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Postoperative cognitive dysfunction (POCD) affects the outcome of millions of patients each year. Aging is a risk factor for POCD. Here, we showed that surgery induced learning and memory dysfunction in adult mice. Transplantation of feces from surgery mice but not from control mice led to learning and memory impairment in non-surgery mice. Low intensity exercise improved learning and memory in surgery mice. Exercise attenuated surgery-induced neuroinflammation and decrease of gut microbiota diversity. These exercise effects were present in non-exercise mice receiving feces from exercise mice. Exercise reduced valeric acid, a gut microbiota product, in the blood. Valeric acid worsened neuroinflammation, learning and memory in exercise mice with surgery. The downstream effects of exercise included attenuating growth factor decrease, maintaining astrocytes in the A2 phenotypical form possibly via decreasing C3 signaling and improving neuroplasticity. Similar to these results from adult mice, exercise attenuated learning and memory impairment in old mice with surgery. Old mice receiving feces from old exercise mice had better learning and memory than those receiving control old mouse feces. Surgery increased blood valeric acid. Valeric acid blocked exercise effects on learning and memory in old surgery mice. Exercise stabilized gut microbiota, reduced neuroinflammation, attenuated growth factor decrease and preserved neuroplasticity in old mice with surgery. These results provide direct evidence that gut microbiota alteration contributes to POCD development. Valeric acid is a mediator for this effect and a potential target for brain health. Low intensity exercise stabilizes gut microbiota in the presence of insult, such as surgery.

A single-crystal islands (SCI) technique using low thermal budget pulse laser process is proposed and demonstrated to fabricate single-crystal silicon islands over amorphous dielectric for monolithic 3-D and back-end-of-line (BEOL) FinFET circuits. By laser recrystallizing mask-defined a-Si islands encapsulated with conformal silicon nitride film, designed single-crystal Si islands can be obtained. The single crystallinity of the island are verified with SECCO Etch, high-resolution electron microscopy (HREM), transmission electron microscopy (TEM), and electron backside scattering (EBSD). About 40 nm FinFETs were successfully fabricated in the SCI Si islands and shown to exhibit excellent electrical performance and low variability that are compatible with the FinFETs fabricated on commercial silicon-on-insulator (SOI) wafer.

Solid supported or ligand capped gold nanomaterials (AuNMs) emerged as versatile and recyclable heterogeneous catalysts for a broad variety of conversions in the ongoing catalytic ′gold rush′. Existing at the border of homogeneous and heterogeneous catalysis, AuNMs offer the potential to merge high catalytic activity with significant substrate selectivity. Owing to their strong binding towards the surface atoms of AuMNs, NHCs offer tunable activation of surface atoms while maintaining selectivity and stability of the NM even under challenging conditions. This work summarizes well‐defined catalytically active NHC capped AuNMs including spherical nanoparticles and atom‐precise nanoclusters as well as the important NHC design choices towards activity and (stereo‐)selectivity enhancements., NHC stabilized gold nanomaterials are emerging as a promising material for catalysis, and this report aims to introduce them and review the current state of art.

Increasing the work function of borophene over a large range is crucial for the development of borophene-based anode materials for highly efficient electronic devices. In this study, the effect of fluorine adsorption on the structures and stabilities, particularly on the work function, of α-borophene (BBP), was systematically investigated via first-principles density functional theory. The calculations indicated that BBP was well-stabilized by fluorine adsorption and the work functions of metallic fluorine-adsorbed BBPs (Fn-BBPs) sharply increased with increasing fluorine content. Moreover, the work function of F-BBP was close to that of the frequently used anode material Au and even, for other Fn-BBPs, higher than that of Pt. Furthermore, we have comprehensively discussed the factors, including substrate deformation, charge transfer, induced dipole moment, and Fermi and vacuum energy levels, affecting the improvement of work function. Particularly, we have demonstrated that the charge redistribution of the substrate induced by the bonding interaction between fluorine and the matrix predominantly contributes to the observed increase in the work function. Additionally, the effect of fluorine adsorption on the increase in the work function of BBP was significantly stronger than that of silicene or graphene. Our results concretely support the fact that Fn-BBPs can be extremely attractive anode materials for electronic device applications.

In order to improve the biological activities of polysaccharides from Enteromorpha prolifra (EP), the crude EP was degraded in the presence of pectinase and glucoamylase. The reaction conditions for the hydrolysis of EP were optimized as: hydrolysis temperature 45.2 °C, total enzyme concentration 48.5 U/mL, with an activity ratio of pectinase to glucoamylase 3.4:1, pH 4.5, degradation time 3 h. In vitro antioxidant activity of the enzymatic degraded polysaccharides from E. prolifra (EEP) obtained under the optimal conditions was significantly improved when compared to that of EP. The IC50 values of EEP to scavenge DPPH, hydroxyl and superoxide anion radicals were found to be 3.31, 3.02 and 3.90 mg/mL, respectively, while those values for EP were 19.57, 5.96 and 5.51 mg/mL, respectively. At 5 mg/mL, the ferric iron reducing power of EEP was 1.41 times higher than that of EP; the ferrous chelating ability of EEP was 89.6%, being much than that of EP (54.9%). Furthermore, EEP was found to have stronger tyrosinase inhibitory effects than EP. At 3.0 mg/mL, the inhibition rates of EEP on monophenolase and diphenolase activity of mushroom tyrosinase were measured as 32.7% and 39.1%, respectively, while those values for EP were 16.3% and 21.1%, respectively. The inhibition of EEP on diphenolase activity of mushroom tyrosinase was reversible and of competitive-uncompetitive mixed-type. EEP prepared in this study may find application in food industry and cosmetics.

