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This paper mainly discusses the mechanical characteristics of steel-reinforced reactive powder concrete (SRRPC) columns with different geometrical dimensions after high-temperature treatment. The bearing capacity, axial stiffness, and ductility of 35 SRRPC column specimens after high-temperature treatment are investigated, considering two parameters: concrete cover thickness (30–100 mm) and slenderness ratio (3–50). The findings indicate that (1) the ultimate bearing capacity increases by 26.0–135.7% as the concrete cover thickness increases and decreases by 1.5–92.0% as the slenderness ratio increases. (2) The axial stiffness increases by 18.9–92.5% as the concrete cover thickness increases and sharply decreases by 31.9–92.6% as slenderness ratio increases, and change degree decreases. (3) As concrete cover thickness and slenderness ratio increase, the displacement ductility coefficient declines, and degree of decrease in displacement ductility coefficient becomes progressively smaller. (4) The bearing capacity, stiffness, and ductility are extremely sensitive to concrete cover thickness, followed by slenderness ratio. Considering confining effect of stirrups and section steel on concrete in the core area, methods for calculating bearing capacity after high-temperature treatment are proposed. From the perspectives of preventing buckling instability and cracking of components after high temperature, two methods for determining the critical concrete cover thickness are given. Finally, the calculation formula of the stability coefficient corresponding to various slenderness ratios after high-temperature exposure is provided, which provides a reference for postfire evaluation and reinforcement of SRRPC structure. [ABSTRACT FROM AUTHOR]

Quantum computing has already demonstrated great computational potential across multiple domains and has received more and more attention. However, due to the connectivity limitations of Noisy Intermediate-Scale Quantum (NISQ) devices, most of the quantum algorithms cannot be directly executed without the help of inserting SWAP gates. Nevertheless, more SWAP gates lead to a longer execution time and, inevitably, lower fidelity of the algorithm. To this end, this paper proposes an optimized qubit mapping algorithm based on a dynamic look-ahead strategy to minimize the number of SWAP gates inserted. Firstly, a heuristic algorithm is proposed based on maximizing physical qubit connectivity to generate the optimal initial qubit mapping, which reduces the need for logical qubit shifts during subsequent SWAP gate insertion. Secondly, in the form of directed acyclic graphs, we identify quantum gates that violate the constraints of physical coupling and insert SWAP gates to remap qubits, thereby overcoming the limitations of qubit interactions. Finally, the optimal SWAP gate insertion strategy is built by comparing the cost of different SWAP gate insertion strategies through a multi-window look-ahead strategy to reduce the number of SWAP gates inserted. The experimental results show that the strategy in this paper decreases the number of SWAP gate insertions and significantly reduces the depth of quantum circuits when performing qubit mapping compared with state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Chromatin states are functionally defined by a complex combination of histone modifications, transcription factor binding, DNA accessibility and other factors. Current methods for defining chromatin states cannot measure more than one aspect in a single experiment at single-cell resolution. Here we introduce nanobody-tethered transposition followed by sequencing (NTT-seq), an assay capable of measuring the genome-wide presence of up to three histone modifications and protein–DNA binding sites at single-cell resolution. NTT-seq uses recombinant Tn5 transposase fused to a set of secondary nanobodies (nb). Each nb–Tn5 fusion protein specifically binds to different immunoglobulin-G antibodies, enabling a mixture of primary antibodies binding different epitopes to be used in a single experiment. We apply bulk-cell and single-cell NTT-seq to generate high-resolution multimodal maps of chromatin states in cell culture and in human immune cells. We also extend NTT-seq to enable simultaneous profiling of cell surface protein expression and multimodal chromatin states to study cells of the immune system. Cell surface protein expression and multiple epigenetic features are mapped simultaneously in single cells. [ABSTRACT FROM AUTHOR]

