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Increasing evidence indicates that macrophages play an important role in angiogenesis and bone regeneration. Because the phenotypic polarization of macrophage is extremely sensitive to the pore size of materials, poly(ether-ether-ketone) (PEEK) scaffolds with pore sizes of 0, 200, and 400 μm were prepared, and the influence of pore size-mediated macrophage polarization on subsequent angiogenesis and osteogenesis was examined. The interaction results of macrophages and scaffolds indicated that macrophages were responsive to the pore size of three-dimensional (3D)-printed PEEK scaffolds, and large pore size scaffolds showed greater potential in inducing M1 to M2 transition of macrophage and enhanced macrophage secretion of high concentrations of osteogenesis-related and angiogenesis-related cytokines. When human umbilical vein endothelial cells (HUVECs) and bone marrow mesenchymal stem cells (BMSCs) were cultured in the conditioned medium derived from co-culture of macrophages and scaffolds, HUVECs showed good angiogenic responses in terms of cell migration and angiogenic gene expression, while BMSCs showed good osteogenic differentiation effect in in vitro mineralization and osteogenesis-related gene expression. The results of bone defect repair showed that the bone volume/total volume ratio and trabecular thickness of the large pore size PEEK scaffold were significantly higher, and it had better biomechanical properties and achieved a better osseointegration effect. Our data demonstrate that large-pore PEEK scaffolds promote angiogenesis and osteogenic differentiation in vitro and osseointegration in vivo, most likely because scaffolds with larger pore size are able to mediate a higher degree of M1 to M2 transition in macrophages.

There are no approved epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for EGFR-mutated non-small cell lung cancer (NSCLC) without EGFR T790M mutation after progression on first- or second-generation EGFR-TKIs.We conducted this phase I, open-label, multicenter, dose-escalation/dose-expansion study to evaluate the safety, tolerability, antitumor activity, and pharmacokinetics of FCN-411, a TKI targeting EGFR, HER2, and HER4, in patients with EGFR-mutated advanced NSCLC whose disease had progressed during treatment of EGFR-TKIs. Adult patients with stage IIIB-IV NSCLC harboring EGFR mutations (exon 18/19/20/21) who had progressed on prior EGFR-TKIs were enrolled. In the dose-escalation phase, patients received 4 mg, 8 mg, 12 mg, and 16 mg FCN-411 once daily until the maximum tolerated dose (MTD). In the dose-expansion phase, patients received FCN-411 at the recommended phase II dose (RP2D) continuously in 21-day cycles. The primary endpoints were safety, tolerability, MTD, and RP2D.From July 23, 2018 to September 29, 2020, 77 patients were enrolled, including 30 with EGFR T790M mutation in tumor tissues. The cut-off date was February 1, 2021. No dose-limiting toxicities were observed. The most common grade ≥ 3 treatment-emergent adverse events among all patients were diarrhea (8; 10.4%) and dermatitis acneiform (7; 9.1%). Ten of 67 evaluable patients achieved confirmed partial response, with an objective response rate (ORR) of 14.9% (95% confidence interval [CI], 8.3-24.0); the ORR was 33.3%, 14.0%, 0, and 25.0% at 4 mg, 8 mg, 12 mg, and 16 mg, respectively. Besides, the ORR in patients without and with EGFR T790M mutation was 20.5% and 7.4%, respectively. Moreover, 39 patients achieved stable disease across all doses, and the disease control rate was 73.1% (95% CI, 60.9-83.2). Median progression-free survival was 4.1 (95% CI, 2.9-5.3) months. Median duration of response and overall survival have not been reached.FCN-411 was well tolerated and demonstrated preliminary antitumor activity in patients with EGFR-mutated NSCLC after progression on EGFR-TKIs, especially in those without EGFR T790M mutation. The RP2D was defined as 8 mg once daily. Future studies are warranted.ClinicalTrials.gov, NCT03420079.

Do external uncertainties hold back or accelerate firms’ strategic change? To examine this issue, we develop a theoretical framework on the relationship between policy uncertainty caused by political turnover and the level of a firm’s strategic change and also theorize how political connections and financial resources affect firms’ response in the form of strategic change to environmental uncertainty. We test our framework with 16,451 firm-year observations of listed firms in China from 2008 to 2015 and find that political turnover has a negative influence on the level of a firm’s strategic change. Moreover, this influence is mitigated by political connections and/or financial resources.