For nanofibrous aerogels, a three-dimensional porous structure with interwoven nanofibers as a pore wall has become an urgent demand, and it remains to be a challenge to ensure the mechanical stability and thermal insulation. Other than the reported nanofiber as raw materials to generate three-dimensional cellular nanofibrous aerogels, an alternative low-cost and facile procedure has been proposed here via tactfully utilizing polymer sponge as a template attached with reactive particles, followed by a carbothermal reduction process to realize nanowire growth and their replacement of the original framework. The resulting spongy aerogels with numerous interlaced SiC/Si3N4 nanowires as a skeleton exhibit an ultrahigh porosity of 99.79%. Meanwhile, compressive elasticity after a compression at strain of 35% for 400 cycles, a low thermal conductivity of 23.19 mW/(m K), an excellent absorption capacity of 33.9-95.3 times for varied organic solvents removal, along with flexibility in shape design favored by the initial organic sponge make this nanofibrous aerogel an ideal material for heat shielding, absorption, or catalyst support.

Homologous recombination (HR) repairs DNA double-strand breaks (DSBs) in the S and G2 phases of the cell cycle1–3. Several HR proteins are preferentially recruited to DSBs at transcriptionally active loci4–10, but how transcription promotes HR is poorly understood. Here we develop an assay to assess the effect of local transcription on HR. Using this assay, we find that transcription stimulates HR to a substantial extent. Tethering RNA transcripts to the vicinity of DSBs recapitulates the effects of local transcription, which suggests that transcription enhances HR through RNA transcripts. Tethered RNA transcripts stimulate HR in a sequence- and orientation-dependent manner, indicating that they function by forming DNA–RNA hybrids. In contrast to most HR proteins, RAD51-associated protein 1 (RAD51AP1) only promotes HR when local transcription is active. RAD51AP1 drives the formation of R-loops in vitro and is required for tethered RNAs to stimulate HR in cells. Notably, RAD51AP1 is necessary for the DSB-induced formation of DNA–RNA hybrids in donor DNA, linking R-loops to D-loops. In vitro, RAD51AP1-generated R-loops enhance the RAD51-mediated formation of D-loops locally and give rise to intermediates that we term ‘DR-loops’, which contain both DNA–DNA and DNA–RNA hybrids and favour RAD51 function. Thus, at DSBs in transcribed regions, RAD51AP1 promotes the invasion of RNA transcripts into donor DNA, and stimulates HR through the formation of DR-loops. RNA transcripts stimulate homologous recombination through the formation of DR-loops, intermediate structures that contain both DNA–DNA and DNA–RNA hybrids.

Background Cardiac fibrosis will increase wall stiffness and diastolic dysfunction, which will eventually lead to heart failure. Asenapine maleate (AM) is widely used in the treatment of schizophrenia. In the current study, we explored the potential mechanism underlying the role of AM in angiotensin II (Ang II)-induced cardiac fibrosis. Methods Cardiac fibroblasts (CFs) were stimulated using Ang II with or without AM. Cell proliferation was measured using the cell counting kit-8 assay and the Cell-Light EdU Apollo567 In Vitro Kit. The expression levels of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were detected using immunofluorescence or western blotting. At the protein level, the expression levels of the components of the transforming growth factor beta 1 (TGFβ1)/mitogen-activated protein kinase (MAPK) signaling pathway were also detected. Results After Ang II stimulation, TGFβ1, TGFβ1 receptor, α-SMA, fibronectin (Fn), collagen type I (Col1), and collagen type III (Col3) mRNA levels increased; the TGFβ1/MAPK signaling pathway was activated in CFs. After AM pretreatment, cell proliferation was inhibited, the numbers of PCNA -positive cells and the levels of cardiac fibrosis markers decreased. The activity of the TGFβ1/MAPK signaling pathway was also inhibited. Therefore, AM can inhibit cardiac fibrosis by blocking the Ang II-induced activation through TGFβ1/MAPK signaling pathway. Conclusions This is the first report to demonstrate that AM can inhibit Ang II-induced cardiac fibrosis by down-regulating the TGFβ1/MAPK signaling pathway. In this process, AM inhibited the proliferation and activation of CFs and reduced the levels of cardiac fibrosis markers. Thus, AM represents a potential treatment strategy for cardiac fibrosis.

Solid polymer electrolytes with relatively low ionic conductivity at room temperature and poor mechanical strength greatly restrict their practical applications. Herein, we design semi-interpenetrating network polymer (SNP) electrolyte composed of an ultraviolet-crosslinked polymer network (ethoxylated trimethylolpropane triacrylate), linear polymer chains (polyvinylidene fluoride-co-hexafluoropropylene) and lithium salt solution to satisfy the demand of high ionic conductivity, good mechanical flexibility, and electrochemical stability for lithium metal batteries. The semi-interpenetrating network has a pivotal effect in improving chain relaxation, facilitating the local segmental motion of polymer chains and reducing the polymer crystallinity. Thanks to these advantages, the SNP electrolyte shows a high ionic conductivity (1.12 mS cm-1 at 30 °C), wide electrochemical stability window (4.6 V vs. Li+ /Li), good bendability and shape versatility. The promoted ion transport combined with suppressed impedance growth during cycling contribute to good cell performance. The assembled quasi-solid-state lithium metal batteries (LiFePO4 /SNP/Li) exhibit good cycling stability and rate capability at room temperature.

