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Accurately capturing the changing patterns of ecological quality in the urban agglomeration on the northern slopes of the Tianshan Mountains (UANSTM) and researching its significant impacts responds to the requirements of high-quality sustainable urban development. In this study, the spatial and temporal distribution patterns of remote sensing ecological index (RSEI) were obtained by normalization and PCA transformation of four basic indicators based on Landsat images. It then employed geographic detectors to analyze the factors that influence ecological change. The result demonstrates that: (1) In the distribution of land use conversions and degrees of human disturbance, built-up land, principally urban land, and agricultural land, represented by dry land, are rising, while the shrinkage of grassland is the most substantial. The degree of human disturbance is increasing overall for glaciers. (2) The overall ecological environment of the northern slopes of Tianshan is relatively poor. Temporally, the ecological quality changes and fluctuates, with an overall rising trend. Spatially, ecological quality is low in the north and south and high in the center, with high values concentrated in the mountains and agriculture and low values in the Gobi and desert. However, on a large scale, the ecological quality of the Urumqi–Changji–Shihezi metropolitan area has worsened dramatically compared to other regions. (3) Driving factor detection showed that LST and NDVI were the most critical influencing factors, with an upward trend in the influence of WET. Typically, LST has the biggest influence on RSEI when interacting with NDVI. In terms of the broader region, the influence of social factors is smaller, but the role of human interference in the built-up area of the oasis city can be found to be more significant at large scales. The study shows that it is necessary to strengthen ecological conservation efforts in the UANSTM region, focusing on the impact of urban and agricultural land expansion on surface temperature and vegetation.

In this study, electrodeposition combined with anodization was employed to prepare a nanoporous tin oxide film on a pure copper substrate. It was found that annealing temperature played a critically significant role in regulating the crystallinity, pore size, and contents of different oxidation states of the anodized tin oxide film to affect the electrochemical performance. The study verified that SnO

The morphology and orientation evolution of Cu6Sn5 grains formed on (001)Cu and (011)Cu single crystal substrates under temperature gradient (TG) were investigated. The initial orientated prism-type Cu6Sn5 grains transformed to non-orientated scallop-type after isothermal reflow. However, the Cu6Sn5 grains with strong texture were revealed on cold end single crystal Cu substrates by imposing TG. The Cu6Sn5 grains on (001)Cu grew along their c-axis parallel to the substrate and finally merged into one grain to form a fully IMC joint, while those on (011)Cu presented a strong texture and merged into a few dominant Cu6Sn5 grains showing about 30° angle with the substrate. The merging between neighboring Cu6Sn5 grain pair was attributed to the rapid grain growth and grain boundary migration. Accordingly, a model was put forward to describe the merging process. The different morphology and orientation evolutions of the Cu6Sn5 grains on single crystal and polycrystal Cu substrates were revealed based on crystallographic relationship and Cu flux. The method for controlling the morphology and orientation of Cu6Sn5 grains is really benefitial to solve the reliability problems caused by anisotropy in 3D packaging.

In this study, the anodized iron oxide films with micro-nano structure were prepared by a combination of heat treatment and anodization. The adjustment of these oxide films at the micron-scale was achieved by heat treatment on substrate to modify the position of the cementite and ferrite. The distribution and existing forms of carbon on cementite and ferrite determine the morphology of their respective anodization. It was found annealing at 300 °C can improve the crystallinity of iron oxide and maintain the original micro-nano structure. Although the crystal quality of iron oxide can be further improved with higher annealing temperature, it would result in the collapse of nanoporous structures and the reconstruction of the surface morphology. Furthermore, anodized samples made from those with lamellar ferrite and cementite show better specific capacitance. The iron oxide film on the annealed substrate obtained the highest specific capacitance of 35.3 mF/cm2 at a scan rate of 20 mV/s in our samples.

A novel real-complex hybrid modal response spectrum method (RCHM-RSM) based on the modal superposition of the superstructure is proposed for base-isolated (BI) structures in this paper. In contrast to the traditional analysis method, the method can increase the accuracy of the structural response and avoid complex calculations. Additionally, the direct use of the damping matrix of superstructures for BI structures was found to cause an overestimation of the damping effect and consequently underestimate the deformation of the superstructure. Thus, a new scheme is proposed for determining the damping matrix for BI structures, and general expressions of the damping matrix of the superstructure and the damping constant of the isolation layer are presented. Using the proposed method to construct the damping matrix of BI structures, the equivalent load associated with the coupling damping between the structure and support can be determined when the displacement–velocity input model (D–VIM) is adopted. Analytical expressions of structural matrices are presented for a shear-type model of a BI structure, and a numerical investigation is conducted to demonstrate the feasibility and effectiveness of the proposed methods. The results show that the proposed method (RCHM-RSM) has the advantages of simple calculations and high accuracy. The numerical results obtained also confirm that the direct use of the damping matrix of superstructures for the BI structure will underestimate the superstructure response, while the displacement input model (DIM) overestimates the deformation of the isolation layer and underestimates superstructure responses, the analysis results by using D–VIM are consistent with the acceleration input model (AIM), so the D–VIM should be used instead of the DIM.

