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This study evaluated the antitumor activity and safety of pemigatinib in previously treated Chinese patients with advanced cholangiocarcinoma and fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements.Pemigatinib provided clinical benefits for previously treated patients with cholangiocarcinoma carrying FGFR2 fusions or rearrangements and was approved for this indication in multiple countries.In this ongoing, multicenter, single-arm, phase II study, adult patients with locally advanced or metastatic cholangiocarcinoma carrying centrally confirmed FGFR2 fusions or rearrangements who had progressed on ≥1 systemic therapy received 13.5 mg oral pemigatinib once daily (3-week cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was objective response rate (ORR) assessed by an independent radiology review committee.As of January 29, 2021, 31 patients were enrolled. The median follow-up was 5.1 months (range, 1.5-9.3). Among 30 patients with FGFR2 fusions or rearrangements evaluated for efficacy, 15 patients achieved partial response (ORR, 50.0%; 95% confidence interval [CI], 31.3-68.7); 15 achieved stable disease, contributing to a disease control rate of 100% (95% CI, 88.4-100). The median time to response was 1.4 months (95% CI, 1.3-1.4), the median duration of response was not reached, and the median progression-free survival was 6.3 months (95% CI, 4.9-not estimable [NE]). Eight (25.8%) of 31 patients had ≥grade 3 treatment-emergent adverse events. Hyperphosphatemia, hypophosphatasemia, nail toxicities, and ocular disorders were mostlygrade 3, except for 2 events ≥grade 3.The encouraging antitumor activity and favorable safety profile support the use of pemigatinib as a treatment in previously treated Chinese patients with cholangiocarcinoma and FGFR2 rearrangements.

Purpose Evidence indicates that the actin-binding protein Coronin 3, which is aberrantly expressed in various cancers, is associated with cancer development and progression. However, little is known about the role of Coronin 3 in glioma tumorigenesis. Here, we aimed to explore the biological function and regulatory mechanism of Coronin 3 in glioblastoma (GBM). Materials and methods Coronin 3 level in human GBM clinical samples and cell lines was investigated. The shRNA knockdown strategy was used to assess the tumor characteristics of GBM cell lines. The role of β-catenin in Coronin 3-mediated oncogenic phenotypes was evaluated. Results Coronin 3 was found to be highly upregulated in glioma cell lines. Furthermore, knockdown of Coronin 3 significantly inhibited the growth of glioma cells both in vivo and in vitro and suppressed the expression of Wnt/β-catenin pathway genes, including β-catenin, Cyclin D1, and c-Myc. Moreover, we demonstrated that Coronin 3 regulates the expression of β-catenin in glioma. Our results revealed that Coronin 3-stimulated tumor growth was β-catenin-dependent. Conclusion Our study reveals a new molecular mechanism of Coronin 3 in promoting glioma growth and development through regulating the Wnt/β-catenin signaling pathway.

TLR3 and IL-10 play a crucial role in antiviral defence. However, there is a controversy between TLR3 rs3775291 and IL-10 rs1800871 polymorphisms and the risk of hepatitis B virus (HBV) infection. The purpose of this study is to explore the relationship between the two single nucleotide mutations and the risk of HBV infection by meta-analysis. Medline, EMBASE, Web of Science, CNKI, China Wanfang database were searched for the case-control studies on the relationship between TLR3 rs3775291 and IL-10 rs1800871 polymorphism and susceptibility to HBV, updated to June 2020. The data were analysed by Stata 15.0 software. A total of 22 articles were included. The results showed that in the analysis of IL10 rs1800871 polymorphism and the risk of HBV infection, the pooled OR was 1.21 (95% CI 1.06–1.37), 1.28 (95% CI 1.04–1.56) and 1.20 (95% CI 1.06–1.37) and 1.40 (95% CI 1.07–1.83) in the allele model (C vs. T), dominant model (CC+CT vs. TT), recessive model (CC vs. CT+TT) and homozygous model (CC vs. TT), respectively. There was no statistical significance in the heterozygote model. A subgroup analysis of the Asian population showed similar results. The analysis of TLR3 rs3775291 polymorphism and the risk of HBV showed that in the allele model (T vs. C), the pooled OR was 1.30 (95% CI 1.05–1.61). Except for the recessive model, no significances were found in other genetic models. In conclusion, TLR3 rs3775291 and IL-10 rs1800871 polymorphisms are associated with the risk of HBV. Allele C and genotype CC at IL10 rs1800871 loci, as well as allele T and genotype TT at TLR rs3775291 loci, may increase susceptibility to Hepatitis B infection.

ObjectiveThere is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of Trametes robinophila Murr (Huaier granule) to address this unmet need.Design and resultsA total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI −12.59 to −2.50; p=0.0018), respectively.ConclusionsThis is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group.Trial registrationNCT01770431; Post-results.

