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Titanium alloy has high deformation resistance and low electrical conductivity, so it is difficult to form by traditional electromagnetic forming (TEMF) at room temperature. Direct pulse current electromagnetic forming (DPCEMF) simultaneously combines electromagnetic forming and pulse current heating. This study investigates the microstructure evolution and deformation mechanism of titanium alloy sheet during DPCEMF through the microscopic characterization. Results show that the β phase volume fraction of DPCEMF-0.3 enhanced 262.5 % compared with that of TEMF-0.3. The KAM distribution of DPCEMF-0.3 is uniform and average KAM value is obviously smaller compared to the TEMF-0.3, which is indicated that the dislocation density decreases in DPCEMF. And the average Schmidt factor value of DPCEMF-0.3 specimen is larger than the TEMF-0.3, indicating a more favorable slip system activating in the DPCEMF. Although the electromagnetic field and high strain rate deformation could accelerate phase transition during the DPCEMF, the most important factor that promoted the phase transition was the electric pulse and thermal effects. The drift electrons of pulse current can push dislocations when the high density pulse current passes through the DPCEMF specimen, reduce the dislocation density, and enhance dislocation mobility. At the same time, the dynamic recrystallization inhibited directional grain growth, resulting in a large reduction in texture strength and a diffused orientation. The deformation mechanism of DPCEMF is dislocation plane-slip. The main softening mechanisms of DPCEMF are electropulsing thermal effect and dynamic recrystallization.

The wettability of shale is an important factor affecting oil and gas extraction, and conventional experimental methods are difficult to study at the nanoscale. Moreover, most existing studies are qualitatively based on the wettability of rock surfaces with little consideration for their impact on the CO2-EOR. This study employs molecular dynamics simulation methods to conduct an in-depth analysis of the role of rock surface wettability in the CO2-enhanced oil recovery (EOR) process. The research findings indicate that as the surface hydroxyl content increases, the adsorption affinity for CO2is enhanced, with the selectivity increasing exponentially from 0.74 in the strongly oleophilic wetting (SOW) pore to 3.62 in the strong hydrophilic wetting (SHW) pore. Additionally, variations in wettability result in different types of CO2displacement. As oil wettability decreases, the contact interface between CO2and oil changes from a convex to a concave shape. Moreover, different types of wettability result in different dynamic contact angle changes over time, which significantly impacts various displacement stages. A comprehensive comparison shows that pores exhibiting oil-wet characteristics reduce the efficiency of the CO2-EOR. Finally, the investigation explored the influence of pore structure on oil displacement efficiency. In double pores, when the larger pores exhibit hydrophobic characteristics, they further accelerate the displacement speed of the smaller pores. In connected pores, the presence of notch speeds up the displacement effect within the smaller pores, reducing the impact of wettability on displacement efficiency. This study deeply analyzes the role of shale surface wettability in the CO2-EOR process, revealing the impact of wettability on the CO2adsorption affinity, fluid displacement, oil displacement efficiency, and flow characteristics of shale oil, providing an important theoretical basis for optimizing the CO2-EOR process by adjusting wettability.

This article presents a 3.3–4.5-GHz fractional- $N$ analog sampling phase-locked loop (SPLL). A merged constant-slope digital-to-time converter and sampling phase detector (CSDTC-SPD) allows phase error detection as well as quantization noise (QN) cancellation in a single ramp generation, which reduces the source of noise and nonlinearity. A modified multimodulus divider (MMDIV) with two phase retimers reduces the required CSDTC-SPD linear range and decreases the noise from the CSDTC-SPD. To verify the principle, a prototype SPLL was implemented and fabricated in a conventional 40-nm CMOS technology. The measured results show the merits of an rms jitter of 203 fs with 2.4-mW power, which leads to a phase-locked loop (PLL) figure of merit (FoM) of −250 dB.

This article reported the application of wrist-ankle acupuncture with the ultrasound-guided interfascial plane block (Transversus abdominis plane block,TAPB; Rectus sheath block, RSB; Rhomboid intercostal and sub–serratus block, RISSB) in two emergency laparotomy in elderly frail patients. These cases were successfully completed with only a small dosage of narcotic analgesics, and the patient's spontaneous breathing was preserved and the vital signs of the patients were stable with the Visual Analogue Scale (VAS) of 2 points and the oxygen saturation level over 95%. Both patients recovered soon after the surgery. The combination of wrist-ankle acupuncture and interfascial plane block to preserve spontaneous breathing during laparotomy in elderly frail patients in China had not been previously reported.

Urban green space promotes the health of urban residents, enhances urban ecosystem biodiversity, mitigates environmental pollution, and attenuates urban heat island effect. However, urban vegetation cover is highly heterogeneous and difficult to quantify. In this study, the variation of urban fractional vegetation cover (FVC) in 328 cities in China from 1990 to 2022 was quantified based on Landsat satellite data at a 30-m resolution. It was found that from 1990 to 2005, due to increases in building density and impervious surfaces in cities, the national mean urban vegetation cover decreased from 0.38 to 0.35. After 2005, urban vegetation cover began to reverse, reaching 0.45 in 2022. This increasing trend was most pronounced in newly built urban districts. The decrease in average urban vegetation cover before 2005 was mainly due to the expansion of low vegetation cover areas, while the increase in urban vegetation cover after 2005 manifested as the expansion of high vegetation cover areas. The reversal in the trend of urban vegetation cover change after 2004 is related to the gradual implementation of national policies requiring increased urban green space coverage. The urban gross domestic product (GDP) showed the highest correlation with changes in urban vegetation cover. For large and medium-sized cities, the top three factors influencing vegetation cover were GDP, urban population, and temperature. However, for cities in arid/semi-arid regions, changes in vegetation cover were more sensitive to climatic factors (such as precipitation). Although the urban vegetation cover in China has substantially increased in recent years, the urban green space in small-sized cities and in the old urban districts of large-sized cities still have room to improve.

