Tumor microenvironment-responsive size-changeable and biodegradable HA-CuS/MnO2 nanosheets for MR imaging and synergistic chemodynamic therapy/phototherapy.

Tumor microenvironment (TME)-responsive size-changeable and biodegradable nanoplatforms for multimodal therapy possess huge advantages in anti-tumor therapy. Hence, we developed a hyaluronic acid (HA) modified CuS/MnO2 nanosheets (HCMNs) as a multifunctional nanoplatform for synergistic chemodynamic therapy (CDT)/photothermal therapy (PTT)/photodynamic therapy (PDT). The prepared HCMNs exhibited significant NIR light absorption and photothermal conversion efficiency because of the densely deposited ultra-small sized CuS nanoparticles on the surface of MnO2 nanosheet. They could precisely target the tumor cells and rapidly decomposed into small sized nanostructures in the TME, and then efficiently promote intracellular ROS generation through a series of cascade reactions. Moreover, the local temperature elevation induced by photothermal effect also promote the PDT based on CuS nanoparticles and the Fenton-like reaction of Mn2+, thereby enhancing the therapeutic efficiency. Furthermore, the T1-weighted magnetic resonance (MR) imaging was significantly enhanced by the abundant Mn2+ ions from the decomposition process of HCMNs. In addition, the CDT/PTT/PDT synergistic therapy using a single NIR light source exhibited considerable anti-tumor effect via in vitro cell test. Therefore, the developed HCMNs will provide great potential for MR imaging and multimodal synergistic cancer therapy.

An undefined cystatin CsCPI1 from tea plant Camellia sinensis harbors antithrombotic activity.

Tea consumption has been linked to a decreased risk of cardiovascular disease (CVD) mortality, which imposes a heavy burden on the healthcare system; however, which components in tea cause this beneficial effect is not fully understood. Here we uncovered a cystatin (namely CsCPI1), which is a cysteine proteinase inhibitor (CPI) of the tea plant (Camellia sinensis) that promotes antithrombotic activity. Since thrombosis is a common pathogenesis of fatal CVDs, we investigated the effects of CsCPI1, which showed good therapeutic effects in mouse models of thrombotic disease and ischemic stroke. CsCPI1 significantly increases endothelial cell production of nitric oxide (NO) and inhibits platelet aggregation. Notably, CsCPI1 exhibited no cytotoxicity or resistance to pH and temperature changes, which indicates that CsCPI1 might be a potent antithrombotic agent that contributes to the therapeutic effects of tea consumption against CVD. Specifically, the antithrombotic effects of CsCPI1 are distinct from the classical function of plant cystatins against herbivorous insects. Therefore, our study proposes a new potential role of cystatins in CVD prevention and treatment, which requires further study.

Revealing and modeling of fire products in gas-phase for epoxy/black phosphorus-based nanocomposites.

This work aims at revealing and optimizing the mechanism, to promote the design of phosphorus-based flame retardants (PFRs) for controlling the spread of fire risk caused by the continuous spread of polymers. Herein, we synthesized about 10 nm TiO2 grown in situ on the surface of BP through a simple hydrothermal procedure to introduce it into epoxy (EP/BP-TiO2). In the first place, EP/BP-TiO22.0 nanocomposite achieves a reduction of 58.96% and 50.35% in PHRR and THR, respectively. Secondly, the pyrolysis of BP from Pn to P4, P3 and P2 is revealed. As a guide, P4 is established as a characteristic product of the analytical model for evaluating the effects in the gas phase for BP-based hybrids. Finally, this work clarifies the enhancement path for BP-TiO2 is optimized for the capturing of OH· and H· radicals by P4(POx). Crucially, this study reveals and controls the mechanism of the BP-based hybrids at the molecular level, which is expected to provide a promising analytical model for broad market PFRs design to address the risks and challenges of casualties and ecology caused by composites fire.

Dnah9 mutant mice and organoid models recapitulate the clinical features of patients with PCD and provide an excellent platform for drug screening.

