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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.

Dynamic epigenomic reprogramming occurs during mammalian oocyte maturation and early development. However, the underlying transcription circuitry remains poorly characterized. By mapping cis-regulatory elements using H3K27ac, we identified putative enhancers in mouse oocytes and early embryos distinct from those in adult tissues, enabling global transitions of regulatory landscapes around fertilization and implantation. Gene deserts harbour prevalent putative enhancers in fully grown oocytes linked to oocyte-specific genes and repeat activation. Embryo-specific enhancers are primed before zygotic genome activation and are restricted by oocyte-inherited H3K27me3. Putative enhancers in oocytes often manifest H3K4me3, bidirectional transcription, Pol II binding and can drive transcription in STARR-seq and a reporter assay. Finally, motif analysis of these elements identified crucial regulators of oogenesis, TCF3 and TCF12, the deficiency of which impairs activation of key oocyte genes and folliculogenesis. These data reveal distinctive regulatory landscapes and their interacting transcription factors that underpin the development of mammalian oocytes and early embryos.

Based on classical nucleation and growth theory, the phase evolution of martensite α′ phase of additively manufactured Ti-6.9Al-6.8Zr-2.3Mo-2.2V-0.7Nb alloy under different annealing temperatures (600–960 °C) was systematically investigated. The results show that: Owing to insufficient diffusion of alloy elements during laser deposition, numerous β-stabilizing elements are retained in α′ phase and the microstructure is made up of 95.4% α′ phase and 4.6% β phase. According to TEM, EBSD, SEM/EDX results, the α′ phase can be divided into α′ phase containing more β-stabilizing elements (α′β), α′ phase containing more Al (α′Al). Under annealing condition, martensite decomposition tends to occur at the α′/α' interfaces and the matrix of α′βphase. In the matrix of α′βphase, fine adjacent α′ phase precipitates at β phase because a lot of β-stabilizing elements are consumed by precipitated β phase, thus improving the precipitation of adjacent α′ phase. The decomposition of α′ phase is controlled by diffusion of alloy elements. As the temperature increases, the diffusion of alloy elements and degree of α′ martensitic decomposition become more sufficient. When the Al content in the α′ phase reaches that in equilibrium α phase, the lattice parameters of α′ phase increase from a = 2.97 Å, c = 4.72 Å to a = 3.04 Å, c = 4.77 Å and meanwhile the α′ martensitic decomposition is finished.

The GLP-1 receptor, one of the most successful drug targets for the treatment of type 2 diabetes and obesity, is known to engage multiple intracellular signaling proteins. However, it remains less explored how the receptor interacts with proteins on the cell membrane. Here, we present a ligand-based proximity labeling approach to interrogate the native cell membrane interactome for the GLP-1 receptor after agonist simulation. Our study identified several unreported putative cell membrane interactors for the endogenous receptor in either a pancreatic β cell line or a neuronal cell line. We further uncovered new regulators of GLP-1 receptor-mediated signaling and insulinotropic responses in β cells. Additionally, we obtained a time-resolved cell membrane interactome map for the receptor in β cells. Therefore, our study provides a new approach that is generalizable to map endogenous cell membrane interactomes for G-protein-coupled receptors to decipher the molecular basis of their cell-type-specific functional regulation.

The immune response to SARS-CoV-2 antigen after infection or vaccination is defined by the durable production of antibodies and T cells. Population-based monitoring typically focuses on antibody titer, but there is a need for improved characterization and quantification of T cell responses. Here, we used multimodal sequencing technologies to perform a longitudinal analysis of circulating human leukocytes collected before and after immunization with the mRNA vaccine BNT162b2. Our data indicated distinct subpopulations of CD8+T cells, which reliably appeared 28 days after prime vaccination. Using a suite of cross-modality integration tools, we defined their transcriptome, accessible chromatin landscape and immunophenotype, and we identified unique biomarkers within each modality. We further showed that this vaccine-induced population was SARS-CoV-2 antigen-specific and capable of rapid clonal expansion. Moreover, we identified these CD8+T cell populations in scRNA-seq datasets from COVID-19 patients and found that their relative frequency and differentiation outcomes were predictive of subsequent clinical outcomes.

