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In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to be important tumor-associated regulatory factors. LncRNA growth arrest-specific transcript 5 (Gas5) acts as an anti-oncogene in most cancers. Whether Gas5 acts as an oncogene or anti-oncogene in hepatocellular carcinoma (HCC) remains unclear. In the present study, the expression and role of Gas5 in HCC were investigated in vitro and in vivo. Lower expression levels of Gas5 were determined in HCC tissues and cells by quantitative reverse transcription-polymerase chain reaction. Overexpressed Gas 5 lentiviral vectors were constructed to analyze their influence on cell viability, migration, invasion, and apoptosis. Fluorescence in situ hybridization was used to identify the subcellular localization of Gas5. Protein complexes that bound to Gas5 were isolated from HepG2 cells through pull-down experiments and analyzed by mass spectrometry. A series of novel Gas5-interacting proteins were identified and bioinformatics analysis was carried out. These included ribosomal proteins, proteins involved in protein folding, sorting, and transportation in the ER, some nucleases and protein enzymes involved in gene transcription, translation, and other proteins with various functions.78 kDa glucose-regulated protein (GRP78) was identified as a direct target of Gas5 by Rip-qPCR and Western blot analysis assay. Gas5 inhibited HepG2 cell growth and induced cell apoptosis via upregulating CHOP to activate the ER stress signaling pathway. Further studies indicated that the knockdown of CHOP by shRNA partially reversed Gas5-mediated apoptosis in HepG2 cells. Magnetic resonance imaging showed that the ectopic expression of Gas5 inhibited the growth of HCC in nude mice. These findings suggest that Gas5 functions as a tumor suppressor and induces apoptosis through activation of ER stress by targeting the CHOP signal pathway in HCC.

Two new alkaloids, leptocarpinine B (1) and corydamine acid (2), with thirteen known alkaloid compounds (3–15), were isolated from Hypecoum leptocarpum. The structures of the isolated compounds were determined based on spectroscopic data analyses, including IR, ESI-MS, 1 D, and 2 D NMR. In addition, all the isolates were evaluated for cytotoxic activities. Compound 6 showed moderate cytotoxicity against human ovarian cancer cell lines (A2780), human cervical cancer cell lines (HeLa), and human hepatocellular carcinomas cell lines (HepG2).

High oxygen content of microalgae-derived bio-oil limits their direct use in modern motors. In this study, instead of noble metal-catalyzed two-step hydrodeoxygenation, MgAl layered double hydroxid...

Lithium phosphorus oxynitride (LiPON) has paved the way for thin film solid-state battery technology development and has shown application in a large range of fields since its first reported synthe...

The aim of this work was to analyze the recrystallization behavior of cold rolled Aluminum/graphene composites during annealing. The Aluminum/graphene composite was cold rolled firstly, and then annealed at different temperature (250°C, 300°C, 350°C, 400°C) and for various time (1 h, 2 h, 8 h, 32 h). Full recrystallization did not occur until the annealing temperature was above 300 °C. With annealing temperature increasing from 250 to 300°C, the hardness of the composites decreased from 49.6 to 27.6 HV. Grain growth were not observed at high annealing temperature and longer annealing time, which suggested that Graphene has strong pinning effect on the grain boundary of Aluminum.

Moringa oleifera Lam. is an essential herb used for the treatment of inflammation, diabetes, high blood pressure, and other diseases. In this study, phenolic extracts of M. oleifera leaves were obtained and analyzed. The results showed that the main identifiable phenols were astragalin, chlorogenic acid, isoquercitrin, kaempferitrin, luteolin, quercetin, and rutin. The effects of M. oleifera polyphenol extract (MOPE) on experimental colitis induced by 3% dextran sulfate sodium (DSS) were investigated. The results showed that oral administration of MOPE significantly alleviated the symptoms of DSS-induced colitis. MOPE significantly reduced weight loss, the disease activity index, colon shortening, and mucosal damage. In addition, MOPE attenuated the infiltration of CD3+ T cells, CD177+ neutrophils, and F4/80+ macrophages and significantly inhibited the secretion of IL-6 and TNF-α. After the MOPE administration, the expression of proteins associated with the NF-κB signaling pathway changed. Specifically, compared with that of the DSS group, the protein expression of NF-κB p65 and p-IκBα was downregulated, and the expression of IκBα was upregulated. This study revealed the anti-inflammatory effects and mechanisms of MOPE in the colon, indicating its potential use in preventing inflammation-driven diseases.

Betula alnoides is a fast-growing and native timber species prevalently planted in tropical and subtropical areas of southern China. Despite the large-scale development of B. alnoides plantations, knowledge of its association with arbuscular mycorrhizal fungi (AMF) is limited. In the present study, we chose young (3-year-old sapling, P3y) and middle-aged (12-year-old stand, P12y) B. alnoides plantations and adjacent native forest (N) in the Puwen Tropical Forest Experimental Station located in Xishuangbanna prefecture of Yunnan Province, southwestern China, as study materials and explored the change in AMF community composition in the plantation chronosequence. In addition, we combined morphological methods and Illumina MiSeq sequencing techniques to analyze rhizosphere soil AMF. The results indicated that the AMF richness and diversity indexes of B. alnoides at two ages tended to be similar to those of natural growing trees in native forest. However, the specific AM fungal compositions were distinctly different, providing evidence of the conservation value of the native forest, which harbors a unique AMF diversity. Hierarchical cluster analysis further revealed that the AMF community composition of trees in the mid-aged stand (P12y) was more similar to that of naturally growing B. alnoides (N) than that of the young-aged trees (P3y), which proved the considerable resilience of AMF to the establishment of the B. alnoides plantation. A set of at least five soil properties (available phosphorus, available nitrogen, organic matter, total nitrogen and silt content) was found to play a significant role in shaping the AMF communities. These results contribute to the understanding of the impacts of B. alnoides plantations on AMF diversity and composition. Such information is critical for the efficient planting and sustainable management of B. alnoides plantations.

Porous carbons with a high porosity were successfully produced from fast pyrolysis pine wood char via a thermochemical method in which KOH was used as chemical activator. The effects of various weight ratios of KOH to pyrolysis char (0.65:1, 0.7:1, 1.0:1, 1.35:1, and 1.7:1) on the physical properties of activated carbons were investigated. When the weight ratio of KOH to pyrolysis char was 1.35:1, the prepared activated carbon had the highest surface area of 1140 m2/g with a total pore volume of 0.71 cm3/g, a microporous surface area of 957 m2/g, and a microporous specific volume of 0.51 cm3/g. As the weight ratio of KOH to pyrolysis char increased from 0.65 to 1.35, the prepared activated carbon had increases in total surface area, total pore volume, microporous surface area, and specific volume of micropores. However, there was a reverse trend when the weight ratio of KOH to pyrolysis char was higher than 1.35. The use of nitrogen as a flow gas resulted in much more developed activated carbon than without nitrogen. The experiment results suggested that activated carbon with high surface area could be prepared from pyrolysis char by adjusting the activation conditions.