Wide-field telescopes are widely utilized to observe geosynchronous objects, with low cost and high performance. In geosynchronous object detection, stars produce the most false alarms. Thus, star-suppression is required to improve the accuracy of geosynchronous object detection. However, traditional methods involve false identification and missing identification due to the significant distortion of wide-field telescopes and undersampling of faint images. Distortion could lead to the observed positions of stars deviating from their theoretical positions, while faint and undersampling images could result in inaccurate centroid extraction. In this study, a method was proposed for analyzing the motion and structural characteristics of stars, space objects, and noise, focusing on maintaining a high star identification rate and low false identification rate with the mentioned errors. First, the invariance of the star structure under the influence of projection transformation and distortion was strictly derived. Second, two types of star-pair indices were suggested. Assessment of the structural stability was added to the foundation of the centroid matching. For accurate identification of stars, the influence of dynamic distortion was effectively inhibited using the established star-structure evaluation system. Our method achieves lightweight, straightforward, and rapid detection without requiring any prior star catalog or telescope distortion model. The experiment demonstrates that the performance of the proposed method is superior to that of previous methods influenced by distortion and centroid positioning error.

Quasi-1D nanoribbons provide a unique route to diversifying the properties of their parent 2D nanomaterial, introducing lateral quantum confinement and an abundance of edge sites. Here, a new family of nanomaterials is opened with the creation of arsenic–phosphorus alloy nanoribbons (AsPNRs). By ionically etching the layered crystal black arsenic–phosphorus using lithium electride followed by dissolution in amidic solvents, solutions of AsPNRs are formed. The ribbons are typically few-layered, several micrometers long with widths tens of nanometers across, and both highly flexible and crystalline. The AsPNRs are highly electrically conducting above 130 K due to their small band gap (ca. 0.035 eV), paramagnetic in nature, and have high hole mobilities, as measured with the first generation of AsP devices, directly highlighting their properties and utility in electronic devices such as near-infrared detectors, quantum computing, and charge carrier layers in solar cells.

This article presents a state trajectory control scheme for a switched-capacitor-based resonant converter consisting of two half-bridge circuits with four switches. The proposed technique can not only bring an improved dynamic response of output voltage regulation but also ensure that the converter benefits from soft-switching operation. The analysis in the two state planes provides insight into the switching modes of the converter and creates an accurate behavior framework in the geometrical domain. As a result, a finite-state-machine controller is designed based on the planning of the state trajectories. The switching conditions are exploited to obtain fast start-up and step-load transient responses. The proposed control method is verified with experimental results of a 14.5-V, 5.8-A converter prototype.

Aristolochic acid I (AAI) is a well established nephrotoxin and human carcinogen. Cytosolic NAD(P)H quinone oxidoreductase 1 (NQO1) plays an important role in the nitro reduction of aristolochic acids, leading to production of aristoloactam and AA-DNA adduct. Application of a potent NQO1 inhibitor dicoumarol is limited by its life-threatening side effect as an anticoagulant and the subsequent hemorrhagic complications. As traditional medicines containing AAI remain available in the market, novel NQO1 inhibitors are urgently needed to attenuate the toxicity of AAI exposure. In this study, we employed comprehensive 2D NQO1 biochromatography to screen candidate compounds that could bind with NQO1 protein. Four compounds, i.e., skullcapflavone II (SFII), oroxylin A, wogonin and tectochrysin were screened out from Scutellaria baicalensis. Among them, SFII was the most promising NQO1 inhibitor with a binding affinity (KD= 4.198 μmol/L) and inhibitory activity (IC50= 2.87 μmol/L). In human normal liver cell line (L02) and human renal proximal tubular epithelial cell line (HK-2), SFII significantly alleviated AAI-induced DNA damage and apoptosis. In adult mice, oral administration of SFII dose-dependently ameliorated AAI-induced renal fibrosis and dysfunction. In infant mice, oral administration of SFII suppressed AAI-induced hepatocellular carcinoma initiation. Moreover, administration of SFII did not affect the coagulation function in short term in adult mice. In conclusion, SFII has been identified as a novel NQO1 inhibitor that might impede the risk of AAI to kidney and liver without obvious side effect.

Stamping of fiber reinforced plastic (FRP) composite sheet, especially the woven fabrics and their prepregs, has been extensively researched. However, for small-batch production, high cost and long cycle due to design of complicated molds are still critical issues in composite manufacturing. In this paper, a novel hybrid process is proposed to reduce manufacturing costs and cycles of composite parts in small-batch production with the combination of incremental sheet forming and autoclave process. To verify the process feasibility, two-point incremental sheet forming of a typical pyramid part using plain fabric prepreg was preliminarily studied through experimental and numerical methods. A metal-fiber-metal (MFM) sandwich panel configuration consisting of two dummy sheets and core fabric prepreg layer was used to prevent the woven fabric from directly contacting the forming tool and support die, which can avoid viscous friction and guarantee the practicability of the ISF process. Based on the mechanical properties of the plain weave obtained from uniaxial tension and bias extension tests, a continuous approach-based finite element model (FEM) was established in PAM-FORM. Next, cross section profiles, peripheral outlines and shear angle distributions were extracted from experimental and simulation results. The corresponding comparison results were used to evaluate prediction accuracy of the established FE model. Finally, the influence of fabric layer on dummy sheets, fabric deformation history and the influence of friction coefficient on simulation results were analyzed.

