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Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in ADD3 with BA risk (odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.49-1.99; p = 4.07 × 10 -11 ). An eQTL analysis revealed that the risk allele of rs17095355 was associated with increased expression of ADD3 . Single-cell RNA-sequencing data and immunofluorescence analysis revealed that ADD3 was moderately expressed in cholangiocytes and weakly expressed in hepatocytes. Immuno-fluorescent staining showed abnormal deposition of ADD3 in the cytoplasm of BA hepatocytes. No ADD3 auto-antibody was observed in the plasma of BA infants. In the HLA gene region, no variants achieved genome-wide significance. HLA-DQB1 residue Ala57 is the most significant residue in the MHC region (OR = 1.44, 95% CI = 1.20-1.74; p = 1.23 × 10 -4 ), and HLA-DQB1 was aberrantly expressed in the bile duct cells. GWAS stratified by cytomegalovirus (CMV) IgM status in 87 CMV IgM (+) BA cases versus 141 CMV IgM (-) BA cases did not yield genome-wide significant associations. These findings support the notion that common variants of ADD3 account for BA risk. The HLA genes might have a minimal role in the genetic predisposition of BA due to the weak association signal. CMV IgM (+) BA patients might not have different genetic risk factor profiles compared to CMV IgM (-) subtype.

Background: In view of the low accuracy of the prognosis model of esophageal squamous cell carcinoma (ESCC), this study aimed to optimize the least squares support vector machine (LSSVM) algorithm to determine the uncertain prognostic factors using a Cloud model, and consequently, to establish a new high-precision prognosis model of ESCC., Methods: We studied 4,771 ESCC patients(training samples) from the Surveillance, Epidemiology, and End Results (SEER) database and 635 ESCC patients(validation samples) from the Henan Provincial Center for Disease Control and Prevention (HCDC) database, with the same exclusion criteria and inclusion criteria for both databases, and obtained permission to obtain a research data file in the SEER database from the National Cancer Institute. The independent risk factors were analyzed using the log-rank method, survival curves, univariate and multivariate Cox analysis. Finally, the independent prognostic factors were used to construct the nomogram, random forest and Cloud-LSSVM prognostic models were utilized for validation., Results: The overall median survival time of the SEER database was 14 months (HCDC samples was 46 months), the mean survival time was 26.5 months (HCDC samples was 36.8 months), and the 3-year survival rate was 65.8%. This is because most of the patients with Henan samples are early ESCC, and most of the Seer patients are T3 and T4 people. The multivariate Cox analysis showed that age at diagnosis (P<0.001), sex (P=0.001), race (P=0.002), differentiation grade (P<0.001), pathologic T category (P<0.001), and pathologic M category (P<0.001) were the factors affecting the prognosis of ESCC patients. The SEER data and HCDC database results showed that the accuracy of the Cloud-LSSVM (C-index =0.71, 0.689) model is higher than the differentiation grade (C-index =0.548, 0.506), random forest (C-index =0.649, 0.498), and nomogram (C-index =0.659, 0.563). This new model can realize the unity of the randomness and fuzziness of the Cloud model and utilize the powerful learning and non-linear mapping abilities of LSSVM., Conclusions: Due to the difference of clans between training samples and test samples, the accuracy of prediction is generally not high, but the accuracy of Cloud-LSSVM model is much higher than other models. The new model provides a clear prognostic superiority over the random forest, nomogram, and other models., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1058/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

To systematically investigate the prophages carrying in Porphyromonas gingivalis (P. gingivalis) strains, analyze potential antibiotic resistance genes (ARGs) and virulence genes in these prophages. We collected 90 whole genome sequences of P. gingivalis from NCBI and utilized the Prophage Hunter online software to predict prophages; Comprehensive antibiotic research database (CARD) and virulence factors database (VFDB) were adopted to analyze the ARGs and virulence factors (VFs) carried by the prophages. Sixty-nine prophages were identified among 24/90 P. gingivalis strains, including 17 active prophages (18.9%) and 52 ambiguous prophages (57.8%). The proportion of prophages carried by each P. gingivalis genome ranged from 0.5% to 6.7%. A total of 188 antibiotic resistance genes belonging to 25 phenotypes and 46 different families with six mechanisms of antibiotic resistance were identified in the 17 active prophages. Three active prophages encoded 4 virulence genes belonging to type III and type VI secretion systems. The potential hosts of these virulence genes included Escherichia coli, Shigella sonnei, Salmonella typhi, and Klebsiella pneumoniae. In conclusion, 26.7% P. gingivalis strains carry prophages, while the proportion of prophage genes in the P. gingivalis genome is relatively low. In addition, approximately 39.7% of the P. gingivalis prophage genes have ARGs identified, mainly against streptogramin, peptides, and aminoglycosides. Only a few prophages carry virulence genes. Prophages may play an important role in the acquisition, dissemination of antibiotic resistance genes, and pathogenicity evolution in P. gingivalis., Competing Interests: Declaration of Competing Interest The authors have no confilcts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Biliary atresia (BA) is a destructive, obliterative cholangiopathy characterized by progressive fibro-inflammatory disorder and obliteration of intra- and extrahepatic bile ducts. The Jagged1 ( JAG1 ) gene mutations have been found in some isolated BA cases. We aim to explore the association of common variants in JAG1 with isolated BA risk in the Chinese Han population. Methods: We genotyped 31 tag single nucleotide polymorphisms covering the JAG1 gene region in 333 BA patients and 1,665 healthy controls from the Chinese population, and performed case-control association analysis. The expression patterns of JAG1 homologs were investigated in zebrafish embryos, and the roles of jag1 a and jag1b in biliary development were examined by morpholino knockdown in zebrafish. Results: Single nucleotide polymorphisms rs6077861 [ P Allelic = 1.74 × 10 -4 , odds ratio = 1.78, 95% confidence interval: 1.31-2.40] and rs3748478 ( P Allelic = 5.77 × 10 -4 , odds ratio = 1.39, 95% confidence interval: 1.15-1.67) located in the intron region of JAG1 showed significant associations with BA susceptibility. The JAG1 homologs, jag1a and jag1b genes were expressed in the developing hepatobiliary duct of zebrafish, especially at 72 and 96 h postfertilization. Knockdown of both jag1a and jag1b led to poor biliary secretion, sparse intrahepatic bile duct network and smaller or no gallbladders compared with control embryos in the zebrafish model. Conclusion: Common genetic variants of JAG1 were associated with BA susceptibility. Knockdown of JAG1 homologs led to defective intrahepatic and extrahepatic bile ducts in zebrafish. These results suggest that JAG1 might be implicated in the etiology of BA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bai, Pei, Zhou, Song, Pan, Gong, Wu, Yu, Cui, Gu, Chu and Cai.)