Indoleamine 2,3‑dioxygenase (IDO) is one of the most important proteins protecting the embryos from the mother's immune system during pregnancy; however, little is known about the regulation of expression of this protein at the maternal‑fetal interface. In the current study, chorionic villi and decidua were collected from women at early stages of pregnancy. Samples of chorionic villi and decidua were cultured in medium containing different concentrations of 17β‑estradiol and estriol respectively, with or without fulvestrant. Western blot analysis and/or immunofluorescent staining were used to detect the expression of transforming growth factor β (TGF‑β) and IDO in chorionic villi and decidua tissues. Both TGF‑β and IDO were expressed in chorionic villi and decidua. The expression levels of these two proteins increased the most in samples of chorionic villi and decidua cultured in medium containing 17β‑estradiol at the concentration of 10 ng/ml, or estriol at the concentration of 1 µg/ml. This increase could be reversed when fulvestrant was added in the medium at the concentration of 10 µg/ml. IDO expression increased in a dose‑dependent manner in tissue samples cultured in medium containing TGF‑β. The results of the current study revealed that administration of estrogen at doses similar to those observed in healthy pregnant women may upregulate the expression of IDO by TGF‑β, suggesting that estrogen may prevent allogeneic fetal rejection and may be used as an immunomodulator.

Hierarchical porous carbons (HPCs) hold great promise in energy-related applications owing to their excellent chemical stability and well-developed porous structures. Attention has been drawn toward developing new synthetic strategies and precursor materials that permit greater control over composition, size, morphology, and pore structure. There is a growing trend of employing metal-organic frameworks (MOFs) as HPC precursors as their highly customizable characteristics favor new HPC syntheses. In this article, we report a biomimetically grown bacterial-templated MOF synthesis where the bacteria not only facilitate the formation of MOF nanocrystals but also provide morphology and porosity control. The resultant HPCs show improved electrochemical capacity behavior compared to pristine MOF-derived HPCs. Considering the broad availability of bacteria and ease of their production, in addition to significantly improved MOF growth efficiency on bacterial templates, we believe that the bacterial-templated MOF is a promising strategy to produce a new generation of HPCs.

A new labdane-type diterpenoid, ent-19-ol-13-epi-manoyl oxide,19-undecane ester, together with ten known diterpenes, were isolated from the ethanolic crude extract of the fresh tubers of Sagittaria trifolia L. The chemical structures of these compounds were determined by extensive 2-D NMR experiments and by comparison with the data reported in the literature. These compounds showed different inhibitory effects on various human cancer cells. Among these, compound 11 exhibited potential inhibition effects against human colon cancer cells. Moreover, flow cytometry demonstrated that compound 11 arrested the cell cycle at the G1 phase and induced cellular apoptosis, accompanied by mitochondrial membrane potential reduction. Mechanistic studies revealed that treatment with compound 11 inhibited IKKα/β phosphorylation and IκBα phosphorylation, which subsequently caused the blockage of NF-κB p65 phosphorylation and nuclear translocation. Compound 11 also inhibited the expression of c-Myc, Cyclin D1, and Bcl-2, the downstream targets of NF-κB. Therefore, our findings provided insight into the anticancer components of Sagittaria trifolia L. tubers, which could facilitate their utilization as functional food ingredients.

A novel Gram-positive, non-motile, non-flagellated, strictly anaerobic, non-spore-forming and dumbbell-shaped, coccoid- or chain-shaped bacterium, designated strain LZLJ-3T, was isolated from a mud fermentation cellar which has been used for the production of Chinese strong-flavour liquor for over 100 years. Strain LZLJ-3T grew at 20–40 °C (optimum, 37 °C), at pH 6.0–8.0 (optimum, pH 8.0) and with NaCl concentrations up to 1 % (w/v; optimum, 0 %). Phylogenetic trees established based on 16S rRNA gene sequences showed that strain LZLJ-3T belonged to the genus Blautia of the family Lachnospiraceae, with the highest sequence similarity to Blautia stercoris GAM6-1T (91.7 %) and Blautia faecicola KGMB01111T (91.7 %). Comparative genome analysis showed that the orthologous average nucleotide identity (OrthoANI) and genome-to-genome distance (GGD) values between strain LZLJ-3T and B. stercoris GAM6-1T were respectively 69.1 and 22.9 %; the OrthoANI and GGD values between strain LZLJ-3T and B. faecicola KGMB01111T were respectively 70.86 and 36 % . The DNA G+C content of strain LZLJ-3T genome was 42.1 mol%. The predominant celluar fatty acids (>10 %) of strain LZLJ-3T were C16 : 0 FAME (27.9 %), C14 : 0 FAME (17.6 %) and C16 : 0 DMA (13.0 %). Arabinose, glucose and maltose could be utilized by strain LZLJ-3T as sole carbon sources for growth, with weak utilization of raffinose and l-fucose. API ZYM analysis gave positive reactions with α-galactosidase, β-galactosidase, α-glucosidase and β-glucosidase. The major end product of glucose fermentation was acetic acid. Based on the results of phenotypic, genotypic and phylogenetic analyses, strain LZLJ-3T is considered to represent a novel species of Blautia , for which the name Blautia liquoris sp. nov. is proposed. The type strain is LZLJ-3T (=KCTC 25163T=CGMCC 1.5299T=JCM 34225T).

SCOPE The proliferation and differentiation of intestinal stem cells (ISCs) are the basis of intestinal renewal and regeneration, and gut microbiota plays an important role in it. Dietary nutrition has the effect of regulating the activity of ISCs; however, the regulation effect of α-linolenic acid (ALA) has seldom been reported. METHODS AND RESULTS After intervening mice with different doses of ALA for 30 days, it is found that ALA (0.5 g kg-1 ) promotes small intestinal and villus growth by activating the Wnt/β-catenin signaling pathway to stimulate the proliferation of ISCs. Furthermore, ALA administration increases the abundance of the Ruminococcaceae and Prevotellaceae, and promotes the production of short-chain fatty acids (SCFAs). Subsequent fecal transplantation and antibiotic experiments demonstrate that ALA on the proliferation of ISCs are gut microbiota dependent, among them, the functional microorganism may be derived from Ruminococcaceae. Administration of isobutyrate shows a similar effect to ALA in terms of promoting ISCs proliferation. Furthermore, ALA mitigates 5-fluorouracil-induced intestinal mucosal damage by promoting ISCs proliferation. CONCLUSION These results indicate that SCFAs produced by Ruminococcaceae mediate ALA promote ISCs proliferation by activating the Wnt/β-catenin signaling pathway, and suggest the possibility of ALA as a prebiotic agent for the prevention and treatment of intestinal mucositis.

Phytoextraction strategy by harvesting dead leaves provides non-stop phytoremediation and a great saving in disposal cost of hazardous plant residues. This strategy is entirely dependent upon the amount of cadmium (Cd) accumulated in dead leaves. However, it is unknown that whether the leaf Cd accumulation is associated with its senescence and how to regulate its Cd accumulation. This study showed that Cd was preferentially and consistently distributed to and accumulated in the senescent leaves with the new leaf emergence and the old leaf dieback under 75 µM of Cd stress in tall fescue (Festuca arundinacea). Individual leaf monitoring from its emergence to senescence showed that Cd concentration increased exponentially with the leaf life cycle, while leaf biomass decreased gradually after 14 d of leaf emergence. The total amount of Cd accumulated in the leaf showed an exponential increase during leaf senescence, regardless of the leaf biomass loss. Our results demonstrated that leaf Cd accumulation was significantly associated with its senescence and the highest Cd accumulated in dead leaves could be contributed from the continuous Cd input during the leaf senescent process, indicating that further regulatory studies should be focused on the leaf senescence process to achieve higher Cd accumulation and phytoextraction efficiency by harvesting dead leaves.

