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We describe the design, synthesis, and structure–activity relationship (SAR) of heterobifunctional RET ligand-directed degraders (LDDs) derived from three different second-generation RET inhibitors. These LDDs are composed of a target binding motif (TBM) that binds to the RET protein, a linker, and a cereblon binding motif (CBM) as the E3 ligase recognition unit. This led to the identification of a series of pyrazolopyridine-based heterobifunctional LDDs, as exemplified by compound 39. LDD 39demonstrated high in vitro inhibitory and degradation potency against both RET wild-type and the two representative mutants, V804M and G810R. Importantly, in PK/PD studies, 39exhibited a differentiated and favorable in vivo profile compared to the corresponding tyrosine kinase inhibitor (TKI), compound 3. Robust and sustained degradation of total-RET (tRET) protein and inhibition of phospho-RET (pRET) signaling were observed in TPC-1 xenograft tumors driven by RET and the RET/G810R mutant following a single dose of LDD 39at 15 and 75 mg/kg, respectively.

The bonding interface serves as the stress load transfer surface of the bonded structure, and its quality detection is very important for the bonded structure strength and service safety of key components in the fields of ocean engineering equipment, wind turbines and aerospace. The laser spallation technique represents an effective method for localized inspection of bonding quality through the generation of high strain rate shock waves induced by a pulsed laser. However, a thorough understanding of the propagation and failure mechanism of shock waves is essential to gain insights into the energy reference level for delamination within the bonded structure. Due to the limitation of laser pulse width, previous research has mainly focused on the influence of laser power density. The influence of the key components of laser energy, pulse width, and spot diameter on the bonded structure has not been thoroughly explored. Therefore, this article independently designed a variable pulse width Nd: YAG laser and established a numerical model of laser shock spalling damage for metal bonded structural components based on Abaqus. The accuracy of the model was verified by comparing the back surface velocity obtained from simulation and experiment. Based on this premise, an investigation was conducted into the influence of laser parameters on the propagation and failure evolution of laser-induced shock waves in bonded structures. The results show that both laser energy and laser pulse width exert an influence on shock wave propagation in the bonded structure, while spot diameter does not play a pivotal role in spalling. Higher laser energy leads to greater increases in height at the back face of the sample, peak back face particle velocity, depth, and area of interfacial spalling. However, there are no significant changes in the spalling location observed. As the laser pulse width increases, the height of the back face of the sample remains nearly unchanged. The maximum depth tensile stress decreases and the spalling location changes. The modulation of laser energy and pulse width offers a viable approach for employing the laser spallation technique in non-destructive testing of weak bonding within composite material bonded structures.

The prevalent majority of foldable mobile phone products in the market are in the form of droplet shaped, which is formed by the combined action of the middle floating plate, the side floating plate, and the chassis of the hinge mechanism. This paper attempts to adjust the position of easy‐pull adhesive pasted on the side floating plate, the length of easy‐pull adhesive pasted on the chassis, and the raising height of the middle floating plate, aiming to reinforce the bending performance of the flexible module. Without changing the module stack and trajectory of the fixture plate, these modification strategies are effective and economical. The results displayed that by reasonable alteration, the cohesive peeling risk of OCA can be improved by 59.4% on average, and the EL peeling risk can be reduced by 31.6%. This research provides a potentially effective method to improve the bending performance of foldable module.

In this paper, the concept of crossed foldable display module is proposed as follows: there are two foldable axes, and the two foldable axes intersect vertically. In order to realize the crossed foldable display, it needs to be designed in terms of modules, hinges and so on, especially the module support layer in the intersection area. In this paper, the steps of structural design, numerical simulation and sample verification are used to obtain two kinds of support layers suitable for crossed foldable modules, which can be folded hundreds of thousands of times without failure in the whole module test verification, providing a new form for flexible display.

This study focuses on the enhancement of back‐impact resistance in flexible OLED modules, a critical aspect for the durability of modern slim‐profile electronic devices. Under rear compressive forces, flexible OLED modules are prone to bending towards the glass cover, placing the outermost touch layer under significant tensile strain. The brittle nature of the inorganic film within the touch layer, coupled with its low fracture elongation, predisposes it to crack initiation under stress. This mechanical vulnerability can lead to catastrophic failure of the OLED functionality due to moisture and oxygen infiltration, manifesting as black spots on the display. Addressing this, we propose a dual‐faceted approach: optimizing stress distribution by the module design and enhancing the tensile strength of the touch layer's inorganic film, achieving a sixfold increase in the module's resistance to back compression. This paper outlines the experimental setup, finite element method (FEM) simulations, and the resultant implications for flexible OLED module design and durability.

