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Lung cancer has a high incidence and mortality worldwide. Among them, non-small cell lung cancer (NSCLC) accounts for the majority. In terms of treatment, targeted therapy is a more effective option for NSCLC patients with genetic mutations when compared with chemotherapy. Currently, there are a number of targeted drugs targeting different mutations in NSCLC on the market, among which, icotinib (Conmona®) is an oral small molecule epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). It’s approved as first-line treatment for locally advanced or metastatic NSCLC patients with EGFR-mutant, for monotherapy to treat locally advanced or metastatic non-small cell lung cancer (NSCLC) after the failure of at least one prior chemotherapy regimen (primarily platinum-based combination chemotherapy) and approved as postoperative adjuvent therapy for stage Ⅱ-ⅢA NSCLC with EGFR-mutant in China. What’s more, there are many other usages and further clinical trials are underway. Here, we review the status and progress of icotinib in the treatment of EGFR-mutant NSCLC.

Flavonoids are the main medicinal ingredients in Camellia nitidissima, but the regulatory mechanism of flavonoid biosynthesis in flowers is unclear; therefore, the flavonoids in C. nitidissima have not been effectively used. The present study performed full-length transcriptome sequencing of C. nitidissima flower. Furthermore, the reported RNA-sequencing data of C. nitidissima petals were reanalyzed using the full-length transcriptome as a reference, and the regulatory mechanism of flavonoid synthesis in petals was elucidated. The analysis identified 43,350 isoforms annotated in non-redundant protein (Nr), Kyoto Encyclopedia of Genes and Genomes (KEGG), EuKaryotic Orthologous Groups (KOG), and Swiss-Prot databases, among which 34,602 aligned to Camellia sinensis genes. A total of 11,857 differentially expressed genes (DEGs), including 112 related to flavonoid synthesis, were identified by pairwise comparison. Subsequently, analysis of the phylogeny and the conserved motifs of R2R3-MYB using the proteins sequences identified three R2R3-MYB transcription factors that regulated flavonoid biosynthesis. Weighted gene co-expression network analysis (WGCNA) identified phenylalanine ammonia-lyase (PAL) and 4-coumarate: CoA ligase(4CL) as the hub genes and showed that bHLH79 interacted with PAL. Finally, validated the expression of seven DEGs involved in flavonoid biosynthesis using real-time quantitative PCR (qRT-PCR). Thus, the present study generated and used the full-length transcriptome as the reference to analyze the transcriptome of petals and proposed a possible regulatory mechanism of flavonoid synthesis in C. nitidissima. The study's findings unravel the genetic mechanisms underlying flavonoid synthesis and suggest candidate genes for the genetic improvement of C. nitidissima.

Flexible conductive structures are essential for the fabrication of commercial integrated electronic devices. Developing efficient processes for manufacturing these structures with high conductivity and stability is significant. Based on a modifiable cost-effective Cu-based ionic liquid precursor, here we present an in situ laser patterning technique to manufacture flexible electrodes. The fabricated Cu structure has excellent conductivity, approximately comparable to bulk Cu, while its oxidation resistance could be further enhanced through introducing an additional carbon source to form a Cu@C microstructure. The chemical and electrical stabilities are evaluated. This method provides a possible bottom-up route for manufacturing microelectronic devices in one step, as we demonstrated through a flexible heater.

Efficient manufacturing of composite structure is one of the key challenges in the fabrication of flexible devices. Laser direct writing provides a solution due to its area selectivity, controllability and rapid processing. In this study, one-step patterning of Cu/CuxO structure with tunable composition on flexible substrate has been realized with laser direct writing on Cu precursor film. An integrated humidity sensor that combines a CuxO-rich porous sensing structure with a conductive Cu-rich structure has been fabricated. The one-step-written device showed high sensitivity to human breathing. This work highlights the promise of this one-step mask-less laser writing as an efficient, rapid and low-cost composite structure fabrication process for flexible devices.