In this paper, we introduce the concept of the stability of a sequence of modules over Hecke algebras. We prove that a finitely generated consistent sequence of the representations of Hecke algebras is representation stable.

Aim To explore the immunoregulatory effects of circ_CELF1 in non-small cell lung cancer (NSCLC). Methods The mRNA level of circ_CELF1 in primary tissue samples was analyzed by qRT-PCR. The assays of CCK-8, colony formation, wound healing as well as Transwell were employed for measurement of cancer cell malignant transformation. The murine subcutaneous tumor model was used to assess the tumorigenesis of NSCLC in vivo. The assays of circRNA precipitation, RNA immunoprecipitation, and luciferase reporter were performed to study the relationship between circ_CELF1, miR-491-5p, and EGFR. Results circ_CELF1 is upregulated in primary cancer tissues from patients with NSCLC, and a high level of circ_CELF1, is associated with malignant characteristics and poor outcomes of patients with NSCLC. Enforced expression of circ_CELF1 exacerbated the malignant transformation of NSCLC cells. Mechanistically, through directly interacting with miR-491-5p, circ_CELF1 acted as a miRNA sponge that increased the expression of the miR-491-5p target gene EGFR, eventually promoting the progression of NSCLC and increasing cancer resistance to immunotherapy. Conclusion Our data demonstrate that upregulation of circ_CELF1 elicits both oncogenic and immunoregulatory effects on the development of NSCLC. We believe that circ_CELF1 can act as a potential therapeutic target for the treatment of NSCLC.

Marginal zinc deficiency is more common than severe zinc deficiency, and the effect of marginal zinc deficiency on male reproduction is unknown. This study investigated the effect of marginal zinc deficiency on spermatogenesis and its mechanism. Male ICR mice were fed normal zinc (30 mg/kg) and marginal zinc deficiency (10 mg/kg) diets for 35 days. Zinc-dependent proteins and enzymes were measured as biomarkers of zinc levels in the body. Metallothionein and Cu-Zn SOD levels in the control group were higher than those in the marginal zinc deficiency group. Hematoxylin and eosin staining showed that the marginal zinc deficiency diet caused histopathological changes in the testis and destruction of the sperm head under scanning electron microscopy. Sperm parameters and sex hormone levels were also affected by marginal zinc deficiency. In addition, marginal zinc deficiency led to alter expression level of several important spermatogenesis-related genes in the epididymis and testes. These results indicate that although zinc intake in marginal zinc deficiency is close to the recommended reference value, low zinc intake interferes with the expression of genes related to spermatogenesis and may lead to sperm abnormalities in mice.

Summary Background Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II–IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study. Methods In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18–70 years, had histopathogically confirmed stage II–IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m2 on days 1 and 8 of each cycle plus cisplatin 75 mg/m2 on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov , NCT02448797 . Findings Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6–36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4–not reached) in the icotinib group and 22·1 months (16·8–30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24–0·55]; p Interpretation Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II–IIIA NSCLC after complete tumour resection. Funding Betta Pharmaceuticals Translation For the Chinese translation of the abstract see Supplementary Materials section.

Carburizing is the main damage form of ethylene cracking furnace tubes. In this process, the microstructure of the furnace tube would change and the element diffuses and redistributes. After serving for about 41000h, the radiation section of a plum blossom tube of SC-1 tubular cracking furnace from a petrochemical company was tested and analyzed in this article. Results show that the higher the service temperature, the more serious the carburizing of the furnace tube. In the inner-wall carburized zone of the middle temperature section of the furnace tube with an initial C content of 0.1wt%, the maximum C content reaches 1.83wt% and the number of carbides increases obviously as well as its organizational morphology changes from fine granular to coarse block or chain like and its organizational type changes from single M23C6 to the coexistence of M23C6, M7C3 and MC type carbides. The Cr and C elements in the carburized zone are mainly concentrated in the grain boundary area in the form of carbides. At the same time, the diffusion of alloy elements causes Cr deficiency in the matrix, and the carbide deficiency zone appears in the subsurface of the inner wall.