The insulation system is an important part of the fusion magnet coils and its role is to mechanically support, insulate, fix, and protect superconducting magnets. The insulation materials used for the China Fusion Engineering Test Reactor (CFETR) Central Solenoid Model Coil (CSMC) are glass-fiber reinforced plastics. Internal defects may be generated in the composite insulation structure during manufacture or service life. The inspection of the composites has many difficulties, mainly due to the multiple interfaces and different elastic properties. This article investigated the microstructure of the insulation system and defined the test objects for non-destructive test(NDE). Phased array ultrasonic test (PAUT) technology was developed to evaluate the integrity of the insulation system.

High myopia (HM) is the primary cause of blindness, with the microstructural organization and composition of collagenous fibers in the cornea and sclera playing a crucial role in the biomechanical behavior of these tissues. In a previously reported myopic linkage region, MYP5 (17q21–22), a potential candidate gene, LRRC46(c.C235T, p.Q79X), was identified in a large Han Chinese pedigree. LRRC46 is expressed in various eye tissues in humans and mice, including the retina, cornea, and sclera. In subsequent cell experiments, the mutation (c.C235T) decreased the expression of LRRC46 protein in human corneal epithelial cells (HCE-T). Further investigation revealed that Lrrc46−/−mice (KO) exhibited a classical myopia phenotype. The thickness of the cornea and sclera in KO mice became thinner and more pronounced with age, the activity of limbal stem cells decreased, and microstructural changes were observed in the fibroblasts of the sclera and cornea. We performed RNA-seq on scleral and corneal tissues of KO and normal control wild-type (WT) mice, which indicated a significant downregulation of the collagen synthesis-related pathway (extracellular matrix, ECM) in KO mice. Subsequent in vitrostudies further indicated that LRRC46, a member of the important LRR protein family, primarily affected the formation of collagens. This study suggested that LRRC46is a novel candidate gene for HM, influencing collagen protein VIII (Col8a1) formation in the eye and gradually altering the biomechanical structure of the cornea and sclera, thereby promoting the occurrence and development of HM.

In this paper, a method for further improving the efficiency of top emission organic light‐emitting diodes (TE‐OLEDs) by phosphorescent sensitized fluorescent organic light‐emitting diodes (PSF‐OLEDs) was provided. The maximum current efficiency (CE) of PSF‐OLEDs realized an improvement of nearly 40% compared with the phosphorescent device, which exhibited great potential in high‐efficiency OLEDs.

Foldable AMOLED panel are getting more attention due to portability and size extensibility. If there is a drop or collision impact during use, it is easy to cause panel crack or peeling, which has become a major problem affecting the development of foldable AMOLED panel. We designed the panel impact device and tested the anti‐impact energy and failure mode of the foldable AMOLED panel. Meanwhile, the stress process in the impact process is analyzed in detail based on finite element mechanics simulation. In addition, we also propose schemes to improve the anti‐impact performance of the foldable AMOLED panel through systematic anti‐impact experiments and simulation analysis, including increasing the bending stiffness of the foldable module and optimizing the pattern design of metal supporting material.

AMOLED flexible display are becoming popular, but the waviness in the middle of the display screen has greatly affected the user experience. Waviness will become more visible with the usage time, which is still the main concern of foldable products in the display industry. But the middle crease has become one of the main reasons why the sales of folding mobile phones have not been popular as present, mainstream mobile phone and screen manufacturers are in the analysis stage of Waviness mechanism. Therefore, this article mainly analyzes the causes of waviness in the folding screen from multiple factors, and draws its main influence mechanism. In this paper, based on the theoretical analysis and simulation results, the development direction of Film and OCA properties is proposed, which provides the possibility for the waviness‐free foldable AMOLED display.

The tearing process of the display screen module assembly induces stress on the panel, potentially causing panel failure and having adverse effects on production yield. However, the tearing of the screen involves numerous influencing factors, and there is currently a lack of systematic investigations into the individual effects of these factors. This work focuses on the aperture position on the panel in the tearing process by finite element analysis, analyzing the influences of aperture size, tearing direction, and the modulus of polarizing film and back plate film. The improvement recommendations resulting from this analysis were implemented in practical production, and no instances of aperture issues attributed to tearing were observed in the production of around three thousand screen modules.

