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The present work demonstrated the potential of different agro-waste mixtures to produce ethanol. The forest soil bacterium (Streptomyces sp.) was exploited for the saccharification of the agro-waste mixture formulated by extreme vertices mixture design and the hydrolysate produced by saccharification was used for fermentation. The best formulation contained 43.33% orange peel, 33.33 % pumpkin pulp + seeds, and 23.33% pomegranate peel which exhibited significantly high reducing sugar (22.36 ± 0.54 mg/g dry weight) among all other mixtures. The hydrolysate of this mixture when supplemented with 2% w/v fructose produced a maximum of 7.86 ± 0.08% v/v ethanol by the yeast isolated from the brewer’s spent grains. Thus, easily available waste could be a promising source for yeast isolation and feedstock for ethanol production. Further, this study aids to reduce the risk of health, and environmental pollution, and developing the economy.

This study empirically examines the impact of individual motivation on innovation performance, where innovative behavior serves as a mediating construct, and discusses whether the innovation climate has a moderating effect. This study combines the Cognitive Evaluation Theory and behavioral performance to develop a new theoretical method for explaining the relationships between individual motivation, innovative behavior, and innovation performance. Data collected via a field study of 250 subjects who participated in a science and technology competition were analyzed using a PLS-SEM model. Barron and Kenny's mediation test and the bootstrapping method were used to evaluate the model and confirm the mediation and moderation effects, respectively. Robustness checks were conducted to exclude nonlinearity and heterogeneity in the model. The results show that individual motivation positively promotes innovation performance, in which innovative behavior plays an intermediary role, and that innovation climate moderates the relationship between innovative behavior and innovation performance. According to the results of this field study, stimulators concerning motivation and climate should be primarily considered by managers to boost innovation performance.

This study was aimed to compare the relative activities of the purified pomegranate peels polyphenols (PPPs) with some other plant polyphenols including punicalagin, ellagic acid, gallic acid, phlorizin, and epigallocatechin gallate (EGCG) on the lipid metabolism regulation, and the cholesterol efflux mechanisms of PPPs and punicalagin were also investigated. In this paper, a convenient and accurate in vitro HL7702 steatosis hepatic cell model was applied to evaluate the lipid-lowering effects of the tested polyphenols. The results showed that PPPs possessed the strongest lipid-lowering effects. Prevention group (treated with polyphenols when establishing of steatosis model) was more effective than treatment group (treated with polyphenols after establishment of steatosis model). Punicalagin displayed the strongest lipid-lowering effects among all the tested components of pomegranate peel polyphenols. Moreover, PPPs and punicalagin (10, 20, 40 μg/mL) significantly increased the mRNA expression of LXRα (Liver X receptor alpha) and its target genes-ABCA1 (ATP-binding cassette transporter A1) in a dose-dependent manner in HL7702 steatosis hepatic cells. The high mRNA expression of LXRα and ABCA1, next to lovastatin, was observed in cells treated with 40 μg/mL of PPPs. These in vitro findings suggested that PPPs might have great potential in the clinic treatment of hyperlipemia.

Tumor-associated macrophages (TAMs) play dual roles in tumor progression. TAMs are known to induce programmed death ligand-1 (PD-L1) expression in cancer cells. However, the regulatory effects of PD-L1 in melanoma cells on TAM phenotypical switching remain underexplored. Herein, our findings indicated that CD163 and MRC1 levels were significantly elevated in metastatic melanomas compared with primary melanomas, correlating with CD274 expression and predicted patient clinical outcomes. To study the mechanisms regulating M2-like polarization, PD-L1 was knocked out in both YUMM1.7 and B16-F10 melanoma cells. The data revealed that knocking out PD-L1 (PD-L1 KO ) in melanoma resulted in a decelerated in vivo growth rate, accompanied by a significantly increased M1/M2 ratio, more dendritic cells, and enhanced activation of CD8 + T cells compared with wild-type (WT) melanoma cells. These alterations were associated with decreased expression of M2-associated chemokines (CCL2, CCL3, and CXCL2) and cytokines (IL6, IL10, and TGFβ1). Mice harboring PD-L1 KO melanomas exhibited elevated levels of CD8 + T cells in both the tumor-draining lymph nodes and the bloodstream compared with mice with PD-L1 WT melanomas. Treatment with extracellular vesicles (EVs) derived from PD-L1 KO melanoma resulted in a reduced tumor growth rate and fewer M2-like macrophages in the tumors compared with EVs from PD-L1 WT melanomas. Therefore, our data suggest that PD-L1 in melanoma and melanoma-derived EVs induces M2-like polarization, contributing to local and regional immune suppression., Competing Interests: Disclosure Statement None declared., (Copyright © 2024. Published by Elsevier Inc.)

