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Recently, double network (DN) gels with dynamic non‐covalent interaction such as hydrogen bonds has drawn much attention as an innovative material having both high water content and high mechanical strength. Research efforts have identified DN gels as a promising class of materials due to their unique network architecture. These gels comprise two interpenetrating networks formed by different types of polymer. Herein, we report a tough DN hydrogel with high mechanical strength and high swelling ability. The DN gel is synthesized via a two‐step network formation. The first network gel was synthesized via frontal polymerization. Then, the first gel is immersed in an aqueous solution of a second monomer and carrying out a second polymerization in the presence of first network. The spectroscopic analysis and thermal behavior with differential scanning calorimeter measurements corroborated the existence of hydrogen bonds. The mechanical test and microscopic morphology were further explored to explain the strength and high imbibing characteristics. We expect that this facile strategy may explore a dynamic and tunable hydrogel to expand its potential applications in biomedical field.

Drug repositioning is a strategy of repurposing approved drugs for treating new indications, which can accelerate the drug discovery process, reduce development costs, and lower the safety risk. The advancement of biotechnology has significantly accelerated the speed and scale of biological data generation, offering significant potential for drug repositioning through biomedical knowledge graphs that integrate diverse entities and relations from various biomedical sources. To fully learn the semantic information and topological structure information from the biological knowledge graph, we propose a knowledge graph convolutional network with a heuristic search, named KGCNH, which can effectively utilize the diversity of entities and relationships in biological knowledge graphs, as well as topological structure information, to predict the associations between drugs and diseases. Specifically, we design a relation-aware attention mechanism to compute the attention scores for each neighboring entity of a given entity under different relations. To address the challenge of randomness of the initial attention scores potentially impacting model performance and to expand the search scope of the model, we designed a heuristic search module based on Gumbel-Softmax, which uses attention scores as heuristic information and introduces randomness to assist the model in exploring more optimal embeddings of drugs and diseases. Following this module, we derive the relation weights, obtain the embeddings of drugs and diseases through neighborhood aggregation, and then predict drug–disease associations. Additionally, we employ feature-based augmented views to enhance model robustness and mitigate overfitting issues. We have implemented our method and conducted experiments on two data sets. The results demonstrate that KGCNH outperforms competing methods. In particular, case studies on lithium and quetiapine confirm that KGCNH can retrieve more actual drug–disease associations in the top prediction results.

The metasurface analogue of electromagnetically induced transparency (EIT) provides a chip-scale platform for achieving light delay and storage, high Qfactors, and greatly enhanced optical fields. However, the literature relies on the coupling between localized and localized or localized and collective resonances, limiting the Qfactor and related performance. Here, we report a novel approach for realizing collective EIT-like bands with a measured Qfactor reaching 2750 in silicon metasurfaces in the near-infrared regime, exceeding the state of the art by more than 5 times. It employs the coupling between two collective resonances, the Mie electric dipole surface lattice resonance (SLR) and the out-of-plane/in-plane electric quadrupole SLR (EQ-SLR). Remarkably, the collective EIT-like resonance can have diverging Qfactor and group delay due to the bound state in the continuum characteristics of the in-plane EQ-SLR. With these findings, our study opens a new route for tailoring light flow in metasurfaces.

SCH23390 is a widely used D1dopamine receptor (D1R) antagonist that also elicits some D1R-independent effects. We previously found that the benzazepine, SKF83959, an analog of SCH23390, produces positive allosteric modulation of the Sigma-1 receptor (Sig1R). SCH23390 does not bind to the orthodoxic site of Sig1R but enhances the binding of 3H (+)-pentazocine to Sig1R. In this study, we investigated whether SCH23390 functions as an allosteric modulator of Sig1R. We detected increased Sig1R dissociation from binding immunoglobulin protein (BiP) and translocation of Sig1R to the plasma membrane in response to SCH23390 in transfected HEK293T and SH-SY5Y cells, respectively. Activation of Sig1R by SCH23390 was further confirmed by inhibition of GSK3β activity in a time- and dose-dependent manner; this effect was blocked by pretreatment with the Sig1R antagonist, BD1047, and by knockdown of Sig1R. SCH23390 also inhibited GSK3β in wild-type mice but not in Sig1R knockout mice. Finally, we showed that SCH23390 allosterically modulated the effect of the Sig1R agonist SKF10047 on inhibition of GSK3β. This positive allosteric effect of SCH23390 was further confirmed via promotion of neuronal protection afforded by SKF10047 in primary cortical neurons challenged with MPP+. These results provide the first evidence that SCH23390 elicits functional allosteric modulation of Sig1R. Our findings not only reveal novel pharmacological effects of SCH23390 but also indicate a potential mechanism for SCH23390-mediated D1R-independent effects. Therefore, attention should be paid to these Sig1R-mediated effects when explaining pharmacological responses to SCH23390.

In this work, using the multiple threshold voltages (multi- ${V}_{\text {Ths}}{)}$ coupling technology introduces an innovative approach to leverage AlGaN/GaN-based high-electron-mobility transistor (AlGaN/GaN HEMT) for high linearity millimeter-wave (mm-W) applications. As a result of optimizing the etching depth of the recessed trench ( ${H}_{R}$ ), the fabricated composite HEMT demonstrated a remarkably flat transconductance ( ${G}_{m}$ ) plateau, and well-maintained profile of small-signal characteristics as a function of gate voltage. As a consequence, at a biased drain voltage of 10 V and a frequency of 30 GHz, the composite HEMT achieved the highest ratio of output third-order intercept point (OIP3) to DC power consumption ( ${P}_{\text {DC}}{)}$ , denoted as (OIP3/ ${P}_{\text {DC}}{)}$ , measuring ~ 9.3 dB. Simultaneously optimizing the bias conditions, the devices showcased a remarkable combination of high one-tone saturated output power density reaching 6.5 W/mm and two-tone OIP3/ ${P}_{\text {DC}}$ of ~ 6.1 dB, achieved at a biased drain voltage of 25 V. The experimental results provide compelling evidence of the attractiveness of the multi- ${V}_{\text {Ths}}$ coupling technique for millimeter wave RF transmitters.