Dynamic regulation of cell-extracellular matrix (ECM)-material interactions is crucial for various biomedical applications. In this study, a light-activated molecular switch for the modulation of cell attachment/detachment behaviors was established on monolayer graphene (Gr)/n-type Silicon substrates (Gr/Si). Initiated by light illumination at the Gr/Si interface, pre-adsorbed proteins (bovine serum albumin, ECM proteins collagen-1, and fibronectin) underwent protonation to achieve negative charge transfer to Gr films (n-doping) through π-π interactions. This n-doping process stimulated the conformational switches of ECM proteins. The structural alterations in these ECM interactors significantly reduced the specificity of the cell surface receptor-ligand interaction (e.g., integrin recognition), leading to dynamic regulation of cell adhesion and eventual cell detachment. RNA-sequencing results revealed that the detached bone marrow mesenchymal stromal cell sheets from the Gr/Si system manifested regulated immunoregulatory properties and enhanced osteogenic differentiation, implying their potential application in bone tissue regeneration. This work not only provides a fast and feasible method for controllable cells/cell sheets harvesting but also gives new insights into the understanding of cell-ECM-material communications.

The homo-charges accumulated inside the polymeric insulation of high voltage dc (HVdc) cables increase the electrical field beyond the uniform value, whereas the hetero-charges reduce it. Such uneven electrical field distribution is detrimental to HVdc cables’ longevity and thus, needs to be identified accurately. To this end, this article proposes a deep learning (DL) framework for the automated detection of space charges in HVdc cable insulation. The space charges inside the cross-linked polyethylene (XLPE) insulation samples were measured under varying electric fields (10–50 kV/mm) as well as at different temperatures (30 °C–70 °C) conditions. The obtained space charge profiles corresponding to no charge, hetero-charge, and homo-charge categories were fed to two benchmark convolutional neural network (CNN) models, i.e., AlexNet and VGGNet16, for automated feature extraction and classification purpose. The convolutional blocks of the two CNN models were sequentially fine-tuned using transfer learning (TL) to observe the variation in classification accuracies. The proposed approach delivers appreciably high classification accuracies irrespective of varying electric field and temperature conditions with reduced computational time toward distinguishing different categories of space charge accumulations compared to other CNN models. Hence, it can be potentially used for real-time HVdc insulation diagnostic purposes.

Following the conceptual design, the engineering design of the dc magnet and cable-in-conduit conductor (CICC) for the Super-X test facility has been done in 2021. Totally three types of conductors with different structures were designed for the three pairs of coils in the dc magnet, respectively. High-Jc Nb3Sn strand (Jc ∼2200 A/mm2 at 12 T, 4.2 K) was applied to high field and middle field coils for reducing the radius of the dc magnet. In order to qualify if the designed parameters of the conductors could fulfill the performance criteria, three pairs of short samples have been manufactured and tested successfully in the SULTAN facility at SPC, Switzerland. Test results and analysis show that dc performance of the three types of conductors can meet the design criteria. The conductor qualification process including the sample preparation, test results, and analysis are presented in this article. The HFC and LFC conductors exhibit different ac loss behavior to the MFC conductor, which is discussed in the article.

A gate driver on array (GOA) circuit was proposed for low-temperature polysilicon and oxide (LTPO) thin-film transistor (TFT) hybrid-driven active matrix organic light-emitting diode (AMOLED) displays with both high and low refresh rate operation. The GOA generates multiple types of scanning signals by reusing shift registers so that three signal pulses are output parallelly within a single stage to scan p- and n-type switching TFTs and emission TFT of the AMOLED pixels, respectively, leading to a 30% reduction in the layout area. Furthermore, the pulse-width of the scan signals for the emission TFT can be programed simply by changing the number of input pulses to vary refresh rates. The fabricated GOAs work well even with the pulse width reduced to $2.9 \mathbf {\mu }\text{s}$ .

ABSTRACTHelicopter-borne wide-angle synthetic aperture radar (SAR) can be used in a wide range of military and civil applications because of their high resolution and mobility. The absolute geometric positioning accuracy is an important index for SAR image quality assessment. However, the effectiveness of using traditional geometric calibration methods with helicopter-borne SAR images obtained by time-domain imaging algorithms remains to be verified. Based on the range-Doppler model, a high-precision geometric calibration method for helicopter-borne SAR is proposed in this study and verified by experiments using real data with different resolutions. The results show that after calibration, the positioning accuracy of SAR images with 20 m and 1 m resolutions is improved from 51.33 m to 4.71 m and from 62.49 m to 3.03 m, respectively. These results verify the effectiveness of the proposed method.

