The impact of PET/CT and brain MRI for metastasis detection among patients with clinical T1-category lung cancer: Findings from a large-scale cohort study.

PURPOSE: [18F]-FDG PET/CT and brain MRI are common approaches to detect metastasis in patients of lung cancer. Current guidelines for the use of PET/CT and MRI in clinical T1-category lung cancer lack risk-based stratification and require optimization. This study stratified patients based on metastatic risk in terms of the lesions' size and morphological characteristics. METHODS: The detection rate of metastasis was measured in different sizes and morphological characteristics (solid and sub-solid) of tumors. To confirm the cut-off value for discriminating metastasis and overall survival (OS) prediction, the receiver operating characteristic (ROC) analysis was performed based on PET/CT metabolic parameters (SUVmax/SUVmean/SULpeak/MTV/TLG), followed by Kaplan-Meier analysis for survival in post-operation patients with and without PET/CT plus MRI. RESULTS: 2,298 patients were included. No metastasis was observed in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm. The cut-off of PET/CT metabolic parameters on discriminating metastasis were 1.09 (SUVmax), 0.26 (SUVmean), 0.31 (SULpeak), 0.55 (MTV), and 0.81 (TLG), respectively. Patients undergoing PET/CT plus MRI exhibited longer OS compared to those who did not receive it in solid nodules ≥ 8.0 mm & sub-solid nodules ≥ 10.0 mm (HR, 0.44; p < 0.001); in solid nodules ≥ 8.0 mm (HR, 0.12; p<0.001) and in sub-solid nodules ≥ 10.0 mm (HR; 0.61; p=0.075), respectively. Compared to patients with metabolic parameters lower than cut-off values, patients with higher metabolic parameters displayed shorter OS: SUVmax (HR, 12.94; p < 0.001), SUVmean (HR, 11.33; p <0.001), SULpeak (HR, 9.65; p < 0.001), MTV (HR, 9.16; p = 0.031), and TLG (HR, 12.06; p < 0.001). CONCLUSION: The necessity of PET/CT and MRI should be cautiously evaluated in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm, however, these examinations remained essential and beneficial for patients with solid nodules ≥ 8.0 mm and sub-solid nodules ≥ 10.0 mm.

Data-Driven Design of Nickel-Free Superelastic Titanium Alloys.

In this paper, a CatBoost model for predicting superelastic strains of alloys was established by utilizing features construction and selection as well as model filtering and evaluation based on 125 existing data points of superelastic titanium alloys. The alloy compositions of a TiNbMoZrSnTa system were optimized and three nickel-free titanium alloys with potentially excellent superelastic properties were designed using the Bayesian optimization algorithm using a superelastic strain as the optimization target. The experimental results indicated that only Ti-12Nb-18Zr-2Sn and Ti-12Nb-16Zr-3Sn exhibited clear superelasticity due to the absence of relevant information about the alloys' ß stability in the machine learning model. Through experimental optimization of the heat treatment regimens, Ti-12Nb-18Zr-2Sn and Ti-12Nb-16Zr-3Sn ultimately achieved recovery strains of 4.65% after being heat treated at 853 K for 10 min and 3.01% after being heat treated at 1073 K for 30 min, respectively. The CatBoost model in this paper possessed a certain ability to design nickel-free superelastic titanium alloys but it was still necessary to combine it with existing knowledge of material theory for effective utilization.

Versatile Composite Binder with Fast Lithium-Ion Transport for LiCoO2 Cathodes.

The low ionic conductivity of LiCoO2 limits the rate performance of the overall electrode. Here, a polymeric composite binder composed of poly(vinylidene fluoride) (PVDF) and poly(ethylene oxide) (PEO) is reported to efficiently improve the ion transport in the LiCoO2 electrode. This is where the lithium-ion transport channel constructed by oxygen atoms of PEO can afford the electrode a lithium-ion transport number (tLi+) as high as 0.70 with the optimized composite binder in a mass ratio of 1:1 (O5F5), significantly higher than that of traditional PVDF (0.44). As a result, the O5F5 binder endows the LiCoO2 electrode with an impressive capacity of 90 mAh g-1 even at 15 C, which is twice as high as the PVDF electrode. In addition, the initial Coulombic efficiency of the LiCoO2 electrode with the O5F5 binder is close to 100% and the capacity retention is 91% after 100 cycles at 1 C. This study overcomes the problem of slow ion conductivity of the LiCoO2 electrode, providing an easy method for developing high-rate cathode binders.