In this study, novel recyclable composite BiOBr/chitin-Fe3O4was synthesized by a solvothermal method using magnetic chitin chelating bismuth oxybromide (BiOBr) as precursor. The morphology, structure, photoelectric properties and chemical composition of the obtained samples were explored extensively by various characterization techniques. Due to the introduction of Fe3O4and chitin, the composite BiOBr/chitin-Fe3O4has multi-functions in enlarging photo response performance, reducing the band gap, increasing specific surface area and inhibiting recombination rate, which are essential to improve the photocatalytic efficiency. Using ciprofloxacin as target pollutant, the composite showed excellent photocatalytic performance under visible light irradiation, the apparent rate constant value of BiOBr/chitin-Fe3O4is 5.8 times higher than that of pure BiOBr. The composite BiOBr/chitin-Fe3O4could be recycled and reused conveniently and effectively, and the catalyst possessed good photocatalytic stability with the degradation efficiency remaining unchanged even after five times circle. The possible degradation mechanism was discussed on the basis of experiments.

Unit commitment (UC) problems faced by Independent System Operators on a daily basis are becoming increasingly complex due to the recent push for renewables and the consideration of sub-hourly UC to accommodate the increasing variability in the net load. A disruptive solution methodology to address the growing complexity is therefore required. Quantum computing offers a promise to overcome the combinatorial complexity through the use of the so-called “qubits.” To make the best use of near-term quantum computers to solve UC problems with a much larger number of binary variables than the number of qubits available, this paper devises a novel solution methodology based on a synergistic combination of quantum computing and Surrogate Lagrangian Relaxation (SLR) to solve UC problems. Our new contributions include: 1) A Quantum-SLR (QSLR) algorithm incorporating quantum approximate optimization algorithm (QAOA) into the SLR method, which overcomes the fundamental difficulties of previous LR-based quantum methods such as zigzagging of multipliers and the need to know or estimate the optimal dual value for convergence; 2) A Distributed QSLR framework (D-QSLR) capable of coordinating local quantum/classical computing resources with those within neighborhoods and, in the meantime, protecting data privacy; 3) A Quantized UC model to obtain accurate commitment unit subproblems decision by using a quantum machine; and 4) A time-unit-decomposed quantum UC approach to overcoming the quantum resources’ limitations. Promising quantum test results validate the effectiveness of QSLR and the scalability of the UC-oriented D-QSLR algorithm, which demonstrate QSLR’s enormous potential in UC optimization.

An integrative power flow approach is established for networked microgrids. Our new contributions include: 1) A distributed augmented power flow (APF) algorithm for networked microgrids is devised to incorporate hierarchical control effects in/among microgrids; 2) Based upon APF, an enhanced distributed continuation power flow (CPF$^+$) algorithm is established to explore operating regions of droop coefficients and power interchanges for static voltage stability assessment; and 3) A programmable distributed platform is designed to coordinate power interchanges and support plug-and-play while protecting local customers’ privacy. RTDS experiments validate the high fidelity of APF, while its scalability and convergence performance are verified on medium and large networked microgrids. Extensive tests demonstrate the effectiveness of CPF$^+$ in quantifying secure operation regions of networked microgrids.

Quantum-empowered electromagnetic transients program (QEMTP) is a promising paradigm for tackling EMTP’s computational burdens. Nevertheless, no existing studies truly achieve a practical and scalable QEMTP operable on today’s noisy-intermediate-scale quantum (NISQ) computers. The strong reliance on noise-free and fault-tolerant quantum devices–which appears to be decades away– hinder practical applications of current QEMTP methods. This paper devises a NISQ-QEMTP methodology which for the first time transitions the QEMTP operations from ideal, noise-free quantum simulators to real, noisy quantum computers. The main contributions lie in: (1) design of shallow-depth QEMTP quantum circuits for mitigating noises on NISQ quantum devices; (2) practical QEMTP linear solvers incorporating executable quantum state preparation and measurements for nodal voltage computations; (3) a noise-resilient QEMTP algorithm leveraging quantum resources logarithmically scaled with power system dimension; (4) a quantum shifted frequency analysis (QSFA) for accelerating QEMTP by exploiting dynamic phasor simulations with larger time steps; (5) a systematical analysis on QEMTP’s performance under various noisy quantum environments. Extensive experiments systematically verify the accuracy, efficacy, universality and noise-resilience of QEMTP on both noise-free simulators and IBM real quantum computers.

By considering the line pattern of acoustic-resolution photoacoustic microscopy (AR-PAM) vessel images, we develop modified algorithms for synthetic aperture focusing technique (SAFT) and deconvolution based on a directional approach to enhance images. The modified algorithms consist of Fourier accumulation SAFT (FA-SAFT) and directional model-based (D-MB) deconvolution. To evaluate the performance of our algorithms, we conduct a series of imaging experiments and apply our algorithms, and existing SAFT and deconvolution algorithms are also applied for side-by-side comparison. By imaging tungsten wire phantom, our algorithms enable full width at half maximum of 26 − 31 µm over depth of focus of 1.8 mm and minimum resolvable distance of 46 − 49 µm, besting existing SAFT and deconvolution algorithms. Imaging of leaf skeleton phantom and in vivo imaging of mouse blood vessels also prove that our algorithm is capable of providing high-resolution, high-signal-to-noise ratio, and good-fidelity results for complex structures and for in vivo applications, especially for the images with the line pattern. The proposed directional approach can not only be used in AR-PAM but also in other imaging modalities to deal with the line pattern, such as FA-SAFT for ultrasound imaging and D-MB deconvolution for optical coherence tomography angiography.