The competitive growth of Cu3Sn and Cu6Sn5 in the multi-reflow processes induced by temperature, time, and cooling rate was systematically studied in this work. Results indicated that the thickness proportion of Cu3Sn in the IMC layer was highly promoted in the temperature-increased multi-reflow process and slightly increased with a fluctuation in the isothermal multi-reflow process, while obviously decreased in the temperature-decreased multi-reflow process. The proportion of Cu3Sn grew following the increase of reflow temperature, time, and cooling rate and the thickness of Cu3Sn formed at the central of the Cu6Sn5 bottom was higher than that formed at the edge. The results have a significant meaning in understanding and controlling the competitive growth of Cu3Sn and Cu6Sn5 and improving the reliability of solder joints.

Designing means and methods to detect the presence of interfacial bubbles and intermetallic compounds (IMCs) during hot dipping solder coating of Cu ribbon, can help in the production of defect-free PV ribbons. A mechanistic study of Cu 6 Sn 5 IMC grain growth and bubble morphology evolution at the solder-substrate interface is performed with phase field simulation. A machine learning model is utilized to identify the occurrence of bubble(s) and IMC at the material interface of liquid solder and solid Cu. The datasets for the microstructural images consisting of bubble(s), IMC and planar solder/Cu interface are generated using in situ synchrotron radiation (SR) imaging experiment techniques. The integration of in situ SR radiography based non-destructive testing experiments with convolutional neural network model to intelligently detect the interfacial microstructures paves the path for potential industrial application of this technique in the smart manufacturing of defect free and reliable PV ribbon material.

The production of an all-triploid population by mating tetraploid males with diploid females is the best and most fundamental method for the large-scale production of triploid oysters. Obtaining a stable tetraploid population is essential for guaranteed production in industrialized triploid cultivation. C. hongkongensis and C. sikamea are important oyster breeding species in southern China, and have great economic value. However, there are not any published data on inducing tetraploid C. hongkongensis or C. sikamea. Therefore, we investigated tetraploid induction in these two oyster species by inhibiting the PB1 release in diploid fertilized eggs using Cytochalasin B (CB) under 31 °C, 15 ‰ salinity. The results confirmed that the optimal tetraploid induction conditions for C. hongkongensis were a CB concentration of 0.50 mg/L with induction starting at 9.0 min after fertilization, and stopping at 21.0 min after fertilization; the induction efficiency index reached 0.123 under these conditions. The optimal tetraploid induction conditions for C. sikamea were a CB concentration of 0.50 mg/L, with induction starting at 7.5 min after fertilization and stopping at 18 min after fertilization; the induction efficiency index could be as high as 0.281 under these conditions. However, we confirmed that the tetraploid rate decreased with larval growth, and no tetraploids were detected in the juvenile period of either C. hongkongensis or C. sikamea. This may be attributed to the very low survival of the tetraploid larvae induced by this method, especially as most tetraploid larvae died during the first three days. In summary, it is simple to directly induce tetraploid C. hongkongensis and C. sikamea larvae by inhibiting the PB1 release of diploid zygotes, but the low survival rate makes it challenging to obtain viable juvenile tetraploids.

Background To investigate the expression and diagnostic value of seven autoantibodies (P53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE, and CACE) in lung cancer patients. Methods A total of 370 patients were admitted to the Thoracic Surgery of the First Affiliated Hospital of Suzhou University from 2017 to 2019, including 305 patients with lung cancer and 65 patients with benign lesions. The concentrations of the seven autoantibodies were determined by enzyme linked immunosorbent assay (ELISA).The expression levels of each antibody were compared between the two groups, and the levels of each antibody between lung cancer patients with different pathological types were also compared. We aimed to analyze the diagnostic efficiency of single antibody detection combined with seven antibodies, and also to explore whether there were differences among the positive rates of each antibody in sex, age, smoking history, pathological classification, and clinical stages in the lung cancer group. Results The expression levels of seven autoantibodies in the lung cancer group were higher than those in the benign lesion group. In the lung cancer group, the expression levels of the seven autoantibodies did not vary statistically among different pathological types. The area under the curve of combined detection of the seven antibodies reached 0.735, and the Y-index reached 0.35, which was higher than that of single antibody detection. P53 exhibited the highest sensitivity and lowest specificity; meanwhile, PGP9.5, SOX2, GAGE7, GBU4-5, and MAGEA1 exhibited low sensitivity and high specificity. The sensitivity and specificity of the CAGE were approximately 60%, respectively. There was no statistical difference in the positive rate of each antibody in age, smoking history, and clinical stage. The positive rate of MAGEA1 and CAGE was statistically different in sex, and the positive rate of MAGEA1 was statistically different in pathological classification. Conclusions The seven autoantibodies of lung cancer can potentially be used as an auxiliary examination method for the early diagnosis of lung cancer.