ABSTRACTObjectiveTo explore the correlation between hyoid bone (HB) positions and facial growth patterns (facial patterns) in Chinese adults; to identify any significant difference in HB position among subjects with different facial patterns in various dental ages.MethodsLateral cephalometric radiographs of 197 Chinese subjects were divided into nine groups based on their dental ages and facial patterns. Seven measurements were used to define HB position. Regression, correlation analyses, and one-way ANOVA were carried out.ResultsSignificant correlations were found between facial patterns and anteroposterior HB positions. The HB was more anterior in the horizontal group after mixed dentition and further away from the mandibular plane in the vertical group of adults. Vertical HB positions were insignificantly different in any stage.ConclusionHB position and facial patterns were correlated. There were significantly different HB positions among people with different facial patterns in various dental ages.

Graphical Abstract: In the current work, different contents of Sr were added to the Al-6.5Si-20Cu-1.5Ni filler metal to improve the microstructure and brazing properties of filler metals which were used to braze 6063 aluminum alloy. When the addition of Sr was 0.08 wt.%, the brittle phases primary Si and Al-Si in the filler metal were refined completely and the shear strength of brazed joint achieved the greatest.

The yield of wheat in wheat–rice rotation cropping systems in the Yangtze River Plain, China, is adversely impacted by waterlogging. A raised bed planting (RBP) pattern may reduce waterlogging and increase the wheat yield after rice cultivation by improving the grain number per spike. However, the physiological basis for grain formation under RBP conditions remains poorly understood. The present study was performed over two growing seasons (2018/2019 and 2019/2020) to examine the effects of the planting pattern (i.e., RBP and flat planting (FP)) on the floret and grain formation features and leaf photosynthetic source characteristics of wheat. The results indicated that implementation of the RBP pattern improved the soil–plant nitrogen (N) supply during floret development, which facilitated balanced floret development, resulting in a 9.5% increase in the number of fertile florets per spike. Moreover, the RBP pattern delayed wheat leaf senescence and increased the photosynthetic source capacity by 13.9%, which produced more assimilates for grain filling. Delayed leaf senescence was attributed to the resultant high leaf N content and enhanced antioxidant metabolism. Correspondingly, under RBP conditions, 7.6–8.6% more grains per spike were recorded, and the grain yield was ultimately enhanced by 10.4–12.7%. These results demonstrate that the improvement of the spike differentiation process and the enhancement of the leaf photosynthetic capacity were the main reasons for the increased grain number per spike of wheat under the RBP pattern, and additional improvements in this technique should be achievable through further investigation.

Carbapenems and colistin are vital antimicrobials used to treat Enterobacteriaceae-caused infections. The present study aimed to characterize the coexistence mechanism of carbapenem and colistin resistance in an Escherichia coliisolated from retail chicken meat. A total of 4 E. coliisolates co-harboring carbapenem resistance gene blaNDM(2 E. coliisolates with blaNDM-5 and2 with blaNDM-9) and colistin resistance gene mcr-1. Antimicrobial susceptibility testing exhibited that all the 4 E. colistrains had multidrug resistance profile and consistent with the resistance genes they carried. MLST showed that 3 E. coliisolates belonged to a pathogenic E. colilineage ST354, which is closely associated with human infections and pose a serious threat to public health. Whole genome sequencing (WGS) showed that 4 mcr-1-positive plasmids with sizes of 60.4 kb to 67.4 kb all belonged to the IncI2 type. A total of 5 blaNDM-harboring plasmids ranged from 99.0 kb to 138.3 kb, among which 4 plasmids belonged to unknow type and only pCS5L-NDM belonged to IncFIA/IncFIB group of hybrid plasmids, a novel carrier for blaNDM. Comparative analysis exhibited that the mcr-1or blaNDM-carrying plasmids of E. colistrains from chicken meat showed high identity with that from Enterobacteriaceaeof human origin, which indicated the risk of mcr-1or blaNDMdissemination from retail meat to human. The simultaneous occurrence of mcr-1and blaNDMin E. coliemphasizes the significant of antimicrobial resistance surveillance in retail meat.

We propose and experimentally demonstrate a novel strategy to achieve dual-band symmetry-protected bound states in the continuum (BICs) in silicon metasurfaces. This strategy is based on the hybridization of Mie surface lattice resonances (SLRs) in periodic silicon bipartite nanodisk arrays, of which the central nanodisk displaced from the center of the unit cell. We show that dual-band electric quadrupole and magnetic dipole BICs can be supported in such a system, and transfer to quasi-BICs with ultrahigh measured quality factors up to 1240 at the Γ point. Taking advantage of the SLR characteristics, we show that the spectral separation and the quality factors of these two quasi-BICs can be conveniently tuned by varying the nanodisk diameter or the lattice period. Making use of these dual-band quasi-BICs, we numerically obtain bulk sensitivities above 480 nm/RIU and high figures of merit up to 1200. We also show that when the central nanodisk is not displaced but has different diameter, the silicon bipartite nanodisk array supports an electric dipole BIC that was referred to as subradiant SLR in the literature. Our work provides a new approach for realizing and tuning dual-band BICs, and the obtained ultrahigh-Qquasi-BICs can find potential applications in nonlinear optics, multimodal lasing, and optical sensing.

