Deep Reinforcement Learning-Based Energy Consumption Optimization for Peer-to-Peer (P2P) Communication in Wireless Sensor Networks.

The fast development of the sensors in the wireless sensor networks (WSN) brings a big challenge of low energy consumption requirements, and Peer-to-peer (P2P) communication becomes the important way to break this bottleneck. However, the interference caused by different sensors sharing the spectrum and the power limitations seriously constrains the improvement of WSN. Therefore, in this paper, we proposed a deep reinforcement learning-based energy consumption optimization for P2P communication in WSN. Specifically, P2P sensors (PUs) are considered agents to share the spectrum of authorized sensors (AUs). An authorized sensor has permission to access specific data or systems, while a P2P sensor directly communicates with other sensors without needing a central server. One involves permission, the other is direct communication between sensors. Each agent can control the power and select the resources to avoid interference. Moreover, we use a double deep Q network (DDQN) algorithm to help the agent learn more detailed features of the interference. Simulation results show that the proposed algorithm can obtain a higher performance than the deep Q network scheme and the traditional algorithm, which can effectively lower the energy consumption for P2P communication in WSN.

Three New Benzophenone Derivatives from Selaginella tamariscina.

Six compounds including three new benzophenones, selagibenzophenones D-F (1-3), two known selaginellins (4-5) and one known flavonoid (6), were isolated from Selaginella tamariscina. The structures of new compounds were established by 1D-, 2D-NMR and HR-ESI-MS spectral analyses. Compound 1 represents the second example of diarylbenzophenone from natural sources. Compound 2 possesses an unusual biphenyl-bisbenzophenone structure. Their cytotoxicity against human hepatocellular carcinoma HepG2 and SMCC-7721 cells and inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells were evaluated. Compound 2 showed moderate inhibitory activity against HepG2 and SMCC-7721 cells, and compounds 4 and 5 showed moderate inhibitory activity to HepG2 cells. Compounds 2 and 5 also exhibited inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production.

Enhancing cytotoxicity of daunorubicin on drug-resistant leukaemia cells with microparticle-mediated drug delivery system.

Multidrug resistance is considered as a major obstacle for effective tumour chemotherapy. With the ability to deliver drugs into tumour cells, microparticles may act as a drug delivery vehicle to overcome drug resistance. In the present study, we developed an approach employing daunorubicin-loaded microparticles to surmount the drug resistance in leukaemia. The microparticles, derived from the drug-sensitive cells K562 and the drug-resistant cells K562/ADR, composed of cellular material, can effectively package drugs using intracellular and extracellular drug-loading method, respectively. The results demonstrated that the microparticles significantly improved the drug anti-tumour effect, which was influenced by the preparation methods and the source of donor cells. We further confirmed that the uptake of microparticles is mediated by an energy-driven endocytic process and mainly associated with clathrin-independent endocytosis and macropinocytosis. These results indicated that the microparticle could serve as a promising drug vehicle for the treatment of drug-resistant leukaemia.

Vanadium and chromium-contaminated soil remediation using VFAs derived from food waste as soil washing agents: A case study.

Food waste (FW) is environmentally unfriendly and decays easily under ambient conditions. Vanadium (V) and chromium (Cr) contamination in soils has become an increasing concern due to risks to human health and environmental conservation. Volatile fatty acids (VFAs) derived from FW was applied as soil washing agent to treat V and Cr-contaminated soil collected from a former V smelter site in this work. The Community Bureau of Reference (BCR) three-step sequential extraction procedure was used to identify geochemical fractions of V and Cr influencing their mobility and biological toxicity. Optimal parameters of a single washing procedure were determined to be a 4 h contact time, liquid-solid ratio of 10:1, VFAs concentration of 30 g/L, and reaction temperature of 25 °C, considering for typical soil remediation projects and complete anaerobic fermentation of FW. Under the optimal conditions, butyric acid fermentation VFAs attained removal rates of 57.09 and 23.55% for extractable fractions of V and Cr, respectively. Simultaneously, a multi-washing process under a constant liquid-solid ratio using fresh and recycled VFAs was conducted, which led to an improvement on the total removal efficiency of toxic metals. The washing procedure could reach the pollution thresholds for several plants, such as of S. viridis, K. scoparia, M. sativa, and E. indica. This strategy enhances the utilization of VFAs derived from food waste, has a positive effect on V and Cr-contaminated soil remediation, wastewater control of soil washing and FW disposal.