Highlights An up-bottom laser erasing process utilizing electrochemical corrosion has been integrated into the bottom-up writing process.The presented erased laser writing technology exhibits excellent reproducibility for sustainable manufacturing of flexible highly conductive Cu structure.The suitability of the writing-erasing-rewriting process for repairing failure patterns and reconfiguring circuits has been demonstrated. Supplementary Information The online version contains supplementary material available at 10.1007/s40820-021-00714-3., Integrating construction and reconstruction of highly conductive structures into one process is of great interest in developing and manufacturing of electronics, but it is quite challenging because these two involve contradictive additive and subtractive processes. In this work, we report an all-laser mask-less processing technology that integrates manufacturing, modifying, and restoring of highly conductive Cu structures. By traveling a focused laser, the Cu patterns can be fabricated on the flexible substrate, while these as-written patterns can be selectively erased by changing the laser to a defocused state. Subsequently, the fresh patterns with identical conductivity and stability can be rewritten by repeating the writing step. Further, this erasing–rewriting process is also capable of repairing failure patterns, such as oxidation and cracking. Owing to the high controllability of this writing–erasing–rewriting process and its excellent reproducibility for conductive structures, it opens a new avenue for rapid healing and prototyping of electronics. Supplementary Information The online version contains supplementary material available at 10.1007/s40820-021-00714-3.

For the first time, defect-free butt welds of titanium alloy/steel were successfully fabricated via friction stir welding. Joints were produced by employing rotation speed varied at 600 and 950 rpm with a constant travel speed of 47.5 mm/min. An increasing of rotation speed leads to thicken the intermetallic compound layer, coarsen the grain size and thus decrease the joint microhardness. Thanks to the solid-state joining process, only a thin FeTi layer was formed at the interface even rotation speed increased to 950 rpm. As a result, all obtained joints fractured at the base steel material. The work carried out clearly shows the good weldability of titanium alloy to steel via friction stir welding.

Camellia nitidissima Chi is an ornamental plant of the genus Camellia L. Its flowers contain a lot of flavonoids and polyphenols. Flavonoid 3'-hydroxylase (F3'H) plays an important role in the synthesis of flavonoids, polyphenols and anthocyanins. We cloned CnF3'H from the petal of C. nitidissima (GenBank code: HQ290518.1). The full length of CnF3'H was 1859 bp, with an open reading frame of 1577 bp, and encoded 518 amino acid. A phylogenetic tree analysis showed that CnF3'H was closely related to Camellia sinensis L. and C. sinensis cultivar Zhonghuang. CnF3'H was expressed in flowers, leaves, fruits, sepals, petals and stamens of C. nitidissima, and during the flowering process the expression level in flower decreased initially and then increased. CnF3'H expression was significantly positive correlated with polyphenol contents in C. nitidissima. A CnF3'H-EGFP expression vector was constructed to do the subcellular localization, we found that CnF3'H was obviously localized in the nuclear envelope and cytomembrane. In transgenic tobacco flowers, the total polyphenol content and various polyphenol constituents were significantly increased with high CnF3'H expression level, while total flavonoid contents and some flavonol constituents were increased slightly. These findings suggest that CnF3'H can promote the synthesis of polyphenols better than flavonoids.

Camellia nitidissima Chi. is an ornamental plant of the genus Camellia L. Its flowers contain a lot of flavonoids and polyphenols. Flavonoid 3′-hydroxylase (F3′H) plays an important role in the synthesis of flavonoids, polyphenols and anthocyanins. We used PCR amplification, quantitative PCR, High-performance liquid chromatography, subcellular localization, and agrobacterium-mediated leaf disk method to study the the function of CnF3′H. The full length of CnF3′H was 1859 bp (GenBank code: HQ290518.1), with an open reading frame of 1577 bp, and encoded 518 amino acid. A phylogenetic tree analysis showed that CnF3′H was closely related to Camellia sinensis L. and C. sinensis cultivar Zhonghuang. CnF3′H was expressed in flowers, leaves, fruits, sepals, petals and stamens of C. nitidissima, and during the flowering process the expression level in flower decreased initially and then increased. CnF3′H expression was significantly positive correlated with polyphenol contents in C. nitidissima. A CnF3′H-EGFP expression vector was constructed to do the subcellular localization, we found that CnF3′H was obviously localized in the nuclear envelope and cytomembrane. In transgenic tobacco flowers, the total polyphenol content and various polyphenol constituents were significantly increased with high CnF3′H expression level, while total flavonoid contents and some flavonol constituents were increased slightly. These findings suggest that CnF3′H promotes the synthesis of polyphenols better than flavonoids.

