Modifications in soil fertility and microbiota structure driven by invasive plants can initiate a self-promoting mechanism that facilitates their invasion process. This study aimed to resolve how the progression of invasion affects the chemical, biochemical and microbial properties of soil using Conyza canadensis, a widespread and noxious invasive farmland weed, as a model. Different stages of the invasion process were simulated by growing C. canadensis and a non-invasive crop, Lactuca sativa, at different relative densities. Increasing invasion levels (i.e. increasing invader relative densities) resulted in altered properties of the soil, with an overall increase in nutrient supply and enzymatic activities as invasion intensified. Threshold changes in available nitrogen, organic matter and catalase activity in the soil were identified at invasion levels of 69%, 50% and 47%, respectively. Increasing invasion levels also affected the structure of the soil microbiota, with substantial changes occurring in the relative abundance for a number of bacterial and fungal taxa, including some that are relevant to nutrient cycling. Such changes in soil abiotic and biotic composition driven by C. canadensis might lead to positive plant-soil feedbacks that could promote the establishment and spread of the invasive weed.

Diabetic nephropathy (DN) is one of the most important complications&nbsp, of&nbsp, diabetes，&nbsp, and the leading cause of end-stage renal disease (ESRD). While Chromium picolinate (CrPic) supplementation has been found to be effective in treating diabetes, its effects on diabetic-induced nephropathy have not been studied. Therefore, in this study, CrPic (1 mg kg &minus, 1 d &minus, 1) was administered to a DN rat model by oral gavage for eight weeks to investigate its effects. The results show that CrPic supplementation caused a decrease in levels of blood glucose, serum insulin, blood urea nitrogen (BUN), serum creatinine, and urinary albumin in DN rats. It also reversed renal pathological changes, including renal glomerular sclerosis and interstitial fibrosis. In addition, the oxidative defense system in the kidneys of DN rats was found to be improved, the biological activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) increased, and the content of malondialdehyde (MDA) lowered. Immunohistochemical results reveal that the expression levels of renal transforming growth factor-&beta, 1 (TGF-&beta, 1), Smad 2, and Smad 3 decreased significantly in the kidneys of rats in the CrPic-treated group. CrPic administration was thus found to ameliorate diabetic nephropathy in SD rats via an antioxidative stress mechanism, as well the ability to inhibit TGF-&beta, 1/Smad2/3 expression. This study suggests that CrPic could be a potential renal-protective nutrient against diabetic nephropathy.

In this study, we successfully synthesized d-α-tocopheryl polyethylene glycol 2000 succinate (TPGS2k) and prepared TPGS2k-modified poly(lactic-co-glycolic acid) nanoparticles (TPGS2k/PLGA NPs) loaded with 7-ethyl-10-hydroxycamptothecin (SN-38), designated TPGS2k/PLGA/SN-38 NPs. Characterization measurements showed that TPGS2k/PLGA/SN-38 NPs displayed flat and spheroidal particles with diameters of 80-104 nm. SN-38 was encapsulated in TPGS2k emulsified PLGA NPs with the entrapment efficiency and loading rates of SN-38 83.6 and 7.85%, respectively. SN-38 could release constantly from TPGS2k/PLGA/SN-38 NPs in vitro. TPGS2k/PLGA/SN-38 NPs induced significantly higher cytotoxicity on A549 cells and the multidrug resistance (MDR) cell line (A549/DDP cells and A549/Taxol cells) compared with free SN-38. Further studies on the mechanism of the NPs in increasing the death of MDR cells showed that following the SN-38 releasing into cytoplasm the remaining TPGS2k/PLGA NPs could reverse the P-gp mediated MDR via interfering with the structure and function of mitochondria and rather than directly inhibiting the enzymatic activity of P-gp ATPase. Therefore, TPGS2k/PLGA NPs can reduce the generation of ATP and the release of energy for the requisite of P-gp efflux transporters. The results indicated that TPGS2k/PLGA NPs could become the nanopharmaceutical materials with the capability to reversal MDR and improve anticancer effects of some chemotherapy drugs as P-gp substrates.