Glioblastoma is a common malignant primary intracranial tumor characterized by rapid invasive growth and a high recurrence rate after surgery. MicroRNAs (miRNAs) are involved in cell proliferation, differentiation, and apoptosis, and abnormal miRNA expression is associated with the occurrence and progression of various tumors, including glioblastomas. The aim of this study was to determine the levels of miR-148a and integrin subunit alpha 9 (ITGA9) in glioblastoma tissues and cells and their involvement in cancer cell proliferation and migration. Glioblastoma tissues from 19 patients and two glioblastoma cell lines (U87 and LN229) were used in this study. The effects of miR-148a on cell viability, proliferation, colony formation, migration, and invasion were assessed. Glioblastomas were xenografted in nude mice to examine the effects of miR-148a overexpression on tumor growth in vivo. Levels of ITGA9 mRNA and protein in glioblastoma tissues were detected by quantitative reverse transcription PCR and western blot analysis, respectively. The interaction between miR-148a and ITGA9 was determined by a dual-luciferase reporter gene assay. We found that the overexpression of miR-148a decreases the proliferation, clustering, migration, and invasiveness of U87 and LN229 cells and inhibits the tumorigenicity of xenografted glioblastomas. We confirmed that ITGA9 is the target of miR-148a. Restoration of ITGA9 expression reversed the decreased viability, migration, and invasiveness of glioblastoma cells induced by miR-148a overexpression. Our findings indicate that miR-148a can suppress the malignant phenotype of glioblastoma by targeting ITGA9 and identify ITGA9 as a potential therapeutic target for glioblastoma.

We study the quadrature squeezing and entanglement in a cavity optomechanical system (COMS). In our model, a flying atom sequentially passes through and interacts with the COMS and a Ramsey pulse zone, and subsequently the atomic state is detected. In this way, the photon-phonon squeezing and entanglement can be generated. The dynamic evolution of the squeezing and entanglement in the presence of losses are examined by using the master equation method.

Stimulated Brillouin scattering (SBS) and stimulated Raman scattering (SRS) are two kinds of emblematic inelastic scattering processes resulting from the interaction of high-intensity laser with matter. Generally, competition between SBS and SRS is a common phenomenon in many substances. In liquid or high-pressure gas, if a single longitudinal mode laser is used as a pump source, both SBS and SRS can be excited, but the SBS will become very strong due to higher gain and optical phase conjugation. In comparison, the SRS gain is typically 2 orders of magnitude smaller than the SBS gain so that most of the pump laser energy is spent on the SBS and the SRS is greatly suppressed. To improve the output energy of SRS in liquid medium, a method of suppressing the SBS process by controlling temperature of medium is proposed. The SRS generation system using broadband pulse laser of 532 nm in wavelength as a pumping source is designed, the output energy of forward SRS (FSRS) and backward SBS (BSBS) in water with different temperatures are measured, and the physical mechanisms of the influences of water temperature, pumping linewidth and thermal defocusing on the output energy of SRS are analyzed. The experimental results indicate that by reducing the water temperature, the SBS process can be significantly suppressed, and the beam distortion caused by thermal defocusing effect can be reduced, thus effectively improving the output energy of SRS. Unlike the single longitudinal mode laser, when the pump source is handled in multiple longitudinal modes with a wide linewidth, the gain of FSRS is higher than that of the backward SRS (BSRS). Meanwhile, since the SBS gain coefficient is restricted by the linewidth of the pump laser, the FSRS process is dominant and both backward SBS and BSRS are significantly suppressed. It is necessary to state that none of the influence of backward SRS, self-focusing, optical breakdown and other non-linear effects on the output energy of SRS is considered in this paper, and only the effectiveness of reducing temperature to improve the energy output of forward SRS is verified from the perspective of temperature change. The results are of great significance for the multi-wavelength conversion of SRS in liquid medium.

Fluid dispensing is a process of delivering fluid materials in a controllable manner and has found extensive applications in electronics packaging manufacturing. Among various dispensing approaches, the rotary-screw-driven dispensing method has high versatility for dispensing a wide range of fluid materials. Given the fact that the flow rate of material dispensed has significant effects on the quality of electronics packaging, knowledge of the flow rate in rotary screw dispensing systems through mathematical models is desired. This paper presents the development of an integrated dynamic flow-rate model for rotary-screw-driven dispensing systems. The model is composed of two interconnected submodels, one model for the dynamics of the screw-driving system and the other for the flow-rate dynamics in the screw channel. Without loss of generality, a phenomenological model in the form of a linear state space model is adopted for the dynamics of the screw-driving system, and by considering the fluid compressibility, the flow-rate dynamics in the screw channel is represented. Dispensing experiments were performed for model parameter estimation and then for model verification. The results illustrate that the model developed can be used to predict the flow rate in the rotary-screw-driven dispensing systems.