[Preparation of CD123 mono-antibody modified tanshinone â ¡A loaded immunoliposome and its in vitro evaluation].

In the study, we developed a novel formulation, CD123 mono-antibody (mAb) modified tanshinone ⅡA loaded immunoliposome (CD123-TanⅡA-ILP) to achieve the targeted drug delivery for leukemia cells. Orthogonal test was used to optimize liposome preparation, and the TanⅡA-loaded PEGylated liposomes (TanⅡA-LP) of S100PC-Chol-(mPEG2000-DSPE)-TanⅡA at 19∶5∶1∶1 molar ratio were prepared by the thin film hydration-probe ultrasonic method. A post-insertion method was applied to prepare CD123-TanⅡA-ILP via thiolated mAb conjugated to the terminal of maleimide-PEG2000-DSPE. The cellular uptake assay was measured by flow cytometry, and the inhibitory effect of CD123-TanⅡA-ILP on NB4 cells proliferation was tested by using MTT assay. The results of cellular uptake assay showed that CD123-ILP could significantly increase the drug uptake of NB4 cells as compared with free drugs and LP. The IC50 values at 48 h incubation were 20.87, 11.71, 7.17 µmol•L⁻¹ respectively for TanⅡA，TanⅡA-LP and CD123-TanⅡA-ILP. CD123-ILP demonstrated a potential and promising targeted drug delivery strategy for acute myelogenous leukemia (AML) treatment.

Casticin suppresses self-renewal and invasion of lung cancer stem-like cells from A549 cells through down-regulation of pAkt.

A subpopulation of cancer stem cells is recognized as the cause of tumorigenesis and spreading. To investigate the effects of casticin (5,3'-dihydroxy-3,6,7,4'-tetramethoxyflavone), derived from Fructus Viticis Simplicifoliae, on lung cancer stem cells, we isolated and identified a subpopulation of lung cancer stem-like cells (LCSLCs) from non-small-cell lung carcinoma A549 cells with the features including self-renewal capacity and high invasiveness in vitro, elevated tumorigenic activity in vivo, and high expression of stemness markers CD133, CD44, and aldehyde dehydrogenase 1 (ALDH1), using serum-free suspension sphere-forming culture method. We then found that casticin could suppress the proliferation of LCSLCs in a concentration-dependent manner with an IC50 value of 0.4 µmol/L, being much stronger than that in parental A549 cells. In addition, casticin could suppress the self-renewal and invasion of LCSLCs concomitant with decreased CD133, CD44, and ALDH1 protein expression and reduced MMP-9 activity. Further experiments showed that casticin suppressed self-renewal and invasion at least partly through down-regulation of Akt phosphorylation. In conclusion, casticin suppressed the characteristics of LCSLCs, suggesting that casticin may be a candidate compound for curing lung cancer via eliminating cancer stem cells.

Progress in regulating inflammatory biomaterials for intervertebral disc regeneration.

Intervertebral disc degeneration (IVDD) is rising worldwide and leading to significant health issues and financial strain for patients. Traditional treatments for IVDD can alleviate pain but do not reverse disease progression, and surgical removal of the damaged disc may be required for advanced disease. The inflammatory microenvironment is a key driver in the development of disc degeneration. Suitable anti-inflammatory substances are critical for controlling inflammation in IVDD. Several treatment options, including glucocorticoids, non-steroidal anti-inflammatory drugs, and biotherapy, are being studied for their potential to reduce inflammation. However, anti-inflammatories often have a short half-life when applied directly and are quickly excreted, thus limiting their therapeutic effects. Biomaterial-based platforms are being explored as anti-inflammation therapeutic strategies for IVDD treatment. This review introduces the pathophysiology of IVDD and discusses anti-inflammatory therapeutics and the components of these unique biomaterial platforms as comprehensive treatment systems. We discuss the strengths, shortcomings, and development prospects for various biomaterials platforms used to modulate the inflammatory microenvironment, thus providing guidance for future breakthroughs in IVDD treatment.

