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Ab initio calculations have been carried out to investigate the adsorption, dissociation, and diffusion of atomic and molecular hydrogen on the Fe-doped ZrCo (110) surface. It is found that the adsorption of H2 on doped surface seems thermodynamically more stable with more negative adsorption energy than that on the pure surface, and the dissociation energy of H2 on doped surface is much bigger therefore. However, compared with the pure system, there are fewer adsorption sites for spontaneous dissociation. After dissociation, the higher hydrogen adsorption strength sites would promote the H atom diffusion towards them where they can permeate into the bulk further. Furthermore, the ZrCo (110) surface possesses much higher hydrogen permeability and lower hydrogen diffusivity than its corresponding ZrCo bulk. Moreover, further comparison of the present results to analogous calculations for pure surface reveals that the Fe dopant facilitates the H2 molecule dissociation. Unfortunately, this does not improve the hydrogen storage performance of ZrCo alloy due to the H atom diffusion on the surface and into bulk are prevented with higher reaction energetic barriers by doping Fe. Consequently, ZrCo (110) surface modified with Fe atoms should not be preferred as a result of its terrible hydrogen permeability. A clear and deep comprehending of the inhibiting effect of Fe dopant on the hydrogen storage of ZrCo materials from the perspective of the surface adsorption of hydrogen are obtained from the present results.

Polysaccharides are good chelating agents for metal ions, which are often used to synthesize polysaccharide metal ion complexes. With carboxymethyl pachymaran (CMP) as the substrate, carboxymethyl pachymaran iron (CMPF), carboxymethyl pachymaran selenium (CMPS), and carboxymethyl pachymaran zinc (CMPZ) were synthesized by response surface methodology, and their biological characteristics were studied. The results showed that the CMP was a β‐polysaccharide, and the degree of carboxymethylation was 0.6352. The polysaccharide metal ion complexes were characterized by physicochemical methods, scanning electron microscopy, Fourier transform infrared spectroscopy, circular dichroism spectroscopy, and nuclear magnetic resonance spectroscopy. All the polysaccharides and complexes possessed antioxidant activity in vitro with scavenging activities to ABTS, superoxide anions, and ferrous ions. CMPF, CMPS, and CMPZ caused significant inhibition of A2780 cell proliferation, promoted the production of reactive oxygen species, and induced apoptosis in a human ovarian cancer cell line (A2780 cells). These results suggest that the CMP complex may be an effective candidate drug for cancer treatment in the field of functional food and pharmacology.

Formic acid intercalated Mg-Al layered double hydroxide (Mg-Al Fo-LDH) was prepared by calcination reduction intercalation assembly technology. The structure of the deicing additive was characterized by fourier transform infrared (FTIR) and X-ray diffraction (XRD). The freezing point of aqueous solution with different quality of deicing additive and the surface freezing point and adhesion of asphalt mixture were tested. The results show that formic acid ion has been intercalated into the interlayer of Mg-Al layered double hydroxide by FTIR and XRD patterns. The freezing point of 5wt% Mg-Al Fo-LDH aqueous solution reaches -9.32 °C, while the surface freezing point of the asphalt mixture mixed with 5wt% Mg-Al Fo-LDH is -6.5°C. At -8 °C, the adhesion force of the surface ice layer is 78.4N, and after the asphalt mixture is soaked in water, the surface freezing point and adhesion force of the ice layer do not change.

Luminescent cuprous complexes are important coordination compounds due to their relative abundance, low cost and ability to display excellent luminescence. The structures of two CuIP2S-type cuprous complexes, namely, iodido(thiourea-κS)bis(triphenylphosphane-κP)copper(I), [CuI(CH4N2S)(C18H15P)2] or [CuI(TU)(TPP)2] (I), and (2,3-dihydrobenzimidazole-2-thione-κS)iodidobis(triphenylphosphane-κP)copper(I), [CuI(C7H6N2S)(C18H15P)2] or [CuI(DHBIT)(TPP)2] (II), are described. In these two structures, the complex molecules of both are constructed by one copper(I) centre, one iodide ion, two TPP ligands and one thione ligand (TU for I and DHBIT for II). The copper(I) centres of I and II are both located in a distorted CuIP2S tetrahedron and are coordinated by two P atoms from two TPP ligands, one S atom from the thione ligand and the I atom. The UV–Vis absorption and photoluminescence properties of these CuIP2S-type cuprous complexes have been studied using crystalline powder samples. Detailed time-dependent density functional theory (TD-DFT) calculations and wavefunction analysis reveal that the pale-blue–green phosphorescence emission should originate from intra-ligand (TPP for I and DHBIT for II) charge transfer, with a small component of the metal-to-ligand charge transfer 3(IL+ML)CT excited state.

Studies on GaAsBi-based devices have been deeply carried out in recent years, strongly driven by their excellent performance. Despite the growing interest in GaAsBi, the systematic researches on its vibrational and thermodynamic properties are still lacking. Hence, in this work, the structural, vibrational and thermodynamic properties of GaBixAs1-x are studied systematically by performing ab initio calculations. Firstly, the calculation structure constants of GaBixAs1-x are in accordance with other available data in the literature. Next, the results of the vibrational frequencies indicate that the phonon frequencies of GaBixAs1-x undergo a sharp decline when the bismuth concentration x is elevated. Besides the reduction of the phonon densities of states at the specified wave vector, the optical branches of GaBixAs1-x narrow and the attenuation of longitudinal modes is greater than that of transverse modes with the enhancement of the Bi concentration x. Then, the splitting degree $$\left( {\delta \omega } \right)$$ suggests that the ionic strength for GaBixAs1-x is declined when increasing the Bi composition. Finally, the thermodynamic functions of GaBixAs1-x ranging from $$\Delta F$$ , $$\Delta E$$ , $$C_{v}$$ and $$S$$ are predicted. In addition, the calculation values of the Debye temperature for GaBixAs1-x also confirm the change trend of phonon frequencies of the system.

Copper oxide is considered as a potential anode material for lithium-ion batteries (LIBs), which have attracted huge amounts of research ardor owning to the high capacity and ultrahigh theoretical ...