As artificial receptors for protein recognition, epitope-imprinted polymers combined with fluorescence sensing based on quantum dots (QDs) can be potentially used for biological analysis and disease diagnosis. However, the usual way for fabrication of QD sensors through unoriented epitope imprinting is confronted with the problems of disordered imprinting sites and low template utilization. In this context, a facile and efficient oriented epitope surface imprinting was put forward based on immobilization of the epitope templates via thiol-disulfide exchange reactions. With N-succinimidyl 3-(2-pyridyldithio)-propionate (SPDP) as a heterobifunctional reagent, cysteine-modified epitopes of cytochrome c were anchored on the surface of pyridyl disulfide functionalized silica nanoparticles sandwiching CdTe QDs. After surface imprinting via a sol-gel process, the epitope templates were removed from the surface-imprinted layers simply by reduction of the thiol-disulfide, affording oriented epitope-imprinted sites. By this method, the amount of epitope templates was only 1/20 of traditionally unoriented epitopes. The resulting sensors demonstrated significantly enhanced imprinting performance and high sensitivity, with the imprinting factor increasing from 2.6 to 3.9, and the limit of detection being 91 nM. Such epitope-oriented surface-imprinted method may offer a new design strategy for the construction of high-affinity protein recognition nanomaterials with fluorescence sensing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Vascular calcification in diabetes patients is a major independent risk factor for developing diabetic cardiovascular complications. However, the mechanisms by which diabetes leads to vascular calcification are complex and not yet fully understood. Our previous study revealed that miR-32-5p is a potential new diagnostic marker for coronary artery calcification. In this study, we found that miR-32-5p levels were significantly greater in the plasma of type 2 diabetes patients with coronary artery calcification and were positively correlated with the coronary artery calcification score. In type 2 diabetic mice, miR-32-5p levels were also elevated in the aorta, and knockout of miR-32-5p inhibited the osteogenic differentiation of vascular smooth muscle cells in vivo. Furthermore, overexpression of miR-32-5p promoted vascular smooth muscle cell calcification, while antagonism of miR-32-5p inhibited vascular smooth muscle cell calcification under high-glucose conditions. GATA binding protein 6 (GATA6) was identified as the key target gene through which miR-32-5p promotes vascular smooth muscle cell calcification. Overexpression of GATA6 antagonized the effects of miR-32-5p on vascular calcification. Additionally, high glucose levels were shown to induce the upregulation of miR-32-5p by activating CCAAT/enhancer binding protein beta (CEBPB). These results suggest that miR-32-5p is an important procalcification factor in vascular calcification associated with type 2 diabetes and identify the CEBPB/miR-32-5p/GATA6 axis as a potential biomarker and therapeutic target for preventing and treating vascular calcification in type 2 diabetes., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Proliferative verrucous leucoplakia (PVL) is a rare but slow-growing, aggressive leucoplakia lesion associated with the highest malignant transformation rate in oral potentially malignant disorders (OPMDs). With increasing attention paid to PVL, it is urgent for us to analyse and summarise the publications globally using comprehensive bibliometric studies to help researchers propose possible future research directions and guide them to further conduct relevant studies in the domain., Objectives: The purpose of the study was to evaluate global academic productivity, impact, and collaboration of potentially malignant oral disorder PVL utilising bibliometrics based on annual number of publications, countries and regions, institution, authors, journals, citations and co-occurrences of author keywords over the last 20 years., Methods: This study searched publications pertaining to proliferative verrucous leucoplakia in the Web of Science Core Collection, spanning from 2003 to 2023. Utilizing VOSviewer, R software, Bibliometric online analysis platform, CiteSpace software, and Microsoft Excel, we conducted a bibliometric and visualised analysis of PVL., Results: The quantity of pertinent publications in this research domain displays a fluctuating but overall upward trend. In aggregate, there are 148 articles and 61 reviews, encompassing research contributions from 44 countries, 45 institutions, and involving 831 authors. Among these publications, the USA, Spain, and UK emerged as the predominant contributing nations. Predominantly, articles found their publication venue in "Pathology Research and Practice." Notably, the author with the highest number of publications and most influence is Warnakulasuriya S. The top 3 keywords include "Proliferative Verrucous Leucoplakia," "Squamous-Cell Carcinoma," "Oral Leucoplakia," and "Potentially Malignant Disorders.", Conclusion: In this investigation, statistical analysis and network visualisation were conducted to reveal the research progress, trends, and trending topics on PVL via a thorough bibliometric analysis. We found that current publications comprise mainly case reports, there is a significant research need to explore the molecular mechanisms, specific diagnostic criteria, and effective management options for PVL. Our work should serve as a key reference and a directional guide for future research in this domain., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Tick-borne encephalitis virus (TBEV) is a common virus in Europe and Asia, causing around 10,000 to 10,500 infections annually. It affects the central nervous system and poses threats to public health. However, the exact molecular mechanisms of TBE pathogenesis are not yet fully understood due to the complex interactions between the virus and its host. In this study, a comprehensive analysis was conducted to characterize the serum metabolome and proteome of adult patients infected with TBEV, in comparison to a control group of healthy individuals. Liquid chromatography tandem mass spectrometry (LC-MS) was employed to monitor metabolic and proteomic alternations throughout the progression of the disease, significant physiological changes associated with different stages of the disease were identified. A total of 44 proteins and 115 metabolites exhibited significantly alternations in the sera of patients diagnosed with TBE. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of these metabolites and proteins revealed differential enrichment of genes associated with the extracellular matrix, complement binding, hemostasis, lipid metabolism, and amino acid metabolism between TBE patients and healthy controls. We gained valuable understanding of the specific metabolites implicated in the host's responses to TBE, establishing a basis for further research on TBE disease. SIGNIFICANCE: The current investigation revealed a comprehensive and systematic differences on TBE using LC-MS platform from human serum samples of TBE patients and healthy individuals providing the immune response to the invasion of TBE., Competing Interests: Declaration of competing interest The authors declare that there are no financial or other potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