We report herein an unprecedented atroposelective dynamic kinetic resolution of Bringmann's lactones with C-nucleophiles. By the use of activated isocyanides as the reagent, a wide range of novel axially chiral oxazole-substituted biaryl phenols were accessed in high yields with high enantioselectivities. Key to the success of this process lies in the tandem atroposelective addition of isocyanides to the lactone substrate followed by a rapid cyclization, overcoming the challenge of stereochemical leakage induced by lactol formation.

During the past two decades, metal-organic frameworks (MOFs) have received significant interest because these materials possess beautiful structural motifs and unique applications. Light-emitting MOFs sensors are favorable because these materials have large surface area and excellent framework stability, which can differentiate analytical objects for applications toward environmental protection, homeland security and human health. In this work, under the powerful solvo-thermal conditions, a bi-functional ligand with large conjugated biphenyl aromatic backbones has been used to prepare the unique ultra-stable three-dimensional(3D) luminescent zinc(II) coordination compound {[Zn2(μ5-L)(μ3-OH)(H2O)2]·(0.75DMAC)}n (1) (DMAC = Dimethylacetamide). In 1, these penta-coordinated L3− ligands and the bridging ligand μ3-OH link together with these neighboring zinc(II) centers, which ultimately constructs the 3D nano-porous coordination material of 1. 1D rhombic channel with a corresponding edge distance of 12.167(6) A × 10.912(1) A can be found between central metal(II) vertices along the crystallographic b axis. The calculation using the PLATON program shows the total solvent area is 581.7 A3, which occupies 25.2% of the unit cell's volume (2306.9 A3). Powder X-ray diffraction (PXRD) pattern has been performed confirming the purity of these bulky samples 1. It is worth noting that 1 shows excellent chemical stability, which can maintain structural integrity not only in various solvents but also aqueous environments with pH varying from 2 to 12. Photo-luminescent measurements show that 1 can perform highly sensitive and real-time chemical sensing of nicotinamide with good reusability, high Ksv quenching efficiency (2.24 × 104 M−1) and low detection limit values (0.14 μM). Meanwhile 1 also shows visual photo-luminescent detection of tetraphenylboron (BPh4-, Ph = phenyl) anion in aqueous solutions with high Ksv quenching efficiency (1.16 × 105 M−1) and low detection limit values (0.028 μM). To the best of our knowledge, 1 presents the first example of an ultra-stable 3D zinc(II) nano-porous metal organic material as the bi-functional re-generable luminescent probe for nicotinamide and tetraphenylboron.

Background Human hepatocellular carcinoma (HCC) lacks effective curative therapy and there is an urgent need to develop a novel molecular-targeted therapy for HCC. Selective tyrosine kinase inhibitors have shown promise in treating cancers including HCC. Tyrosine kinases c-Met and Trks are potential therapeutic targets of HCC and strategies to interrupt c-Met and Trks cross-signaling may result in increased effects on HCC inhibition. Methods The effects of Indo5 on c-Met and Trks activity were determined with in vitro kinase activity assay, cell-based signaling pathway activation, and kinases-driven cell transformation. The in vivo anti-tumor activity was determined with xenograft mice and liver orthotopic mice models. The co-expression of c-Met and TrkB in 180 pairs of HCC and adjacent normal tissues were detected using immunohistochemical staining. Results Indo5, a novel lead compound displayed biochemical potency against both c-Met and Trks with selectivity over 13 human kinases. Indo5 abrogated HGF-induced c-Met signaling activation and BDNF/NGF-induced Trks signal activation, c-Met or TrkB-mediated cell transformation and migration. Furthermore, Indo5 significantly decreased the growth of HCC cells in xenograft mice and improved the survival of mice with liver orthotopic tumors. In addition, co-expression of c-Met and TrkB in HCC patients was a predictor of poor prognosis, and combined inhibition of c-Met and TrkB exerted a synergistic suppressive effect on HCC. Conclusions These findings indicate that Indo5 is associated with marked suppression of c-Met and Trks co-expressing HCC, supporting its clinical development as an antitumor treatment for HCC patients with co-active c-Met and Trks signaling. Electronic supplementary material The online version of this article (10.1186/s13046-019-1104-4) contains supplementary material, which is available to authorized users.

Heteroatom-doped carbon dots (CDs), due to their excellent fluorescence performance and multifunctional characteristics, have always been a focus of scientists. Herein, we reported a facile one-step solvothermal method for the synthesis of dual-emission nitrogen and sulfur co-doped (N,S)-CDs with a photoluminescence quantum yield (PLQY) of 29.7%. The synthesized CDs retain highly excitation-independent properties at a wide range of excitation wavelengths. To further investigate the optical properties and surface chemistry of the (N,S)-CDs, several characterization methods were used in this study, including fluorescence spectrophotometry, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and Raman spectroscopy. The as-prepared (N,S)-CDs exhibited two obvious maximum emission wavelengths of 600 and 650 nm with the best excitation wavelength of 560 nm, and emitted bright red fluorescence under UV light (365 nm). The (N,S)-CDs were developed into WLEDs with a comparable CRI and as a sensitive sensor for water in ethanol, suggesting the outstanding application prospects of the as-synthesized (N,S)-CDs.

Cranberries (Vaccinium macrocarpon) are full of polyphenols, which display various health benefits. Most studies have focused on extractable polyphenols (EPs) rather than non-extractable polyphenols (NEPs) but NEPs may possess important biological functions. The objective of this work was to characterize EP and NEP fractions from whole cranberries and determine their potential as anti-inflammation and anti-colon-cancer agents. Our results showed that of the identified polyphenols, anthocyanins were the major ones in the cranberry EP fraction, while phenolic acids were most abundant in the NEP fraction. The oxygen radical absorbance capacity (ORAC) of the NEPs was significantly higher than that of the EPs. Both the EPs and NEPs showed anti-inflammatory effects in inhibiting LPS-induced production of nitric oxide in macrophages. At the concentrations tested, the NEPs showed significantly higher inhibition of the production of nitric oxide in macrophages than the EPs, which was accompanied by decreased expression of inducible nitric oxide synthase (iNOS) and increased expression of HO-1. EP and NEP samples showed anti-cancer capacities in HCT116 cells. And the NEPs showed stronger inhibitory effects on the viability and colony formation capacity of human colon cancer HCT116 cells than the EPs. In a flow cytometry analysis, the NEPs caused cell cycle arrest at the G0/G1 phase and induced significant cellular apoptosis in colon cancer cells. Overall, our results suggested that both the EP and NEP fractions from cranberries were bioactive, and importantly, the NEP fraction showed promising anti-inflammation and anti-colon-cancer potential., This work was partly supported by U.S. Department of Agriculture (NIFA 2019-67017-29249), Leo and Anne Albert Charitable Trust, UMass Cranberry Health Research Center/UMass President's S&T Initiative.

The reaction of a new pentadentate Schiff base hydrazide ligand, (E)-methyl N′-(2-hydroxy-3-methoxybenzylidene)hydrazinecarboxylate (HL), with lanthanide nitrate, and sodium acetate in the presence of triethylamine, resulted in a novel family of octanuclear neutral compounds, [Ln8(μ3-O)4(L)8(CH3COO)4(CO3)2]·xH2O, where Ln = Gd (1), Tb (2), Dy (3), or Ho (4). Compounds 1–4 contained two unusual Ln4 boat-shaped units, which were held by four L− chelating ligands, two μ3-O2−, and one μ4-CO32−. These structures were interconnected by four CH3COO− ions, forming a novel Ln8 cluster. Magnetic studies revealed antiferromagnetic Gd⋯Gd interactions in Gd8, which exhibited a significant magnetocaloric effect and a magnetic entropy change as large as 32.49 J K−1 kg−1 at a field of 7 T at 2 K. In addition, Dy8 exhibited a frequency dependent slow relaxation of magnetization at a zero applied direct current magnetic field.