Tyrosinase (TYR) is an important polyphenolic oxidase enzyme and usually regards as a biomarker of melanoma cancer. Highly effective tracking TYR activity in vivo will help to study the mechanism of TYR in living organisms and forecasts related diseases. In this study, we present a novel TYR-activatable fluorescent probe (CHMC-DOPA) for tracking TYR activity in vitro and in vivo. CHMC-DOPA is constructed by incorporating dopamine (DOPA) moiety into a fluorescent chloro-hydroxyl-merocyanine (CHMC) scaffold. Upon exposure to TYR, the dopamine unit in CHMC-DOPA is oxidized to a dopaquinone derivative, and an intramolecular photo-induced electron transfer (PET) process between CHMC fluorophore and o-dopaquinone will take place, the fluorescence of CHMC-DOPA is quenched rapidly. Therefore, the evaluation of TYR activity is established in terms of the relationship between fluorescence quenching efficiency and TYR activity. In our experiments, CHMC-DOPA shows various advantages, such as fast response (8⬰min), low concentration of TYR activation (0.5 U/mL), good water-solubility, as well as the lowest detection limit (0.003 U/mL) compared with previously reported works. Furthermore, CHMC-DOPA also exhibits excellent cell membrane permeability and low cytotoxicity, which is successfully used to monitor endogenous TYR activity in living cancer cells and zebrafish models. CHMC-DOPA performs well, and we anticipate that this newly designed novel platform will provide an alternative for high effective monitoring TYR activity in biosystems.

RGAs are widely used in molecular component examination, impurity analysis, leak detection and test of vacuum system performance. However, RGAs have different sensitivities to different gases, and the sensitivities can change quickly and depend on so many parameters, which make its ability severely limited. In this work we established a new practical method to precisely measure noble gas ratio of argon -xenon gas mixture. Gaseous argon and xenon were controlled, respectively, by two mass flow controller (MFC). A variable leak valve (VLV) was used to introduce the gas mixture sample into the RGA measurement chamber. Gas mixtures with xenon concentration from 200ppm to 20000ppm (by mass) were introduced and tested by RGA. The time stability of RGA-measurement system was optimized to 2.1%. A good linearity of MFC-RGA response was achieved, verifying the reliability of RGA in measuring noble gas mixture with component concentration down to several hundred ppm level. Since the approach we used in our experiment is gas-species independent, we believe that it can be popularized to other gas species when properly applied.

As a natural abundant high-carbon resource, the use of coal to develop carbon nanomaterials is an important research topic. In recent years, a variety of carbon materials with different morphologies and nanotextures have been designed and constructed using coal and their derivatives as precursors, and their use in energy storage, catalysis, adsorption and absorption have been explored. State-of-the-art research on carbon nanomaterials derived from coals of different rank and their derivatives are summarized with specific attention to the synthesis strategies and structure control. The use of these coal-derived carbons for energy storage, such as secondary batteries and supercapacitors, is also discussed in terms of their structural features. The review aims to provide valuable insight into the present challenges and inspire new ideas for the development of advanced coal-derived carbon materials.

Atherosclerosis (AS) is the leading cause of heart attacks, stroke, and peripheral vascular disease. Berberine (BBR), a botanical medicine, has diversified anti-atherosclerotic effects but with poor absorption. The aim of this study was to develop an effective BBR-entrapped nano-system for treating AS in high-fat diet (HFD)-fed Apoe(−/−) mice, and also explore the possible underlying mechanisms involved. Three d-α-tocopherol polyethylene glycol (PEG) succinate (TPGS) analogues with different PEG chain lengths were synthesized to formulate BBR-entrapped micelles. HFD-fed Apoe(−/−) mice were administered with optimized formula (BBR, 100 mg/kg/day) orally for 5 months. The artery plaque onset and related metabolic disorders were evaluated, and the underlying mechanisms were studied. Our data showed that, BT1500M increased BBR deposition in liver and adipose by 107.6% and 172.3%, respectively. In the Apoe(−/−) mice, BT1500M ameliorated HFD-induced hyperlipidemia and lipid accumulation in liver and adipose. BT1500M also suppressed HFD-induced chronic inflammation as evidenced by the reduced liver and adipose levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β); and decreased plasma level of TNF-α, IL-6, IL-1β, interferon-γ (IFN-γ), monocyte chemotactic protein (MCP), and macrophage inflammatory factor (MIP). The mechanism study showed that BT1500M changed Ampk and Nf-κb gene expression, and interrupted a crosstalk process between adipocytes and macrophages. Further investigation proved that BT1500M decreased endothelial lesion and subsequent macrophage activation, cytokines release, as well as cholesteryl ester gathering in the aortic arch, resulting in ameliorated artery plaque build-up. Our results provide a practical strategy for treating AS using a BBR-entrapped nano-system., Graphical abstract BT1500M, which increased gut-absorption and intra-cellular uptake of berberine, modulated AMPK and NF-κB expression, and improved dyslipidemia and inflammation induced by high fat diet. The endothelial injury and subsequent macrophage infiltration and cholesteryl ester gathering in the aortic arch were decreased, resulting in the inhibition of artery plaque build-up.Image 1

This study used response surface methodology to determine the optimal conditions for extraction of polysaccharides from Pyracantha. fortuneana (PSPF), and studied the mechanism of PSPF-inducing apoptosis in human ovarian carcinoma Skov3 cells. Response surface methodology (RSM) were adopted to extract PSPF. The maximum value of polysaccharide yield was obtained under these optimal conditions. PSPF had good potential as an antioxidant. Exposure of cells to PSPF resulted in cytotoxicity through the induction of apoptosis, and the reactive oxygen species were increased, mitochondrial membrane potential decreased, DNA damage (detected as γ- H2AX and RAD51 foci) was observed in Skov3 cells. In addition, PSPF could induce apoptosis of cancer cells. Therefore, PSPF should be explored as novel potential antioxidants and an anti-tumor drug in a clinical setting.

Luminescent cuprous complexes are an important class of coordination compounds due to their relative abundance, low cost and ability to display excellent luminescence. The heteroleptic cuprous complex solvate rac-(acetonitrile-κN)(3-aminopyridine-κN)[2,2′-bis(diphenylphosphanyl)-1,1′-binaphthyl-κ2 P,P′]copper(I) hexafluoridophosphate dichloromethane monosolvate, [Cu(C5H6N2)(C2H3N)(C44H32P2)]PF6·CH2Cl2, conventionally abbreviated as [Cu(3-PyNH2)(CH3CN)(BINAP)]PF6·CH2Cl2, (I), where BINAP and 3-PyNH2 represent 2,2′-bis(diphenylphosphanyl)-1,1′-binaphthyl and 3-aminopyridine, respectively, is described. In this complex solvate, the asymmetric unit consists of a cocrystallized dichloromethane molecule, a hexafluoridophosphate anion and a complete racemic heteroleptic cuprous complex cation in which the cuprous centre, in a tetrahedral CuP2N2 coordination, is coordinated by two P atoms from the BINAP ligand, one N atom from the 3-PyNH2 ligand and another N atom from a coordinated acetonitrile molecule. The UV–Vis absorption and photoluminescence properties of this heteroleptic cuprous complex have been studied on polycrystalline powder samples, which had been verified by powder X-ray diffraction before recording the spectra. Time-dependent density functional theory (TD-DFT) calculations and a wavefunction analysis reveal that the orange–yellow phosphorescence emission should originate from intra-ligand (BINAP) charge transfer mixed with a little of the metal-to-ligand charge transfer 3(IL+ML)CT excited state.