Constraining the processes of deformation during tectonic switching from compression to extension is difficult because of the scarcity or absence of associated sedimentary and magmatic rocks and weak metamorphism. The east margin of the eastern North China Craton experienced Early to Middle Jurassic compression and Early Cretaceous extension. However, the period of tectonic quiescence lasting ∼13 million years (between 153 and 140 Ma) during which this transition occurred is poorly understood. This paper reports the identification of small-scale N-S-trending thrust and sinistral strike-slip faults (TSS) and NW-trending thrust and dextral strike-slip faults (TDS) in the Tongyuanpu-Aiyang region, which is part of the northern Liaodong Peninsula. Calculation of the tectonic stress field using striations, fault planes and kinematics reveals a NW-SE-oriented maximum principal axis (σ1) and sub-horizontal σ2 and σ3. Assemblages of N-S-trending TSS and NW-trending TDS were arranged with right stepping and resulted in local uplift and erosion at the junctions between fault terminations, which partitioned the Early and Middle Jurassic basins into residual smaller volcanic-sedimentary basins. These basins were unconformably overlain by small Early Cretaceous volcanic-sedimentary basins, such as those at Tongyuanpu and Fangjiaweizi. Magmatic ages and the timing of basin formation constrain the initiation of tectonic switching to 156–153 Ma, and its termination to 140–139 Ma. We suggest that R-R′ Riedel shears controlled the formation of the N-S-trending TSS and NW-trending TDS. The R-R′ shears were produced by continued sinistral strike-slip and northward growth along the Bohai Bay segment of the Tan-Lu fault zone during the Late Jurassic to early Early Cretaceous, simultaneous with a gradual weakening in the tectonic stress field during a switch in the direction of subduction of the Palaeo-Pacific plate from NW-ward to NNW-ward. This tectonic switching might have promoted the dissolution of gold and migration of gold-bearing fluids.

Flexible in-plane architecture micro-supercapacitors (MSCs) are competitive candidates for on-chip miniature energy storage applications owing to their light weight, small size, high flexibility, as well as the advantages of short charging time, high power density, and long cycle life. However, tedious and time-consuming processes are required for the manufacturing of high-resolution interdigital electrodes using conventional approaches. In contrast, the laser processing technique enables high-efficiency high-precision patterning and advanced manufacturing of nanostructured electrodes. In this review, the recent advances in laser manufacturing and patterning of nanostructured electrodes for applications in flexible in-plane MSCs are comprehensively summarized. Various laser processing techniques for the synthesis, modification, and processing of interdigital electrode materials, including laser pyrolysis, reduction, oxidation, growth, activation, sintering, doping, and ablation, are discussed. In particular, some special features and merits of laser processing techniques are highlighted, including the impacts of laser types and parameters on manufacturing electrodes with desired morphologies/structures and their applications on the formation of high-quality nanoshaped graphene, the selective deposition of nanostructured materials, the controllable nanopore etching and heteroatom doping, and the efficient sintering of nanometal products. Finally, the current challenges and prospects associated with the laser processing of in-plane MSCs are also discussed. This review will provide a useful guidance for the advanced manufacturing of nanostructured electrodes in flexible in-plane energy storage devices and beyond.

Wet etching of silicon carbide typically exhibits poor etching efficiency and low aspect ratio. In this study, an etching structure that exploits anisotropic charge carrier flow to enable high-throughput, external-bias-free wet etching of high-aspect-ratio SiC micro/nano-structures is demonstrated. Specifically, by applying a catalytic metal coating at the bottom surface of a SiC wafer while introducing patterned ultraviolet light illumination from its top surface, spatial charge separation across the wafer is achieved, i.e., photogenerated electrons are channeled to the bottom to participate in the reduction reaction of an oxidant in the etchant solution, while holes flow to the top to trigger oxidation of SiC and subsequent etching. Such design largely suppresses recombination-induced charge losses, and when used in combination with a top metal catalyst mask, the structure yields a remarkable vertical etching rate of 0.737 µm min

Based on the coherence theory for non-stationary optical fields, we introduce a new class of partially coherent pulse sources with multi-cosine-Gaussian correlated Schell-model (MCGCSM) and derive the analytic expression for the temporally mutual coherence function (TMCF) of an MCGCSM pulse beam when it propagates through dispersive media. The temporally average intensity (TAI) and the temporal degree of coherence (TDOC) of the MCGCSM pulse beams spreading in dispersive media are investigated numerically, respectively. Our results show that over propagation distance, the evolution of pulse beams is from the primary single beam into multiple subpulses or form flat-topped TAI distributions by controlling source parameters. Moreover, when the chirp coefficient s

This study investigates the impact of accounting firms joining global accounting firm networks and associations (AF N&As) on audit quality and audit pricing in China. We find that after their accou...