BackgroundA large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers.MethodsA total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed.Findings155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBPand TBK1. By burden analysis, rare variants in SOD1, FUSand TARDBPcontributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBPp.Gly294Val and FUSp.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBPand C9orf72were associated with poor prognosis, in FUSlinked with younger age of onset, and C9orf72repeats tended to affect cognition.ConclusionsOur data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

Septic cardiomyopathy (SCM) is a severe complication caused by sepsis, resulting in a high mortality rate. The current understanding of the pathogenic mechanism of SCM primarily involves endocardial injury, microcirculation disturbance, mitochondrial dysfunction and fibrosis. Heparanase (HPA), an endo-β-D-glucuronidase, has been implicated in inflammation, immune response, coagulation promotion, microcirculation disturbance, mitochondrial dysfunction and fibrosis. Therefore, it was hypothesized that HPA may play an important role in the pathogenesis of SCM. The present study provides a summary of various pathophysiological changes and mechanisms behind the involvement of HPA in SCM. It also presents a novel perspective on the pathogenic mechanism, diagnosis and treatment of SCM.

The mechanism by which electromagnetic forming (EMF) enhances the formability of metals is unclear owing to the coupling effect of multi-physics fields. In the present work, the associated formability improvement mechanisms were qualitatively categorized and illustrated. This was realized by comparing the formability of fully annealed 2219 aluminum alloy (AA 2219-O) sheet under quasi-static (QS), electromagnetic dynamic (EM), and mechanical dynamic (MD) tensile loadings. It was found that the forming limit of AA 2219-O sheet under EM tensile loading was significantly (45.4%) higher than that under QS tensile loading, and was marginally (3.7%–4.3%) higher than that under MD tensile loading. In addition, the forming limit of AA 2219-O sheet demonstrated a negative dependency on the strain rate within the range of the dynamic tensile tests conducted. The deformation conditions common to EM and MD tensile loadings were responsible for the significant formability improvement compared with QS tensile loading. In particular, the inertial effect was dominant. The different deformation conditions that distinguish EM tensile loading from MD tensile loading resulted in the marginal improvement in formability. This was caused by the absence of a sustaining contact force at the later deformation stage and the lower strain rate. The body force exerted little influence on the formability improvement, and the thermal effect under the two dynamic tensile loadings was negligible. [ABSTRACT FROM AUTHOR]

Multi-point die electromagnetic incremental forming is a novel forming method, which is aimed at large-sized sheet metal forming combining electromagnetic incremental forming with multi-point die. The multi-point die can form different curved surfaces without replacing the die; as a result, multi-point die electromagnetic incremental forming can form large-sized workpieces with different curved shapes. A finite element model of multi-point die electromagnetic incremental forming is established. The deformation process of large-sized workpieces is discussed during the first discharge of coil. The influence of multistep forming on the forming quality of sheet metals is explained. Simulation results are basically consistent with the experimental ones. The feasibility of this technology is verified through the experiment of multi-point electromagnetic incremental forming.

With the continuous growth of the amount of information, the scale of green data centre is becoming larger and larger, and it is more and more widely used, the construction of green index system of green data centre has become a key problem to be solved urgently. This paper studied on the basic index system of green data centre, with the help of PUE, CEI and TCO index analysis, it is made in depth analysis of the factors affecting the green index of the green data centre, factor analysis is used from nine aspects such as annual average temperature, annual precipitation, air quality index, earthquake belt and fixed assets of information transmission enterprises, the mathematical model of evaluating the operation advantage of green data centre is constructed, to made quantitative analysis and evaluation classification, and according to the calculation, the comparison results of green data centre development area are obtained.

To observe the influence of wrist-ankle acupuncture (WAA) on postoperative nausea and vomiting (PONV) undergoing radiofrequency ablation (RFA) in thyroid nodule and its analgesic effect.

Designing environmentally friendly, low cost and efficient photocatalysts is vitally important for degradation of organic pollutants. Herein, a ternary composite-ZnO/ACSC@TiO2, constituted by activated coconut shell derived biochar (ACSC), TiO2and ZnO, was successfully synthesized by two-step hydrothermal method. It demonstrated that TiO2could be uniformly wrapped on ACSC surface during first step to form core-shell structures (ACSC@TiO2). It was beneficial not only to enhance adsorption capacity for organic pollutants and absorption ability for light, but also to form C-doped TiO2with a relatively narrow bandgap to expand light absorption of TiO2from UV to visible light. Subsequently, ZnO was introduced through second step to generate type-II heterojunctions with ACSC@TiO2, which further reduced bandgap value of the ternary photocatalyst to promote photogenerated carrier generation and efficiently diminished recombination of e--h+pairs. As expected, the optimal prepared catalyst with 10 wt% of ZnO (10%ZnO/ACSC@TiO2) exhibited excellent adsorptive and photocatalytic abilities for removal of tetracycline (TC) and Rhodamine B (RhB) with different initial concentrations. Particularly, its total removal efficiency for TC and RhB was 97.6% and 99.4%, respectively under 300 W xenon lamp irradiation (25 mg/L of organic pollutants, 1.0 g/L catalyst and natural pH in 60 min). Investigations on catalytic mechanism and degradation pathways proved that 10%ZnO/ACSC@TiO2could remove RhB and TC by deep degradation. Its enhanced synergy of adsorption and photocatalysis could efficiently accelerate mineralization rates of RhB and TC. This biomass derived biochar-based ternary composite as photocatalyst with optimized energy band structures and microstructures would have good industrial application potential.