Combinatorial cancer therapies based on nanomedicine have emerged as a promising strategy to achieve potentiated treatment efficiency. Herein, cisplatin (CDDP) prodrug (Pt-CD) and a mitochondria-targeted near-infrared (NIR) photosensitizer IR780 were combined to construct a multifunctional nanomedicine IR780@Pt NPs through a supramolecular self-assembly strategy. Targeted mitochondrial dysfunction of cancer cells was sufficiently induced under NIR laser irradiation through both photothermal and photodynamic effects, inhibiting the overactive mitochondrial energy pathways of cancer cells. The mitochondrial dysfunction significantly attenuated the crosstalk between mitochondria and nucleus viathe cellular ATP energy chain, leading to obvious down-regulation of the key proteins of the nucleotide excision repair (NER) pathway. Thereby, the chemotherapeutic effect of CDDP could be significantly potentiated because of reduced DNA lesion repair capacity by ERCC1-XPF nuclease system. Moreover, IR780@Pt NPs exhibited excellent NIR fluorescence and photoacoustic (PA) imaging capacity for in vivoimaging-guided NIR laser treatment. Ultimately, the IR780@Pt NPs mediated combinatorial chemophototherapy achieved potentiated anticancer efficacy against cancer cells in vitroand tumor inhibition performance in vivo. Overall, this study highlighted the significance of nanomedicine mediated targeted induction of mitochondrial dysfunction to potentiate chemotherapy for efficient combinatorial cancer therapy.

Macroscopic self-assembly has increasingly attracted numerous concerns because of the facile fabrication of complex structures and diversified morphologies. Key challenges still remain to design high-performance building blocks to increase the efficiency and diversity of macroscopic self-assembly. Here, we designed triple noncovalent interactions (carboxyl-Zn2+coordination, host–guest interactions, and hydrogen bonding interactions) to enhance the interactions between self-healing fibers, constructing multidimensional nonwoven fiber-based fabrics through macroscopic self-assembly without further postprocessing. Profiled from the strong interactions generated from triple noncovalent interactions, ordered two-dimensional plane and three-dimensional spiral gel fabrics were fabricated using polyvinyl pyrrolidone/gel-based fibers as building blocks toward a human motion sensor. Moreover, we demonstrated that the macroscopic self-assembly strategy is universal to construct three-dimensional film-based fabrics toward wound dressing based on the triple noncovalent interactions between two-dimensional films. This macroscopic self-assembly approach provides an alternative strategy to fabricate gel fabrics for various applications.

The accurate identification of tissue origin in patients with metastatic cancer is critical for effective treatment selection but remains a challenge. The aim of this study is to develop a gene expression assay for tumor molecular classification and integrate it with clinicopathologic evaluations to identify the tissue origin for cancer of uncertain primary (CUP). A 90-gene expression signature, covering 21 tumor types, was identified and validated with an overall accuracy of 89.8% (95% CI, 0.87–0.92) in 609 tumor samples. More specifically, the classification accuracy reached 90.4% (95% CI, 0.87–0.93) for 323 primary tumors and 89.2% (95% CI, 0.85–0.92) for 286 metastatic tumors, with no statistically significant difference (P = 0.71). Furthermore, in a real-life cohort of 141 CUP patients, predictions by the 90-gene expression signature were consistent or compatible with the clinicopathologic features in 71.6% of patients (101/141). Findings suggest that this novel gene expression assay could efficiently predict the primary origin for a broad spectrum of tumor types and support its diagnostic utility of molecular classification in difficult-to-diagnose metastatic cancer. Additional studies are ongoing to further evaluate the clinical utility of this novel gene expression assay in predicting primary site and directing therapy for CUP patients.

Regulated upon activation, normal T-cell expressed, and secreted (RANTES) is a chemokine actively involved in the initiation and progression of atherosclerosis (AS), which is the major cause of ischemic cerebrovascular disease (ICVD). This study aimed to determine the associations between circulating RANTES level and overall AS conditions of cardiac and cerebral vessel beds in patients with ICVD.

The theory of heat conduction paths has been widely recognized and widely studied in the research about the thermal conductivity of thermal conductive polymer composites at present. Encapsulating polymer pellets with thermally conductive fillers and processing them into thermally conductive polymer composites is a simple and effective method for constructing heat conduction paths. It is meaningful to investigate the related heat conduction mechanism of this method. Otherwise, this approach can significantly preserve the performance of the polymer substrate, making it highly valuable for practical material applications. In this work, polyethylene-octene elastomer (POE) pellets were encapsulated with thermal conductive fillers by physical absorption. Subsequently, the composite films containing heat conduction paths were fabricated using the encapsulated POE pellets through a heating press. Alumina (Al2O3), boron nitride (BN), and alumina/boron nitride hybrid (Al2O3/BN) fillers were used to prepare Al2O3@POE, BN@POE, and BN/Al2O3@POE composite films to investigate the influence of filler shapes on heat conduction path construction. The influence of the constitute and density of heat conduction paths on the thermal conductivity of composite films was analyzed by infrared thermal imaging, finite element analysis, and thermal resistance theory in detail. Owing to the reserved good adhesion and flexibility of the POE substrate, the composite films could be directly used as thermal interface materials for chip cooling, which presented a good heat dissipation effect. Furthermore, a series of integrated composite materials were prepared by the combination of encapsulated pellets with various functional films (copper foil, aluminum foil, and graphite sheet) through a one-pot heating press, exhibiting a good electromagnetic shielding effect. The performance of the composites and the corresponding preparation method demonstrate the strong significance of this research for practical applications.

In the original publication the display of Fig. 1 is incorrect. The correct figure is available in this correction.