Photodynamic therapy (PDT) has emerged as a potent novel therapeutic modality that induces cell death through light-induced activation of photosensitizer. But some photosensitizers have characteristics of poor water-solubility and non-specific tissue distribution. These characteristics become main obstacles of PDT. In this paper, we synthesized a targeting drug delivery system (TDDS) to improve the water-solubility of photosensitizer and enhance the ability of targeted TFR positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co-glycolide (PLGA) and carboxymethyl chitosan (CMC) nanoparticle loaded with a photosensitizer hypocrellin A (HA), named TF-HA-CMC-PLGA NPs. Morphology, size distribution, Fourier transform infrared (FT-IR) spectra, encapsulation efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo-cytotoxicity with strong reactive oxygen species (ROS) generation and apoptotic cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs was investigated with an A549 (TFR positive) tumor-bearing model in male athymic nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and slight side effects in normal organs were observed. The results indicated that TDDS has great potential to enhance PDT therapeutic efficacy.

Hypocrellin A (HA), a perylenequinoid pigment isolated from a traditional Chinese medicinal fungus, exhibits excellent antiviral and antitumor properties. However, its hydrophobicity, photodegeradation and dark cytotoxity hamper its clinical application. The aim of the present study is to prepare and evaluate HA loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles, which can be dispersed in water. In this present study, an oil-in-water (O/W) emulsion solvent evaporation technique was employed to fabricate hypocrellin A loaded poly(D,L-lactic-co-glycolic) nanoparticles. The physiochemical properties and morphological characteristics were examined. The photostability, uptake and in vitro phototoxicity and dark toxicity toward A549 cells were evaluated. Scanning electron microscopy (SEM) and confocal laser microscopy (CLSM) images combined with dynamic light scattering (DLS) measurements and surface charge (ζ-potential) results showed that the as-prepared HA-loaded nanoparticles had a narrow dispersity with a surface charge of −5.8 mV. The physicochemical properties of the as-prepared nanoparticles were characterized by differential scanning calorimetry (DSC), X-ray powder diffractometry (XRD) and Fourier transform infrared (FTIR) spectroscopy. The encapsulation efficiency and drug content were 55.1% and 5.0%, respectively. UV-vis spectra and the results from photobleaching experiments indicated that encapsulation could enhance the photostability of HA. In vitro experiments demonstrated that HA loaded PLGA nanoparticles were taken up by A549 cells and significantly exhibited reduced dark cytotoxicity, while maintaining excellent anti-tumor property and ROS production ability. These promising results suggested that nanotechnology provide an intriguing possibility for HA being a potent photosensitizer (PS) in clinical photodynamic therapy (PDT).

Invasive plants are a huge burden on the environment, and modify local ecosystems by affecting the indigenous biodiversity. Invasive plants are generally less affected by pathogens, although the underlying molecular mechanisms responsible for their enhanced resistance are unknown. We investigated expression profiles of three defense hormones (salicylic acid, jasmonic acid, and ethylene) and their associated genes in the invasive weed, Alternanthera philoxeroides, and its native congener, A. sessilis, after inoculation with Rhizoctonia solani. Pathogenicity tests showed significantly slower disease progression in A. philoxeroides compared to A. sessilis. Expression analyses revealed jasmonic acid (JA) and ethylene (ET) expressions were differentially regulated between A. philoxeroides and A. sessilis, with the former having prominent antagonistic cross-talk between salicylic acid (SA) and JA, and the latter showing weak or no cross-talk during disease development. We also found that JA levels decreased and SA levels increased during disease development in A. philoxeroides. Variations in hormonal gene expression between the invasive and native species (including interspecific differences in the strength of antagonistic cross-talk) were identified during R. solani pathogenesis. Thus, plant hormones and their cross-talk signaling may improve the resistance of invasive A. philoxeroides to pathogens, which has implications for other invasive species during the invasion process.