Biochemical, metabolic, and immune responses of mud crab (Scylla paramamosain) after mud crab reovirus infection.

Mud crab reovirus (MCRV) is a serious pathogen that leads to large economic losses in the mud crab farming. However, the molecular mechanism of the immune response after MCRV infection is unclear. In the present study, physiological, transcriptomic, and metabolomic responses after MCRV infection were investigated. The results showed that MCRV infection could increase lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities. MCRV infection decreased antioxidant enzyme activity levels, induced oxidative stress, and caused severe histological damage. Transcriptome analysis identified 416 differentially expressed genes, including 354 up-regulated and 62 down-regulated genes. The detoxification, immune response, and metabolic processes-related genes were found. The results showed that two key pathways including phagocytosis and apoptosis played important roles in response to MCRV infection. The combination of transcriptomic and metabolomic analyses showed that related metabolic pathways, such as glycolysis, citrate cycle, lipid, and amino acid metabolism were also significantly disrupted. Moreover, the biosynthesis of unsaturated fatty acids was activated in response to MCRV infection. This study provided a novel insight into the understanding of cellular mechanisms in crustaceans against viral invasion.

Assaying of Cu2+ with near-infrared l-cysteine-capped CdSeTe/CdS quantum dots and its effect on cell imaging.

Near-infrared (NIR) core-shell CdSeTe/CdS quantum dots (QDs) modified with l-cysteine were synthesized in aqueous solution. The QDs had a special NIR-emitting spectrum, high fluorescence stability and low cytotoxicity. In addition, they exhibited an obvious fluorescence quenching when Cu2+ was present. An NIR nanosensor was prepared for rapidly, sensitively, and selectively determining Cu2+ in solution quantitatively and monitoring the changes in Cu2+ in cells with fluorescence imaging in a semiquantitative way. The linear relationship between the relative fluorescence intensity (F0 /F) and the concentration of Cu2+ from 5.12 × 10-8  M to 2.56 × 10-5  M in solution was observed using an NIR fluorescence spectrophotometer with R2 equal to 0.9958. Moreover, in the experiment with the fluorescence microscope, F0 /F versus the concentration of Cu2+ from 5.00 × 10-8  M to 7.68 × 10-6  M also showed a good linear relationship with R2 equal to 0.9817. Practical water sample ion detecting experiments had good accuracy and recovery rates. Cell experiments showed that the NIR imaging intensity of cells was inversely proportional to the concentration of copper ions, therefore NIR QDs have great potential for detection of metal ions in solution and in cells.

Comprehensive Effects of Near-Infrared Multifunctional Liposomes on Cancer Cells.

Multifunctional theranostic systems are a recent important development of medical research. We combined the characteristics of near-infrared luminescent quantum dots and thermosensitive magnetoliposomes to develop a multifunctional nano-diagnostic material. This system is based on near-infrared magnetic thermosensitive liposomes, which encapsulate drugs and can control drug localization and release. After incubating cancer cells with the liposomes, the state of the cells was analyzed in real time by near-infrared imaging. Cell viability was significantly inhibited by heat treatment or alternating magnetic field treatment, which thus improved the anti-cancer properties of the liposomes. In the future, by combining near-infrared imaging technology and an external high-frequency alternating magnetic field, we could not only detect cancer cells noninvasively but also conduct image-guided treatments for cancer.

Energy-Efficient Online Resource Management and Allocation Optimization in Multi-User Multi-Task Mobile-Edge Computing Systems with Hybrid Energy Harvesting.

Mobile Edge Computing (MEC) has evolved into a promising technology that can relieve computing pressure on wireless devices (WDs) in the Internet of Things (IoT) by offloading computation tasks to the MEC server. Resource management and allocation are challenging because of the unpredictability of task arrival, wireless channel status and energy consumption. To address such a challenge, in this paper, we provide an energy-efficient joint resource management and allocation (ECM-RMA) policy to reduce time-averaged energy consumption in a multi-user multi-task MEC system with hybrid energy harvested WDs. We first formulate the time-averaged energy consumption minimization problem while the MEC system satisfied both the data queue stability constraint and energy queue stability constraint. To solve the stochastic optimization problem, we turn the problem into two deterministic sub-problems, which can be easily solved by convex optimization technique and linear programming technique. Correspondingly, we propose the ECM-RMA algorithm that does not require priori knowledge of stochastic processes such as channel states, data arrivals and green energy harvesting. Most importantly, the proposed algorithm achieves the energy consumption-delay trade-off as [ O ( 1 / V ) , O ( V ) ] . V, as a non-negative weight, which can effectively control the energy consumption-delay performance. Finally, simulation results verify the correctness of the theoretical analysis and the effectiveness of the proposed algorithm.