A concise pixel circuit with interleaved Emit signals is proposed for active matrix organic light‐emitting diode (AMOLED) displays, on the basis of low‐temperature polycrystalline silicon oxide (LTPO) TFTs. The oxide TFT can be re‐used for both initialization and threshold voltage extraction periods, using interleaved Emit signals of adjacent lines with overlapped waveforms. The proposed pixel circuit consists of 1 oxide TFT and 5 p‐type LTPS TFTs, while only 2~3 types of line‐by‐line scanning driving signals, i.e. the Emit signal and the Scan signal, are required. Implementation of the proposed pixel circuit shows that the occupation can be reduced to 40 μm × 56.7 μm. Furthermore, optimization of the pixel circuit shows the emission current error is less than 2.3% with threshold voltage variation of ± 0.5 V, while refresh rate from 1 to 120 Hz can achieved.

Improving the light output efficiency of OLED devices through micro lens is an important technological direction. Preparing high refractive index interfaces through inkjet printing is a mature production solution, but has limitations on screen borders. If high refractive index adhesive is used, it will also face limitations such as lower material refractive index and viscosity. In this paper, we propose a new micro lens structure to overcome the limitations of relative low refractive index of adhesive (n~1.6) and some problems encountered in the manufacturing process. Introducing a new low refractive index interface on the OC layer can expand the difference in refractive index, further improve efficiency, which does not require additional complex processes. This structure has good stability and can additionally improve the light output efficiency by about 5%, and it may become a potential technical improvement solution.

Dexmedetomidine (Dex) has been used in surgery to improve patients' postoperative cognitive function. However, the role of Dex in stress-induced anxiety-like behaviors and cognitive impairment is still unclear. In this study, we tested the role of Dex in anxiety-like behavior and cognitive impairment induced by acute restrictive stress and analyzed the alterations of the intestinal flora to explore the possible mechanism. Behavioral and cognitive tests, including open field test, elevated plus-maze test, novel object recognition test, and Barnes maze test, were performed. Intestinal gut Microbe 16S rRNA sequencing was analyzed. We found that intraperitoneal injection of Dex significantly improved acute restrictive stress-induced anxiety-like behavior, recognition, and memory impairment. After habituation in the environment, mice (male, 8 weeks, 18–23 g) were randomly divided into a control group (control, N= 10), dexmedetomidine group (Dex, N= 10), AS with normal saline group (AS + NS, N= 10) and AS with dexmedetomidine group (AS + Dex, N= 10). By the analysis of intestinal flora, we found that acute stress caused intestinal flora disorder in mice. Dex intervention changed the composition of the intestinal flora of acute stress mice, stabilized the ecology of the intestinal flora, and significantly increased the levels of Blautia(A genus of anaerobic bacteria) and Coprobacillus. These findings suggest that Dex attenuates acute stress-impaired learning and memory in mice by maintaining the homeostasis of intestinal flora.

Because of the complexity and difficulty of realizing a multi-wavelength soliton state, reports on its internal dynamic characteristics are scarce. In this study, the switching and periodic soliton explosion processes of the multi-wavelength soliton state in a negative dispersion passively mode-locked fiber laser are realized. The generation of the multi-wavelength soliton state undergoes the process of noise, oscillation, and stable mode-locking, and the splitting and annihilation of solitons with different group velocities directly impact the generation and disappearance of three wavelengths. Positive and negative dispersion lead to different group velocities of solitons. The presence and displacement of solitons with different group velocities cause soliton collisions, which lead to soliton explosions. A soliton experiences relative phase oscillation, chaos, and oscillation, as well as convergence and separation before and after an explosion. With an increase in parameters related to pump power, single-soliton oscillation, multi-wavelength solitons, and chaos are found in experiments and simulations, proving the relevance and reliability between simulation and experimental results. This work promotes the dynamical study of multi-soliton collisions in nonlinear science and the development of chaos theory in multi-comb lasers.

Japanese Politeness: An Enquiry Yasuko Obana (2021) Routledge

•A fractional mapping method based on a generalized fractional auxiliary equation is proposed.•Fractional soliton and periodical wave solutions are constructed by Mittag–Leffler function.•The effect of fractional order is explained.