In this paper, a new dual-training method for a time-delay reservoir computing (RC) system based on a single vertical-cavity surface-emitting laser (VCSEL) is proposed and demonstrated experimentally for the first time. The prediction performance of the RC system by using the dual-training method has been experimentally and numerically investigated. Here, the dual-training method is defined as performing a further RC based on the difference between the target value and the predicted value of the traditional single training. It is found that enhanced prediction performance of the RC system can be obtained by employing the dual-training method, compared to the traditional single training method. More specifically, the NMSE values of the RC system with the dual-training method applied can be improved to 760% compared with the single training method in experiments. Besides, the effects of injection power, bias currents, feedback strength, and frequency detuning are also considered. The proposed dual-training method is of great significance to the performance enhancement of the RC and has an important promotion effect on the application of the RC in the future.

Background: The aim of this study was to identify prognostic markers for esophageal squamous cell carcinoma (ESCC) and build an effective prognostic nomogram for ESCC. Methods: A total of 365 patients with ESCC from three medical centers were divided into four cohorts. In the discovery phase of the study, we analyzed transcriptional data from 179 cancer tissue samples and identified nine marker genes using edgeR and rbsurv packages. In the training phase, penalized Cox regression was used to select the best marker genes and clinical characteristics in the 179 samples. In the verification phase, these marker genes and clinical characteristics were verified by internal validation cohort (n = 58) and two external cohorts ( n = 81, n = 105). Results: We constructed and verified a nomogram model based on multiple clinicopathologic characteristics and gene expression of a patient cohort undergoing esophagectomy and adjuvant radiochemotherapy. The predictive accuracy for 4-year overall survival (OS) indicated by the C-index was 0.75 (95% CI, 0.72-0.78), which was statistically significantly higher than that of the American Joint Committee on Cancer (AJCC) seventh edition (0.65). Furthermore, we found two marker genes (TM9SF1, PDZK1IP) directly related to the OS of esophageal cancer. Conclusion: The nomogram presented in this study can accurately and impersonally predict the prognosis of ESCC patients after partial resection of the esophagus. More research is required to determine whether it can be applied to other patient populations. Moreover, we found two marker genes directly related to the prognosis of ESCC, which will provide a basis for future research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Jiao, Shen, Chen, Zhao, Li, Gu, Lan, Ruan, Liu, Xu, Yuan, Qi and Gao.)

Hirschsprung disease (HSCR) has a higher incidence in children with Down syndrome (DS), which makes trisomy 21 a predisposing factor to HSCR. DSCAM and BACE2 are close together on the HSCR-associated critical region of chromosome 21. Common variants of DSCAM and rare variants of BACE2 were implicated to be associated with sporadic HSCR. However, the submucosal neuron defect of DS mouse model could not be rescued by normalization of Dscam . We aimed to explore the contribution of DSCAM and BACE2 to the development of the enteric nervous system (ENS) and HSCR susceptibility. We genotyped 133 tag single-nucleotide polymorphisms (SNPs) in DSCAM and BACE2 gene region in 420 HSCR patients and 1,665 controls of Han Chinese. Expression of DSCAM and BACE2 homologs was investigated in the developing gut of zebrafish. Overexpression and knockdown of the homologs were performed in zebrafish to investigate their roles in the development of ENS. Two DSCAM SNPs, rs430255 ( P Addtive = 0.0052, OR = 1.36, 95% CI: 1.10-1.68) and rs2837756 ( P Addtive = 0.0091, OR = 1.23, 95% CI: 1.05-1.43), showed suggestive association with HSCR risk. Common variants in BACE2 were not associated with HSCR risk. We observed dscama , dscamb , and bace2 expression in the developing gut of zebrafish. Knockdown of dscama , dscamb , and bace2 caused a reduction of enteric neurons in the hindgut of zebrafish. Overexpression of DSCAM and bace2 had no effects on neuron number in the hindgut of zebrafish. Our results suggested that common variation of DSCAM contributed to HSCR risk in Han Chinese. The dysfunction of both dscams and bace2 caused defects in enteric neuron, indicating that DSCAM and BACE2 might play functional roles in the occurrence of HSCR. These novel findings might shed new light on the pathogenesis of HSCR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lu, Yu, Cui, Yu, Song, Bai, Wu, Gu, Wang, Cai and Chu.)