The popularity bias is an outstanding challenge in recommendation systems. Prevalent work based on contrastive learning (CL) alleviates this issue but neglects the relationship among data, which limits the ability of CL and leads to a loss of personalized features of users/items, and thus degrades the performance of the recommendation systems. In this paper, we propose a model-agnostic contrastive learning framework, called Relationship-aware Contrastive Learning (ReACL), to make recommendations to users. ReACL framework utilizes the relationship homophily among data to achieve a uniform distribution for node and align the relevant features to preserve personalized features and avoids the problem of popularity bias. We first combine a graph of user-item interaction with that of a social network to mine views on the relationships of users on social networks as well as those of item commonality. We then apply these two views to construct contrastive learning pairs on the user and item sides, respectively. We design two sample selectors and an augmented contrastive loss function to preserve personalized features. Furthermore, we jointly optimize the tasks of supervised learning and contrastive learning. Finally, we conduct extensive experiments on four public datasets, and the results show that the proposed ReACL framework outperforms state-of-the-art algorithms. [ABSTRACT FROM AUTHOR]

Despite advances in characterizing the structures and functions of G protein-coupled receptors (GPCRs), our understanding of GPCR activation and signaling is still limited by the lack of information on conformational dynamics. It is particularly challenging to study the dynamics of GPCR complexes with their signaling partners because of their transient nature and low stability. Here, by combining cross-linking mass spectrometry (CLMS) with integrative structure modeling, we map the conformational ensemble of an activated GPCR-G protein complex at near-atomic resolution. The integrative structures describe heterogeneous conformations for a high number of potential alternative active states of the GLP-1 receptor–Gscomplex. These structures show marked differences from the previously determined cryo-EM structure, especially at the receptor–Gsinterface and in the interior of the Gsheterotrimer. Alanine-scanning mutagenesis coupled with pharmacological assays validates the functional significance of 24 interface residue contacts only observed in the integrative structures, yet absent in the cryo-EM structure. Through the integration of spatial connectivity data from CLMS with structure modeling, our study provides a new approach that is generalizable to characterizing the conformational dynamics of GPCR signaling complexes.

Graphical abstract:

In order to meet the functional requirements of professional skiers for ski underwear, such as warmth, breathability, moisture absorption, sweat drainage, and stretch elasticity, six single-sided jacquard knit fabric structures were designed and then knitted with polyester and DRYARN. Then, 12 fabrics were acquired and ranked comprehensively by the one-way analysis of variance and grey correlative analysis based on entropy. According to the fabric properties and sweat distribution on the human skin surface, the professional ski underwear was zoning designed and the wearing experiment and evaluation were carried out on the “Newton” sweated manikin system. The analysis results show that the fabric with DRYARN®material has better air permeability and moisture permeability. Thermal resistance, Clo value, and permeability play important roles in comprehensive evaluation. The results of wearing experiment show that the seamless professional ski underwear woven based on body mapping sportswear has superior function and reasonable design, which can provide technical support for the design of professional seamless ski underwear.

Nonstationary fuzzy inference systems (NFISs) model the variation in opinions of individual experts and expert groups. They have the capability similar to type-2 fuzzy systems in some regards with less computational costs. This paper presents a nonstationary fuzzy neural network (NFNN) model by combining NFISs and neural networks (NNs). The proposed model synthesizes the logical inference and language expression abilities of NFIS with the learning mechanism of NNs. Hence, it makes NNs more translatable and also achieves self-learning of fuzzy rules. Besides, a fuzzy c-means network (FCMnet) clustering and a modified conjugate gradient method with constrained Armijo-type rule (MCGA) are proposed to initialize and train NFNN, respectively. The proposed FCMnet first combines the fuzzy c-means (FCM) algorithm with NNs. Thus, it not only improves the performance of FCM, but also makes NNs more interpretable. For MCGA, we construct a specific conjugate coefficient to ensure the sufficient descent property and propose a constrained Armijo-type rule to search a suitable learning rate in each iteration. By adopting these two techniques, MCGA achieves a fast convergence speed. In addition, both weak and strong convergence results are proven rigorously. Experiments on 14 datasets are carried out to illustrate the competitive performance of our models. [ABSTRACT FROM AUTHOR]

A series of novel ortho-terphenylene viologen derivatives (o-TPV2+) with through-space conjugation (TSC) via the combination of ortho-terphenylene skeletons with viologen structure is reported. Their optoelectronic properties can be adjusted by N-arylation or N-alkylation reactions. Compared with other viologen derivatives, o-TPV2+not only exhibits strong photoluminescence but also retards the charge recombination process and stabilizes the diradical state without forming a quinoid structure due to the special TSC effect. Based on their special redox characteristics, o-TPV2+was applied to the photocatalytic oxidative coupling of benzylamine with 96% yield. In addition, pTA-o-TPV2+(tethered with p-toluic acid)-modified g-C3N4was used for visible-light-driven hydrogen production for the first time, exceeding 15 times the rate over unmodified g-C3N4.

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.

