Search

Purpose: To develop a novel index that combines the locations and magnitudes of corneal alterations to improve discrimination of eyes with subclinical keratoconus from normal eyes., Methods: A Scheimpflug-based tomography system was used to image 252 eyes (normal: 78 eyes, subclinical keratoconus: 71 eyes, and keratoconus: 103 eyes) of 252 patients from two clinical centers. Coordinates and magnitudes of the maximum corneal protrusion alterations were extracted from curvature, elevation, and pachymetry maps. A location consistency index (LCI) was calculated from the Euclidean distances among these locations. A logistic regression model, named the location consistency enhanced score (LCES), which combined the LCI and the magnitudes of these maximum alterations, was trained and tested in two different datasets., Results: The LCI in eyes with subclinical keratoconus was 7.8 ± 2.6 µm, which was significantly different from that in normal eyes (11.8 ± 3.9 µm) and eyes with keratoconus (5.8 ± 2.4 µm) (all P < .001). The LCI could differentiate eyes with subclinical keratoconus from normal eyes with a sensitivity of 67.6%, specificity of 83.3%, and area under the receiver operating characteristic curve (AUC) of 0.81. Combining the magnitudes of these maximum alterations with the LCI for the LCES yielded a sensitivity of 90.0% and a specificity of 74.4% for differentiating eyes with subclinical keratoconus from normal eyes (AUC: 0.91)., Conclusions: The LCI can assist in differentiating eyes with subclinical keratoconus from normal eyes. The LCES is a potential new index to assist in a confirmatory test of eyes with subclinical keratoconus. [ J Refract Surg . 2022;38(1):35-42.] .

Purpose: Mitochondrial DNA (mtDNA) variations have been implicated in various cancer types. Several attempts have been made in benign parathyroid adenoma (PA); however, mtDNA variants and copy number alterations have not been investigated in parathyroid carcinoma (PC). The present study aimed to explore the variations in the mitochondrial genome in parathyroid neoplasms., Methods: In this study, ultradeep targeted sequencing of mtDNA was performed in 12 cases with PC and 25 cases with PA. Germline and somatic variants in the mitochondrial genome were analysed according to clinical features. The mtDNA copy number relative to nuclear DNA was measured., Results: A total of 821 germline variants and 23 somatic mutations were identified. All 160 germline nonsynonymous variants in the coding sequence (CDS) were predicted to be likely benign, and germline variants frequently occurred (26.3%) in the displacement loop region. Tumour somatic mutation in a CDS with heteroplasmic factor (HF) >0.8 showed a higher mtDNA copy number (p = 0.039). Using Spearman's rank test, tumour mtDNA copy number revealed a positive correlation with serum levels of intact parathyroid hormone and calcium., Conclusion: Our results demonstrate that null recurrent mtDNA mutational hotspots were PC specific. An increased mtDNA copy number in parathyroid neoplasms was associated with somatic CDS mutations with a high HF and major clinical features. Larger cohort investigations should be performed in future analyses., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Accumulation of lipid droplets (LDs) induces cardiac dysfunctions in type 2 diabetes patients. Recent studies have shown that hydrogen sulphide (H 2 S) ameliorates cardiac functions in db/db mice, but its regulation on the formation of LDs in cardiac tissues is unclear. Db/db mice were injected with NaHS (40 μmol·kg -1 ) for twelve weeks. H9c2 cells were treated with high glucose (40 mmol/L), oleate (200 µmol/L), palmitate (200 µmol/L) and NaHS (100 µmol/L) for 48 hours. Plasmids for the overexpression of wild-type Hrd1 and Hrd1 mutated at Cys115 were constructed. The interaction between Hrd1 and DGAT1 and DGAT2, the ubiquitylation level of DGAT1 and 2, the S-sulfhydration of Hrd1 were measured. Exogenous H 2 S ameliorated the cardiac functions, decreased ER stress and reduced the number of LDs in db/db mice. Exogenous H 2 S could elevate the ubiquitination level of DGAT 1 and 2 and increased the expression of Hrd1 in cardiac tissues of db/db mice. The S-sulfhydration of Hrd1 by NaHS enhanced the interaction between Hrd1 and DGAT1 and 2 to inhibit the formation of LD. Our findings suggested that H 2 S modified Hrd1 S-sulfhydration at Cys115 to reduce the accumulation of LDs in cardiac tissues of db/db mice., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: The aim of this paper was to identify an immunotherapy-sensitive subtype for estrogen receptor-positive breast cancer (ER+ BC) patients by exploring the relationship between cancer genetic programs and antitumor immunity via multidimensional genome-scale analyses. Methods: Multidimensional ER+ BC high-throughput data (raw count data) including gene expression profiles, copy number variation (CNV) data, single-nucleotide polymorphism mutation data, and relevant clinical information were downloaded from The Cancer Genome Atlas to explore an immune subtype sensitive to immunotherapy using the Consensus Cluster Plus algorithm based on multidimensional genome-scale analyses. One ArrayExpress dataset and eight Gene Expression Omnibus (GEO) datasets (GEO-meta dataset) as well as the Molecular Taxonomy of Breast Cancer International Consortium dataset were used as validation sets to confirm the findings regarding the immune profiles, mutational features, and survival outcomes of the three identified immune subtypes. Moreover, the development trajectory of ER+ BC patients from the single-cell resolution level was also explored. Results: Through comprehensive bioinformatics analysis, three immune subtypes of ER+ BC (C1, C2, and C3, designated the immune suppressive, activation, and neutral subtypes, respectively) were identified. C2 was associated with up-regulated immune cell signatures and immune checkpoint genes. Additionally, five tumor-related pathways (transforming growth factor, epithelial-mesenchymal transition, extracellular matrix, interferon-γ, and WNT signaling) tended to be more activated in C2 than in C1 and C3. Moreover, C2 was associated with a lower tumor mutation burden, a decreased neoantigen load, and fewer CNVs. Drug sensitivity analysis further showed that C2 may be more sensitive to immunosuppressive agents. Conclusion: C2 (the immune activation subtype) may be sensitive to immunotherapy, which provides new insights into effective treatment approaches for ER+ BC., 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. The reviewer WC declared a shared affiliation, with one of the authors, HC, to the handling editor at time of review., (Copyright © 2021 Ma, Chen, Yang, Ke, Wang, Huang and Li.)

