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Perlite is one of the major constituents of the radioactive thermal insulation waste (RTIW) originating from nuclear power plants and, for proper waste management, a significant reduction in its volume is required prior to disposal. In this work, the volume reduction of perlite is studied by high-temperature treatment method with using K2CO3 as a flux. The perlite is ground with 0–30 wt% K2CO3, and differential thermal analysis/thermogravimetric analysis is used to monitor the glass transition temperature (Tg) and weight loss. The Tg varied between ~772.2 and 837.1 °C with the minima at ~643.5 °C with the addition of ~10 wt% K2CO3. It is observed that compared to the pure perlite the volume reduction ratio (VRR) increases with the addition of K2CO3. The VRR of 11.20 is observed with 5 wt% K2CO3 at 700 °C, as compared to VRR of 5.56 without K2CO3 at 700 °C. The X-ray photoelectron spectroscopy and scanning electron microscopy are used to characterize perlite samples heat-treated without/with 5 wt% K2CO3 at 700 °C. Moreover, the atomic absorption spectroscopy indicates that the proposed heat-treatment procedure is able to completely retain the radionuclides present in the perlite RTIW.

The root bark of Morus alba L. has cytotoxic activity against several types of cancer cells. However, little is known about its chemopreventive mechanisms and bioactive metabolites. In this study, we showed that M. alba L. root bark extracts (MRBE) suppressed s-catenin response transcription (CRT), which is aberrantly activated in various cancers, by promoting the degradation of s-catenin. In addition, MRBE repressed the expression of the s-catenin/T-cell factor (TCF)-dependent genes, c-myc and cyclin D1, thus inhibiting the proliferation of RPMI-8226 multiple myeloma (MM) cells. MRBE induced apoptosis in MM cells, as evidenced by the increase in the population of annexin V-FITC-positive cells and caspase-3/7 activity. We identified ursolic acid in MRBE through LC/mass spectrum (MS) and observed that it also decreased intracellular s-catenin, c-myc, and cyclin D1 levels. Furthermore, it suppressed the proliferation of RPMI-8226 cells by stimulating cell cycle arrest and apoptosis. These findings suggest that MRBE and its active ingredient, ursolic acid, exert antiproliferative activity by promoting the degradation of s-catenin and may have significant chemopreventive potential against MM.

To obtain a material that adsorbs nitrogen oxide (NOx) gas with high efficiency, we used sulfuric acid (H2SO4)-treated activated carbon (AC). The proposed H2SO4-treated AC was treated by dipping and spray coating in a H2SO4 solution. For structural analysis, scanning electron microscopy and Brunauer–Emmett–Teller measurements were performed on general and H2SO4-treated ACs. The composition of the atoms on the surface and inner pore structure of both ACs was confirmed through energy dispersive X-ray spectroscopy measurements. From the structural analysis, it was confirmed that the structure of H2SO4-treated AC was similar to that of general AC, indicating that it was not affected by the H2SO4 solution. There was no significant difference in the inner pore structures of general and H2SO4-treated ACs through specific surface area analysis, which indicates that the physical adsorption of NOx gas for the H2SO4-treated AC is similar to that of general AC. Based on the atomic composition analysis, it was confirmed that sulfur ions were largely present on the inner pore structure than the surface of H2SO4-treated AC. These results indicate that the chemical adsorption of sulfur ions and NOx gas in the inner pore structure occurred rather than physical adsorption. The results of this study are expected to be applicable to the field of materials that remove harmful gases.

Ambient particulate matter (PM) is a major contributor to environmental air pollution-associated skin damage. However, most published studies are observational or epidemiologic and have not mechanistically investigated the effects of air pollutants on cellular senescence and aging, particularly in combination with ultraviolet (UV) radiation. Herein, we analyzed whether UVA aggravates the PM-induced inflammatory cascade, which contributes to the aging of skin-derived cells. We hypothesized that cellular senescence is involved in PM&UVA-induced aging and tested whether an l-ascorbic acid compound (LAC), containing vitamin E and ferulic acid, can inhibit PM&UVA-induced aging. PM&UVA-exposed HDFs showed further elevated reactive oxygen species (ROS) levels detected by flow cytometry. We then demonstrated that PM induces MAPK signaling activation and the expression of AhR and NF-κB, responses that are both exacerbated by UVA. The levels of inflammatory cytokines, IL-1β and IL-6, were significantly higher in the PM&UVA-exposed group which resulted in increased transcription of MMPs, causing downregulation of type I collagen. Meanwhile, treatment with LAC reduced the levels of ROS and inflammatory cytokines. Additionally, PM&UVA-induced SA-β-gal production (staining assay) was reduced by LAC. These findings suggest a role of atmospheric pollution and UVA radiation in cellular senescence induction. Our findings also suggest a possible role of AhR inhibition by topical antioxidants to prevent atmospheric pollution-induced skin aging.

Dermal papilla cells (DPCs) tend to aggregate both in vitro and in vivo, which increases the hair inductivity of DPCs. However, the underlying mechanism of spheroid formation is unknown. We investigated whether collagen expression in human DPCs (hDPCs) is involved in the spheroid formation and hair inductivity of hDPCs and further examined the underlying molecular mechanism of collagen upregulation. The expression of diverse collagens, such as COL13A1 and COL15A1, was upregulated in three dimensional (3D)-cultured or intact DPCs, compared to 2D-cultured hDPCs. This collagen expression was a downregulated in aged hair follicle, and aged DPCs were difficult to aggregate. Blocking of COL13A1 and COL15A1 by small interfering RNA reduced aggregation, while induced senescence of hDPCs in vitro. Further, transforming growth factor-β2 (TGF-β2) expression decreases with aging, and is involved in regulating the expression of COL13A1 and COL15A1. Addition of recombinant TGF-β2 delayed cellular senescence, and recovered spheroid formation in aged hDPCs by upregulating collagen levels. On the contrary, knock-out of TGF-β2 induced the aging of DPCs, and inhibited spheroid formation. These results suggested that COL13A1 and COL15A1 expression is downregulated with aging in DPCs, and upregulation of collagen by TGF-β2 induces the spheroid formation of DPCs. Therefore, TGF-β2 supplement in DPC culture medium could enhance the maintenance and hair inductivity of DPCs.