The dump truck in coal mine, mountain and other bad conditions of overload transportation, the turning shaft often breaks, through material analysis of dump truck turning shaft and method of theoretical calculation and finite element analysis, making force analysis to the stress concentrated area, find the reasons for turning shaft fracture.

The mechanism of pituitary gland tumour (PGT) is unclear. Aberrant immune tolerance is associated with the pathogenesis of tumour. Vitamin D and vitamin D receptor (VDR) are involved in the immune regulation. Interleukin (IL)-10 is one of the important immune regulatory molecules. This study aims to elucidate the role of VDR in the regulation of IL-10 in peripheral B cells of PGT patients. In this study, the peripheral blood samples were collected from PGT patients and healthy subjects. B cells were purified from the blood samples and analysed by RT-qPCR and Western blotting. The correlation between the expression of IL-10 and VDR in the B cells was assessed. We observed that the serum VitD levels were negatively correlated with IL-10 expression in peripheral B cells of patients with PGT. Low levels of VDR expression were found in peripheral B cells of PGT patients. Exposure to VitD suppressed the expression of IL-10 in B cells. The VDR bounds the transcription factor of IL-10 to interfere with the expression of IL-10 in B cells. The VDR agonists inhibited IL-10 expression in B cells from PGT patients. In conclusion, modulation of the expression of VDR can regulate the expression of IL-10 in peripheral B cells of PGT patients, which may contribute to the treatment of PGT.

The knife-gap accuracy of rolling-cut bilateral shear is one of the key factors influencing the cutting quality. This paper through the site of a high strength low alloy steel shear test, a linear regression equation for the relation between knife-gap and plate thickness is obtained and optimize by using MATLAB Toolbox, after optimization of the linear regression equation can be conveniently used, reduce knife-gap adjustment time, improve production efficiency, reduce shearing defects.

Simple description the background of hydraulic hybrid technology, scope of application. Put forward the idea of hybrid hydraulic system design based on the car's braking performance, the main elements parameter calculation. Simulation results show that the braking process is smooth, brake energy recovery, the system design and parameter calculation of reasonable.

Motor plays an important role in the dynamic property of the rotary-screw-driven dispensing system. Dynamic model of the motor was developed and validated in this paper. The output angle displacement and input voltage were measured from photoelectric digital encoder which is used to measure the angle displacement of the motor. In order to realize data smooth processing, Alpha-Beta filter was used. Discrete model of the motor was developed based on the Least Square Method and Model Selection criterion. Computational studies show that the system is equivalent to second order system. Moreover, the model was validated based on the experiment results under the different applied pressure and angular speed of motor. It is revealed that there is a good fit between experiment data and model simulation.

MicroRNA-378 (miR-378) is dysregulated in multiple malignancies and is associated with tumor progression. However, the expression and mechanism of miR-378 in pituitary adenoma (PA) remains to be elucidated. In the present study, the role and mechanism of miR-378 in PA tumorigenesis and development was investigated. It was revealed that the levels of miR-378 expression were markedly downregulated in PA tissues. CCK-8 and wound healing assays revealed that transfection with miR-378 mimics was able to markedly inhibit the proliferation and migration of GH3 cells. Furthermore, quantitative polymerase chain reaction analysis demonstrated that ring finger protein 31 (RNF31) was upregulated in PA specimens and the levels of RNF31 expression was negatively regulated by miR-378. In addition, knockdown of RNF31 markedly suppressed cell proliferation and migration in GH3 cells. In conclusion, the present study provides a molecular basis for the function of miR-378/RNF31 in the progression of human PA, indicating a potential novel target for the treatment of PA.

Metal surface treatment by silane provides an alternative replacer to the existing toxic hexavalent chromium passivation technique. This article deals with the two fundamental aspects, viz reactivity and processability, of different hydrolyzing silane systems. By conductivity determination, the conversion of Si-OC2H5 into Si-OH and Si-OH condensation were studied for different hydrolyzing systems. The optimum hydrolyzed system was proposed based the desired balance of reactivity and processability.

According to Faraday's law of electromagnetic induction,the electromagnetic vibration energy harvester can convert the mechanical vibration of human running or walking to electrical energy, the harvester output is through detection/rectification, two-stage of energy storage, stabilize voltage which is able to reach stable voltage of 4.2V,current of 355mA.The whole system doesn’t need external power supply, the electromagnetic vibration energy harvester has produced two part of the electric energy, a part used to storage, and another part provided power supply for circuit chips. Characteristic of the selected chip is low power and high stability. Analyzing the energy harvester’s structure and principles, a basic electronic circuit for storing the electrical energy is also introducing. The amount of output electrical energy about energy harvester is controlled by magnetic field strength, amplitude and frequency of human movement.