The spatial layout of public service facilities (PSFs) markedly influences residents’ quality of life. Based on Baidu map data, spatial information on 27,552 PSFs across eight categories was collected for urban Dalian, China, and analyzed using the nearest neighbor index and nuclear density. Then, PSF accessibility across eight dimensions of residential quarters was calculated based on the cumulative opportunity method, and its impact on housing prices was analyzed. The results revealed the following: (1) The degree of spatial agglomeration for PSFs varied, with that of business facilities being higher than that of other public welfare facilities. The distribution of business facilities was characterized by a dense center and sparse periphery, whereas public welfare facilities were laid out in a relatively balanced “multi-center” distribution across the study area. (2) Significant spatial differences in the number and types of accessible resident facilities were identified. The number of accessible PSFs in the core area of central urban regions was large and the types were relatively complete, whereas the accessible PSFs in the western and northern marginal areas were limited in number, few in type, and lacking across certain categories, such as educational facilities and life services. (3) The spatial distribution of PSF accessibility was unbalanced. The accessibility of various PSFs in the Shahekou District was the highest, followed by that in the Zhongshan, Xigang, and Ganjingzi Districts. (4) The accessibility of educational, sport, and cultural facilities, and the total accessibility and greening rate of residential areas were the most significantly positively correlated with housing prices; however, the number of households in residential areas and the distances between residential areas and large shopping centers were significantly negatively correlated. Our findings will expand the research perspective of PSFs, provide a basis for meeting residents’ needs and a rational allocation of PSFs, and provide references for people’s decisions to buy houses.

Lung cancer is associated with the greatest number of cancer-related deaths worldwide. Lung adenocarcinoma (LUAD) accounts for 85% of all cases of lung cancer. Despite recent advances in treatment, the 5-year survival rate remains less than 15%. Thus, the diagnostic and therapeutic role of LUAD remain to be further studied. The prolyl 3-hydroxylase family member 4 (P3H4) is involved in various cancers, but little is known about its role in LUAD. Our study demonstrated that the P3H4 gene was upregulated in LUAD. Clinically, the expression of P3H4 was positively correlated with an advanced TNM stage and shorter survival. Functionally, P3H4 plays a significant role in the metastasis and proliferation of LUAD both in vitro and in vivo. Mechanistically, P3H4 might interact with EGFR to regulate the metabolic substances. Our study indicated that P3H4 is a critical gene in the malignant progression of LUAD and represents a potential biomarker and therapeutic target.

The Belt and Road Initiative (BRI), which was first put forward by China in late 2013, has made a significant contribution to international economic activities and inevitably reshaped the pattern of carbon dioxide (CO

Objectives: Tumor microenvironment plays an important role in tumor progression. Cancer-associated fibroblasts (CAFs) are the main cell types in the tumor microenvironment. Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer. In this study, we will explore the molecular mechanism of CAFs promoting the effect of esophageal squamous cell carcinoma. Methods: Exosomes secreted by HEEC cells (normal esophageal epithelial cells) and EC109 cells (ESCC cells) were extracted and labeled as EXO-HEEC and EXO-EC109, respectively. Morphology of exosomes was observed by electron microscope. The expression of exosome specific marker protein was detected by Western blot. The expression of miR-29b-3p in exosomes was detected by qRT-PCR. EC109 cell line was constructed to interfere with miR-29b-3p. Tumor cell proliferation was detected by CCK-8 assay and tumor cell invasion was detected by Transwell assay.Results: We demonstrated hypomethylation of the promoter of NAA60 in ESCC-associated fibroblasts, and that overexpression of NAA60 induces the transformation of fibroblasts into cancer-associated fibroblasts. In addition, our results showed that the expression level of NAA60 increased significantly after DNMT3A interference, and miR-29b-3p was most significantly expressed in exosomes and miR-29b-3p had the best binding with DMNT3A. Further experiments confirmed that interference of miR-29b-3p inhibited the progression of ESCC cells through NAA60 hypomethylation after transferring from CAFs to cancer cells. Conclusions: This study showed that CAFs promote ESCC progression through exosomal miR-29b-3p, and suggested that inhibition of CAFs-derived miR-29b-3p maybe an alternative approach for ESCC treatment.

A mathematical model of argon gas flow in a slot plug was developed to investigate the flow parameters of the argon gas at the exit of the slot plug. Gas compressibility and the heat transfer between argon gas and the plug have been considered in the model. The simulated velocity and density of argon gas at the plug exit were different from the calculated results obtained in previous studies. Velocity measurements of the argon gas at the exit verified the simulated results. Another mathematical model of argon gas stirring in a ladle with velocities and densities of the injected argon gas at the plug exit from the simulation and previous studies was established. The results of the model of argon gas stirring showed that the velocity and density of the argon gas at the plug exit affect the simulated results of the velocity of molten steel and the uniformity of the velocity distribution of the molten steel.