CYJ-27, a synthetic analog of decursin, prevents the generation of proinflammatory cytokines and oxidative stress. In this study, the effects of CYJ-27 on the regulation of inducible nitric oxide synthase (iNOS), heme oxygenase (HO)-1, and cyclooxygenase (COX-)2 were characterized in lipopolysaccharide (LPS)-treated human umbilical vein endothelial cells (HUVECs). In addition, the effects of CYJ-27 on the production of iNOS and representative proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, were tested in the lung tissues of LPS-treated mice. CYJ-27 promoted the expression of HO-1, suppressed NF-κB-luciferase activity, and reduced COX-2/PGE2 and iNOS/NO, resulting in a diminution in phosphorylated-STAT-1. Furthermore, CYJ-27 promoted the nuclear translocation of Nrf2, enhanced the combination of Nrf2 to antioxidant response elements, and diminished IL-1β production in LPS-activated HUVECs. CYJ-27-downregulated iNOS/NO expression was rescued after the RNAi suppression of HO-1. In LPS-treated mice, CYJ-27 significantly diminished iNOS production in the lung tissues and TNF-α expression in the bronchoalveolar lavage fluid. These findings indicate that CYJ-27 exerts anti-inflammatory activities by regulating iNOS through downregulation of both NF-κB activation and phosphorylated-STAT-1. Hence, it can act as a template for the development of novel substances to treat inflammatory diseases.

Macrophage activation is a key contributing factor for excessive inflammatory responses of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Geranylgeranyl diphosphate synthase (GGPPS) plays a key role in the development of inflammatory diseases. Our group previously showed that GGPPS in alveolar epithelium have deleterious effects on acute lung injury induced by LPS or mechanical ventilation. Herein, we examined the role of GGPPS in modulating macrophage activation in ALI/ARDS. We found significant increased GGPPS expression in alveolar macrophages in patients with ARDS compared with healthy volunteers and in ALI mice induced by LPS. GGPPS-floxed control ( GGPPSfl/fl) and myeloid-selective knockout ( GGPPSfl/fl LysMcre) mice were then generated. Interestingly, using an LPS-induced ALI mouse model, we showed that myeloid-specific GGPPS knockout significantly increased mortality, aggravated lung injury, and increased the accumulation of inflammatory cells, total protein, and inflammatory cytokines in BALF. In vitro, GGPPS deficiency upregulated the production of LPS-induced IL-6, IL-1β, and TNF-α in alveolar macrophages, bone marrow-derived macrophages (BMDMs), and THP-1 cells. Mechanistically, GGPPS knockout increased phosphorylation and nuclear translocation of NF-κB p65 induced by LPS. In addition, GGPPS deficiency increased the level of GTP-Rac1, which was responsible for NF-κB activation. In conclusion, decreased expression of GGPPS in macrophages aggravates lung injury and inflammation in ARDS, at least partly by regulating Rac1-dependent NF-κB signaling. GGPPS in macrophages may represent a novel therapeutic target in ARDS.

Human epidermal growth factor receptor 2 (HER2), as a receptor tyrosine kinase of EGF receptor family, whose mutation is often associated with even if less frequency but poor prognosis and shorter survival in pulmonary malignant tumor. HER2 status include mutation, overexpression, amplification and also some rare genotypes, detected by next generation sequencing (NGS), immunohistochemistry (IHC), and also fluorescence in situ hybridization (FISH). Different genotypes represent different therapeutic targets and indicate different clinical prognosis concluded by previous studies. Unfortunately, no standard guidelines for first-line treatment are widely recognized, and current therapeutic schedules include chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Especially for patients with advanced metastasis, chemotherapy is based as a systemic therapy using studies of breast cancer or EGFR-positive lung adenocarcinoma as a template. Studies already explored treatment including EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and afatinib, and also trastuzumab and its conjugation like HER2-targeted antibody-drug conjugate trastuzumab emtansine (T-DM1) and conjugate trastuzumab deruxtecan (T-DXd). Also, he researches explored combination therapy with chemotherapy and TKIs or monoclonal antibodies. This review describes commonly used therapies for HER2-positive/HER2-overexpression patients and general relationship between genotypes of HER2, drug selection and final prognosis in order to provide suggestions for future diagnosis and treatment.

The ceramic support with pore gradient structure was modified by the chloroform solution of 1 H, 1 H, 2 H, 2 H-perfluorodecytriethoxysilane (FAS) to prepare hydrophobic FAS/α-Al2O3 composite membra...