Iodine-Mediated δ-Amination of sp3 C-H Bonds.

We present a direct δ-amination reaction of sp3 C-H bonds, employing molecular iodine (I2) as the sole oxidant under transition-metal-free conditions. This remote C-H functionalization approach is operationally simple and provides facile, efficient access to pyrrolidines and related heterocyclic derivatives from readily accessible substrates.

Effect of Cold Deformation and Heat Treatment on the Microstructures and Mechanical Properties of Au-15Ag-12Cu-6Ni Alloy Sheets.

The evolution of the microstructure and hardness changes in the Au-15Ag-12Cu-6Ni alloy during the processes of cold rolling and annealing were investigated and the heat treatment regimen for the alloy was optimized in this article. The hardness of the alloy continuously increases with the cold rolling reductions, leading to continuous deformation of the grains during the cold rolling process, ultimately resulting in smaller grain sizes. Subsequent annealing induces recovery and recrystallization, achieving complete recrystallization at 700 °C. An intriguing softening effect is observed after annealing at 700 °C, manifesting in a significant reduction in hardness to 238 (Hv0.5). The cold deformation texture of the alloy aligns with the recrystallization texture type, exhibiting only a certain degree of angular deviation. This is primarily characterized by <111>//RD texture and a texture deviating 60° from RD towards TD. The performance of the finished sheet improves with the precipitation of ordered phases AuCu after a 300 °C heat treatment for 0.5 h, resulting in a remarkable hardness of 380 (Hv0.5).

Equivalent Heat Treatments and Mechanical Properties in Cold-Rolled TiNiFe Shape-Memory Alloys.

Heat treatments after cold rolling for TiNiFe shape-memory alloys have been compared. After EBSD analysis and as calculated by the Avrami model and Arrhenius equation, the relationship between the heat-treatment temperature and manufacturing time of TiNiFe alloys is established. Through calculation, it can be found that TiNiFe alloys can obtain similar microstructures under the annealing processes of 823 K for 776 min, 827 K for 37 min, and 923 K for 12.5 min. And the recrystallization fractions are all around 50%. Nevertheless, the tensile properties and recovery stress of the alloys show almost similar values. And based on the feasibility of the annealing process, it is believed that annealing at 873 K for 37 min is the optimal choice to obtain a recrystallization fraction φR = 50%.

Iodine-Mediated α-C-H Amination of Carbonyl Compounds via Nitrogen-Directed Oxidative Umpolung.

A new synthetic strategy for direct C(sp3)-H amination of carbonyl compounds at their α-carbon has been established employing molecular iodine and nitrogen-directed oxidative umpolung. In this transformation, iodine acts not only as an iodinating reagent but also as a Lewis acid catalyst, and both the nitrogen-containing moiety and the carbonyl group in the substrate play important roles. This synthetic approach is applicable to a broad variety of carbonyl substrates, including esters, ketones, and amides. Its features also include no requirement for transition metals, mild reaction conditions, short reaction times, and gram-scale synthesis.

In Situ Prepared Three-Dimensional Covalent and Hydrogen Bond Synergistic Binder to Boost the Performance of SiOx Anodes for Lithium-Ion Batteries.

Polymer binders play an important role in enhancing the electrochemical performance of silicon-based anodes to alleviate the volume expansion for lithium-ion batteries. It is difficult for common one-dimensional (1D) linear binders to limit the volume expansion of a silicon-based electrode when combined with silicon-based particles with scant binding points. Therefore, it is necessary to design a three-dimensional (3D) network structure, which has multiple binding points with the silicon particles to dissipate the mechanical stress in the continuous charge and discharge circulation. Here, a covalent and hydrogen bond synergist 3D network green binder (poly(acrylic acid) (PAA)-dextrin 9 (Dex9)) was prepared by the simple in situ thermal condensation of a one-dimensional liner binder PAA and Dex in the electrode fabrication process. The optimized SiOx@PAA-Dex9 electrode exhibits an initial Coulombic efficiency (ICE) of 82.4% at a current density of 0.2 A g-1. At a high current density of 1 A g-1, it retains a capacity of 607 mAh g-1 after 300 cycles, which is approximately twice as high as that of the SiOx@PAA electrode. Furthermore, the results of in situ electrochemical dilatometry (ECD) and characterization of electrode structures demonstrate that the PAA-Dex9 binder can effectively buffer the huge volume change and maintain the integrity of the SiOx electrodes. The research overcomes the low electrochemical stability difficulty of the 3D binder and sheds light on developing the simple fabrication procedure of an electrode.