3D Molybdenum Disulfide Nanospheres Loaded with Metformin to Enhance SCPP Scaffolds for Bone Regeneration.

Conventional strontium-doped calcium polyphosphate (SCPP) ceramics have attracted a lot of attention due to good cytocompatibility and controlled degradation. However, their poor mechanical strength, brittleness, and difficulty in eliminating unavoidable postoperative inflammation and bacterial infections in practical applications limit their further clinical application. In this study, carboxylated molybdenum disulfide nanospheres (MoS2-COOH) were first prepared via a one-step hydrothermal method. The optimal doping concentration of MoS2-COOH was then incorporated into SCPP to overcome its poor mechanical strength. To further enhance the anti-inflammatory properties of scaffolds, metformin (MET) was loaded onto MoS2-COOH through covalent bond cross-linking (MoS2-MET). Then MoS2-MET was doped into SCPP (SCPP/MoS2-MET) according to the previously obtained concentration, resulting in the controlled and sustained release of MET from the SCPP/MoS2-MET scaffolds for 21 days in vitro. The SCPP/MoS2-MET scaffolds were shown to have good biological activity in vitro to promote stem cell proliferation and the potential to promote mineralization in vitro. It also showed good osteoimmunomodulatory activity could reduce the expression of proinflammatory factors and effectively induce the differentiation of BMSCs under inflammatory conditions, upregulating the expression of relevant osteoblastic cytokines. In addition, SCPP/MoS2-MET scaffolds could effectively inhibit Staphylococcus aureus and Escherichia coli. In vivo experiments also demonstrated better osteogenic potential of SCPP/MoS2-MET scaffolds compared with the other scaffold-samples. Thus, the introduction of carboxylated molybdenum disulfide nanospheres is a promising approach to improve the properties of SCPP and may provide a new modification strategy for inert ceramic scaffolds and the construction of multifunctional composite scaffolds for bone tissue engineering.

Compound-composed Chinese medicine of Huachansu triggers apoptosis of gastric cancer cells through increase of reactive oxygen species levels and suppression of proteasome activities.

BACKGROUND: Huachansu (HCS), a known Chinese patent drug extracted from the Chinese toad skin, is frequently used for the treatment of various advanced cancers, especially gastric cancer, due to the good therapeutic effect. However, it is rather difficult to clarify the active substances and molecular mechanisms involved owing to the lack of appropriate research strategies. We recently proposed the concept and research ideas of compound-composed Chinese medicine formula. PURPOSE: To discover compound-composed Chinese medicine from Huachansu and to explore its mechanism of action in inducing apoptosis of gastric cancer cells. METHOD: Network pharmacology combined with serum pharmacochemistry was utilized to screen the predominant active constituents from HCS against gastric cancer. Then, the compound-composed Chinese medicine of HCS (CCMH) was prepared according to their relative contents in serum. The pharmacological effects and potential mechanisms for CCMH were investigated by assays for cell viability, cell cycle, apoptosis, mitochondrial membrane potential (MMP), proteomics, reactive oxygen species (ROS), N-Acetylcysteine (NAC) antagonism, proteasome activity, and western blot. RESULTS: CCMH was comprised of arenobufagin (11.14%), bufalin (18.67%), bufotalin (7.33%), cinobufagin (16.67%), cinobufotalin (16.74%), gamabufotalin (8.45%), resibufogenin (12.03%), and telocinobufagin (8.97%). CCMH evidently induced proliferation inhibition, cell cycle arrest, apoptosis, and MMP collapse in gastric cancer cells, possessing the better activities than HCS. Proteomic analysis showed that CCMH influenced ROS pathway, ubiquitin proteasome system, and PI3K/Akt and MAPK signaling pathways. CCMH markedly enhanced intracellular ROS levels in gastric cancer cells, which was reversed by NAC. Accordingly, NAC antagonized the apoptosis-inducing effect of CCMH. Significantly decreased proteasome 20S activity by CCMH was observed in gastric cancer cells. CCMH also regulated the expression of key proteins in PI3K/Akt and MAPK signaling pathways. CONCLUSION: CCMH possesses more significant apoptotic induction effects on gastric cancer cells than HCS, which is achieved primarily through suppression of proteasome activities and increase of ROS levels, followed by regulating PI3K/Akt and MAPK signaling pathways. Network pharmacology combined with serum pharmacochemistry is an effective strategy for discovering compound-composed Chinese medicine from traditional Chinese medicine, which can help clarify the pharmacological substances and mechanisms of action for traditional Chinese medicine.