Background Natural killer T (NKT) cells are unconventional T cells that bridge innate and adaptive immunity. NKT cells have been implicated in the development of atopic dermatitis (AD). Objective We aimed to investigate the role of NKT cells in AD development, especially in skin. Methods Global proteomic and transcriptomic analyses were performed by using skin and blood from human healthy–controls and patients with AD. Levels of CXCR4 and CXCL12 expression in skin NKT cells were analyzed in human AD and mouse AD models. By using parabiosis and intravital imaging, the role of skin CXCR4+ NKT cells was further evaluated in models of mice with AD by using CXCR4–conditionally deficient or CXCL12 transgenic mice. Results CXCR4 and its cognate ligand CXCL12 were significantly upregulated in the skin of humans with AD by global transcriptomic and proteomic analyses. CXCR4+ NKT cells were enriched in AD skin, and their levels were consistently elevated in our models of mice with AD. Allergen-induced NKT cells participate in cutaneous allergic inflammation. Similar to tissue-resident memory T cells, the predominant skin NKT cells were CXCR4+ and CD69+. Skin-resident NKT cells uniquely expressed CXCR4, unlike NKT cells in the liver, spleen, and lymph nodes. Skin fibroblasts were the main source of CXCL12. CXCR4+ NKT cells preferentially trafficked to CXCL12-rich areas, forming an enriched CXCR4+ tissue-resident NKT cells/CXCL12+ cell cluster that developed in acute and chronic allergic inflammation in our models of mice with AD. Conclusions CXCR4+ tissue-resident NKT cells may form a niche that contributes to AD, in which CXCL12 is highly expressed.

The performance of an all-vanadium redox flow battery (VRFB) is affected by many factors, among which the crossover of the vanadium ion through the ion-exchange membrane plays an important role in ...

Proton exchange membrane fuel cells (PEMFCs) employ a proton conductive membrane as the separator to transport a hydrogen proton from the anode to the cathode. The membrane's proton conductivity depends on the water content in the membrane, which is affected by the operating conditions. A membrane electrode assembly (MEA) that can self-sustain water is the key component for developing a light-weight and compact PEMFC system without humidifiers. Hence, zeolite is employed to the anode catalyst layer in this study. The effect of the gas diffusion layer (GDL) materials, catalyst loading, binder loading, and zeolite loading on the MEA performance is investigated. The MEA durability is also investigated through the electrochemical impedance spectroscopy (EIS) method. The results suggest that the MEA with the SGL28BCE carbon paper, Pt loadings of 0.1 and 0.7 mg cm−2 in the anode and cathode, respectively, Nafion-to-carbon weight ratio of 0.5, and zeolite-to-carbon weight ratio of 0.3 showed the best performance when the cell temperature is 60 °C and supplies with dry hydrogen and air from the environment. According to the impedance variation measured by EIS, the MEA with zeolite in the anode catalyst layer shows higher and more stable performance than those without zeolite.

An all-vanadium redox flow battery (VRFB) system, with multiple stacks, is typically used for large-scale electrical energy storage applications. In a VRFB system, pumps deliver positive and negati...

Although the combination of chemotherapy and immunotherapy is a hot topic in lung cancer, little is understood regarding the possible mechanisms behind their synergy. Moreover, safety is a major concern for clinicians while performing chemotherapy. Therefore, it is important to determine the appropriate dose and period of chemotherapy for combining it with immunotherapy, and investigate the underlying synergistic mechanism. Here, we showed that carboplatin can induce DNA damage and activate the canonical STING/TBK1/IRF3 pathway and non-canonical STING-NF-κB signaling complex. Further, low-dose carboplatin changed the "cold" tumor into a "hot" tumor via the signaling hub STING, augmenting CD8+ T-cell infiltration, increasing PD-L1 expression, and hence potentiating the anti-tumor effect of PD-1 inhibitors; importantly, there were no adverse effects. Furthermore, knocking down STING in tumor cells effectively reversed PD-L1 upregulation and STING pathway activation, and reduced the anti-tumor effect of low-dose carboplatin and carboplatin-PD-1 inhibitor combination. Our findings collectively reported a previously unexplored role of low-dose carboplatin targeting in the STING pathway and provided an economical, useful and safe option for improving the efficacy of PD-1 inhibitors in lung cancer.

The dehydrogenation mechanisms of ethylene diamine monoborane (EDMB) adducts and its derivatives having CH3, Cl, F, NH2, OCH3, CN, and H substituents at two sites on the ethylene backbone were investigated to explore their potential as liquid organic hydrogen carriers (LOHCs). Using density functional theory calculations, the thermodynamic parameters of the EDMB adducts and dehydrogenation reactions to form cyclic monomers, dimers, and trimers were calculated. In particular, we focused on the free energy barriers of EDMB adducts substituted with Cl/CN, Cl/OCH3, F/CN, F/OCH3, F/F, and NH2/H for cyclic monomer formation, H/CH3, H/CN, Cl/H, and NH2/H for cyclic dimer formation, and H/Cl, H/F, and NH2/H for cyclic trimer formation, which are promising candidates for chemical hydrogen storage. We also explored the formation of cyclic trimers from the selected cyclic monomers with CH3/CH3, H/CH3, and NH2/H substituents. As a result, the dehydrogenation pathways and transition states of the various adducts for the formation for the various cycles were identified, and electrostatic potential surfaces and frontier molecular orbitals calculations were calculated to understand the reaction further. The results obtained indicate the potential of these materials for hydrogen storage, and we hope that this work will encourage the experimental investigation of these materials.

Despite the fact that research into most high-performance thermoelectric (TE) materials is focused on tellurides, compelling demand has arisen to replace tellurium (Te) with selenium (Se) due to the scarcity of Te. Silver bismuth diselenide (AgBiSe2, ABS) has been widely studied in relation to thermoelectric applications due to its intrinsically low thermal conductivity. However, its low power factor (PF) has been considered as an underlying issue preventing improvements of the TE properties of ABS. Here, it is demonstrated that a high PF can be achieved by incorporating Cu into the ABS system via the nestification of conduction bands when a disordering between Ag and Bi occurs. Degenerate electronic bands simultaneously increase the density-of-states effective mass and carrier concentration while not reducing the carrier mobility significantly. Therefore, improved TE performance with a maximum PF of 8.2 μW cm−1 K−2 and a peak zT value of 1.14 was achieved at 773 K, opening a new horizon for the development of environmentally benign TE materials with high performance capabilities.