The valley depolarization dynamics of free holes in monolayer transition-metal dichalcogenides are studied by solving the Boltzmann transport equation in real time fully ab inito . While monolayer MoSe 2 , WS 2 , WSe 2 , and MoTe 2 possess long hole valley lifetimes due to the spin-valley locking effect, monolayer MoS 2 unexpectedly shows ultrafast valley dynamics, with a hole valley lifetime two orders of magnitude shorter than those of the above four materials at room temperature. It is further revealed that the existence of the satellite Γ valley in MoS 2 provides an additional hole relaxation path where the Γ valley acts as an intermediate in the hole relaxation between primary K' and K valleys, and moreover, the strong scattering between primary and satellite valleys ensures the ultrafast valley depolarization. By uncovering the pivotal role of the satellite valley, our results may have significant implications for finely controlling valley depolarization in the multivalley materials.

Background: Hirschsprung's disease (HSCR) is the most common congenital cause of intestinal obstruction in children. Sotos syndrome (SoS) is an overgrowth disorder with constipation and sometimes accompanied by HSCR. NSD1 gene mutation is the main cause of SoS. We aimed to investigate association of NSD1 common single nucleotide polymorphisms (SNPs) with HSCR susceptibility in Chinese Han population., Method: We genotyped 15 SNPs encompassing NSD1 gene region in 420 HSCR patients and 1665 controls on Fludigm EP1 platform. Association analysis was performed between cases and controls., Result: Rs244709 was the most associated SNP with HSCR susceptibility of the sample set (P Allelic  = 9.69 × 10 -5 , OR = 1.37, 95% CI: 1.17-1.61). Gender stratification analysis revealed that NSD1 SNPs were associated with HSCR in males, but not in females. The nonsynonymous coding SNP rs28932178 in NSD1 exon 5 represented the most significant signal in males (P Allelic  = 6.43 × 10 -5 , OR = 1.42, 95% CI: 1.20-1.69). The associated SNPs were expression quantitative trait loci (eQTLs) of nearby genes in multiple tissues. NSD1 expression levels were higher in aganglionic colon tissues than ganglionic tissues (P = 3.00 × 10 -6 )., Conclusion: NSD1 variation conferred risk to HSCR in males, indicating SoS and HSCR may share common genetic factors., Impact: This is the first study to reveal that NSD1 variation conferred risk to Hirschsprung's disease susceptibility in males of Chinese Han population, indicating Sotos syndrome and Hirschsprung's disease may share some common genetic background. This study indicates more attention should be paid to the symptom of constipation in patients with Sotos syndrome. Our results raise questions about the role of NSD1 in the development of enteric nervous system and the pathogenesis of Hirschsprung's disease.