As a neurotoxin, it is necessary to establish a low cost, stable and sensitive method for the quantitative detection of hydrazine. Using Co-ZIF (zeolite imidazole framework) nanorods as precursor, CoS 2 hollow nanotube array heterogeneous structure loaded with Cu nanoparticles were prepared on carbon cloth (CC) by etching, calcination and plasma magnetron sputtering (CoS 2 @Cu HNTA/CC). As a self-supporting electrode, its hollow heterogeneous structure provides a large area of electron transfer channel for the oxidation of the food pollutant hydrazine. In addition, bimetallic synergies and in situ N doping regulated the electronic structure of CoS 2 @Cu HNTA/CC, and thus significantly improved the electrical conductivity and catalytic activity. As an efficient hydrazine sensor with a wide linear range of 1 μM L -1 -10 mM (1 μM-1 mM and 1 mM-10 mM), its sensitivity and the limit of detection are 7996 μA mM -1 cm -2 , 3772 μA mM -1 cm -2 and 0.276 μM (S/N = 3), respectively. This study provides a new strategy for the construction of MOFs (Metal Organic Framework)-derived bimetallic composites and their application in electrochemical sensing., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Xiaoli Xiong reports financial support was provided by Sichuan Department of Science and Technology Program of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Small-sized fluorescent carbon dots (CDs) are gaining increasing attention in the field of biomedical applications. The environmental and biological compatibility of positively charged CDs has been extensively investigated; however, the potential cytotoxicity caused by negatively and particularly neutrally charged small CDs has been significantly overlooked. In this study, we conducted a comprehensive investigation into the cellular membrane disruption effect of weakly negatively charged 3-nm CDs using a combination of various biophysical techniques. Our findings demonstrate that even at a low concentration of 0.5 μg mL -1 , these CDs induce significant perturbations on the cellular membrane, resulting in increased membrane permeability due to asymmetric disruption of the bilayer structure. Furthermore, CDs exhibit distinct mechanisms at different concentrations, including prompt insertion into the bilayer at low concentrations (<20 μg mL -1 ) and a synergistic effect after a threshold time at high concentrations (e.g., 25-200 μg mL -1 ). Moreover, these CDs possess specific antibacterial properties against Acinetobacter baumannii (with a minimum inhibitory concentration of 50 μg mL -1 ) while showing minimal hemolytic or cytotoxic effects on mammalian cells. This study provides comprehensive insights into the biophysical aspects of cellular membrane toxicity caused by small weakly negatively charged CDs and contributes to assessing their potential biomedical applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The recurrent brown tide phenomenon, attributed to Aureococcus anophagefferens (A. anophagefferens), constitutes a significant threat to the Qinhuangdao sea area in China, leading to pronounced ecological degradation and substantial economic losses. This study utilized machine learning and deep learning techniques to predict A. anophagefferens population density, aiming to elucidate the occurrence mechanism and influencing factors of brown tide. Specifically, Random Forest (RF) algorithm was utilized to impute missing water quality data, facilitating its direct application in subsequent algal population prediction models. The results revealed that all four models-RF, Support Vector Regression (SVR), Multilayer Perceptron (MLP), and Convolutional Neural Network (CNN)-exhibited high accuracy in predicting A. anophagefferens population densities, with R 2 values exceeding 0.75. RF, in particular, showed exceptional accuracy and reliability, with an R 2 value surpassing 0.8. Additionally, the study ascertained five critical factors influencing A. anophagefferens population density: ammonia nitrogen, pH, total nitrogen, temperature, and silicate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Deleted in breast cancer 1 (DBC1) is a human nuclear protein that modulates the activities of various proteins involved in cell survival and cancer progression. Oxidized form of nicotinamide adenine dinucleotide (NAD + ) is suggested to bind to the Nudix homology domains (NHDs) of DBC1, thereby regulating DBC1-Poly (ADP-ribose) polymerase 1 (PARP1) interactions, resulting in the restoration of DNA repair. Using Nuclear Magnetic Resonance (NMR) and Isothermal Titration Calorimetry (ITC), we confirmed NAD + and its precursor nicotinamide mononucleotide (NMN) both bind the NHD domain of DBC1 (DBC1 354 - 396 ). NAD + likely interacts with DBC1 354 - 396 through hydrogen bonding, with a binding affinity (8.99 μM) nearly twice that of NMN (17.0 μM), and the key binding sites are primarily residues E363 and D372, in the agreement with Molecular Docking experiments. Molecular Dynamics (MD) simulation further demonstrated E363 and D372's anchoring role in the binding process. Additional mutagenesis experiments of E363 and D372 confirmed their critical involvement of ligand-protein interactions. These findings lead to a better understanding of how NAD + and NMN regulate DBC1, thereby offering insights for the development of targeted therapies and drug research focused on DBC1-associated tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dry eye disease (DED) is currently the most prevalent condition seen in ophthalmology outpatient clinics, representing a significant public health issue. The onset and progression of DED are closely associated with oxidative stress-induced inflammation and damage. To address this, an aldehyde-functionalized F127 (AF127) hydrogel eye drop delivering multifunctional antioxidant Cu 2-x Se nanoparticles (Cu 2-x Se NPs) was designed. The research findings revealed that the Cu 2-x Se nanoparticles exhibit unexpected capabilities in acting as superoxide dismutase and glutathione peroxidase. Additionally, Cu 2-x Se NPs possess remarkable efficacy in scavenging reactive oxygen species (ROS) and mitigating oxidative damage. Cu 2-x Se NPs displayed promising therapeutic effects in a mouse model of dry eye. Detailed investigation revealed that the nanoparticles exert antioxidant, anti-apoptotic, and inflammation-mitigating effects by modulating the NRF2 and p38 MAPK signalling pathways. The AF127 hydrogel eye drops exhibit good adherence to the ocular surface through the formation of Schiff-base bonds. These findings suggest that incorporating antioxidant Cu 2-x Se nanoparticles into a tissue-adhesive hydrogel could present a highly effective therapeutic strategy for treating dry eye disease and other disorders associated with reactive oxygen species. STATEMENT OF SIGNIFICANCE: A new formulation for therapeutic eye drops to be used in the treatment of dry eye disease (DED) was developed. The formulation combines copper-selenium nanoparticles (Cu 2-x Se NPs) with aldehyde-functionalized Pluronic F127 (AF127). This is the first study to directly examine the effects of Cu 2-x Se NPs in ophthalmology. The NPs exhibited antioxidant capabilities and enzyme-like properties. They effectively eliminated reactive oxygen species (ROS) and inhibited apoptosis through the NRF2 and p38 MAPK signalling pathways. Additionally, the AF127 hydrogel enhanced tissue adhesion by forming Schiff-base links. In mouse model of DED, the Cu 2-x Se NPs@AF127 eye drops demonstrated remarkable efficacy in alleviating symptoms of DED. These findings indicate the potential of Cu 2-x Se NPs as a readily available and user-friendly medication for the management of DED., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Circulating tumor cells (CTCs), which shed from solid tumor tissue into blood circulatory system, have attracted wide attention as a biomarker in the early diagnosis and prognosis of cancer. Given their potential significance in clinics, many platforms have been developed to separate CTCs. However, the high-performance isolation of CTCs remains significant challenges including achieving the sensitivity and specificity necessary due to their extreme rarity and severe biofouling in blood, such as billions of background cells and various proteins. With the advancement of CTCs detection technologies in recent years, the highly efficient and highly specific detection platforms for CTCs have gradually been developed, resulting in improving CTC capture efficiency, purity and sensitivity. In this review, we systematically describe the current strategies with surface modifications by utilizing the antifouling property of polymer, peptide, protein and cell membrane for high-performance enrichment of CTCs. To wrap up, we discuss the substantial challenges facing by current technologies and the potential directions for future research and development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Deep eutectic solvents (DESs) possess excellent solubility and selectivity, making them suitable for extracting valuable metals and serving as a green alternative in the recycling process. This work introduces a low-viscosity DES consisting of dimethylthetin, oxalic acid, and water for the comprehensive recovery of cathode materials from LIBs. Leaching parameters such as ratio (1:1), leaching temperature (60 °C), and reaction time (15 min) for were systematically optimized, resulting in a selective separation efficiency of 99.98 % for lithium ions. Furthermore, in-situ regeneration of the precursor can be achieved during the leaching process. Charge-discharge tests indicate that the initial charge and discharge capacities of the regenerated battery are 166.8 mAh/g and 138.4 mAh/g, respectively. The DES demonstrates stability and can be easily recycled by replenishing the consumed components. This proposed strategy facilitates the reintroduction of nonrenewable resources into the supply chain and reduces the environmental impact of heavy metals, aligning with the principles of a circular economy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Leming Ou reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2023. Published by Elsevier B.V.)

Silica is utilized extensively in industrial and commercial applications as a chemical raw material, increasing its exposure and hazardous potential to populations, with silicosis serving as an important representative. Silicosis is characterized by persistent lung inflammation and fibrosis, for which the underlying pathogenesis of silicosis is unclear. Studies have shown that the stimulating interferon gene (STING) participates in various inflammatory and fibrotic lesions. Therefore, we speculated that STING might also play a key role in silicosis. Here we found that silica particles drove the double-stranded DNA (dsDNA) release to activate the STING signal pathway, contributing to alveolar macrophages (AMs) polarization by secreting diverse cytokines. Then, multiple cytokines could generate a micro-environment to exacerbate inflammation and promote the activation of lung fibroblasts, hastening fibrosis. Intriguingly, STING was also crucial for the fibrotic effects induced by lung fibroblasts. Loss of STING could effectively inhibit silica particles-induced pro-inflammatory and pro-fibrotic effects by regulating macrophages polarization and lung fibroblasts activation to alleviate silicosis. Collectively, our results have revealed a novel pathogenesis of silica particles-caused silicosis mediated by the STING signal pathway, indicating that STING may be regarded as a promising therapeutic target in the treatment of silicosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This paper investigates the issue of event-triggered adaptive optimal tracking control for uncertain nonlinear systems with stochastic disturbances and dynamic state constraints. To handle the dynamic state constraints, a novel unified tangent-type nonlinear mapping function is proposed. A neural networks (NNs)-based identifier is designed to cope with the stochastic disturbances. By utilizing adaptive dynamic programming (ADP) of identifier-actor-critic architecture and event triggering mechanism, the adaptive optimized event-triggered control (ETC) approach for the nonlinear stochastic system is first proposed. It is proven that the designed optimized ETC approach guarantees the robustness of the stochastic systems and the semi-globally uniformly ultimately bounded in the mean square of the NNs adaptive estimation error, and the Zeno behavior can be avoided. Simulations are offered to illustrate the effectiveness of the proposed control approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 ISA. Published by Elsevier Ltd. All rights reserved.)