Synthesis of Quinazolinone-Fused Tetrahydroisoquinolines and Related Polycyclic Scaffolds by Iodine-Mediated sp3 C-H Amination.

An iodine-mediated intramolecular sp3 C-H amination reaction producing quinazolinone-fused polycyclic skeletons from 2-aminobenzamide precursors is reported. This reaction does not use transition metals, has a broad substrate scope, and can be used on a gram scale. Under the optimal reaction conditions, a variety of quinazolinone-fused tetrahydroisoquinolines and derivatives of Rutaecarpine were synthesized from readily accessible compounds. The reaction proceeds well with crude 2-aminobenzamide derivatives, allowing for the synthesis of the products from simple 2-aminobenzoic acids and tetrahydroisoquinolines without purification of the 2-aminobenzamide intermediates. Preliminary biological experiments have identified Cereblon (CRBN) inhibitory activity and relevant anti-myeloma medicinal properties in some of these polycyclic products.

Modeling Based on a Two-Step Parameter Identification Strategy for Liquid Crystal Elastomer Actuator Considering Dynamic Phase Transition Process.

Liquid crystal elastomer (LCE) is a promising candidate for actuation in light-driven soft robot applications. Due to the fact that LCE has complex hysteretic nonlinearities, which are highly dependent on the environment, modeling of actuators made of LCE is a very challenging issue. In this article, a model is proposed to describe the deformation of the LCE actuator accurately and analytically by considering the dynamic phase transition process of LCE molecules. First, an overview of the physical process of LCE's deformation is presented, and the schematic of the LCE actuator, as well as the modeling scheme are then introduced. Next, a thermodynamic analysis of the system's free energy is performed to establish the model for the LCE actuator, which gives the relationship between the system's deformation and the temperature. Here, to describe the complex hysteretic nonlinearity in the model, the dynamic process of the phase transition of LCE molecules is exploited. To effectively identify the model parameters, a two-step parameter identification strategy based on the differential evolution algorithm and nonlinear least-squares method is utilized. Finally, experimental results verify the validity of the proposed model. This modeling provides an approach to describe LCE's deformation with high accuracy and can fully reflect the physical nature of LCE's deformation, especially hysteresis. It can be utilized as a basis for accurate control over LCE actuators in photoresponsive soft robot applications.

Numerical Simulation and Process Optimization on Hot Twist-Stretch Straightening of Ti-6Al-4V Alloy Profile.

Ti-6Al-4V profiles prepared by hot extrusion are usually accompanied by bending and twisting. The hot twist-stretch straightening is an effective strategy such that the bending deflection and twisting angle can be simultaneously decreased by a single straightening process. In addition, utilizing stress relaxation effect, the residual stress and springback can be greatly reduced by holding the straightening temperature and strain constant for a period after twist-stretch straightening. In this study, the hot deformation behaviors of the Ti-6Al-4V profile were revealed by experiments. The tensile model was obtained by uniaxial tensile tests within ranges of temperatures (500-700 °C) and strain rates (5 × 10-5-1 × 10-3 s-1). The creep constitutive model was acquired with stress relaxation experiments in ranges of temperatures (500-700 °C) and pre-strain of 1.5%. Then, the coupled thermo-mechanical model of hot twist-stretch straightening was established. Based on orthogonal experiment strategy, the effects of straightening temperature, stretch strain, and holding time on the bending deflection and torsion angle of profile were investigated systematically and the process was optimized. The straightening accuracy is significantly affected by straightening temperature and holding time. By using optimized process parameters in practical straightening experiments, the deflection/length and angle/length after straightening does not exceed 2‱ and 2.5‱°/mm, respectively, which is basically consistent with the numerical simulation result.