Graphite anode materials are widely used in commercial lithium-ion batteries; however, the long electron/ion transportation path restricted its high energy storage. In this experiment, we designed a copper/graphite composite with a dual three-dimensional (3D) continuous porous structure combining used nonsolvent-induced phase separation and heat treatment, in which a large amount of graphite is embedded in the 3D porous copper/carbon architecture. In the novel structure, not only the electron and Li+ transmission performances are improved, but also the space of current collector is fully utilized. Meanwhile, carbonized polyacrylonitrile network stabilizes the interface between graphite and copper matrix. The obtained copper/graphite composite anode has an initial discharge capacity of 524.6 mAh·g−1, a holding capacity of 350 mAh·g−1 and excellent cycle stability (299.3 mAh·g−1 after 180 cycles at 0.1C rate), exhibiting good electrochemical performance. The experimental results show that the mass loading of the copper/graphite composite electrode material is about 4.39 mg·cm−2. We also envisage replacing graphite with other high-capacity active materials to fill the current collector, which can provide a reference for the future development of next-generation advanced electrodes.

This letter reports the fabrication of polycrystalline silicon (poly-Si) tunneling field effect transistors (Tunneling FETs) using green nanosecond laser crystallization (GLC). During the GLC process, the Si is full-melted by laser scanning, hence the recrystallized poly-Si thin films with grain size as large as $1.2~\mu \text{m}$ are attained. This makes it possible to fabricate tunneling FET with high-quali ty poly-Si thin films. Compare with the tunneling FETs fabricated by solid phase crystallization (SPC), the ones via GLC show better subthreshold swing (S.S) of 418 mV/dec. and larger on/off ratio of $6.02 \times 10^{5}$ . Moreover, the activation energy curve is also presented to further demonstrate the con nection between device performance and crystallinity of poly-Si thin films.

Nitrosoarenes (ArNOs) are toxic metabolic intermediates that bind to heme proteins to inhibit their functions. Although much of their biological functions involve coordination to the Fe centers of hemes, the factors that determine N-binding or O-binding of these ArNOs have not been determined. We utilize X-ray crystallography and density functional theory (DFT) analyses of new representative ferrous and ferric ArNO compounds to provide the first theoretical insight into preferential N-binding versus O-binding of ArNOs to hemes. Our X-ray structural results favored N-binding of ArNO to ferrous heme centers, and O-binding to ferric hemes. Results of the DFT calculations rationalize this preferential binding on the basis of the energies of associated spin-states, and reveal that the dominant stabilization forces in the observed ferrous N-coordination and ferric O-coordination are dπ–pπ* and dσ–pπ*, respectively. Our results provide, for the first time, an explanation why in situ oxidation of the ferrous-ArNO compound to its ferric state results in the observed subsequent dissociation of the ligand.

In this paper, we report a 1.84 kV GaN-on-GaN Schottky barrier diode (SBD) corresponds to a low on-resistance of 1.98 mΩ-cm2. The GaN epi-layer was etched to the multi-fins-structure with optimized bevel angle. The fins structure enables to improve the breakdown voltage by means of the uniforme electric field distribution. Afterwards, the GaN fins were capped by atomic layer deposition (ALD)-grown AlN film. The AlN served as a tunneling-barrier layer, which not only passivated the GaN surface but also decreased the turn-on voltage. The AlN-capped SBD shows a turn-on voltage at 0.18 V. Furthermore, the temperature-dependent transfer characteristics suggest the different current tunneling mechanisms at low and high electric field conditions, respectively. The time-dependent dielectric breakdown (TDDB) measurement suggests the surface traps were well passivated by ALD-AlN, which implies that the AlN cap-layer enables to improve the device reliability.

A practical electrophilic aminoselenation of O-homoallyl benzimidate with diselenides promoted by PhICl2/Cu2O has been developed. The easily available and stable diselenides were used as selenium sources. Various selenyl 1,3-oxazines, which are important frameworks in medicinal and biological chemistry, were easily obtained in moderate to good yields for the first time. Easy scaleup and scalability make this method attractive for the preparation of other valuable organoselenides.

Operation characteristics of polycrystalline germanium (poly-Ge) tri-gate junctionless (JL) charge-trapping (CT) flash memory devices with stacked tunneling layer were studied in this work. The programming speeds of poly-Ge tri-gate JL flash device with GeOx/Al2O3/SiO2 tunneling layer are faster than those with GeOx/Al2O3 or GeOx/SiO2 ones, thanks to the modified electric field in the tunneling layer. Better retention characteristics are also achieved due to a larger barrier height and physical thickness, because Ge diffusion is effectively suppressed by adding an Al2O3 between GeOx and SiO2, which can improve the quality of tunneling layer. A poly-Ge CT flash device fabricated with low-temperature process is promising for embedded memory in Ge CMOS or 3D IC.

Indirect selective laser sintering (SLS) was combined with reactive melt infiltration (RMI) to fabricate RB-SiC, and the effects of preform impregnation with different carbon source on the carbonized sample and final RB-SiC were investigated. Results show that the impregnation treatment led to increased bulk density and mechanical strength of samples at all stages. The pore size dwindled and the porosity decreased significantly for the carbonized sample, and the content of Si reduced for the final RB-SiC. The impregnation with PF resin containing 30 % nano carbon black (PFnanoC) seems more promising for the comprehensive properties improvement, the final RB-SiC had a relatively fewer amount of residual pore and carbon and showed superior mechanical properties compared with those of sample impregnated with only PF resin. Kinetics analysis indicates a slower pore-clogging rate under the PFnanoC impregnation condition, which avoided or hindered a too-early infiltration cease during the RMI process.