Microbial dysbiosis in the upper digestive tract is linked to an increased risk of esophageal squamous cell carcinoma (ESCC). Overabundance of Porphyromonas gingivalis is associated with shorter survival of ESCC patients. We investigated the molecular mechanisms driving aggressive progression of ESCC by P. gingivalis. Intracellular invasion of P. gingivalis potentiated proliferation, migration, invasion, and metastasis abilities of ESCC cells via transforming growth factor-β (TGFβ)-dependent Drosophila mothers against decapentaplegic homologs (Smads)/Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) activation. Smads/YAP/TAZ/TEA domain transcription factor1 (TEAD1) complex formation was essential to initiate downstream target gene expression, inducing an epithelial-mesenchymal transition (EMT) and stemness features. Furthermore, P. gingivalis augmented secretion and bioactivity of TGFβ through glycoprotein A repetitions predominant (GARP) up-regulation. Accordingly, disruption of either the GARP/TGFβ axis or its activated Smads/YAP/TAZ complex abrogated the tumor-promoting role of P. gingivalis. P. gingivalis signature genes based on its activated effector molecules can efficiently distinguish ESCC patients into low- and high-risk groups. Targeting P. gingivalis or its activated effectors may provide novel insights into clinical management of ESCC., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: Hirschsprung's disease (HSCR) is a rare genetically heterogeneous congenital disorder. A recent study based on whole genome sequencing demonstrated that common variants at four novel loci, which contained two intronic variants on CASQ2 and PLD1 , and intergenic variants located between SLC4A7 and EOMES at 3p24.1, and between LINC01518 and LOC283028 at 10q11.21, were associated with HSCR susceptibility. To validate these associations with HSCR susceptibility, we performed a case-control study in a Han Chinese sample set. Methods: We selected four previously identified single nucleotide polymorphisms (SNPs) for replication, along with tag SNPs to cover the four associated regions. In total, 61 SNPs were genotyped in 420 HSCR patients and 1,665 healthy controls from the Han Chinese population. Results: None of the 14 tag SNPs in the CASQ2 gene region, including the previously associated rs9428225, showed an association with HSCR. Among the 24 tag SNPs from the SLC4A7 - EOMES region at 3p24.1, rs2642925 [odds ratio (OR) = 1.41, 95% confidence interval (95% CI) = 1.10-1.79; P Additive = 0.007] and the previously associated SNP rs9851320 showed a suggestive association (OR = 1.22, 95% CI = 1.01-1.47; P Additive = 0.042). A non-synonymous SNP, rs2287579, in PLD1 showed a suggestive association with HSCR susceptibility (OR = 1.71, 95% CI = 1.18-2.46; P Additive = 0.004). Additionally, the previously associated PLD1 SNP rs12632766 showed a suggestive significance (OR = 1.20, 95% CI = 1.01-1.42, P Additive = 0.038). In the LINC01518 - LOC283028 region at 10q11.21, three SNPs meet the study-wide significance threshold. Rs17153309 was the most associated SNP (OR = 1.60, 95% CI = 1.34-1.90; P Additive = 1.13 × 10 -7 ). The previously associated SNP rs1414027 also showed significant association (OR = 1.43, 95% CI = 1.20-1.70, P Additive = 3.92 × 10 -5 ). Two associated SNPs at 10q11.21 (rs1414027 and rs624804) were expression quantitative trait loci in digestive tract tissues from GTEx databases. Conclusions: Our results confirmed that variants of the LINC01518-LOC283028 region were associated with HSCR in the Han Chinese population. Additionally, the susceptibility of SNPs in the LINC01518-LOC283028 region were associated with the expression levels of nearby genes. These results provide new insight into the pathogenesis of HSCR., (Copyright © 2020 Niu, Bai, Song, Lu, Wu, Gong, Yu, Wei, Yu, Gu, Cai and Chu.)

Porphyromonas gingivalis has been linked to the development and progression of oesophageal squamous cell carcinoma (ESCC), and is considered to be a high-risk factor for ESCC. Currently, the commonly used methods for P. gingivalis detection are culture or DNA extraction-based, which are either time and labour intensive especially for high-throughput applications. We aimed to establish and evaluate a rapid and sensitive direct quantitative polymerase chain reaction (qPCR) protocol for the detection of P. gingivalis without DNA extraction which is suitable for large-scale epidemiological studies. Paired gingival swab samples from 192 subjects undergoing general medical examinations were analysed using two direct and one extraction-based qPCR assays for P. gingivalis. Tris-EDTA buffer-based direct qPCR (TE-direct qPCR), lysis-based direct qPCR (lysis-direct qPCR) and DNA extraction-based qPCR (kit-qPCR) were used, respectively, in 192, 132 and 60 of these samples for quantification of P. gingivalis. The sensitivity and specificity of TE-direct qPCR was 95.24% and 100% compared with lysis-direct qPCR, which was 100% and 97.30% when compared with kit-qPCR; TE-direct qPCR had an almost perfect agreement with lysis-direct qPCR (κ = 0.954) and kit-qPCR (κ = 0.965). Moreover, the assay time used for TE-direct qPCR was 1.5 h. In conclusion, the TE-direct qPCR assay is a simple and efficient method for the quantification of oral P. gingivalis and showed high sensitivity and specificity compared with routine qPCR.

Biliary atresia (BA) is an idiopathic neonatal cholestatic disease. Recent genome-wide association study (GWAS) revealed that common variation of ADD3 , GPC1 , ARF6 , and EFEMP1 gene was associated with BA susceptibility. We aimed to evaluate the association of these genes with BA in Chinese population. Twenty single nucleotide polymorphisms (SNPs) in these four genes were genotyped in 340 BA patients and 1,665 controls. Three SNPs in ADD3 were significantly associated with BA, and rs17095355 was the top SNP ( P Allele = 3.23×10 -6 ). Meta-analysis of published data and current data indicated that rs17095355 was associated with BA susceptibility in Asians and Caucasians. Three associated SNPs were expression quantitative trait loci (eQTL) for ADD3 . Two GPC1 SNPs in high linkage disequilibrium (LD) showed nominal association with BA susceptibility ( P Allele = 0.03 for rs6707262 and P Allele = 0.04 for rs6750380), and were eQTL of GPC1 . Haplotype harboring these two SNPs almost reached the study-wide significance ( P = 0.0035). No association for ARF6 and EFEMP1 was found with BA risk in the current population. Our study validated associations of ADD3 and GPC1 SNPs with BA risk in Chinese population and provided evidence of epistatic contributions of genetic factors to BA susceptibility.

Centrosymmetric materials with spin-degenerate bands are generally considered to be trivial for spintronics and related physics. In two-dimensional (2D) materials with multiple degenerate orbitals, we find that the spin-orbit coupling can induce spin-orbital locking, generate out-of-plane Zeeman-like fields displaying opposite signs for opposing orbitals, and create novel electronic states insensitive to the in-plane magnetic field, which thus enables a new type of Ising superconductivity applicable to centrosymmetric materials. Many candidate materials are identified by high-throughput first-principles calculations. Our work enriches the physics and materials of Ising superconductivity, opening new opportunities for future research of 2D materials.