Microbial reduction is an economical and environmentally benign route to deal with high-toxic Cr6+widely present in aquatic environments, but faces major challenges such as cytotoxicity and insufficient organic electron donors. Herein, we propose a route for the removal of Cr6+from water using a ternary FeS/reduced graphene oxide/Shewanella oneidensisMR-1 (FeS/rGO/MR-1) hybrid with external electricity supply at an electrode potential of −0.36 V. The biohybrid with excellent redox activity is in-situ biosynthesized by virtue of the versatile metabolic pathway and powerful extracellular electron transfer ability of MR-1 cells without the need of organic carbon sources. The biohybrid is directly used to remove Cr6+under the condition of continuous electricity input, the removal rate is negatively correlated with the applied electrode potential. Compared with binary FeS/MR-1 and rGO/MR-1 counterpart, the FeS/rGO/MR-1 hybrid achieves an improved ability to remove Cr6+at an initial concentration of 20 mg L−1in three consecutive batches due to the synergistic effect. The FeS is the main active component for rapid chemical reduction of Cr6+because of its highly reducible Fe2+and S2-, and rGO acts as the bridge to accelerate electron transfer from the applied electrode to MR-1 cells. Then, the MR-1 cells use the obtained electrons for FeS regeneration, which in turn reduces Cr6+again, resulting in the precipitation of less toxic Cr3+[Cr(OH)3and Cr2O3] in the biohybrid. This study provides a feasible route for removal of toxic Cr6+from water lacking organic electron donor by in-situ synthesis of biohybrid with external electricity supply.

Direct pharmacological inhibition of RAS has remained elusive, and efforts to target CRAF have been challenging due to the complex nature of RAF signaling, downstream of activated RAS, and the poor overall kinase selectivity of putative RAF inhibitors. Herein, we describe 15(LXH254, Aversa, R.; et al. Int. Patent WO2014151616A1, 2014), a selective B/C RAF inhibitor, which was developed by focusing on drug-like properties and selectivity. Our previous tool compound, 3(RAF709; Nishiguchi, G. A.; et al. J. Med. Chem.2017, 60, 4969), was potent, selective, efficacious, and well tolerated in preclinical models, but the high human intrinsic clearance precluded further development and prompted further investigation of close analogues. A structure-based approach led to a pyridine series with an alcohol side chain that could interact with the DFG loop and significantly improved cell potency. Further mitigation of human intrinsic clearance and time-dependent inhibition led to the discovery of 15. Due to its excellent properties, it was progressed through toxicology studies and is being tested in phase 1 clinical trials.

A new kinetically preferable polymorph of 1-(4′-cyanobenzyl)pyridinium bis(maleonitriledithiolato)nickelate (β-[CN-Py][Ni(mnt)2]) was achieved and characterized by element microanalysis for C, H, and N elements, powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) techniques. β-[CN-Py][Ni(mnt)2] shows a magnetostructural phase transition together with a thermal anomaly at ∼192 K. In the high-temperature phase (HTP), the β-[CN-Py][Ni(mnt)2] crystal belongs to monoclinic space group P21/c, and its asymmetric unit is comprised of one pair of CN-Py+and [Ni(mnt)2]−ions. Both CN-Py+and [Ni(mnt)2]−ions form uniform columnar stacks, respectively. In the low-temperature phase (LTP), the space group of the crystal is lowered to triclinic P1̅, its asymmetric unit changes into two pairs of anions and cations, and moreover, both stacks of CN-Py+and [Ni(mnt)2]−ions are dimerized. β-[CN-Py][Ni(mnt)2] features an S= 1/2 Heisenberg regular antiferromagnetic (AFM) linear chain system with |J| = 86(9) K in HTP, while a spin gap is opened with Δ = 568 K in LTP. The magnetic phase transition in β-[CN-Py][Ni(mnt)2] shows the spin-Peierls transition characters from the changes of both crystal structure and magnetic nature.

This paper considers the adaptive error feedback regulation problem for a one-dimensional heat equation with general harmonic disturbance anticollocated with control. We first construct an auxiliary system in which the control and the anticollocated disturbance become collocated and the measured error becomes the output. Then, we design an error feedback adaptive servomechanism for this system, which includes estimators for the parameters characterizing the disturbance and the reference signals. The control is thus designed to regulate the tracking error to zero and keep the states bounded. [ABSTRACT FROM AUTHOR]

Although the fully grouted tension anchorage system (T-anchorage system) has been widely used in the field of anchoring of earthen heritage sites, it has always suffered from the failure of the bolt–slurry interface debonding and the strong attenuation of the shear stress of the bolt–slurry interface along the embedment length. In this article, a new type of fully grouted tension–compression composite anchorage system (TC-anchorage system) is proposed, which is made up of a pressure bearing system with the same diameter of the anchor hole at the end of the tension bolt. The in situ anchorage, pull-out test and interfacial stress–strain monitoring were carried out for the T-anchorage systems and the TC-anchorage systems. This was based on the preliminary analysis and comparison of the structure and working mechanism of the two anchorage systems. The test results show that: the average ultimate load of the TC-anchorage system is about 40% higher than that of the T-anchorage system. TC-anchorage systems have the characteristics of small elastic deformation and large plastic deformation. The strain at the bolt–slurry interface varies progressively along the embedded length with the increase of load in a positive skewness–bimodal–negative skewness curve. The working mechanism of TC-anchorage systems includes three progressive stages: bolt–slurry interface debonding, conical slurry formation and slurry extrusion. The research conclusion provides a reference for the application of TC-anchorage systems in the protection and reinforcement of earthen heritage sites.