N‐heterocyclic carbenes (NHCs) have received significant attention as gold nanoparticle stabilizers due to their strong binding affinity towards gold. However, their tunability is limited by the difficulty in obtaining nonsymmetric NHCs. In this regard, N‐acyclic carbenes (NACs) are attractive alternatives due to their high synthetic versatility, allowing easy tuning of their steric and electronic properties towards specific applications. This work reports the first series of stable and monodisperse NAC‐functionalized gold nanoparticles. These particles with sizes ranging 3.8 to 11.6 nm were characterized using NMR, UV/Vis and TEM. The nanoparticles display good stability at elevated temperatures and for extended periods both dried or dispersed in a medium, as well as in the presence of exogenous thiols. Importantly, these NAC‐stabilized gold nanoparticles offer a promising and versatile alternative to NHC‐stabilized gold nanoparticles., Gold: N‐acyclic carbenes (NACs) have been shown to function as versatile ligand alternatives to N‐heterocyclic carbenes in the synthesis of a new series of stable plasmonic gold nanoparticles. The ease of preparing nonsymmetric NAC ligands and their synthetic tunability renders them especially attractive as gold nanoparticle stabilizers and opens up new possibilities in the design of gold nanoparticles for user‐specified functions (see figure).

The operation characteristics of polycrystalline Si (poly-Si) gate-all-around (GAA) junctionless (JL) charge-trapping (CT) flash memory devices with the Zr-based stacked trapping layer were studied in this work. Devices with the Si3N4/ZrO2 stacked trapping layer show enhanced erasing speeds and comparable retention characteristics in comparison to Si3N4/HfO2 due to many shallow energy traps and smaller valance band offset in the ZrO2 layer. By inserting Al2O3 between Si3N4 and ZrO2 trapping layer, the retention and endurance characteristics are improved. The erasing speed can be further improved by a Zr-rich oxide layer near the tunneling oxide since the energy barrier can confine more injected electrons near the tunneling oxide. The retention characteristic can be improved without sacrificing the erasing speed because some of the shallow traps can be passivated by NH3 plasma treatment on ZrO2. Hence, the ZrO-based stacked trapping layer is very promising for the poly-Si GAA JL CT flash devices for nonvolatile memory applications.

This study aimed to optimize the microencapsulation method for a functional oil using high amylose corn starch (HACS) and assessed its structure and antioxidant capacity. The results showed that the optimal microencapsulation condition is achieved by using 28.5% of functional oil, 15.75% of HACS, and 57.86% of proportion of monoglyceride in emulsifier with 94.86% microencapsulation efficiency. Scanning electron microscopy and particle size measurement showed that the functional oil microcapsules were uniform size, smooth surface, spherical shape, and without cracks in the wall of the capsules. In vitro oil release of microencapsulates results showed that microencapsulated functional oil containing HACS has a better sustained release effect. The microcapsules containing HACS exhibited a lower lipid oxidation rate during storage. In conclusion, microencapsulation of HACS as wall material improved the stability of functional oil and this formulation of microcapsules was satisfactorily applied in powdered food for diabetic patients., Function oil microcapsules could be produced using high amylose corn starch as a wall material. Addition of high amylose corn starch does not affect the efficiency of microencapsulation. The release of function oil can be controlled by adding high amylose corn starch.

A highly efficient electrophilic oxyselenation of propargylic amines with diselenides and CO2 under atmospheric pressure promoted by copper/DTBP is reported. Various biologically important selenyl ...

To investigate the effect of ALA intake on blood lipid profiles, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein (VLDL-C) and ratio of TC to HDL-C. We systematically searched randomized controlled trials of ALA intervention on PubMed, Embase, Cochrane library and related references up to March 2018. The final values were calculated as weighted mean difference (WMD) by using a random effects model. Subgroup analysis and meta-regression were used to explore the source of heterogeneity. Generalized least square was performed for dose-response analysis. Forty-seven studies with 1305 individuals in the ALA arm and 1325 individuals in the control arm were identified. Compared with control group, dietary intake of ALA significantly reduced the concentrations of TG (WMD -0.101 mmol/L; 95% CI: -0.158 to -0.044 mmol/L

Immune thrombocytopenia (ITP) is a common hematological autoimmune disease, in which defective mesenchymal stem cells (MSCs) are potentially involved. Our previous study suggested that MSCs in ITP patients displayed enhanced apoptosis. MicroRNAs (miRNAs) play important roles in ITP by affecting megakaryopoiesis, platelet production and immunoregulation, whereas the roles of miRNAs in ITP-MSCs remain unknown. In a previous study, we performed microarray analysis to obtain mRNA and miRNA profiles of ITP-MSCs. In the present study, we reanalyze the data and identify miR-98-5p as a candidate miRNA contributing to MSC deficiency in ITP. miR-98-5p acts through targeting insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and the subsequent downregulation of insulin-like growth factor 2 (IGF-2) causes inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which is involved in the process of MSC deficiency. Furthermore, miR-98-5p upregulates p53 by inhibiting β-transducin repeat-containing protein (β-TrCP)-dependent p53 ubiquitination. Moreover, miR-98-5p overexpression impairs the therapeutic effect of MSCs in ITP mice. All-trans retinoic acid (ATRA) protects MSCs from apoptosis by downregulating miR-98-5p, thus providing a potential therapeutic approach for ITP. Our findings demonstrate that miR-98-5p is a critical regulator of ITP-MSCs, which will help us thoroughly understand the pathogenesis of ITP., Graphical Abstract, Immune thrombocytopenia (ITP) is a common hematological autoimmune disease, in which defective mesenchymal stem cells (MSCs) are potentially involved. Previous studies suggested that MSCs in ITP patients displayed enhanced apoptosis. Zhang and colleagues performed microarray analysis of ITP-MSCs and identified miR-98-5p as a candidate miRNA contributing to MSC deficiency in ITP. Further experiments were conducted, revealing that miR-98-5p exerts a pro-apoptotic effect through targeting IGF2BP1, and the resulting IGF-2/PI3K pathway inhibition and p53 accumulation are involved in ITP-MSC apoptosis.