Clinical treatment of multidrug resistant (MDR) pathogens‐induced infection is emerging as a growing challenge in global public health due to the limited selection of clinically available antibiotics. Nanozymes as artificial enzymes that mimicked natural enzyme‐like activities, are received great attention for combating MDR pathogens. However, the relatively deficient catalytic activity in the infectious microenvironment and inability to precisely targeting pathogen restrains their clinical anti‐MDR applications. Here, pathogen‐targeting bimetallic BiPt nanozymes for nanocatalytic therapy against MDR pathogen are reported. Benefiting from electronic coordination effect, BiPt nanozymes exhibit dual‐enzymatic activities, including peroxidase‐mimic and oxidase‐mimic activities. Moreover, the catalytic efficiency can be efficiently increased 300‐fold by ultrasound under inflammatory microenvironment. Notably, BiPt nanozyme is further cloaked with a platelet‐bacteria hybrid membrane (BiPt@HMVs), thus presenting excellent homing effect to infectious sites and precise homologous targeting to pathogen. By integrating accurate targeting with highly efficient catalytic, BiPt@HMVs can eliminate carbapenem‐resistant Enterobacteralesand methicillin‐resistant Staphylococcus aureusin osteomyelitis rats model, muscle‐infected mice model, and pneumonia mice model. The work provides an alternative strategy based on nanozymes for clinically addressing MDR bacteria‐induced infections. The biomimetic BiPt nanozymes can precisely deliver to the infectious sites and adherent to pathogen, then exhibit improved peroxidase‐mimic activity and oxidase‐mimic activity by ultrasound irradiation, finally addressing multidrug resistant bacteria infection.

A polyoxometalate-templated silver(I) thiolate nanocluster has been synthesized by a one-pot reaction in high yield. This novel and stable nanocluster exhibits a core–shell structure with a Ag67S36shell and two lacunary Keggin [PW9O34]9–cores, which is fully characterized by X-ray crystallography, X-ray photoelectron spectroscopy, UV–vis, powder X-ray diffraction, and cyclic voltammetry.

Supplemental Digital Content is available in the text.Human epidermal growth factor receptor 2 (HER2) dysregulation is associated with tumorigenesis in gastric/gastroesophageal junction cancer; however, the number of patients with HER2-positive disease is unclear, possibly due to differing scoring criteria/assays. Data are also lacking for early disease. We aimed to assess the HER2-positivity rate using approved testing criteria in a large, real-life multinational population. HER2-positivity was defined as an immunohistochemistry staining score of 3+, or immunohistochemistry 2+ and HER2amplification detected by in situ hybridization. A total of 4949 patients were enrolled and results showed that 14.2% of 4920 samples with immunohistochemistry results were HER2-positive. HER2-positivity was significantly higher in males (16.1% vs. 9.6% in females), in gastroesophageal versus stomach tumors (22.1% vs. 12.9%), in biopsy versus surgical samples (18.3% vs. 13.0%), in intestinal tumor subtypes versus diffuse (21.5% vs. 4.8%) and mixed types (21.5% vs. 8.5%) (P<0.001), in mixed versus diffuse types (8.5% vs. 4.8%), and in “other” versus diffuse types (11.7% vs. 4.8%; P=0.002). There were no significant differences between stages. Patients in the youngest age percentile had significantly lower HER2-positivity rates than patients in the remaining percentiles (9.2% vs. 15.9%, 15.7%, and 15.1%; P<0.001). HER2-positivity was highest in France (20.2%) and lowest in Hong Kong (10.4%). In conclusion, HER-EAGLE, the first study of its kind to be conducted in a large, multinational population of almost 5000 patients, gives valuable insights into the real-world HER2-positivity rate in a gastric/gastroesophageal junction cancer patient population not selected for disease stage or histology.

Layered α-MoO3is a multifunctional material that has significant application in optoelectronic devices. In this study, we show the growth of large-scale, large-size, few-layered (FL) α-MoO3nanosheet directly on technical substrates (SiO2and Si) by physical vapor deposition. We suggest that the growth is self-limiting in the [010] direction because of the re-evaporation and high diffusion capacity of MoOxspecies at high temperature. As-prepared FL α-MoO3is nonconductive and shows poor response to photoillumination with wavelength of 405 and 630 nm. Its work function is strongly altered by the substrate. Improvement of conductivity and photoresponse is observed after the FL device is annealed in vacuum. Line defects along the [001], [100], and [101] directions belonging to the generation of Osand Oavacancy states appear, and the interfacial effect is suppressed. Scanning near-field optical microscope shows that the defects are absorption sites. Kelvin probe force microscope reveals decrease of apparent work function under illumination, which confirms that electrons are excited from defects states. Our findings show that intense studies on defect engineering are required to push forward the application of two-dimensional metal oxides.

Heat dissipation has become a central issue for the development of the microelectronic industry. Thermal interface materials (TIMs) have been widely applied to electron component cooling, which is used to bond the heat spreader and the chip together. Most research on TIMs has only dealt with thermal conductivity enhancement. However, the mechanical properties and adhesion of TIMs are indispensable for practical applications, as well as postcleaning to remove TIMs. A graphene nanosheet/polyolefin elastomer (GNP/POE) film was designed and prepared by a facile method, in which the heat conduction paths were efficiently constructed, and the good mechanical properties of POE were reserved. The thermal conductivity of as-prepared GNP/POE film can reach 1.07 W m–1K–1at an extremely low filler loading of 0.62 wt %. Furthermore, the tensile strength, elongation at break, and adhesion of the prepared GNP/POE film are as good as those of commercial TIM productions. The prepared GNP/POE film can be used as TIMs for chip cooling and exhibits a good heat dissipation effect. Additionally, the prepared GNP/POE film can be peeled off from the chip without residue, after the chip has finished running, which is significant for practical production. This work provides valuable information and insight into the design and fabrication of TIMs in the future.