Nano-enzyme functionalized hydrogels promote diabetic wound healing through immune microenvironment modulation.

Non-healing diabetic wounds often culminate in amputation and mortality. The main pathophysiological features in diabetic wounds involve the accumulation of M1-type macrophages and excessive oxidative stress. In this study, we engineered a nano-enzyme functionalized hydrogel by incorporating a magnesium ion-doped molybdenum-based polymetallic oxide (Mg-POM), a novel bioactive nano-enzyme, into a GelMA hydrogel, to obtain the GelMA@Mg-POM system to enhance diabetic wound healing. GelMA@Mg-POM was crosslinked using UV light, yielding a hydrogel with a uniformly porous three-dimensional mesh structure. In vitro experiments showed that GelMA@Mg-POM extraction significantly enhanced human umbilical vein endothelial cell (HUVEC) migration, scavenged ROS, improved the inflammatory microenvironment, induced macrophage reprogramming towards M2, and promoted HUVEC regeneration of CD31 and fibroblast regeneration of type I collagen. In in vivo experiments, diabetic rat wounds treated with GelMA@Mg-POM displayed enhanced granulation tissue genesis and collagen production, as evidenced by HE and Masson staining. Immunohistochemistry demonstrated the ability of GelMA@Mg-POM to mitigate macrophage-associated inflammatory responses and promote angiogenesis. Overall, these findings suggest that GelMA@Mg-POM holds significant promise as a biomaterial for treating diabetic wounds.

Biopharmaceutical, preclinical pharmacokinetic and pharmaco-dynamic investigations of an orally administered novel 3-nbutylphthalide prodrug for ischemic stroke treatment.

Ischemic stroke (IS) has been contributing in leading causes of disability and death worldwide and the cases are still increasing. In China, naturally sourced compound 3-n-butylphthalide (NBP) is widely applied in clinical practice for IS treatment with established evidences of efficacy and safety. However, NBP is an oily liquid at room temperature and has no active brain targeting ability, quite limiting its broader application in clinical practice. Via intravenous injection (i.v.) a prodrug compound (DB1) we previously developed deriving from NBP had dramatically enhanced the pharmacological effects, where however, this i.v. route still discount future patient compliance. As druggability of DB1 in oral administration has yet to be elaborated, the current study intended to systemically investigate its biopharmaceutical properties, so as to further consider clinical applicability of DB1 oral preparations. Additionally, pharmacokinetics and pharmacodynamics of DB1 via oral administered route were also studied, illustrating broad potential of further DB1 medicine development. After the derivation, aqueous solubility of DB1 improved 3∼400 folds compared with NBP in various pH media, and n-octanol/water partition coefficient kept in the range of 0∼2. In situ single-pass intestinal perfusion on rats showed effective permeability coefficient of DB1 over 10-2 cm/s. In contrast to NBP, oral administration of DB1 could display significant enhanced bioavailability in rats and achieve increased accumulation in brain tissues. As expected, DB1 effectively alleviated oxidative stress damage and reduced infarct volume on ischemia/reperfusion (I/R) modeled rats, resulting in reduced mortality. Additionally, this new prodrug did not add any safety concerns based on NBP. Therefore, biopharmaceutical results and preclinical pharmacodynamic evidences support the conclusion that an oral administration of DB1 may have a good potential for clinical IS treatment.

Cytotoxic flavonoids from the leaves of Callicarpa nudiflora hook.

A new flavonoid glycoside, luteolin-3'-O-ß-D-6″-acetyl glucopyranoside (1), along with six known flavonoids, were isolated from the leaves of Callicarpa nudiflora Hook. The structures of the isolated compounds were established on the basis of extensive spectroscopic analyses. Compound 6 exhibited potent cytotoxicity and compounds 1 and 7 exhibited moderate cytotoxicity against human hepatocellular carcinoma SMMC-7721 cells.