In this paper, we consider boundary output regulation for a one-dimensional wave equation with anti-stable term at control unmatched end. The reference signal and (in-domain and boundary) disturbances are supposed to be generated from a finite-dimensional exosystem. We first design a state feedback regulator by the backstepping approach to make the performance output track the reference signal exponentially. Next, with the measured output, we construct an observer for both wave PDE and exosystem. Based on the observer, an output feedback regulator is developed by replacing the states with their estimations. The closed-loop system is shown to admit a unique bounded solution and the tracking error is shown to decay exponentially. Finally, some numerical simulations are presented to illustrate the effectiveness of the proposed output feedback regulator.

Clouds and aerosols play essential roles in regulating surface incident solar radiation (Rs). It has been suggested that the increased aerosol loading over China is a key factor for the decadal variability in Rsand can explain the bias in its trend from reanalyses because the reanalyses do not include the interannual variability of aerosols. In this study, we compare the Rsderived from sunshine duration at 2,400 weather stations in China and that from five reanalyses from 1980 to 2014. The determining factors for the biases in the mean values and trends of Rsfrom the reanalyses are examined, with the help of Rsand the cloud fraction (CF), from satellite and 2,400 weather stations. Our results show that all reanalyses overestimate the multiyear Rsby 24.10–40.00 W/m2due to their underestimations of CF, which is more obvious in southern China. The biases in the simulated CF in the reanalyses can explain the biases in Rsby 55–41%, and the bias in clear‐sky surface solar radiation (Rc), which is primarily due to biases in aerosol loading, can explain 32–9% of the bias in Rs. The errors in the trend of the simulated CF can explain the errors in the Rstrends in the reanalyses by 73–12%, and the trend errors in the Rccan explain 43–30% of the trend error in Rs. Our study suggests that more work is needed to improve the simulation of aerosols, clouds, and aerosol‐cloud‐radiation interactions in the reanalyses. All reanalyses overestimate the multiyear mean all‐sky Rsover China, which is primarily due to their underestimation of cloud fraction73–12% of the trend biases in all‐sky Rscan be explained by trend bias in cloud fractionThe trend bias in clear‐sky‐surface solar radiation (a proxy for aerosols) explains 43–30% of the trend bias in Rs

In this paper, we consider performance output tracking for coupled wave equations with general external unmatched disturbance. An observer is designed first to estimate the state and disturbance simultaneously. Then we construct a servo system determined completely by the measured output and the reference signal which in turn gives dynamics of reference signal. In the following, an output feedback controller is designed based on this observer and servo system. It is shown that the closed-loop system is well-posed and the performance output is tracking the reference signal. Finally, we present some numerical results to illustrate the effectiveness of the controller. [ABSTRACT FROM AUTHOR]

Sodium borosilicate glasses are candidate materials for high-level radioactive waste vitrification; therefore, understanding the irradiation effects in model borosilicate glass is crucial. Effects of electronic energy deposition and nuclear energy deposition induced by the impact of heavy ions on the hardness and Young’s modulus of sodium borosilicate glass were investigated. The work concentrates on sodium borosilicate glasses, henceforth termed NBS1 (60.0% SiO2, 15.0% B2O3, and 25.0% Na2O in mol%). The NBS1 glasses were irradiated by P, Kr, and Xe ions with 0.3 MeV, 4 MeV, and 5 MeV, respectively. The hardness and Young’s modulus of ion-irradiated NBS1 glasses were measured by nanoindentation tests. The relationships between the evolution of the hardness, the change in the Young’s modulus of the NBS1 glasses, and the energy deposition were investigated. With the increase in the nuclear energy deposition, both the hardness and Young’s modulus of NBS1 glasses dropped exponentially and then saturated. Regardless of the ion species, the nuclear energy depositions required for the saturation of hardness and Young’s modulus were apparent at approximately 1.2 × 1020keV/cm3and 1.8 × 1020keV/cm3, respectively. The dose dependency of the hardness and Young’s modulus of NBS1 glasses was consistent with previous studies by Peuget et al. Moreover, the electronic energy loss is less than 4 keV/nm, and the electronic energy deposition is less than 3.0 × 1022keV/cm3in this work. Therefore, the evolution of hardness and Young’s modulus could have been primarily induced by nuclear energy deposition.

In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Group A served as controls without any treatment. Rats in groups B were injected intraperitoneally with 0.2 mL PBS and those in group C were injected intraperitoneally with 0.2 mL PBS+100 μmol/L, 0.2 mL N-[N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT, a gamma-secretase inhibitor that suppresses Notch signaling) respectively, on postoperative days 1, 3, 7, 10, and 14 in a model of denervation-induced skeletal muscle fibrosis by right sciatic nerve transection. Five rats from each group were euthanized on postoperative days 1, 7, 14, and 28 to collect the right gastrocnemii, and hematoxylin and eosin (HE) staining, immunohistochemistry test, real-time PCR, and Western blotting were performed to assess connective tissue hyperplasia and fibroblast density as well as expression of Notch 1, Jagged 1, and Notch downstream molecules Hes 1 and collagen I (COL I) on day 28. There was no significant difference in HE-stained fibroblast density between group B and C on postoperative day 1. However, fibroblast density was significantly higher in group B than in group C on postoperative days 7, 14, and 28. Notch 1, Jagged 1, Hes 1, and COL I proteins in the gastrocnemius were expressed at very low levels in group A but at high levels in group B. Expression levels of these proteins were significantly lower in group C than in group B (P<0.05), but they were higher in group C than in group A (P<0.05) on postoperative day 28. We are led to conclude that locking the Notch signaling pathway inhibits fibrosis progression of denervated skeletal muscle. Thus, it may be a new approach for treatment of fibrosis of denervated skeletal muscle.