A series of V-substituted α-MnO2(KxMn8–yVyO16·nH2O, y= 0, 0.2, 0.34, 0.75) samples were successfully synthesized without crystalline or amorphous impurities, as evidenced by X-ray diffraction (XRD) and Raman spectroscopy. Transmission electron microscopy (TEM) revealed a morphological evolution from nanorods to nanoplatelets as V-substitution increased, while electron-energy loss spectroscopy (EELS) confirmed uniform distribution of vanadium within the materials. Rietveld refinement of synchrotron XRD showed an increase in bond lengths and a larger range of bond angles with increasing V-substitution. X-ray absorption spectroscopy (XAS) of the as-prepared materials revealed the V valence to be >4+ and the Mn valence to decrease with increasing V content. Upon electrochemical lithiation, increasing amounts of V were found to preserve the Mn–Mnedgerelationship at higher depths of discharge, indicating enhanced structural stability. Electrochemical testing showed the y= 0.75 V-substituted sample to deliver the highest capacity and capacity retention after 50 cycles. The experimental findings were consistent with the predictions of density functional theory (DFT), where the V centers impart structural stability to the manganese oxide framework upon lithiation. The enhanced electrochemistry of the y= 0.75 V-substituted sample is also attributed to its smaller crystallite size in the form of a nanoplatelet morphology, which promotes facile ion access via reduced Li-ion diffusion path lengths.

Unadorned carbon nitride was synthesized via different nitrogen-rich precursors by thermal polymerization and applied to multifungicides for simultaneous photodegradation in the present study. Urea-derived carbon nitride (UCN) was verified to be most efficient in fungicide removal. The influences of catalyst dosage and pH were studied during the photodegradation process. Hydroxyl radical (•OH) and holes (h+) are the active species during photodegradation of each of the eight fungicides within an aqueous environment. The primary photodegradation products and pathways of all eight fungicides were systematically identified using liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. In addition, the UCN catalyst was also applied to potted plants. The experimental results revealed that UCN could reduce fungicide residues in plants grown within a contaminated matrix. This study shows promising applications of the UCN catalyst in alleviating the hazards of pesticide residue.

Graphic abstract:

Specific factors correlated with hypothyroidism in systemic lupus erythematosus (SLE) patients remain unclear. Therefore, we aim to evaluate the prevalence of thyroid dysfunction in Chinese patients with SLE and the relationship between clinical hypothyroidism and SLE.

Although naphthalene diimide (NDI) and its derivatives have been widely used for organic Li-ion batteries (OLIBs), they are limited by a low lithium uptake capacity and ambiguous lithiation mechanism. Herein, we report two isometric thionated-NDI cathodes (cis-2Sand trans-2S) obtained by replacing O with S in the imide groups which improves the battery performance compared with parent NDI (P-NDI). Remarkably, the position of S atoms plays an important role as the potential plateau of cis-2Swas 100 mV higher than trans-2S, 256 mV higher than P-NDI, and the capacity of cis-2Swas twice than that of trans-2S, four times as P-NDIafter 400 cycles. The insituRaman, X-ray photoelectron spectroscopy (XPS), and DFT calculations revealed that the lithiation process occurs on the less electronegative S atoms. For cis-2S, the electron density on the lithiation sites is lower than trans-2Sbecause of a stronger electron inductive effect. This in turn enhances the redox potential and cycling stability of cis-2S. This contribution provides an additional molecular engineering strategy to develop novel organic cathode materials for high performance OLIBs.

Subtype selectivity and functional bias are vital in current drug discovery for G protein-coupled receptors (GPCRs) as selective and biased ligands are expected to yield drug leads with optimal on-target benefits and minimal side-effects. However, structure-based design and medicinal chemistry exploration remain challenging in part because of highly conserved binding pockets within subfamilies. Herein, we present an affinity mass spectrometry approach for screening herbal extracts to identify active ligands of a GPCR, the 5-HT2Creceptor. Using this method, we discovered a naturally occurring aporphine 1857 that displayed strong selectivity for activating 5-HT2Cwithout activating the 5-HT2Aor 5-HT2Breceptors. Remarkably, this novel ligand exhibited exclusive bias toward G protein signaling for which key residues were identified, and it showed comparable in vivoefficacy for food intake suppression and weight loss as the antiobesity drug, lorcaserin. Our study establishes an efficient approach to discovering novel GPCR ligands by exploring the largely untapped chemical space of natural products.

Around implantation, the epiblast (Epi) transits from naïve to primed pluripotency, before giving rise to the three germ layers. How chromatin is reconfigured during this developmental window remains poorly understood. We performed a genome-wide investigation of chromatin landscapes during this period. We find that enhancers in ectoderm are already pre-accessible in embryonic day 6.5 (E6.5) Epi when cells enter a primed pluripotent state. Unexpectedly, strong trimethylation of histone H3 at lysine 4 (H3K4me3) emerges at developmental gene promoters in E6.5 Epi and positively correlates with H3K27me3, thus establishing bivalency. These genes also show enhanced spatial interactions. Both the strong bivalency and spatial clustering are virtually absent in preimplantation embryos and are markedly reduced in fate-committed lineages. Finally, we show that KMT2B is essential for establishing bivalent H3K4me3 at E6.5 but becomes partially dispensable later. Its deficiency leads to impaired activation of developmental genes and subsequent embryonic lethality. Thus, our data characterize lineage-specific chromatin reconfiguration and a unique chromatin state for primed pluripotency.