It has been proven that intra-articular injection of mesenchymal stromal cells (MSCs) can alleviate cartilage damage in osteoarthritis (OA) by differentiating into chondrocytes and protecting inherent cartilage. However, the mechanism by which the OA articular microenvironment affects MSCs' therapeutic efficiency is yet to be fully elucidated. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in various cellular processes, such as osteogenesis and immune regulation. Tryptophan (Trp) metabolites, most of which are endogenous ligand for AHR, are abnormally increased in synovial fluid (SF) of OA and rheumatoid arthritis (RA) patients. In this study, the effects of kynurenine (KYN), one of the most important metabolites of Trp, were evaluated on the chondrogenic and chondroprotective effects of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs). hUC-MSCs were cultured in conditioned medium containing different proportions of OA/RA SF, or stimulated with KYN directly, and then, AHR activation, proliferation, and chondrogenesis of hUC-MSCs were measured. Moreover, the chondroprotective efficiency of short hairpin-AHR-UC-MSC (shAHR-UC-MSC) was determined in a rat surgical OA model (right hind joint). OA SF could activate AHR signaling in hUC-MSCs in a concentration-dependent manner and inhibit the chondrogenic differentiation and proliferation ability of hUC-MSCs. Similar results were observed in hUC-MSCs stimulated with KYN in vitro. Notably, shAHR-UC-MSC exhibited superior therapeutic efficiency in OA rat upon intra-articular injection. Taken together, this study indicates that OA articular microenvironment is not conducive to the therapeutic effect of hUC-MSCs, which is related to the activation of the AHR pathway by tryptophan metabolites, and thus impairs the chondrogenic and chondroprotective effects of hUC-MSCs. AHR might be a promising modification target for further improving the therapeutic efficacy of hUC-MSCs on treatment of cartilage-related diseases such as OA. [ABSTRACT FROM AUTHOR]

Technologies that profile chromatin modifications at single-cell resolution offer enormous promise for functional genomic characterization, but the sparsity of the measurements and integrating multiple binding maps represent substantial challenges. Here we introduce single-cell (sc)CUT&Tag-pro, a multimodal assay for profiling protein–DNA interactions coupled with the abundance of surface proteins in single cells. In addition, we introduce single-cell ChromHMM, which integrates data from multiple experiments to infer and annotate chromatin states based on combinatorial histone modification patterns. We apply these tools to perform an integrated analysis across nine different molecular modalities in circulating human immune cells. We demonstrate how these two approaches can characterize dynamic changes in the function of individual genomic elements across both discrete cell states and continuous developmental trajectories, nominate associated motifs and regulators that establish chromatin states and identify extensive and cell-type-specific regulatory priming. Finally, we demonstrate how our integrated reference can serve as a scaffold to map and improve the interpretation of additional scCUT&Tag datasets.scCUT&Tag-pro measures a histone modification and surface proteins in single cells. [ABSTRACT FROM AUTHOR]

Porous liquids with chemical separation properties are quite well-studied in general, but there is only a handful of reports in the context of identification and separation of non-gaseous molecules. Herein, we report a Type II porous ionic liquid composed of coordination cages that exhibits exceptional selectivity towards l-tryptophan (l-Trp) over other aromatic amino acids. A previously known class of anionic organic–inorganic hybrid doughnut-like cage (HD) is dissolved in trihexyltetradecylphosphonium chloride (THTP_Cl). The resulting liquid, HD/THTP_Cl, is thereby composed of common components, facile to prepare, and exhibit room temperature fluidity. The permanent porosity is manifested by the high-pressure isotherm for CH4 and modeling studies. With evidence from time-dependent amino acid uptake, competitive extraction studies and molecular dynamic simulations, HD/THTP_Cl exhibit better selectivity towards l-Trp than other solid state sorbents, and we attribute it to not only the intrinsic porosity of HD but also the host-guest interactions between HD and l-Trp. Specifically, each HD unit is filled with nearly 5 l-Trp molecules, which is higher than the l-Trp occupation in the structure unit of other benchmark metal-organic frameworks. Porous liquids are potentially useful materials for the identification and separation of non-gaseous compounds. Herein, the authors report a type II porous ionic liquid with permanent porosity and high selectivity towards l-tryptophan (l-Trp) over other aromatic amino acids. [ABSTRACT FROM AUTHOR]