Miniaturized and flexible power resources such as supercapacitors with resistance of high voltage play a critical role as potential energy storage devices for implantable and portable electronics because of their convenience, high power density, and long-term stability. Herein, we propose a novel strategy for the fabrication of high voltage microsupercapacitors (HVMSCs) employing porous laser-induced graphene (from polyimide films with alkalization treatment) followed by laser carving of the polyvinyl alcohol/H3PO4 gel electrolyte to realize a series assembly of supercapacitors and significantly increase the voltage resistance. The results elucidated that HVMSCs (3 mm × 21.15 mm) exhibited excellent capacitive performance including exceptional potential window (10 V), high areal capacitance (244 μF/cm2), acceptable power density (274 μW/cm2) and energy density (3.22 μW h/cm2), good electrochemical stability and flexibility at different bending status (0, 45, 90, 135, and 180°), as well as impressive voltage durability more than 5 V in smaller scale (0.5 mm × 5.5 mm). As such, the HVMSCs have great potential to be integrated with microcircuit modules for the next-generation self-powered systems and storage electronic devices in high voltage applications.

This paper aims to study the endoprosthesis of a patient from the perspective of clearance between the hip bone and the implant. The implant was made with biocompatible titanium Ti-6Al-4V ELI through the additive manufacturing technique known as SLM. FEA was done in ABAQUS to study the stress distribution in the prosthesis with and without the clearance between the bone and the implant. Various loading scenarios were simulated, and the devastating scenario was identified to study the fatigue life safety factor of the prosthesis. The study shows that the clearance plays a pivotal role in the functionality of the implant, and can also become the reason for the deviation from its intended operation contributing towards the revision of the prosthesis.

Joule heaters based on flexible thin films have attracted a significant amount of attention in both academia and the industry. However, it has been highly challenging to fabricate such heaters. In this study, a one-step laser induction method was proposed to prepare fluorine-doped laser-induced graphene (F-LIG) with stable and superhydrophobic properties by confining a 355 nm ultraviolet laser at the interface between the fluorinated ethylene propylene (FEP) film and polyimide (PI) film. The superhydrophobic properties of the F-LIG composite films could be attributed to the doping of fluorine elements and the laser-processed microstructures, which could be tuned by laser processing parameters. Based on the processed F-LIG films, Joule deicing heaters were developed and their deicing efficiencies are 7 times higher than that of the undoped LIG-based deicing heater. The method will provide new means and ideas to develop LIG-based flexible devices.

A nonlinear adaptive backstepping control method was proposed to address the system parameter uncertainty problem in the position control process of an electro-hydraulic servo closed-pump control system. This control strategy fully considers the parameter uncertainty of the nonlinear system and establishes the adaptive rate of the uncertain parameter to adjust the parameter disturbance online in real time, thereby improving the accuracy and robustness of the control system. A pump control system experiment platform was used to verify the feasibility of the controller. The experimental results showed that the proposed control strategy provided a good control effect. The pump control system can be controlled with high precision, with a steady-state control accuracy of ±0.02 mm, which serves as a good foundation for the engineering application and promotion of the pump control system.

An ultra-high sensitivity photonic crystal fiber mid-infrared refractive index (RI) sensor based on surface plasmon resonance is proposed, whose properties are investigated by the finite element method. Gold can be utilized to create excitation between the fundamental mode and surface plasmon polaritons mode. The simulation results indicate that, at the wavelength of 1.7–4.0 μm, the proposed sensor could detect a RI in the range of 1.00–1.31, a maximum sensitivity of 37 000 nm RIU−1, and an optimal resolution of 2.70 × 10−6 RIU is achieved. The result of curve fitting is 0.98185. The proposed mid-infrared RI sensor plays an important role in organic chemistry detection, medical detection, and related fields.

A novel concave-shaped photonic crystal fiber sensor with double loss peaks based on surface plasmon resonance is proposed, whose properties are investigated by the finite element method. Gold can be utilized to generate excitation between the core mode and surface plasmon polariton mode. The simulation results indicate that in the wavelength range of 1.2 to 2.2 μm, the proposed sensor could detect the refractive index (RI) in the range of 1.18–1.30, the wavelength sensitivity of the primary loss peak could reach up to 18 000 nm/RIU and the corresponding resolution is 5.56 × 10−6 RIU in the RI range from 1.26 to 1.27. In addition, the double loss peaks could improve the detection accuracy, and the trough wavelength variation range is small, indicating that the proposed sensor is relatively stable, which improves the practicability of the sensor. This work could have a wide application value in the detection of medical testing, biomolecules, and organic chemistry.