Background EC (esophageal cancer) is a common cancer among people in the world. The molecular mechanism of FAM196B (family with sequence similarity 196 member B) in EC is still unclear. This article aimed to clarify the role of FAM196B in EC. Methods The expression of FAM196B in EC tissues was detected using qRT-PCR. The prognosis of FAM196B in EC patients was determined by log-rank kaplan-Meier survival analysis and Cox regression analysis. Furthermore, shRNA was used to knockdown the expression of FAM196B in EC cell lines. MTT, wound healing assays and western blot were used to determine the role of FAM196B in EC cells. Results In our research, we found that the expression of FAM196B was up-regulated in EC tissues. The increased expression of FAM196B was significantly correlated with differentiation, lymph node metastasis, stage, and poor survival. The proliferation and migration of EC cells were inhibited after FAM196B-shRNA transfection in vitro and vivo. The western blot result showed that FAM196B could regulate EMT. Conclusion These results suggested that FAM196B severs as an oncogene and promotes cell proliferation and migration in EC. In addition, FAM196B may be a potential therapeutic target for EC patients.

Nautilus is the sole surviving externally shelled cephalopod from the Palaeozoic. It is unique within cephalopod genealogy and critical to understanding the evolutionary novelties of cephalopods. Here, we present a complete Nautilus pompilius genome as a fundamental genomic reference on cephalopod innovations, such as the pinhole eye and biomineralization. Nautilus shows a compact, minimalist genome with few encoding genes and slow evolutionary rates in both non-coding and coding regions among known cephalopods. Importantly, multiple genomic innovations including gene losses, independent contraction and expansion of specific gene families and their associated regulatory networks likely moulded the evolution of the nautilus pinhole eye. The conserved molluscan biomineralization toolkit and lineage-specific repetitive low-complexity domains are essential to the construction of the nautilus shell. The nautilus genome constitutes a valuable resource for reconstructing the evolutionary scenarios and genomic innovations that shape the extant cephalopods., Nautilus, the sole surviving externally shelled cephalopod from the Palaeozoic, holds an important phylogenetic position to understand the evolution of cephalopods. A complete genome of Nautilus pompilius sheds light on the evolution of the pinhole eye and biomineralization.

With the popularity of neoadjuvant therapy as first-line treatment, especially for advanced squamous cell carcinoma (SCC), the focus has become accurate individualized treatment. Specifically, toxic side effects of traditional platinum-doublet chemotherapy are high, so treatment with pembrolizumab plus platinum-doublet chemotherapy is safer and more effective. Pembrolizumab is a humanized monoclonal IgG4 kappa anti-PD1 antibody. It is devoid of any cytotoxic activity among the drug effect. Pembrolizumab has been tested clinically in a series of KEYNOTE studies and 12 categories of malignancies have been tested to determine their clinical effects. A 64-year-old man with IIIA SCC of the lung without any surgical contraindications in the preoperative period successfully underwent radical resection and had a great prognosis after neoadjuvant treatment. Chest computed tomography (CT) showed that the left upper lung lesion, hilar and mediastinal lymph nodes were obviously smaller than before, meanwhile, obstructive pneumonia was significantly absorbed. No sign of metastasis was detected by head-abdominopelvic CT and bone scan. Although radiation pneumonitis was an adverse event after postoperative adjuvant therapy, symptoms were relieved with low-dose glucocorticoids. In conclusion, traditional chemotherapy with single agents alone has been gradually replaced by pembrolizumab plus platinum-doublet chemotherapy as a first-line therapy now.

PURPOSE ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079 ), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor ( EGFR) mutation-positive resected stage II-IIIA (N1-N2) non–small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results. METHODS From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR-activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data. RESULTS Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% ( P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP ( P = .316) and 5y DFS rates were 22. 6% and 23.2% ( P = .928), respectively. CONCLUSION Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.