The collision characteristics of the truck fences are very important to occupant safety in car, when the car’s front collisions the tail of truck. This study is a kind of the truck fence structure and simulates its crash. First, simulates the original truck guards. Second, improves the truck fence, and the truck fence is simulated by ANSYS / LS-DYNA. Finally, the simulation results and unimproved simulation results are compared. The results show that the dynamic response characteristics (deformation, velocity and acceleration) and the absorb energy (interna energy and kinetic energy) of the improved model are significantly enhanced.

Helicoverpa hormone receptor 3 (HHR3) is a transcription factor involved in larval molting regulation. To investigate its function and the possibility to improve the insecticidal activity of AcMNPV, HHR3 was expressed in Bac-to-Bac system and an AcMNPV-GFP-HHR3-Polh+ virus was constructed after recovery of the polyhedrin gene. HHR3 expression in Sf21 cells was confirmed by immunofluorescence microscopy. A red color identifying HHR3 was observed using fluorescence microscopy; this confirmed that HHR3 was expressed in Sf21 cells by the introduction of the recombinant virus AcMNPV-GFP-HHR3-Polh+. The AcMNPV-GFP-HHR3-Polh+ infected the hemocytes of H. armigera larvae by hemocoele injection or per oral ingestion. Results showed that AcMNPV-GFP-HHR3-Polh+ resulted in incomplete ecdysis, slower growth and lower median survival time on the Helicoverpa larvae. This recombinant virus may aid in the development of an insecticide that can be used in the field.

The natural ventilation widely used in greenhouses has advantages of saving energy and reducing expense. In order to provide information for climate control of greenhouse, a model was developed to predict the variation of air temperature in the naturally ventilated greenhouse equipped with insect-proof screen. Roof ventilation and combined roof and sidewall ventilation were considered in the model. This model was validated against the results of experiments conducted in the greenhouse when the wind was parallel to the gutters. The model parameters were determined by the least squares method. In the used model, effects of wind speed and window opening height on the air temperature variation were analyzed. Comparison between two types of ventilation showed that there existed a necessary ventilation rate which results in air temperature decrease in natural ventilation under special climatic conditions. In our experiments when wind speed was less than 3.2 ms(-1), wind had a more gradual effect on greenhouse temperature for roof ventilation, compared with combined roof and sidewall ventilation, which had greater air temperature decrease than roof ventilation only.

We propose a novel scheme to generate the entanglement between two cavity optomechanical systems (COMSs) via a flying two-level atom. We derive the analytical expressions for the generated entangled states. We find that there exist two processes for generating entanglement: one is the entanglement transfer between the two phonon-modes, and the other is the entanglement swapping-like process among the two photon-modes and the two phonon-modes. We analyze these two kinds of phenomena, respectively, by adjusting the distance between the two COMSs. Then we discuss the verification of the generated entangled states of the two COMSs, and analyze the decoherence of the generated entangled states. Finally, we discuss the experimental feasibility of our proposal.

Batch culture experiments were used to study the effect of leachate from sediment of Yanghe reservoir on the growth of Microcystis and Anabaena isolated from Yanghe reservoir. The results showed that the growth of Microcystis was significantly inhibited when the addition of anaerobic leachate from sediment in M11 culture medium was high (or = 20% V/V). The maximum biomass of Microcystis was lower than that grown in pure M11 culture medium. But there was an obvious promotion on the growth of Anabaena when anaerobic leachate from sediment was added. The growth rate of Anabaena increased 36.6%, 47.2% and 36.0%, respectively, compared to M11 culture medium when adding 2%, 20% and 50% (V/V) anaerobic leachate. Compared to adding anaerobic leachate, aerobic leachate had no influence on the growth of Microcystis, while the growth rate of Anabaena was promoted by aerobic leachate. The growth rate of Anabaena increased 37.2% compared with M11 when adding 20% (V/V) of aerobic leachate. But after addition of Fe-citrate to the mixed culture medium (50% M11 culture medium +50% anaerobic leachate), the maximum biomass of Microcystis significantly increased. The results suggest that high organic matter concentration decreases iron availability for Microcystis.

Based on statics analyzing of pneumatic four-connecting lever roof-vent opener applied to multi-span plastic greenhouse, by considering intensity requirement, installation error, boundary and other restrictions, optimizing model taking for minimal output thrust of pneumatic cylinder as object is established. Pneumatic cylinders were selected according to optimizing results. Checking the present system meets stability requirements. By changing load and structure parameters, the optimum programme can be used to design four-connecting lever pneumatic roof-vent opener for all kinds of multi-span plastic greenhouses. System installation and application show that the pneumatic roof-vent opener is low electricity consumption, faster response, more convenient installation and propitious opening enhancement as compared with the traditional one.