Simple Summary Insect sex pheromone biosynthesis has received widespread attention, while the terminal pathway related to aldehyde synthesis and metabolism is still poorly understood at a molecular level. Previous studies found that the silkworm, Bombyx mori (Lepidoptera, Bombycidae), has two pheromone compounds, bombykol and bombykal, with a ratio of 11:1, while its closest wild relative, B. mandarina, only uses bombykol as a pheromone. In this study, sex pheromone gland transcriptomes were compared between the domestic and wild silkworms. All the candidate gene families were identified. Then we used the differentially expressed information, tissue and developmental expression profiles, and phylogenetic analysis to identify the putative causal genes involved in the terminal pathway. Our findings provide insights into the aldehyde synthesis and metabolism pathways and evolutionary conservation in moths. Abstract Sex pheromones are vital to sexual communication and reproduction in insects. Although some key enzymes in pheromone production have been well studied, information on genes involved in the terminal pathway is limited. The domestic silkworm employs a pheromone blend containing (E,Z)-10,12-hexadecadienol (bombykol) and analogous (E,Z)-10,12-hexadecadienal (bombykal); whereas, its wild ancestor B. mandarina uses only bombykol. The two closely related moths might be a good model for exploring the genes involved in aldehyde pheromone synthesis and metabolism. By deep sequencing and analyzing the sex pheromone gland (PG) transcriptomes; we identified 116 candidate genes that may be related to pheromone biosynthesis, metabolism, and chemoreception. Spatiotemporal expression profiles and differentially expressed analysis revealed that four alcohol oxidases (BmorAO1; 2; 3; and 4); one aldehyde reductase (BmorAR1); and one aldehyde oxidase (BmorAOX5) might be involved in the terminal pathway. Phylogenetic analysis showed that, except for BmorAO3 and MsexAO3, AOs did not show a conversed orthologous relationship among moths; whereas, ARs and AOXs were phylogenetically conserved. This study provides crucial candidates for further functional elucidation, and which may be utilized as potential targets to disrupt sexual communication in other moth pests.

A response surface method (RSM) was employed to optimize polysaccharide extraction from Panax japonicus (PJPS). Also, carboxymethyl substitution of PJPS (CM-PJPS) was studied using a response surface methodology. A three-variable Box–Behnken design (BBD) methodology was applied. RSM analyses revealed that conditions that maximized polysaccharide yield were as follows: a liquid-to-material ratio 22:1, an extraction temperature of 83.99 °C and an extraction duration of 2.32 h. Under optimum extraction conditions, the average absorbance value of PJPS was 0.6001, and the purity of PJPS was 98.2%. A quadratic regression model for CM-PJPS was obtained via BBD. The optimum extraction conditions for the process were determined to include a 1.38 h reaction time, 1.24 g monochloroacetic acid (MCA) and a reaction temperature of 52.85 °C. Under optimum extraction conditions, the average degree of CM-PJPS substitution was 0.9733. The structure of the PJPS was examined by means of Fourier transform infrared spectroscopy (FTIR). CM-PJPS exhibited the strongest anti-oxidant activity in vitro. In addition, CM-PJPS inhibited Skov3 and A2780 cancer cell proliferation. Our data revealed that CM-PJPS is a promising natural antioxidant with potential value as a food supplement and for treatment of cancer.

An exhaustive analysis based on density functional theory (DFT) simulations of the effect of Hf doping on helium behavior has been performed in ZrCo. The He impurities have been placed both at interstitial positions and substitutional positions from the first nearest neighbor (1nn) of the Hf atom to the sixth nearest neighbor (6nn). In such areas, the electronic charge density is different, and therefore the formation and diffusion of He atoms vary in the surrounding of the Hf atom. The results show that Hf doping reduces the volume of the interstitial sites nearby, resulting in the weakening ability of the interstitial sites to accommodate He atoms. According to the results of formation energy, whether it is the substitutional He or the interstitial He atom, the formation is not only related to the distance of Hf, but more importantly, it is closely related to the unit cell where the He atom is located. In addition, Hf atoms promote the capture of He atoms by vacancies nearby and the migration of He atoms between the tetrahedral positions. The result also validates the well-known knowledge of vacancies as efficient sinks for He atoms in ZrCo. From the lower and lower migration energetic barriers along 3nn → 2nn → 1nn → 1nn pathways, we can infer an increasing mobility of the He atom from 3nn to 1nn. This situation could favor their accumulation surrounding an Hf atom, improving the ability of helium retention. These findings provide really indisputable evidence that the Hf dopant makes a difference in the behavior of He atoms in bulk ZrCo. Therefore, a ZrCo system with Hf doping can be considered as a good candidate for tritium storage material in a future nuclear fusion reactor.

In this study, we extracted lotus root polysaccharide (LRP) and synthesised phosphorylated lotus root polysaccharide (PLP) using response surface methodology (RSM). RSM analyses revealed that the optimal conditions for PLP synthesis were a reaction duration of 7 h, temperature of 70 °C and pH of 11.38. Under these conditions, the predicted degree of substitution (DS%) was determined to be 9.96%. The structure of the LRP1 was examined by ultraviolet (UV) spectroscopy scan, Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) (1H and 13C). The monosaccharide composition of LRP1 was determined to be mannose (0.12%), ribose(0.18%), glucuronic acid(0.60%), galacturonic acid(0.09%), glucose(98.79%) and galactose(0.21%). The number average molecular weight (Mn) and the weight average molecular weight (Mw) of LRP1 were 10236 and 251783 g/mol. LRP1 exhibited high antioxidant activities in scavenging ABTS radicals, Superoxide anion radicals and Metal ion scavenging activity. PLP exhibited strong antioxidant activity in vitro. In addition, PLP inhibited Skov3 cancer cell proliferation and induced reactive oxygen species (ROS) production. Our data revealed that PLP is a promising natural antioxidant with potential value as a food supplement and for the treatment of cancer.

Simple Summary Heat shock protein 70 family is widely distributed in all the organisms, which plays important roles in protein folding and preventing protein denaturation. Heat or cold stress response has been studied in some insects, but there is a lack of systematic investigation on the response of the same species to multiple stressors. Here, we performed genome-wide identification of heat shock protein 70 family in the silkworm, Bombyx mori. Using the silkworm as a model, the transcription profiles of all the genes against heat, cold, and pesticides were studied. Our findings would provide insights into the functional diversification of heat shock proteins 70 in insects. Abstract The 70 kDa heat shock proteins play important roles in protecting organisms against environmental stresses, which are divided into stress-inducible forms (HSP70s) and heat shock cognates (HSC70s). In this study, heat shock protein 70 family was identified in the whole genome of the silkworm. Based on the known nomenclature and phylogenetic analysis, four HSP70s and five HSC70s were classified. Relatively, heat shock cognates were more conservative and were constitutively expressed in various tissues of the silkworm larvae. Under thermal (37 °C and 42 °C) and cold (2 °C) stresses, the expressions of HSP70–1, HSP70–2, and HSP70–3 were up-regulated, and the highest induction reached 4147.3, 607.1, and 1987.3 times, respectively. Interestingly, HSC70–1, HSC70–4, and HSC70–5 also showed slight induced expressions in the fat body and/or midgut under thermal stresses. In addition, the expression of HSP70–1 was induced by dichlorvos and phoxim insecticides, while most HSC70 genes were inhibited. The results suggested that stress-inducible forms play more important roles in adaptation to various stresses than HSC70s.