In this work, a flexible asymmetric semi-rigid bi-functional ligand 5-(4-((1H-1,2,4- triazol-1-yl)methyl)phenyl)-1H-tetrazole (HL) has been employed. A series of unique Cu II and Cu I coordination compounds, namely [Cu( μ 2 -L) 2 (H 2 O) 2 ] n ( 1 ), [Cu( μ 2 -L) 2 (H 2 O) 2 ] n ( 2 ), [Cu( μ 4 -L)] n ( 3 ) and [Cu 2.5 ( μ 4 -L)(CN) 1.5 ] n ( 4 ), have been prepared under hydro(solvo)-thermal conditions. 1 and 2 present scarcely reported temperature induced polymorphic 1D ( 1 ) and 2D ( 2 ) copper(II)-L coordination frameworks. When HL and CuBr 2 are employed to react in the mixed H 2 O/CH 3 CN (1:1) solvent system, the 3D Cu I - HL coordination polymer 3 can be isolated. The Cu I centers in 3 should be the reduction of Cu II ions by CH 3 CN solvent. When CuBr is used to replace CuBr 2 under similar synthetic conditions of 3 , 4 can be isolated. 4 is a unique 3D Cu I cluster-based coordination framework assembled from L − and CN − . PXRD patters of all the bulky samples 1 – 4 also have been determined, which agree well with theoretical PXRD patterns, confirming pure phases. Photo-luminescent measurements also show that complexes 3–4 can behave highly sensitive photo-luminescent sensing of small solvent molecules DMF and NMP. Additionally, 4 also exhibits highly selective and sensitive photo-luminescent discriminating of dichromate anions in aqueous solutions with excellent quenching efficiency (K sv = 2.38 × 10 4 L mol -1 ). The experiment result also demonstrates the broad prospects in the preparation of these novel coordination frameworks using these flexible bi-functional asymmetric semi-rigid ligands as basic building blocks.

In this work, Al-Fe-(Cu) alloys for aluminum cables were designed and the related annealing behaviors were discussed in detail to help understand the influence of processing and heat treatment on the electrical conductivity and mechanical properties of the studied alloys. The interaction between different solute elements was tracked by using hardness and electrical conductivity testing. The microstructure was investigated by using Electron Backscattered Diffraction (EBSD) technique, along with Scanning Electron Microscopy with Backscattered Electron Detector (BSE). The results show that the conductivities of Al-Fe-Cu alloy increased with the elongated annealing time, and reaches its maximum at 6 h, when annealed at temperatures from 275 °C to 375 °C. The addition of Fe to Al can strengthen the alloy and decrease its conductivity slightly, while the addition of Cu will influence the alloy conductivity significantly. The morphologies of precipitates will change with different amount of alloying elements as well.

Astragalin is a flavonoid found in a variety of natural plants. It has anti-inflammatory, anti-oxidant effects and has inhibited effects against several malignant tumor cell types. However, its effects on colon cancer and the molecular mechanisms have remained to be elucidated. In this study, we evaluated the inhibitory effect of astragalin on proliferation and migration of human colon cancer HCT116 cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that astragalin significantly inhibited the proliferation and diffusion of HCT116 cells by induced apoptosis (by modulation of Bax, Bcl-2, P53, caspase-3, caspase 6, caspase 7, caspase 8, caspase 9 protein express) and cell cycle arrest (by modulation of Cyclin D1, Cyclin E, P21, P27, CDK2, CDK4 protein express). Moreover, astragalin suppressed HCT116 cell migration by inhibiting the expression of matrix metalloproteinases (MMP-2, MMP-9). In addition, astragalin significantly downregulated the expression of key proteins in the NF-κB signaling pathway and inhibited the transcriptional activity of NF-κB P65 stimulated with inflammatory cytokines TNF-α, thereby inhibiting the growth of colon cancer cells in vitro. Our further investigations unveiled astragalin gavage significantly reduced the proliferation of colon cancer xenograft in nude mice, in vivo experiments showed that tumor growth was related to decreased expression of apoptotic proteins in tumor tissues and decreased activity of the NF-κB signaling pathway. In summary, our results indicated that astragalin inhibits the proliferation and growth of colon cancer cells in vivo and in vitro via the NF-κB pathway. Therefore, astragalin maybe become a potential plant-derived antitumor drug for colon cancer.

Strawberry is a rich source of phenolics. However, most studies focused on extractable phenolics (EP) while neglecting non-extractable phenolics (NEP). The aim of this study was to characterize EP and NEP from strawberry (Fragaria x ananassa) and determine their anti-inflammatory and anti-colon cancer potentials in cell culture models. NEP contained flavonols, flavanols and phenolic acids that were released through alkaline hydrolysis. NEP dose-dependently inhibited lipopolysaccharides -induced NO production in RAW 264.7 macrophage. Western blotting showed that NEP reduced the expression levels of pro-inflammatory proteins such as iNOS and c-FOS, but increased the expression level of antioxidative protein, such as HO-1. Moreover, NEP markedly suppressed proliferation of human colon cancer HCT116 cells via inducing G2/M phase cell cycle arrest and apoptosis. Collectively, these findings illustrated preventive effects of strawberry NEP against inflammation and colon cancer, shedding light on potential contribution of NEP from strawberry as a health-promoting agent.

A pivotal neuropathological manifestation of synucleinopathies, like Parkinson's disease (PD), is the aggregation of α-synuclein. In a recent cell-to-cell transmission model of α-synuclein, α-synuclein propagation was demonstrated to resemble that of prion proteins in the central nervous system. Furthermore, exosomes, as biomolecule carriers, have been shown to transmit α-synuclein from neuron to neuron. However, the mechanisms underlying exosomal α-synuclein transmission have not been well understood. The NLR family pyrin domain containing 3 protein (NLRP3) inflammasome activation in microglia, and the subsequent release of proinflammatory cytokines, are two crucial pathological events involved in neuroinflammation and PD progression. Research has revealed that the NLRP3 inflammasome may facilitate the secretion of extracellular vesicles, as well as exosomal transmission of proteins like aggregated α-synuclein. However, only a few reports have evaluated these pathogenic mechanisms. Herein we evaluate for the first time the current evidence for the involvement of the NLRP3 inflammasome in microvesicle generation by microglial cells, and the various mechanisms regarding the production, shedding, and content of exosomes in relation to α-synuclein transmission from neuron to neuron. Furthermore, we propose a model of microglial NLRP3 inflammasome-dependent exosome secretion and exosomal α-synuclein transmission in PD. This knowledge may lead to the identification of novel potential targets for drug development and stimulate further research in PD.