Lithium-metal deposition on graphite anodes limits the cycle life and negatively impacts safety of the current state of the art Li-ion batteries. Herein, deliberate interfacial modification of graphite electrodes via direct current (DC) magnetron sputtering of nanoscale layers of Cu and Ni is employed to increase the overpotential for Li deposition and suppress Li plating under high rate charge conditions. Due to their nanoscale, the deposited surface films have minimal impact (∼0.16% decrease) on cell level theoretical energy density. Interfacial properties of the anodes are thoroughly characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and spatially resolved mapping X-ray absorption near edge structure (XANES) spectroscopy. The spectroscopic measurements indicate that the Cu and Ni coatings form oxide upon exposure to an ambient environment, but they are reduced within the electrochemical cell and remain in a metallic state. Li plating is quantified by X-ray diffraction and associated electrochemistry measurements revealing that the surface treatment effectively reduces the quantity of the plated Li metal by ∼50% compared to untreated electrodes. These results establish an effective method using interfacial modification to achieve deliberate control of Li-metal deposition overpotential and reduction of lithium plating on graphite.

The three-dimensional nonlinear finite element model of steel reinforced reactive powder concrete (SRRPC) column was created to analyze mechanical properties after high temperature. Effect of temperature on mechanical behaviors of RPC, section steel and steel bars were taken into account in model. Accuracy of the temperature distribution and the prediction of eccentric bearing capacity after high temperature was verified by comparing experimental results with numerical results. Effects of eccentricity, loading angle, RPC strength, section steel strength and steel ratio on eccentric bearing capacity after high temperature were analyzed. Findings indicate that: there are two typical failure modes of SRRPC columns after high temperature under different eccentric loads, including small and large eccentric compression failure. As eccentricity has increased, residual bearing capacity declines obviously. Increase of RPC strength will greatly increase residual bearing capacity, and improve ductility to a certain extent. Increase of section steel strength and steel ratio can improve residual bearing capacity to a certain extent. Residual bearing capacity is mostly unaffected by the loading angle. Finally, the calculation formula of normal section bearing capacity of SRRPC bias column after high temperature was established based on limit state design method, which has high accuracy and can provide reference for identifying and strengthening composite structures following fire.

A series of chalcogen-containing carborane derivatives were synthesized through a one-pot reaction. The nonconjugated six-membered ring of carborane-fused disulfide (1) can be electrochemically reduced to a dithiolate derivative. The five-membered ring of carborane-fused chalcogenophenes (2−4) showed aromaticity and considerable σ−π conjugation. The dicarborane chalcogenides (5−7) showed intramolecular charge-transfer-induced emission. These chalcogen-containing carborane derivatives provided a useful platform to study the electron interaction systematically and shed some light on the design of carborane-based optoelectronic materials.

The diameters of gold nanorods have profound effects on the analytical performances of the corresponding etching based sensing system.

Affinity mass spectrometry (MS) enables rapid screening of compound mixtures for ligands bound to a specific protein target, yet its current throughput is limited to individually assay pools of 400–2000 compounds. Typical affinity MS screens implemented in pharmaceutical industry laboratories identify putative ligands based on qualitative analysis of compound binding to the target whereas no quantitative information is acquired to discriminate high- and low-affinity ligands in the screening phase. Furthermore, these screens require purification of a stabilized form of the protein target, which poses a great challenge for membrane receptor targets. Here, we describe a new, potentially general affinity MS strategy that allows screening of 20,000 compounds in one pool for highly efficient ligand discovery toward a G protein-coupled receptor (GPCR) target. Quantitative measurement of compound binding to the receptor enables high-affinity ligand selection using both the purified receptor and receptor-embedded cell membranes. This high-throughput, label-free and quantitative affinity MS screen resulted in discovery of three new antagonists of the A2Aadenosine receptor.