Personalized zirconium dioxide (ZrO2) all-ceramic teeth are expected to be widely used in the field of oral restoration. Here, ZrO2 all-ceramic teeth were fabricated for biological engineering by photosensitive resin based digital light processing (DLP) technology. When sintered at 1500 °C for 3 h, dense ZrO2 ceramics were obtained with relative density of 98.02 ± 0.32%, Vickers hardness of 12.62 ± 0.15 GPa and fracture toughness of 6.11 ± 0.36 MPa∙m1/2, which were close to those of the ZrO2 ceramics prepared by dry pressing. To confirm whether the prepared ZrO2 ceramics possessed good biosafety, in vitro biological experiments were further performed with rat bone marrow mesenchymal stem cells (rBMSCs) and preferable cell attachment was observed at the initial stages. Results illustrated that the compositions with cytotoxicity in green samples were completely decomposed after debinding and sintering process, and the ZrO2 ceramics could provide an ideal biocompatible environment for mesenchymal stem cells. This study shows that ZrO2 all-ceramic teeth with personalized structure prepared by DLP technology have good mechanical properties and biocompatibility, exhibiting strong potential in the field of oral restoration.

Circulating miRNAs are promising liquid biopsy biomarkers for noninvasive cancer detection. However, detection of subtle, but meaningful differences in circulating miRNA quantities between diseased and healthy samples remains a key challenge in clinical settings because biomarker signal/noise ratios are often low. Because extracellular vesicles (EVs) are key sources of circulating miRNAs in serum, it was hypothesized that isolating EVs would enrich miRNA biomarkers, leading to enhanced diagnostic ability and improved biomarker performance. This research assessed the performance of EV-miRNAs against serum miRNAs as biomarkers for gastric cancer (GC). It was first determined that polymer-based precipitation (PBP) gave the highest EV-miRNA recovery when compared with ultracentrifugation, column affinity, peptide affinity, and immunobead affinity EV purification. Four PBP reagents were used to isolate EV-miRNAs from 15 GC and 15 healthy controls and 133 GC-related miRNAs were profiled from EV fractions and total serum using real-time quantitative PCR. A PBP reagent that generated the most EV-miRNA biomarkers was selected and used to validate 11 EV-miRNAs in an independent set of 20 GC and 20 controls. Eight of these EV-miRNA biomarkers were found to give better GC detection accuracy (area under the curve, approximately 0.8). Overall, data suggest that EV miRNAs can improve GC detection performance compared with serum miRNAs and led to the identification of eight EV-miRNAs as potential noninvasive biomarkers for GC.

Waterborne polyurethane (WPU) is a new type of polyurethane system, which using water instead of organic solvent as dispersing medium. Because of its non-toxicity and environmental safety, WPU is considered as the development direction of coatings and adhesives. However, the mechanical properties of WPU are worse than that of solvent-based polyurethane, therefore, the modification of WPU has received increasingly attention. Meanwhile numerous evidences demonstrate the excellent properties of cellulose nanofibers (CNFs) such as high aspect ratio, low weight and outstanding mechanical strength. Therefore, there is a high expectation for CNFs to be introduced into WPU as reinforcing filler. In this work, a series of CNFs/WPU nanocomposite films were prepared by solution blending. The structure, morphology, thermal behavior and mechanical properties were investigated. SEM results showed that CNFs were evenly dispersed in the WPU matrix. Tensile tests indicated that the modulus and tensile strength of CNFs/WPU nanocomposite films were improved compared with the neat film. While the break elongation of the nanocomposite films decreased with the increase of CNFs content. The synergistic interaction between CNFs and WPU matrix plays an important role in the enhancement of mechanical properties.

The aim of this study was to examine the antioxidant capacity of Trypsin-hydrolyzed corn silk proteins, specifically radical scavenging, ferric reducing and anti-lipid peroxidation activities, as well as stability after heating and simulated gastrointestinal digestion. Among the 1–5-h hydrolysates, the 1-h Trypsin hydrolysate (T1H) was the strongest. T1H exhibited stronger H2O2 [half maximal effective concentration (EC50) = 156.44 µg/mL] and superoxide (EC50 = 0.33 mg/mL) scavenging activities than glutathione, carnosine and N-acetylcysteine. Radical scavenging activities of T1H were heat-stable (25–100°C), although lost by 20–58% after gastrointestinal digestion. Ferric reducing activity of T1H was heat-stable, even enhanced by 20% after gastrointestinal digestion. Lecithin liposome assay found anti-lipid peroxidation activity of T1H resistant to gastrointestinal peptidases. By contrast, 100°C incubation reduced anti-lipid peroxidation activity of 0.5 mg/mL T1H to 3.5-fold lower than that of 25°C incubation. At 30 µg/mL, T1H (3% hemolysis) was stronger than glutathione (32% hemolysis) in protecting human red blood cells. T1H was 1.5-fold more potent than glutathione and carnosine in alleviating lipid peroxidation in the cells. Overall, T1H demonstrated strong, heat-stable radical scavenging activities, besides partial resistance to gastrointestinal peptidases. T1H was also hematoprotective. T1H is a promising antioxidant for the development of functional food ingredients and nutraceuticals.