Primary cilia dyskinesia (PCD) is a rare genetic disease caused by ciliary structural or functional defects. It causes severe outcomes in patients, including recurrent upper and lower airway infections, progressive lung failure, and randomization of heterotaxy. To date, although 50 genes have been shown to be responsible for PCD, the etiology remains elusive. Meanwhile, owing to the lack of a model mimicking the pathogenesis that can be used as a drug screening platform, thereby slowing the development of related therapies. In the current study, we identified compound mutation of DNAH9 in a patient with PCD with the following clinical features: recurrent respiratory tract infections, low lung function, and ultrastructural defects of the outer dynein arms (ODAs). Bioinformatic analysis, structure simulation assay, and western blot analysis showed that the mutations affected the structure and expression of DNAH9 protein. Dnah9 knock-down (KD) mice recapitulated the patient phenotypes, including low lung function, mucin accumulation, and increased immune cell infiltration. Immunostaining, western blot, and co-immunoprecipitation analyses were performed to clarify that DNAH9 interacted with CCDC114/GAS8 and diminished their protein levels. Furthermore, we constructed an airway organoid of Dnah9 KD mice and discovered that it could mimic the key features of the PCD phenotypes. We then used organoid as a drug screening model to identify mitochondrial-targeting drugs that can partially elevate cilia beating in Dnah9 KD organoid. Collectively, our results demonstrated that Dnah9 KD mice and an organoid model can recapture the clinical features of patients with PCD and provide an excellent drug screening platform for human ciliopathies.

Covalent grafting diazotized black phosphorus with ferrocene oligomer towards smoke suppression and toxicity reduction.

In comparison with the thermal hazard of polymers, noxious smoke and gas produced by the combustion of polymers make the environment self-purification a huge challenge. As a new type of a highly effective flame retardant, black phosphorus (BP) can effectively decrease the thermal hazard of polymers, but its performances in smoke suppression and toxicity reduction are unsatisfactory. In this article, a method of covalently grafting diazotized BP with a ferrocene oligomer was applied to promote the smoke suppression and toxicity reduction efficiency of BP. In our work, the BP-NH nanomaterials with a mass of amino groups on the surface were acquired by diazotizing the BP. Then, the BP-Fe was obtained by covalently grafting the ferrocene chloride salt and nitrogen-containing heterocycles on the surface of BP. The smoke production rate (SPR) and total smoke production (TSP) values of the epoxy resin (EP) decreased by 49.8% and 52.5% with the addition of 2 wt% BP-Fe, respectively. In comparison with previous studies, this work was far more effective than the previous work in smoke suppression and flame retardant. The release of toxic gases (CO and HCN) and volatile organic compounds in the EP was also effectively inhibited at the same time. In addition, the storage modulus and tensile strength of nanocomposites increased by 35.1% and 27.2% with the addition of 1 wt% BP-Fe. This work also provides a new idea on how to simultaneously strengthen the toxic smoke suppression, mechanical properties, and flame retardant of polymer materials.

Soil Phosphorus Pools, Bioavailability and Environmental Risk in Response to the Phosphorus Supply in the Red Soil of Southern China.

Excess phosphorus (P) accumulation in the soil can change the bioavailability of P and increase the leaching risks, but the quantitative evaluation of these responses in acidic red soil is lacking. This study aimed to investigate the composition of soil P fractions under different phosphorus apparent balances (PAB) in acidic red soil and the bioavailability and the leaching change-points of different P fractions. Five phosphorus (P) fertilization rates were applied (0, 16.38, 32.75, 65.50, 131.00 kg P·ha-1) in every sweet corn cultivation from the field experiment, and the treatments were marked as P0, P1, P2, P3, and P4, respectively. The PAB showed negative values in P0 and P1 which were -49.0 and -15.0 kg P·ha-1 in two years, respectively. In contrast, PAB in P2 as well as in P3 and P4 were positive, the content ranging from 40.2 to 424.3 kg P·ha-1 in two years. Per 100 kg ha-1 P accumulate in the soil, the total P increased by 44.36 and 10.41 mg kg-1 in the surface (0-20 cm) and subsurface (20-40 cm) soil, respectively. The content of inorganic P fractions, including solution phosphate (Sol-P), aluminum phosphate (Al-P), iron phosphate (Fe-P), reduction phosphate (Red-P), and calcium phosphate (Ca-P), significantly increased by 0.25, 16.22, 22.08, 2.04, and 5.08 mg kg-1, respectively, in surface soil per 100 kg ha-1 P accumulated in the soil. Path analysis showed that the most important soil P fractions contributing to Olsen-P were Sol-P and Al-P, which can directly affect Olsen-P, and their coefficients were 0.24 and 0.73, respectively. Furthermore, the incubation experiments were conducted in the laboratory to investigate the leaching risk of different P fractions, and they showed Sol-P was a potential source of leaching, and the leaching change-points of Al-P and Fe-P were 74.70 and 78.34 mg·kg-1, respectively. Continuous P that accumulated in soil changed the composition of P fractions, and the bioavailability as well as the leaching risks increased. This is important in optimizing soil P fertilization management in agricultural ecosystems based on the bioavailability and critical levels for leaching of P fractions.

Short term effects of biochar with different particle sizes on phosphorous availability and microbial communities.