The growth mechanism of Cu6Sn5 intermetallic compound (IMC) at Sn/Cu interface reflowed under 250 °C, 275 °C, and 300 °C for a duration of 60 s and undergoing highly pressurized air action (HP), water cooling (WC), air cooling (AC) or furnace cooling (FC) in the aftermath has been outlined. In addition, synchrotron radiation imaging technique has been utilized to in situ observe interfacial Cu6Sn5 grains growth. It has been revealed that the morphologies of Cu6Sn5 grains under HP and AC are both scallop-like, whereas the samples processed with HP and FC bear plane structure and prismatic morphologies. These revelations indicate the secondary growth of Cu6Sn5 grains during the cooling stage as the significant determinant of the final IMC morphology. Thus, continuous growth on the rough surface (M1), spiral dislocation growth (M2), and 2D nucleation and growth (M3), have been proposed to explain the observed morphologies of interfacial Cu6Sn5 grains. M1 has been recognized as the principal mechanism responsible for IMC morphology undergoing water cooling, whereas combination of M1 and M2 decide the morphological feature of interface resulting from air cooling. Finally, all of the three mechanisms (M1, M2 and M3) account for the IMC morphology corresponding to furnace cooling. As all of these three growth mechanisms are affected by the degree of supercooling (ΔT), it is inferred that the ΔT can influence the secondary nucleation of IMC at the cooling stage. With the fact that the homogeneous nucleation occurs at larger ΔT, and the relative favorability for heterogeneous nucleation at smaller ΔT; the growth mechanisms can be mapped with the degree of undercooling. Consequently, the IMC growth mechanisms proposed and their association with ΔT, can be used to obtain an appropriate thickness and morphology of IMC to improve the reliability of solder joints.

Recent studies on the exothermic complex-forming reactions have improved our understanding of complex-forming reactions greatly, however, so far a similar level of study on endothermic ones has been rather limited. In this work, the endothermic complex-forming reaction Si(1D) + H2 → SiH + H and its deuterated isotopic variant are investigated by quantum dynamics (QD) and ring polymer molecular dynamics (RPMD) calculations on a new global ab initio potential energy surface (PES) for the ground electronic state, which is constructed based on 8996 symmetry unique points computed at the icMRCI+Q/aug-cc-pVQZ level. The PES reproduces our ab initio data very well in the dynamically important regions, on which the ro-vibrational energy levels of SiH2 are calculated and general good agreement with experiment is obtained. The integral cross sections and product angular and state distributions are computed in a wide range of collision energies, and interesting dynamics behaviors are revealed. The rate coefficients are also investigated, which display an exponential rise from 2.09 × 10−20 to 6.00 × 10−12 cm3 s−1 for the Si(1D) + H2 reaction as the temperature increases from 300 to 1500 K, in contrast to the nearly temperature-independent behavior of exothermic complex-forming reactions. In addition, the applicability of the RPMD approach is demonstrated, and the kinetic isotope effect is investigated, the ratio of which decreases from 7.89 (300 K) to 1.70 (1500 K). The effects of tunneling and initial rotational excitation are also discussed.

Background: Adenoid cystic carcinoma (ACC) refers to a salivary gland neoplasm. Tracheal adenoid cystic carcinoma that invades the tracheal prominence is a relatively rare tumor among thoracic diseases. Objective: To explore the epidemiology, diagnosis, treatment and future development of tracheal adenoid cystic carcinoma (TACC). Methods: With asymptomatic invasion of the tracheal prominence, a case of tracheal adenoid cystic carcinoma with asymptomatic invasion of the tracheal prominence was reported. The clinical management process and surgical methods were introduced, and related literature was reviewed and summarized. Results: The patient was admitted due to tracheal augmentation mass for half a month. Chest CT at admission displayed the soft tissue density shadow behind the tracheal augmentation process. After the completion of other examinations, tracheal tumor resection and tracheal reconstruction were performed. Postoperative routine pathology exhibited that it was TACC and without inguinal lymph node metastasis. Conclusion: TACC is a low-grade tracheal tumor with low incidence, delayed clinical manifestations and lack of specificity as well. CT and bronchoscopy are helpful for the diagnosis of suspected patients. Meanwhile, radical surgical resection is the first choice of treatment. Adjuvant therapy can improve the therapeutic effect. Targeted immunotherapy is the developing direction of treatment.

Most lung cancer deaths are caused by a distant disseminated disease rather than primary tumors. Understanding the biology behind distant metastasis (DM) is crucial for the effective prediction and reduction of recurrence rates. Genome-wide analysis of the tumor provides a new way to explore the pathogenesis and molecular diagnosis of metastasis in lung adenocarcinoma. In our study, a total of 215 eligible lung adenocarcinoma patients were enrolled. The DNA was extracted from formalin-fixed paraffin-embedded (FFPE) samples from the primary tumors of these patients. Comprehensive molecular profiling was performed using a panel covering the exome of lung cancer-associated driver genes based on targeted next-generation sequencing. Tumor gene alterations were analyzed to investigate the differences in molecular features between lung adenocarcinomas with or without DM. Patients with DM of lung adenocarcinoma had significantly more variations in overall copy number (defined as Copy Number Alteration (CNA) load and Copy Number Instability (CNI) score). Interestingly, the study of the relationship between copy number variation and other molecular features verified that the degree of copy number variation has a positive correlation with mutations of DNA damage repair pathway (DDR). Thus, the additional analysis further revealed that metastatic patients accumulated more mutations in the DDR pathway, suggesting that impaired function of the DDR pathway and copy number variations play important roles in the invasion process of cancer cells. A comprehensive genetic analysis of lung adenocarcinoma revealed significant genomic changes between DM and non-DM patients. This finding may shed new light on the elucidation of lung cancer invasion mechanisms, and provide potential predictors for metastatic lung cancer.