A dearomative tandem spiro-cyclization reaction of N-[(1H-indol-3-yl)methyl]methacrylamide derivatives with sulfinate sodium in the presence of AgNO3 and K2CO3 is reported, which produced sulfonylated spiro[indole-3,3'-pyrrolidines] in medium to excellent yields. The characteristics of this transformation contain good functional group tolerance and ease of operation.

Potato resistant starch (RS) was prepared by microwave-toughening treatment (MTT). This study investigated the beneficial effects of RS on high-fat diet (HFD)-induced hyperlipidemia in C57BL/6J mice by evaluating changes in the gut microbiota. The mice were fed low-fat diet with corn starch, HFD with corn starch, HFD with potato starch (HFP), or HFD with RS (HFR) for 6 weeks. The results showed that the HFR group had lower body weight and total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels compared with the HFP group. Moreover, the brown adipose tissue levels of uncoupling protein 1 (UCP-1), β3-adrenoceptor (β3-AR), peroxisome proliferator-activated receptor-γ (PPAR-γ), and PPAR-γ coactivator-1α (PGC-1α) were increased. Our results showed that RS supplementation increased the Bacteroidetes/Firmicutes ratio and the abundance of short-chain fatty acid-producing Allobaculum, Ruminococcus, and Blautia. Our data suggest that RS prepared by MTT may be used as a prebiotic agent to prevent gut dysbiosis and obesity-related chronic diseases, such as hyperlipidemia, and obesity.

For high-volume manufacturing of 2-D transistors, area-selective chemical reaction deposition (CVD) growth is able to provide good-quality 2-D layers and may be more effective than exfoliation from bulk crystals or wet/dry transfer of large-area as-grown 2-D layers. We have successfully grown continuous and uniform WS2 film comprising around seven layers by area-selective CVD approach using patterned tungsten source/drain metals as the seeds. The growth mechanism is inferred and supported by the transmission electron microscope (TEM) images, as well. The first top-gate MOSFETs of CVD-WS2 channels on SiO x /Si substrates are demonstrated to have good short channel electrical characteristics: ON-/OFF-ratio of 106, a subthreshold swing of 97 mV/decade, and nearly zero drain-induced barrier lowering (DIBL).

A novel tetraphenylethylene-rhodamine-based fluorescent probe amide compound L was synthesized and its sensing properties of metal ions were investigated. It exhibited high sensitivity and high selectivity toward Fe3+ compared with other common metal ions in EtOH-H2O (50 μM, 3:2, V/V, pH 7.0). A fluorescence quenching ratio of 92% at 482 nm and 254-fold enhancement of fluorescence intensity at 582 nm were achieved upon the addition of 4.0 equiv. Fe3+. Under optimal experimental conditions, the fluorescence intensity of probe exhibited a dynamic response range for Fe3+ from 2.0 × 10−5 M to 1.5 × 10−4 M at 482 nm and 3.0 × 10−5 M to 1.5 × 10−4 M at 582 nm, respectively, with a detection limit of 1.56 × 10−7 M. Meanwhile, the binding ratio of L and Fe3+ was confirmed to be 1:1 by electrospray ionization-mass spectrometry (ESI-MS) analysis of L-Fe3+ complex and Benesi-Hildebrand method. According to 1H-nuclear magnetic resonance (NMR) titration and scanning electron microscopy results, the coordination mechanism of probe L with Fe3+ was further elucidated. The binding of Fe3+ to L not only led to the aggregation state dispersed and fluorescence quenching at 482 nm, but also induced spirolactum ring opening of rhodamine and aroused a 254 times fluorescence enhancement at 582 nm together with color variation from colorless to red purple. The developed sensor was successfully employed to determine Fe3+ ion in water samples and proved to be selective and sensitive.

Reactive oxygen species (ROS) inflict multiple types of lesions in DNA, threatening genomic integrity. How cells respond to ROS-induced DNA damage at telomeres is still largely unknown. Here, we show that ROS-induced DNA damage at telomeres triggers R-loop accumulation in a TERRA- and TRF2-dependent manner. Both ROS-induced single- and double-strand DNA breaks (SSBs and DSBs) contribute to R-loop induction, promoting the localization of CSB and RAD52 to damaged telomeres. RAD52 is recruited to telomeric R-loops through its interactions with both CSB and DNA:RNA hybrids. Both CSB and RAD52 are required for the efficient repair of ROS-induced telomeric DSBs. The function of RAD52 in telomere repair is dependent on its ability to bind and recruit POLD3, a protein critical for break-induced DNA replication (BIR). Thus, ROS-induced telomeric R-loops promote repair of telomeric DSBs through CSB–RAD52–POLD3-mediated BIR, a previously unknown pathway protecting telomeres from ROS. ROS-induced telomeric SSBs may not only give rise to DSBs indirectly, but also promote DSB repair by inducing R-loops, revealing an unexpected interplay between distinct ROS-induced DNA lesions.

A non-toxic and low-cost gelcasting system was successfully developed using agar as gelling agent to fabricate silicon nitride ceramic green bodies without cooling crosslink process, and silicon nitride ceramic was obtained by pressureless sintering. The effects of agar contents on rheological behavior of silicon nitride suspension, microstructure and mechanical properties of silicon nitride ceramics were investigated. The silicon nitride ceramic suspension with 45 vol% solid loading using 1.2 wt% ammonium polyacrylate (PAA-NH4) as dispersant was successfully prepared for gelcasting. After removing binder at 800 °C for 2 h and pressureless sintering at 1800 °C for 2 h, the silicon nitride ceramics exhibited homogeneous and interlocking microstructure composed of elongated β-Si3N4 phase, which contributes to its mechanical properties. With the increase of agar powder content from 0.25 wt% to 1.5 wt%, the shrinkage and flexural strength of the silicon nitride ceramics increased firstly and then decreased. When the agar powder content was 0.5 wt%, the silicon nitride ceramics had the optimized flexural strength (218 ± 25 MPa) with relative density of 92.85 ± 2.19% and the shrinkage of 16.03 ± 0.15%. Using agar as gelling agent to prepare silicon nitride ceramics by gelcasting is believed to be a novel and low-cost method, which could be used to prepare other high performance ceramics in the future.