Plant secondary metabolism is complex in its diverse chemical composition and dynamic regulation of biosynthesis. How the functional diversification of enzymes contributes to the diversity is largely unknown. In the flavonoids pathway, dihydroflavonol 4-reductase (DFR) is a key enzyme mediating dihydroflavanol into anthocyanins biosynthesis. Here, the DFR homolog was identified from Camellia nitidissima Chi. (CnDFR) which is a unique species of the genus Camellia with golden yellow petals. Sequence analysis showed that CnDFR possessed not only conserved catalytic domains, but also some amino acids peculiar to Camellia species. Gene expression analysis revealed that CnDFR was expressed in all tissues and the expression of CnDFR was positively correlated with polyphenols but negatively with yellow coloration. The subcellular localization of CnDFR by the tobacco infiltration assay showed a likely dual localization in the nucleus and cell membrane. Furthermore, overexpression transgenic lines were generated in tobacco to understand the molecular function of CnDFR. The analyses of metabolites suggested that ectopic expression of CnDFR enhanced the biosynthesis of polyphenols, while no accumulation of anthocyanins was detected. These results indicate a functional diversification of the reductase activities in Camellia plants and provide molecular insights into the regulation of floral color.

This paper proposes a new gesture recognition system based on Deep Neural Network (DNN) and Leap Motion. The palm model is reconstructed to obtain the feature data, and then the feature data of all experimenters are obtained by the Leap Motion controller. The data are finally put into the DNN model for training to implement the recognition of specific hand gesture after being normalized. By testing with 30000 gesture frames of five volunteers, it is found that the recognition accuracy of the proposed scheme can reach 98%, which indicates that the scheme can complete the specific gesture recognition with a high average recognition rate.

Joining of Mo to Ta is important in manufacturing of high temperature microwave device. However, it is difficult to weld these two refractory metals directly because of their limited weldability. This study presents a laser joining method of Mo and Ta using Ti6Al4V or Ni as filler metal to prevent the mixture of two base metals in molten pool. The bulk of the Mo and Ta remained solid and joined by the liquid filler metal since the melting point of filler metal is considerably lower than that of base metals, resulting in two interfaces formed in each joint. The tensile strength of the Mo/Ni/Ta joint fractured from Ni/Ta interface is 19% lower than that of Mo/Ti6Al4V/Ta joint broken at base metal of Ta due to the formation of IMCs. These results offer a reference to filler metals selection for the joining of Mo to Ta, and highlight a possible method when dissimilar joining of two hard-to-weld metals especially refractory metals.

This paper proposes an approach that utilizes an ellipsoid as the envelope of the intersection of multi-ellipsoids, which is applied to the system's interval estimation. To precisely obtain the estimation result of system state, the Minkowski sum of two ellipsoids, the outer envelope of ellipsoids' intersection, and the simulation of the outer envelope of ellipsoids' intersection are illustrated. Then the method of ellipsoid's intersection is applied to realize the interval estimation of system state. Finally, compare the method of Minkowski sum and intersection with method of Zonotopic Kalman Filter. The simulation reveals the estimation precision of the proposed method is not that good as ZKF method and it needs further optimization.

Dissimilar joining of tantalum (Ta) to molybdenum (Mo) is of great interest in high temperature structural component applications. However, few reports were found about joining of these two hard-to-weld metals. The objective of this experimental study was to assess the weldability of laser butt joining of 0.2 mm-thick Ta and Mo. In order to study cracking mechanism in Ta/Mo joint, similar Ta/Ta and Mo/Mo joints were compared under the same welding conditions. An optical microscope observation revealed presence of intergranular cracks in the Mo/Mo joint, while both transgranular and intergranular cracks were observed in Ta/Mo joint. The cracking mechanism of the Ta/Mo joint was investigated further by micro-hardness testing, micro X-ray diffraction and scanning electron microscopy. The results showed that solidification cracking tendency of Mo is a main reason for crack initiation in the Ta/Mo joint. Low ductility feature in fusion zone most certainly played a role in the transgranular propagation of cracking.

