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Fluoride is a common pollutant from nature, normal life, and production. Adsorption, electro-adsorption, and precipitation are dominant mechanisms corresponding to the adsorption and electro-adsorption technologies for removing fluoride. This paper presents Ti 3 AlC 2 as an effective reagent for removing fluoride under acidic conditions. The adsorption mechanisms of adsorption and electro-adsorption were compared to sedimentation at pH 2 and 1, leading to a higher removal rate of adsorption by pH 2 than at pH 1. The adsorptive behavior of Ti 3 AlC 2 with fluoride includes both multilayer sorption and chemisorption. Furthermore, the precipitation reaction induced a partial change of Ti 3 AlC 2 to MXene. Notably, electro-adsorption was more effective rather than sedimentation at pH 1 in capacitive deionization technology. The Al adsorption sites made it easier to combine fluoride than Ti, and aluminum fluoride was easier to produce than titanium (III) fluoride. These adsorption and electro-adsorption experiments were carried out to elucidate and delineate the performance of Ti 3 AlC 2 for removing fluoride. A molecular model of Ti 3 AlC 2 was also built to calculate adsorption using the density functional theory. Hence, the Ti 3 AlC 2 molecular model combined with XPS and other characterizations of materials provided an effective, easy-to-understand combinative mechanism for removing fluoride. [Display omitted] • Ti 3 AlC 2 was applied to remove fluoride. • The removal of fluoride was investigated by comparison of adsorption and electro-adsorption. • Different ratios of reaction mechanisms were analyzed by adsorption and electro-adsorption. • The reaction mechanisms were studied by combining experiments and density functional theory. [ABSTRACT FROM AUTHOR]

The thermal behavior in aluminum-air battery has prominent effect on its operation performance, however, the investigations to the battery thermal behavior are still scarce. In this paper, an alkaline vehicular traction aluminum-air battery was designed and its thermal behavior was experimentally investigated. The impacts of various parameters were examined, including the ambient temperature, electrolyte concentration, and discharge current density on the battery's temperature-rise, outgoing heat-flux, heat generation rate, and discharge efficiency, etc. It is shown that the battery's temperature-rise, outgoing heat-flux, and heat generation rate increase with the ambient temperature decreases and the electrolyte concentration increases. Furthermore, the battery heat generation rate decreases over the discharge time, particularly it decreases drastically at the first half of discharge. The discharge efficiency of the battery increases with the increases of operating temperature and discharge current density. The battery discharge efficiency varies with the electrolyte concentration, which approaches 78 % under the electrolyte concentration of 3.0 mol L−1, but less than 60 % under the concentrations of 1.0 mol L−1 and 6.0 mol L−1. The present study compensates a vacancy of the thermal behavior characterization for a vehicular traction aluminum-air battery, and the results are of significance in understanding the aluminum-air battery's thermal behavior. • An alkaline Al-air battery is devised. • Proposes a measurement method to characterize the Al-air battery thermal behavior. • Impacts of thermal behavior on Al-air battery operating performance is studied. [ABSTRACT FROM AUTHOR]

The impacts of subcutaneous Lixisenatide on body weight in patients with type 2 DM, remain inadequately understood; consequently, this systematic review and meta -regression analysis of randomized controlled trials (RCTs) was conducted to evaluate the influence of subcutaneous Lixisenatide administration on BW and BMI values in individuals with Type 2 diabetes. A comprehensive literature search was conducted across four databases, spanning from their inception to February 2023. We computed effect sizes employing the random-effects model and reported results in terms of weighted mean differences (WMD) along with their corresponding 95% confidence intervals (CI). 23 articles with 26 RCT arms were included in the meta -analysis. The combined findings from a random-effects model demonstrated a significant reduction in body weight (WMD: −0.97 kg, 95 % CI: −1.10, −0.83, p < 0.001) and BMI (WMD: −0.48 kg/m2, 95 % CI: −0.67, −0.29, P < 0.001) after subcutaneous administration of Lixisenatide. Furthermore, a more pronounced reduction in body weight was discovered in RCTs lasting less than 24 weeks (WMD: −1.56 kg, 95 % CI: −2.91, −0.20, p < 0.001), employing a daily dosage of subcutaneous Lixisenatide lower than 19 µg per day (WMD: −1.94 kg, 95 % CI: −2.54, −1.34, p < 0.001) and with a mean participant age of 60 years or more (WMD: −1.86 kg, 95 % CI: −3.16, −0.57, p = 0.005). Lixisenatide was found to significantly decrease BW and BMI in patients with type 2 DM and could be considered as a therapeutic option for those suffering from weight gain caused by other anti-diabetic agents. However, while prescribing Lixisenatide, careful consideration of patient-specific factors is recommended. [ABSTRACT FROM AUTHOR]

Owing to these phenomena about intercalation and deintercalation lithium-ion, thermal expansion, and external pressure in lithium-ion batteries, the interior separators are often subjected to compression stress. In this study, we have designed a novel model based on the Thiessen Polygon, which is used to describe 3D porous structure of polyethylene (PE) separator. It can simulate the structure evolution of separator during compression. The simulation results show that when the compression stress is up to 60 MPa, the thickness of the separator decreases by nearly 50%, and the porosity decreases from 42.6% to 10%, which severely affects the ionic transmission performance. Additionally, the separator with changed porosity structure under different compression conditions was applied to the electrochemistry-thermal model to simulate the discharge process of the battery. As results, it is found that the discharge capacity is significantly reduced and the temperature is increased due to the structural variation of the separator caused by compression stress. This study develops a novel mechanical model which can be used in the simulation of separator compression process, and involves the simulation of multiple physical fields. And it successfully correlates the mechanical properties of separator with its battery performance. • A novel mechanical model of the PE separator has been developed. • The structure evolution of separator during compression has been simulated. • Compressed separator causes degradation of the battery performance. [ABSTRACT FROM AUTHOR]

It is seen from this figure that the maximum temperature rise of the cell module decreases as the increasing rate of fluid flow. The maximum temperature rise of the cell module is under 40 °C and 36 °C respectively since the flow rate is 0.40 × 10−3 L·s−1 and 1.20 × 10−3 L·s−1, indicating that increasing flow rate increases the cooling capability of the LCP. • A new cooling plate is developed for controlling undesirable cell temperature field. • Inlet and outlet of cooling plate have big impact on cell temperature distribution. • Increasing flow rate decreases cell temperature rise markedly. • Cooling plate channel width has weak impact on cell temperature distribution. • Channel width has great effect on ratio of power consumption of cooling plate. The thermal management for a lithium ion battery cell plays a pivotal role in enhancing the cell performance and reliability for electric vehicles. In this work, a novel serpentine-channel liquid cooling plate with double inlets and outlets is developed for better managing an undesirable temperature distribution of a cell module. With a simplified model for the cell module, numerical analyses are implemented using the software of FloEFD to study effects of flow directions, flow rates and channel widths of the cooling plate on cell temperature distribution under different operating conditions; Likewise, a ratio of power consumption as a non-dimensional number is defined to analyze the hydraulic performance of the developed cooling plate. Results show that locations of the inlet and the outlet as well as flow directions have great impacts on the cell temperature distribution and the ratio of power consumption of the cooling plate. Increasing fluid flow rate substantially decreases the maximum temperature rise of the cell module while it has little effect on the temperature distribution. Moreover, the channel width of the cooling plate has a strong influence on its ratio of power consumption as well as the cell temperature distribution but it has a weak influence on the cell maximum temperature rise. Interestingly, the developed serpentine-channel cooling plate offers one a new method to design a lithium ion battery thermal management system for controlling temperature distribution of a cell module. [ABSTRACT FROM AUTHOR]

It is seen from these two figures that the battery temperature and SOC have a minor effect on its thermal conductivity. Battery thermal conductivity vary with the battery types heavily. • A novel method for determining thermal parameters of lithium ion cells is presented. • Temperature has a linear effect on thermal conductivity and specific heat of cells. • Cell temperature has a higher effect on its specific heat than thermal conductivity. • Cells' thermal conductivity and specific heat vary with the battery types. • The method is more effective to test thermal conductivity and specific heat of cells. Characterizing thermal parameters of a lithium ion battery is a key step to predict the temperature distribution of battery cell modules. In this work, a novel method is developed based on the quasi-steady state heat transfer analysis to determine the thermal conductivity and the specific heat simultaneously. Both prismatic lithium iron phosphate cells and pouch cells with different electrode materials are used in this experimental test. A constant heat flux is applied to the cell surface whereas the heat loss is estimated based upon the temperature drop curve. As such, the quasi-steady state heat transfer can be attained to determine cell thermal parameters. It is observed that cell thermal parameters increase linearly with the increase of the operating temperature. Furthermore, the operating temperature has a more significant influence on the cell specific heat than the thermal conductivity, while the effect of the state of charge has a minimal effect on these two parameters. The current method demonstrates an effective and practical way to determine the thermal conductivity and specific heat of the cell simultaneously. [ABSTRACT FROM AUTHOR]