Due to the scarcity of raw materials and negative environmental effects, it is essential to selectively recover lithium and other transition metals from end-of-life lithium-ion batteries (LIBs). Here, we propose a dual closed-loop process for resource utilization of spent LIBs. As an alternative to strong inorganic acids, deep eutectic solvents (DESs) as green solvents are employed for the recycling of spent LIBs. The DES based on oxalic acid (OA) and choline chloride (ChCl) achieves efficient leaching of valued metals within a short time. Through the coordination adjustment of water, it can form high-value battery precursors directly in DES, changing wastes into valuables. Meanwhile, water as a diluent can achieve the selective separation of lithium ions via filtration. More importantly, DES can be perfectly re-generated and recycled many times, indicating that the process is cost-effective and eco-friendly. As experimental proof, the re-generated precursors were used to produce new Li(Ni 0.5 Co 0.2 Mn 0.3 )O 2 (NCM523) button batteries. The constant current charge-discharge test revealed that the initial charge and discharge values of the re-generated cells were 177.1 and 149.5 mAh/g, respectively, corresponding to the performance of commercial NCM523 cells. The whole recycling process is clean, efficient, and environment-friendly, realizing the double closed loop of spent battery regeneration and deep eutectic solvent re-use. This fruitful research demonstrates DES has excellent potential for recycling spent LIBs and provides an efficient and eco-friendly double closed-loop solution for the sustainable re-generation of spent LIBs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Breast cancer (BC) has posed a fatal threat to women's lives and the search for new methods of diagnosis and treatment is an important way to break the bottleneck of high mortality in BC. Circular RNAs (circRNAs) have been confirmed to be aberrantly expressed in several types of cancers, and this study is intended to elucidate the role and mechanism of circ&#95;0108942 in BC., Materials and Methods: The levels of circ&#95;0108942, microRNA-1178-3p (miR-1178-3p), and transmembrane p24 trafficking protein 3 (TMED3) were measured using real-time quantitative polymerase chain reaction (RT-qPCR) or western blot. Meanwhile, the cell proliferation, migration, invasion, angiopoiesis, and apoptosis were analyzed using 5-ethynyl-2'-deoxyuridine (EdU), transwell, tubule formation, and flow cytometry assays. Protein levels were determined by western blot. In addition, we used dual-luciferase reporter and RNA pull-down assays to identify the interplay between miR-1178-3p and circ&#95;0108942 or TMED3. Lastly, the impact of circ&#95;0108942 on the growth of BC tumors in vivo was analyzed by xenograft models., Results: Circ&#95;0108942 and TMED3 were notably upregulated in BC, and the miR-1178-3p was downregulated. Functionally, silencing circ&#95;0108942 suppressed cell proliferation, migration, invasion and promoted apoptosis in BC cells. In mechanism, circ&#95;0108942 regulated TMED3 expression by sponging miR-1178-3p. Meanwhile, circ&#95;0108942 knockdown also greatly constrained tumor growth in vivo., Conclusion: Circ&#95;0108942 boosted BC progression by regulating miR-1178-3p and thus upregulating TMED3., Competing Interests: Disclosure The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Osteoarthritis (OA) was a chronic degenerative joint disease. The dysregulation of circular RNAs (circRNAs) has been identified in OA progression. However, the function and regulation mechanism of circ&#95;0114876 in OA remains largely unknown., Method: Firstly, we used LPS-treated C28/I2 cells as a cellular model of OA. Quantificational real-time polymerase chain reaction (qRT-PCR) was used to determine the expression levels of circ&#95;0114876, miRNA-1227-3p, and ADAM10 in OA chondrocytes. Cell Counting Kit-8 (CCK8), 5-ethynyl-20-deoxyuridine (EdU) incorporation assays, flow cytometry, Enzyme-linked immunosorbent assay (ELISA) kit, and western blot were applied to confirm cell proliferation, apoptosis, inflammation, and extracellular matrix. of circ&#95;0114876 in vitro. The interaction between circ&#95;0114876 and its downstream target (miR-1227-3p) and mRNA target ADAM metallopeptidase domain 10 (ADAM10), was evaluated by luciferase assay and RNA immunoprecipitation (RIP) assay., Result: Circ&#95;0114876 and ADAM10 were upregulated and miR-1227-3p was decreased in OA tissues and LPS-treated chondrocytes. Low expression of circ&#95;0114876 promoted proliferation and inhibited apoptosis, inflammation, and extracellular matrix of the LPS-treated chondrocytes. Mechanistically, circ&#95;0114876 functioned in human chondrocytes through targeting miR-1227-3p and ADAM10. Furthermore, miRNA-1227-3p inhibitor reversed the effect of circ&#95;0114876 knockdown on the OA chondrocytes, and ADAM10 overexpression reversed the effect of miR-1227-3p mimic on the OA chondrocytes., Conclusion: Circ&#95;0114876 was increased in OA tissues and cells. Circ&#95;0114876 facilitated the progression in the LPS-induced OA cell model via regulating the miR-1227-3p/ADAM10 axis. This study would provide a potentially effective therapeutic strategy for OA progression., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Silica is a very common and important chemical raw material with a wide range of uses. Long-term inhalation of silica particles could cause lung toxicity, of which the most important representative is silicosis. Silicosis is a serious and fatal occupational pulmonary disease, characterized by persistent pulmonary inflammation and fibrosis. Despite intensive research, the toxic mechanism of silicosis caused by silica particles is not completely clear, which deserves further research and exploration. Many studies have indicated that the epithelial cells partially participate in the formation, accumulation, and activation of fibroblasts through epithelial-mesenchymal transition (EMT), which is conducive to the occurrence of fibrosis. Galectin-3 (Gal-3), widely expressed in epithelial cells, was observed to induce EMT in fibrotic diseases and tumors by regulating the GSK-3β and β-catenin. Previous studies have demonstrated that silica particles is indeed involved in the silicosis process by inducing EMT. However, it remains to be further studied whether there is a certain relationship between silica particles and Gal-3 expression, and whether Gal-3 also mediates the development of the silica particles-induced silicosis by regulating GSK-3β/β-catenin signal pathway-mediated EMT. Our research results showed that silica particles could significantly induce Gal-3 expression to promote the development of EMT through activating the GSK-3β/β-catenin signal pathway in mice and in A549 cells, which then significantly exacerbated the pulmonary fibrosis caused by silica particles. And the inhibition of Gal-3 could effectively inhibit the occurrence of EMT, and then effectively alleviate silicosis caused by silica particles. These findings would help us to further clarify the toxicological mechanisms of silicosis caused by silica particles and provide a novel target for prevention and intervention of silicosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Prorocentrum donghaiense Lu (also identified as Prorocentrum shikokuense Hada and Prorocentrum obtusidens Schiller) is a bloom-forming dinoflagellate species distributed worldwide. Blooms of P. donghaiense occur annually in adjacent waters of the East China Sea (ECS), especially in the waters near the Changjiang River Estuary. Blooms of this species have also been reported in nearby Japanese and Korean waters. There has been an apparent bloom-forming species succession pattern in the ECS since 2000, with diatom blooms in the early spring, shifting to long-lasting and large-scale dinoflagellate blooms dominated by P. donghaiense during the spring, and finally ended by diatom and/or Noctiluca scintillans blooms in summer. These bloom succession patterns were closely correlated with changes in environmental factors, such as temperature increase and anthropogenic eutrophication. Decreasing silicate by the construction of the Three Gorges Dam and increasing dissolved inorganic nitrogen flux were mainly influenced by high intensity human activities in the Changjiang River watershed, resulting in low Si/N ratio and high N/P ratios, possibly accelerating outbreak of P. donghaiense blooms. Phosphorous deficiency might be the most critical factor controlling the succession of microalgal blooms from diatoms to dinoflagellates. Prorocentrum donghaiense is a nontoxic species, but it can disrupt marine ecosystem by decreasing phytoplankton biodiversity and changing the structure of the food chain. Prorocentrum donghaiense blooms in the ECS have been intensively studied during the last two decades. Several possible mechanisms that contribute or trigger the annual blooms of this species have been proposed, but further research is required particularly on the aspect of nutrient budget, ecosystem impacts, as well as social-economic impact assessment., (Copyright © 2022. Published by Elsevier B.V.)