Abstract

The oocyte epigenome plays critical roles in mammalian gametogenesis and embryogenesis. Yet, how it is established remains elusive. Here, we report that histone-lysine N-methyltransferase SETD2, an H3K36me3 methyltransferase, is a crucial regulator of the mouse oocyte epigenome. Deficiency in Setd2leads to extensive alterations of the oocyte epigenome, including the loss of H3K36me3, failure in establishing the correct DNA methylome, invasion of H3K4me3 and H3K27me3 into former H3K36me3 territories and aberrant acquisition of H3K4me3 at imprinting control regions instead of DNA methylation. Importantly, maternal depletion of SETD2 results in oocyte maturation defects and subsequent one-cell arrest after fertilization. The preimplantation arrest is mainly due to a maternal cytosolic defect, since it can be largely rescued by normal oocyte cytosol. However, chromatin defects, including aberrant imprinting, persist in these embryos, leading to embryonic lethality after implantation. Thus, these data identify SETD2 as a crucial player in establishing the maternal epigenome that in turn controls embryonic development.

Sodium containing 2 x 4 (0.46nm x 0.92nm) tunnel structured manganese dioxide (Na-2 x 4-MnO2) nanofibers are hydrothermally synthesized. The nanofibrous Na-2 x 4-MnO2 was thoroughly characterized using X-ray diffraction (XRD), thermogravimetric analysis (TGA), inductively coupled plasma optical emission spectroscopy (ICP-OES), N2 sorption, and electron microscopy (SEM and TEM) and is assigned a formula of Na0.25MnO2.0.16H2O. The electrochemistry of Na-2 x 4-MnO2 in non-aqueous Li, Na and Mg batteries is compared for the first time and first cycle delivered capacities were found to be 152mAh/g, 86mAh/g, and 307mAh/g, respectively. Characterization of the active material after electrochemical tests demonstrated that Na-2 x 4-MnO2 preserved both its crystallographic structure and nanofibrous morphology after cycling in Na and Li cells, however, Na-2 x 4-MnO2 lost its crystalline structure after cycling in a Mg based system.

A strategy for the microstructural design to achieve a critical upper limit of uniform nano α precipitates by controlling the amount of dislocations in the pre-deformed matrix after short time aging treatment was proposed in Ti–10Mo–8V–1Fe–3.5Al (all in wt.%, TB3 alloy) β alloy. The optimal processes focused on the interaction of defects, mainly point defects and dislocations that are generated during cold rolling (CR). Texture evolution of α and β phases was also specified. Amount of nano-scaled α precipitates was characterized by the number density of precipitates observed by SEM, which is saturated at ∼204.1μm−2. For the CR 20% sample, a good combination of tensile strength (∼1400MPa) and elongation (∼12%) was achieved after secondary aging at 550 for 1h, which provides an enlightenment for the re-engineering of traditional precipitate-hardening alloys.

The selective construction of various dibora[10]annulenes through mild boron–tin exchange reactions is reported. Dibora[10]annulenes exhibit optical and electrochemical properties of value for future sensing applications. Controlled addition of the Lewis base pyridine to dibora[10]annulenes instigates a selective ring-opening reaction. This work explores a new area of boron chemistry that represents the first step in the potential formation of dibora[10]annulene-derived polymers.

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. 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. 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 sirt3knockout mice were further confirmed by the in vitro experiments. 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.

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.

Transition metal-mediated atom transfer radical polymerization (ATRP) is well known as one of successful reversible deactivation radical polymerizations for synthesizing various designable structures. However, the resultant polymers are usually contaminated or colored by large amounts of metal catalyst, which does not facilitate its industrialization. How to efficiently separate and recycle the metal catalyst has triggered lots of interest in green chemistry and ATRP. In this review, we mainly focus on a recyclable liquid/liquid thermo-regulated phase separable catalysis (TPSC) strategy applied in ATRP, which provides a facile and efficient method combining homogeneous reaction with heterogeneous separation just by simply changing temperature. TPSC-based ATRP systems include but not limit to the following systems: fluorous biphasic system, lower alcohol/alkane biphasic system, poly(ethylene glycol) (PEG) biphasic system and thermo-regulated ionic liquids biphasic system and so on.

Crystallite size reduction is a strategy utilized to increase deliverable capacity by decreasing the path length for lithium ion diffusion. However, reduction in crystallite size may also exacerbate unfavorable reactions within a battery limiting cycle life. Here, differences in capacity retention are observed for silver containing a-MnO2 (silver hollandite, AgHol), with two crystallite sizes. Under 30 mA/g discharge, the smaller crystallite size material (AgHol-S, 5 nm) delivers 266 mAh/g initial capacity with 91% capacity decrease from cycles 2-50. In contrast, the larger crystallite size material (AgHol-L, 14 nm) has an initial capacity of 129 mAh/g and only 9% decrease from cycles 2-50. A second electrochemical test was conducted using a capacity limit rather than a voltage limit. Under those test conditions, the structural distortion for the two materials observed by X-ray absorption spectroscopy (XAS) was similar, yet the terminal voltage decrease was more significant for the small crystallite sized sample. Determination of Mn dissolution revealed Mn solubility 5.4X higher for AgHol-S than AgHol-L with accompanying higher Mn deposition on the negative electrode and increased cell impedance. This study provides quantitative determination of capacity fade as related to structural distortion and transition metal dissolution as related to crystallite size.