Description, RGX-202, a small-molecule creatine transporter SLC6A8 inhibitor, suppresses colorectal cancer and modulates human creatine levels., Colorectal cancer (CRC) is a leading cause of cancer mortality. Creatine metabolism was previously shown to critically regulate colon cancer progression. We report that RGX-202, an oral small-molecule SLC6A8 transporter inhibitor, robustly inhibits creatine import in vitro and in vivo, reduces intracellular phosphocreatine and ATP levels, and induces tumor apoptosis. RGX-202 suppressed CRC growth across KRAS wild-type and KRAS mutant xenograft, syngeneic, and patient-derived xenograft (PDX) tumors. Antitumor efficacy correlated with tumoral expression of creatine kinase B. Combining RGX-202 with 5-fluorouracil or the DHODH inhibitor leflunomide caused regressions of multiple colorectal xenograft and PDX tumors of distinct mutational backgrounds. RGX-202 also perturbed creatine metabolism in patients with metastatic CRC in a phase 1 trial, mirroring pharmacodynamic effects on creatine metabolism observed in mice. This is, to our knowledge, the first demonstration of preclinical and human pharmacodynamic activity for creatine metabolism targeting in oncology, thus revealing a critical therapeutic target.

Background: It remains uncertain whether vitamin D3 (vitD3) supplementation is beneficial for remission of Crohn's disease (CD). The influence of vitD3 supplementation on Infliximab (IFX) effectiveness was analyzed in Chinese CD patients.Methods: In this retrospective cohort study, moderate-to-severe CD patients, who were bio-naïve and prescribed with IFX treatment for at least 54 weeks, were recorded from January 2014 to December 2019. VitD3 supplementation was defined as patients additionally took oral vitD3 (125 IU/d) within 3 days after the first infusion and persisted in the whole follow-up period. Disease activity was assessed using Harvey-Bradshaw Index (HBI). Serum cytokine profiles (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were quantitatively analyzed in a subset of all patients at baseline and 54-week after intervention.Results: Among 73 enrolled patients, 37 took vitD3 regularly (D3-patients), the others (non-D3-patients) did not. At 54-week, the mean 25-hydroxyvitaminD level increased in D3-patients (20.33 vs. 15.07 ng/mL, P < 0.001). The clinical remission rate was higher in D3-patients compared to non-D3-patients (83.8 vs. 61.6%, P = 0.030). The decrease of HBI from baseline to 54-week was more in D3-patients than non-D3-patients (7.41 ± 3.0 vs. 6.28 ± 2.75, P = 0.023). Furthermore, vitD3 supplementation was independently related to the increase of remission rate at 54-week in D3-patients (β = −1.667, P = 0.015). The benefit of vitD3 supplementation was significant only in patients with deficient vitD3 (all P < 0.05), but not in non-deficient vitD3. A total of nine patients (four non-D3-patients and five D3-patients) were selected to determine serum cytokine profiles after 54-week IFX treatment. In non-D3-patients, the decreases of TNF-α and IL-6 at 54-week were more obvious than at baseline (P = 0.032, 0.022, respectively). In D3-patients, however, only IL-10 increased at 54-week compared with its baseline value (P = 0.037).Conclusions: VitD3 supplementation could improve IFX effectiveness in CD patients, especially for patients with vitD3 deficiency. This beneficial effect of vitD3 supplementation probably arose from the up-regulation of IL-10.Trial Registration: NCT04606017.

Soluble Klotho (sKL) is closely related to insulin resistance, which is a major factor in the progression of diabetic cardiomyopathy (DCM). The purpose of this study was to investigate the role of sKL in the regulation of DCM and the mechanism involved. A mouse model of type 2 diabetes was induced by high-fat diet and streptozotocin injection. An insulin-resistant cardiac fibroblast model was established by high glucose and high insulin. KL gene overexpression was achieved in vivo and vitro through transfection with an adenovirus-harboring KL-cDNA. Gene overexpression was used to evaluate the role of sKL in the pathophysiologic characteristics of DCM. Insulin-resistant cardiac fibroblasts reduced sKL expression and collagen deposition. Diabetic mice constructed by streptozotocin exhibited severe insulin resistance, inflammation, fibrosis, left ventricular dysfunction, and sKL downregulation. The overexpression of sKL mitigated insulin resistance and metabolic disturbance; inflammation, fibrosis, and upregulated collagen I/III content ratio in diabetic state were significantly reduced. Our findings were accompanied by notable moderation of cardiac function. Further, blunted phosphorylation of Akt was restored with sKL gene overexpression, and activated phosphorylation of extracellular signal-regulated kinase 1/2 in DCM was reduced. Our results suggest that sKL protein overexpression exerts a defensive measure by ameliorating selective insulin resistance in mouse DCM, thus revealing its underlying mechanism for potential human DCM treatment.