Despite the increasing interest for biochar as a soil amendment, a knowledge gap remains on different particle size of biochar on soil phosphorous (P) availability and its impacts on microbial community. We hypothesized that biochar particle size and incubation temperature can significantly influence soil P availability and microbial community in subtropical acidic soil. A laboratory incubation study was established to investigate the effects of soil pH, available P and soil microbial responses to biochar addition having varying particle sizes using paddy soil and red soil under different incubation temperatures (15 °C & 25 °C). Biochar produced via pyrolysis of spent mushroom substrate feedstock was sieved into three particle sizes ((≤0.5 mm (fine), 0.5-1.0 mm (medium) and 1.0-2.0 mm (large)). The results exhibited that the fine particle biochar resulted in significantly higher release of P, soil pH, available P and bacterial species richness while simultaneously reducing the activities of phosphatase enzyme in both soils. Apprehending the impact of biochar particle size and incubation temperature, principal coordinate analysis (PCoA) predicted that soil microbial communities with fine particle biochar and high incubation temperature (25 °C) clustered separately. Redundancy analysis depicted that fine particle biochar had a direct association with available P and soil pH while high incubation temperature depicted a strong affinity for microbial communities. Hence, it is suggested that fine particle biochar and high incubation temperature may provide better habitat for microorganisms compared to the other particle sizes which may be due to improved soil pH and available P. However, a long term study of different biochar particles application in subtropical acidic soil needs to be pursued further for a more comprehensive understanding on this issue.

Variations in eco-enzymatic stoichiometric and microbial characteristics in paddy soil as affected by long-term integrated organic-inorganic fertilization.

To investigate the effects of different nutrient management regimes on the soil chemical, eco-enzymatic stoichiometric and microbial characteristics, soil samples were collected from a 30-year, long-term field experiment with six plots growing rice. The results showed that as integrated fertilization increased, so did the concentrations of soil total or available nutrients and microbial biomass carbon (MBC). Our results also found enhanced soil basal respiration and cumulative carbon mineralization compared to chemical fertilization alone at the same nutrient doses. The activities of soil protease (Pro), ß-glucosidase (ßG), N-acetyl-glucosaminidase (NAG) and acid phosphatase (AP) from the integrated fertilization treatments were significantly higher than those of the treatments without organic manure, so did the activities of soil leucyl aminopeptidase (LAP) and urease (Ure) from the treatment with organic manure in addition to farmer practise fertilization (NPKM2). The stoichiometric ratios, expressed as lnßG/ln(NAG+LAP)/lnPro/lnUre/lnAP, ranged from 1:0.94:1.04:0.67:1.01 to 1:0.98:1.10:0.78:1.25, indicating that the acquisition of C, N and P changed consistently and synchronously under different nutrient management strategies. Integrated fertilization was more beneficial to the acquisition and utilization of soil organic carbon compared to low-molecular-weight organic nitrogen. We concluded that protease and urease should be considered in eco-enzymatic stoichiometric assessments for the hydrolysis of proteins, amino acids, carbohydrates and phosphomonoesters in soil, and integrated fertilization with chemical fertilizers and organic manure should be recommended as a preferable nutrient management system for intensive rice cultivation.

Variations of Escherichia coli O157:H7 Survival in Purple Soils.

Escherichia coli O157:H7 is a well-recognized cause of human illness. Survival of Escherichia coli O157:H7 in five purple soils from Sichuan Province was investigated. The dynamics of E. coli O157:H7 survival in purple soils were described by the Weibull model. Results showed that this model is suitable to fit survival curves of E. coli O157:H7 in purple soils, with the calculated td value (survival time needed to reach the detection limit of 100 CFU·g-1) ranging from 2.99 days to 26.36 days. The longest survival time of E. coli O157:H7 was observed in neutral purple soils (24.49 days), followed by alkalescent purple soil (18.62 days) and acid purple soil (3.48 days). The redundancy analysis (RDA) revealed that td values were significantly enhanced by soil nutrition (total organic carbon (OC), total nitrogen (TN), available potassium (AK) and the ratio of humic acid to fulvic acid (Ha/Fa)), but were significantly suppressed by iron and aluminum oxide.

Baicalin attenuates lipopolysaccharide induced inflammation and apoptosis of cow mammary epithelial cells by regulating NF-κB and HSP72.