In order to extend the application of graphene oxide (GO) in the area of electronic industries, enhancing the electrical properties of GO as a cost-effective alternative for graphene seems mandatory. Engineering the electrical properties of GO can be achieved in two different approaches: the oxygen functional group reduction and doping GO with chemical dopants. Here, both approaches were utilized to tune the electrical properties of GO toward its application as cathode; first, GO was doped with alkali metal dopants, and later, the doped samples were thermally reduced. Energy-dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy were utilized to study the chemical composition of the doped samples. The even distribution of the dopants on the GO surface presented via the EDX elemental map, with no sign of particle development. After doping GO with alkali metals followed by thermal reduction, the sheet resistance of the doped samples was decreased from 311.0 kΩ/sq to as low as 32.1 kΩ/sq. Moreover, the optical properties of GO were effectively engineered via the different doping agents. The ultra-violet photoelectron spectroscopy showed that the shift of the work function of GO was as high as 1.74 eV, after doping followed by thermal reduction.

Dekkera anomala YAE-1 strain separated from "airag" (Mongolian fermented mare's milk) produces β-glucosidase, which can convert ginsenoside Rb1 from Panax ginseng. Ginseng-derived bioactive components such as ginsenoside Rb1 have various immunological and anticancer activities. Airag was collected from five different mare milk farms located near Ulaanbaatar, Mongolia. YAE-1 strains were isolated from airag to examine the hydrolytic activities of β-glucosidase on Korean Panax ginseng using an API ZYM kit. Supernatants of selected cultures having β-glucosidase activity were examined for hydrolysis of the major ginsenoside Rb1 at 40°C, pH 5.0. The YAE-1 strain was found to be nearly identical at 99.9% homology with Dekkera anomala DB-7B, and was thus named Dekkera anomala YAE-1. This strain exerted higher β-glucosidase activity than other enzymes. Reaction mixtures from Dekkera anomala YAE-1 showed great capacity for converting ginsenoside Rb1 to ginsenoside Rd. The β-glucosidase produced by Dekkera anomala YAE-1 was able to hydrolyze ginsenoside Rb1 and convert it to Rd during fermentation of the ginseng. The amount of ginsenoside Rd was highly increased from 0 to 1.404 mg/ml in fermented 20% ginseng root at 7 days.

It is unclear how acid-induced lung injury alters the regional lung volume response to mechanical ventilation (MV) and how this impacts protein expression. Using a mouse model, we investigated the separate and combined effects of acid aspiration and MV on regional lung volumes and how these were associated with the proteome. Adult BALB/c mice were divided into four groups: intratracheal saline, intratracheal acid, saline/MV, or acid/MV. Specific tidal volume (sVt) and specific end-expiratory volume (sEEV) were measured at baseline and after 2 h of ventilation using dynamic high-resolution four-dimensional computed tomography (4DCT) images. Lung tissue was dissected into 10 regions corresponding to the image segmentation for label-free quantitative proteomic analysis. Our data showed that acid aspiration significantly reduced sVt and caused further reductions in sVt and sEEV after 2 h of ventilation. Proteomic analysis revealed 42 dysregulated proteins in both Saline/MV and Acid/MV groups, and 37 differentially expressed proteins in the Acid/MV group. Mapping of the overlapping proteins showed significant enrichment of complement/coagulation cascades (CCC). Analysis of 37 unique proteins in the Acid/MV group identified six additional CCC proteins and seven downregulated proteins involved in the mitochondrial respiratory chain (MRC). Regional MRC protein levels were positively correlated with sEEV, while the CCC protein levels were negatively associated with sVt. Therefore, this study showed that tidal volume was associated with the expression of CCC proteins, while low end-expiratory lung volumes were associated with MRC protein expression, suggesting that tidal stretch and lung collapse activate different injury pathways. NEW & NOTEWORTHY This study provides novel insights into the regional response to mechanical ventilation in the setting of acid-induced lung injury and highlights the complex interaction between tidal stretch and low-end-expiratory lung volumes; both of which caused altered regulation of different injury pathways.

The global incidence of Mycobacterium abscessus (Mabc), a rapidly growing nontuberculous mycobacterial strain that causes treatment-refractory pulmonary diseases, is increasing. Despite this, the host factors that allow for protection against infection are largely unknown. In this study, we found that sirtuin 3 (SIRT3), a mitochondrial protein deacetylase, plays a critical role in host defense against Mabc infection. Mabc decreased SIRT3 and upregulated mitochondrial oxidative stress in macrophages. SIRT3 deficiency led to increased bacterial loads, histopathological, and mitochondrial damage, and pathological inflammation during Mabc infection. Administration of scavengers of mitochondrial reactive oxygen species significantly decreased the in vivo Mabc burden and excessive inflammation, and induced SIRT3 expression in infected lungs. Notably, SIRT3 agonist (resveratrol) significantly decreased Mabc growth and attenuated inflammation in mice and zebrafishes, indicating the key role for SIRT3 in metazoan host defense. Collectively, these data strongly suggest that SIRT3 is a host-directed therapeutic target against Mabc infection by controlling mitochondrial homeostasis.