Evidence has documented the tumor-promoting properties of long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) in many cancers. However, little is known about its role in gallbladder cancer. Here, we aimed to characterize the functional relevance of lncRNA FOXD2-AS1 in gallbladder cancer and the possible mechanisms associated with methylation of MutL homolog-1 (MLH1). Initially, microarray-based gene expression profiling of gallbladder cancer was employed to identify differentially expressed lncRNAs. Next, the expression of lncRNA FOXD2-AS1 was examined, and the cell line presenting with the highest lncRNA FOXD2-AS1 expression was selected for subsequent experimentation. Then, the interaction between lncRNA FOXD2-AS1 and MLH1 was identified. The effect of lncRNA FOXD2-AS1 on proliferation, migration, invasion, and apoptosis as well as tumorigenicity of transfected GBC-SD cells was examined with gain- and loss-of-function experiments. We found that lncRNA FOXD2-AS1 was highly expressed, while MLH1 was poorly expressed in gallbladder cancer cells. Besides, lncRNA FOXD2-AS1 could promote MLH1 methylation by recruiting DNMT1 to the MLH1 promoter, and consequently inhibit MLH1 transcription. Silencing of lncRNA FOXD2-AS1 or overexpression of MLH1 inhibited gallbladder cancer cell proliferation, invasion, and migration, while facilitating cell apoptosis in vitro as well as retarding tumor growth in vivo. Thus, silencing of lncRNA FOXD2-AS1 suppressed the progression of gallbladder cancer via upregulation of MLH1 by inhibiting MLH1 promoter methylation. These findings present lncRNA FOXD2-AS1 knockdown as a potential candidate for the treatment of gallbladder cancer.

In order to verify the feasibility of applying high-JcNb3Sn strand in fusion magnet, a full-size cable-in-conduit conductor (CICC) with short twist pitch (STP) cable pattern was manufactured and tested in SULTAN facility at SPC, Switzerland. Three levels of cyclic electromagnetic (EM) load were applied on the sample stepwise, no visible decrease of current sharing temperature (Tcs)was observed until the EM load increased to 80 kA × 10.8 T, after that the Tcsdecreased dramatically with the EM cycles, which suggested that irreversible deformation, causing a change in the strain state, or even damage has occurred in the superconducting strands. For investigating the reason which caused the conductor performance degradation, the tested conductor was dissected for metallographic observation. Eight segments which subjected to different EM loads were extracted from one of the legs, the geometric feature changes of the cable cross-sections were analyzed and compared. A good correlation was found between the decrease of the Tcsand deformation of the cable cross section. A mass of cracks were found on the sub-elements of strands in the segment which subjected to highest EM load, but the amount of crack is much lower in other segments. Combining the analyses, it is speculated that the critical EM load which causes irreversible degradation is between 850 kN/m and 870 kN/m for this conductor. The results could be a reference in high-JcNb3Sn CICC design.

This paper demonstrates a novel low‐temperature‐poly‐Si thin‐film transistors (LTPS TFTs) gate driver with tunable width for low‐grey level brightness adjustment of active‐matrix organic light‐emitting diode (AMOLED) display. The width of output pulses can be tuned accordingly by changing the number of input pulses, to avoid changing the frequency, duty ratio, or increasing the numbers of the external clock‐lines. The proposed circuit still works well when outputting 10 ms pulse with leakage current above 1.45 nA.

In this paper, pixel circuit design method using low‐temperature poly‐silicon and oxides (LTPO) thin film transistors (TFTs) for active‐matrix organic light‐emitting diode (AMOLED) are derived in detail. Through calculation and SPICE simulation of a typical 7TFT‐1C LTPO pixel circuit, the optimum value for the capacitor is selected as 0.1 pF for accurate VTHcompensation and high resolution above 490 pixels per inch (PPI). Moreover, to reduce the relative current error rate to 3 %, the maximum allowable threshold voltage shift is limited within −0.98 V and 0.44 V for IGZO TFT, and within −0.3 V to 0.31 V for the driving TFT (LTPS). This research provides guidelines for AMOLED display development using LTPO TFTs.