A control strategy combining adaptive backstep sliding mode control and dead-zone inverse compensation control in a series was proposed to solve the problem of system parameter uncertainty and system dead-zone in the process of position control in an electro–hydraulic servo closed pump control system. Firstly, an adaptive backstepping sliding mode controller was designed by introducing the sliding mode control principle. Secondly, the smooth dead-zone inverse function was constructed by using the smooth continuous index function to design the dead-zone inverse compensation controller, which is combined with the adaptive sliding mode controller to form a series controller. Finally, the feasibility of the controller was verified by using the pump control servo system of a lithium battery pole strip mill. The experimental results show that, compared with traditional PID control, the control strategy displayed no excessive overshoot before the steady state, the steady-state control accuracy could reach ±0.002 mm, and the time required to reach the steady state was 1 s to 2 s shorter, which shows this method’s ability to effectively improve the position control accuracy of the pump control system, as well as its dynamic response performance.

This paper proposes that the separation of the roles of CEO and board chairman is a result of, rather than a solution to large shareholder agency problem. We support this view by examining the prob...

As a cost-effective, facile and scalable technology, direct laser writing technology has been widely reported for modifying the surface properties of polymers. In this work, the modification induced in polyimide (PI) films by the pulsed Nd:YAG laser has been investigated. The formation mechanism of surface morphologies of the laser-induced PI films was clarified through laser Mie scattering. Various laser powers, scanning speeds and pulse repetition frequencies were applied to modify surface properties, including surface morphologies, carbonization characteristics and wettability. Analysis of the morphological changes in the PI film surface layer was performed via a three-dimensional optical microscope. The degree of carbonization was measured using the grey-scale extraction tool in the Adobe Photoshop software. It is found that the laser fluence incident on a PI film is closely related to the density of floating carbonized particles generated by the high-temperature carbonization and the high-pressure release of the excited atoms in PI film. Meanwhile, the density of carbonized particle group and the number of cavities in PI film mainly depend on the unscattered static laser fluence regardless of the dynamic laser fluence. And the degree of laser Mie scattering can be inferred by the degree of carbonization of the cavity-free surface and the distribution ratio of the small-sized cavities with diameters of ≤15 μm. Within the range of the studied processing conditions, the laser power and pulse repetition frequency exhibited a greater sensitivity to the carbonization area rate of cavity defects and the wettability than the scanning speed.

Carbon fibers (CFs) are often chopped through conventional metal cutting tools. The wear of cutting tool is unavoidable, resulting in low productivity and unsteady product quality. In this work, cutting CFs by fiber laser was studied. The laser absorptivities of three types of CFs and sizing amounts were measured to evaluate their photothermal conversion properties. The cutting-off mechanism of CF was clarified by its kerf cross-sectional morphology and multiphysics simulations. The morphology, chemical composition and mechanical properties around the CF kerf were analyzed to investigate the characteristics of laser cutting method. In addition, the effect of laser parameters and sizing amounts on CF tow cutting were investigated. Results show that laser-cutting CF in the heat affected zone has poor mechanical properties compared to mechanical cutting CF, but composite nonwoven fabrics made by either of them have substantially equal tensile strength. The critical cutting-off speed of the three CFs has a linear relationship with the laser power. Compared to mechanical cutting, laser cutting of CF tows can reduce about 50% energy consumption. And the laser cutting speed can be adjusted within a large range, whereas the mechanical cutting speed is only determined within a relatively narrow range. This low-energy consumption and speed-adjustable cutting method shows great potential to produce chopped CF-based high-quality composites.