Impaired megakaryocyte (MK) maturation and reduced platelet production are important causes of immune thrombocytopenia (ITP). However, MK distribution and bone marrow (BM) niche alteration in ITP are unclear. To investigate the maturation and distribution of MKs in the BM niche and examine the components of BM niche regulation of MK migration, BM and peripheral blood were obtained from 30 ITP patients and 28 healthy donors. Nestin+ mesenchymal stem cells (MSCs) and CD41+ MKs were sorted by fluorescence-activated cell sorting. The components of the BM niche and related signaling were analyzed via immunofluorescence, flow cytometry, enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and western blot analysis. The number of MKs in the BM vascular niche was reduced in ITP. Moreover, the concentrations of CXCL12 and CXCR4+ MKs in the BM were decreased in ITP. Further investigation demonstrated that nestin+ MSCs and CXCL12 messenger RNA (mRNA) in nestin+ MSCs were both reduced whereas the apoptosis of nestin+ MSCs was significantly increased in ITP. Sympathetic nerves, Schwann cells, the proportion of β3-adrenoreceptor (β3-AR)+ nestin+ MSCs, and β3-AR mRNA in nestin+ MSCs were all markedly reduced in ITP. Moreover, matrix metalloproteinase 9, vascular endothelial growth factor (VEGF), and VEGF receptor 1 were significantly reduced in ITP. Our data show that impaired MK distribution mediated by an abnormal CXCL12/CXCR4 axis is partially involved in reduced platelet production in ITP. Moreover, sympathetic neuropathy and nestin+ MSC apoptosis may have an effect on the alterations of BM CXCL12 in ITP.

To observe the glycemic variation (GV) in uncontrolled Graves’ disease (GD) patients with normal glucose metabolism measured by continuous glucose monitoring (CGM). This was a single-center, open-label, observational study. From January 2017 to October 2017, 20 GD patients with normal glucose metabolism and 24 healthy control subjects were recruited. Serum samples were obtained at 0, 30, and 120 min after oral glucose loading for glucose, insulin, and C-peptide level measurements. Fasting plasma fasting free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone concentrations were also detected. All participants were subjected to a 3-day CGM after baseline data were collected. The primary endpoint was the difference in the mean amplitude of the glycemic excursions between the two groups. Compared with the healthy subjects, the GD patients had higher mean amplitude of glycemic excursions (MAGE) (P< 0.01). Multiple linear stepwise regression analysis showed that FT4 level was an independent factor for the MAGE. Interestingly, the GD patients had a significant prolongation in the time to peak glucose, especially after breakfast (P< 0.01), and the elevation in the incremental area under the curve of glucose after breakfast till 4 hours later. Uncontrolled GD patients with normal glucose metabolism had a greater GV, and the FT4 level may contributed to the increased GV.

Impaired megakaryocyte (MK) maturation and reduced platelet production are important causes of immune thrombocytopenia (ITP). However, MK distribution and bone marrow (BM) niche alteration in ITP are unclear. To investigate the maturation and distribution of MKs in the BM niche and examine the components of BM niche regulation of MK migration, BM and peripheral blood were obtained from 30 ITP patients and 28 healthy donors. Nestin+mesenchymal stem cells (MSCs) and CD41+MKs were sorted by fluorescence-activated cell sorting. The components of the BM niche and related signaling were analyzed via immunofluorescence, flow cytometry, enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and western blot analysis. The number of MKs in the BM vascular niche was reduced in ITP. Moreover, the concentrations of CXCL12 and CXCR4+MKs in the BM were decreased in ITP. Further investigation demonstrated that nestin+MSCs and CXCL12 messenger RNA (mRNA) in nestin+MSCs were both reduced whereas the apoptosis of nestin+MSCs was significantly increased in ITP. Sympathetic nerves, Schwann cells, the proportion of β3-adrenoreceptor (β3-AR)+nestin+MSCs, and β3-AR mRNA in nestin+MSCs were all markedly reduced in ITP. Moreover, matrix metalloproteinase 9, vascular endothelial growth factor (VEGF), and VEGF receptor 1 were significantly reduced in ITP. Our data show that impaired MK distribution mediated by an abnormal CXCL12/CXCR4 axis is partially involved in reduced platelet production in ITP. Moreover, sympathetic neuropathy and nestin+MSC apoptosis may have an effect on the alterations of BM CXCL12 in ITP.

Due to limited direct measurements, regional or global terrestrial evapotranspiration (ET) is generally derived from a combination of meteorological and satellite observations. Although the inhomogeneity of the observed climate data has been widely reported, its impact on the calculated ET has not been adequately quantified. This study aimed to calculate ET using the modified Penman‐Monteith (MPM) model with raw and homogenized meteorological data. Additionally, we compared the calculated ET with those estimates from variable methods (water balance, satellite‐based, and reanalysis) in China and its six major river basins from 1982 to 2020. During the overlapping period of 1997–2018, ET calculated from raw input data decreased slightly at −0.39 mm yr−2(p= 0.64) in China, whereas homogenized ET showed a significant increasing trend of 0.93 mm yr−2(p= 0.02), with a better agreement with water balance ET (1.93 mm yr−2, p= 0). Global Land Evaporation Amsterdam Model (GLEAM) and Modern‐Era Retrospective Analysis for Research and Applications, version 2 (MERRA2) could reproduce the increasing trends with 2.08 mm yr−2(p= 0) and 2.59 mm yr−2(p= 0). The intercomparison of input variables (solar radiation, relative humidity, wind speed, precipitation, and air temperature) among ET products revealed substantial differences, which can account for the discrepancies in ET estimates. Homogenized ET, GLEAM and MERRA2 exhibited significant increasing trends in China and most river basins from 1982 to 2020. Our findings underscore the importance of utilizing homogenized input data for more accurate ET estimation. Regional or global terrestrial evapotranspiration (ET) is generally derived from a combination of meteorological and satellite observations. Previous studies have highlighted inhomogeneity issues in meteorological observations in China, which can introduce uncertainty to the ET estimated. However, the uncertainty of ET estimates has not been quantified. In this study, we recalculated ET in China using an energy partition model with raw and homogenized meteorological inputs from 1982 to 2020. We also compared ET estimates obtained from different methods (water balance, satellite‐based, and reanalysis) to analyze trends in China and its major river basins over the same period. The study revealed that inhomogeneity in the input data distorted the calculated trends of ET. Calculated China's ET using raw and homogenized data in the modified Penman‐Monteith modelImproved ET trend with homogenized data, aligning better with water balance ET over ChinaHomogenized ET exhibits a significant increasing trend of 0.90 mm yr−2(p= 0) from 1982 to 2020 across China Calculated China's ET using raw and homogenized data in the modified Penman‐Monteith model Improved ET trend with homogenized data, aligning better with water balance ET over China Homogenized ET exhibits a significant increasing trend of 0.90 mm yr−2(p= 0) from 1982 to 2020 across China