A diet high in sodium chloride (NaCl) can affect renal function damage and increase urinary calcium excretion, leading to bone loss. in renal tubules, Na-Cl co-transporter (NCC) and chloride channel 5 (CLC-5) are involved in regulating urinary calcium excretion. In addition, some cytokines, such as Bone morphogenetic protein 7 (BMP-7) and 1α-hydroxylase, are synthesized by renal tubules, which target on bone and play important roles on bone metabolism. However, the specific mechanisms between NaCl and these ion channels or cytokines still need investigations from many aspects. This study, in culture normal rat renal tubular epithelial NRK-52E cells, showed that high concentrations of NaCl significantly inhibited the cell viability and increased the cell apoptosis. High concentration of NaCl reduce bone mineral density (BMD), as demonstrated by the significantly increased mRNA and protein levels of NCC and osteopontin (OPN), but decreased the levels of CLC-5, BMP-7, and 1α-hydroxylase. In addition, we found that ovariectomized (OVX) rats on a high-salt diet for 12 weeks had altered levels of these indices in the renal cortices. Moreover, the BMD in fourth and fifth lumbar vertebra (LV4 and 5) and femurs were significantly decreased and bone microstructure was destroyed of these rats. We also demonstrated that high concentration of NaCl enhanced the inhibition of these cytokines which is beneficial to increase BMD, induced by modulating ion channels NCC and CLC-5. In conclusion, our results indicate that high concentration of NaCl reduce BMD by regulating ion channels NCC and CLC-5., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Prorocentrum obtusidens Schiller (formerly P. donghaiense Lu), a harmful algal species common in the East China Sea (ECS), often thrives with the depletion of phosphate. Three cruises in the spring of 2013 sampled an entire P. obtusidens bloom process to investigate the dynamics of alkaline phosphatase activity (APA) and phosphorus (P) status of the bloom species using both bulk and cell-specific assays. Unlike previous studies, the bloom of P. obtusidens occurred in a phosphate replete environment. Very high APA, with an average of 76.62 ± 90.24 nmol L -1  h -1 , was observed during the early-bloom phase, a value comparable to that in low phosphate environments. The alkaline phosphatase (AP) hydrolytic kinetics also suggested a more efficient AP system with a lower half-saturation constant (K s ), but higher maximum potential hydrolytic velocity (V max ) in this period. The APA decreased significantly with an average of 24.98 ± 30.98 nmol L -1  h -1 when the bloom reached its peak. The lack of a correlation between dissolved inorganic phosphate (DIP) or dissolved organic phosphate (DOP) concentration and APA suggested that the APA was regulated by the internal P growth demand, rather than the external P availability during the phosphate replete P. obtusidens bloom. These findings facilitate an understanding of the P. obtusidens acclimation strategy with respect to P variations in terms of AP expression during blooms in the ECS., (Copyright © 2021. Published by Elsevier B.V.)

Cadmium is an environmental metal pollutant that has been a focus of research in recent years, which is reported to cause bone disease; however, its skeletal toxicity and the mechanism involved are not yet fully known. Therefore, this study used MC3T3-E1 subclone 14 cells to determine the mechanism of cadmium toxicity on bone. Cadmium chloride (Cd) significantly reduced cell viability in a concentration-dependent manner. Exposure to Cd inhibited osteoblast-related proteins (Runx2, Col-1, STC2) and decreased alkaline phosphatase (ALP) activity. Cd caused Exportin-1 accumulation and induced DNA damage. Cd significantly down-regulated caspase 9 and induced cleaved-PARP, cleaved-caspase 3 protein level. Treatment with JNK inhibitor, SP600125, suppressed cadmium-induced elevation in the ratio of phosphorylation of JNK to JNK. Inhibition of caspase with pan-caspase inhibitor, Z-VAD-FMK, prevented MC3T3-E1 subclone 14 cells from cadmium-induced reduction of Runx2, STC2, caspase 9, and accumulation of cleaved PARP and cleaved caspase 3. Cd-induced cell survival enhanced by SP600125 but rescued by Z-VAD-FMK or KPT-335. These results suggest that cadmium cytotoxicity on bone involved exportin 1 accumulation, phosphorylation of JNK, induction of DNA damage and pro-apoptosis, which was induced by activation of caspase-dependent pathways., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Phosphorus (P) is a potential limiting nutrient for primary production in the East China Sea (ECS). Four cruises over four seasons were conducted during 2009-2011 to evaluate the dynamics of alkaline phosphatase (AP) activity (APA) and the P status of phytoplankton in the ECS. Sampling for bulk and single-cell APA assays was performed across the ECS, which included the Changjiang River diluted water (CDW), the mid-shelf surface water (MSW), and the Kuroshio surface water (KSW) masses. The results showed that the distribution patterns of APA varied between water masses and with season. Higher APA was normally observed in the CDW, which was influenced by the Changjiang River plume. In the CDW, phytoplankton were P-stressed during the late spring with an average bulk APA of 20.4 ± 19.5 nmol h -1  L -1 , which strengthened during the late summer (average APA maximizing at 106.2 ± 133.3 nmol h -1  L -1 ) and remained severe during the late autumn (average APA of 48.7 ± 34.1 nmol h -1  L -1 ) until reducing during the winter (average APA of 9.1 ± 13.6 nmol h -1  L -1 ). The variation patterns of APA and the P status of phytoplankton in the MSW were similar but with slight variations. In the KSW, a certain amount of APA occurred during the late spring and late autumn (averages of 18.7 ± 19.8 and 23.1 ± 18.7 nmol h -1  L -1 , respectively). Single-cell APA coincided with the bulk APA to exhibit the temporal and spatial P-stress status of the dominant micro-phytoplankton. Phytoplankton were the main AP producers in the CDW, especially during the late summer, while pico-plankton contributed most to AP in the MSW and KSW. Our results suggest that phytoplankton suffer P-stress in most seasons, and emphasize the importance of AP in the recycling of organic P to support primary production in the P-deficient ECS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Labile ferrous iron (Fe 2+ ) plays important biochemical functions in many physiologically essential processes. It is very important to find an effective method to detect Fe 2+ . Herein, a simple and effective Fe 2+ fluorescent probe (FeP1) has been constructed via a unique strategy of Fe 2+ -induced reducing reaction. As expected, FeP1 exhibited a 'turn-on' fluorescence response toward Fe 2+ over various small analytes, with high selectivity and excellent sensitivity (DL = 18 nM) for the detection of Fe 2+ in Tris-DMSO (4:1, pH = 7.4, v/v) solution. Moreover, the probe can act in different real samples, such as physiological saline and living cells., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “A simple and effective dansyl acid based “turn-on” fluorescent probe for detecting labile ferrous iron in physiological saline and live cells”., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The nitrogen uptake kinetics and physiological growth of Karenia mikimotoi and Skeletonema costatum sensu lato grown on different N substrates and concentrations were compared in the laboratory. In the presence of three N substrates, both species preferred to take up NH 4 . K. mikimotoi and S. costatum s.l. showed the highest substrate affinities for urea and NO + . K. mikimotoi and S. costatum s.l. showed the highest substrate affinities for urea and NO 3 - . Different with S. costatum s.l., K. mikimotoi grew slowly and steady and the physiological and growth activities in N-depleted conditions were higher than those in N-replete conditions. Our results suggested that K. mikimotoi shows a greater readiness for uptake and assimilation of urea, and that this species is more competitive in an N-depleted environment when compared with S. costatum s.l.3 - or NH 4 + . Different with S. costatum s.l., K. mikimotoi grew slowly and steady and the physiological and growth activities in N-depleted conditions were higher than those in N-replete conditions. Our results suggested that K. mikimotoi shows a greater readiness for uptake and assimilation of urea, and that this species is more competitive in an N-depleted environment when compared with S. costatum s.l., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