Selaginellins I and J, two new alkynyl phenols, from Selaginella tamariscina (Beauv.) Spring.

Selaginellins I (1) and J (2), two new compounds, were isolated from Selaginella tamariscina (Beauv.) Spring and were characterized as (R,S)-4-((2',4'-dihydroxy-4-(hydroxymethyl)-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene)cyclohexa-2,5-dienone (1) and (R,S)-4-((3-((3,4-dihydroxyphenyl)ethynyl)-4'-hydroxy-4-(hydroxymethyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene)cyclohexa-2,5-dienone (2) on the basis of UV, IR, 1D and 2D NMR, and HR-ESI-MS spectroscopic analysis.

Two new selaginellin derivatives from Selaginella tamariscina (Beauv.) Spring.

Two new selaginellin derivatives, selaginellins K (1) and L (2), were isolated from Selaginella tamariscina (Beauv.) Spring and characterized as 2-formyl-4,4'-dihydroxy-3-[(4-hydroxyphenyl)ethynyl]biphene and 4,4'-dihydroxy-2-methyl-3-[(4-hydroxyphenyl)ethynyl]biphene on the basis of their spectroscopic data including UV, IR, 1D, and 2D NMR as well as HR-ESI-MS spectroscopic analysis.

Novel brain-targeting 3-n-butylphthalide prodrugs for ischemic stroke treatment.

Currently, ischemic stroke is the leading cause of disability and death worldwide, and the performance of corresponding drugs is often unsatisfactory owing to the complex pathological processes and the impediment of the blood-brain barrier (BBB). Here, we employed various tertiary amino groups, including different linear, cyclic, and bimolecular drug structures, to modify 3-n-butylphthalide (NBP), a natural product used for ischemic stroke treatment, which has poor bioavailability, to generate a series of six prodrugs. These prodrugs showed significantly improved solubility and cellular uptake, which were primarily driven by putative pyrilamine cationic transporters. They also displayed more efficient brain delivery in vivo, reaching as high as 21.5-fold brain accumulation increase compared with NBP, leading to much higher bioavailability and stronger therapeutic effects. The toxicity of these molecules is also lower or similar to that of unmodified NBP. We showed that the tertiary amino group-modified NBP prodrugs are effective and safe for treating ischemic stroke with significantly enhanced druggability; hence, they have potential for further clinical development.

A new flavonoid from Selaginella tamariscina (Beauv.) Spring.

A new flavonoid, 6-(2-hydroxy-5-carboxyphenyl)-apigenin (1), together with two new natural products, 3-(4-hydroxyphenyl)-6,7-dihydroxy coumarin (2), 1-methoxy-3-methylanthraquinone (3) and four known compounds, were isolated from Selaginella tamariscina (BEAUV.) SPRING. The structures of the new isolated compounds were elucidated on the basis of 1D and 2D NMR as well as ESI-HR-MS spectroscopic analysis.

Review of plant-vanadium physiological interactions, bioaccumulation, and bioremediation of vanadium-contaminated sites.

Vanadium is a multivalent redox-sensitive metal that is widely distributed in the environment. Low levels of vanadium elevate plant height, root length, and biomass production due to enhanced chlorophyll biosynthesis, seed germination, essential element uptake, and nitrogen assimilation and utilization. However, high vanadium concentrations disrupt energy metabolism and matter cycling; inhibit key enzymes mediating energy production, protein synthesis, ion transportation, and other important physiological processes; and lead to growth retardation, root and shoot abnormalities, and even death of plants. The threshold level of toxicity is highly plant species-specific, and in most cases, the half maximal effective concentration (EC50) of vanadium for plants grown under hydroponic conditions and in soil varies from 1 to 50 mg/L, and from 18 to 510 mg/kg, respectively. Plants such as Chinese green mustard, chickpea, and bunny cactus could accumulate high concentrations of vanadium in their tissues, and thus are suitable for decontaminating and reclaiming of vanadium-polluted soils on a large scale. Soil pH, organic matter, and the contents of iron and aluminum (hydr)oxides, phosphorus, calcium, and other coexisting elements affect the bioavailability, toxicity, and plant uptake of vanadium. Mediation of these conditions or properties in vanadium-contaminated soils could improve plant tolerance, accumulation, or exclusion, thereby enhancing phytoremediation efficiency. Phytoremediation with the assistance of soil amendments and microorganisms is a promising method for decontamination of vanadium polluted soils.