Ovarian carcinoma is the leading cause of death from gynecologic malignancies. The oncogenic role of anaplastic lymphoma kinase (ALK) is well characterized in many hematopoietic and solid tumors. ALK expression in ovarian carcinoma has been reported but the exact status of ALK protein and its association with clinicopathologic features requires further investigation. ALK expression was determined by immunohistochemistry in 110 primary ovarian carcinomas, including 85 cases of serous carcinoma and 25 cases of mucinous carcinoma. Fluorescence in situ hybridization (FISH) and real-time reverse transcription polymerase chain reaction (RT-PCR) were used for evaluating ALKtranslocation in ALK-positive ovarian carcinomas. Among 110 ovarian carcinomas, 23 (20.9%) cases were ALK positive by immunohistochemistry. All ALK-positive cases were ovarian high-grade serous carcinoma. ALK expression was detected in 23/85 (27.1%) ovarian serous carcinoma and 0/25 (0%) in ovarian mucinous carcinoma. None of the 23 ALK IHC-positive cases harbored ALKgene translocations by FISH or RT-PCR. ALK protein expression was associated with patient age, tumor stage, and histologic type. Specifically, the probability of ALK protein expression was significantly higher in high-grade serous carcinomas in older patients (above 50 y) with advanced disease (FIGO stage III and IV) compared with the low-grade serous and mucinous carcinomas in younger patients with relatively early disease. In conclusion, aberrant ALK expression is observed in ovarian serous carcinoma but not in mucinous carcinoma, is independent of gene translocation, and might be associated with progression and prognosis.

Carcinoma of unknown primary, wherein metastatic disease is present without an identifiable primary site, accounts for ~3–5% of all cancer diagnoses. Despite the development of multiple diagnostic workups, the success rate of primary site identification remains low. Determining the origin of tumor tissue is, thus, an important clinical application of molecular diagnostics. Previous studies have paved the way for gene expression-based tumor type classification. In this study, we have established a comprehensive database integrating microarray- and sequencing-based gene expression profiles of 16 674 tumor samples covering 22 common human tumor types. From this pan-cancer transcriptome database, we identified a 154-gene expression signature that discriminated the origin of tumor tissue with an overall leave-one-out cross-validation accuracy of 96.5%. The 154-gene expression signature was first validated on an independent test set consisting of 9626 primary tumors, of which 97.1% of cases were correctly classified. Furthermore, we tested the signature on a spectrum of diagnostically challenging tumors. An overall accuracy of 92% was achieved on the 1248 tumor specimens that were poorly differentiated, undifferentiated or from metastatic tumors. Thus, we have identified a 154-gene expression signature that can accurately classify a broad spectrum of tumor types. This gene panel may hold a promise to be a useful additional tool for the determination of the tumor origin.

Carcinoma of unknown primary, wherein metastatic disease is present without an identifiable primary site, accounts for ~3–5% of all cancer diagnoses. Despite the development of multiple diagnostic workups, the success rate of primary site identification remains low. Determining the origin of tumor tissue is, thus, an important clinical application of molecular diagnostics. Previous studies have paved the way for gene expression-based tumor type classification. In this study, we have established a comprehensive database integrating microarray- and sequencing-based gene expression profiles of 16 674 tumor samples covering 22 common human tumor types. From this pan-cancer transcriptome database, we identified a 154-gene expression signature that discriminated the origin of tumor tissue with an overall leave-one-out cross-validation accuracy of 96.5%. The 154-gene expression signature was first validated on an independent test set consisting of 9626 primary tumors, of which 97.1% of cases were correctly classified. Furthermore, we tested the signature on a spectrum of diagnostically challenging tumors. An overall accuracy of 92% was achieved on the 1248 tumor specimens that were poorly differentiated, undifferentiated or from metastatic tumors. Thus, we have identified a 154-gene expression signature that can accurately classify a broad spectrum of tumor types. This gene panel may hold a promise to be a useful additional tool for the determination of the tumor origin.

This study discusses high-carbon characteristics, the unsustainability of China's development, and the fact that China needs to transform its development mode. China's low-carbon transition must include industry structure adjustment, energy saving and efficiency increases, energy structure improvement, carbon sink development, adaptation capability, and low-carbon pilot schemes.

ABSTRACTBacitracins are mixtures of structurally related cyclic polypeptides with antibiotic properties. They act by interfering with the biosynthesis of the bacterial cell wall. In this study, we analyzed an avian necrotic enteritis strain of Clostridium perfringensthat was resistant to bacitracin and produced NetB toxin. We identified a bacitracin resistance locus that resembled a bacitracin resistance determinant from Enterococcus faecalis. It contained the structural genes bcrABDand a putative regulatory gene, bcrR. Mutagenesis studies provided evidence that both bcrAand bcrBare essential for bacitracin resistance, and that evidence was supported by the results of experiments in which the introduction of both the bcrAand bcrBgenes into a bacitracin-susceptible C. perfringensstrain was required to confer bacitracin resistance. The wild-type strain was shown to contain at least three large, putatively conjugative plasmids, and the bcrRABDlocus was localized to an 89.7-kb plasmid, pJIR4150. This plasmid was experimentally shown to be conjugative and was sequenced. The sequence revealed that it also carries a tpeLtoxin gene and is related to the pCW3 family of conjugative antibiotic resistance and toxin plasmids from C. perfringens. The bcrgenes were located on a genetic element, ICECp1, which is related to the Tn916family of integrative conjugative elements (ICEs). ICECp1appears to be the first Tn916-like element shown to confer bacitracin resistance. In summary, we identified in a toxin-producing C. perfringensstrain a novel mobile bacitracin resistance element which was experimentally shown to be essential for bacitracin resistance and is carried by a putative ICE located on a conjugative plasmid.

The BiOBr crystals doped with N and/or S have been prepared by a facile and rapid solvothermal method using urea and/or thiourea as doped resource. The morphologies and structures of the as-prepared samples were characterized by SEM, TEM, XRD, XPS and PL spectrum. Their electronic structures have been investigated and discussed using first principles based on the density functional theory. The photocatalytic properties of the products can be adjusted by the content and species of dopants.