The interplay of magnetism and topology is a key research subject in condensed matter physics, which offers great opportunities to explore emerging new physics, such as the quantum anomalous Hall (QAH) effect, axion electrodynamics, and Majorana fermions. However, these exotic physical effects have rarely been realized experimentally because of the lack of suitable working materials. Here, we predict a series of van der Waals layered MnBi 2 Te 4 -related materials that show intralayer ferromagnetic and interlayer antiferromagnetic exchange interactions. We find extremely rich topological quantum states with outstanding characteristics in MnBi 2 Te 4 , including an antiferromagnetic topological insulator with the long-sought topological axion states on the surface, a type II magnetic Weyl semimetal with one pair of Weyl points, as well as a collection of intrinsic axion insulators and QAH insulators in even- and odd-layer films, respectively. These notable predictions, if proven experimentally, could profoundly change future research and technology of topological quantum physics.

Intestinal villus atrophy is a major complication of total parenteral nutrition (TPN). Our previous study revealed that TPN-induced villus atrophy is accompanied by elevated expression of CUGBP, Elav-like family member 1 (CELF1); however, its mechanism of action has not been fully understood. Herein, we report a pivotal role of CELF1/p53 axis, which induces a sustained antiproliferative signal, leading to suppressed proliferation of intestinal epithelial cells (IECs). By using a rat model of TPN, we found synchronous upregulation of CELF1 and p53 in jejunum mucosa, accompanied by a 51% decrease in crypt cell proliferation rate. By using HCT-116 cells as an IEC model in vitro, we found that the expression of CELF1 altered dynamically in parallel to proliferation rate, suggesting a self-adaptive expression pattern in IECs in vitro. Furthermore, ectopic overexpression of CELF1 elicited a significant antiproliferative effect in HCT-116, Caco-2, and IEC-6 cells, whereas knockdown of CELF1 elicited a significant proproliferative effect. Moreover, cell-cycle assay revealed that ectopic overexpression of CELF1 induced sustained G2 arrest and G1 arrest in HCT-116 and IEC-6 cells, respectively, which could be abolished by p53 silencing. Mechanistically, polysomal profiling and nascent protein analysis revealed that regulation of p53 by CELF1 was mediated through accelerating its protein translation in polysomes. Taken together, our findings revealed a sustained suppression of IEC proliferation evoked by CELF1/p53 axis, which may be a potential therapeutic target for the treatment of TPN-induced villus atrophy.-Yan, J.-K., Zhang, T., Dai, L.-N., Gu, B.-L., Zhu, J., Yan, W.-H., Cai, W., Wang, Y. CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition.

The pleiotropic pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF), represents an important link between chronic inflammation and tumorigenesis. Although accumulating evidence demonstrates that MIF overexpression is implicated in the development and progression of multiple cancers, including esophageal squamous cell carcinoma (ESCC), the molecular mechanisms underlying its tumor-promoting roles in ESCC remain unclear. In the present study, we observed that MIF is overexpressed in ESCC and correlated significantly with lymph node metastasis, advanced clinical stage, and poor survival of ESCC. MIF knockdown attenuated the proliferation, migration, and invasion of ESCC cells in vitro and in vivo. Moreover, blockage of MIF expression decreased the activation of the Akt, MEK/ERK, and NF-κB pathways and enhanced sensitivity to apoptosis. Meanwhile, repression of MIF expression resulted in activation of glycogen synthase kinase 3 beta (GSK3β) and subsequent decrease of active β-catenin, as well as its downstream targets including cyclin D1, matrix metalloproteinase (MMP)-7, c-myc, and c-Jun. Collectively, our results provided mechanistic insights into the tumor-promoting role of MIF in ESCC, and suggested that MIF represents a potential therapeutic target for treatment of ESCC., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We have investigated the structural, electrical and magnetic properties as well as the phonon modes of hexagonal rare-earth manganites (RMnO3, R  =  Pr, Nd, Pm, Sm, Gd, Tb, Dy, Ho, Er, Tm and Lu) under chemical pressure, hydrostatic pressure and epitaxial strain by first-principles calculations. The magnetic ground state of RMnO3 is found to have Γ4 magnetic configuration and to be stable under all considered external conditions. In contrast, the K3 phonon mode, which is the primary order parameter and responsible for the 'improper ferroelectricity', is greatly influenced by pressure and epitaxial strain. Consequently, the electric polarization is enhanced by 56.7% when the chemical pressure increases from R  =  Pr to R  =  Lu. The hydrostatic pressure can also improve the polarization to a certain degree, e.g. by 14.7% from 0 GPa to 40 GPa in LuMnO3. Finally, the dependence of polarization on the epitaxial strain is also given, revealing that the compressive strain could promote the ferroelectricity while tensile strain will suppress it.