Since the D614G substitution in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, the variant strain has undergone a rapid expansion to become the most abundant strain worldwide. Therefore, this substitution may provide an advantage for viral spreading. To explore the mechanism, we analyzed 18 viral isolates containing S proteins with either G614 or D614 (S-G614 and S-D614, respectively). The plaque assay showed a significantly higher virus titer in S-G614 than in S-D614 isolates. We further found increased cleavage of the S protein at the furin substrate site, a key event that promotes syncytium formation, in S-G614 isolates. The enhancement of the D614G substitution in the cleavage of the S protein and in syncytium formation has been validated in cells expressing S protein. The effect on the syncytium was abolished by furin inhibitor treatment and mutation of the furin cleavage site, suggesting its dependence on cleavage by furin. Our study pointed to the impact of the D614G substitution on syncytium formation through enhanced furin-mediated S cleavage, which might increase the transmissibility and infectivity of SARS-CoV-2 strains containing S-G614. IMPORTANCE Analysis of viral genomes and monitoring of the evolutionary trajectory of SARS-CoV-2 over time has identified the D614G substitution in spike (S) as the most prevalent expanding variant worldwide, which might confer a selective advantage in transmission. Several studies showed that the D614G variant replicates and transmits more efficiently than the wild-type virus, but the mechanism is unclear. By comparing 18 virus isolates containing S with either D614 or G614, we found significantly higher virus titers in association with higher furin protease-mediated cleavage of S, an event that promotes syncytium formation and virus infectivity, in the S-G614 viruses. The effect of the D614G substitution on furin-mediated S cleavage and the resulting enhancement of the syncytium phenotype has been validated in S-expressing cells. This study suggests a possible effect of the D614G substitution on S of SARS-CoV-2; the antiviral effect through targeting furin protease is worthy of being investigated in proper animal models.

Circular RNAs (circRNAs) are implicated in various human cancers, including colorectal cancer (CRC). The objective of this study was to investigate the function and regulatory mechanism of a novel circRNA, circFAM120B, in CRC development. The expression of circFAM120B, miR-645 and TGF-beta receptor II (TGFBR2) mRNA was detected by quantitative real-time polymerase chain reaction. Cellular biological functions, including cell proliferation, migration/invasion, and glycolysis metabolism, were assessed using CCK-8 assay, colony formation assay, transwell assay, and glycolysis stress test, respectively. Glycolysis progression was also monitored by lactate production and glucose consumption. The expression of glycolysis-related markers and TGFBR2 at the protein level was detected by western blot. The interaction between miR-645 and circFAM120B or TGFBR2 was predicted by bioinformatics analysis and verified by pull-down assay, dual-luciferase reporter assay and RIP assay. In vivo animal experiments were performed to further explore the function of circFAM120B. The expression of circFAM120B was decreased in CRC tissues and cells. CircFAM120B overexpression blocked CRC cell proliferation, migration/invasion, and glycolysis metabolism. MiR-645 was a target of circFAM120B, and miR-645 restoration reversed the effects of circFAM120B overexpression. In addition, TGFBR2 was a target of miR-645, and miR-645 inhibition-suppressed CRC cell proliferation, migration/invasion and glycolysis were restored by TGFBR2 knockdown. Moreover, circFAM120B activated the expression of TGFBR2 by targeting miR-645. TGFBR2 also blocked tumor growth in vivo by targeting the miR-645/TGFBR2 axis. CircFAM120B inhibited CRC progression partly by mediating the miR-645/TGFBR2 network, which explained the potential mechanism of circFAM120B function in CRC.

Mimicking the superstructures and functions of natural chiral materials is beneficial to understand specific biological activities in living organisms and broaden applications in the fields of chemistry and materials sciences. However, it is still a great challenge to construct water-soluble, double-helical polymers with multiple responsiveness. Herein, we report for the first time a straightforward, general strategy to address this issue by taking advantage of Passerini multicomponent polymerization-induced assembly (PMPIA). The polymerization-induced generation of supramolecular interactions in chiral α-acyloxy amides drives the assembly of polymers and improves their stability in various solvents. This double-helical polymer is sensitive to metal ions, temperature, pH, and solvents, making both the superstructure and the AIE effect reversibly adjustable. Meanwhile, the hydrogen-bonding-assisted cyclization of photolabile α-acyloxy amides accelerates the degradation of helical polymers under visible-light irradiation. It is anticipated that this novel PMPIA strategy opens new horizons to inspire the design of advanced chiral/helical polymers with multiple functions., Passerini multicomponent polymerization-induced assembly is reported to design a water-soluble, AIE-active, double-helical polymer with reversible multi-responsiveness to external stimuli and rapid visible-light degradability.

Due to the advantages of low electrical resistance and size miniaturization, Cu to Cu has become the important trends in microelectric interconnect fabrication. Robust Cu to Cu bonding with low temperature, ambient pressure (under N2 or air) and short processing time is strongly requested for advanced IC and substrate packaging, MEMS hermetic sealing, and flexible electronics assembly as well. Ultrasonic technique has recently be adopted in direct copper bonding, this study focuses on the influences of surface physical features on direct bonding between two copper electro-deposits. Experimental results show that joints consisting of hard bumps bonded with soft Cu surface exhibit improved bonding strength. They also indicate that the bonding temperature at 100°C with the protection of N2 and higher surface roughness both positively contribute to the joint strength.

Structural maintenance of chromosomes (SMC) complexes are critical chromatin modulators. In eukaryotes, the cohesin and condensin SMC complexes organize chromatin, while the Smc5/6 complex directly regulates DNA replication and repair. The molecular basis for the distinct functions of Smc5/6 is poorly understood. Here, we report an integrative structural study of the budding yeast Smc5/6 holo-complex using electron microscopy, cross-linking mass spectrometry, and computational modeling. We show that the Smc5/6 complex possesses several unique features, while sharing some architectural characteristics with other SMC complexes. In contrast to arm-folded structures of cohesin and condensin, Smc5 and Smc6 arm regions do not fold back on themselves. Instead, these long filamentous regions interact with subunits uniquely acquired by the Smc5/6 complex, namely the Nse2 SUMO ligase and the Nse5/Nse6 subcomplex, with the latter also serving as a linchpin connecting distal parts of the complex. Our 3.0-Å resolution cryoelectron microscopy structure of the Nse5/Nse6 core further reveals a clasped-hand topology and a dimeric interface important for cell growth. Finally, we provide evidence that Nse5/Nse6 uses its SUMO-binding motifs to contribute to Nse2-mediated sumoylation. Collectively, our integrative study identifies distinct structural features of the Smc5/6 complex and functional cooperation among its coevolved unique subunits.