(Deoxy)guanosine-5'-triphosphate (5'-(d)GTP), the precursor for synthesizing DNA or RNA in vivo, is an important raw material for various modern biotechnologies based on PCR. In this study, we investigated the application of whole-cell catalysts constructed by bacterial cell surface display in biosynthetic reactions of 5'-(d)GTP from (deoxy)guanosine-5'-monophosphate (5'-(d)GMP). By N-terminal or N- and C-terminal fusion of the ice nucleation protein, we successfully displayed the GMP kinase of Lactobacillus bulgaricus and the acetate kinase of E. coli on the surface of E. coli cells. A large amount of soluble target protein was obtained upon induction with 0.2 mM IPTG at 25 °C for 30 h. The conversion of dGMP was up to 91% when catalysed by the surface-displayed enzymes at 37 °C for 4 h. Up to 95% of the GMP was converted after 3 h of reaction. The stability of the whole-cell catalyst at 37 °C was very good. The enzyme activity was maintained above 50% after 9 rounds of recovery. Our research showed that only one-twentieth of the initial substrate concentration of added ATP was sufficient to meet the reaction requirements., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The picoplanktonic pelagophyte Aureococcus anophagefferens could trigger harmful algal blooms (HABs) to discolor water in brown, known as brown tide. Since 2009, large-scale brown tides, caused by A. anophagefferens, had been occurred in early summer for three consecutive years in the coastal waters of Qinhuangdao, China and resulted considerable deleterious effects on the scallop mariculture industry. The causes for the occurrence of brown tides were not fully understood. Therefore, we conducted a one-year survey from June 2013 to May 2014 to study the seasonal succession of the phytoplankton community, including A. anophagefferens and its relationship with environmental variables in the area. The results revealed that the population dynamics of the phytoplankton community were significant variation with seasonal succession, in which A. anophagefferens played an important role during the entire year. The trend of the whole diversity index indicated that the community structure became more stable in winter. The results of principle component analysis (PCA) applied to the environmental factors indicated four major seasonal groups in the environmental variables. The water temperature, silicate and total nitrogen were contributed to the environment in summer, autumn and spring, respectively. In addition, a few another environmental factors commonly contributed to the winter waterbody, indicated that the aquatic environment is more complex in the cold season. The result revealed that the phytoplankton community structure and its variation were mainly affected by the hydrological factors, by using the redundancy analysis (RDA) for the relationship between dominant species and the environment. Furthermore, we inferred Chaetoceros decipiens as a potential species for the breakout of harmful algae blooms (HABs) by RDA ordination. We concluded that the key factor for the seasonal variations in the dynamics of phytoplankton community could be the hydrological parameters in Qinghuangdao coastal area. This research may provide more insight into the occurrence mechanism of brown tide., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Brown tides of Aureococcus anophagefferens have occurred annually in the coastal waters of Qinhuangdao since 2009. High levels of dissolved organic matter (DOM) are always measured during bloom periods. Study focusing on the effect of DOM on the occurrences of brown tides in this area is scare by far. To analyze the efficiency of DOM hydrolysis by different groups of microorganisms and the possible influence of DOM on the formation of brown tides, extracellular enzymes such as α, β-glucosidases (α, β-GLUs), leucine aminopeptidase (LAP) and alkaline phosphatase (AP) as well as other environmental parameters were analyzed during a pre-bloom period of A. anophagefferens in June 2014. Dissolved organic nitrogen (DON) and phosphorus (DOP) contributed more than half of the total dissolved nutrient pools. Approximately 60-70% of the enzyme activities were associated with phytoplankton of size >5 μm. The hydrolysis rates of LAP were approximately 5 to 20 fold higher than those of AP and α, β-GLUs. The ratios of β-GLU activities: LAP activities indicated the hydrolysis potential related to proteins rather than polysaccharides. The differences in turnover time among the enzymes suggested that DOP was firstly hydrolyzed and recycled in the water in the early minutes, followed by the hydrolysis of DON and dissolved organic carbon (DOC)(in hours). Results suggest that the hydrolysis of DOM, in particular DOP, might significantly contribute to the occurrences of brown tides in the coastal waters of Qinhuangdao, China., (Copyright © 2018 Elsevier B.V. All rights reserved.)

p27 mediates cell cycle arrest by binding to and inhibiting cyclin-dependent kinase/cyclin complexes, but p27 can also contribute to pro-oncogenic signaling upon mislocalization to the cytoplasm. Cytoplasmic p27 stimulates cell migration by associating with RhoA and interfering with the exchange of GDP from RhoA stimulated by guanine nucleotide exchange factors. We used biophysical methods to show that the N-terminus of p27 directly interacts with RhoA in vitro. The affinity of p27 for RhoA is low, with an equilibrium dissociation constant of hundreds of micromolar; however, at high concentrations, p27 interfered with guanine nucleotide exchange factor-mediated nucleotide exchange from RhoA. We also show that promotion of cell migration in scratch wound cell healing assays requires full-length p27 despite the C-terminus being dispensable for the direct interaction between p27 and RhoA in vitro. These results suggest that there may be an unidentified factor(s) that associates with the C-terminus of p27 to enhance its interactions with RhoA and promote cell migration., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To investigate the epidemiological features of child and adolescent (≤18 years old) patients managed for traumatic skull fractures (TSKFs) and associated traumatic brain injury (TBI)., Design: 393 Patients who were children and adolescent who had TSKFs admitted to our university affiliated hospitals between January 2003 and December 2010. The incidence and patterns were summarized with respect to different age group, admission time and etiology., Setting: Two university-affiliated hospitals from January 2003 to May 2010., Results: The most common etiologies were motor vehicle collisions (MVCs) (166, 42.2%) and high fall (101, 25.7%). The most common skull fracture sites were parietal fractures (n=111, 28.2%) and basilar skull fracture (n=111, 28.2%). A total of 300 (76.3%) patients suffered TBI and 23 (5.9%) patients suffered OCI. The most common intracranial hemorrhage was epidural hemorrhage (n=94, 23.9%). The frequencies of emergency admission, medical insurance and associated injuries were 56.2% (n=221), 22.4% (n=88) and 37.2% (n=146). The frequencies of TBI and associated injuries were significantly increased from 53.45% to 76.3% and from 6.9% to 41.6% with age, respectively., Conclusions: MVCs were the most common etiologies. Parietal and basilar skull fractures, epidural hemorrhages were the most common fracture sites and intracranial hemorrhage., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A novel nano-CaCO 3 /polystyrene nanocomposite adsorbent (NPS-8) was synthesized for efficient bilirubin removal from human plasma. A comparison with the polystyrene adsorbent (PS-8), which was without the incorporation of nano-CaCO 3 , revealed that NPS-8 had superior bilirubin adsorption capacity and mechanical strength. The resulting nano-CaCO 3 reinforced PS-8 (NPS-8) was tested by transmission electron microscopy (TEM), scanning electron microscopy (SEM), mechanical strength test, and bilirubin adsorption assays. The adsorption results indicated that NPS-8 displayed better adsorption capacity for bilirubin (91%) than that of PS-8 (75.88%). The mechanical strength of NPS-8 was significantly greater than that of PS-8. In addition, both PS-8 and NPS-8 possessed good blood compatibility properties (a negligible hemolytic activity and platelet adhesion). Therefore, a conclusion could be drawn that NPS-8 has a high potential as an efficient bilirubin adsorbent for blood purification in clinical practice. At the same time, the success of organic-inorganic nanocomposite adsorbents might provide a new insight into the improvement of adsorbents in hemoperfusion., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Recently, several studies have indicated that circular RNAs (circRNAs) play significant roles in various disease; however, little is known about the chronology of estrogen receptor beta (ERβ) deficiency and altered circRNA expression, or their relationship with osteogenesis. Herein, we show through western-blot and quantitative real-time PCR assays, that when ERβ is silenced, the expression of osteogenesis-related proteins and mRNAs were down-regulated. We then performed RNA-Seq to analyze differential circRNA expression between the control and ERβ knockdown group. This analysis revealed that, 146 circRNAs were differentially expressed by fold-change≥2.0, p ≤ 0.05, and, among this group, 68 circRNAs were down-regulated, while 78 were up-regulated. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and PANTHER pathway analyses were performed to predict the function of these differentially expressed circRNAs. Finally, co-expressed targets gene, and circRNA-microRNA network were constructed for predicted miRNA sponges. This research suggested that ERβ may through 2:27713879|27755789/2:240822115|240867796-miR-328-5p-mRNA axis to regulate osteogenic differentiation., (Copyright © 2017. Published by Elsevier Inc.)