• CZ48 was incorporated into PLA microbubbles via a double emulsion technique. • The encapsulation efficiency and drug-loading content were ˜85.73% and 26.07%. • The half-life time of CZ48 and CPT of CZ48-loaded microbubbles was enhanced. • Controlled release of CZ48–loaded microbubbles was achieved in vitro and in vivo. CZ48, a prodrug of camptothecin (CPT) with derivative resistant to lactone hydrolysis, suffers from limited application for cancer treatment due to poor water-solubility, thus causing its low bioavailability and absorption in vivo. To echo this problem, CZ48 was incorporated into poly (lactic acid) (PLA) microbubbles via a double emulsion technique (W/O/W), and the successful loading was confirmed by X-ray diffraction (XRD) patterns and confocal laser scanning microscope (CLSM). The obtained CZ48-loaded microbubbles had a diameter ranging from 0.5 to 6.7 μm, and the encapsulation efficiency and drug-loading content were as high as 85.73 ± 2.41% and 26.07 ± 0.76%, respectively. The in vitro drug release demonstrated that only about 55% of CZ48 was released for CZ48-loaded PLA microbubbles in 48 h. In contrast, over 90% of CZ48 was released for free CZ48 crystals sample in only 5 h. Besides, in vivo pharmacokinetic studies further revealed that the availability of both CZ48 and its metabolite CPT were obviously enhanced after the incorporation of CZ48 into PLA microbubbles. To be noted, the value of AUC 0-∞ of the CZ48-loaded microbubbles was about 5-fold higher than that of free CZ48 suspension, implying a much higher anticancer effect of the CZ48-loaded microbubbles. The half-life time (T 1/2) of both CZ48 and CPT of the CZ48-loaded microbubbles were also significantly longer than that of the free CZ48, indicating a delayed release time for the microbubbles. Hence, this work promotes a promising drug carrier system for the controlled release of CZ48 as well as other drugs with poor water-solubility. [ABSTRACT FROM AUTHOR]

• Vitamin D catabolism via Cyp24a1 modulates postnatal and pregnancy-associated mammary gland development. • Cyp24a1 gene deletion in the mammary epithelium inhibits luminal epithelial proliferation but not apoptosis. • Luminal mammary epithelial cells are more sensitive to 1,25(OH)2D with the ablation of Cyp24a1 activity. Active vitamin D (1,25(OH)2D) has been shown to regulate numerous cell processes in mammary cells. Degradation of 1,25(OH)2D is initiated by the mitochondrial enzyme, 25-hydroxyvitamin D 24-hydroxylase (CYP24 A1), and provides local control of 1,25(OH)2D bioactivity. Several reports of the association between elevated CYP24 A1 activity and breast cancer incidence, suggest that CYP24 A1 may be a target for therapeutic intervention. Whether CYP24 A1 activity within the mammary epithelium regulates 1,25(OH)2D levels and mammary gland development is yet to shown. We have used a conditional knockout of the Cyp24a1 gene specifically in the mammary epithelium to demonstrate reduced terminal end bud number, ductal outgrowth and branching during puberty and alveologenesis at early pregnancy, by inhibiting proliferation but not apoptosis in both basal and luminal MECs. In vitro study showed increased sensitivity of luminal MECs to lower levels of 1,25(OH)2D with the ablation of Cyp24a1 activity. In summary, Cyp24a1 within MECs plays an important role in modulating postnatal and pregnancy-associated mammary gland development which provides support for inhibiting CYP24 A1 as a potential approach to activating the vitamin D pathway in breast cancer prevention and therapy. [ABSTRACT FROM AUTHOR]

We report fabrication and photovoltaic properties of flexible dye-sensitized solar cells (FDSSCs) based on stainless steel mesh (SSM)-supported core-shell ZnO/TiO 2 nanorods photoanode and Pt nanoparticles- coated SSM counter electrode (Pt/SSM CE). The core-shell ZnO/TiO 2 structures were prepared via simple chemical bath deposition, and optimal conversion efficiency of 2.84% was achieved. When aluminum foil membrane was introduced on the back of the FDSSCs as reflecting film (Rf) for improving utilization of sunlight, the conversion efficiency of FDSSCs was increased from 2.84% to 3.12%. The relative improvement of 218% was achieved in conversion efficiency compared with similar device without TiO 2 buffer layer and reflecting film (0.98%). Meanwhile, the Pt CE based on SSM possessed of higher catalytic ability and longer stability compared with ITO/PET-based Pt CE. [ABSTRACT FROM AUTHOR]

Abstract The purpose of present HUVE cells and mice study was to investigate the combined effects of carnosine and asiatic acid (AA) against diabetic progression. In HUVE cells, high glucose decreased cell viability, reduced Bcl-2 mRNA expression and increased Bax mRNA expression. The co-treatment of 0.5 μM carnosine plus 0.5 μM AA led to greater cell viability and Bcl-2 mRNA expression than 1 μM carnosine or 1 μM AA treatment alone. This combination more significantly decreased the production of DNA fragmentation, tumor necrosis factor (TNF)-alpha, reactive oxygen species (ROS), and nuclear factor kappa B binding activity than carnosine or AA treatment alone. In diabetic mice, the combination of 0.25% carnosine plus 0.25% AA in diet resulted in higher final body weight, and lower levels of plasma glucose and triglyceride than 0.5% carnosine or 0.5% AA treatment alone. Carnosine and AA combination caused more reduction in renal levels of leukin-6, TNF-alpha and ROS than carnosine or AA treatment alone. This combination also more significantly limited renal cyclooxygenase-2 activity and p-p38 phosphorylation than carnosine or AA treatment alone. These novel findings support that this combination is a more powerful remedy for diabetic control. Graphical abstract Effects of carnosine (Car) and/or AA upon NF-κB p50/65 binding activity (OD value/mg protein). HUVE cells were pre-treated with 1 μM Car, 1 μM AA or 0.5 μM Car+0.5 μM AA for 24 h incubation at 37 °C. Then, cells were treated with DMEM containing high glucose (33 mM), and followed by incubating for another 24 h at 37 °C. Normal group had no Car, AA, or high glucose. Control group had no Car or AA, but with high glucose. Data are mean ± SD (n = 6). Values with different alphabet among bars are significantly different at P < 0.05 as analyzed by Dunnett's t -test. Image 1 Highlights • HUVE cell line and diabetic mice were used to examine the combined effects of carnosine and asiatic acid (AA). • Co-treatment of carnosine plus AA led to grater HUVE cell viability and Bcl-2 mRNA expression. • In diabetic mice, carnosine and AA combination caused more reduction in renal IL-6, TNF-alpha and ROS generation. • This combination led to more decrease in renal cyclooxygenase-2 activity and p-p38 phosphorylation. • These findings support that this combination is a powerful remedy for diabetic control. [ABSTRACT FROM AUTHOR]

Graphical abstract It is found that the average heat generation rate of the lithium-ion battery cell has a quadratic relationship with the operating temperatures and operating currents. Tested results of the heat generation rate show a good agreement with results calculated as per widely used Bernardi's heat generation model. Highlights • Reveals a method for testing specific heat and heat generation of a Lithium ion cell. • Increasing temperature linearly increases the specific heat of Lithium ion cell. • Heat generation of Lithium ion cell quadratically increases with increasing current. • Tested results of heat generation via new method and Bernardi model are consistent. Abstract The specific heat and the heat generation rate are the key thermal properties for lithium ion battery cells. Nonetheless, there exists large scattering in data of thermal properties due to factors such as battery temperature nonuniformity during experimental measurement. In this work, a novel calorimetric method for measuring thermal properties of a lithium ion battery cell is proposed by introducing a temperature even out process to minimize the effect of the temperature difference across the battery. Through this method, the specific heat and the heat generation rate can be characterized for the electrochemical batteries. Thermal parameters of a prismatic lithium iron phosphate battery cell are determined for the wide temperature range at varying operating currents. It is found that the specific heat of the lithium ion battery cell has a linear relationship with the operating temperature, whereas the heat generation rate has a quadratic relationship with the operating current. The measured heat generation rate shows a good agreement with calculated results as per Bernardi's heat generation model. This new method allows one to obtain thermal properties of lithium ion battery cells at a lower cost and in a shorter time. [ABSTRACT FROM AUTHOR]