Recent large-scale transcriptome analyses have revealed that the human genome contains more than just protein-coding genes. Indeed, a large number of transcripts, including long non-coding RNAs (lncRNAs), lack protein-coding capacity, and increasing evidence suggests that lncRNAs could have a critical role in the regulation of diverse cellular processes, such as stem cell pluripotency, development, cell growth and apoptosis, and cancer invasion and/or metastasis. Furthermore, the aberrant expression of several lncRNAs is closely linked to cancer invasion and/or metastasis. Although the underlying molecular mechanisms by which lncRNAs regulate cancer invasion and/or metastasis are not clearly understood, recent studies have revealed that aberrant lncRNAs expression affects the progression of cancer. In this review, we highlight recent findings regarding the roles of lncRNAs in cancer invasion and/or metastasis.

Recent large-scale transcriptome analyses have revealed that the human genome contains more than just protein-coding genes. Indeed, a large number of transcripts, including long non-coding RNAs (lncRNAs), lack protein-coding capacity, and increasing evidence suggests that lncRNAs could have a critical role in the regulation of diverse cellular processes, such as stem cell pluripotency, development, cell growth and apoptosis, and cancer invasion and/or metastasis. Furthermore, the aberrant expression of several lncRNAs is closely linked to cancer invasion and/or metastasis. Although the underlying molecular mechanisms by which lncRNAs regulate cancer invasion and/or metastasis are not clearly understood, recent studies have revealed that aberrant lncRNAs expression affects the progression of cancer. In this review, we highlight recent findings regarding the roles of lncRNAs in cancer invasion and/or metastasis.

MicroRNAs (miRNAs) that exert function by posttranscriptional suppression have recently brought insight in our understanding of the role of non-protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer (CRC) and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues (NCTs), and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitroand metastasis in vivo.Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phenocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potential tumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.

Long non-coding RNAs (lncRNAs) are a class of newly identified non-coding RNA molecules that are emerging as key regulators of tumor initiation and development. Colorectal cancer (CRC) remains a major health problem worldwide, and there remains a need to further refine the current screening approaches as well as provide tailored diagnostic and therapeutic approaches. Multiple dysregulated lncRNAs participate in tumorigenesis through a variety of molecular mechanisms, and various regulatory factors frequently contribute to the aberrant expression of lncRNAs in CRC, thereby allowing malignant transformation. Additionally, the association of dysregulated lncRNAs with specific developmental stages and clinical outcomes indicates their potential as strong diagnostic and prognostic predictors as well as therapeutic targets. Here we provide a brief overview of the known functions of CRC-associated lncRNAs, describe some potential molecular mechanisms that underlie changes in lncRNA expression in CRC, and attempt to uncover their clinical and therapeutic potential.

Long non-coding RNAs (lncRNAs) are a class of newly identified non-coding RNA molecules that are emerging as key regulators of tumor initiation and development. Colorectal cancer (CRC) remains a major health problem worldwide, and there remains a need to further refine the current screening approaches as well as provide tailored diagnostic and therapeutic approaches. Multiple dysregulated lncRNAs participate in tumorigenesis through a variety of molecular mechanisms, and various regulatory factors frequently contribute to the aberrant expression of lncRNAs in CRC, thereby allowing malignant transformation. Additionally, the association of dysregulated lncRNAs with specific developmental stages and clinical outcomes indicates their potential as strong diagnostic and prognostic predictors as well as therapeutic targets. Here we provide a brief overview of the known functions of CRC-associated lncRNAs, describe some potential molecular mechanisms that underlie changes in lncRNA expression in CRC, and attempt to uncover their clinical and therapeutic potential.

In essence, international climate negotiation is a serious and responsible global effort, despite various conflicts, to establish a rational international climate regime. In essence, tackling climate changes is leading the globe to actualize sustainable development of all humankind along the low-carbon, green, and cyclic-development path. Thus, climate negotiation should be driving all parties to achieve a global climate regime arrangement in a constructive way. Therefore, this paper suggests focusing on the following three major recommendations: early developed countries take the lead in committing positively to absolute emission reduction; the developing countries contribute according to their abilities and stages of development; the developed countries perform real deeds using their funds and technology. Based on substantial breakthrough that would be made, progressive supplement and improvement could be accomplished through the mechanism of review and adjustment under the Convention framework. This path represents a combination of bottom-up and top-down. The ultimate way out of international climate negotiation lies in win-win cooperation. Profound reasons for China to participate proactively and practically in international climate negotiation, based on its actual conditions, are the internal wants and needs of its scientific and sustainable development, as well as the undertaking of international responsibilities as a responsible, large, developing country.

In this paper, we compare the estimation performances of 7 different kernels (i.e., Uniform, Triangular, Epanechnikov, Biweight, Triweight, Cosine and Gaussian) when using them to conduct the probability density estimation with Parzen window method. We firstly analyze the efficiencies of these 7 kernels and then compare their estimation errors measured by mean squared error (MSE). The theoretical analysis and the experimental comparisons show that the mostly-used Gaussian kernel is not the best choice for the probability density estimation, of which the efficiency is low and estimation error is high. The derived conclusions give some guidelines for the selection of kernel in the practical application of probability density estimation.

Activation and infiltration of T cells and macrophages are key features of renal tubulointerstitial injury. The costimulatory molecule V-set and immunoglobulin domain-containing protein-4 (VSIG4), which is exclusively expressed on macrophages, is capable of inhibiting the T cell response. However, it is unclear whether VSIG4 is involved in renal tubulointerstitial injury. This study was designed to investigate the role of VSIG4 in renal tubulointerstitial injury and the related T cell infiltration. The unilateral ureteric obstruction (UUO) model of renal inflammation and tubulointerstitial fibrosis was established in VSIG4 transgenic knock-out C57BL/6 mice (VSIG4-/-) and wild-type C57BL/6 mice (VSIG4+/+). Comparative analysis of renal biological indices were assessed by quantitative real-time PCR and immunofluorescence staining. Both the VSIG4-/-and VSIG4+/+mice showed UUO-related temporal changes in renal expression of CD3, CD4 and CD8 T cell markers, with the protein levels being significantly lower in the VSIG4+/+UUO mice. Moreover, at each time point examined the UUO VSIG4+/+mice showed significantly lower renal mRNA levels of the cytokines interleukin (IL)-2, interferon- and tumor necrosis factor-, but significantly higher IL-10, than the UUO VSIG4-/-mice. The macrophage-expressed VSIG4 may act to alleviate renal tubulointerstitial injury via inhibition of T cell infiltration and secretion of inflammation related factors.