With the continuous development of building structures and the increasing demand for use, the composite structure of steel reinforced reactive powder concrete (SRRPC) with excellent bearing capacity, stiffness, ductility, fire resistance and seismic performance was proposed. In this paper, the SRRPC column model was established by finite element software ABAQUS to investigate mechanical characteristics, and consistency within the model and the test results were verified from the aspects of failure phenomenon, load-displacement curve and bearing capacity. On this basis, the influence of calculated length, section steel strength, reinforcing bar strength, stirrup ratio and concrete strength on the mechanical characteristics of SRRPC columns was investigated. The consequences show that: (1) The bearing capacity rose with the rise of concrete strength, section steel strength, reinforcing bar strength and stirrup ratio, and decreased with the rise of calculated length. (2) On the basis of sensitivity analysis of parameters, bearing capacity is highly sensitive to concrete strength and section steel strength, generally to stirrup ratio and calculated length, and minimally to reinforcing bar strength. (3) The load entering the elastic-plastic stage increased with the rise of concrete strength, section steel strength and stirrup ratio, and decreased with the increase of calculated length. (4) The stiffness increased in each phase with the rise of concrete strength, section steel strength, reinforcing bar strength and stirrup ratio, and changed the most in phase C (0.5–0.75 Pu). The stiffness in each phase decreased with the increase of the calculated length, and changed the most in phase B (0.25∼0.5 Pu). Finally, the calculation method of bearing capacity was proposed.

Fast-growing poplar with characteristics of fast growth, convenient processing, and strong adaptability is widely planted all over the world, but it is difficult to be directly used as structural timber due to its loose fibers and low strength. In order to enhance mechanical properties of fast-growing poplar, a new type of steel plate reinforced glulam fast-growing poplar is developed. Nine columns are tested including one fast-growing poplar column, two glued-laminated timber (glulam) columns and six steel plate reinforced glulam columns. The influencing factors include the steel plate thickness and eccentricity. Based on test results, axial stiffness, failure mode, load-displacement and load-strain relationships were investigated. Test results indicate that ultimate load and axial stiffness of steel plate reinforced glulam columns were respectively increased by 134.5–177.5% and 168.5–244.1% compared to fast-growing poplar column. With the increase of steel plate thickness and decrease of eccentricity, ultimate load increased by 10.9–18.3% and 27.2–92.3%, respectively. It was found that steel plate thickness and eccentricity have great impacts on bearing capacity of steel plate reinforced glulam columns. In addition, bearing capacity equation for steel plate reinforced glulam columns was established and test results coincide quite well with calculated results with difference of less than 5%.

Developing efficient photosensitizers for C–P bond construction is highly important and remains a challenge due to the urgently needed for the synthesis of modified nucleosides, nucleotides, and other phosphine-containing ligands. Herein, two pyrene-tethered bismoviologen derivatives (Py-BiV2+) were designed and synthesized for visible-light-induced C–P bonds formation. The photochemical and electrochemical properties of Py-BiV2+were studied systemically, certifying fine-tunable opto-electronic properties through the number of pyrene groups (4, n = 1; 6, n = 2). The prepared Py-BiV2+showed strong light absorption, while retaining good redox features and chromic response features that were inherent to viologens. 4exhibited accelerated photoinduced electron transfer in the presence of the electron donor (pyrene) and the generated 4′ (radical cation) showed higher stability. Accordingly, Py-BiV2+directly served as photosensitizers for the first time in the visible-light-induced C(sp3)–P and C(sp2)–P bonds formation. As expected, these novel viologen derivatives exhibited good catalytic performance and good substrate expansibility under ambient conditions.

Coordination of cell division and cell fate is crucial for the successful development of mammalian early embryos. Aurora kinases are evolutionarily conserved serine/threonine kinases and key regulators of mitosis. Aurora kinase B (AurkB) is ubiquitously expressed while Aurora kinase C (AurkC) is specifically expressed in gametes and preimplantation embryos. We found that increasing AurkC level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis. Changing AurkB level had the opposite effect. The kinase domains of AurkB and AurkC were responsible for their different ability to phosphorylate Histone H3 Serine 10 (H3S10P) and regulate metaphase timing. Using an Oct4-photoactivatable GFP fusion protein (Oct4-paGFP) and fluorescence decay after photoactivation assay, we found that AurkB overexpression reduced Oct4 retention in the nucleus. Finally, we show that blastomeres with higher AurkC level elevated pluripotency gene expression, which were inclined to enter the inner cell mass lineage and subsequently contributed to the embryo proper. Collectively, our results are the first demonstration that the activity of mitotic kinases can influence cell fate decisions in mammalian preimplantation embryos and have important implications to assisted reproduction.