The dissimilar joining of shape memory alloys to Ti alloys is critically important in many industrial applications. However, joining these two alloys is a considerable challenge due to the formation of brittle intermetallics. In this paper, the dissimilar laser welding of 200-μm-thick NiTiNb and Ti6Al4V alloys was successfully achieved by the addition of a niobium filler wire with a diameter of 300 μm. The morphology, microstructure, phase composition and mechanical behavior of the obtained joints were studied by optical microscopy, scanning electron microscopy, transmission electron microscopy, micro X-ray diffraction, and tensile testing. Variations in the laser power changed the degree of Nb dilution in the weld metal, which affected the amount of intermetallic compounds (IMCs), NiTi, and Ti2Ni formed. All the welds consisted of a dendritic (Nb, Ti) solid solution and varied IMCs. The tensile strength of the joints depended on the amount of IMCs, which decreased with increasing Nb addition. All the tensile specimens fractured along the continuous IMC region in the weld. The highest tensile strength of the joint reached 82% that of the weaker base metal, Ti6Al4V, when the niobium filler was melted completely.

In this paper, we design a novel controller based on modular bus software and hardware architecture. The proposed controller uses the FPGA as the hardware carrier, and integrates the external expansion type Avalon bus with the discrete IP module structure to realize the all-digital, efficient and reliable fast closed-loop regulation power control. Based on the requirements of the original related functions, the digital controller greatly reduces the FPGA resource consumption and improves the efficiency of hardware resources. Meanwhile, it provides a powerful experimental data reference for the modular design of the digital power controller. Moreover, the designed controller is successfully applied on Cooler Storage Ring of the Heavy Ion Research Facility in Lanzhou (HIRFL-CSR) six-pole magnet power supply.

The criminisi algorithm is a useful image inpainting approach, but it cost high computational complexity. In order to reduce the computational complexity of image inpainting, an improved Criminisi algorithm is proposed in this paper based on biogeography optimization (BBO). According to the characteristic of Criminisi, the new method uses the migration and mutation of BBO to search the best matching block and overcome the shortcomings of the Criminisi algorithm by searching the best matching block in the unbroken regions in the image. Experimental results show that this algorithm reduces the computational complexity significantly for Criminisi algorithm with maintaining still the good performance.

Friction stir spot welding (FSSW) of Al to Ti alloys has broad applications in the aerospace and automobile industries, while its narrow joining area limits the improvement of mechanical properties of the joint. In the current study, an Al-coating was prepared on Ti6Al4V alloy by hot-dipping prior to joining, then a Zn interlayer was used during friction stir joining of as-coated Ti alloy to the 2014-Al alloy in a lap configuration to introduce a brazing zone out of the stir zone to increase the joining area. The microstructure of the joint was investigated, and the joint strength was compared with the traditional FSSW joint to confirm the advantages of this new process. Because of the increase of the joining area, the maximum fracture load of such joint is 110% higher than that of the traditional FSSW joint under the same welding parameters. The fracture load of these joints depends on the joining width, including the width of solid-state bonding region in stir zone and brazing region out of stir zone.

The recast layer is an undesirable surface residue after the electric discharge machining of materials, which would affect the following brazing process and cause microstructure and property degradation. In this study, the effects of the recast layer composed of carbon-containing γ solid solution on the microstructure and mechanical properties of Ni-based single crystal superalloy were investigated. After brazing, the formation of carbo-borides, borides, and Kirkendall voids near the joint interface could be eliminated via the aging process to recovery the microstructure and property.

CuO nanoplates are fabricated and formulated into a nano ink to print Pt/CuO/Pt memory device. Laser sintering is used to create interconnections between CuO nanoplates and reduces CuO to Cu2O to promote the formation of the conductive filaments. The ratio of the resistance at high and low resistance state increases 10 - 100 times after laser sintering. Moreover, controllable multilevel resistance has been proved in this device. This ink-printing assisted with laser sintering process enables to rapid, low-cost, and large-scale fabricating of memory devices with controllable properties.

Adding Ni as filler material is one of the effective methods to restrain the cracks in laser-welded joints of NiTi/stainless steel (SS), while the formation of Ni3Ti at the NiTi/Ni interface result in uneven distribution of the microstructure of the joint, which limits tensile strength of the joint. In this study, post-weld heat treatment (PWHT) at 650 °C and 850 °C were applied on a defect-free NiTi/Ni/SS joint to improve its mechanical properties. As the PWHT temperature increases, more Ni3Ti was observed at the weld metal. This precipitation strengthened the weld metal, resulting in the average hardness of the weld metal increased from 375 HV0.2 to 493 HV0.2. Owing to the homogenization of microstructure of joints after PWHT, the tensile strength of the joint improved. The highest joint average strength reached 643 MPa at 850 °C PWHT, which is about 2.12 times higher than that of the as-welded joint.