Dopant-free carrier selective contacts have garnered significant interest for the development of high-efficiency silicon solar cells due to their low-temperature processing and suppression of free-carrier absorption. In this work, we investigate thermally-evaporated molybdenum oxides (MoO x ) functioning as a hole-selective contact (HSC) for silicon heterojunction (Si HJT) solar cells. The high work function of MoO x results in upward energy band bending at the MoO x /n-type Si interface, which facilitates the hole transport and blocks the electron. We compare the optical properties of MoO x with different thickness settings of 3, 10, and 15 nm, where the optical bandgap is fitted via the tauc plot and ranging between 3.46, 3.44, and 3.42 eV, respectively. The absorption spectra of MoO x , MoO x with an intrinsic amorphous silicon (a-Si(i)) layer, and sputtered tin-doped indium oxides (ITO) are also presented. The transmission electron microscopy further reveals a 2.8nm-thick silicon oxides layer in between the MoO x and silicon interface. Preliminary results show that the Si HJT cell with a 15 nm-thick MoO x layer achieves a power conversion efficiency (PCE) of 20.3% and an open-circuit voltage (Voc) of 651.9mV, possibly limited by the pyramidal surface morphology and the a-Si(i) interface passivation layer.

Nicotine contained in traditional cigarettes, hookahs, and e-cigarettes is an important risk factor for cardiovascular disease. Our previous study showed that macroautophagic flux impairment occurred under nicotine stimulation. However, whether nicotine influences mitochondrial dynamics in neonatal rat ventricular myocytes (NRVMs) is unclear. The purpose of this study was to explore the effects and potential mechanism of nicotine on mitophagy, mitochondrial dynamics, apoptosis, and the relationship between these processes in NRVMs. Our results showed that nicotine exposure increased mitochondria-derived superoxide production, decreased mitochondrial membrane potential, and impaired PINK1/Parkin-mediated mitophagic flux in NRVMs. Interestingly, nicotine significantly promoted dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and suppressed mitofusin (MFN)-mediated fusion, which was also observed in the bafilomycin A1-treated group. These results suggest that mitophagic flux impairment may contribute to Drp-1-mediated mitochondrial fission. Finally, nicotine caused excessive mitochondrial fission and contributed to apoptosis, which could be alleviated by mdivi-1, an inhibitor of Drp1. In addition to CTSB, as we previously reported, the enzyme activity of cathepsin L (CTSL) was also decreased in lysosomes after stimulation with nicotine, which may be the main cause of the hindered mitophagic flux induced by nicotine in NRVMs. Pretreatment with Torin 1, which is an inhibitor of mTOR, activated CTSL and ameliorated nicotine-induced mTOR activation and mitophagy impairment, decreased mitochondria-derived superoxide production, and blunted mitochondrial fission and apoptosis. Pretreatment with the ROS scavenger N-acetyl-cysteine (NAC) or inhibitors of p38 and JNK, which could also alleviate mitophagy impairment, exhibited similar effects as Torin1 on mitochondria. Taken together, our study demonstrated that nicotine treatment may lead to an increase in Drp1-mediated mitochondrial fission by blocking mitophagic flux by weakening the enzyme activity of CTSL and activating the ROS/p38/JNK signaling pathway. Excessive mitochondrial fission induced by nicotine ultimately leads to apoptosis. Torin1 restored the decreased CTSL enzyme activity by removing excessive ROS and alleviated the effects of nicotine on mitophagic flux, mitochondrial dynamics, and apoptosis. These results may provide new evidence on the relationship between mitophagic flux and mitochondrial dynamics and new perspectives on nicotine’s effects on mitochondrial dynamics in cardiomyocytes.

This study aims to construct a high-temperature-resistant microbial consortium to effectively degrade oily food waste by Fed-in-situ biological reduction treatment (FBRT). Oil degrading bacteria were screened under thermophilic conditions of mineral salt medium with increased oil content. The oil degradation and emulsification ability of each stain was evaluated and their synergetic improvement was further confirmed. Consortium of Bacillus tequilensis, Bacillus licheniformis, Bacillus sonorensis and Ureibacillus thermosphaericus was selected and applicated as bacterial agents in FBRT under 55 °C. Changes in pH, moisture, bacterial community and key components of food waste were monitored for 5 days during processing. Facilitated by the bacterial consortium, FBRT gave superior total mass reduction (86.61 ± 0.58% vs. 67.25 ± 1.63%) and non-volatile solids reduction (65.91 ± 1.53% vs. 28.53 ± 2.29%) compared with negative control, the feasibility and efficiency of present FBRT providing a promising in-situ disposal strategy for rapid reduction of oily food waste.

Background Berberine (BBR) from the widely used Chinese herbal medicine Huanglian has an array of pharmacological and biochemical properties, including anti-neoplastic activity. However, the specific mechanisms underlying these properties are unknown. The aim of this study was to explore the anti-tumor mechanisms of BBR in non-small cell lung cancer (NSCLC). Methods The effects of BBR on NSCLC tumor development and programmed cell death were investigated both in vivo and in vitro. Luciferase reporter assays were used to determine whether tissue factor (TF) was a target of miR-19a. Results BBR suppressed NSCLC growth and promoted apoptosis in NSCLC cells by modulating miR-19a and TF expression. Luciferase assays showed that TF was a direct inhibitory target of miR-19a in NSCLC cells. BBR induced apoptosis through the miR-19a/TF/MAPK axis. Conclusion The results suggest that BBR induces apoptosis of NSCLC cells via the miR-19a/TF/MAPK signaling pathway.

In this work, carbon quantum dots (C-dots) was successfully synthesized by hydrothermal treatment using dried leaves as green precursor for metal sensing. The performance of C-dots when detecting metal ions in water will be evaluated by testing with different types of metal stock solutions. Quenching effect of fluorescence C-dots solution was observed in the presence of different metal ions. C-dots is more selective towards Fe3+ compared to other metal ions.