Purpose: FH-2001 is a FGFR/VEGFR targeted drug that can reduce the expression level of PD-L1 in tumor cells by down-regulating the cMYC gene. The anti-tumor activity of FH-2001 has been confirmed in preclinical studies. Apart from exerting potent anti-proliferative effect on FGFR-driven tumors, FH-2001 may be able to overcome primary and secondary resistance of conventional immune checkpoint inhibitors or increase the response rate through PD-L1 regulation. This first-in-human study evaluated the safety, tolerability, pharmacokinetics and anti-tumor activity of FH-2001 in patients with advanced solid tumors. Methods: This open-label, non-randomized, multicenter phase I study has two parts. The first part comprised a dose escalation and a dose expansion phase to evaluate the safety, tolerability and determine the maximum tolerated dose(MTD)and phase II recommended dose (RP2D) of FH-2001. The dose escalation phase enrolled patients with advanced solid tumors with planned dose levels for 1, 2, 4, 8, 12 or 16 mg. The accelerated titration design was used in the dose escalation phase for 1 and 2 mg dose, and if grade 2 or higher drug-related adverse events (TRAEs) occurred during the dose-limiting toxicity (DLT) period between cycle 0 and 1 with 25 days, dose escalation would subsequently follow the 3+3 design. All other doses utilized the 3+3 design. Patients first received a single dose of FH-2001, and if no DLT or other unacceptable occurred, patients subsequently receive FH-2001 once daily in 21-day cycles. FH-2001 at a dose where objective efficacy was observed or reached effective exposure were selected for dose expansion. In the dose expansion phase, patients with advanced solid tumors harboring FGFR gene aberrations were enrolled, with 6-12 patients at each dose level, and they received FH-2001 once-a-day continuously in 21-day cycles. RP2D was determined based on the safety, pharmacokinetic/pharmacodynamic and preliminary efficacy data that were available in the first part of the study. The second part of the study commenced after RP2D was confirmed, which is a two-cohort study to evaluate the efficacy and safety of FH-2001. The first cohort comprised patients with advanced solid tumors who had progressed on prior treatment with an immune checkpoint inhibitor. The second cohort included patients with locally advanced or metastatic solid tumors with FGFR gene aberrations. Approximately 30 patients were enrolled in each cohort. Safety was assessed throughout the study and for 30 days after the last dose. Tumor response was assessed by the investigators according to RECIST v1.1. Pharmacokinetics and pharmacodynamics were evaluated at prespecified time points. Citation Format: Zhengbo Song, Ai-min Hui, Zhuli Wu, Huilong Liu, Xiangdong Cheng. A phase I open-label study of FGFR/VEGFR inhibitor FH-2001 in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT527.

BACKGROUND: To systematically evaluate the physical image quality of low-dose computed tomography (LDCT) on CT scanners from 5 different manufacturers using a phantom model. METHODS: CT images derived from a Catphan 500 phantom were acquired using manufacturer-specific iterative reconstruction (IR) algorithms and deep learning image reconstruction (DLIR) on CT scanners from 5 different manufacturers and compared using filtered back projection with 2 radiation doses of 0.25 and 0.75 mGy. Image high-contrast spatial resolution and image noise were objectively characterized by modulation transfer function (MTF) and noise power spectrum (NPS). Image high-contrast spatial resolution and image low-contrast detectability were compared directly by visual evaluation. CT number linearity and image uniformity were compared with intergroup differences using one-way analysis of variance (ANOVA). RESULTS: The CT number linearity of 4 insert materials were as follows: acrylic (95% CI: 120.35 to 121.27; P=0.134), low-density polyethylene (95% CI: –98.43 to –97.43; P=0.070), air (95% CI: –996.16 to –994.51; P=0.018), and Teflon (95% CI: 984.40 to 986.87; P=0.883). The image uniformity values of GE Healthcare (95% CI: 3.24 to 3.83; P=0.138), Philips (95% CI: 2.62 to 3.70; P=0.299), Siemens (95% CI: 2.10 to 3.59; P=0.054), Minfound (95% CI: 2.35 to 3.65; P=0.589), and Neusoft (95% CI: 2.63 to 3.37; P=0.900) were evaluated and found to be within ±4 Hounsfield units (HU), with a range of 0.99–2.76 HU for standard deviations. There was no statistically significant difference in CT number linearity and image uniformity across the 5 CT scanners under different radiation doses with IR and DLIR algorithms (P>0.05). The resolution level at 10% MTF was 6.98 line-pairs-per-centimeter (lp/cm) on average, which was similar to the subjective evaluation results (mostly up to 7 lp/cm). DLIR at all 3 levels had the highest 50% MTF values among all reconstruction algorithms. For image low-contrast detectability, the minimum diameter of distinguishable contrast holes reached 4 mm at a 0.5% resolution. Increasing the radiation dose and IR strength reduced the image noise and NPS curve peak frequency while improving image low-contrast detectability. CONCLUSIONS: This study demonstrated that the image quality of CT scanners from 5 different manufacturers in LDCT is comparable and that the CT number linearity is unbiased and can contribute to accurate bone mineral density quantification.