This study reports in-situ cesium-doped graphene (G/Cs) coating obtained by introducingCs2CO3into the atmospheric pressure chemical vapor deposition (APCVD) furnace dur-ing graphene deposition on copper. The successful Cs-doping of the graphene coating wasconfirmed via X-ray photoelectron spectroscopy (XPS). As compared to the spectra of puregraphene coating, the XPS spectra of the G/Cs coating revealed a shift of the C1s and Cs3d5/2peaks to higher and lower binding energies, respectively; thus, implying the n-type charac-ter of the doping and indicating a charge transfer between Cs and graphene. Raman resultsshow that a pure graphene coating is composed of fewer layers, fewer defects, and largerdomain size than the G/Cs coating. Ultraviolet photoelectron spectroscopy was utilized tostudy the work function of graphene and the G/Cs and revealed that doping graphene withCs dopants reduced the work function of graphene by 1.2 eV. Electrochemical testing during15-day immersion in 0.1 M NaCl indicated the destructive effect of the G/Cs coating on theCu substrate. The results showed that the G/Cs coating exhibits a higher corrosion rate andlower corrosion resistance than even the bare metal itself. This work was supported by Agencia Estatal de Investigación (Ministerio de Ciencia, Innovación y Universidades of Spain, grant No.: ESP2017-82092-ERC (AEI)); SN work is supported by Comunidad de Madrid (Spain) (grant No.: 2018/T2IND/11352); GSA work is supported by the Ministerio de Ciencia, Innovación y Universidades of Spain (grant No.: RYC-2014-15357). The authors thank the National Research Foundation of the Ministry of Education, Republic of Korea (Basic Science Research Program grant No.: 2018R1A2B5A02023190) and Ministry of Education, Science and Technological Development of Serbia (Contract No. 451-03-68/2020-14/200135) for financial support.

During the operation of an all-vanadium redox flow battery (VRFB), the electrolyte flow of vanadium is a crucial operating parameter, affecting both the system performance and operational costs. Th...

The interface between oxide/oxide layers shows an inhomogeneous charge transport behavior, which reveals a high conductivity owing to interface-doped. One typical example is the hetero-interface between ZnO film and other wide band gap oxides (e.g., Al2O3, TiO2, and HfO2). It is thus quite evident that the ZnO/other oxides hetero-interface contains high density electron carriers effectively screening the gate-induced electric field. Thus, an extremely weak gate modulation in ZnO film was showed, resulting in very low on/off ratio of 1.69 in top-gate field-effect-transistor (TG-FET) configuration. So, to extend the usage of ZnO TG-FET is not quite possible toward further practical application. Herein, we clarified the correlation of inhomogeneous region in oxide/oxide hetero-junction by systematically study. Our work suggests that a self-assembly of molecules (SAM) buffer layer is suitable for tuning the inhomogeneous charge transport in ZnO film, which not only reduces the interface trap density, but also effectively enhances the gate electric field modulation at the hetero-interface. We further report the robust fabrication of TG-FET arrays based on ZnO thin film, using an ultra-thin alkylphosphonic acid molecule monolayer as buffer layer. Our device demonstrates a pronounced ultrahigh on/off ratio of ≥ 108, which is 8-order of magnitude higher than that of a device without buffer layer. For the highly reliable arrays, our device exhibits a high yield of over 93% with an average on/off ratio of ~107 across the entire wafer scale, mobility (18.5 cm2/(V·s)), an extended bias-stressing (~ 2,000 s) and long-stability (~ 150 days) under ambient conditions.

Sanmiao pill (SMP), a Chinese traditional formula, had been used to treat gouty arthritis (GA). However, the active compounds and underlying mechanism remained unclear. Hence, network pharmacology and molecular docking were utilized to explore bioactive compounds and potential mechanism of action of SMP in treating GA. In the study, the compounds of SMP, corresponding targets, and GA-related targets were mined from various pharmacological databases. Then, herb-compound-target, compound-target, PPI, and target-pathway networks were constructed. Ultimately, molecular docking was carried out to verify the predicted results. The results indicated that 47 active compounds, 338 targets, and 144 disease targets were collected. Network analysis implied thatPhellodendron chinenseSchneid. played a vital role in the whole formula. Moreover, 7 compounds (quercetin, kaempferol, wogonin, rutaecarpine, baicalein, beta-sitosterol, and stigmasterol) and 4 targets (NFKB1, RELA, MAPK1, and TNF) might be the kernel compounds and targets of SMP against GA. According to GOBP and KEGG pathway enrichment analysis and target-pathway network, SMP might exert a therapeutic role in GA by regulating numerous biological processes and pathways, including lipopolysaccharide-mediated signaling pathway, positive regulation of transcription, Toll-like receptor signaling pathway, JAK-STAT signaling pathway, NOD-like receptor signaling pathway, and MAPK signaling pathway. The results of molecular docking showcased that 11 pairs of compound with targets had tight binding strength. Thereinto, 4 compounds of MAPK1 and 5 compounds of NFKB1 possessed a better combination, suggesting that MAPK1 and NFKB1 might be considered as therapeutic targets in treatment of GA. This study verified that SMP had synergistic effect on GA by multicomponents, multitargets, and multipathways.

This study provides a comparative analysis of experiments-based enhancements and sensitivity evaluations for the structural design of an automatic ocean salt collector under various load conditions. The sizing variables of the structural members were considered as design factors. The strength and weight performances were selected as output responses. The design of experiments used in the comparative study consisted of the orthogonal array design, Box–Behnken design, and central composite design. The response surface model, one of the metamodels, was applied to the approximate model generation. The design enhancement performance metrics, including numerical costs and weight minimization, according to the design of experiments, were compared from the best design case results. The central composite design method showed the most enhanced design results for the structural design of the automatic ocean salt collector.