Abstract With growing demand for economic, eco-friendly, easy-manufacturing and renewable portable power source, flexible dye-sensitized solar cells (FDSSCs) exhibit a promising potential in the field of portable power sources. However, FDSSCs surfer from low conversion efficiency and poor stability, which hinder their applications. In this work, we have summarized recent development and challenges according to respective functions of their vital components (substrate, semiconductor film, sensitizer, electrolytes and counter electrode) as well as their effects on photoelectric conversion efficiency. Meanwhile, typical fabrication approaches have been analyzed for increasing the incident photon to current efficiency (IPCE). The approaches in rigid dye-sensitized solar cells (DSSCs) for improving performance are also introduced to provide the favorable direction for accelerating FDSSCs' application in field of potable power source. [ABSTRACT FROM AUTHOR]

The biologically active form of vitamin D 3 (1,25(OH) 2 D) regulates epithelial cell differentiation, proliferation, and apoptosis, lending weight to clinical evidence linking vitamin D 3 insufficiency to breast cancer incidence and mortality. Local dysregulation of vitamin D 3 metabolism has been identified in patients with breast cancer, implying that disruption of 1,25(OH) 2 D signaling may contribute to breast cancer development in an autocrine or paracrine manner. Mouse mammary glands express the critical enzymes responsible for 1,25(OH) 2 D synthesis (Cyp2r1 and Cyp27b1), degradation (Cyp24a1), as well as the vitamin D 3 receptor (Vdr), and genetically modified mouse models have revealed a great deal about the role of vitamin D 3 in cancer initiation and progression. Ablation of Vdr or Cyp27b1 in murine models of mammary cancer reduces the anti-tumor effects of vitamin D 3 , while elevation of Cyp24a1 levels increases degradation of 1,25(OH) 2 D, leading to diminished anti-tumor effects. This review discusses the recent transgenic mouse models of vitamin D 3 metabolism and the Vdr signaling network, and how these contribute to mammary gland development, and cancer tumorigenesis and progression. Collectively, these mouse models have helped clarify mechanisms of action of vitamin D 3 signaling and suggest that activation or restoration of the vitamin D 3 regulated pathway is a potential approach for human breast cancer prevention. [ABSTRACT FROM AUTHOR]

• Two flow regimes were observed in membrane assisted reactive crystallization (MARC). • Reversible transitions between liquid layer and droplet can be achieved on membrane surface. • Controllable mixing and ions diffusion conditions were achieved via MARC. • Crystals with narrow nano/micro size distribution were obtained via MARC. Herein, membrane-assisted reactive crystallization (MARC) with effective interfacial flow regimes was proposed to achieve the effective mass transfer control during reactive crystallization. Three tube-shell side solution systems (EtOH-H 2 O, Butanol-H 2 O and H 2 O-H 2 O) were chosen to form different flow regimes on the membrane surface, including the microscale liquid layer and the uniform droplets. The fundamental mechanisms of 'rising and falling tide' phenomenon, and flexible layer thickness control were uncovered. A force analysis model was established to illustrate the transition behavior of the droplet and liquid layer on the membrane surface. Molecular simulations additionally demonstrated that MARC implemented various ion diffusion conditions in different solution systems. Compared to the conventional reactive crystallization, MARC with multiple flow regimes can achieve effective control of CaCO 3 crystal size ranging from 700 nm to 3 μm and obtain uniform size distribution (coefficient of variation less than 15.1 %), which shed light on the advanced material manufacture with reactive crystallization process. [ABSTRACT FROM AUTHOR]

As various heat-resistant polymer separators come out, although they possess better thermal stability and superior affinity to liquid electrolyte than commercial polyolefin separator, the porous structure and chemical stability of these novel separators should be paid more attention. In this work, we prepare a thin polyacrylonitrile/cellulose acetate (PAN/CA) composite nanofiber separator and discuss the importance of chemical stability in the ester-based electrolyte. The addition of CA decreases the PAN/CA fiber diameter from 310 nm to 210 nm. However, CA containing a lot of ester groups is easy to be dissolved by liquid electrolyte for the property of similarity and compatibility. Hence, the obtained PAN/CA composite nanofiber separator is treated via alkaline hydrolysis process, and some ester groups are transformed to be hydroxyl groups. Noteworthily, hydroxyl-rich PAN/CA composite nanofiber separator not only remains stable in electrolyte, but also possesses an improved lithium-ion transport property for reducing concentration polarization effect. As a result, the LiCoO 2 /Li half cells employing the hydroxyl-rich composite nanofiber separator exhibits better capacity retention (118.5 mAh g−1 after 300 cycles) and superior rate performance (143.1 mAh g−1 at 3C). Therefore, this multi-functional groups decorated composite nanofiber separator with excellent chemical stability is a candidate for next-generation lithium-based battery. [Display omitted] • PAN/CA composite separator are successfully prepared by electrospinning. • PAN/CA separator possesses outstanding ionic transport property. • Li-symmetric cell with PAN/CA separator obtains a dendrite free Li deposition. • Half-cell with PAN/CA separator exhibits excellent electrochemical performance. [ABSTRACT FROM AUTHOR]

Ethanol was used to induce acute hepatotoxicity in mice. Effects of cinnamic acid (CA) and syringic acid (SA) post-intake for hepatic recovery from alcoholic injury was investigated. Ethanol treated mice were supplied by CA or SA at 40 or 80 mg/kg BW/day for 5 days. Results showed that ethanol stimulated protein expression of CYP2E1, p47 phox , gp91 phox , cyclooxygenase-2 and nuclear factor kappa B in liver. CA or SA post-intake restricted hepatic expression of these molecules. Ethanol suppressed nuclear factor erythroid 2-related factor (Nrf2) expression, and CA or SA enhanced Nrf2 expression in cytosolic and nuclear fractions. Ethanol increased the release of reactive oxygen species, oxidized glutathione, interleukin-6, tumor necrosis factor-alpha, nitric acid and prostaglandin E 2 . CA or SA lowered hepatic production of these oxidative and inflammatory factors. Histological data revealed that ethanol administration caused obvious foci of inflammatory cell infiltration, and CA or SA post-intake improved hepatic inflammatory infiltration. These findings support that cinnamic acid and syringic acid are potent nutraceutical agents for acute alcoholic liver disease therapy. However, potential additive or synergistic benefits of cinnamic and syringic acids against ethanol-induced hepatotoxicity need to be investigated. [ABSTRACT FROM AUTHOR]

Multiple epidemiological studies have shown that high vitamin D 3 status is strongly associated with improved breast cancer survival. To determine the molecular pathways influenced by 1 alpha, 25-dihydroxyvitamin D 3 (1,25D) in breast epithelial cells we isolated RNA from normal human breast and cancer tissues treated with 1,25D in an ex vivo explant system. RNA-Seq revealed 523 genes that were differentially expressed in breast cancer tissues in response to 1,25D treatment, and 127 genes with altered expression in normal breast tissues. GoSeq KEGG pathway analysis revealed 1,25D down-regulated cellular metabolic pathways and enriched pathways involved with intercellular adhesion. The highly 1,25D up-regulated target genes CLMN , SERPINB1 , EFTUD1 , and KLK6 were selected for further analysis and up-regulation by 1,25D was confirmed by qRT-PCR analysis in breast cancer cell lines and in a subset of human clinical samples from normal and cancer breast tissues. Ketoconazole potentiated 1,25D-mediated induction of CLMN , SERPINB1 , and KLK6 mRNA through inhibition of 24-hydroxylase (CYP24A1) activity. Elevated expression levels of CLMN, SERPINB1 , and KLK6 are associated with prolonged relapse-free survival for breast cancer patients. The major finding of the present study is that exposure of both normal and malignant breast tissue to 1,25D results in changes in cellular adhesion, metabolic pathways and tumor suppressor-like pathways, which support epidemiological data suggesting that adequate vitamin D 3 levels may improve breast cancer outcome. [ABSTRACT FROM AUTHOR]