The effectiveness and stability of epithelial barrier depend on apical junctional complexes, which consist of tight junctions (TJs) and adherens junctions (AJs). E-cadherin is the primary component of AJs, and it is essential for maintenance of cell-to-cell interactions and regulates the epithelial barrier. However, the exact mechanism underlying E-cadherin expression, particularly at the posttranscriptional level, remains largely unknown. RNA-binding proteins CUG-binding protein 1 (CUGBP1) and HU antigen R (HuR) are highly expressed in the intestinal epithelial tissues and modulate the stability and translation of target mRNAs. Here, we present evidence that CUGBP1 and HuR interact directly with the 3'-untranslated region of E-cadherin mRNA and regulate E-cadherin translation. CUGBP1 overexpression in Caco-2 cells inhibited E-cadherin translation by increasing the recruitment of E-cadherin mRNA to processing bodies (PBs), thus resulting in an increase in paracellular permeability. Overexpression of HuR exhibited an opposite effect on E-cadherin expression by preventing the translocation of E-cadherin mRNA to PBs and therefore prevented CUGBP1-induced repression of E-cadherin expression. Elevation of HuR also abolished the CUGBP1-induced epithelial barrier dysfunction. These findings indicate that CUGBP1 and HuR negate each other's effects in regulating E-cadherin translation by altering the recruitment of E-cadherin mRNA to PBs and play an important role in the regulation of intestinal barrier integrity under various pathophysiological conditions., (Copyright © 2016 the American Physiological Society.)

Background and Aims: Elevated intestinal permeability of lipopolysaccharide (LPS) is a major complication for patients with parenteral nutrition (PN), but the pathogenesis is poorly understood. Intestinal P-glycoprotein (P-gp) is one of the efflux transporters that contribute to restricting the permeability of lipopolysaccharide via transcellular route. P-gp expression may be regulated by PN ingredients, and thus this study sought to investigate the effect of PN on the expression of P-gp and to elucidate the underlying mechanism in vitro., Methods: Caco-2 cells were treated with PN ingredients. Changes in P-gp expression and function were determined and the role of ERK-FOXO 3a pathway was studied. Transport studies of FITC-lipopolysaccharide (FITC-LPS) across Caco-2 cell monolayers were also performed., Results: Among PN ingredients, soybean oil-based lipid emulsion (SOLE) exhibited significant inhibitory effect on P-gp expression and function. This regulation was mediated via activation of ERK pathway with subsequent nuclear exclusion of FOXO 3a. Importantly, P-gp participated in antagonizing the permeation of FITC-LPS (apical to basolateral) across Caco-2 cell monolayers. SOLE significantly increased the permeability of FITC-LPS (apical to basolateral), which was associated with impaired P-gp function., Conclusions: The expression and function of intestinal P-gp is suppressed by SOLE in vitro., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

First-principles calculations show that strain-induced topological phase transition is a universal phenomenon in those narrow-gap semiconductors for which the valence band maximum (VBM) and conduction band minimum (CBM) have different parities. The transition originates from the opposite responses of the VBM and CBM, whose magnitudes depend critically on the direction of the applied strain. Our work suggests that strain can play a unique role in tuning the electronic properties of topological insulators for device applications, as well as in the achievement of new topological insulators.

We investigate the low-energy electron dynamics in two-dimensional ultrathin film of magnetically doped topological insulators in the context of gate-tuned coherent spin manipulation. Our first-principles calculations for such film unambiguously identify its spin-resolved topological band structure arising from spin-orbit coupling and time-reversal symmetry breaking. Exploiting this characteristic, we predict a negative birefraction for chiral electron tunneling through a gate-controlled p-n interface in the film, analogous to optical birefringence. By fine-tuning the gate voltage, a series of unusual phenomena, including electron double focusing, spatial modulation of spin polarizations, and quantum-interference-induced beating patterns, could be efficiently implemented, offering a powerful platform to establish spin-resolved electron optics by all-electrical means.

Objective: To observe the improvement in post-stroke dysphagia after treatment of nape acupuncture and rehabilitation training., Methods: Eighty patients who were in compliance with the inclusive criteria were randomized into a conventional treatment group and a nape acupuncture group, 40 cases in each one, according to the admission sequence. In the conventional treatment group, on the basis of general medication, the rehabilitation training of swallowing function was applied. In the nape acupuncture group, on the basic treatment as the conventional treatment group, nape acupuncture group was given., Results: After treatment, the improvements in bedside water swallowing test, SSA, VFSS and pharynx transit time were all superior to those before treatment for the patients in the two groups (all P < 0.05). The improvements in bedside water swallowing test, SSA, VFSS and pharynx transit time in the nape acupuncture group were all superior to those in the conventional treatment group (all P < 0.05). The total effective rate was 85.0% (34/40) in the nape acupuncture group, which was higher than 65.0% (26/40) in the conventional treatment group, indicating the significantly statistical difference between the two groups (P < 0.05)., Conclusion: Nape acupuncture combined with rehabilitation training significantly improves swallowing function of the patients after stroke.

It is highly desirable to integrate graphene into existing semiconductor technology, where the combined system is thermodynamically stable yet maintain a Dirac cone at the Fermi level. First-principles calculations reveal that a certain transition metal (TM) intercalated graphene/SiC(0001), such as the strongly bound graphene on SiC with Mn intercalation, could be such a system. Different from freestanding graphene, the hybridization between graphene and Mn/SiC leads to the formation of a dispersive Dirac cone of primarily TM d characters. The corresponding Dirac spectrum is still isotropic, and the transport behavior is nearly identical to that of freestanding graphene for a bias as large as 0.6 V, except that the Fermi velocity is half that of graphene. A simple model Hamiltonian is developed to qualitatively account for the physics of the transfer of the Dirac cone from a dispersive system (e.g., graphene) to an originally nondispersive system (e.g., TM).