Design, synthesis and biological evaluation of novel triazoloquinazolinone and imidazoquinazolinone derivatives as allosteric inhibitors of SHP2 phosphatase.

ABSTRCTA series of novel triazoloquinolinone and imidazoquinazolinone derivatives were designed and synthesised, and their biological activities against SHP2 protein and melanoma A357 cell line were evaluated in vitro. The results show that some target compounds have moderate to excellent inhibitory activity on SHP2 protein and melanoma A357 cell line. Structure-activity relationships (SARs) showed that both imidazoquinazolinone and triazoloquinazolinone derivatives have good SHP2 protein kinase and melanoma cell line A357 inhibitory activity. The results of molecular docking also showed that the cores of imidazoquinazolinone and triazoloquinazolinone have a certain affinity for SHP2 protein at the same time. Compared with SHP244, the target compounds have quite good liver microsomal stability and has more drug potential. The most promising compound B1 has a strong inhibitory effect on the melanoma cell line A357 at 100 µM (76.15% inhibition).

Microstructure and Texture Evolution during Superplastic Deformation of SP700 Titanium Alloy.

The superplastic tensile test was carried out on SP700 (Ti-4.5Al-3V-2Mo-2Fe) titanium alloy sheet at 760 °C by the method of maximum m value, and the microstructure characteristics were investigated to understand the deformation mechanism. The results indicated that the examined alloy showed an extremely fine grain size of ~1.3 µm and an excellent superplasticity with fracture elongation of up to 3000%. The grain size and the volume fraction of the ß phase increased as the strain increased, accompanied by the elements' diffusion. The ß-stabilizing elements (Mo, Fe, and V) were mainly dissolved within the ß phase and diffused from α to ß phase furthermore during deformation. The increase in strain leads to the accumulation of dislocations, which results in the increase in the proportion of low angle grain boundaries by 15%. As the deformation process, the crystal of α grains rotated, and the texture changed, accompanied by the accumulation of dislocations. The phase boundary (α/ß) sliding accommodated by dislocation slip was the predominant mechanism for SP700 alloy during superplastic deformation.

Effect of 'Q' Ratio on Texture Evolution of Ti-3Al-2.5V Alloy Tube during Rolling.

Ti-3Al-2.5V alloy was usually the α phase of HCP structure at room temperature which had obvious anisotropy. During tube rolling, α grain would be influenced by stress-strain state, deformation amount, 'Q' ratio to result the preferred orientation and formed texture. In order to obtain radial texture tube by rolling and improve the service quality of tube in the pipeline system, Φ25 mm Ti-3Al-2.5V alloy tubes was selected as billet for the experiment, and four kinds of tubes with outer diameter of Φ16mm was produced by single pass cold rolling with 'Q' ratios ranging from 0.65 to 2.0. The effect of 'Q' ratio on the texture of Ti-3Al-2.5V tube was studied. The result indicted that the initial texture of the tube is radial-circumferential equally distributed, and the radial basal texture enhances gradually with increasing 'Q' ratio. Since the angle between the C-axis of grain and the radial axis of RD decreases, the C-axis of grain distributes to the radial direction, and the more grain orientation from {112X} pyramidal to {0001} basal plane. The different 'Q' ratio would lead to different strain along the radial direction, circumferential direction, axial direction, thus affected the crystal orientation and distribution during tube rolling deformation. When 'Q' > 1, the tube mainly produced radial basal texture. By comparison with 'Q' < 1, the tube mainly produced circumferential basal texture. As a result, when the initial texture of the tube is radial-circumferential equally distributed, the ideal radial texture of the tube can be obtained by choosing rolling process with 'Q' > 2.0.

Pithecellobium clypearia: Amelioration Effect on Imiquimod-Induced Psoriasis in Mice Based on a Tissue Metabonomic Analysis.