In this paper, we consider the error feedback regulator problem for a 1-D wave equation with velocity recirculation. There are harmonic disturbances in all channels of the system and the reference signal is also a harmonic type. We first introduce an invertible transformation such that the disturbances are only on the left boundary, which is non-collocated with the control. Then we propose an adaptive error-based observer by utilizing the measurable non-collocated tracking error and its derivative. Next, an observer-based error feedback controller is constructed to regulate the tracking error to zero asymptotically and make all internal signals bounded. Finally, the results are illustrated with simulations. • Output regulation for a 1-D wave equation with velocity recirculation. • The disturbances appear in all channels and the reference signal is also a harmonic type. • The well-posedness of the closed-loop system and the achievement of the control objectives are verified. [ABSTRACT FROM AUTHOR]

The equalization management system is an essential guarantee for the safe, stable, and efficient operation of the power battery pack, mainly composed of the topology of the equalization circuit and the corresponding control strategy. This article proposes a novel active balancing control strategy to address the issue of individual cell energy imbalance in battery packs. Firstly, to achieve energy equalization under complex conditions, a two-layer equalization circuit topology is designed, and the efficiency and loss of energy transfer in the equalization process are studied. Furthermore, a directed graph-based approach was proposed to represent the circuit topology equivalently as a multi-weighted network. Combined with a multi-weighted optimal matching algorithm, aims to determine the optimal energy transfer path and reduce equalization losses. In addition, a fuzzy controller that can dynamically adjust the equalization current with the state parameter of the cell as the input condition is designed to optimize the equalization efficiency. Matlab/Simulink software is used to build and simulate the model. The experimental results indicate that, under the same static state, the newly proposed control strategy improves efficiency by 6.08% and enhances equalization speed by 42.03% compared to the maximum value equalization method. The method also effectively improves energy utilization under the same charging and discharging states.

Scutellaria baicalensisGeorgi, also known as huang-qin in traditional Chinese medicine, is a widely used herbal remedy due to its anticancer, antivirus, and hepatoprotective properties. The S. baicalensisgenome was sequenced many years ago; by contrast, the proteome as the executer of most biological processes of S. baicalensisin the aerial parts, as well as the secondary structure of the roots (xylem, phloem, and periderm), is far less comprehensively characterized. Here we attempt to depict the molecular landscape of the non-model plant S. baicalensisthrough a multi-omics approach, with the goal of constructing a highly informative and valuable reference dataset. Furthermore, we provide an in-depth characterization dissection to explain the two distinct flavonoid biosynthesis pathways that exist in the aerial parts and root, at the protein and phosphorylated protein levels. Our study provides detailed spatial proteomic and phosphoproteomic information in the context of secondary structures, with implications for the molecular profiling of secondary metabolite biosynthesis in non-model medicinal plants.

Purpose: Osteoporosis is a condition characterized by decreased bone density and bone strength, commonly observed among older individuals. Caveolin-3 (CAV3) is a principal structural protein of the caveolae membrane domains, which has been reported to participate in cell signaling as well as the maintenance of cell structure. The aim of the current study was to investigate the effects involved with the silencing of CAV3 on bone formation among osteoporotic rat models via the Wnt signaling pathway. Methods: Osteoporosis was initially induced by means of ovariotomy among rat models in order to determine the expression of CAV3. Then, to confirm the specific function and mechanism of CAV3 from an osteoporosis perspective, the CAV3 expression vector was constructed and transfected into the osteoblasts of the osteoporotic rats. Afterward, the mRNA and protein expressions of CAV3, β-catenin, low-density lipoprotein receptor-related protein 5 (LRP5), T-cell factor (TCF), and Wnt3a in addition to cell proliferation and apoptosis were detected accordingly. Results: Positive expression of CAV3 exhibited diminished levels in the bone tissues of osteoporotic rats. The osteoblasts of the osteoporotic rats treated with overexpressed CAV3 displayed elevated mRNA and protein expression levels of β-catenin, LRP5, TCF, and Wnt3a. Increased cell proliferation and decreased cell apoptosis were also observed, while the osteoblasts of the osteoporotic rats treated with si-CAV3 exhibited an opposite result. Conclusion: Overexpressed CAV3 promotes bone formation and suppresses the osteoporosis progression via the activation of the Wnt signaling in rat models, suggesting CAV3 as a potential target biomarker in the treatment of osteoporosis.