The flavonoids metabolic pathway plays central roles in floral coloration, in which anthocyanins and flavonols are derived from common precursors, dihydroflavonols. Flavonol synthase (FLS) catalyses dihydroflavonols into flavonols, which presents a key branch of anthocyanins biosynthesis. The yellow flower of Camellia nitidissima Chi. is a unique feature within the genus Camellia, which makes it a precious resource for breeding yellow camellia varieties. In this work, we characterized the secondary metabolites of pigments during floral development of C. nitidissima and revealed that accumulation of flavonols correlates with floral coloration. We first isolated CnFLS1 and showed that it is a FLS of C. nitidissima by gene family analysis. Second, expression analysis during floral development and different floral organs indicated that the expression level of CnFLS1 was regulated by developmental cues, which was in agreement with the accumulating pattern of flavonols. Furthermore, over-expression of CnFLS1 in Nicotiana tabacum altered floral colour into white or light yellow, and metabolic analysis showed significant increasing of flavonols and reducing of anthocyanins in transgenic plants. Our work suggested CnFLS1 plays critical roles in yellow colour pigmentation and is potentially a key point of genetic engineering toward colour modification in Camellia.

Mo (VI)-imprinted chitosan (CTS)/triethanolamine (TEA) gel beads (Mo (VI)-ICTGBs) (ICTGBs = imprinted chitosan triethanolamine gel beads) were prepared by using ion-imprinted technology, in which TEA and molybdate solution were used in coagulation bath. The spectrum of FT-IR implies that bonding are formed between TEA and the primary hydroxyl of CTS, and ion gel reaction happen between CTS and molybdate; XRD patterns also prove the change among CTS, TEA and molybdate. SEM images and N2 adsorption show that the surface area increases obviously after eluting Mo (VI) ions. The adsorption isotherm of Mo (VI)-ICTGBs imply that the adsorption process is according with Freundlich model. Adsorption kinetics suggests that the pseudo-second order adsorption mechanism is predominant for this adsorbent system of Mo (VI)-ICTGBs. The Mo (VI)-ICTGBs show high adsorption capacity and good selectivity for Mo (VI) anions in the coexistence system at pH = 6.0. The Mo (VI)-ICTGBs have a good application prospect, because it is with a simple and rapid technique and good durance.

Construction of small town plays an important role in the progress of the urbanization in China. And better planning of small town is very important on promoting economic development and the construction of spiritual civilization of town and city. The current planning situations of 16 small towns which had powerful economy in Shandong province were investigated by surveying weather and natural environment factors, the economy and population status and land arrangement, measuring land area and taking relative photos. The results were as follows. Firstly, small town usually had small population density and land area. A dop tendency of economic degree was demonstrated from east to west. Besides, there were wide differences of natural conditions in these towns. Secondly, most land arrangements were unreasonable, the land proportions were imbalance. Generally there was a lack of completed transportation land and green space.

Camellia changii Ye, a rare and endangered species, has a phenotype that sepals frequently transform into petals. We assumed that this change would cause single C. changii Ye turned double flowers and this was confirmed by the double flowers we found in grafted C. changii Ye. The microstructure of floral organs showed that: in perfect petals, the anthocyanin is distributed in the upper and lower epidermis; in petaloid sepals, anthocyaninin had both sepal and petal identities and sepals gradually transformed into petals; in spot-petaloid sepals, anthocyaninin is only distributed in upper epidermis. B-function gene GLOBOSA1 (GLO1) and GLOBOSA2 (GLO2) had high expression at the part with petal identity and had low or no expression at or near the part with sepal identity and these kinds of expression showed that gene played an important role in determining petal identity. B-function gene DEFICIENS (DEF) and TOMATO MADS BOX GENE6 (TM6) had high expression at the fused part of the stamens and this implied the importance of gene when stamen is transformed into petal. Thus, B-function gene is very important when C. changii Ye evolved into double flowers. Key words: Petaloid phenotype, double flowers, B-function gene, Camellia changii Ye, real-time polymerase chain reaction (PCR).