The a‐IGZO TFTs integrated gate driver circuit with inter‐frame memory module and isolated bootstrapping node structure is proposed for AMOLED display. The driver can provide progressive display signal, inter‐frame detection signal and standby detection signal. Compared with conventional ones, the proposed inter‐frame memory shows enhanced driving ability due to the introduce of voltage bootstrapping function. Besides, the proposed gate driver can tolerate larger threshold voltage variations (ΔVth) than the conventional circuit due to the isolated bootstrap node structure.

The sulfuric acid industry produces large volumes of spent catalyst containing vanadium. To develop an efficient method for vanadium recovery, hydrogen peroxide was used to oxidize sulfur in the spent catalyst, forming sulfuric acid, which, in turn, leached the metals from the catalyst. Experimental results showed that the leaching efficiency of vanadium gradually increased with hydrogen peroxide concentration; other parameters had minor effects. The hydrogen peroxide concentration, stirring rate, and pH had negative effects on leaching percent of potassium. Leaching efficiency of iron decreased with an increase in leaching time, stirring rate, and pH; with the increase in hydrogen peroxide concentration and liquid:solid ratio, leaching efficiency of iron first increased and then decreased. The optimum leaching conditions for vanadium were hydrogen peroxide concentration of 148 g/L, leaching time of 5 min, leaching temperature of 25 °C, stirring rate of 300 r/m, and liquid:solid ratio of 3:1, and leaching efficiencies of vanadium, potassium, and iron were 92.2%, 48.2%, and 46.3%, respectively. For potassium and iron, the leaching efficiencies of 70.9% and 70.5% were achieved using pure water leaching under the conditions of leaching time of 30 min, liquid to solid ratio of 4:1, and the temperature of 25 °C.

The bactericidal/permeability increasing protein (BPI) has an important function of nonspecific killing of Gram-negative bacteria. In this study, qPCR was used to detect the expression of the BPIgene in twelve tissues of Meishan piglets from birth to weaning. BPIgene overexpression, bacterial adhesions count and indirect immunofluorescence were applied to analyze the relationship between BPIgene expression and the infectivity of Escherichia coliand Salmonella.The results showed that the BPIgene was expressed highly in duodenum, jejunum and ileum (fold changes of relative expression levels were more than 10 000, 500 and 200, respectively). The expression of the BPIgene at 35 days of age was significantly higher (P<0.01) than that at all other days. Transcription of the BPIgene was up-regulated 2 401-fold in porcine intestinal epithelial (IPEC-J2) cells that were transfected with the BPIgene overexpression lentivirus (IPEC-J2-BPI), and significantly higher (P<0.01) than that in negative control cells (IPEC-J2-NC). Protein expression levels in IPEC-J2-BPI cells were also increased. When IPEC-J2 cells were incubated with E. coliand Salmonella,respectively, for 2, 4, 6, 8, 10 and 12 h, the number of bacterial adhesions in IPEC-J2-BPI cells was significantly less (P<0.05) than that in IPEC-J2-NC cells. The results of indirect immunofluorescence analysis showed that the number of bacterial adhesions in IPEC-J2-BPI cells was significantly less (P<0.01) than that in IPEC-J2-NC cells. These results demonstrated that the BPIgene might play an important role in regulating weaning stress especially intestinal-mediated immune response. Overexpression of the BPIgene at the cellular level could significantly enhance the anti-bactericidal ability against Gram-negative bacteria such as E. coliand Salmonella.This has important biological significance in piglet resistance to bacterial diarrhea.