Baicalin is the main ingredient of traditional Chinese herbal medicine, Scutellaria baicalensis, which has been widely used clinically as an anti-inflammatory agent. However, molecular mechanism of action of this drug is not yet clear. In the present study, the protective mechanism of baicalin against lipopolysaccharide (LPS) induced inflammatory injury in cow mammary epithelial cells (CMECs) was explored. For this purpose, in vitro cultured CMECs were treated with baicalin (10µg/mL) and LPS (10µg/mL) for 24 and 12h, respectively, and the cell viability was measured by using cell counting kit-8 (CCK-8). The results revealed that LPS induced inflammatory responses, as p-p65/p65 and p-IκBα/IκBα ratios and TNF-α and IL-1ß production was increased in the CMECs. Both Bcl-2/Bax ratio and cell viability were decreased and caspase-3 cleaved following LPS treatment, indicating apoptosis of CMECs. Moreover, both LPS and baicalin increased HSP72 expression of the CMECs. However, cellular inflammatory responses and apoptosis were significantly reduced in baicalin treated CMECs. In conclusion, baicalin ameliorated inflammation and apoptosis of the CMECs induced by LPS via inhibiting NF-κB activation and up regulation of HSP72.

[Effects of Salidroside on Tic Behavior of Tourette Syndrome Model Rats].

OBJECTIVE: To observe the effect of salidroside on tic behavior and in vivo dopamine DA) and serotonin (5-HT) levels in Tourette syndrome (TS) model rats. METHODS: Forty rats were randomly divided into the blank control group, the TS model group, the haloperidol-treated group (0.5 mg/kg x d(-1)), and the salidroside-treated group (50 mg/kg x d(-1)), 10 in each group. TS rat model was induced by imino-dipropio-nitrile (IDPN). Peritoneal injection of haloperidol and salidroside was started from the 4th day of modeling in the haloperidol-treated group and the salidroside-treated group respectively. Normal saline was peritoneally injected to rats in the blank control group and the TS model group respectively. Stereotyped behavior was scored, and changes of DA and 5-HT levels in blood and striatum were measured before modeling, after modeling, and after intervention. RESULTS: Compared with the blank control group, the score of the tic behavior was elevated (P < 0.01) , levels of DA and 5-HT in plasma and striatum were reduced in the model group (P < 0.01, P < 0.05). Compared with the same group after modeling, the tic behavior score decreased and plasma DA levels increased in the two treated groups after intervention (P < 0.01). 5-HT content increased in the salidroside-treated group (P < 0.01). Compared with the model group after intervention, the tic behavior score was significantly reduced (P < 0.01), and DA levels in plasma and striatum were elevated (P < 0.01, P < 0.05) in the salidroside-treated group and the haloperidol-treated group. Compared with the haloperidol-treated group, the tic behavior score increased (P < 0.01), DA levels in plasma and striatum were lowered (P < 0.01, P < 0.05), the 5-HT level increased in plasma and striatum (P < 0.01, P < 0.05) in the salidroside-treated group. CONCLUSIONS: In the salidroside-treated group, the tic behavior was significantly reduced, and DA levels in plasma and striatum were elevated. Its mechanism might be related to regulating activities of dopamine neurons in striatum.

[Effects of green tea polyphenol on the behaviour of Alzheimer' s disease like mice induced by D-galactose and Abeta25-35].

OBJECTIVE: To study the effects of green tea polyphenol (GTP) on the behaviour of Alzheimer' s Disease like mice induced by D-galactose and Abeta25-35. METHODS: D-galactose (120 mg/kg) was intraperitoneally injected into mice for 12 weeks and Abeta25-35 (4nmol) was injected by icv to establish Alzheimer' s Disease like mice. The protective and therapeutic effects of GTP were determined by using water maze test, step down test, step through test and open field test. RESULTS: GTP ameliorated the deleterious effects of D-galactose and Abeta25-35, and thereby improved the animal' s learning and memory, prolonged latency time, and the error numbers were significantly reduced. At the same time the autonomic activities were significantly increased. CONCLUSION: GTP can improve the behaviour of Alzheimer' s Disease like mice induced by D-galactose and Abeta25-35.

[Experimental studies of anti-proliferative effects of marinesponge extracts S1 - S3 on human lung adenocarcinoma and hepatocarcinoma cells].

OBJECTIVE: To study the anti-proliferative effects of marinesponge extract-S1 - S3 on human lung adenocarcinoma GLC-82, hepatocarcinoma 7402 and gastric carcinoma MCG-803 cells in vitro. METHODS: The parameters were got by MTT assay. RESULTS: After human lung adenocarcinoma GLC-82, hepatocarcinoma 7402 and gastric carcinoma MCG-803 cells were treated by marinesponge extract-S1 - S3 for 48h, the growth of lung adenocarcinoma GLC-82 and hepatocarcinoma 7402 cells were inhibited significantly by the S3 and the IC50 were 2. 714 microg/ml and 2. 598 microg/ml respectively; but no significant effect on the gastric carcinoma MCG-803 cells. The marinesponge extracts S1 and S2 don't show inhibitive effect on the proliferation of those three tumor cells. CONCLUSION: Marine-sponge extract S3 can inhibit the proliferation of lung adenocarcinoma GLC-82 and hepatocarcinoma 7402 cells significantly.