Unlabelled: OBJECTIVE To compare the differences in the scores of blood stasis syndrome (BSS) in three subtypes of acute ischemic stroke (AIS) based on modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, and to explore the influencing factors of BSS., Methods: Patients with AIS were classified by modified TOAST criteria. The BSS score was determined in 418 patients of atherosclerosis thrombosis (AT), cardioembolism (CE), and small artery disease (SAD) subtypes. The BSS scores were compared in the three subtypes. Univariate analysis and multivariable Logistic analysis were carried out to analyze the influencing factors of BSS., Results: As for the BSS score, CE (120.08 +/- 14.91) > AT (79.56 +/- 11.43) > SAD (37.88 +/- 8.32), and there was statistical difference among different subtypes (P < 0.01). Univariate analysis indicated that age, heart disease, carotid stenosis, NIHSS, GCS, and multiple infarction positions had significant effects on BSS. Multiple Logistic regression analysis suggested that age (OR: 1.71, 95% CII: 1.13-2.74, P = 0.034), heart disease (OR: 2.05,95% CI: 1.52-4.15, P = 0.000), carotid stenosis (OR: 2.74, 95% CI: 1.65-4.55, P = 0.007), and multiple infarction positions (OR: 3.46, 95% CI: 2.16-6.62, P = 0.005) were independent influencing factors of BSS., Conclusions: Different TOAST subtypes of BSS had different BSS scores, which was helpful to indicate the reasons for BSS. Age, heart disease, carotid stenosis, and multiple infarction positions were independent influencing factors of BSS.

We have performed first-principles calculations of graphene edge stresses, which display two interesting quantum manifestations absent from the classical interpretation: the armchair edge stress oscillates with a nanoribbon width, and the zigzag edge stress is noticeably reduced by spin polarization. Such quantum stress effects in turn manifest in mechanical edge twisting and warping instability, showing features not captured by empirical potentials or continuum theory. Edge adsorption of H and Stone-Wales reconstruction are shown to provide alternative mechanisms in relieving the edge compression and hence to stabilize the planar edge structure.

Spin-polarized density functional calculations reveal that magnetism can be induced by carbon adatoms on boron nitride nanotubes (BNNTs) and BN hexagonal sheets. As a result of the localization of impurity states, these hybrid sp-electron systems are spin-polarized, with a local magnetic moment of 2.0 mu(B) per C adatom regardless of the tube diameter and the bonding between the C atom and the BNNTs/BN sheets. An analysis of orbital hybridization indicates that two valence electrons participate in the bonding and the remaining two electrons of the C adatom are confined at the adsorption site and contribute to the magnetism accordingly. The effective interaction distance between the C-induced magnetic moments is evaluated. In terms of the diffusion barrier and the adsorption energy of C adatoms on the BN nanotubes/sheets, a fabrication method for BN-C-based functional nanodevices is proposed, and a series of virtual building blocks for functional devices are illustrated.

The intrinsic transport properties of zigzag graphene nanoribbons (ZGNRs) are investigated using first-principles calculations. It is found that although all ZGNRs have similar metallic band structure, they show distinctly different transport behaviors under bias voltages, depending on whether they are mirror symmetric with respect to the midplane between two edges. Asymmetric ZGNRs behave as conventional conductors with linear current-voltage dependence, while symmetric ZGNRs exhibit unexpected very small currents with the presence of a conductance gap around the Fermi level. This difference is revealed to arise from different coupling between the conducting subbands around the Fermi level, which is dependent on the symmetry of the systems.

Using first-principles calculations based on density-functional theory, we systematically study the adsorption of O(2) molecules on ultrathin Pb(111) films ranging from 3 to 11 monolayers (MLs). It is found that no matter how thick the film is, the O(2) molecule prefers to adsorb at the threefold hcp hollow site where it lies parallel to the surface. The adsorption mechanism is discussed from the hybridization of p orbitals of O(2) and Pb. The adsorption energy of O(2) on the Pb(111) film, about several hundred meV, shows a 2 ML oscillation with the thickness. This study well confirms the modulation of the surface reactivity of Pb films induced by the quantum well states, which is compatible with the previous experimental observation.

We simulate the phase transition processes of aligned crystalline boron nitride (BN) nanotube bundles under transverse pressure, and investigate the phase transition mechanism and transition conditions. The antiparallel polar bonds rule, associated with the interaction between the tubes, is demonstrated to be crucial to such phase transitions. And the curvature of the tubes can greatly affect the phase transition behavior. We discover a unique sp(2)-sp(3)-sp(2) transition and a series of new BN crystal phases including a novel porous sheet-stacking-up form with the lightest density (2.01 g/cm(3)), which could be used in highly efficient energy storage.