The anode oxygen evolution reaction (OER) is known to largely limit the efficiency of electrolyzers owing to its sluggish kinetics. While crystalline metal oxides are promising as OER catalysts, their amorphous phases also show high activities. Efforts to produce amorphous metal oxides have progressed slowly, and how an amorphous structure benefits the catalytic performances remains elusive. Now the first scalable synthesis of amorphous NiFeMo oxide (up to 515 g in one batch) is presented with homogeneous elemental distribution via a facile supersaturated co-precipitation method. In contrast to its crystalline counterpart, amorphous NiFeMo oxide undergoes a faster surface self-reconstruction process during OER, forming a metal oxy(hydroxide) active layer with rich oxygen vacancies, leading to superior OER activity (280 mV overpotential at 10 mA cm-2 in 0.1 m KOH). This opens up the potential of fast, facile, and scale-up production of amorphous metal oxides for high-performance OER catalysts.

The ultrasensitive bioassays are increasingly demanded for disease diagnosis and environmental monitoring. The combined unique natures of the components in nanocomposites have led to their wide applications in bioanalysis. In the current study, a simple strategy for preparing polyethyleneimine-functionalized reduced graphene oxide-hemin-bovine serum albumin (PEI-rGO-Hemin-BSA) nanocomposites as peroxidase mimetics was demonstrated. The developed nanocomposites of PEI-rGO-Hemin-BSA showed an excellent peroxidase-like activity. Importantly, through the glutaradelhyde crosslinking, PEI-rGO-Hemin-BSA could be further simply combined with various oxidases such as glucose oxidase, cholesterol oxidase, lactate oxidase and choline oxidase for the detection and quantitative measurement of multiple metabolites including glucose, cholesterol, l-lactate, and choline. The developed detection strategy, which is sensitive, convenient, low-costed, and in tiny sample consumption, could be expected wide applications in the disease diagnosis and management of metabolite disorders.

Tigecycline is one of the last-resort antibiotics to treat complicated infections caused by both multidrug-resistant Gram-negative and Gram-positive bacteria1. Tigecycline resistance has sporadically occurred in recent years, primarily due to chromosome-encoding mechanisms, such as overexpression of efflux pumps and ribosome protection2,3. Here, we report the emergence of the plasmid-mediated mobile tigecycline resistance mechanism Tet(X4) in Escherichia coli isolates from China, which is capable of degrading all tetracyclines, including tigecycline and the US FDA newly approved eravacycline. The tet(X4)-harbouring IncQ1 plasmid is highly transferable, and can be successfully mobilized and stabilized in recipient clinical and laboratory strains of Enterobacteriaceae bacteria. It is noteworthy that tet(X4)-positive E. coli strains, including isolates co-harbouring mcr-1, have been widely detected in pigs, chickens, soil and dust samples in China. In vivo murine models demonstrated that the presence of Tet(X4) led to tigecycline treatment failure. Consequently, the emergence of plasmid-mediated Tet(X4) challenges the clinical efficacy of the entire family of tetracycline antibiotics. Importantly, our study raises concern that the plasmid-mediated tigecycline resistance may further spread into various ecological niches and into clinical high-risk pathogens. Collective efforts are in urgent need to preserve the potency of these essential antibiotics. Plasmid-encoded tet(X) genes from Escherichia coli in China confer high-level tigecycline resistance.

The incorporation of defects, such as vacancies, into functional materials could substantially tailor their intrinsic properties. Progress in vacancy chemistry has enabled advances in many technological applications, but creating new type of vacancies in existing material system remains a big challenge. We show here that ionized nitrogen plasma can break bonds of iron-carbon-nitrogen-nickel units in nickel-iron Prussian blue analogues, forming unconventional carbon-nitrogen vacancies. We study oxygen evolution reaction on the carbon-nitrogen vacancy-mediated Prussian blue analogues, which exhibit a low overpotential of 283 millivolts at 10 milliamperes per square centimeter in alkali, far exceeding that of original Prussian blue analogues and previously reported oxygen evolution catalysts with vacancies. We ascribe this enhancement to the in-situ generated nickel-iron oxy(hydroxide) active layer during oxygen evolution reaction, where the Fe leaching was significantly suppressed by the unconventional carbon-nitrogen vacancies. This work opens up opportunities for producing vacancy defects in nanomaterials for broad applications., Defect-engineering offers a promising route to vary material properties and reactivities, although the achievable defect types are limited. Here, the authors introduced unusual CN-vacancies in Prussian blue analogue pre-catalysts that can limit Fe leaching and improve oxygen evolution performances.

Three new perovskite-like hybrid iodobismuthates with two quaternary ammonium cations, namely (BnNEt3)3(Bi2I9) (1) (BnNEt3)4(Bi4I16) (2) and (n-Bu4N)2n(Bi4I14)n (3) (Bn = benzyl, n-Bu = n-butyl), have been synthesized by reacting BiI3 with the quaternary ammonium iodide in molar ratio 2:3 (1), 1:1(2), and 2:1 (3), respectively. All hybrids were characterized by elemental analysis, X-ray diffraction and UV–Vis spectroscopic analysis. Single-crystal X-ray diffraction revealed that hybrids 1 and 2 are di-nuclear and tetra-nuclear cluster structures respectively, while 3 is a polymeric chain structure based on a (Bi4I14) tetra-nuclear cluster unit. Their optical band-gaps have been determined as 2.19 eV(1), 2.16 eV(2), 2.02 eV(3), respectively. The optical band gaps exhibit a structure-related decrease from 1 to 3, in agreement with their color changes and the density functional theory (DFT) calculation results. The DFT calculations also reveal that there is a inversely proportional relationship between the optical Eg and the aggregation degree of the BiI6 octahedra in the hybrid iodobismuthate clusters.

The design of highly efficient non-noble-metal electrocatalysts for large-scale hydrogen production remains an ongoing challenge. We report here a Ni2P nanoarray catalyst grown on a commercial Ni foam substrate, which demonstrates an outstanding electrocatalytic activity and stability in basic electrolyte. The high catalytic activity can be attributed to the favorable electron transfer, superior intrinsic activity, and the intimate connection between the nanoarrays and their substrate. Moreover, the unique "superaerophobic" surface feature of the Ni2P nanoarrays enables a remarkable capability to withstand internal and external forces and release the in situ generated H2 bubbles in a timely manner at large current densities (such as >1000 mA cm-2) where the hydrogen evolution becomes vigorous. Our results highlight that an aerophobic structure is essential to catalyze gas evolution for large-scale practical applications.