Background: Minimal change disease is a common cause of nephrotic syndrome in adults. Higher relapse rate put patients at risk of steroids toxicity due to long-term exposure. Rituximab has been suggested to maintain long time remission and withdraw steroids and other immunosuppressants with fewer adverse events. However, optimal dose and dosing interval have not been explored., Methods: Twenty-five patients were enrolled from 2017-10 to 2020-03 in Nanfang Hospital in China. Clinical and biological data were extracted from medical records and laboratory databases. Therapy composed of 375mg/m 2 rituximab once three weeks for 3 dose and corticosteroid was applied. Complete remission was defined as reduction of proteinuria to 0.3g/d. Remission rate, relapse rate, steroids used before and after rituximab therapy and adverse effects were documented at a mean time of 14.71 months., Results: Twenty-two patients achieved complete remission for an average of 3.26 months and only 3 patients experienced one relapse respectively during the follow-up period. The mean remission maintenance time was 11.6 months, and was 5 months after steroids withdrawal. Steroids dose at last follow-up was 6.09mg/d, which was significantly reduced compared to 28.15mg/d before rituximab. Relapse rate before and after rituximab was 1.43 and 0.1, respectively. Only four minor adverse events were recorded., Conclusions: Therapy consisted of 375mg/m 2 rituximab once three weeks for 3 dose combined with corticosteroid is effective in inducing remission in adult patients with minimal change disease. Both of the relapse rate and dose of steroids used are significantly decreased with fewer side effects.

Objectives: To analyze the clinical characteristics and renal pathological manifestations of patients with monoclonal gammopathy (MG) and kidney injury. Methods: This was a multicenter retrospective cohort study conducted at four tertiary hospitals in China. The study population comprised patients with MG admitted from January 1 2013 to December 31 2020. Hospitalization records, laboratory data, and kidney biopsy reports of all patients were collected from the electronic hospital information systems. The study outcomes included kidney disease progression and major hemorrhagic complications after kidney biopsy. Results: We identified 1,164 patients with MG, 782 (67.2%) of whom had underlying kidney injury. Of 101 patients who underwent kidney biopsy, 16 had malignant neoplasms. Amyloid nephropathy was the most common finding ( n = 34, 33.7%), followed by membranous nephropathy ( n = 18, 17.8%) and membranoproliferative nephritis ( n = 8, 7.9%). Among 85 patients with non-malignant hematologic conditions who underwent kidney biopsy, 43 had MG of renal significance (MGRS) related lesions and 42 had MG-unrelated lesions. The risk of kidney disease progression was higher in patients with kidney injury than in patients without kidney injury. Conclusion: Among patients with MG and kidney injury, only 12.9% underwent kidney biopsy and more than 40% of these patients had MG-unrelated lesions. A kidney biopsy is safe and essential to maximize the possibility of correct diagnosis for patients with clinically suspected MG of renal significance (MGRS)., Competing Interests: LW and XL were employed by the company Kingmed Diagnostic Laboratory Ltd, Guangzhou, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2021 Nie, Wang, Wan, Kong, Ou, Jia, Zhang, Luo, Liu, Wang, Cao, Chen, Zhao, Chan and Wang.)