Digestive system cancers account for nearly half of all cancers around the world and have a high mortality rate. Cell culture and animal models represent cornerstones of digestive cancer research. However, their ability to enable cancer precision medicine is limited. Cell culture models cannot retain the genetic and phenotypic heterogeneity of tumors and lack tumor microenvironment (TME). Patient-derived xenograft mouse models are not suitable for immune-oncology research. While humanized mouse models are time- and cost-consuming. Suitable preclinical models, which can facilitate the understanding of mechanisms of tumor progression and develop new therapeutic strategies, are in high demand. This review article summarizes the recent progress on the establishment of TME by using tumor organoid models and microfluidic systems. The main challenges regarding the translation of organoid models from bench to bedside are discussed. The integration of organoids and a microfluidic platform is the emerging trend in drug screening and precision medicine. A future prospective on this field is also provided. [ABSTRACT FROM AUTHOR]

• The reduced graphene oxide (rGO)/Li-Al-LDH composite nanosheets by hydrothermal method. • This kind of rGO/Li-Al-LDH nanosheets layer is expected to improve the wettability of liquid electrolytes and thermal stability. • The rGO/Li-Al-LDH@PP composite separator exhibits enhanced lithium-ion transport property. • The rGO/Li-Al-LDH@PP composite separator can be applied in Li||LiFePO 4 half cells. Lithium metal batteries (LMBs) with ultra-high theoretical energy density are a prospective candidate to replace current lithium-ion batteries (LIBs). However, there are still two non-negligible problems of lithium dendrites and the volume expansion effect of LMBs. In this study, reduced graphene oxide (rGO)/Li-Al-LDH composite nanosheets were firstly prepared via a hydrothermal method and then vacuum filtered onto commercial polypropylene (PP) separator. This kind of rGO/Li-Al-LDH nanosheets layer is expected to improve the wettability of liquid electrolytes and thermal stability. Furthermore, rich- Li-Al LDH can promote more ionic carriers and channels, which exhibits higher-efficiency lithium-ion transport properties. Meanwhile, rGO with a graphitic-like structure is able to disperse the concentration of electrons at the sharp point when lithium dendrites arise. As a result, the discharge capacity of the Li||LiFePO 4 cells based on the rGO/Li-Al-LDH@PP separator is still 1.852 mAh after 250 cycles and the capacity decay rate is just 4.24%. It is demonstrated that a feasible and effective strategy for the modified separator can enhance the electrochemical performance of LMBs. [Display omitted] The functional coat is a superior strategy to optimize the interface among the electrode, separator, and liquid electrolyte. In our study, we have synthesized reduced graphene oxide (rGO)/Li-Al-LDH composite nanosheets by hydrothermal method. Li-Al-LDH possesses plenty of octahedral vacancies and abundant lithium-ion diffusion pathways. Meanwhile, rGO with a graphitic-like structure is able to disperse the concentration of electrons at the sharp point when lithium dendrites arise. The prepared rGO/Li-Al-LDH@PP composite separator exhibits increased lithium-ion transference number (0.39) and enhanced ionic conductivity (0.74 mS cm−1) when compared with bare PP separator. The cell has excellent cycle performance. The discharge capacity of the Li||LiFePO 4 cells based on the rGO/Li-Al-LDH@PP separator is still 1.852 mAh after 250 cycles and the capacity decay rate is just 4.24%. At the same time, it also improves the rate performance and Coulomb efficiency of the cell. [ABSTRACT FROM AUTHOR]

Ceramic composite separator is more competitive than traditional polyolefin separator in the field of power supply for superior thermal stability and wettability of liquid electrolyte. In this study, we develop a two-steps method that modifies SiO 2 with acrylamide (AM) by grafting process and prepare a functional SiO 2 composite separator (PE/SiO 2 -AM). This kind of composite separator exhibits similar size-shrinkage (8.8%) to that of PE/SiO 2 composite separator at the tested temperature, lower than 18.1% of bare PE separator, and is electrochemically stable below 4.5 V (vs. Li/Li+). In addition, the Li-symmetric cells employing PE/SiO 2 -AM composite separator have the lowest overpotential and an improved lithium-ion transference number of 0.44. It is demonstrated from DFT calculation that the electron-rich species of imide group is able to uniformly disperse lithium-ion flux at the interface of electrolyte/lithium anode, and contributes to lithium-ion transport process. After assembling the LiCoO 2 /Li half cells, the cell with PE/SiO 2 -AM composite separator displays better cycle performance and higher discharge capacity when compared with other separators. Therefore, functional ceramic separator would be more attractive for next-generation lithium metal battery with high energy density. The functional coat is a superior strategy to optimize the interface among the lithium metal anode, separator and liquid electrolyte. In our study, we have synthesized uniform-size SiO 2 particles and have modified their surface with acrylamide (AM) by a bridge media of vinyl trimethoxysilane (VTMS). AM is a kind of monomer with negative charge property, which is able to stabilize the distribution of lithium-ion at this interface of electrolyte/electrode and affect the space charge layer (C d). This enhanced space charge layer can facilitate the conduction of Li+ (X c = 1/(2πC d)). [Display omitted] • A functional SiO 2 composite separator with imide group (PE/SiO 2 -AM) was prepared. • PE/SiO 2 -AM composite separator exhibits the smallest size-shrinkage separator. • PE/SiO 2 -AM composite separator possesses an improved lithium-ion transference number of 0.44. • The electron-rich species of imide group is able to uniformly disperse the flux of lithium ion. [ABSTRACT FROM AUTHOR]

[Display omitted] • Flower-like calcium phosphate coating is successfully formed on the surface of modified PE separator. • The obtained composite separator exhibits stronger affinity to electrolyte and absorbs more liquid electrolyte. • CaP@PE separator possess an improved ionic conductivity (0.52 mS cm−1) and lithium-ion transference number (0.36). • Cell assembled with CaP@PE separator exhibits excellent cycle performance and rate performance. The organic–inorganic composite separator possesses great thermal stability and electrolyte wettability, which is normally prepared via the slurry containing binder. However, this preparation is involved with large amounts of organic solvent that is harmful to health. In this paper, we design a novel method that combines the crosslinking technology and biomimetic mineralization process to prepare a Ca 3 (PO 4) 2 inorganic coating modified polyethylene separator (CaP@PE). The obtained composite separator exhibits stronger affinity to electrolyte, and its porous coating structure can store more liquid electrolyte, thus the ionic conductivity is promoted from 0.27 mS cm−1 to 0.52 mS cm−1 and the lithium-ion transference number is increased from 0.26 to 0.36. Compared with PE separator, CaP@PE separator shows better thermal stability at high temperature. Due to the improved ionic transport performance and reduced charge transfer impedance, LiCoO 2 /Li half-cell employing CaP@PE separator displays superior cycle stability and capacity retention ability after 150 cycles at a current density of 1C. Even at a high rate of 5C (7.5 mA cm−2), the cell with CaP@PE separator still exhibits a discharge capacity of 0.80 mAh. This work provides a promising separator to optimize the electrochemical performance and safety performance in lithium-ion battery. [ABSTRACT FROM AUTHOR]

Cold storage is the primary postharvest technology used to maintain fruit quality and is generally employed to prolong the storage life of ‘Nanguo’ pears ( Pyrus ussuriensis Maxim). However, pericarp browning gradually appeared when ‘Nanguo’ pears were kept at 20 °C after storage for 120 and 180 d at 0 °C. In this study, changes in the browning substrate and activity of key enzyme, membrane permeability, and the extent of membrane lipid peroxidation were investigated. Changes in the activity and gene expression of enzymes involved in the membrane lipid metabolism pathway were also studied. Significantly higher polyphenol oxidase (PPO) activity and lower total phenolic content were observed in fruit when browning occurred. Fruit kept for 180 d in cold storage showed a significant increase in membrane permeability and malondialdehyde (MDA) content compared to fruit stored for 60 and 120 d. This increase occurred late in cold storage and was maintained during subsequent shelf life. The activity of lipoxygenase (LOX) was remarkably increased and levels of PuPLD and PuLOX transcripts were markedly up-regulated during cold storage. During shelf life after cold storage, when pericarp browning occurred, the activities of phospholipase D (PLD) and LOX were significantly higher and expressions of PuPLD and PuLOX were significantly increased. These results indicated that the severity of pericarp browning during shelf life is related to the duration of cold storage. Pericarp browning resulted from membrane damage, possibly due to expression of PuPLD and PuLOX . [ABSTRACT FROM AUTHOR]