Adhesion G protein-coupled receptors (aGPCRs) are essential for a variety of physiological processes such as immune responses, organ development, cellular communication, proliferation and homeostasis1–7. An intrinsic manner of activation that involves a tethered agonist in the N-terminal region of the receptor has been proposed for the aGPCRs8,9, but its molecular mechanism remains elusive. Here we report the G protein-bound structures of ADGRD1 and ADGRF1, which exhibit many unique features with regard to the tethered agonism. The stalk region that proceeds the first transmembrane helix acts as the tethered agonist by forming extensive interactions with the transmembrane domain; these interactions are mostly conserved in ADGRD1 and ADGRF1, suggesting that a common stalk–transmembrane domain interaction pattern is shared by members of the aGPCR family. A similar stalk binding mode is observed in the structure of autoproteolysis-deficient ADGRF1, supporting a cleavage-independent manner of receptor activation. The stalk-induced activation is facilitated by a cascade of inter-helix interaction cores that are conserved in positions but show sequence variability in these two aGPCRs. Furthermore, the intracellular region of ADGRF1 contains a specific lipid-binding site, which proves to be functionally important and may serve as the recognition site for the previously discovered endogenous ADGRF1 ligand synaptamide. These findings highlight the diversity and complexity of the signal transduction mechanisms of the aGPCRs.Cryo-electron microscopy structures of the adhesion G protein-coupled receptors ADGRD1 and ADGRF1 provide insight into how these receptors are activated in an intrinsic manner through a ‘stalk’ region that acts as a tethered agonist. [ABSTRACT FROM AUTHOR]

Tryptophan 2,3-dioxygenase (TDO2) was an initial rate-limiting enzyme of the kynurenine (Kyn) pathway in tryptophan (Trp) metabolism. We undertook this study to determine a comprehensive analysis of TDO2 expression in immune cells and assess the characterization of immune cell phenotype in TDO2 knockout mice. The expression of TDO2 in various tissues of DBA/1 mice was detected by quantitative real-time PCR (qPCR) and immunohistochemistry. Both flow cytometry and immunofluorescence were used to analyze the expression of TDO2 in immune cells. Furthermore, TDO2 knockout (KO) mice were generated by CRISPR/Cas9 technology to detect immune cell phenotype. TDO2 protein level in liver was tested by western blot. High-performance liquid chromatography was used to detect the level of Trp and Kyn. Flow cytometry was used to test the proportions of splenic lymphocyte subsets in wild-type (WT) and TDO2 KO mice. We found that TDO2 was expressed in various tissues and immune cells, and TDO2 staining was mainly observed in the cytoplasm of cells. There was no difference in the development of immune cells between TDO2 KO mice and WT mice, including T cells, B cells, memory B cells, plasma cells, dendritic cells, and natural killer cells. Interestingly, the reduced M1/M2 ratio was observed in the peritoneal macrophages of TDO2 KO mice. Taken together, these findings enriched the known expression profile of TDO2, especially its expression in immune cells. Our study suggested that TDO2-mediated Trp-Kyn metabolism pathway might be involved in the immune response. [ABSTRACT FROM AUTHOR]

High-quality tellurium zinc cadmium (CZT) crystal materials and tellurium cadmium mercury (MCT) epitaxial materials are the key materials for the preparation of high-performance MCT-cooled detectors. Studying the relationship between material defects and device imaging is essential for improving the material quality and device performance. In this work, we summarize the defects of the CZT single crystal and the surface defects of the MCT film. Furthermore, we demonstrate the effect of CZT and MCT material defects and lattice matching on the imaging performance of the chips, and summarize the material quality improvement and the standard control methods. Through processes such as heat treatment, the size of the inclusions is controlled to be less than 20 μm and the density is less than 20 cm−2. A focal plane array (FPA) with good uniformity imaging (NETD 14.9 mK, defective pixel rate 0.03%) can be obtained by improving the material preparation level and formulating suitable material selection standards. Based on the continuous improvement of yield of FPA preparation process, MCT detectors can be fabricated in batches based on the optimized material quality. [ABSTRACT FROM AUTHOR]

For evaluating the influence of the Chinese renminbi (RMB) joining in the special drawing right (SDR) basket on RMB's internationalization, the authors systemically study the risk spillover networks and examine the dynamic relationship of exchange rates among the SDR currencies including the US dollar (USD), European Union euro (EUR), Japanese yen (JPY) and British pound (GBP). The empirical results demonstrate that the USD takes a dominant position and holds the biggest risk spillover to other currencies, and the RMB's inclusion to the SDR basket makes the risk spillover to get average, giving rise to the SDR currency system more stable to a certain degree. The inclusion of the RMB in the SDR not only can reduce the systematic risk of the SDR, but also has a certain impact on the international exchange rate markets. Nowadays, in front of the growing trade friction, more such researches could help to effectively deal with the currency disputes. [ABSTRACT FROM AUTHOR]