Preparation, environmental application and prospect of biochar-supported metal nanoparticles: A review.

Biochar is a low-cost, porous, and carbon-rich material and it exhibits a great potential as an adsorbent and a supporting matrix due to its high surface activity, high specific surface area, and high ion exchange capacity. Metal nanomaterials are nanometer-sized solid particles which have high reactivity, high surface area, and high surface energy. Owing to their aggregation and passivation, metal nanomaterials will lose excellent physiochemical properties. Carbon-enriched biochar can be applied to overcome these drawbacks of metal nanomaterials. Combining the advantages of biochar and metal nanomaterials, supporting metal nanomaterials on porous and stable biochar creates a new biochar-supported metal nanoparticles (MNPs@BC). Therefore, MNPs@BC can be used to design the properties of metal nanoparticles, stabilize the anchored metal nanoparticles, and facilitate the catalytic/redox reactions at the biochar-metal interfaces, which maximizes the efficiency of biochar and metal nanoparticles in environmental application. This work detailedly reviews the synthesis methods of MNPs@BC and the effects of preparation conditions on the properties of MNPs@BC during the preparation processes. The characterization methods of MNPs@BC, the removal/remediation performance of MNPs@BC for organic contaminants, heavy metals and other inorganic contaminants in water and soil, and the effect of MNPs@BC properties on the remediation efficiency were discussed. In addition, this paper summarizes the effect of various parameters on the removal of contaminants from water, the effect of MNPs@BC remediation on soil properties, and the removal/remediation mechanisms of the contaminants by MNPs@BC in water and soil. Moreover, the potential directions for future research and development of MNPs@BC have also been discussed.

7-Difluoromethyl-5,4'-dimethoxygenistein, a novel genistein derivative, has therapeutic effects on atherosclerosis in a rabbit model.

Genistein is a phytoestrogen that is known to have a protective effect on the vascular endothelial wall. However, it exhibits poor bioavailability, which limits the use of genistein to treat cardiovascular and cerebrovascular diseases. A novel genistein derivative, 7-difluoromethyl-5,4'-dimethoxygenistein (dFMGEN), has shown a better protective effect on vascular endothelial damage in vitro than genistein. In this study, we further evaluated therapeutic effects of dFMGEN on the vascular endothelial wall and atherosclerosis in a rabbit model in vivo. There were 5 groups: the GEN group (genistein 5 mg/kg per day), lovastatin group (lovastatin 5 mg/kg per day), dFMGEN group (dFMGEN 5 mg/kg per day), model control group (the same amount of vehicle solvent), and the normal control group; all feedings administered via intragastric administration. We demonstrated that dFMGEN (1) attenuated the development of atherosclerosis, (2) reduced serum total cholesterol and low-density lipoprotein cholesterol concentrations, (3) decreased lipid peroxidation in the rabbit atherosclerosis model, and (4) increased smooth muscle cell and collagen content in atheroma of thoracic aortas. These results provide an experimental foundation for dFMGEN's potential effects in preventing and treating atherosclerosis, acute coronary syndromes, and potentially ischemia-reperfusion injury during acute myocardial infarction and cerebral infarction.

7-difluoromethyl-5,4'-dimethoxygenistein, a novel agent protecting against vascular endothelial injury caused by oxidative stress.