Numerous studies have indicated that nano-titanium dioxide (TiO 2 ) can induce neurotoxicity in vitro and in vivo , however, it is unclear whether nano-TiO 2 affects neurite outgrowth of hippocampal neurons. In order to investigate the mechanism of neurotoxicity, rat primary cultured hippocampal neurons on the fourth day of culture were exposed to 5, 15, and 30 μg/mL nano-TiO 2 for 24 h, and nano-TiO 2 internalization, dendritic growth, glutamate metabolism, expression of N-methyl- d -aspartate (NMDA) receptor subunits (NR1, NR2A and NR2B), calcium homeostasis, sodium current (I Na ) and potassium current (I K ) were examined. Our findings demonstrated that nano-TiO 2 crossed the membrane into the cytoplasm or nucleus, and significantly suppressed dendritic growth of primary cultured hippocampal neurons in a concentration-dependent manner. Furthermore, nano-TiO 2 induced a marked release of glutamate to the extracellular region, decreased glutamine synthetase activity and increased phosphate-activated glutaminase activity, elevated intracellular calcium ([Ca 2+ ]i), down-regulated protein expression of NR1, NR2A and NR2B, and increased the amplitudes of the I Na and I K . In addition, nano-TiO 2 increased nitric oxide and nitrice synthase, attenuated the activities of Ca 2+ -ATPase and Na + /K + -ATPase, and increased the ADP/ATP ratio in the primary neurons. Taken together, these findings indicate that nano-TiO 2 inhibits neurite outgrowth of hippocampal neurons by interfering with glutamate metabolism and impairing NMDA receptor function. [ABSTRACT FROM AUTHOR]

Protective effects of maslinic acid (MA) at 10, 15 or 20 mg/kg body weight/day against alcohol-induced acute hepatotoxicity in mice were examined. Mice were administrated by MA for 3 weeks, and followed by alcohol treatment. Results showed that MA pre-intake at three doses resulted in its accumulation in the liver; and dose-dependently lowered cytochrome P450 2E1 activity and protein expression at 23.5–51.2% and 21.4–62.3%, respectively ( P  <   0.05). MA pre-intake decreased subsequent alcohol-induced reactive oxygen species, interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, nitric oxide and prostaglandin E 2 production; retained glutathione content; maintained catalase and glutathione peroxidase activities; and declined cyclooxygenase-2 and total nitric oxide synthase activities in the liver ( P  <   0.05). Furthermore, MA pre-intake suppressed 17.3–51.7% nuclear factor kappa (NF-κ)B p50, 23.5–58.8% NF-κB p65, 25.6–62.4% p-p38 and 24.1–63.0% p-JNK expression in the liver ( P  <   0.05). Histological data indicated that MA intake at test doses attenuated hepatic inflammatory infiltrate. These findings support that maslinic acid is a potent preventive agent against acute alcoholic liver disease. [ABSTRACT FROM AUTHOR]

Highlights: [•] TiO2 NPs exposure resulted in hippocampus injury and decreased spatial recognition of mice. [•] TiO2 NPs exposure resulted in decreased long-term potentiation. [•] TiO2 NPs exposure caused down-regulation of NR2A and NR2B expression in hippocampus. [•] TiO2 NPs decreased expression of CaMKIV, CREB-1 and FosB/DFosB. [Copyright &y& Elsevier]

Highlights: [•] Ultrasound RF data of normal and coagulated porcine liver tissues is collected. [•] Wavelet analysis is used to compute the mean scatterer spacing (MSS) of normal and coagulated tissues. [•] Microwave-induced thermal lesions are detected by MSS differences between normal tissues and thermal lesions. [•] We propose a new method for evaluation of microwave-induced thermal lesions. [Copyright &y& Elsevier]

Abstract: Background: Several clinical risk factors have been reported to be associated with the prognosis of acute lung injury (ALI). However, these studies have included a general trauma patient population, without singling out the severely injured multiple-trauma patient population. Objectives: To identify the potential risk factors that could affect the prognosis of ALI in multiple-trauma patients and investigate the prognostic effects of certain risk factors among different patient subpopulations. Methods: In this retrospective cohort study, severely injured multiple-trauma patients with early onset of ALI from several trauma centers were studied. Potential risk factors affecting the prognosis of ALI were examined by univariate and multivariate logistic analyses. Results: There were 609 multiple-trauma patients with ALI admitted to the emergency department and emergency intensive care unit during the study period. The nine risk factors that affected prognosis, as indicated by the unadjusted odds ratios with 95% confidence intervals, were the APACHE II (Acute Physiology and Chronic Health Evaluation II) score, duration of trauma, age, gastrointestinal hemorrhage, pulmonary contusion, disseminated intravascular coagulation (DIC), multiple blood transfusions in 6 h, Injury Severity Score (ISS), and aspiration of gastric contents. Specific risk factors also affected different patient subpopulations in different ways. Conclusions: Patients older than 65 years and with multiple (> 10 units) blood transfusions in the early stage after multiple trauma were found to be independent risk factors associated with deterioration of ALI. The other factors studied, including pulmonary contusion, APACHE II score ≥ 20, ISS ≥ 16, gastrointestinal hemorrhage, and aspiration of gastric contents, may predict the unfavorable prognosis of ALI in the early stage of trauma, with their effects attenuating in the later stage. Duration of trauma ≥ 1 h and the presence of DIC may also indicate unfavorable prognosis during the entire treatment period. [Copyright &y& Elsevier]

Abstract: Apoptotic effects of oleanolic acid (OA) and ursolic acid (UA) on human liver cancer HepG2, Hep3B, Huh7 and HA22T cell lines were examined. OA or UA at 2, 4, 8μmol/L were used and their effects on cell viability, DNA fragmentation, mitochondrial membrane potential (MMP), activity of Na+–K+-ATPase, caspase-3 and caspase-8, cell adhesion, level of intercellular adhesion molecule (ICAM)-1 and vascular endothelial growth factor (VEGF) in these cell lines were determined. OA or UA treatments concentration-dependently decreased cell viability and increased DNA fragmentation in HepG2 and Hep3B cell lines (P <0.05). However, these two compounds reduced viability and increased DNA fragmentation in Huh7 cell only at 4 and 8μmol/L (P <0.05). OA or UA treatments concentration-dependently lowered MMP in HepG2, Hep3B and HA22T cell lines (P <0.05). These two compounds also concentration-dependently diminished Na+–K+-ATPase activity and VEGF level in four test cell lines (P <0.05). Besides Huh7 cell, OA or UA treatments concentration-dependently elevated caspase-3 and caspase-8 activities in other three cell lines (P <0.05). Besides HA22T cell, these two compounds concentration-dependently inhibited cell adhesion and decreased ICAM-1 level in other three cell lines (P <0.05). These findings support that OA and UA are potent anti-cancer agents to cause apoptosis in these liver cancer cell lines. [Copyright &y& Elsevier]

Abstract: A series of novel C-12′ substituted vinflunine derivatives have been synthesized. Several compounds in this series possess comparable in vitro cytotoxic potency against A549 cell lines. [Copyright &y& Elsevier]

Thermal characteristics of lithium-ion battery cells are crucial in the thermal design of power battery packs for electric vehicles. In this paper, a calibration calorimetry method of considering the heat loss is proposed to investigate the thermal characteristics of a commercial cylindrical 21700 cell. In the meantime, an existing heat-flux meter method is employed to analyze the present method effectiveness. Furthermore, a cell thermal model by considering the physical specifications and thermal parameters is established to predict the cell's temperature rise during its operation. It is shown that the proposed calibration calorimetry method matches well with the existing heat-flux meter method in determining the cell heat generation rate. The cell heat generation rate increases as the decreasing temperature and the increasing discharge rate, and there exists a quadratic-relationship in them between each other. The established thermal model to predict the cell temperature rise is effective with accuracy of within 3.0 °C. This work is fast and cost-effective in characterizing the thermal characteristics of the commercial cylindrical cells, without resorting to the specialized instruments. • A calibration calorimetry method to analyze cell thermal characteristics is proposed. • The present method is compared with the heat flux meter method. • Cell heat generation is increased at ascending discharge rate and lower temperature. • The established thermal model predicts cell temperature profile is highly feasible. [ABSTRACT FROM AUTHOR]