Pithecellobium clypearia Benth. (accepted name: Archidendron clypearia (Jack) I.C.Nielsen; Mimosaceae), a popular traditional Chinese medicine, has a significant anti-inflammatory effect. The crude water extract of the aerial part of P. clypearia has been clinically applied to treat upper respiratory tract infections, acute gastroenteritis, laryngitis, and pharyngitis. However, the therapeutic mechanism of ethanol fraction of water extract (ESW) of P. clypearia to treat psoriasis should be complemented. The aim of our research was to clarify the protective effects of ESW from P. clypearia against psoriasis-like skin inflammation induced by imiquimod (IMQ) in mice with efficacy indexes and target tissue (spleen and serum) metabolomics. The ingredient of ESW was analyzed by ultrahigh-performance liquid chromatography combined with tandem mass spectrometry (UHPLC-MS/MS) method. The imiquimod-induced psoriatic mouse model was employed to investigate the effect of ESW against psoriasis, where the treatment method was implemented for 6 days both topically (Gel at 5%) and orally (at 2.4 g/kg p.o.). Traditional pharmacodynamic indicators (phenotypic characteristics, psoriasis area and severity index (PASI) score, H&E staining, immunohistochemical staining, the thickness of epidermis, body weight change, and spleen index) were conducted to appraise the efficacy of ESW. Furthermore, a gas chromatography-mass spectrometer (GC-MS) coupled with multivariate analysis was integrated and applied to obtain serum and spleen metabolic profiles for clarifying metabolic regulatory mechanisms of ESW. The current study illustrated that ESW is composed mainly of gallic acid, ethyl gallate, quercitin, 7-O-galloyltricetiflavan, quercetin, and myricetin by UHPLC-MS/MS analysis. ESW could distinctly improve IMQ-induced psoriasis in mouse through reducing PASI score, alleviating tissue damage, restoring spleen index, and inhibiting proliferating cell nuclear antigen (PCNA) expression in psoriasis-like skin tissue. From the metabolomics study, 23 markers with significant changes are involved in eight main pathways in spleen and serum samples, including linoleic acid metabolism and glycine, serine, and threonine metabolism. The current study showed that ESW had obvious antipsoriasis effects on IMQ-induced psoriasis in mice, which might be attributed to regulating the dysfunction of differential biomarkers and related pathways. In summary, ESW of P. clypearia showed a favourable therapeutic effect on IMQ-induced psoriasis, and metabolomics provided insights into the mechanisms of ESW to the treatment of psoriasis.

A General Position Control Method for Planar Underactuated Manipulators With Second-Order Nonholonomic Constraints.

The study on the stabilization of planar underactuated manipulators without gravity is well recognized as a major challenge since the system includes a second-order nonholonomic constraint when the passive link is not located at the first link. It is important to solve this difficulty for applications such as systems working in aerospace or underwater. This article presents a position control method based on bidirectional motion planning and intelligent optimization for this kind of system. The control objective is to move the end effector of the manipulator from its initial position to a given target position. The differential evolution algorithm is applied to solve the target angles of all links corresponding to the target position of the end effector. Then, bidirectional motion planning is performed, which consists of forward and backward motions. Each motion is planned by designing a trajectory for every active link based on their initial and target angles. During the forward motion, all active links except the first one are moved to their target angles, and the first active link and the passive link to the intermediate angles. For the backward motion, the first active link is moved to its target angle, the other active links remain at their target angles, and the passive link will be moved to its target angle at the same time. The planned trajectories are chosen based on the time-scaling method and differential evolution algorithm to make sure that the forward and backward planned motions can be connected smoothly. Finally, the trajectory tracking controllers for all active links are designed based on the sliding-mode control method. The proposed control method is verified on planar four-link underactuated manipulators with different passive joints. This strategy has the advantage that it works for planar underactuated manipulators with a second-order nonholonomic constraint whose passive link can be at different positions. Meanwhile, by combining intelligent optimization with bidirectional motion planning, the control process becomes simpler and more effective.

Dynamic modeling of dielectric elastomer actuator with conical shape.

With desirable physical performances of impressive actuation strain, high energy density, high degree of electromechanical coupling and high mechanical compliance, dielectric elastomer actuators (DEAs) are widely employed to actuate the soft robots. However, there are many challenges to establish the dynamic models for DEAs, such as their inherent nonlinearity, complex electromechanical coupling, and time-dependent viscoelastic behavior. Moreover, most previous studies concentrated on the planar DEAs, but the studies on DEAs with some other functional shapes are insufficient. In this paper, by investigating a conical DEA with the material of polydimethylsiloxane and considering the influence of inertia, we propose a dynamic model based on the principles of nonequilibrium thermodynamics. This dynamic model can describe the complex motion characteristics of the conical DEA. Based on the experimental data, the differential evolution algorithm is employed to identify the undetermined parameters of the developed dynamic model. The result of the model validation demonstrates the effectiveness of the model.