The “self-homing” of cancer cells to primary or metastatic tumor sites indicates that they could serve as vehicles for self-targeted cancer therapy; this suggests a promising method for treating end-stage cancer. Inspired by this, we propose that engineering cancer cells to carry efficient “coup” molecules for in situ activation of immune cells in or near tumor sites to attack tumors is a promising strategy for cancer therapy. Therefore, herein we explored the potential of engineered tumor cells to enhance their anticancer activity by stimulating immune cells. We armed tumor cell surfaces with specific glycopolymer–ligands that bind to lectins on macrophages or dendritic cells by combining HaloTag protein (HTP) fusion technique with reversible addition–fragmentation chain transfer (RAFT) polymerization. We demonstrated that two synthetic well-defined glycopolymers containing, respectively, N-acetylglucosamine and N-acetylmannosamine units, were introduced and stably presented on the cell surfaces via the ...

The effects of silicon (Si) on the release of tritium over lithium titanate (Li2TiO3) surface (001) are investigated using periodic density functional theory (DFT) calculations. DFT results show th...

We investigated the effect of Pd and Ni dopants on the formation and desorption of tritiated water (T2O) molecules from the Li2TiO3 (001) surface using first-principles calculations coupled with the climbing-image nudged elastic band method. We calculated the energy barriers for T2O production and desorption on the pure Li2TiO3 surface to be 0.94 and 0.64 eV, respectively. The Pd and Ni dopants enhanced T2O formation by reducing the formation energy of O vacancies, and T2O generated spontaneously on the dopant surface. Moreover, we found that dopant atoms affect the charge transfer of neighboring atoms, which leads to orbital hybridization and the generation of a chemical bond between the O and T on the doped Li2TiO3 surface. In addition, desorption of T2O from the doped Li2TiO3 surface requires a relatively low energy (

The interactions of dopants with point defects such as that between vacancies and helium can affect helium evolution and ultimately the macroscopic properties of materials. Herein, the microscopic vacancy trapping mechanism for He defects and the formation of small HemVacn (consisting of m He atoms and n vacancies) clusters in pure and Ti-doped ZrCo systems are investigated by carrying out an extensive set of first-principles calculations based on density functional theory. Our results uncover the following: the helium atom can segregate from the adjacent interstitial (tetrahedral and octahedral) sites towards the vacancy center spontaneously, and therefore, a single He atom is energetically favorable to occupy a vacancy whether in the pure or in the doped system. The dopant Ti can act as a trapping center for He impurities similar to a vacancy. Moreover, it can improve the trapping ability and increase the trapping radius of the vacancies for helium. As for the effect of the Ti atom on the trapping of multiple helium atoms by the vacancy, the higher barrier in the doped systems than in the pure one implies that doping inhibits the formation of large HemVac clusters. Furthermore, in order to evaluate the effect of dopant Ti on the stability of He atoms in multiple vacancies, the binding energies of a helium atom, a vacancy (Vac), and a self-interstitial atom (SIA) to a helium–vacancy cluster (HemVacn) were obtained and compared with that of the pure system. The results suggest that the cluster growth can be inhibited by the dopant Ti, and therefore, the formation of large helium bubbles is also hindered. All the binding energies do not depend much on the cluster size but primarily on the helium-to-vacancy ratio (m/n) of the clusters. The stability of the clusters is decided by the competitive processes among the emission of He atoms, vacancies, and SIAs, and also depends on the helium-to-vacancy ratio. The present results provide an in-depth explanation for the effect of the dopant on helium behavior and could aid future tritium storage material design.

Macrophages comprise the front line of defense against various pathogens. Classically activated macrophages (M1), induced by IFN-γ and LPS, highly express inflammatory cytokines and contribute to inflammatory processes. By contrast, alternatively activated macrophages (M2) are induced by IL-4 and IL-13, produce IL-10, and display anti-inflammatory activity. Adenylate kinase 4 (Ak4), an enzyme that transfers phosphate group among ATP/GTP, AMP, and ADP, is a key modulator of ATP and maintains the homeostasis of cellular nucleotides which is essential for cell functions. However, its role in regulating the function of macrophages is not fully understood. Here we report that Ak4 expression is induced in M1 but not M2 macrophages. Suppressing the expression of Ak4 in M1 macrophages with shRNA or siRNA enhances ATP production and decreases ROS production, bactericidal ability and glycolysis in M1 cells. Moreover, Ak4 regulates the expression of inflammation genes, including Il1b, Il6, Tnfa, Nos2, Nox2, and Hif1a, in M1 macrophages. We further demonstrate that Ak4 inhibits the activation of AMPK and forms a positive feedback loop with Hif1α to promote the expression of inflammation-related genes in M1 cells. Furthermore, RNA-seq analysis demonstrates that Ak4 also regulates other biological processes in addition to the expression of inflammation-related genes in M1 cells. Interestingly, Ak4 does not regulate M1/M2 polarization. Taken together, our study uncovers a potential mechanism linking energy consumption and inflammation in macrophages.

Summary Bacteria and archaea apply CRISPR-Cas surveillance complexes to defend against foreign invaders. These invading genetic elements are captured and integrated into the CRISPR array as spacer elements, guiding sequence-specific DNA/RNA targeting and cleavage. Recently, in vivo studies have shown that target RNAs with extended complementarity with repeat sequences flanking the target element (tag:anti-tag pairing) can dramatically reduce RNA cleavage by the type VI-A Cas13a system. Here, we report the cryo-EM structure of Leptotrichia shahii LshCas13acrRNA in complex with target RNA harboring tag:anti-tag pairing complementarity, with the observed conformational changes providing a molecular explanation for inactivation of the composite HEPN domain cleavage activity. These structural insights, together with in vitro biochemical and in vivo cell-based assays on key mutants, define the molecular principles underlying Cas13a’s capacity to target and discriminate between self and non-self RNA targets. Our studies illuminate approaches to regulate Cas13a’s cleavage activity, thereby influencing Cas13a-mediated biotechnological applications.