• Develops a lightweight liquid cooling solution to cool a prismatic hard cased cell. • Effect of fluid flowing on cell thermal distribution is studied numerically. • Dimensionless analysis of cooling performance in cooling plate is performed. • Effectiveness of the lightweight solution was authenticated by an experimental test. The lightweight thermal design is a critical factor that must be taken into consideration during the lithium-ion battery pack manufacturing for electric vehicles. This work develops a lightweight liquid cooling solution to cool a prismatic hard-cased cell from its small lateral surfaces. The effects of fluid flow directions, flow rates, channel dimensions, and cooling mediums on the cell′s thermal distribution were studied. Meanwhile, a dimensionless analysis for the cooling plate performance was imposed. The simulation effectiveness was corroborated through experiments. Simulations show that the lightweight thermal design has a similar cooling effect with the conventional thermal design; crucially, the former can lower the cooling plate weight by 57% compared with the later. Effect of increasing fluid flow rate on minimizing the cell′s temperature rise and difference is positive and negative, respectively. Increasing fluid flow rate and channel width can promote the cooling plate performance. The glycol aqueous solution outperforms the liquid water to weaken the cell′s temperature difference. Experiments authenticating that an excellent effectiveness residing in the current lightweight thermal design to control the cell thermal profile within a desirable level. This work would be valuable for one to design a lightweight cooling system for a battery pack consists of prismatic hard-cased cells. [ABSTRACT FROM AUTHOR]

Purposing to the thermal profile management of typical format 21700 lithium-ion battery cells, this study develops a cellular liquid cooling jacket to meet their requirements. To this end, the effects of fluid flowing, channel dimension, and cooling medium on the cell thermal profile were investigated numerically, and then the simulation effectiveness was authenticated experimentally as per a constructed test bench. Meanwhile, a non-dimensional analysis for the optimum design of cellular cooling jacket was implemented. The results show that the interlaced flow directions can capture a lower temperature standard deviation and a more even thermal distribution. The non-dimensional analysis reveals that the increasing fluid flow rate and channel size can effectively promote the performance of high-efficiency and low-impedance in the designed cellular cooling plate. The glycol aqueous solution to minimize cell's temperature difference and temperature standard deviation is under a stronger capability than that of the liquid water. Experimental verification indicates that the developed cellular cooling jacket is of great control effectiveness to the thermal profile of the cylindrical 21700 cells. A benefit inside this study for the thermal management system designing for the power battery pack of composing with the cylindrical 21700 cells. • A cellular cooling jacket is developed to control thermal profile of a 21700 cell. • Impact of fluid flowing on 21700 cell thermal profiles is studied numerically. • Dimensionless analysis of the cellular cooling jacket performance is conducted. • The effectiveness of battery pack thermal design is verified by a built test bench. • The thermal design is of great effectiveness to control 21700 cell thermal field. [ABSTRACT FROM AUTHOR]

The thermophysical parameters such as thermal conductivity and specific heat play a vital part in the thermal design of the power battery pack composed of cylindrical lithium ion battery cells. This work proposes a quasi steady state method with considering heat loss to measure the thermophysical parameters of two classes of 21700 and 18650 cylindrical cells, respectively. To this end, the theoretical model and the corresponding measurement method were developed in consideration of the heat loss, and the two cells' thermophysical parameters were experimentally determined over a wide operating temperature range of −20–60 °C. The results show that both of the thermal conductivity and the specific heat of the cells increase linearly with the increase of the operating temperature. In comparison, the cell temperature has a greater influence on the specific heat than that of the thermal conductivity. The experimental verification reveals that the measurement error is behind 5.1%. Having a short measurement time within 930s, the present work provides a fast and convenient solution on determining the thermophysical parameters of the cylindrical cells without resorting to the costly instruments. • Proposes a quasi steady state method to measure cylindrical cell thermal parameters. • Cost-effectiveness and fast in current method to derive the cell thermal parameters. • Cell thermal parameters linearly increase as increasing temperature of −20–60 °C. • Experimental verification reveals that the current method is highly feasible. [ABSTRACT FROM AUTHOR]

• Micro antisolvent layer on the membrane interface was observed and investigated. • Tube side pressure and shell side velocity can regulation the antisolvent layer. • MAAC with intensified mass transfer rendered the desire product property. Herein, an interfacial mass transfer process based on hollow fiber membrane assisted antisolvent crystallization (MAAC) was studied via real-time microscopic and computational fluid dynamic (CFD) method. The micro-scale antisolvent liquid layer was clearly detected on the antisolvent/solution interface. The antisolvent concentration and layer thickness were determined by different refractive index of the mixing fluid. CFD simulation results also confirmed the formation of uniform supersaturation gradient, indicating the approximate two-dimensional liquid layer mass transfer on the membrane surface. The competition effect between the feed solution shear force and antisolvent permeation flow rendered the high adjustability of the liquid layer features. Experimental comparison between MAAC and conventional AC indicated that crystal production obtained by MAAC possessed narrower size distribution and great morphology without defects. This novel interfacial liquid layer mass transfer mechanism opens a new approach for novel antisolvent crystallization with intensified interfacial mass transfer. [ABSTRACT FROM AUTHOR]

The commercial polyolefin separator plays a key role in guaranteeing the safety and is also involved in transporting ions inside the battery. However, polyolefin separator composed of C–H chains has nonpolar surface and presents worse affinity to liquid electrolyte. In this study, we firstly have activated polyethylene (PE) separator using γ-irradiation. And then the polar methyl acrylate (MA) monomer has been successfully grafted onto the surface of activated separator with induction of ultraviolet (UV). The obtained PE-g-MA separator has MA modification layer with the ester functional group. As a result, PE-g-MA separator exhibits higher lithium ion transference number of 0.49 than bare PE separator (0.29), it is believed that the enhanced interaction between PE-g-MA separator wall and solvent is beneficial to the desolvation of lithium ion. Moreover, PE-g-MA separator has lower activation energy of 52.1 kJ/mol than pristine PE separator (56.5 kJ/mol), it confirms that lithium ion is easier to migrate across the interface of electrode/PE-g-MA separator filled with liquid electrolyte. The LiCoO 2 /Li half cells employing PE-g-MA separator possess cycling stability and higher capacity at high current density. Therefore, the PE separator modified with polar group is expected to be applied in the high-power supply. • PE-g-MA separator is successfully prepared by UV-induced graft. • PE-g-MA separator exhibits higher lithium ion transference number. • The stronger interaction between solvent and PE-g-MA separator wall facilitates lithium ion transporting. • The PE separator modified with polar group is expected to be applied in the high-power supply. [ABSTRACT FROM AUTHOR]