In-Situ SEM Observation on Fracture Behavior of Titanium Alloys with Different Slow-Diffusing ß Stabilizing Elements.

The fracture-behaviors of two Ti-Al-Sn-Zr-Mo-Nb-W-Si alloys with different slow-diffusing ß stabilizing elements (Mo, W) were investigated through in-situ tensile testing at 650 °C via scanning electron microscopy. These alloys have two phases: the α phase with hcp-structure (a = 0.295 nm, c = 0.468 nm) and the ß phase with bcc-structure (a = 0.332 nm). Three-dimensional atom probe (3DAP) results show that Mo and W mainly dissolve in the ß phase, and they tend to cluster near the α/ß phase boundary. Adding more slow-diffusing ß stabilizing elements can improve the ultimate tensile strength and elongation of the alloy at 650 °C. During tensile deformation at 650 °C, microvoids mainly initiate at α/ß interfaces. With increases in the contents of Mo and W, the ß phase content increases and the average phase size decreases, which together have excellent accommodative deformation capability and will inhibit the microvoids' nucleation along the interface. In addition, the segregation of Mo and W near the α/ß interface can reduce the diffusion coefficient of the interface and inhibit the growth of microvoids along the interface, which are both helpful to improve the ultimate tensile strength and plasticity.

Self-repaired Process of a Traumatized Maxillary Central Incisor with Pulp Infarct after Horizontal Root Fracture Monitored by Laser Doppler Flowmetry Combined with Tissue Oxygen Monitor.

Achieving a precise diagnosis of the pulp status of traumatized teeth is difficult. The time to interfere through endodontic treatment for these teeth is greatly dependent on the doctor's experience. A 24-year-old male patient suffered a traumatic injury to tooth #9 that resulted in an apical root horizontal fracture 3 days before he came to the hospital. The injured tooth showed no response to pulp sensitivity testing at the first visit and was discolored 1 week later. Tooth #9 was immobilized to its adjacent teeth for 4 weeks by a composite splint. The patient was asked to make regular follow-up appointments for 72 weeks. The changes in the pulp microcirculation of tooth #9 after the injury were recorded using laser Doppler flowmetry (LDF) and a tissue oxygen monitor (OXY). The LDF was used to directly measure the pulpal blood flow, and the OXY was used to detect the tissue oxygen saturation and total hemoglobin at each appointment. Tooth #9 survived a period of pulp infarct that started at week 4 and showed complete revascularization within 10 weeks. The color of the tooth returned to normal after revascularization. The tooth responded to sensitivity testing at week 58, and radiographic examinations confirmed its hard tissue was healing. Without other clinical signs besides tooth discoloration and an absence of response to pulp sensitivity testing, the complete self-repair of pulp can be expected in teeth with pulp infarct after a horizontal root fracture, and more than 1 year of follow-up is recommended. The use of LDF combined with OXY monitoring has great value in the timely and precise reflection of changes in pulp status after dental trauma.

Conformational selection or induced fit for Brinker and DNA recognition.

Brinker is the key target protein of the Drosophila Decapentaplegic morphogen signalling pathway. Brinker is widely expressed and can bind with DNA. NMR spectra suggest that apo-Brinker is intrinsically unstructured and undergoes a folding transition upon DNA-binding. However, the coupled mechanism of binding and folding is poorly understood. Here, we performed molecular dynamics (MD) simulations for both bound and apo-Brinker to study the mechanism. Room-temperature MD simulations suggest that Brinker becomes more rigid and stable upon DNA-binding. Kinetic analysis of high-temperature MD simulations shows that both bound and apo-Brinker unfold via a two-state process. The time scale of tertiary unfolding is significantly different between bound and apo-Brinker. The predicted Φ-values suggest that there are more residues with native-like transition state ensembles (TSEs) for bound Brinker than for apo-Brinker. The average RMSD differences between bound and apo-Brinker and Kolmogorov-Smirnov (KS) test analysis illustrate that Brinker folding upon DNA-binding might obey induced-fit mechanism based on MD simulations. These methods can be used for the research of other biomolecular folding upon ligand-binding.