An analytical H2 controller design approach of homogeneous multi-agent systems with time delays is presented to improve consensus performance. Firstly, a closed-loop multi-input multi-output framework in frequency domain is introduced, and a consensus tracking condition is given. Secondly, the decomposition method is utilized to simplify the analysis of internal stability and H2 performance index of the whole system to a set of independent optimization problems. Finally, the H2 optimal controller can be computed from all the stabilizing controllers. The contributions of the new approach are that the design procedure is conducted analytically for arbitrary delayed multi-agent systems, and a simple quantitative tuning way is developed to trade off the nominal performance and robustness. The simulation examples show the effectiveness of the proposed control strategy., (Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.)

Neotuberostemonine is a potent antitussive alkaloid extracted from Stemona tuberosa. However, the pharmacokinetics, tissue distribution and excretion of pure neotuberostemonine have not been reported. The present study was aimed to investigate the pharmacokinetic parameters of neotuberostemonine by developing an ultra-high performance liquid chromatography-tandem mass spectrometry method. Neotuberostemonine and tetrahydropalmatine (internal standard, IS) in bio-samples were extracted by protein precipitation with methanol and successfully separated on a Zorbax Extend C18 column by using a mobile phase of acetonitrile and a mixture of 0.1% formic acid and 5mM ammonium acetate. The detection was performed by using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/z 376.1→302.0 for neotuberostemonine and 355.8→192.0 for IS. After oral administration of neotuberostemonine in rats, the Cmax and AUC0-∞ were 11.37ng/mL and 17.68ng·h/mL at 20mg/kg and 137.6ng/mL and 167.4ng·h/mL at 40mg/kg, and the t1/2 were 2.28 and 3.04h at 20 and 40mg/kg, respectively. The high neotuberostemonine concentrations were found in intestine, stomach and liver, and there was no long-term accumulation of neotuberostemonine in tissues. Total recoveries of neotuberostemonine were only 0.90% (0.19% in bile, 0.05% in urine and 0.66% in feces), which might be resulted from the intestine and liver first-pass effects, indicating that neotuberostemonine may be mainly excreted as its metabolites. All above results would provide helpful information for the further pharmacological and clinical studies of neotuberostemonine and the crude drug., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Mixotrophy is found in almost all classes of phytoplankton in a wide range of aquatic habitats ranging from oligotrophic to eutrophic marine and freshwater systems. Few studies have addressed how the nutritional status of the predator and/or the prey affects mixotrophic metabolism despite the realization that mixotrophy is important ecologically. Laboratory experiments were conducted to examine changes in growth rates and physiological states of the toxic haptophyte Prymnesium parvum when fed Rhodomonas salina of varying nutritional status. Haemolytic activity of P. parvum and prey mortality of R. salina were also measured. P. parvum cultures grown to be comparatively low in nitrogen (low-N), phosphorus (low-P) or low in both nutrients (low-NP) were mixed with low-NP, low-N, and low-P R. salina in all possible combinations, i.e., a 3×3 factorial design. N deficiency was obtained in the low-N cultures, while true P deficiency may not have been obtained in the low-P cultures. Mortality rates of R. salina (both due to ingestion and/or cell rupture as a function of grazing or toxic effects) were higher when R. salina cells were low-P, N-rich, regardless of the nutritional state of P. parvum. Mortality rates were, however, directly related to the initial prey:predator cell ratios. On the other hand, growth of the predator was a function of nutritional status and a significant positive correlation was observed between growth rates of P. parvum and cell-specific depletion rates of N, whereas no such relationship was found between P. parvum growth rates and depletion rates of P. In addition, the greatest changes in chlorophyll content and stoichiometric ratios of P. parvum were observed in high N:P conditions. Therefore, P. parvum may show enhanced success under conditions of higher inorganic N:P, which are likely favored in the future due to increases in eutrophication and altered nutrient stoichiometry driven by anthropogenic nutrient loads that are increasingly enriched in N relative to P., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Pressure ulcers (PUs) are serious skin injuries whereby the wound healing process is frequently stalled in the inflammatory phase. Myeloid-derived suppressor cells (MDSCs) accumulate as a result of inflammation and promote cutaneous wound healing by mechanisms that are not fully understood. Recently, MDSCs have been shown to differentiate into fibrocytes, which serve as emerging effector cells that enhance cell proliferation in wound healing. We postulate that in wound healing MDSCs not only execute their immunosuppressive function to regulate inflammation but also stimulate cell proliferation once they differentiate into fibrocytes. In the current study, by using full-thickness and PU mouse models, we found that Kruppel-like factor 4 (KLF4) deficiency resulted in decreased accumulation of MDSCs and fibrocytes, and wound healing was significantly delayed. Conversely, KLF4 activation by the plant-derived product Mexicanin I increased the number of MDSCs and fibrocytes and accelerated the wound healing. Collectively, our study revealed a previously unreported function of MDSCs in cutaneous wound healing and identified Mexicanin I as a potential agent to accelerate PU wound healing.