Thermally induced phase separation (TIPS) is used to prepare polyethylene (PE) micro-porous membrane, consisting of melt blending, fast cooling, stretching and extracting process, which determine the pore-structure of the PE membrane. In this study, we tried to extract PE/liquid paraffin (LP) oil membrane to obtain PE porous membrane by n-hexane (n-PE) and dichloromethane (d-PE). The n-PE membrane would shrink by 10% for extractant volatilizing, less than 15% of the d-PE membrane after the extraction. These PE membranes were applied into symmetrical cells and LiCoO 2 /Li cells. As a result, the LiCoO 2 /Li cell based on n-PE separator exhibited better capacity retention (98%) than d-PE separator (91%) after 80 cycles at a current density of 1C rate for higher ionic conductivity. And the LiCoO 2 /Li cell with d-PE separator had higher capacity at 2C and 3C, it could be attributed to stronger interaction between solvent and wall of d-PE separator with the smaller and curved pore. In addition, the method that electrochemical impedance spectroscopy (EIS) technique carried out with cyclic voltammetry (CV) and charge-discharge curves is successfully applied to monitor the variety of impedance during the cycles, which is helpful to explore the mechanism of capacity attenuation. • The effect of extraction process on electrochemical performance of PE separator was explored. • n-PE membrane exhibited better capacity retention during the cycles, while d-PE membrane had a better C-rate performance. • EIS could be applied to monitor the variety of impedance inside the cell. • The equivalent circuit of EIS results of LiCoO 2 should contain positive region, separator region and negative region. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is known to increase the risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis C (CHC). We aimed to evaluate whether metformin reduces HCC risk among individuals with DM and CHC after successful antiviral therapy. Individuals with CHC who achieved a sustained virological response (SVR) after interferon-based therapy were enrolled in a large-scale, multicenter cohort in Taiwan (T-COACH). Cases of HCC at least 1 year after SVR were identified through linkage to the catastrophic illness and cancer registry databases. Of 7,249 individuals with CHC enrolled in the study, 781 (10.8%) had diabetes and 647 (82.8%) were metformin users. During a median follow-up of 4.4 years, 227 patients developed new-onset HCC. The 5-year cumulative HCC incidence was 10.9% in non-metformin users and 2.6% in metformin users, compared to 3.0% in individuals without DM (adjusted hazard ratio [aHR] 2.83; 95% CI 1.57-5.08 and aHR 1.46; 95% CI 0.98-2.19, respectively). Cirrhosis was the most important factor significantly associated with higher HCC risk in Cox regression analysis, followed by DM non-metformin use, older age, male sex, and obesity; whereas hyperlipidemia with statin use was associated with a lower HCC risk. Using the two most crucial risk factors, cirrhosis and DM non-metformin use, we constructed a simple risk model that could predict HCC risk among individuals with CHC after SVR. Metformin use was shown to reduce the risk of all liver-related complications. Metformin use greatly reduced HCC risk after successful antiviral therapy in individuals with diabetes and CHC. A simple risk stratification model comprising cirrhosis and DM non-metformin use could predict long-term outcomes in individuals with CHC after SVR. The current study provides evidence that metformin could reduce hepatocellular carcinoma (HCC) incidence after successful antiviral therapy among those with diabetes and chronic hepatitis C in a large-scale nationwide cohort study. Although successful antiviral therapy greatly reduces HCC risk in individuals with chronic hepatitis C, those with cirrhosis, diabetes, obesity, and the elderly remain at high risk of HCC development. We demonstrated that a simple risk model composed of two crucial unfavorable factors, cirrhosis and diabetes without metformin use, predicts the risk of HCC and major liver-related complications after successful antiviral therapy in individuals with chronic hepatitis C. Metformin use is highly recommended for individuals with diabetes and chronic hepatitis C after viral eradication to reduce the risk of HCC. [Display omitted] • Diabetes mellitus is associated with an increased risk of HCC in individuals with CHC. • Diabetes mellitus still increases the risk of HCC after successful antiviral therapy. • Use of metformin for DM greatly reduces HCC risk after successful antiviral therapy. • A simple risk stratification model could predict the risk of HCC and other major liver-related complications. [ABSTRACT FROM AUTHOR]

Post-stroke depression (PSD) is one of the most common neuropsychiatric consequence of stroke, affecting cognitive function, recovery of somatic function, and patient survival. The aim of this study was to evaluate whether Chaihu-Shugan-San, a traditional Chinese medicine formula used clinically to treat depression, could improve symptoms in a rat model for PSD, to investigate the potential mechanisms, and to validate the findings in an in vitro oxygen and glucose deprivation (OGD) model. Male rats were subjected to middle cerebral artery occlusion (MCAO) and to chronic unpredictable mild stress (CUMS). The rats were then allocated to experimental groups (n = 15) that were treated with Chaihu-Shugan-San, a JAK-STAT3 inhibitor, a GSK3β overexpressing virus, or an empty virus (control). The subjects allocated to each group, as well as those that received no treatment and rats that did not undergo MCAO/CUMS, were then subjected to forced swimming, tail suspension, and sugar water preference tests, and their neurological deficit score was determined. Inflammatory factor levels and the expression of proteins related to the JAK/STAT3-GSK3β/PTEN/Akt pathway were measured, and the synaptic ultrastructure was observed using transmission electron microscopy. Flow cytometry showed microglia polarization towards the M1 phenotype in an in vitro PSD model, which was reversed after treatment with a GSK3β overexpression virus, Chaihu-Shugan-San, or a JAK-STAT3 inhibitor. The results showed that Chaihu-Shugan-San has a therapeutic effect on an in vivo model for PSD and can regulate microglia polarization through the activation of the JAK/STAT3-GSK3β/PTEN/Akt pathway, suggesting that it exerts its effect via the inhibition of neuroinflammation. [Display omitted] • Post-stroke depression (PSD) is a common neuropsychiatric consequence of stroke. • We used both an in vivo and an in vitro model to evaluate potential therapies for PSD. • Chaihu-Shugan-San, a traditional Chinese medicine formula, improved PSD symptoms. • This effect involved the activation of the JAK/STAT3-GSK3β/PTEN/Akt pathway. [ABSTRACT FROM AUTHOR]

For sodium-ion batteries, polyanionic cathode materials have been mainly studied due to their advantages of high safety, low-cost and environmental friendliness. However, some shortcomings of low intrinsic conductivity and slow reaction kinetics limit its further application. In our study, a uniform and dense amorphous carbon layer is coated onto the surface of fluorophosphate (Na 2 FePO 4 F/C) via high-energy ball milling and heat-treatment process. According to the results of SEM and TEM, it is seen that the surface of the active particles would be composited with a carbon layer. When the heat treatment temperature is 650 °C, the ratio of I D /I G of Raman is the largest, indicating that the highest disorder degree of the carbon layer. The obtained Na 2 FePO 4 F/C-650 has the largest initial discharge specific capacity (120 mAh·g−1 at 0.1 C), and the specific capacity retention rate is 76.54% at 10 C for 1000 cycles. Furthermore, the sodium-ion diffusion coefficient of Na 2 FePO 4 F/C-650 measured using AC impedance is up to 4.91 × 10−12 cm2·s−1. It could be resulted from the fact that amorphous carbon layer can absorb more sodium ions and is beneficial to ion diffusion kinetics according to the DFT calculation. This study has proposed a new idea to modify cathode material and facilitated the commercial application of Na 2 FePO 4 F. The functional carbon layer is an effective strategy to improve the conductivity and ionic reaction kinetics of cathode materials. In this study, Na 2 FePO 4 F/C composite cathode material with a uniform and dense amorphous carbon layer have been synthesized through high-energy ball milling and heat treatment process. This amorphous carbon layer can absorb more sodium ions and is beneficial to the ion diffusion kinetics. What's more, the sodium-ion diffusion coefficient of the obtained Na 2 FePO 4 F/C-650 is up to 4.91 × 10−12 cm2· s −1. [Display omitted] [ABSTRACT FROM AUTHOR]

A series of novel asperphenamate derivatives were designed and synthesized, including series I (the A-phenyl group replaced with various aromatic heterocycles) and series II (the acyl group substituted by sulfonyl group). All compounds have been screened for their antiproliferative activity in vitro against MCF-7, HeLa, and BEL-7402 cell lines by the standard MTT method. Structure–activity relationship studies displayed the heterocycle type played an important role in activity. Six-membered ring derivatives displayed more potency than five-membered ring and the sulfonyl group in A-ring region made an important contribution to activity. Among all derivatives, tosyl derivative 8c exhibited the greatest potency in three human cancer cell lines. Especially in MCF-7 cells, the cellular potency of 8c was approximately 3.0-fold more potent than that of cisplatin. Firstly, the mechanism of cell death induced by 8c in MCF-7 cells was investigated. The results showed that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest. Further studies indicated that 8c might induce autophagic cell death in HeLa and BEL-7402 cell lines. [ABSTRACT FROM AUTHOR]