Cinobufagin: a promising therapeutic agent for cancer.

OBJECTIVES: Cinobufagin is a natural active ingredient isolated from the traditional Chinese medicine Venenum Bufonis (Chinese: Chansu), which is the dried secretion of the postauricular gland or skin gland of the Bufo gargarizans Cantor or Bufo melanostictus Schneider. There is increasing evidence indicating that cinobufagin plays an important role in the treatment of cancer. This article is to review and discuss the antitumor pharmacological effects and mechanisms of cinobufagin, along with a description of its toxicity and pharmacokinetics. METHODS: The public databases including PubMed, China National Knowledge Infrastructure and Elsevier were referenced, and 'cinobufagin', 'Chansu', 'Venenum Bufonis', 'anticancer', 'cancer', 'carcinoma', and 'apoptosis' were used as keywords to summarize the comprehensive research and applications of cinobufagin published up to date. KEY FINDINGS: Cinobufagin can induce tumour cell apoptosis and cycle arrest, inhibit tumour cell proliferation, migration, invasion and autophagy, reduce angiogenesis and reverse tumour cell multidrug resistance, through triggering DNA damage and activating the mitochondrial pathway and the death receptor pathway. CONCLUSIONS: Cinobufagin has the potential to be further developed as a new drug against cancer.

Visible-Ultraviolet Upconversion Carbon Quantum Dots for Enhancement of the Photocatalytic Activity of Titanium Dioxide.

Visible-ultraviolet upconversion carbon quantum dots (CQDs) are synthesized with a hydrothermal method using l-glutamic acid (l-Glu) and m-phenylenediamine (MPD) and then combined with commercial nano-TiO2 to prepare CQDs/TiO2 composites. The fluorescence spectra prove that the prepared CQDs can convert approximately 600 nm visible light into 350 nm ultraviolet light. In photocatalysis experiments, CT-1, a CQDs/TiO2 composite with 1:1 molar ratio of l-Glu to TiO2, has the best degradation efficiency for methyl orange (MO). Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) experiments confirm that CT-1 is composed of quasi-spherical nano-TiO2 and CQDs with a crystal plane of graphitic carbon. CT-1 can degrade 70.56% of MO (40 ppm) within 6 h under the irradiation of a 600 nm light source, which is close to its degradation rate of 78.75% under 365 nm ultraviolet light. The apparent rate constant of CT-1 degradation equation is 12.7 times that of TiO2. Free radical scavenging experiments and electron spin resonance (ESR) tests show that the degradation ability should be attributed to the existence of h+ and •OH under visible light. Therefore, we provide a simple and low-cost solution with heavy-metal-free products to improve the photocatalytic performance of TiO2.

The Protective Effect of Liquiritin in Hypoxia/Reoxygenation-Induced Disruption on Blood Brain Barrier.