This article introduces, in low voltage circuit breaker on the switch instantaneous performance detecting station, in order to adapt to the requirement of modern high-speed automated production test, the main factors affecting the detection speed - switch measurement point method is studied, the improvement, the existing method of "contact switch" to replace "non-contact switch method, through theoretical derivation and experimental proof, proved that the new method is feasible and economical.

The conventional view of gene regulation in biology has centered around protein-coding genes via the central dogma of DNAmRNAprotein. The discovery of thousands of long non-coding RNAs (lncRNAs) has certainly changed our view of the complexity of mammalian genomes and transcriptomes, as well as many other aspects of biology including transcriptional and posttranscriptional regulation of gene expression. Accumulating reports of misregulated lncRNA expression across numerous cancer types suggest that aberrant lncRNA expression may be a major contributor to tumorigenesis. Here, we summarize recent data about the biological characteristics of lncRNAs in cancer pathways. These include examples with a wide range of molecular mechanisms involved in gene regulation. We also consider the medical implications, and discuss how lncRNAs can be used for cancer diagnosis and prognosis, and serve as potential therapeutic targets. As more examples of regulation by lncRNA are uncovered, one might predict that the large transcripts will eventually rival small RNAs and proteins in their versatility as regulators of genetic information.

The conventional view of gene regulation in biology has centered around protein-coding genes via the central dogma of DNA→mRNA→protein. The discovery of thousands of long non-coding RNAs (lncRNAs) has certainly changed our view of the complexity of mammalian genomes and transcriptomes, as well as many other aspects of biology including transcriptional and posttranscriptional regulation of gene expression. Accumulating reports of misregulated lncRNA expression across numerous cancer types suggest that aberrant lncRNA expression may be a major contributor to tumorigenesis. Here, we summarize recent data about the biological characteristics of lncRNAs in cancer pathways. These include examples with a wide range of molecular mechanisms involved in gene regulation. We also consider the medical implications, and discuss how lncRNAs can be used for cancer diagnosis and prognosis, and serve as potential therapeutic targets. As more examples of regulation by lncRNA are uncovered, one might predict that the large transcripts will eventually rival small RNAs and proteins in their versatility as regulators of genetic information.

In this paper, the real-time defects inspection was implemented via use of paralleled structure and high-speed operation of FPGA. The hardware circuit based on FPGA was established. According to signal characteristics of polymeric film defects, the preprocessing scheme of defect images based on FPGA was designed. The defect data were packed according to the defined format. Data processed were transferred to PC through USB2.0 real-timely to reconstruct defect microscopic images. The quantity of transferred data was decreased tremendously by this method. The inspecting speed was greatly improved.

The work presented in this paper focuses on the output of temperature compensation system of diesel engine piezoresistive pressure transducer, it is nonlinear and influenced easily by environmental temperature. The paper studied the method of using improved neural network algorithm based on LabVIEW and MATLAB to increase the precision and efficiency of pressure detection. In order to eliminate the temperature influence, this paper proposed the method of using improved back propagation neural network on LabVIEW platform, which realized the communication between LabVIEW and MATLAB. The experimental results show that, with the using of Matlab Script node, the system benefits from the huge computing power of MATLAB to train the network based on the static calibration data of transducer, and makes temperature compensation more efficient and accurate.

Coal and gas outburst is a strong dynamic phenomenon in the process of coal mining, which the fierce degree and destroy effect is beyond imagination, also can cause the occurrence of secondary disasters, such as fire, gas explosion. Especially in coal roadway excavation face, it is frequent. Therefore, the reasonable prediction and evaluation for associated factors of coal and gas outburst in coal roadway excavation working face is important and guiding significant for coal production, sustained and healthy development. With the mathematical model of grey synthetically relational degree analysis, we gain quantitative analysis of six prediction indexes of coal and gas outburst, and determine the best predictors, provide quantitative basis for the selection of coal and gas outburst prediction indexes.

Abstract: Circulating DNA is a potential biomarker for tumor diagnosis and prognosis. This study was aimed to quantify the circulating DNA in plasma from patients with hepatocellular carcinoma (HCC) using quantitative PCR and evaluate its potential clinical value. Blood samples were collected from 72 patients with HCC, 37 with liver cirrhosis or chronic hepatitis and 41 healthy volunteers. Plasma DNA was extracted and quantified by a real-time quantitative PCR method. The diagnostic and prognostic value of plasma DNA analysis for HCC was evaluated. DNA levels in the HCC plasma (median: 173 ng/mL) were significantly higher than those in the healthy controls (9 ng/mL) or control benign patients (46 ng/mL) (P < 0.001). The area under the receiver-operation characteristic (ROC) curve (AUC) assessing plasma DNA was 0.949 for healthy controls and 0.874 for control patients. Plasma DNA detection could discriminate HCC from normal controls with 90.2% sensitivity and 90.3% specificity at the cut-off value of 18.2 ng/mL. Combined ROC analyses using plasma DNA and serum AFP revealed an elevated AUC of 0.974 with 95.1% sensitivity and 94.4% specificity in discriminating HCC from normal controls. The plasma DNA levels were positively associated with tumor size (P = 0.012), and were significantly elevated in HCC patients with intrahepatic spreading or vascular invasion (P = 0.035). The overall survival time of patients with high plasma DNA levels showed a shortened tread when compared with that of patients with low plasma DNA concentrations (P = 0.071). Plasma DNA may be a valuable noninvasive tool for the detecting and predicting the metastasis potential of HCC; and the prognostic value of plasma DNA needed further investigation.