Heterochromatin, a type of condensed DNA in eukaryotic cells, has two main categories: Constitutive heterochromatin, which contains H3K9 methylation, and facultative heterochromatin, which contains H3K27 methylation. Methylated H3K9 and H3K27 serve as docking sites for chromodomain-containing proteins that compact chromatin. M33 (also known as CBX2) is a chromodomain-containing protein that binds H3K27me3 and compacts chromatin in vitro. However, whether M33 mediates chromatin compaction in cellulo remains unknown. Here we show that M33 compacts chromatin into DAPI-intense heterochromatin domains in cells. The formation of these heterochromatin domains requires H3K27me3, which recruits M33 to form nuclear bodies. G9a and SUV39H1 are sequentially recruited into M33 nuclear bodies to create H3K9 methylated chromatin in a process that is independent of HP1α. Finally, M33 decreases progerin-induced nuclear envelope disruption caused by loss of heterochromatin. Our findings demonstrate that M33 mediates the formation of condensed chromatin by forming nuclear bodies containing both H3K27me3 and H3K9me3. Our model of M33-dependent chromatin condensation suggests H3K27 methylation corroborates with H3K9 methylation during the formation of facultative heterochromatin and provides the theoretical basis for developing novel therapies to treat heterochromatin-related diseases.

Structural maintenance of chromosomes (SMC) complexes are critical chromatin modulators. In eukaryotes, the cohesin and condensin SMC complexes organize chromatin, while the Smc5/6 complex directly regulates DNA replication and repair. The molecular basis for Smc5/6’s distinct functions is currently poorly understood. Here, we report an integrative structural study of the budding yeast Smc5/6 complex using electron microscopy, cross-linking mass spectrometry, and computational modeling. We show that while the complex shares a similar overall organization with other SMC complexes, it possesses several unique features. In contrast to the reported folded-arm structures of cohesin and condensin, our data suggest that Smc5 and Smc6 arm regions do not fold back on themselves. Instead, these long filamentous regions interact with subunits uniquely acquired by the Smc5/6 complex, namely the Nse2 SUMO ligase and the Nse5-Nse6 subcomplex. Further, we show that Nse5-Nse6 subcomplex adopts a novel structure with an extensive dimerization interface and multiple domains contacting other subunits of the Smc5/6 complex. We also provide evidence that the Nse5-Nse6 module uses its SUMO-binding motifs to contribute to Nse2-mediated sumoylation. Collectively, our integrative multi-scale study identifies distinct structural features of the Smc5/6 complex and functional cooperation amongst its co-evolved unique subunits.

Hydrogen economy has emerged as a very promising alternative to the current hydrocarbon economy, which involves the process of harvesting renewable energy to split water into hydrogen and oxygen and then further utilization of clean hydrogen fuel. The production of hydrogen by water electrolysis is an essential prerequisite of the hydrogen economy with zero carbon emission. Among various water electrolysis technologies, alkaline water splitting has been commercialized for more than 100 years, representing the most mature and economic technology. Here, the historic development of water electrolysis is overviewed, and several critical electrochemical parameters are discussed. After that, advanced nonprecious metal electrocatalysts that emerged recently for negotiating the alkaline oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are discussed, including transition metal oxides, (oxy)hydroxides, chalcogenides, phosphides, and nitrides for the OER, as well as transition metal alloys, chalcogenides, phosphides, and carbides for the HER. In this section, particular attention is paid to the catalyst synthesis, activity and stability challenges, performance improvement, and industry-relevant developments. Some recent works about scaled-up catalyst synthesis, novel electrode designs, and alkaline seawater electrolysis are also spotlighted. Finally, an outlook on future challenges and opportunities for alkaline water splitting is offered, and potential future directions are speculated.

We propose to measure the coherent elastic neutrino nucleus scattering (CE$\nu$NS) using a dual-phase liquid argon time projection chamber (TPC) with 200kg fiducial mass. The detector is expected to be adjacent to the JUNO-TAO experiment and to be about 35m from a reactor core with 4.6GW thermal power at Taishan. The antineutrino flux is approximately 6$\times10^{12}$cm$^{-1}$s$^{-1}$ at this location, leading to more than 11,000 coherent scattering events per day in the fiducial mass. However, the nuclear recoil energies concentrate in the sub-keV region, corresponding to less than ten ionisation electrons in the liquid argon. The detection of several ionisation electrons can be achieved in the dual-phase TPC due to the large amplification in the gas region. With a feasible detection threshold of four ionisation electrons, the signal rate is 955 per day. The detector is designed to be shielded well from cosmogenic backgrounds and ambient radioactivities to reach a 16% background-to-signal ratio in the energy region of interest. With the large CE$\nu$NS sample, the expected sensitivity of measuring the weak mixing angle $\sin^{2}\theta_{W}$, and of limiting the neutrino magnetic moment are discussed. In addition, a synergy between the reactor antineutrino CE$\nu$NS experiment and the dark matter experiment is foreseen., Comment: 14 pages, 10figures. Submitted to RDTM

Volatile pesticides impair olfactory function in workers/farmers and insects, but data on molecular responses and mechanisms are poorly understood. This study aims to reveal the mechanisms of olfactory dysfunction in the silkworm after exposure to volatile dichlorvos. Our results demonstrated that acute exposure for 12 h significantly reduced electroantennogram responses, and over 62.50% of the treated male moths cannot locate the pheromone source. Transcriptional and proteomic responses of the antennae and heads were investigated. A total of 101 differentially expressed genes (DEGs) in the antennae, 138 DEGs in the heads, and 43 differentially expressed proteins (DEPs) in the heads including antennae were revealed. We discovered that upregulations of Arrestin1 and nitric oxide synthase1 (NOS1) may inhibit cyclic nucleotide-gated channels and hinder calcium influx in the antennae. In the central nervous systems (CNS), downregulations of tyrosine hydroxylase (TH) and tyrosine decarboxylase (TDC) may inhibit olfactory signal transduction by reducing the second messenger biosynthesis. Meanwhile, an abnormal increase of brain cell apoptosis was revealed by Annexin V-mCherry staining, often leading to persistent neurologic impairment. Taken together, this study highlighted olfactory dysfunction caused by dichlorvos, which may provide a novel perspective for understanding the toxicity mechanism of volatile pesticides in other organisms.

Hydroxide exchange membrane fuel cells offer possibility of adopting platinum-group-metal-free catalysts to negotiate sluggish oxygen reduction reaction. Unfortunately, the ultrafast hydrogen oxidation reaction (HOR) on platinum decreases at least two orders of magnitude by switching the electrolytes from acid to base, causing high platinum-group-metal loadings. Here we show that a nickel-molybdenum nanoalloy with tetragonal MoNi4 phase can catalyze the HOR efficiently in alkaline electrolytes. The catalyst exhibits a high apparent exchange current density of 3.41 milliamperes per square centimeter and operates very stable, which is 1.4 times higher than that of state-of-the-art Pt/C catalyst. With this catalyst, we further demonstrate the capability to tolerate carbon monoxide poisoning. Marked HOR activity was also observed on similarly designed WNi4 catalyst. We attribute this remarkable HOR reactivity to an alloy effect that enables optimum adsorption of hydrogen on nickel and hydroxyl on molybdenum (tungsten), which synergistically promotes the Volmer reaction., The lack of efficient and cost-effective catalysts for hydrogen oxidation reaction (HOR) hampers the application of hydroxide exchange membrane fuel cells. Here, authors reported bimetallic MoNi4 and WNi4 nanoalloys with marked HOR activity in alkali, among which MoNi4 outperforms the Pt/C catalyst.