Objectives: To examine the extent social support mediates resilience and quality of life in Wenchuan earthquake survivors., Study Design: Originals., Methods: Self-report psychological questionnaires, the standard Chinese 12-item Short Form (SF-12v2), the Resilience Scale for Adults (RSA), and the Social Support Rating Scale (SSRS) were used to interview a total of 2080 survivors from 19 counties in the 2008 Wenchuan Earthquake area. A regression analysis was conducted to evaluate the mediating effect of social support on quality of life., Results: Males and individuals with a higher level of education were found to have a better quality of life. The association between resilience and quality of life improved after social support was included, suggesting that at least a part of this association was mediated by the level of social support provided., Conclusions: This analysis highlighted that the level of resilience and quality of life after an earthquake was associated with the level of social support. This result has clear policy implications, and indicates that more focus needs to be placed on policies that aim for the provision of early mental health intervention and social support to improve the quality of life of earthquake survivors., (Copyright © 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

A huge amount of kernel cake, which contains a variety of toxins including phorbol esters (tumor promoters), is projected to be generated yearly in the near future by the Jatropha biodiesel industry. We showed that the kernel cake strongly inhibited plant seed germination and root growth and was highly toxic to carp fingerlings, even though phorbol esters were undetectable by HPLC. Therefore it must be detoxified before disposal to the environment. A mathematic model was established to estimate the general toxicity of the kernel cake by determining the survival time of carp fingerling. A new strain (Streptomyces fimicarius YUCM 310038) capable of degrading the total toxicity by more than 97% in a 9-day solid state fermentation was screened out from 578 strains including 198 known strains and 380 strains isolated from air and soil. The kernel cake fermented by YUCM 310038 was nontoxic to plants and carp fingerlings and significantly promoted tobacco plant growth, indicating its potential to transform the toxic kernel cake to bio-safe animal feed or organic fertilizer to remove the environmental concern and to reduce the cost of the Jatropha biodiesel industry. Microbial strain profile essential for the kernel cake detoxification was discussed., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objectives: Prostate stem cell antigen (PSCA), a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein, is highly expressed in both local and metastatic prostate cancer (CaP). Elevated PSCA expression has been shown to correlate with malignant phenotype and clinical progression. The purpose of the current study is to investigate the therapeutic potential of small interference RNA (siRNA) targeting PSCA on human CaP cells., Materials and Methods: A set of two siRNAs directed different regions of human PSCA (siRNA-PSCA) were designed and transfected into a human CaP PC-3M cell line. The silencing effect was screened by RT-PCR and Western blotting. The biological effects of siRNA-PSCA on PC-3M cells were investigated by examining the cell proliferation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle distribution through flow cytometry, and migration and invasion potencies through transwell invasion assay upon the PSCA silencing., Results: PC-3M cells had positive PSCA expression on immunocytochemical assay. PSCA expression was depleted at 48 hours after transfection with siRNA-PSCA. Silencing of PSCA significantly suppressed cell proliferation. Cell cycle assay showed that the anti-proliferation effect of siRNA-PSCA was mediated by arresting cells in the G0/G1 phase rather than apoptosis. Furthermore, PSCA knockdown resulted in a marked decrease of cell migration and invasion capabilities in PC-3M cells., Conclusions: The present study provides the first evidence that silencing PSCA using siRNA can inhibit the proliferation and invasiveness properties of human CaP cells, which may provide a promising therapeutic strategy for CaP and open a novel avenue toward the investigation of the role of PSCA overexpression in cancers., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: Variants in hepatic lipase (HL) gene which is a lipolytic enzyme involved in the metabolism of plasma lipoprotein and regulating lipid and lipoprotein metabolism are potential candidate genes for type 2 diabetes. Association of the polymorphisms in the promoter region of the HL gene (LIPC) to the plasma HDL-C concentration has been investigated. In this study, we investigated whether the G-250A polymorphism of LIPC is associated with type 2 diabetes in Chinese Han population., Subjects and Methods: A total of 130 patients with type 2 diabetes and 133 healthy subjects as control were randomly selected from January 2008 to January 2011 in endocrine wards of Zhengzhou People's Hospital. The G-250A polymorphisms were studied by polymerase chain reaction and restriction fragment length polymorphism. A logistic regression analysis was performed to determine the association between the rare allele and type 2 diabetes mellitus., Results: The frequency of the -250A allele was 0.297 in the T2DM group and 0.388 in the control group (P<0.05), with the difference remaining significant., Conclusions: Patients who are carrying of the -250A allele in the promoter of the LIPC gene are susceptible to type 2 diabetes mellitus in Chinese Han population., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the parents' perceived unmet needs in early childhood healthcare services among Indigenous, non-English-speaking background (NESB) and English-speaking background (ESB) children and the related barriers., Method: Data was from the Longitudinal Study of Australian Children (LSAC). Rao-Scott chi-square was used to examine the level of parents' perceived unmet needs in three ethnic groups in early childhood healthcare services over a 12 month period. Survey logistic regression was used to assess the association between the groups of infants and the barriers to utilisation., Results: Ten per cent of Australian infants have at least one parents' perceived unmet need in early childhood healthcare services. NESB (15.3%) and Indigenous (15.1%) infants were more likely than ESB infants (9.9%, p<0.001) to have parents' perceived unmet needs in health care services. The barriers to service access include cost, transport problems, child care difficulties, service availability and family reasons. Parents of ESB infants were more likely to cite operating hours as the major barrier to accessing services., Conclusion: There were parents' perceived unmet needs in a number of health services for all Australian infants, but at different levels by Indigenous, NESB and ESB groups. The most common barrier to services utilisation related to cost or private health insurance, availability and accessibility of service provision and other socioeconomic issues., Implications: Policy attention and operational changes are required to improve equity in accessing early childhood services, as well as to improve the overall access to healthcare services for all Australian infants., (© 2011 The Authors. ANZJPH © 2011 Public Health Association of Australia.)

Concentrations of OCPs in rain, canopy throughfall, and runoff water were measured in the Beijing metropolitan area during the rainy seasons from 2006 to 2007. This study was conducted to calculate the fluxes of OCPs in rain and canopy throughfall, as well as their contributions to runoff. At urban sites, the contribution of HCB and ΣHCHs from rainfall accounted for approximately 50% of the mass in runoff. At the site with significant coverage of landscaping trees, the HCB, ΣHCHs, and ΣDDTs from the net canopy throughfall accounted for approximately 10% of the mass in the runoff. Based on the data obtained in this study, loadings of OCPs (in μg) in rain, net canopy throughfall, and runoff water were calculated. The input of OCPs from rain and canopy throughfall water accounted for a significant portion of urban runoff. In cities undergoing rapid urban sprawl, monitoring and control of the transport of OCPs in urban runoff are essential for effective control of environmental hazards in surface water bodies., (Copyright © 2010 Elsevier B.V. All rights reserved.)

An improved liquid chromatographic method with on-line solid phase extraction (SPE) and tandem mass spectrometric detection was optimised for quantification of the anti-HIV peptide Sifuvirtide in human plasma. The SPE sorbents, loading buffer composition and other aspects of the on-line SPE column were investigated in detail for efficiently extracting the interesting peptides and simultaneously discarding the large amount of proteins. The gradient elution program was optimised on the analysis column to decrease the matrix effect and obtain excellent selectivity. The multiple charge ion at m/z 946.4 of Sifuvirtide was quantified by a linear ion trap mass spectrometer, operating in the positive mode, and selective reaction monitoring (SRM) acquisition. Method validation results demonstrated that the linear calibration curve covered a range of 6.1-6250 ng/mL, and the correlation coefficients (r(2)) were above 0.992. The lower limit of detection (LLOD) with a signal-to-noise (S/N) ratio higher than 10 was 6.1 ng/mL. The accuracy ranged from -7.6 to 10.6%, and the intra- and inter-batch precisions were less than 8.7% and 5.5%, respectively. Finally, more than nine hundred of samples from a clinical trial was completely analyzed using this on-line SPE coupled HPLC-MS/MS system in one single week, due to the rapid run-time of individual sample (6.5 min)., (Copyright 2010 Elsevier B.V. All rights reserved.)