Currently, the highly sensitive detection of Alzheimer's Disease (AD) biomarkers, namely presenilin 1, amyloid β-protein (Aβ), and acetylcholine (ACh), is vital to helping us prevent and diagnose AD. In this work, a novel metal-organic framework [Er(L)(DMF)1.27]n (Er-MOF) (H3L = terphenyl-3,4'',5-tricarboxylic acid) has been synthesized by solvothermal and ultrasonic methods. Further, through the post-synthesis assembly strategy, the fluorescent dye thioflavine T (ThT) has been introduced into Er-MOF to construct a dual-emission ThT@Er-MOF ratiometric fluorescent sensor. This is the first time that ThT@Er-MOF has been successfully applied in the highly sensitive detection of three main Alzheimer's disease biomarkers in the cerebrospinal fluid through three different low cost and facile detection strategies. Firstly, with the spilted DNA strategy, this is the first time that ThT@Er-MOF can be applied in the label-free detection of SSODN (part of the presenilin 1 gene). Secondly, for the detection of Aβ, because ThT can be specifically combined with Aβ and has an excellent characteristic fluorescence band, the dual-emission ThT@Er-MOF sensor can be selectively applied to detect Aβ over the analog protein, which shows far more sensitivity than other Aβ sensors. Thirdly, through the acetylcholine esterase (AchE) enzymatic cleavage and release strategy, ThT@Er-MOF enhances the detection of acetylcholine (ACh) with a low limit of detection (LOD) value (0.03226 nM). It should be noticed that the three different detection methods are low cost and facile. This study also provides the first example of utilizing laser scanning confocal microscopy (LSCM) to investigate the fluorescence resonance energy transfer (FRET) detection mechanism by ThT@Er-MOF in more detail. The location of FRET occurrence and FRET efficiency can also be investigated by LSCM, which can be helpful to understand the FRET detection process by these unique MOF-based hybrid materials.

Increasing catalytic activity and durability of atomically dispersed metal-nitrogen-carbon (M-N-C) catalysts for the oxygen reduction reaction (ORR) cathode in proton-exchange-membrane fuel cells remains a grand challenge. Here, a high-power and durable Co-N-C nanofiber catalyst synthesized through electrospinning cobalt-doped zeolitic imidazolate frameworks into selected polyacrylonitrile and poly(vinylpyrrolidone) polymers is reported. The distinct porous fibrous morphology and hierarchical structures play a vital role in boosting electrode performance by exposing more accessible active sites, providing facile electron conductivity, and facilitating the mass transport of reactant. The enhanced intrinsic activity is attributed to the extra graphitic N dopants surrounding the CoN4 moieties. The highly graphitized carbon matrix in the catalyst is beneficial for enhancing the carbon corrosion resistance, thereby promoting catalyst stability. The unique nanoscale X-ray computed tomography verifies the well-distributed ionomer coverage throughout the fibrous carbon network in the catalyst. The membrane electrode assembly achieves a power density of 0.40 W cm-2 in a practical H2 /air cell (1.0 bar) and demonstrates significantly enhanced durability under accelerated stability tests. The combination of the intrinsic activity and stability of single Co sites, along with unique catalyst architecture, provide new insight into designing efficient PGM-free electrodes with improved performance and durability.

Although preclinical and clinical studies have shown the benefits of bone morphogenetic protein-2 (BMP2) in bone regeneration, there are increasing concerns about its side effects. These are mainly due to the high dosage of BMP2 which is necessary to obtain the desired clinical results. Previously our group has developed a novel controlled-release delivery system; the biomimetic calcium phosphate coating incorporated with BMP2. It can be used at much lower concentrations of BMP2 than those used in the commercially available product and still produce similar biological effects. In this study, we made a primarily biological evaluation of BMP2 incorporated beta-tricalcium phosphate (β-TCP) for bone regeneration in critical-sized bone defects. Critical-sized calvarial defects were created in rats. They were divided into four groups as follows: (1) empty defects (control), (2) defects filled with β-TCP, (3) defects filled with BMP2 incorporated β-TCP, (4) defects filled with autologous bone. Eight weeks after the operation, the efficiency of the materials was evaluated using histology and histomorphometry. Moreover, the safety of the materials was evaluated using routine blood examination, blood biochemistry examination and histopathological examination of viscera. BMP2 incorporated β-TCP demonstrated an efficiency of bone regeneration that was comparable with autologous bone, with the highest levels of new bone formation (38.3±8.4 mm3 versus 30.1±9.9 mm3, p < 0.05). All clinical lab index of blood in these four groups were within the normal range. Moreover, no change related to the treatment was noted in the histopathological examination of viscera. The results from the present study demonstrated that BMP2 incorporated β-TCP could be a promising substitute for autologous bone used for bone regeneration. Future clinical trials and preclinical trials with large animal models are necessary to investigate the safety and efficacy of BMP2 incorporated β-TCP.

A series of binuclear lanthanide compounds, derived from the Schiff-base ligand 4-bromo-2-((quinolin-8-ylimino)methyl)phenol (HL), namely [Ln2(L)2(CH3CH2CH2 COO)2(NO3)2(MeOH)2] (Ln = Gd (1), Tb (2), Dy (3), Ho (4)), has been synthesized. Compounds 1–4 have a similar dinuclear lanthanide core bridged by a butyrate ion. Magnetic studies reveal that compound 1 has a weak ferromagnetic interaction. On the other hand, compound 3 displays slow magnetic relaxation under an external dc field with the anisotropic barrier of 27.08 K and pre-exponential factor τ0 = 4.12 × 10−6 s. Therefore the Dy(III) compound is a field-induced SMM.

Hierarchical porous carbons (HPCs) hold great promise in energy-related applications owing to their excellent chemical stability and well-developed porous structures. Attention has been drawn toward developing new synthetic strategies and precursor materials that permit greater control over composition, size, morphology, and pore structure. There is a growing trend of employing metal-organic frameworks (MOFs) as HPC precursors as their highly customizable characteristics favor new HPC syntheses. In this article, we report a biomimetically grown bacteria-templated MOF synthesis where the bacteria not only facilitate the formation of MOF nanocrystals, but also provides morphology and porosity control. The resultant HPCs show improved electrochemical capacity behavior compared to pristine MOF derived HPCs. Considering the broad availability of bacteria and ease of its production, in addition to significantly improved MOF growth efficiency on bacterial templates, we believe that bacteria-templated MOF is a promising strategy to produce a new generation of HPCs.

Gambogic acid (GA) is a naturally derived potent anticancer agent with extremely poor biocompatibility. In the present study, a novel of redox/pH dual-responsive multifunctional magnetic complex micelle (sPEG/HA/CSO-SS-Hex/Fe3O4/GA), which consisted of a reducible hexadecanol-modified chitosan oligosaccharide polymer micelle (CSO-SS-Hex) coated with hyaluronic acid (HA) and DCA grafted sheddable PEG-PLL (sPEG) copolymers and loaded with gambogic acid (GA) and Fe3O4 nanoparticles were developed for parenteral delivery for the treatment of triple negative breast cancer (TNBC). The ex vivo study showed that the sPEG shielded cationic HA/CSO-SS-Hex/Fe3O4/GA core at physiological pH but quickly shed off to re-expose the core due to its charge reversible property. The sPEG/HA/CSO-SS-Hex/Fe3O4/GA micelles effectively facilitated tumor-targeted GA delivery by HA, which is a targeting ligand for CD44 receptor of TNBC cells, meanwhile increase GA uptake at the acidic condition but diminished the drug uptake at neutral pH. The in vitro cellular uptake study and in vivo biodistribution and antitumor activity of the formulations were determined, all results showed that the complex micelle enhanced TNBC tumor cellular uptake and fast drug release due to the combined effect of magnet targeting, CD44 receptor-mediated internalization and redox/pH dual-responsive drug release. Hence, tumor-targeted delivery of GA with redox/pH dual-responsive multifunctional magnetic complex micelle sPEG/HA/CSO-SS-Hex/Fe3O4/GA might have potential implications for the chemotherapy of TNBC.