Background: Stroke is the second leading cause of death in human life health, but current treatment strategies are limited to thrombolytic therapy, and because of the tight time window, many contraindications, and only a very small number of people can benefit from it, new therapeutic strategies are needed to solve this problem. As a physical barrier between the central nervous system and blood, the blood-brain barrier (BBB) maintains the homeostasis of the central nervous system. Maintaining the integrity of the BBB may emerge as a new therapeutic strategy. Liquiritin (LQ) is a flavonoid isolated from the medicinal plant Glycyrrhiza uralensis Fisch. ex DC. (Fabaceae), and this study aims to investigate the protective effects of LQ on brain microvascular endothelial cells (BMECs), to provide a new therapeutic strategy for stroke treatment, and also to provide research ideas for the development of traditional Chinese medicine (TCM). Methods: The protective effects of LQ on HBMECs under the treatment of hypoxia reoxygenation (H/R) were investigated from different aspects by establishing a model of H/R injury to mimic ischemia-reperfusion in vivo while administrating different concentrations of LQ, which includes: cell proliferation, migration, angiogenesis, mitochondrial membrane potential as well as apoptosis. Meanwhile, the mechanism of LQ to protect the integrity of BBB by antioxidation and inhibiting endoplasmic reticulum (ER) stress was also investigated. Finally, to search for possible targets of LQ, a proteomic analysis approach was employed. Results: LQ can promote cell proliferation, migration as well as angiogenesis and reduce mitochondrial membrane potential damage and apoptosis. Meanwhile, LQ can also reduce the expression of related adhesion molecules, and decrease the production of reactive oxygen species. In terms of mechanism study, we demonstrated that LQ could activate Keap1/Nrf2 antioxidant pathway, inhibit ER stress, and maintain the integrity of BBB. Through differential protein analysis, 5 disease associated proteins were found. Conclusions: Studies have shown that LQ can promote cell proliferation, migration as well as angiogenesis, and reduce cell apoptosis, which may be related to its inhibition of oxidative and ER stress, and then maintain the integrity of BBB. Given that five differential proteins were found by protein analysis, future studies will revolve around the five differential proteins.

Improvement of self-cleaning waterborne polyurethane-acrylate with cationic TiO2/reduced graphene oxide.

UV curable waterborne polyurethane acrylate (WPUA) with surfactant-modified TiO2/reduced graphene oxide (TiO2/rGO) nanocomposites were prepared and analyzed to improve their mechanical performance and self-cleaning ability. TiO2/rGO nanocomposites were prepared by a simple hydrothermal method with nano-TiO2 and graphene oxide, and modified with cationic surfactant (CTAB) to obtain a cationic TiO2/rGO (C-TiO2/rGO). Then, the obtained C-TiO2/rGO was incorporated into anionic waterborne polyurethane acrylate by in situ fabrication to obtain a composite emulsion (C-TiO2/rGO-WPUA). The results of Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) showed that CTAB was successfully intercalated into TiO2/rGO, and TiO2 nanoparticles were evenly distributed on graphene sheets with good dispersibility. Compared to UV-cured neat WPUA and C-TiO2/rGO-WPUA, the mechanical properties and thermal stability of the composites were significantly improved. When the content of C-TiO2/rGO was 0.5%, the UV-cured composites had overall excellent performance. In particular, the WPUA composites exhibited good self-cleaning ability in photocatalysis. The photocatalytic degradation rate of methyl orange in 0.5% C-TiO2/rGO-WPUA reached 88.3% under 6 h visible light irradiation.

Complete Genome Sequence of Vibrio campbellii LMB 29 Isolated from Red Drum with Four Native Megaplasmids.

Vibrio spp. are the most common pathogens for animals reared in aquaculture. Vibrio campbellii, which is often involved in shrimp, fish and mollusks diseases, is widely distributed in the marine environment worldwide, but our knowledge about its pathogenesis and antimicrobial resistance is very limited. The existence of this knowledge gap is at least partially because that V. campbellii was originally classified as Vibrio harveyi, and the detailed information of its comparative genome analysis to other Vibrio spp. is currently lacking. In this study, the complete genome of a V. campbellii predominant strain, LMB29, was determined by MiSeq in conjunction with PacBio SMRT sequencing. This genome consists of two circular DNA chromosomes and four megaplasmids. Comparative genome analysis indicates that LMB29 shares a 96.66% similarity (average nucleotide identity) with the V. campbellii ATCC strain BAA-1116 based on a 75% AF (average fraction) calculations, and its functional profile is very similar to V. campbellii E1 and V. campbellii CAIM115. Both type III secretion system (T3SS) and type VI secretion system (T6SS), along with the tlh gene which encodes a thermolabile hemolysin, are present in LMB29 which may contribute to the bacterial pathogenesis. The virulence of this strain was experimental confirmed by performing a LDH assay on a fish cell infection model, and cell death was observed as early as within 3 h post infection. Thirty-seven antimicrobial resistance genes (>45% identity) were predicted in LMB29 which includes a novel rifampicin ADP ribosyltransferase, arr-9, in plasmid pLMB157. The gene arr-9 was predicted on a genomic island with horizontal transferable potentials which may facilitate the rifampicin resistance dissemination. Future researches are needed to explore the pathogenesis of V. campbellii LMB29, but the availability of this genome sequence will certainly aid as a basis for further analysis.