Multifunctional NiCoTi metal oxide catalysts (denoted herein as NiCoTi-x, where x is the molar ratio Ni + Co:Ti) were successfully prepared by thermal treatment of NiCoTi layered double hydroxide (LDH) precursors. The NiCoTi-x catalysts were then applied to the hydrogenation of 5-hydroxymethylfurfural (HMF) to 2,5-dimethylfuran (DMF). The Ni:Co:Ti molar ratio in the catalysts was found to strongly influence both catalyst activity and product selectivity. A NiCoTi-8 catalyst, containing Ni, Co and Ti in a 4:4:1 molar ratio (i.e. Ni + Co/Ti = 8), displayed outstanding performance for HMF hydrogenation at 200 °C and 1.5 MPa, evidenced by a 90.7% HMF conversion and 95.8% selectivity to DMF. A ternary metal oxide catalyst derived from a layered double hydroxide was proposed for the efficient and selective hydrogenation of 5-hydroxymethylfurfural to 2,5-methylfuran.

To predict the nonlinear viscoelastic behavior of polymer melts and solutions under medium amplitude oscillatory shear (MAOS) flow, we summarized known analytical MAOS material functions and derived new analytical solutions from several continuum- or molecular-based constitutive models [Johnson–Segalman, Phan-Thien–Tanner, Leonov, Larson, Pom-Pom, coupled double-convection-reptation with chain stretch (cDCR-CS), and Rouse linear entangled polymers (Rolie-Poly)]. All constitutive models discussed in this study were classified as time-strain separable or inseparable models. Whereas linear viscoelastic behavior of all constitutive models under small amplitude oscillatory shear flow was identical, the frequency-dependent signatures of four MAOS moduli (first-harmonic elastic and viscous MAOS moduli and third-harmonic elastic and viscous MAOS moduli) were model-specific, though all analytical solutions exhibited negative first-harmonic elastic MAOS moduli. In particular, tube-based constitutive models displayed a sign change in first-harmonic viscous MAOS modulus when chain retraction of the models after deformation was not instantaneous. In addition, two models for entangled linear polymers, that is, the Rolie-Poly and cDCR-CS models, displayed a second sign change in third-harmonic elastic MAOS modulus when finite chain extensibility was introduced. These results suggest that chain relaxation dynamics can be reflected in signatures of MAOS moduli. We extended single-mode predictions into multimode versions to predict the behavior of weakly or moderately entangled polystyrene solutions (effective entanglement number

Background This trial aimed to investigate the treatment response, survival profiles and treatment-related adverse events (AEs) of apatinib plus docetaxel in advanced non-squamous non-small cell lung cancer (NSCLC) patients with wild-type epidermal growth factor receptor (EGFR). Methods Thirty advanced non-squamous NSCLC patients with wild-type EGFR were recruited in this multi-center, phase II trial. All patients received apatinib (orally 500 mg, once daily until disease progression, intolerable toxicity, or death) plus docetaxel (intravenously 60 mg/m2 at day 1 every 3 weeks for 4-6 cycles). The treatment response, progression-free survival (PFS), overall survival (OS) and treatment-related AEs were evaluated. Results One patient lacked response and survival assessment due to early lost follow-up, therefore, 29 patients were included in response and survival analysis. There was no (0.0%) patient achieved complete remission, 8 (27.6%) patients achieved partial remission, 20 (69%) patients with stable disease, and 1 (3.4%) patient with progressive disease, resulting in objective response rate and disease control rate of 27.6% and 96.6%, respectively. According to the survival data, median PFS was 5.3 months (95% CI: 3.6-6.9 months) and median OS was 9.6 months (95% CI: 6.33-12.9 months). For safety, totally 30 patients were included in the analysis. Common non-hematologic AEs included hypertension (66.7%), hand-foot syndrome (40.0%), proteinuria (36.7%); common hematologic AEs included leukopenia (26.7%), thrombocytopenia (23.3%), neutropenia (16.7%). Notably, majority of AEs were at grade 1-2, and the overall AEs were tolerable. Conclusions Apatinib plus docetaxel is an effective and tolerable treatment option for advanced non-squamous NSCLC with wild-type EGFR.

Context NOTCH signaling is activated in endometriotic lesions, but the exact mechanisms remains unclear. IL-6, which is increased in the peritoneal fluid of women with endometriosis, induces NOTCH1 through E-proteins including E2A and HEB in cancer. Objective To study the role of E-proteins in inducing NOTCH1 expression under the regulation of IL-6 in endometriosis. Setting and Design The expression of E-proteins and NOTCH1 was first investigated in endometrium of women with endometriosis and the baboon model of endometriosis. Regulation of E-proteins and NOTCH1 expression was examined after IL-6 stimulation and siRNA mediated inhibition of E2A or/and HEB in human endometriotic epithelial cells (12Z) in vitro, and subsequently following IL-6 treatment in the mouse model of endometriosis in vivo. Results E2A, HEB, and NOTCH1 were significantly upregulated in glandular epithelium (GE) of ectopic endometrium compared to eutopic endometrium in both women and the baboon model. IL-6 treatment upregulated the expression of NOTCH1 together with E2A and HEB in 12Z cells. Small interfering RNA inhibition of E2A and HEB or HEB alone decreased NOTCH1 expression. Binding efficiency of both E2A and HEB was significantly higher at the binding sites on the human NOTCH1 promoter after IL-6 treatment. Finally, IL-6 treatment resulted in a significantly increased number of endometriotic lesions along with increased expression of E2A, HEB, and NOTCH1 in GE of the lesions compared with the vehicle group in an endometriosis mouse model. Conclusions IL-6 induced NOTCH1 expression is mediated by E-proteins in the ectopic GE cells, which may promote endometriotic lesion development.