Currently, procaterol has been widely used as an asthma wonder drug; however, the overuse of procaterol easily leads to arrhythmia, and tachycardia decreased blood pressure. Metal organic frameworks (MOFs) are a new class of hybrid porous materials that have attracted great attention in the past 20 years. These metal-organic framework composites have highly efficient host-guest interactions and are excellent fluorescent sensing materials. In this work, an effective detection method to control the amount of procaterol was designed. A unique three-dimensional (3D) cluster-based metal-organic framework (MOF), namely [Zn2L(DEF)3]n (Zn-MOF, H4L=[1,1′:4′,1′'-terphenyl]- 3,3′',5,5′'-tetracarboxylic acid) can be prepared through the solvothermal method. Furthermore, through postsynthesis strategies, Eu3+ is loaded into cluster-based Zn-MOF to form dual-emission Eu3+@Zn-MOF, which can be employed as a ratiometric photoluminescent sensor for detecting the amount of wonder drug procaterol with a high K sensing constant value (6.12 ☓ 105 [M−1]) and a low limit of detection (LOD) value (46.10 nM). In addition, HCO3- can be effectively detected with a low LOD value (8.28 nM) in procaterol solution while other anions do not respond, which also reveals the pharmacological effects between HCO3- and procaterol. Furthermore, in the HCO3- solution, Eu3+@Zn-MOF exhibits a more sensitive sensing performance for the procaterol with high sensitivity and excellent recovery. On the other hand, Eu3+@Zn-MOF is a highly sensitive ratiometric temperature sensor in the range of 298−353 K. The detection sensitivity of Eu3+@Zn-MOF towards procaterol under the different physicochemical temperatures of the human body (303 K, 308 K, and 313 K) is also compared, This comparision indicates that temperature of 303 K has an enhanced sensing performance for procaterol in comparison with other detection temperatures. In conclusion, with the help of HCO3- and a suitable temperature (303 K), the detection sensitivity of Eu3+@Zn-MOF towards procaterol can be significantly improved and enhanced.

In this work, a CSC-1 type horizontal rotating micro-bomb combustion-solution isoperibol multifunctional calorimeter was constructed. There are three main differences between the structure of this calorimeter and the existing calorimeters: (1) two functions, i.e. the measurements of combustion heat and solution heat were integrated together; (2) Dewar bottle was used as a shared calorimetric container for the determination of combustion heat and solution heat; (3) submersible magnetic mixer replaced the traditional mechanical rod mixer. The energy equivalent of combustion system in the calorimeter was calibrated with NIST SRM 39j benzoic acid, giving the result of (1181.94 ± 0.23) J⋅K−1. Furthermore, the standard specific energy of combustion of salicylic acid was measured using the combustion system, and the result showed that the standard specific energy of combustion of salicylic acid was – (21884.9 ± 5.4) J·g−1 at 298.15 K. Then, the standard molar enthalpy of formation of salicylic acid was calculated to be Δ f H m o [ C 7 H 6 O 3 (s), 298.15 K ] = - ( 589.27 ± 2.98 ) kJ⋅mol−1. In addition, the energy equivalent of solution system in the calorimeter was calibrated with electrical energy, giving the result of (5.28084 ± 0.00261) J·mV−1. And the standard specific enthalpy of solution of KCl was measured by the solution system in water at 298.15 K, the results indicated that the standard specific and molar enthalpy of solution of KCl (1100 H2O, 298.15 K) were (235.33 ± 0.03) J·g−l and (17543.2 ± 8.9) J·mol−l, respectively. All these results demonstrated that the calorimetric systems of combustion and solution in the developed calorimeter are reliable and feasible.

This study investigated the adsorptive removal and subsequent degradation of sulfamethoxazole (SMX) from a synthetic urine by biochar (BC). The BCs used in this study were prepared using two different feedstocks with different temperatures. Element analysis and Fourier transform infrared spectroscopy (FTIR) results suggested that the aromaticity of one of the BCs, 700HSBC was significantly different from the 700PSBC although both of them were prepared at the same temperature (700 °C) with similar pore size distributions and specific surface areas. Due to the presence of abundant aromatic structures, 700HSBC showed a higher SMX uptake than 700PSBC, suggesting that the π–π interaction was the main adsorption mechanism. The removal of SMX from the urine was significantly enhanced by adding hydrogen peroxide to the 700HSBC. The carbonate radicals degradation of SMX mechanism was proposed and verified. With 700HSBC having abundant aromatic structures acting as π-electron donors, it could be an efficient activator for peroxymonocarbonate (HCO4-) to generate carbonate radicals. Hence, it could be concluded that the aromatic structures on BCs play a key role in both of the adsorption and hydrogen peroxide degradation of the SMX resulting in its removal from urine.

Chang Liu,1,* Xiao-Na Liu,1,* Gui-Ling Wang,1 Yu Hei,1 Shuai Meng,1 Ling-Fei Yang,1 Lan Yuan,2 Ying Xie1 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Department of Pharmaceutics, School of Pharmaceutical Sciences, 2Medical and Healthy Analysis Center, Peking University, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: As the global population ages, cancer rates increase worldwide, and degenerative diseases of the central nervous system (CNS), brain tumors, and inflammation threaten human health more frequently. We designed a dual-mediated (receptor-mediated and adsorption-mediated) liposome, named transferrin–cell penetrating peptide–sterically stabilized liposome (TF-CPP-SSL), to improve therapy for gliomas through combining molecular recognition of transferrin receptors (TF-Rs) on the blood–brain barrier (BBB) and glioma cells with the internalization and lysosomal escaping ability of CPP. Based on the systematic investigation of structure–activity relations on the cellular level, we constructed TF-CPP-SSL rationally by conjugating TF and CPP moieties to the liposomes via PEG3.4K and PEG2.0K, respectively, and found the optimum densities of TF and CPP were 1.8% and 4%, respectively. These liposomes had the highest targeting efficacy for brain microvascular endothelial cell and C6 cell uptake but avoided capture by normal cells. Fluorescence resonance energy transfer technology and coculture models of BBB and glioma C6 cells indicated that TF-CPP-SSL was transported across the BBB without drug leakage, liposome breakup, or cleavage of ligand. TF-CPP-SSL offered advantages for crossing the BBB and entering into glioma C6 cells. Real-time confocal viewing revealed that TF-CPP-SSL was entrapped in endosomes of glioma C6 cells and then escaped from lysosomes successfully to release the liposomal contents into the cytosol. Entrapped contents, such as doxorubicin, could then enter the nucleus to exert pharmacological effects. Keywords: dual ligand-modified liposomes, transferrin, cell-penetrating peptide, real-time confocal, fluorescence resonance energy transfer, tumor targeting

Cadmium (Cd) contamination of the soil is one of the most serious environmental problems of agricultural production. Phytoremediation has attracted increasing attention because it can safely remove the soil contaminates via plant uptake, accumulations and plant harvesting. However, the high Cd toxicity to plant tissues and treatment of the large amount of hazardous plant residues from phytoremediation have limited its commercial implementation. Here we show that the leaves of the tall fescue (Festuca arundinacea) can excrete Cd out to avoid Cd toxicity in plant tissues. Cd specific fluorescence spectroscopy with laser confocal scanning microscope, screening electron microscope with energy dispersive spectroscopy and guttation fluids analysis confirmed that leaf hydathodes were the pathway of Cd excretion in tall fescue. Element analysis showed that Cd was preferentially excreted out when compared to the ion nutrients. The amount of leaf Cd excretion was linearly increased in response to the Cd stress period. The phytoremediation efficiency was evaluated to remove 14.4% of soil Cd annually by the leaf Cd excretion in our experimental system. These findings indicate that a novel strategy of Cd phytoexcretion based on washing-off and collection of leaf surface Cd is feasible to avoid Cd toxic in plant tissues and the high treatment cost of hazardous plant residues.