Tooth root supports dental crown and bears occlusal force. While proper root shape and size render the force being evenly delivered and dispersed into jawbone. Yet it remains unclear what shape and size of a biological tooth root (bio-root), which is mostly determined by the scaffold geometric design, is suitable for stress distributing and mastication performing. Therefore, this study hypothesized scaffold fabricated in proper shape and size is better for regeneration of tooth root with approving biomechanical functional features. In this study, we optimized shape and size of scaffolds for bio-root regeneration using computer aided design (CAD) modeling and finite element analysis (FEA). Statical structural analysis showed the total deformation (TD) and equivalent von-mises stress (EQV) of the restored tooth model mainly concentrated on the scaffold and the post, in accordance with the condition in a natural post restored tooth. Design sensitivity analysis showed increasing the height and upper diameter of the scaffold can tremendously reduce the TD and EQV of the model, while increasing the bottom diameter of scaffold can, to some extent, reduce the EQV in post. However, increase on post height had little influence on the whole model, only slightly increased the native EQV stress in post. Through response surface based optimization, we successfully screened out the optimal shape of the scaffold used in tissue engineering of tooth root. The optimal scaffold adopted a slightly tapered shape with the upper diameter of 4.9 mm, bottom diameter of 3.4 mm; the length of the optimized scaffold shape was 9.4 mm. While the analysis also suggested a height of about 9 mm for a metal post with a diameter of 1.4 mm suitable for crown restoration in bio-root regeneration. In order to validate the physiological function of the shape optimized scaffold in vivo , we transplanted the shape optimized treated dentin matrix (TDM) scaffold, seeding with dental stem cells, into alveolar bone of swine and further installed porcelain crown. Results showed that tooth root has not only been successfully regenerated histologically but also performed masticatory function and maintained stable for three months after crown restoration. Our results suggested that TDM scaffold with 9.4 mm in length and 4.9 mm/3.4 mm in upper/bottom diameter is a suitable biological scaffold for tooth root regeneration. These results also provided a recommendable design protocol for fabricating other scaffolds in tooth root reconstruction. [ABSTRACT FROM AUTHOR]

Abstract: We studied the responses of soil fauna to a simulated nitrogen deposition in nursery experimental plots in Subtropical China. Dissolved NH4NO3 was applied to the soil by spraying twice per month for 16 months, starting in January 2003 with treatments of 0, 5, 10, 15 and 30 gN/(m2-a). Soil fauna was sampled after 6, 9, 13 and 16 months of treatment in three soil depths (0-5 cm, 5-10 cm, 10-15 cm). Soil available N increased in correspondence with the increasing N treatment, whereas soil pH decreased. Bacterial and fungal densities were elevated by the N treatment. Soil fauna increased in the lower nitrogen treatments but decreased in the higher N treatments, which might indicate that there was a threshold around 10 gN/(m2a) for the stimulating effects of N addition. The N effects were dependent on the soil depth and sampling time. The data also suggested that the effects of the different N treatments were related to the level of N saturation, especially the concentration of NO3" in the soil. [Copyright &y& Elsevier]

Abstract Li metal has been regarded as the most promising anode material for next high-energy batteries. However, the dendrite growth during the lithium deposition and low Coulombic efficiencies have restricted their practical applications. In the paper, we investigate the electrodeposition process of lithium metal under different current density in detail and firstly use diethylenetriamine as additive to adjust the deposition of lithium metal in LiPF 6 -PC and LiPF 6 -EC/DEC electrolyte. The result shows that trace diethylenetriamine can react with lithium anode producing R-N-Li and LiF, which greatly improves the morphology of lithium deposition by adjusting the components of the SEI film. The content of fast ionic conductors in SEI film (e.g., R-N-Li and LiF) can be identified by the X-ray photoelectron spectroscopy. The electrochemical impedance spectroscopy confirms diethylenetriamine could increase the ionic conductivity of the interface between the anode and electrolyte. Galvanostatic curves also show that the LiPF 6 -PC electrolyte with 0.2 vol% diethylenetriamine and LiPF 6 -EC/DEC electrolyte with 0.1 vol% diethylenetriamine has better cycling stability than blank group. Highlights • Our research has clearly demonstrated the behavior of metallic lithium in cathode deposition, lithium deposition law related to current density. • We firstly developed diethylenetriamine as nitrogenous organic additive to stabilize lithium electrode with 0.2 vol% amount. • The LiPF 6 -PC electrolyte with 0.2 vol% diethylenetriamine shows better stability of lithium electrode and high ionic conductivity than blank electrolyte. [ABSTRACT FROM AUTHOR]

Amyloid beta (Aβ) peptides in cerebrospinal fluid are extensively estimated for identification of Alzheimer’s disease (AD) as diagnostic biomarkers. Unfortunately, their pervasive application is hampered by interference from Aβ propensity of self-aggregation, nonspecifically bind to surfaces and matrix proteins, and by lack of quantitive standardization. Here we report on an alternative Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method for simultaneous measurement of human amyloid beta peptides Aβ1-38, Aβ1-40 and Aβ1-42 in cerebrospinal fluid (CSF) using micro-elution solid phase extraction (SPE). Samples were pre-processing by the mixed-mode micro-elution solid phase extraction and quantification was performed in the positive ion multiple reaction monitoring (MRM) mode using electrospray ionization. The stable-isotope labeled Aβ peptides 15 N 51 - Aβ1-38, 15 N 53 - Aβ1-40 and 15 N 55 - Aβ1-42 peptides were used as internal standards. And the artificial cerebrospinal fluid (ACSF) containing 5% rat plasma was used as a surrogate matrix for calibration curves. The quality control (QC) samples at 0.25, 2 and 15 ng/mL were prepared. A “linear” regression (1/x 2 weighting): y = ax + b was used to fit the calibration curves over the concentration range of 0.1–20 ng/mL for all three peptides. Coefficient of variation (CV) of intra-batch and inter-batch assays were all less than 6.44% for Aβ1-38, 6.75% for Aβ1-40 and 10.74% for Aβ1-42. The precision values for all QC samples of three analytes met the acceptance criteria. Extract recoveries of Aβ1-38, Aβ1-40 and Aβ1-42 were all greater than 70.78%, both in low and high QC samples. The stability assessments showed that QC samples at both low and high levels could be stable for at least 24 h at 4 °C, 4 h at room temperature and through three freeze-thaw cycles without sacrificing accuracy or precision. And no significant carryover effect was observed. This validated UHPLC/MS/MS method was successfully applied to the quantitation of Aβ peptides in real human CSF samples. Our work may provide a reference method for simultaneous quantitation of human Aβ1-38, Aβ1-40 and Aβ1-42 from CSF. [ABSTRACT FROM AUTHOR]

Biotransformation mediated by microbes can affect the biogeochemical cycle of arsenic. However, arsenic biotransformation mediated by earthworm-related microorganisms has not been well explored, especially the role played by earthworm skin microbiota. Herein, we reveal the profiles of arsenic biotransformation genes (ABGs) and elucidate the microbial communities of the earthworm gut, skin, and surrounding soil from five different soil environments in China. The relative abundance of ABGs in the earthworm skin microbiota, which were dominated by genes associated with arsenate reduction and transport, was approximately three times higher than that in the surrounding soil and earthworm gut microbiota. The composition and diversity of earthworm skin microbiota differed significantly from those of the soil and earthworm gut, comprising a core bacterial community with a relative abundance of 96% Firmicutes and a fungal community with relative abundances of 50% Ascomycota and 13% Mucoromycota. In addition, stochastic processes mainly contributed to the microbial community assembly across all samples. Moreover, fungal genera such as Vishniacozyma and Oomyces were important mediators of ABGs involved in the biogeochemical cycle of arsenic. This is the first study to investigate earthworm skin as a reservoir of microbial diversity in arsenic biotransformation. Our findings broaden the current scientific knowledge of the involvement of earthworms in the arsenic biogeochemical cycle. [Display omitted] • Profiles of ABG in the earthworm skin dominated by arsenate reduction and transport were observed. • The earthworm skin microbiota differed significantly from those of the soil and earthworm gut. • Stochastic processes strongly shaped the microbial community assembly of earthworm gut and skin. • The earthworm skin as a reservoir of microbial diversity played a vital role in arsenic biotransformation. [ABSTRACT FROM AUTHOR]

Two novel andrographolide analogues with the structural motif of Δ 8,17 -alkene exo -to- endo isomerization, AI78 and AI89 , were semi-synthesized firstly. Two series of derivatives were designed and synthesized based on the synthetic pathway (including series I: olefin isomerizing to endocyclic Δ 8,9 and series II: olefin isomerizing to endocyclic Δ 7,8 ). The anti-influenza virus activity in vitro for all derivatives was evaluated. Among the compounds synthesized, compound 38 with benzyl amino group showed the greatest potency against H3N2 and was approximately 1.5-fold more potent than that of Lianbizhi, andrographolide analogue used clinically in China. Adamantyl derivative, 43 , presented the lowest toxicity, with a higher TC 50 and TI values than Lianbizhi. The structure–activity relationships studies of the synthetic analogues indicated that the endocyclic Δ 7,8 -double bond is preferable for anti-viral effect. Furthermore, the introduction of the fatty amino attached to the rigid skeleton at C-17 is beneficial for activity. [ABSTRACT FROM AUTHOR]