Low-cost red phosphorus (RP) can be completely transformed into black phosphorus (BP) in a solid-state through a ball milling process and a sintering process. With the addition of 1.5 wt.% Sn, RP was fully crystallized into Sn-doped BP and the electrical conductivity was also enhanced to 1625 S m−1 at 300 K, 16 times higher than the 100 S m−1 of pure BP. This study reveals the mechanisms of the complete phase transformation from amorphous RP to crystalline BP with the help of Sn, and electrical enhancement, due to the role of Sn as a p-type dopant.

Periodontitis is an inflammatory disease induced by local infection in tooth‐supporting tissue. Periodontitis is associated with systemic bone diseases, but little is known about the mechanism of the causal effect of periodontitis on systemic bone resorption. Bacteria‐derived extracellular vesicles (EVs) act as natural carriers of virulence factors that are responsible for systemic inflammation. In this study, we investigated the role of EVs derived from Filifactor alocis, a Gram‐positive, anaerobic periodontal pathogen, in systemic bone loss and osteoclast differentiation. F. alocis EVs accumulated in the long bones of mice after intraperitoneal administration. These EVs induced proinflammatory cytokines, osteoclastogenesis, and bone resorption via Toll‐like receptor 2 (TLR2). The phase separation of F. alocis EVs showed that amphiphilic molecules were responsible for the induced bone resorption and osteoclastogenesis. The osteoclastogenic effects of F. alocis EVs were reduced by lipoprotein lipase. Proteomic analysis of the amphiphilic molecules identified seven lipoproteins. Our results indicate that lipoprotein‐like molecules in F. alocis EVs may contribute to systemic bone loss via TLR2.

The generator is the most popular mobile power device and backup power device in the world. It is very important for human life. Therefore, it is important to develop more efficient combustion technology in order to save energy and reduce air pollution. In this paper, a novel technology of hydrogen and oxygen compound gasoline fuel is developed. Hydrogen and oxygen gases are produced from an electrolytic cell and then mixed with the intake gasoline and air. The compound fuel is sucked into the engine combustion chamber. The hydrogen and oxygen gases can be produced immediately without any storage device of hydrogen. The experimental results show that this technology can increase the power generation and decrease emission pollution due to promoting combustion efficiency. In addition, the spark plug seat temperature increases due to higher heat value of hydrogen. This technique can reduce carbon monoxide and HC, but increase carbon dioxide. The research and development of this technique can achieve the goals of energy saving, emission reduction, relative safety, easy refitting and low refitting expense. Moreover, this research possesses academic innovation and industrial application.

MXenes have attracted great interests as supercapacitors due to their metallic conductivity, high density, and hydrophilic nature. Herein we report Ti3 C2 -Cu/Co hybrids via molten salt etching in which the existence of metal atoms and their interactions with MXene via surficial O atoms were elucidated by XAFS for the first time. The electrochemical investigation of Ti3 C2 -Cu electrode demonstrated the pseudocapacitive contribution of Cu and a splendid specific capacitance of 885.0 F g-1 at 0.5 A g-1 in 1.0 M H2 SO4 . Symmetric supercapacitor Ti3 C2 -Cu//Ti3 C2 -Cu was demonstrated with operating voltage of 1.6 V, areal capacitance of 290.5 mF cm-2 at 1 mA cm-2 , and stability over 10 000 cycles. It delivered an areal energy density of 103.3 μWh cm-2 at power density of 0.8 mW cm-2 , based on which a supercapacitor pouch was fabricated. It provides deeper insights into the molten salt mechanism and strategies for designing MXene-based materials for electrochemical energy storage.

In this study we tested whether a protein corona is formed around extracellular vesicles (EVs) in blood plasma. We isolated medium‐sized nascent EVs of THP1 cells as well as of Optiprep‐purified platelets, and incubated them in EV‐depleted blood plasma from healthy subjects and from patients with rheumatoid arthritis. EVs were subjected to differential centrifugation, size exclusion chromatography, or density gradient ultracentrifugation followed by mass spectrometry. Plasma protein‐coated EVs had a higher density compared to the nascent ones and carried numerous newly associated proteins. Interactions between plasma proteins and EVs were confirmed by confocal microscopy, capillary Western immunoassay, immune electron microscopy and flow cytometry. We identified nine shared EV corona proteins (ApoA1, ApoB, ApoC3, ApoE, complement factors 3 and 4B, fibrinogen α‐chain, immunoglobulin heavy constant γ2 and γ4 chains), which appear to be common corona proteins among EVs, viruses and artificial nanoparticles in blood plasma. An unexpected finding of this study was the high overlap of the composition of the protein corona with blood plasma protein aggregates. This is explained by our finding that besides a diffuse, patchy protein corona, large protein aggregates also associate with the surface of EVs. However, while EVs with an external plasma protein cargo induced an increased expression of TNF‐α, IL‐6, CD83, CD86 and HLA‐DR of human monocyte‐derived dendritic cells, EV‐free protein aggregates had no effect. In conclusion, our data may shed new light on the origin of the commonly reported plasma protein ‘contamination’ of EV preparations and may add a new perspective to EV research.

Understanding the mechanism of thermal energy transport in a single nanotube (NT) is essential for successfully engineering nanostructured conducting polymers to apply to thermoelectrics or flexible electronic devices. We report the characterization of the in-plane thermal energy transport in a single poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) NT via direct measurement of the in-plane thermal conductivity (κ). We also demonstrate that the in-plane κ of PEDOT:PSS NT can be tuned within the range of 0.19 to 1.92 W·m-1·K-1 merely by changing the solvent used to treat the NTs in the post-fabrication stage. The in-plane thermal energy transport in a pristine NT, with its low in-plane κ, is primarily due to phonons; in a sulfuric acid-treated NT however, significant electronic contributions lead to a high in-plane κ. The present study will contribute to understanding the mechanism of thermal energy transport in highly disordered structures, such as conducting polymers, and to designing highly efficient polymer-based devices in which in-plane κ plays a pivotal role in determining the energy conversion efficiency.