Lung cancer is the leading cause of cancer-related death worldwide and in China (1). According to the statistics of the National Cancer Center of China, there were 733,300 new cases of non-small cell lung cancer (NSCLC) and approximately 610,200 related deaths in 2015 (2). For patients with early staged disease, surgery is the mainstay of treatment, and it is commonly followed by adjuvant chemotherapy for patients with locally advanced resectable NSCLC. Although complete surgical resection may be curative for NSCLC, 25–70% of patients (with different proportion according to stage) eventually relapse despite complete resection (3). Platinum-based adjuvant chemotherapy has been shown to marginally increase the 5-year survival rate of patients by 4–8% (4-6). Even after treatment with surgery and indicated adjuvant therapies in eligible cases, approximately 20–30% of stage I, 50% of stage II, and 60% of stage IIIA patients still die within 5 years (7). In the past decade, experts have conducted a number of investigations on the perioperative management of resectable NSCLC; however, progress remains slow, and patients still have a high risk of recurrence and death. Neoadjuvant therapy is defined as any therapy delivered prior to definitive local therapy intended to increase the cure rate. It provides several theoretical benefits in managing such patients with NSCLC. In the setting of, neoadjuvant therapy given prior to radical surgery this approach can also have the goals of downstaging, improving the resection rate, and more promptly treating subclinical micro-metastases than adjuvant approaches, delivered after the definitive local therapy. In addition, the compliance with neoadjuvant therapy has been shown to be better than in the adjuvant setting, and the biological effect of the neoadjuvant therapy can be analyzed directly in the resected tumor specimens (8). A meta-analysis on patients with stage IB‒IIIA NSCLC that compared chemotherapy plus subsequent surgery vs. surgery alone showed that the 5-year survival rate was 5% higher after receiving neoadjuvant chemotherapy (NCT) (9). Therefore, the comprehensive NSCLC data suggest that, for resectable NSCLC, NCT improves survival compared with surgery alone but appear to show no significant survival benefit compared with adjuvant chemotherapy (10). In the last 5 years, immune checkpoint inhibitors (ICIs) have profoundly changed the treatment paradigm for patients with advanced NSCLC (11-15). Immunotherapy has provided hope for long-term survival benefits to a minority of patients with metastatic lung cancer. For treatment-naive patients with driver mutation-negative NSCLC, the 5-year survival rate of single agent pembrolizumab was 23.2%; for the previously treated patients with driver mutation-negative NSCLC, the 5-year survival rates of single agent pembrolizumab and nivolumab were 15.5% and 16%, respectively (16,17). Given the profound impact made by immunotherapy drugs for patients with advanced disease, significant attention has been directed in recent years toward investigating the potential role for early-stage NSCLC patients, and whether they, too, can achieve long-term benefits from the inclusion of immunotherapy into their treatment algorithms. Many phase Ib/II clinical trials have reported promising results, and a series of large-scale phase III clinical trials are underway. However, these various investigations have employed different strategies of neoadjuvant immunotherapy, in terms of the specific regimens as well as number of treatment cycles (18). To better guide Chinese thoracic surgeons in the neoadjuvant immunotherapy of NSCLC, well-known thoracic surgeons in China participated in an in-depth discussion on the hot topics and controversial issues of neoadjuvant immunotherapy and formed the Expert consensus on neoadjuvant immunotherapy for non-small-cell lung cancer by incorporating the latest evidence on neoadjuvant immunotherapy.

BACKGROUND: Esophageal cancer (EC) with a high incidence of malnutrition is a highly malignant digestive tract tumor. We investigated the effect of enteral nutrition (EN) support combined with enhanced recovery after surgery (ERAS) on the nutritional status, immune function, and prognosis of patients with EC after Ivor-Lewis operation. METHODS: One hundred patients were randomly divided into the observation group (n=42) and the control group (n=58). The patients in observation group were treated with EN combined with ERAS intervention after Ivor-Lewis operation, and the patients in control group were treated with conventional postoperative EN intervention. The situation of operation, nutritional status, immune function recovery and prognosis between the two groups were compared. RESULTS: There was no statistically significant difference in operation time or intraoperative blood loss between the two groups (P>0.05). The chest tube removal time and oral feeding time of the observation group after operation were shorter than those of the control group (P0.05); however those indexes were significantly decreased in the control group after the intervention (P0.05). CONCLUSIONS: EN combined with ERAS was more beneficial to the improvement of nutritional status and immune function recovery of patients with EC after Ivor-Lewis operation. It also shortened the length of hospital stay.