Design and development of novel materials can have a profound impact on the electrochemical properties of energy storage systems. Silver ion when electrochemically reduced to generate conductive silver metal in-situ can provide enhanced conductivity in electrochemical energy storage systems. In this research, Ag2O surface modified silver hollandite (AgxMn8O16, a-MnO2 structure) has been successfully synthesized and its physical, chemical, and electrochemical properties have been studied. The electrochemical tests indicate a higher functional capacity can be delivered with higher Ag2O loading, consistent with an increase in the electric conductivity of the material. This result demonstrates the ability to modulate conductivity in materials by design.

The objective of this study was to evaluate the diagnostic performance of serum thyroglobulin (S-Tg), thyroglobulin in fine-needle aspiration washout (FNA-Tg) and fine-needle aspiration cytology (FNAC) in the detection of lateral metastatic lymph nodes (LNs) in patients with thyroid carcinoma.

Efficient conduction of both electrons and cations (e.g., Li+) has a profound effect on the current and capacity of lithium-based batteries. With this study, we focus on cathode effects, with the preparation of pure silver hollandite materials with variable silver ion content within (intra-tunnel) and on the surface of a-MnO2 tunneled materials, followed by the measurement and analysis of impedance and electrochemistry data. Specifically, pure AgxMn8O16-y materials with low (x = 1.13) and high (x = 1.54) intra-tunnel silver content are compared with AgxMn8O16-y*aAg2O (a = 0.25, 0.63, 1.43) composites prepared via a new Ag2O coating strategy. When the Ag2O (a = 0, 0.25) content is low, the material with higher intra-tunnel silver (x = 1.53) content delivers up to [?]5-fold higher capacity accounted for by a [?]10-fold lower impedance than its lower intra-tunnel silver (x = 1.13) counterpart. In the presence of high Ag2O content (a = 0.63, 1.43), both composites exhibit comparable impedance but the lower intra-tunnel silver (x = 1.13) composite delivers up to [?]1.5-fold higher capacity than higher intra-tunnel silver composite, highlighting the key role of Li+ transport under those conditions. Our results demonstrate material design strategies which can significantly increase electronic and ionic conductivities.

Silver hollandite (Ag1.4Mn8O16) has been synthesized by an aqueous, low-temperature co-precipitation technique to afford silver hollandite with distinct crystallite sizes (10 and 15 nm, identified as S-Ag1.4Mn8O16 and L-Ag1.4Mn8O16, respectively) and equivalent silver content (x), allowing for the deconvolution of electrochemical effects related to crystallite size and silver content. The as-prepared silver hollandite materials were confirmed to be structurally analogous. Notably, TEM imaging reveals a high degree of bundling of S-Ag1.4Mn8O16 nanorods compared to L-Ag1.4Mn8O16 which facilitates more intimate connection of the S-Ag1.4Mn8O16 material with enhanced interparticle contact. The electrochemical behavior and lithium diffusion properties were investigated by galvanostatic cycling, CV, electrochemical impedance, pulsed-discharge experiments, and ex-situ XAS analysis of cycled cathodes. Lithium based electrochemical cells containing S-Ag1.4Mn8O16 delivered a capacity 15X higher than L-Ag1.4Mn8O16 on cycle 1. Ex-situ XAS demonstrated structural change for S-Ag1.4Mn8O16 and formation of Ag0 on insertion of 3.8 Li+ intercalation. However, the samples of L-Ag1.4Mn8O16 were lithiated by a more limited 0.25 molar equivalents, where no significant structural changes were observed. The findings affirm crystallite size significantly impacts electrochemistry independent of cation occupancy of the a-MnO2 type structure.

Steel reinforced concrete (SRC) special-shaped columns have the advantages of high spatial utilization, flexible layout and good economic benefits, which are used in high-rise buildings. However, this composite structure has the disadvantages of high steel content and large fire area, which makes it easier to suffer damage in fire, and even cause the collapse of buildings. This paper presents mechanical properties of SRC cross-shaped columns exposed to high temperature. Seven SRC cross-shaped column specimens were analyzed. Temperature field distribution, failure mode, deformation and fire resistance of specimens were obtained under different axial compression ratios (0.4, 0.6) and eccentricity (0, 40, 60, 80 mm). The results showed that: (1) All specimens were in a condition of compression failure and section steel had partial bending failure with the concrete falling off. (2) The larger eccentricity and axial compression ratio were, the earlier cracks appeared, and the more cracks appeared, the more serious concrete shedding of specimen were. Moreover, the cracks were concentrated especially on the side of loading point (i.e., two sides close to the point where the applied load is located), and the cracks are adjacent to the support of specimen, which appear in the whole length of specimen. (3) Axial compression ratio had a significant influence on fire resistance of SRC cross-shaped columns, and influence of eccentricity on fire resistance was generally little compared with axial compression ratio. The fire resistance declined by 43.48–69.14% as axial compression ratio increased from 0.4 to 0.6. Fire resistance declined by 5.45–45.31% as eccentricity increased from 0 to 80 mm, and it was significantly reduced by 28.12–45.31% when axial compression ratio was 0.6. Finally, fire resistance calculation method of SRC cross-shaped column was obtained, which provided reference for fire resistance design of SRC structure.