Silicon nanoparticles (Si NPs) wrapped by graphene in carbon nanofibers were obtained via electrospinning and subsequent thermal treatment. In this study, water-soluble poly(vinyl alcohol) (PVA) with low carbon yield is selected to make the process water-based and to achieve a high silicon yield in the composite. It was also found that increasing the amount of graphene helps keep the PVA fiber morphology after carbonization, while forming a graphene network. The fiber SEM and HRTEM images reveal that micrometer graphene is heavily folded into sub-micron scale fibers during electrospinning, while Si NPs are incorporated into the folds with nanospace in between. When applied to lithium-ion battery anodes, the Si/graphene/carbon nanofiber composites show a high reversible capacity of ∼2300 mAh g(-1) at a charging rate of 100 mA/g and a stable capacity of 1191 mAh g(-1) at 1 A/g after more than 200 cycles. The interconnected graphene network not only ensures the excellent conductivity but also serves as a buffering matrix for the mechanic stress caused by volume change; the nanospace between Si NPs and folded graphene provides the space needed for volume expansion.

Hard carbon (HC) is recognized as a promising anode material with outstanding electrochemical performance for alkali metal-ion batteries including lithium-ion batteries (LIBs), as well as their analogs sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs). Herein, a comprehensive review of the recent research is presented to interpret the challenges and opportunities for the applications of HC anodes. The ion storage mechanisms, materials design, and electrolyte optimizations for alkali metal-ion batteries are illustrated in-depth. HC is particularly promising as an anode material for SIBs. The solid-electrolyte interphase, initial Coulombic efficiency, safety concerns, and all-climate performances, which are vital for practical applications, are comprehensively discussed. Furthermore, commercial prototypes of SIBs based on HC anodes are extensively elaborated. The remaining challenges and research perspectives are provided, aiming to shed light on future research and early commercialization of HC-based SIBs.

Solid state electrolytes are very promising to enhance the safety of lithium ion batteries. Two classes of solid electrolytes, polymer and ceramic, can be combined to yeild a hybrid electrolyte that can syngergistically combine the properties of both materials. Chemical stability, thermal stability, and high mechanical moduli of ceramaic electrolytes against dendrite penetration can be combined with the flexibility and ease of processing of polymer electrolytes. By laminating a polymer electrolyte with a ceramic electrolyte, the stability of the solid electrolyte is expected to improve against lithium metal, and the ionic conductivity could remain close to the value of the original polymer electrolyte as long as an appropriate thickness of the ceramic eletrolyte is applied. Here we report a bilayered lithium-ion conducting hybrid solid electrolyte consisting of a blended polymer electrolyte (BPE) laminated with a thin layer of the inorganic solid electrolyte lithium phosphorous oxynitride (LiPON). The hybrid system was thoroughly studied. First, we investigated the influence of polymer chain length and lithium salt ratio on the ionic conductivity of the BPE based on poly(ethylene oxide) (PEO) and poly(propylene carbonate) (PPC) with the salt lithium bis(trifluoromethanesulfonyl)imide (LiTFSI). The optimized BPE consisted of 100k molecular weight PEO, 50k molecular weight PPC, and 25(w/w) % LiTFSI, (denoted as PEO100PPC50LiTFSI25) which exhibited an ionic conductivity of 2.11x10-5 S/cm, and the ionic conductivity showed no thermal memory effects as the PEO crystallites were well distrupted by PPC and LiTFSI. Secondly, the effects of LiPON coating on the BPE were evaluated as a function of thickness down to 20 nm. The resulting bilayer structure showed an increase in the voltage window from 5.2 to 5.5V (vs Li/Li+) and thermal activation energies that approached the activation energy of the BPE when thinner LiPON layers were used, resulting in similar ionic conductivities for 30nm LiPON coatings on PEO100PPC50LiTFSI25. Coating BPEs with a thin layer of LiPON is shown to be an effective strategy to improve the long-term stability against lithium.

Solid-state electrolytes play an important role in the development of new generations of technology including lithium metal batteries. Lithium conducting solid materials offer a solution to the safety issues that are present in lithium-ion batteries (LIBs). Conventional LIBs typically use highly flammable organic solvents as a transport medium for lithium ions, potential risks that arise due to these solvents include fire, volatilization, and explosions. Solid polymer electrolytes (SPEs) are great as electrolyte material because fabrication of the electrolyte films is cheap, and processing is simple. However, SPEs can have stability issues when in contact with lithium metal for extended periods which is a problem for cells required to offer long lifetimes. Poly (ethylene oxide) (PEO) has been extensively studied since the conception of SPEs, due to its ability to solvate ions due to its polar ether groups. However, PEO, being a semi-crystalline polymer, exhibits thermal history effects due to recrystallization behavior. Amorphous SPEs are highly desirable because there are no recrystallization kinetics at play, and the properties are consistent regardless of the thermal history. Poly(propylene carbonate) (PPC), an amorphous, biodegradable polymer, can offer high ionic conductivities. Blending PEO and PPC offers a solution to resolve the thermal history effects of PEO by interfering with the crystalline structures in blended electrolyte systems with the salt lithium bis(trifluoromethanesulfonyl)imide (LiTFSI). Inorganic solid electrolytes (ISEs) can offer better chemical stability and excellent mechanical properties compared to SPEs; however, brittleness may decrease the structural stability over time. Thin films ISE’s also tend to cost much more than SPEs due to the fabrication methods required such as electron beam evaporation, and chemical vapor deposition. Lithium phosphorous oxynitride (LiPON), produced through RF magnetron sputtering, was developed in the 1990s at Oakridge National Laboratories and offers great electrochemical stability against lithium and relatively high ionic conductivities on the order of 10-6 S/cm at room temperature. A new bilayer lithium-ion conducting hybrid solid electrolyte (HSE) consisting of a blended polymer electrolyte (BPE) coated with a thin layer of the ISE LiPON, has been prepared. PEO and PPC are blended in a 1:1 mass ratio, then the salt LiTFSI is incorporated. BPE films are then produced through a facile solution casting method using acetonitrile as the solvent. Structure-property relationships are then systematically evaluated to understand the effects of molecular weight and mass loading of LiTFSI on the BPE systems. Influences of molecular weight and salt loading on crystallinity is observed though X-ray diffraction and optical microscopy of the BPE films. Ionic conductivity is evaluated through impedance spectroscopy between two stainless steel blocking electrodes, thermal history measurements were taken by heating and cooling the SPE while recording EIS at specified temperatures. The best BPE based on ionic conductivity, consists of 100k molecular weight PEO, 50k molecular weight PPC, and 25(w/w)% LiTFSI, (denoted as PEO100PPC50LiTFSI25) and exhibits an ionic conductivity of ~2x10-5S/cm. Temperature dependent EIS shows that the lowest molecular weight polymers offer lower activation energies as a result of the higher degree of free volume and molecular motion of the polymer chain. The optimized BPE system is then coated with various thicknesses of LiPON. The effects of LiPON coating are evaluated and show promise for the development of lithium stable solid electrolytes. Linear sweep voltammetry (LSV) is used to assess the anodic voltage stability against lithium metal. Incorporating very thin layers of LiPON down to 20nm on the BPE shows an increase in the voltage window of the electrolyte system from 5.2 to 5.5V (vs Li/Li+). However, the incorporation of LiPON decreases the ionic conductivity of the BPE. Thinner layers of LiPON show the ionic conductivity approaches that of the BPE, with thicker LiPON layers offering lower ionic conductivies. To assess the stability against lithium metal over time, impedance spectroscopy is used. Cells consisting of the solid electrolyte against lithium metal are prepared, and impedance measurements are taken over a 20-day period to assess the changes in charge transfer resistance. From these measurements, it has been shown that only a 30nm thin layer of LiPON is required to improve the stability of the resulting HSE. Therefore, coating BPEs with a thin layer of LiPON is shown to be an effective strategy to improve the long-term stability of solid-state lithium ion conductors.