ABSTRACTThe multiresistance gene cfrwas identified for the first time in an Enterococcus faecalisisolate of animal origin. The 32,388-bp plasmid pEF-01, which carried the cfrgene, was sequenced completely. Three copies of the insertion sequence IS1216were identified in pEF-01, and the detection of a cfr- and IS1216-containing amplicon by inverse PCR suggests that IS1216may play a role in the dissemination of cfrby a recombination process.

Support vector regression is used to establish a kind of patch near-field acoustic holography. The regression functions are constructed by treating the measured data on the patch holography as training samples, and then the data outside the measurement aperture are extrapolated. The experimental results show that the extrapolation of the sound pressure outside the smaller initial hologram aperture may be realized easily and effectively, and the reconstruction accuracy is satisfactory.

Iridium carbides with various stoichiometries were investigated by using the first-principles method. It is found that iridium carbides with the iridium germanide structures usually exhibit a better elastic property. Among these studied iridium carbides, tetragonal IrC2with the RhSn2structure has the largest bulk modulus and trigonal IrC4with the IrGe4structure is found to exhibit the largest shear modulus and smallest Poisson’s ratio. Moreover, Ir4C5with the Ir4Ge5structure is a semiconductor and has high bulk and shear moduli. We also found that the shear modulus of iridium carbides with the iridium germanide structures basically increases with the increased carbon content, except Ir4C5; this is due to the fact that only Ir4C5with the Ir4Ge5structure exhibits a semiconductor property, whereas other structures all present metallic. The eight structures for IrC4are all ductile, except for the IrGe4structure of IrC4showing brittleness. On the basis of the comparison of the crystal structure, elastic constants, elastic moduli, and electronic structure for iridium carbides, we expect that Ir4C5and IrC4with the iridium germanide structures are potential ultrahard materials.

First-principles calculations were carried out to investigate the structural stability of synthesized orthorhombic Ta2N3. It is found that the stoichiometric orthorhombic Ta2N3is unstable below 20 GPa. However, it can be stabilized by a small amount of nitrogen vacancies or oxygen substitution into nitrogen sites. The calculated electron localization function indicates that both the formation of nitrogen vacancy and the substitution of oxygen atom can enhance the Ta−N bonding, which is essential for the structural stability. Furthermore, both oxygen substitution and nitrogen vacancy plays a similar role in stabilizing the orthorhombic lattice of Ta2N3. The results of our calculations show that nitrogen vacancies or oxygen substitution into nitrogen sites can alter the charge distribution over the unit cell, which leads to a new arrangement of atoms and enhanced Ta−N bonds.

Early detection and stratification of patients with colorectal cancer (CRC) are major challenges, particularly in the context of the development of new therapies. Several screening strategies are already in place in various countries, but compliance remains a major issue, mainly due to logistics or discomfort for the patients. In this study, we hypothesized that transcriptional signatures associated with leukocytes in peripheral blood can be informative to the identification of CRC patients. Gene expression was studied using RNA extracted from whole blood samples collected in PAXgene tubes and DNA microarrays. Analyzing 119 CRC patients and 101 colonoscopy-negative control (CNC) samples, we observed 327 differentially expressed genes (DEG), mostly associated with immune cell activation and trafficking. Natural Killer (NK) cell signaling and cytotoxicity associated genes appeared to undergo major changes in CRC peripheral blood samples. These changes were more pronounced in the advanced stages of the disease. A summarizing score of the expression of 10 genes related to NK cells interestingly revealed a marked heterogeneity within the CRC Stage IV group, suggesting possible further stratification of the patients. This study shows the potential of transcriptomics in peripheral blood to discover biomarkers and provides new insight on the immune response in colorectal cancer. In addition to preparing a possible alternative to current screening modalities, these results also show that the expression analysis of genes like those related to NK cells should allow the stratification of patients with colorectal cancer, opening the door to personalized medicine.

The machining deformation of the sewing-needle body that is the typical miniature thin-plate part is analyzed. The result demonstrated that not only one kind of stress occurred in the milling of sewing-needle part. The magnitude of cutting force is an important parameter determined the extent of machining deformation. The experimental test of the milling cutting force is developed. The cutting force and the mode of milling can influence the dimension changing that resulted the dimension error.

A geometrically nonlinear model for thin-walled, single-cell composite beams is developed by using variational formulation and the variational-asympotical method. The structural modeling is split into two parts: a two-dimensional analysis over the cross section, and a geometrically nonlinear analysis of a beam along the beam span. The nonlinear model is based on the assumption of moderate beam deflection, accounting for the pitch angle and extends the linear analysis model for anisotropic thin-walled beams. By employing the Galerkin’s method, an nonlinear algebraic equations is derived and then solved by means of an incremental Newton-Raphson method. Numerical results are obtained for one cantilevered box beam: Circumferentially Uniform Stiffness(CUS), under external load to investigate the effect of geometric nonlinearity and the effects of the fiber orientation, laminate stacking sequence, are also addressed.

The free vibration model of a rotating composite thin-walled closed-section beams is presented in this paper. The two-dimensional cross-sectional analysis based on the variational-asymptotical method(VAM) is combined with the Hamilton’s principle to derive the equations of motion and associated boundary conditions of the beams. The Galerkin method is employed in order to solve the coupled differential equations. The natural frequency results obtained for the present model are compared with those of the existing models. Numerical results are obtained for the laminated composite cantilevered box beam with Circumferentially Uniform Stiffness(CUS) configuration, the effects of the fiber orientation, pitch and precone on the natural frequencies associated with coupled vibration modes are investigated.