Three papers in this issue of Natureuse highly sensitive ChIP–seq assays to describe the dynamic patterns of histone modifications during early mouse embryogenesis, showing that oocytes have a distinctive epigenome and providing insights into how the maternal gene expression program transitions to the zygotic program.

In mammals, extensive chromatin reorganization is essential for reprogramming terminally committed gametes to a totipotent state during preimplantation development. However, the global chromatin landscape and its dynamics in this period remain unexplored. Here we report a genome-wide map of accessible chromatin in mouse preimplantation embryos using an improved assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) approach with CRISPR/Cas9-assisted mitochondrial DNA depletion. We show that despite extensive parental asymmetry in DNA methylomes, the chromatin accessibility between the parental genomes is globally comparable after major zygotic genome activation (ZGA). Accessible chromatin in early embryos is widely shaped by transposable elements and overlaps extensively with putative cis-regulatory sequences. Unexpectedly, accessible chromatin is also found near the transcription end sites of active genes. By integrating the maps of cis-regulatory elements and single-cell transcriptomes, we construct the regulatory network of early development, which helps to identify the key modulators for lineage specification. Finally, we find that the activities of cis-regulatory elements and their associated open chromatin diminished before major ZGA. Surprisingly, we observed many loci showing non-canonical, large open chromatin domains over the entire transcribed units in minor ZGA, supporting the presence of an unusually permissive chromatin state. Together, these data reveal a unique spatiotemporal chromatin configuration that accompanies early mammalian development.

AbstractA new kind of micro-electrolysis ceramic fillers (MCF) used to deal with acrylonitrile simulation wastewater was investigated. Scrap iron, powdered activated carbon (PAC), and clay were employed as raw materials to produce the raw MCF. The raw MCF was calcined at 500–600°C for 20–30 min in anoxic condition. The raw materials mass ratio of MCF was determined as 60% clay, 32% scrap iron, and 8% PAC. The microstructure and physical properties which include bulk density (997.2 kg/m3), grain density (1675.0 kg/m3), water absorption (18.0%), porosity (41.3%), and specific surface area (30.52 m2/g) were determined. The effects of pH value, hydraulic retention time (HRT), and aeration on CODCrand acrylonitrile removal efficiency were studied. The results showed that the optimal conditions were influent pH of 3, HRT of 6 h, and aeration–liquid ratio (A/L) of 10. And the removal efficiency of CODCrand acrylonitrile was 68.8 and 73.9% under the optimal conditions. When micro-electrolysis reactor ran 40 d continuously, the removal efficiency of CODCrand acrylonitrile was stable and the fillers did not become hardened. The system still had a good capacity for wastewater treatment.

Background: Hypertension, diabetes, dyslipidemia, and obesity are prevalent in patients with bullous pemphigoid (BP) and are all components of metabolic syndrome (MS). However, the prevalence of MS in patients with BP is unknown. We aimed to evaluate the relationship between MS and BP and to define the clinical and laboratory characteristics of patients with both conditions.Methods: This retrospective case–control study was conducted for 12 years at Peking Union Medical College (162 with BP and 162 age and sex-matched controls). The components of MS were analyzed and logistic regression was used to identify independent risk factors for BP. In addition, the clinical and laboratory characteristics of patients with BP ± MS were compared.Results: The prevalence of MS in patients with BP was 35.2% and that in controls was 14.8% (p< 0.001). After adjustment for sex and age, multivariate analysis demonstrated a positive correlation between BP and MS [odds ratio (OR) 2.490, 95% confidence interval (CI) 1.040–5.963], diabetes (OR 1.870, 95% CI 1.029–3.396), and overweight or obesity (OR 1.807, 95% CI 1.026–3.182). In the BP group, participants with MS were older (p= 0.006), were less likely to present erythema (p= 0.028), and had higher serum C3 (p= 0.007) and incidence of infection within 1 year of their diagnosis (p= 0.035) than participants without MS.Conclusion: MS and its components hyperglycemia and overweight were found to be independently associated with BP. Therefore, clinicians should screen for MS in patients with BP, especially if they are older, present less erythema, or have a high serum C3.