Black ginseng (BG), which is ginseng that has been steamed and dried nine times, and its main protopanaxatriol-type ginsenosides Rg4, Rg6, Rh4, and Rg2 have been reported to exhibit various forms of biological activity, including antiseptic, antidiabetic, wound-healing, immune-stimulatory, and anti-oxidant activity. The aim of the this study was to examine the effects of [Formula: see text] (a rare protopanaxatriol-type ginsenoside fraction; Rg2, Rg4, Rg6, Rh1, and Rh4) on heme oxygenase-1 (HO-1) induction and on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-)2 in lipopolysaccharide (LPS)-activated human pulmonary artery endothelial cells (HPAECs). [Formula: see text] was tested to determine its effect on iNOS protein expression and inflammatory markers (interleukin [IL]-1[Formula: see text] and tumor necrosis factor [TNF]-[Formula: see text] in the lung tissue of LPS-treated mice. The results showed that [Formula: see text] induced the expression of HO-1, reduced LPS-activated NF-[Formula: see text]B-luciferase activity, and inhibited iNOS/NO and COX-2/PGE2, which contributed to the inhibition of STAT-1 phosphorylation. In particular, [Formula: see text] induced the translocation of Nrf2 from the cytosol to the nucleus by increasing Nrf2-ARE activity and decreased IL-1[Formula: see text] production in LPS-activated HPAECs. This reduction in iNOS/NO expression due to [Formula: see text] was reversed by siHO-1 RNA transfection. In LPS-treated mice, [Formula: see text] significantly reduced lung tissue iNOS protein levels and TNF-[Formula: see text] levels in the bronchoalveolar lavage fluid. In conclusion, these findings indicate that [Formula: see text] has a critical anti-inflammatory effect due to its ability to regulate iNOS via the inhibition of p-STAT-1 and NF-[Formula: see text]B, and thus it may be suitable for the treatment of inflammatory disease.

Currently there is tremendous interest in the discovery of catalysts which can selectively hydrogenate biomass-derived 5-hydroxymethylfurfural (HMF) to 2,5-dimethylfuran (DMF). Herein, a highly selective catalyst for this transformation was developed, by adsorption of a cobalt porphyrin (CoTAPP) onto a nickel–aluminium layered double hydroxide (NiAl-LDH) support, followed by a pyrolysis step at 500 °C under a N2 atmosphere. The obtained catalyst (denoted here as Co–N–C/NiAl-MMO), comprising cobalt species (Co0 and CoOx) and N-doped carbon on a NiAl mixed metal oxide support, showed outstanding initial selectivity (99.9%) for the hydrogenation of HMF to DMF at 170 °C in tetrahydrofuran (THF). This is one of the highest selectivities reported to date for this reaction, with the reaction temperature being very mild. After 3 cycles of catalytic tests, with catalyst regeneration by heating at 300 °C in N2 between tests, the HMF conversion efficiency and DMF selectivity of Co–N–C/NiAl-MMO had both decreased by >70% compared to the initial values. This deactivation resulted from the loss of surface basic sites needed for H2 activation, as well as a change in the Co speciation on the catalyst surface (i.e. Co0 oxidation to CoOx). Results guide the development of improved catalysts for the selective conversion of HMF to DMF.

BACKGROUND: Bevacizumab is a monoclonal antibody (mAb) against vascular endothelial growth factor (VEGF) and used for treatments of various cancers. Due to the high costs of bevacizumab treatments, a biosimilar provides an affordable alternative therapy for cancer patients. METHODS: In this randomized, double-blind, multicenter, phase 3 study, locally advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) patients with wild-type epidermal growth factor receptor were enrolled and randomized (1:1) into IBI305 or bevacizumab groups. Patients received 6 cycles of paclitaxel/carboplatin plus IBI305 or bevacizumab 15 mg/kg intravenously followed by IBI305 or bevacizumab 7.5 mg/kg maintenance until disease progression, unacceptable toxicity or death. The primary endpoint was confirmed objective response rate (ORR) by an independent radiological review committee (IRRC) and secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS) and safety. RESULTS: A total of 450 NSCLC patients were enrolled (224 in IBI305 group and 226 in bevacizumab group). ORRs were 44.3% for IBI305 and 46.4% for bevacizumab, and the ORR ratio was 0.95 (90% CI: 0.803 to 1.135), within the predefined equivalence margin of 0.75 to 1.33. No significant difference in PFS (7.64 vs. 7.77 m, P=0.9987) was observed between the 2 groups. Serious adverse events (AEs) occurred in 33.5% (75/224) of patients in the IBI305 group and 37.6% (85/226) in the bevacizumab group. AEs ≥ grade 3 were similar in the IBI305 and bevacizumab groups [84.4% (189/224) vs. 89.8% (203/226), P=0.085]. CONCLUSIONS: IBI305 is similar to bevacizumab in terms of efficacy and safety. TRIAL REGISTRATION: Clinicaltrials.org Identifier: NCT02954172. Registered on 3 November 2016. Https://clinicaltrials.gov/.

Characterizing dispersion quality of polymer nanocomposite (PNC) is as important as dispersing nanosized fillers in the polymer matrix. In this study, to quantify the dispersion quality of PNCs, we...