Hereditary spastic paraplegias (HSPs) are genetic neurodegenerative diseases. HSPs are characterized by lower-extremity weakness and spasticity. However, there is no specific clinical treatment strategy to prevent or reverse nerve degeneration in HSPs. Mutations in receptor expression-enhancing protein 1 (REEP1) are well-recognized and relatively common causes of autosomal dominant HSPs. REEP1 modifies the endoplasmic reticulum (ER) shape, and is implicated in the ER stress response. Defects in the ER stress response seem to be crucial mechanisms underlying HSP neurodegeneration. Here, we report that REEP1−/− mice exhibit progressive motor deficits, along with denervation of neuromuscular junctions and increased ER stress. Moreover, marked axonal degeneration and morphological abnormalities are observed. In this study, we treated both REEP1−/− and wild-type (WT) mice with salubrinal, which is a specific inhibitor of ER stress, and we observed increased nerve-muscle connections and enhanced motor functions. Our data highlight the importance of ER homeostasis in HSPs, providing new opportunities for HSP treatment., Summary: Endoplasmic reticulum (ER) stress plays an important role in hereditary spastic paraplegias (HSPs) pathology, providing new opportunities for HSP treatment.

Copy number variants (CNVs) are the gain or loss of DNA segments in the genome that can vary in dosage and length. CNVs comprise a large proportion of variation in human genomes and impact health conditions. To detect rare CNV associations, kernel-based methods have been shown to be a powerful tool due to their flexibility in modeling the aggregate CNV effects, their ability to capture effects from different CNV features, and their accommodation of effect heterogeneity. To perform a kernel association test, a CNV locus needs to be defined so that locus-specific effects can be retained during aggregation. However, CNV loci are arbitrarily defined and different locus definitions can lead to different performance depending on the underlying effect patterns. In this work, we develop a new kernel-based test called CONCUR (i.e., copy number profile curve-based association test) that is free from a definition of locus and evaluates CNV-phenotype associations by comparing individuals’ copy number profiles across the genomic regions. CONCUR is built on the proposed concepts of “copy number profile curves” to describe the CNV profile of an individual, and the “common area under the curve (cAUC) kernel” to model the multi-feature CNV effects. The proposed method captures the effects of CNV dosage and length, accounts for the numerical nature of copy numbers, and accommodates between- and within-locus etiological heterogeneity without the need to define artificial CNV loci as required in current kernel methods. In a variety of simulation settings, CONCUR shows comparable or improved power over existing approaches. Real data analyses suggest that CONCUR is well powered to detect CNV effects in the Swedish Schizophrenia Study and the Taiwan Biobank., Author summary Copy number variants comprise a large proportion of variation in human genomes. Large rare CNVs, especially those disrupting genes or changing the dosages of genes, can carry relatively strong risks for neurodevelopmental and neuropsychiatric disorders. Kernel-based association methods have been developed for the analysis of rare CNVs and shown to be a valuable tool. Kernel methods model the collective effect of rare CNVs using flexible kernel functions that capture the characteristics of CNVs and measure CNV similarity of individual pairs. Typically kernels are created by summarizing similarity within an artificially defined “CNV locus” and then collapsing across all loci. In this work, we propose a new kernel-based test, CONCUR, that is based on the CNV location information contained in standard processing of the variants and which obviates the need for arbitrarily defined CNV loci. CONCUR quantifies similarity between individual pairs as the common area under their copy number profile curves and is designed to detect CNV dosage, length and dosage-length interaction effects. In simulation studies and real data analysis, we demonstrate the ability of the CONCUR test to detect CNV effects under diverse CNV architectures with power and robustness over existing methods.

We have measured the properties of scintillation light in liquid argon doped with xenon concentrations from 165 ppm to 10,010 ppm using a $^{22}$Na source. The energy transfer processes in the xenon-doped liquid argon are discussed in detail, and a new waveform model is established and used to fit the average waveform. The time profile of the scintillation photon in the xenon-doped liquid argon and of the TPB emission are presented. The quantities of xenon-doped are controlled by a Mass Flow Controller which is calibrated via a Redusial Gas Analyzer to ensure that the xenon concentration is accurate. In addition, a successful test of $^{83{\rm m}}$Kr as a calibration source has been implemented in the xenon-doped liquid argon detector for the first time. By comparing the light yield of the $^{22}$Na and $^{83{\rm m}}$Kr, it can be concluded that the scintillation efficiency is almost same over the range of 41.5 keV to 511 keV., Comment: 17 pages, 16 figures

Codonopsis pilosula is a kind of traditional Chinese medicine used to treat weak spleens, stomach problems, anemia, and fatigue. Polysaccharide is one of main components of Codonopsis pilosula. In this study, response surface methodology (RSM) was used to optimize the extraction parameters of Codonopsis pilosula polysaccharides (CPP) by fermentation. The exaction temperature (°C), yeast liquid volume (2 mg/ml, ml), and time (h) were employed effects. Results indicated that the best extraction conditions were the following: extraction temperature 24.75°C, yeast liquid volume 2.96 ml (5.92 mg), and a fermentation time of 21.03 hr. After purification with DE52 and Sephadex G-100, the molecular structure was determined by ultraviolet-visible (UV) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) (1H and 13C). The monosaccharide composition of CPP1 was determined to be mannose (1.76%), glucose (97.38%), and arabinose (0.76%). CPP1 exhibited high antioxidant activities in scavenging ABTS radicals, ferreous ions, and superoxide ion radicals. Thus, CPP1 could be used as an antioxidant or functional food.

This paper demonstrated the fabrication of a facile, low-cost, and self-powered platform for point-of-care fitness level and athletic performance monitoring sensor using electrochemical lithography method and its application in body fluid sensing. Flexible Au/prussian blue electrode was employed as the indicating electrode, where the color change was an indication of fitness level and athletic performance. A piece of Al foil, Au/multiwalled carbon nanotubes (MWCNTs)-glucose dehydrogenase, and Au/polymethylene blue-MWCNTs-lactic dehydrogenase electrodes were used for the detection of ionic strength, glucose, and lactic acid in sweat, respectively, which allows the sensor to work without any extra instrumentation and the output signal can be recognized by the naked eyes. The advantages of these sensors are (1) self-powered; (2) readily applicable to the detection of any electroactive substance by an electrochromic material; (3) easy to fabricate via two steps of EDP; and (4) point-of-care. By assembling the energy and sensing components together through a transparent adhesive tape, the proposed self-powered wearable biosensor exhibits superior performances, indicating its broad applied prospect in the point-of-care diagnoses.