Objectives Health-related quality of life (HRQoL) data complement conventional clinical endpoints when comparing adjuvant gefitinib with chemotherapy in patients with early-stage non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. This study aimed to assess changes in HRQoL with adjuvant gefitinib vs chemotherapy in this patient group. Materials and methods In the phase III ADJUVANT trial, patients with completely resected, stage II–IIIA (N1–N2), EGFR-mutant NSCLC were randomized (1:1) to receive either gefitinib for 24 months or vinorelbine plus cisplatin (VP) every 3 weeks for four cycles. HRQoL was assessed as a secondary endpoint using the Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L), Lung Cancer Symptom Scale (LCSS) questionnaires, and Trial Outcome Index (TOI) composite score. HRQoL dynamics, improvements, and time to deterioration were compared between groups. Results At baseline, 104 of 106, and 80 of 87 patients receiving gefitinib and VP, respectively, completed two questionnaires (FACT-L and LCSS). Baseline scores were balanced between groups. Although HRQoL fluctuated and gradually improved in both groups, longitudinally higher scores were reported with gefitinib than VP (FACT-L, odds ratio 418.16, 95 % confidence interval [CI] 2.75–63509.05, p = 0.019; LCSS, 1.13, 1.04–1.22, p = 0.003; TOI, 88.39, 4.40–1775.05, p = 0.003). Time to deterioration in HRQoL was delayed with gefitinib compared with VP (FACT-L, median 69 vs 6 weeks, hazard ratio 0.62, 95 % CI 0.42–0.90, p = 0.013; LCSS, median 45 vs 6 weeks, 0.63, 0.43–0.93, p = 0.020; TOI, median 164 vs 9 weeks, 0.51, 0.33–0.77, p = 0.001). Conclusion Adjuvant gefitinib is associated with improved HRQoL over VP, supporting its use in patients with stage II–IIIA (N1–N2), EGFR-mutant NSCLC.

Background Gonad development and differentiation is an essential function for all sexually reproducing species, and many aspects of these developmental processes are highly conserved among the metazoa. However, the mechanisms underlying gonad development and gametogenesis remain unclear in Tridacna squamosa, a large-size bivalve of great ecological value. They are protandrous simultaneous hermaphrodites, with the male gonad maturing first, eventually followed by the female gonads. In this study, nine gonad libraries representing resting, male and hermaphrodite stages in T. squamosa were performed to identify the molecular mechanisms. Results Sixteen thousand four hundred ninety-one unigenes were annotated in the NCBI non-redundant protein database. Among the annotated unigenes, 5091 and 7328 unigenes were assigned to Gene Ontology categories and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway database, respectively. A total of 4763 differentially expressed genes (DEGs) were identified by comparing male to resting gonads, consisting of 3499 which were comparatively upregulated in males and 1264 which were downregulated in males. Six hundred-ninteen DEGs between male and hermaphroditic gonads were identified, with 518 DEGs more strongly expressed in hermaphrodites and 101 more strongly expressed in males. GO (Gene Ontology) and KEGG pathway analyses revealed that various biological functions and processes, including functions related to the endocrine system, oocyte meiosis, carbon metabolism, and the cell cycle, were involved in regulating gonadal development and gametogenesis in T. squamosa. Testis-specific serine/threonine kinases 1 (TSSK1), TSSK4, TSSK5, Doublesex- and mab-3-related transcription factor 1 (DMRT1), SOX, Sperm surface protein 17 (SP17) and other genes were involved in male gonadal development in Tridacna squamosal. Both spermatogenesis- (TSSK4, spermatogenesis-associated protein 17, spermatogenesis-associated protein 8, sperm motility kinase X, SP17) and oogenesis-related genes (zona pellucida protein, Forkhead Box L2, Vitellogenin, Vitellogenin receptor, 5-hydroxytryptamine, 5-hydroxytryptamine receptor) were simultaneously highly expressed in the hermaphroditic gonad to maintain the hermaphroditism of T. squamosa. Conclusion All these results from our study will facilitate better understanding of the molecular mechanisms underlying giant clam gonad development and gametogenesis, which can provided a base on obtaining excellent gametes during the seed production process for giant clams.