Prohibitin (PHB), an evolutionarily conserved mitochondrial inner membrane protein, is highly expressed in cells that require strong mitochondrial function. Recently, we demonstrated that the deletion of Phb in spermatocytes results in impaired mitochondrial function. In addition, PHB expression in the mitochondrial sheath of human sperm has a significantly negative correlation with mitochondrial reactive oxygen species levels, but a positive one with mitochondrial membrane potential and sperm motility. These results suggest that mitochondrial PHB expression plays a role in sperm motility. However, the mechanism of PHB-mediated regulation of sperm motility remains unknown. Here, we demonstrate for the first time that PHB interacts with protein kinase B (AKT) and exists in a complex with phospho-PHB (pT258) and phospho-AKT in the mitochondrial sheath of murine sperm, as determined using colocalization and coimmunoprecipitation assays. After blocking AKT activity using wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), murine sperm have significantly ( P < 0.05) decreased levels of phospho-PHB (pT258) and the total and progressive motility. Furthermore, significantly ( P < 0.05) lower levels of phospho-PI3K P85 subunit α+γ (pY199 and pY467) and phospho-AKT (pS473; pT308) are found in sperm from infertile asthenospermic and oligoasthenospermic men compared with normospermic subjects, which suggest a reduced activity of the PI3K/AKT pathway in these infertile subjects. Importantly, these sperm from infertile subjects also have a significantly ( P < 0.05) lower level of phospho-PHB (pT258). Collectively, our findings suggest that the interaction of PHB with AKT in the mitochondrial sheath is critical for sperm motility, where PHB phosphorylation (pT258) level and PI3K/AKT activity are key regulatory factors.

A novel tridecanuclear nanoscopic cluster {ZnGd12} have been synthesized by using the Schiff-base ligand, 2-methoxy-6-[(2-methylindole-2-carboxyl-1-ylidene) methyl]phenol (H2L), with zinc chloride and gadolinium nitrate in the presence of triethylamine as deprotonation reagent. Single-crystal X-ray diffraction analysis revealed that the central core of the cluster {ZnGd12} is unprecedented and composed of a beautiful structure built by two monocapped triangular prisms [ZnGd6] sharing the ZnII vertex. Magnetic studies reveal that {ZnGd12} shows promise as a low-temperature magnetic refrigerant with the magnetic field entropy of 30.79 J kg−1 K−1 at a magnetic field of 7 T–2 T.

Long noncoding RNAs (lncRNAs) function through a diverse array of mechanisms that are not presently fully understood. Here, we sought to find lncRNAs differentially regulated in cancer cells resistant to either TNF-related apoptosis-inducing ligand (TRAIL) or the Mcl-1 inhibitor UMI-77, agents that act through the extrinsic and intrinsic apoptotic pathways, respectively. This work identified a commonly up-regulated lncRNA, ovarian adenocarcinoma-amplified lncRNA (OVAAL), that conferred apoptotic resistance in multiple cancer types. Analysis of clinical samples revealed OVAAL expression was significantly increased in colorectal cancers and melanoma in comparison to the corresponding normal tissues. Functional investigations showed that OVAAL depletion significantly inhibited cancer cell proliferation and retarded tumor xenograft growth. Mechanically, OVAAL physically interacted with serine/threonine-protein kinase 3 (STK3), which, in turn, enhanced the binding between STK3 and Raf-1. The ternary complex OVAAL/STK3/Raf-1 enhanced the activation of the RAF protooncogene serine/threonine-protein kinase (RAF)/mitogen-activated protein kinase kinase 1 (MEK)/ERK signaling cascade, thus promoting c-Myc-mediated cell proliferation and Mcl-1-mediated cell survival. On the other hand, depletion of OVAAL triggered cellular senescence through polypyrimidine tract-binding protein 1 (PTBP1)-mediated p27 expression, which was regulated by competitive binding between OVAAL and p27 mRNA to PTBP1. Additionally, c-Myc was demonstrated to drive OVAAL transcription, indicating a positive feedback loop between c-Myc and OVAAL in controlling tumor growth. Taken together, these results reveal that OVAAL contributes to the survival of cancer cells through dual mechanisms controlling RAF/MEK/ERK signaling and p27-mediated cell senescence.

Adenosine is a promising cytotoxic reagent for tumors, long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been indicated to play critical roles in tumorigenesis, ILF3 has been recognized as a MEG3-binding protein, however, the roles of adenosine and MEG3 on hepatoma are still ambiguous. To clarify the effects of MEG3 on the adenosine-induced cytotoxicity in hepatoma, MEG3 and ILF3 lentivirus were transduced into human hepatoma HepG2 cells to stimulate overexpression of MEG3 (OE MEG3) and overexpression of ILF3 (OE ILF3), furthermore, ILF3 small interfering RNA (siRNA) was also applied to downregulate the expression of ILF3. In this study, autophagy was markedly inhibited by low concentration of adenosine, which present by not only inhibited transformation from LC3-I to LC3-II and autophagosomes formation, but also the elevation of mTOR and reduction of beclin-1 proteins. Furthermore, low concentration of adenosine also exerted marked cytotoxicity representing induced cell apoptosis together with reductions of cell viability and migration, which were also markedly enhanced by OE MEG3. Novelly and excitingly, adenosine markedly stimulated MEG3 expression, OE MEG3 markedly decreased the ILF3 expression in HepG2 cells, and the adenosine-induced autophagy inhibition, together with the ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR were also boosted by OE MEG3. More interestingly, OE ILF3 increased autophagy, whereas downregulated ILF3, especially in the case of adenosine, led to marked autophagy inhibition by decreasing beclin-1. The present study demonstrates autophagy inhibition is involved in the adenosine-induced cytotoxicity in HepG2 cells, the cytotoxicity can be synergized by OE MEG3 via downregulated ILF3 to activate PI3K/Akt/mTOR and inactivate the beclin-1 signaling pathway. In conclusion, MEG3 and inhibition of autophagy might be potential targets for augmenting adenosine-induced cytotoxicity in hepatoma.

The adhesion energy of kerogen in continental and marine shale was innovatively discovered using the colloid probe technique with atomic-force microscopy (AFM). AFM results indicated that the adhesion force of kerogen was higher than the inorganic material in both the continental and marine shale samples. The chemical elements in the two kinds of samples were measured by energy-dispersive X-ray analysis with scanning electron microscopy (SEM). The chemical compositions of kerogen involved C═C bonding, C═O bonding, pyridine nitrogen, and pyrrole nitrogen, whereas the primary constituent involving inorganic matter was Si–O bonding. These results were confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The high percentages of C═C and C═O bonding in kerogen are attributed to the large dipole on the kerogen surface which allowed kerogen to contain liquid and gaseous hydrocarbons.