We demonstrate that the electronic devices built on patterned graphene nanoribbons (GNRs) can be made with atomic-perfect-interface junctions and controlled doping via manipulation of edge terminations. Using first-principles transport calculations, we show that the GNR field effect transistors can achieve high performance levels similar to those made from single-walled carbon nanotubes, with ON/OFF ratios on the order of 10(3)-10(4), subthreshold swing of 60 meV per decade, and transconductance of 9.5 x 10(3) Sm-1.

Ab initio calculations show that (5,5) and (6,6) single-walled gallium nitride nanotubes (GaN NTs) in bundles could aggregate spontaneously to form new condensed phases when bundled tubes are close enough under hydrostatic pressure. The new GaN phases have typical porous structures, constructed by alternating tetragons and hexagons around the original tube walls. Owing to the different compatibilities of the chirality of the tube with the symmetry of the array, the new phase formed from (5,5) GaN NT bundles is triclinic and that from (6,6) ones is hexagonal. These porous GaN phases possess tetrahedral bonding corresponding to sp(3) hybridization, different from sp(2) hybridized bonding in individual GaN NTs. The interaction between tubes not only controls the structural transformation but also influences the electronic structure of porous GaN. We expect that the two-dimensional-channeled porous structure of GaN is advantageous for the usage of GaN as the molecular sieve and as the excellent dilute magnetic semiconductor by considerable magnetic doping.

Our calculations demonstrate that the intrinsic magnetism of boron nitride nanotubes (BNNTs) can be induced by their open ends, and the resulting magnetic moment is sensitive to the chirality of BNNTs. It is found that BNNTs, a pure sp-electron system, present a tremendous spin-splitting larger than 1 eV and that B-rich-ended and N-rich-ended BNNTs exhibit "conjugate", spin-polarized, deep-gap states. Tremendous spin-splitting effects combined with considerable local spin-polarizations at the open ends make BNNTs significant for applications of nanoscale spintronics such as spin-polarized electron emitters.

Chemical functionalization of carbon nanotubes with Stone-Wales (SW) defects by carboxyl (COOH) groups is investigated by density functional calculations. Due to the localized donor states induced by the SW defect, the binding of the COOH group with the defective carbon nanotube is stronger than that with the perfect one. A quasi-tetrahedral bonding configuration of carbon atoms, indicating sp3 hybrid bonding, is formed in the adsorption site. The charge distribution analysis shows that, in comparison with benzoic acid, the localized or delocalized pi states on the nanotube would affect the polarities of chemical bonds of the COOH group without losing the acidity. Furthermore, it is found that the double-adsorption system (two COOH groups are respectively adsorbed on two individual carbon atoms of the SW defect) is more energetically favorable than the monoadsorption one. The adsorption of COOH groups leads to a significant change of the electronic states around the Fermi level, which is advantageous for the electrical conductivity. The functionalization by introducing functional groups on the topological defects provides a pathway for applications of carbon nanotubes in chemical sensors and nanobioelectronics.

We perform first-principles calculations to explore the physical origin of hydrogen-induced semiconductor surface metallization observed in beta-SiC(001)-3 x 2 surface. We show that the surface metallization arises from a novel mechanism of n-type doping of surface band via formation of hydrogen bridge bonds (i.e., Si-H-Si complex). The hydrogen strengthens the weak Si-Si dimers in the subsurface by forming hydrogen bridge bonds, and donates electron to the surface conduction band.

Monte Carlo simulations based on a first-principles-derived Hamiltonian are conducted to study the properties of Pb(Zr1-xTix)O3 alloys compositionally modulated along the [100] pseudocubic direction near the morphotropic phase boundary. It is shown that compositional modulation causes the polarization to continuously rotate away from the modulation direction, resulting in the unexpected triclinic and C-type monoclinic ground states and huge enhancement of electromechanical responses (the peak of piezoelectric coefficient is as high as 30,000 pC/N). The orientation dependence of dipole-dipole interaction in modulated structure is revealed as the microscopic mechanism to be responsible for these anomalies.

We investigate electronic transport properties of the squashed armchair carbon nanotubes, using tight-binding molecular dynamics and the Green's function method. We demonstrate a metal-to-semiconductor transition while squashing the nanotubes and a general mechanism for such a transition. It is the distinction of the two sublattices in the nanotube that opens an energy gap near the Fermi energy. We show that the transition has to be achieved by a combined effect of breaking of mirror symmetry and bond formation between the flattened faces in the squashed nanotubes.

Field observation on the population fluctuation of Oncomelana snail at low density was carried out in the ditches and rivers in Wuxi, Ludong and Lugao counties (or city) from 1987 to 1990. The results showed that the environment of the observed places is an important factor in the population fluctuation of the snails at low density. When the environment is appropriate, even one pair of the snails may multiply to a large population. Results of successive observation for 3 years on 1, 5 and 10 pairs of snails within nylon cages in ditches showed that the density of the snails increased by 171.5, 69.5 and 28.4 folds respectively and the population of the snails increased by 354, 135 and 75 folds respectively. The population in 2 of the observed ditches with one pair of snails each even multiply by 543 and 426.5 folds. While in natural field condition, the population fluctuation of residual snails varied in different places. In one ditch it multiplied by 34.7 folds, but in another river the population almost unchanged. No natural elimination of snails could be found in all observed places. It was suggested that the snail surveillance should be conducted persistently and any snail once be found, it should be timely eradicated.