ABSTRACTHepatocellular carcinoma (HCC) is recognized for its high mortality rate worldwide. Based on intensive studies, long non-coding RNA (lncRNA) expression exerts significant effects on tumor suppression. Herein, we investigated the molecular mechanism of lymphoid enhancer-binding factor-1 antisense RNA 1 (LEF1-AS1) in HCC cells. Microarray-based gene expression analysis was adopted to predict and verify the differentially expressed genes in HCC, which predicted cell division cycle-associated 7 (CDCA7) and LEF1-AS1 to be highly expressed in HCC. The expression of LEF1-AS1, CDCA7, CCAAT/enhancer-binding protein beta (CEBPB) and enhancer of zeste homolog 2 (EZH2) was determined by means of reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. LncMap was used to predict the lncRNA-transcription factor-gene interaction in HCC. ChIP, RIP assay and dual luciferase reporter gene assay were employed to verify the relationship between the transcription factor and gene. Silencing of LEF1-AS1 could downregulate CDCA7 expression through CEBPB. Overexpression of LEF1-AS1, EZH2 and CDCA7 promoted proliferation and invasion in HCC cells. LEF1-AS1 promoted CDCA7 expression to further upregulate EZH2. Tumor formation in nude mice was assessed to verify the experimental results. Silencing of LEF1-AS1 inhibited the growth of tumors in vivo. Collectively, silencing LEF1-AS1 inhibited the proliferation and invasion of HCC cells by down-regulating EZH2 through the CEBPB-CDCA7 signaling pathway, which provides scientific evidence for the treatment of HCC.Abbreviations: HCC: Hepatocellular carcinoma; lncRNA: long non-coding RNA; LEF1-AS1: lymphoid enhancer-binding factor-1 antisense RNA 1; EZH2: enhancer of zeste homolog 2; CDCA7: cell division cycle-associated 7; GEO: Gene Expression Omnibus; NC: negative control; oe: overexpressed; RT-qPCR: reverse transcription quantitative polymerase chain reaction; PBS: phosphate buffered saline; HRP: horseradish peroxidase; OD: optical density; RIP: Radioimmunoprecipitation; ChIP: Chromatin immunoprecipitation; WT: wild type.

Myopia presents a formidable challenge, especially in children, where clinical management involves the use of atropine and 7-methylxanthine, necessitating multiple doses, strong side effects and encountering suboptimal compliance due to children's resistance. In response to these issues, our research proposes a self-generated electricity-driven drug delivery system (EDDDS) designed for precision myopia treatment. The EDDDS intelligently releases therapeutic drugs, such as atropine, at ocular tissues using drug-coated nanogenerators, aiming to effectively slow down the progression of myopia. This system combines nanotechnology and smart drug delivery mechanisms to achieve controlled and responsive drug administration. The nanogenerators embedded in the EDDDS generate electric fields that trigger drug release upon closing eyes conditions, providing targeted treatment. Simultaneously, the weak voltage can effectively relieve the ciliary muscle, offering additional benefits for myopia management. In vitro and in vivo experiments have demonstrated the efficacy and potential of the EDDDS in precisely modulating myopia progression. The proposed EDDDS holds significant promise as an advanced and high-precision therapeutic approach for myopia management. Its potential to address the limitations of current treatments makes it a promising avenue for future research and clinical applications.

IGZO TFT has been widely used in flat‐panel displays and its good electrical characteristics are the key to make high‐performance products. This paper investigated the influence of Top‐Gate effect caused by drain overlap capacitance on the transfer characteristic and output characteristic of IGZO TFT (W/L=15.6um/8um) by experimental measurements and TCAD simulations.

It is demonstrated that novel back‐channel‐etch type oxide TFTs (InGaZnSnOx target material for oxide semiconductor) with below 10% threshold voltage uniformity, better stability and above 10cm2/V·s electron mobility in G4.5 factory. From etch‐stop type to back‐channel‐etch type, ultra‐high definition 15.6 inch notebook display with only 1.2mm left and right border has designed and manufactured for the first time by the way of singleside gate driver in panel.

Background:Hepatocellular carcinoma (HCC) (about 85–90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. Summary:This guideline presents official recommendations of the National Health and Family Planning Commission of the People’s Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. Key Messages:The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

A unique gate driver with novel 1‐to‐N architecture is proposed. It is achieved by sharing the inter‐stage transfer unit between adjacent N stages, resulting in the reduction of TFT number per stage to narrow the border. An embodiment is demonstrated within 5.5” FHD LCDs using ESL oxide TFT technology.

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 robinophilaMurr (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.

The challenge of linking intergenic mutations to target genes has limited molecular understanding of human diseases. Here we show that H3K27ac HiChIP generates high-resolution contact maps of active enhancers and target genes in rare primary human T cell subtypes and coronary artery smooth muscle cells. Differentiation of naive T cells into T helper 17 cells or regulatory T cells creates subtype-specific enhancer–promoter interactions, specifically at regions of shared DNA accessibility. These data provide a principled means of assigning molecular functions to autoimmune and cardiovascular disease risk variants, linking hundreds of noncoding variants to putative gene targets. Target genes identified with HiChIP are further supported by CRISPR interference and activation at linked enhancers, by the presence of expression quantitative trait loci, and by allele-specific enhancer loops in patient-derived primary cells. The majority of disease-associated enhancers contact genes beyond the nearest gene in the linear genome, leading to a fourfold increase in the number of potential target genes for autoimmune and cardiovascular diseases.