Based on a novel algorithm, known as the upper-layer-solution-aware (USA), a new algorithm, in which the penalty method is introduced into the empirical risk, is studied for training feed-forward neural networks in this paper, named as USA with penalty. Both theoretical analysis and numerical results show that it can control the magnitude of weights of the networks. Moreover, the deterministic theoretical analysis of the new algorithm is proved. The monotonicity of the empirical risk with penalty term is guaranteed in the training procedure. The weak and strong convergence results indicate that the gradient of the total error function with respect to weights tends to zero, and the weight sequence goes to a fixed point when the iterations approach positive infinity. Numerical experiment has been implemented and effectively verifies the proved theoretical results. [ABSTRACT FROM AUTHOR]

mime-subtype="jpeg" mimetype="image" xlink:href="S2159685919000429_figAb" xmlns:xlink="http://www.w3.org/1999/xlink" /> Solid state batteries are an emerging alternative to traditional liquid electrolyte cells that provide potential for safe and high-energy density power sources. This report describes a self-forming, solid state battery based on the Li/I2 couple using an LiI-rich LiI(3-hydroxypropionitrile)2 electrolyte (LiI–LiI(HPN)2). As the negative and positive active materials are generated in situ, the solid electrolyte–current collector interfaces play a critical role in determining the electrochemical response of the battery. Herein, we report the investigation of solid electrolyte–current collector interfaces with a self-forming LiI–LiI(HPN)2 solid electrolyte and the role of varying interface design in reducing resistance during cycling. [ABSTRACT FROM AUTHOR]

Objective: Many studies have confirmed the glucose-lowering effect of berberine in type 2 diabetes patients. Although the mechanism of action of berberine involves the improvement of insulin sensitivity, its hypoglycemic mechanism remains elusive. Here we show a new mechanism by which berberine antagonizes glucagon signaling and find that SIRT3 is involved in the hypoglycemic effect of berberine.Methods: Gene knockout and overexpression were used to assess the inhibitory effect of berberine on SIRT3. Downstream signaling pathways and the hypoglycemic effect of SIRT3 were evaluated by immunoblotting and metabolic monitoring.Results: We found that berberine led to mitochondrial dysfunction and AMP accumulation by inhibiting deacetylase SIRT3. We confirmed that AMP accumulation activated the AMPK signaling pathway and further promoted glucose uptake. Simultaneously, AMP accumulation reduced cyclic AMP (cAMP) levels and abrogated the phosphorylation of critical protein targets of protein kinase A (PKA). Furthermore, we found that phosphoenolpyruvate carboxykinase 1 (PEPCK1) is a key gluconeogenesis enzyme that can be stabilized by glucagon. Berberine caused significant PEPCK1 ubiquitination and degradation by antagonizing glucagon and was accompanied by high levels of PEPCK1 acetylation. Interestingly, berberine-induced glucagon inhibition is independent of AMPK activation. The in vivo data from sirt3 knockout mice were further confirmed by the in vitro experiments.Conclusions: Berberine promotes glucose uptake and inhibits gluconeogenesis by inhibiting SIRT3, and regulating mitochondria-related pathways may provide a novel approach to the development of antidiabetic drugs. [ABSTRACT FROM AUTHOR]