1. Genistein is known to protect the vascular endothelium. However, genistein exhibits poor bioavailability, which limits its use in the treatment of cardiovascular diseases. 7-Difluoromethyl-5,4'-dimethoxygenistein (dFMGEN), prepared by the difluoromethylation and alkylation of genistein, is a new active chemical entity. The protective effects of dFMGEN against vascular endothelial injury caused by oxidative stress were investigated in the present study. 2. Human umbilical vein endothelial cells were treated with either genistein (10 micromol/L) or various concentrations of dFMGEN (0.1, 0.3, 1, 3 and 10 micromol/L) for 30 min before exposure to 1 mmol/L H(2)O(2) for 24 h. The generation of reactive oxygen species (ROS) was assessed by fluorescence flow cytometry, the release of lactate dehydrogenase (LDH) was examined by biochemical assay, cell viability was measured by the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay, cell apoptosis was detected by flow cytometry and the expression of caspase 3 was examined by western blot analysis. 3. Pretreatment with 0.1, 0.3, 1, 3 and 10 micromol/L dFMGEN decreased the generation of ROS and the release of LDH in H(2)O(2)-exposed vascular endothelial cells, enhanced cell viability in a concentration-dependent manner over the concentration range 0.1-10 micromol/L, suppressed H(2)O(2)-induced apoptosis of vascular endothelial cells and downregulated the expression of caspase 3. The protective effect of 10 micromol/L dFMGEN against oxidative stress-induced endothelial injury was stronger than that of 10 micromol/L genistein. 4. The results of the present study suggest that dFMGEN can protect against vascular endothelial injury caused by oxidative stress.

Synthesis of genistein derivatives and determination of their protective effects against vascular endothelial cell damages caused by hydrogen peroxide.

A series of genistein derivatives, prepared by alkylation and difluoromethylation, were tested for their inhibitory effects on the hydrogen peroxide induced impairment in human umbilical vein endothelial (HUVE-12) cells in vitro. The HUVE-12 cells were pretreated with either the vehicle solvent (DMSO), genistein, or different amounts of the genistein derivatives for 30 min before exposed to 1 mM hydrogen peroxide for 24 h. Cell apoptosis was determined by flow cytometry with propidium iodide (PI) staining. Cellular injury was estimated by measuring the lactate dehydrogenase (LDH) release. Data suggested that the genistein derivatives possessed a protective effect on HUVE-12 cells from hydrogen peroxide induced apoptosis and reduced LDH release. Among these derivatives, 7-difluoromethyl-5,4'-dimethoxygenistein exhibited the strongest activity against hydrogen peroxide induced apoptosis of HUVE-12 cells.

A novel immunoliposome mediated by CD123 antibody targeting to acute myeloid leukemia cells.

The application of the tumor targeting antibody-mediated immunoliposomes (ILP) provides us a potential effective strategy for treating malignancies, such as acute myeloid leukemia (AML). CD123, which is specifically overexpressed on AML cells, plays an important role in cell cycling and enhances the cell resistance to the apoptotic stimuli. Given such a unique role of CD123 in AML cells, we aim to develop a novel drug targeting delivery system using CD123 monoclonal antibody (mAb) in this study. On the basis of the daunorubicin (DNR) loaded PEGylated liposomes (DNR-LP), a post-insertion method was applied to covalently attach the anti-CD123 mAb onto the surface of the liposomes to obtain the anti-CD123 mAb modified immunoliposomes (CD123-ILP). Immunoliposomes with different anti-CD123 mAb density (mAb/liposomal S100PC, molar ratio, 0.06%, L-CD123-ILP and 0.14%, H-CD123-ILP) were prepared, respectively. The expressions of CD123 in KG-1a, Kasumi-1, HL-60, NB4 and THP-1 cells were determined by flow cytometry. The cell binding and uptake assays revealed that CD123-ILP was internalized into the CD123+ AML cells, while the MTT assay indicated that CD123-ILP had stronger inhibitory effect on the growth of THP-1 and KG-1a cells, in which CD123 were highly expressed. Furthermore, in vitro drug release studies of DNR-LP and CD123-ILP showed a sustained release profile for both systems, which were further confirmed by in vivo pharmacokinetics study of liposomal DNR in rats. In this study, we reported the development of CD123-ILP for the first time by our best knowledge, which offered a promising drug targeting delivery system against CD123+ AML cells.