Frizzled receptors (FZDs) are class-F G-protein-coupled receptors (GPCRs) that function in Wnt signalling and are essential for developing and adult organisms1,2. As central mediators in this complex signalling pathway, FZDs serve as gatekeeping proteins both for drug intervention and for the development of probes in basic and in therapeutic research. Here we present an atomic-resolution structure of the human Frizzled 4 receptor (FZD4) transmembrane domain in the absence of a bound ligand. The structure reveals an unusual transmembrane architecture in which helix VI is short and tightly packed, and is distinct from all other GPCR structures reported so far. Within this unique transmembrane fold is an extremely narrow and highly hydrophilic pocket that is not amenable to the binding of traditional GPCR ligands. We show that such a pocket is conserved across all FZDs, which may explain the long-standing difficulties in the development of ligands for these receptors. Molecular dynamics simulations on the microsecond timescale and mutational analysis uncovered two coupled, dynamic kinks located at helix VII that are involved in FZD4 activation. The stability of the structure in its ligand-free form, an unfavourable pocket for ligand binding and the two unusual kinks on helix VII suggest that FZDs may have evolved a novel ligand-recognition and activation mechanism that is distinct from that of other GPCRs. The crystal structure of the Frizzled 4 receptor transmembrane domain is reported to a resolution of 2.4 Å in a ligand-free state. [ABSTRACT FROM AUTHOR]

The recognition of adverse environmental impact of acid rain is a prerequisite for finding feasible approaches to alleviate such damage to plants. We studied the regulation of nitrogen and phosphorus absorption by plasma membrane H-ATPase and its expression at transcriptional levels in rice roots exposed to acid rain under hydroponic conditions. At pH 5.0 and 3.5, acid rain increased activity of plasma membrane H-ATPase by increasing transcriptional levels of OSA1, 4, 5, 6, 7, 8, 9, and 10 and promoted ammonium absorption. However, nitrates and phosphorus contents in roots were decreased by acid rain (pH 3.5) due to a decrease in the H gradient. At pH 2.5, acid rain decreased nitrogen and phosphorus content in roots by decreasing plasma membrane H-ATPase activity and its expression at transcriptional levels ( OSA1- OSA10) as well as synthesis of ATP and inhibited the growth. After a 5-day recovery (without acid rain), all the parameters in roots treated with acid rain (pH 5.0 or 3.5) were greater than the data measured during the exposure period. However, all the parameters in roots treated with acid rain (pH 2.5) could not be recovered because heavy acid rain caused irreversible inhibition on plasma membrane H-ATPase activity. Hence, we concluded that plasma membrane H-ATPase plays a role in adaptation of rice seedlings to acid rain by regulating the absorption of nitrogen and phosphorus. [ABSTRACT FROM AUTHOR]

Acid rain caused a severe loss on agricultural productivity, aggravating the challenge for achieving sustainable food production to feed the increasing globe population. To clarify the mechanism on adaptation of rice root to acid rain, we studied the root morphology and growth regulated by nutrient absorption under hydroponic conditions. Our results show that acid rain (pH 5.0 or 3.5) increased the density of root hair and root volume by increasing concentrations of K, Na, and Ca in rice roots, and the root dry weight was increased. However, strong acid rain (pH 2.5) decreased the root length, surface area, volume, and number of root tips by decreasing the concentrations of K, Na, and Mg in rice root, and fresh and dry weight were both decreased. After a 5-day recovery, the root morphology of rice seedlings treated with acid rain (pH 5.0 or 3.5) was recovered to the control levels, and the concentrations of K, Na, Ca, and Mg also had no difference from the control ( p < 0.05). However, the root growth treated with strong acid rain (pH 2.5) was still lower than the control because the inhibition on root activity and hydrolytic activity of plasma membrane H-ATPase might have exceeded the self-regulating capacity of rice seedlings, and the absorption of mineral nutrient could not sustain the growth. Hence, we concluded that the adaption of root morphology of rice seedlings to acid rain was related to regulation of mineral nutrient absorption in rice root. [ABSTRACT FROM AUTHOR]

Palindromic sequences are important DNA motifs related to gene regulation, DNA replication and recombination, and thus, investigating the evolutionary forces shaping the distribution pattern and abundance of palindromes in the genome is substantially important. In this article, we analyzed the abundance of palindromes in the genome, and then explored the possible effects of several genomic factors on the palindrome distribution and abundance in Drosophila melanogaster. Our results show that the palindrome abundance in D. melanogaster deviates from random expectation and the uneven distribution of palindromes across the genome is associated with local GC content, recombination rate, and coding exon density. Our data suggest that base composition is the major determinant of the distribution pattern and abundance of palindromes and the correlation between palindrome density and recombination is a side-product of the effect of compositional bias on the palindrome abundance. [ABSTRACT FROM AUTHOR]