Purpose: Hyperparathyroidism is the third most common endocrine disease. Parathyroid adenoma (PA) accounts for approximately 85% of cases of primary hyperparathyroidism, but the molecular mechanism is not fully understood. Herein, we aimed to investigate the genetic and transcriptomic profiles of sporadic PA., Methods: Whole-exome sequencing (WES) and transcriptome sequencing (RNA-seq) of 41 patients with PA and RNA-seq of 5 normal parathyroid tissues were performed. Gene mutations and characterized expression changes were identified. To elucidate the molecular mechanism underlying PA, unsupervised consensus clustering of RNA-seq data was performed. The correlations between the sequencing data and clinicopathological features of these patients were analyzed., Results: Previously reported PA driver gene mutations, such as MEN1 (9/41), mTOR (4/41), ZFX (3/41), CASR (3/41), EZH2 (2/41) and FAT1 (2/41), were also identified in our cohort. Furthermore, somatic mutation of EZH1 , which had not been reported in PA, was found in 4 samples. RNA-seq showed that the expression levels of 84 genes were upregulated and 646 were downregulated in PA samples compared with normal samples. Unsupervised clustering analysis of RNA-seq data clustered these patients into 10 subgroups related to mutation or abnormal expression of a group of potential pathogenic genes., Conclusion: MEN1 , EZH2 , CASR , EZH1, ZFX , mTOR and FAT1 mutations in PA were revealed. According to the RNA-seq data clustering analysis, cyclin D1, β-catenin, VDR, CASR and GCM2 may be important factors contributing to the PA gene expression profile., 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 Hu, Zhang, Wang, Cui, Li, Wang, Hua and Liao.)

Aim: This study aimed to identify the epidemiological characteristics and transmission dynamics of paediatric cases., Methods: Information on 1369 paediatric cases with COVID-19 from 8 December 2019 to 7 March 2020 in Hubei province was extracted from the National Infectious Disease Surveillance System. The analysis included epidemic curves, temporal-spatial distribution, clinical classification and interval times between onset and diagnosis., Results: Among 1369 paediatric cases, the median age was 9 years and 58.2% of them were males. The proportion of severe and critical cases in children was lower than that in adults and the proportion of asymptomatic cases in children was five times greater than for adult cases. The first paediatric case was reported on 2 January 2020, and the daily number of new paediatric cases remained high from 1 February through to 22 February. The epidemiological curve of paediatric cases lagged behind that of adults by 19 days, and the first spike of the epidemic curve in senior high school students occurred 1 week earlier than in other paediatric groups. The proportion of clustered cases among children was about twice that for adults. The median of the interval in paediatric cases between onset and diagnosis, isolation and notification were 3, 0 and 3 days, respectively, and all of those were significantly shorter than in adults., Conclusions: The epidemic curve of child cases lagged behind that of adult cases by 19 days, and the major form of transmission observed was in clusters., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Escalating global water scarcity necessitates high-performance desalination membranes, for which fundamental understanding of structure-property-performance relationships is required. In this study, we comprehensively assess the ionization behavior of nanoporous polyamide selective layers in state-of-the-art nanofiltration (NF) membranes. In these films, residual carboxylic acids and amines influence permeability and selectivity by imparting hydrophilicity and ionizable moieties that can exclude coions. We utilize layered interfacial polymerization to prepare physically and chemically similar selective layers of controlled thickness. We then demonstrate location-dependent ionization of carboxyl groups in NF polyamide films. Specifically, only surface carboxyl groups ionize under neutral pH, whereas interior carboxyl ionization requires pH >9. Conversely, amine ionization behaves invariably across the film. First-principles simulations reveal that the low permittivity of nanoconfined water drives the anomalous carboxyl ionization behavior. Furthermore, we report that interior carboxyl ionization could improve the water-salt permselectivity of NF membranes over fourfold, suggesting that interior charge density could be an important tool to enhance the selectivity of polyamide membranes. Our findings highlight the influence of nanoconfinement on membrane transport properties and provide enhanced fundamental understanding of ionization that could enable novel membrane design., Competing Interests: The authors declare no competing interest.

Parathyroid carcinoma (PC) is a rare endocrine malignancy with poor outcomes. Although some mutations such as CDC73 have been found in patients, the molecular mechanism of PC still needs extensive data to clarify. Whole-genome sequencing (WGS) was performed with frozen samples from 23 PC patients. Peripheral leukocytes were collected from 14 patients and served as controls. Somatic and germline gene alterations, copy number abnormalities and structural variants were detected. Inactivating CDC73 mutations were identified in 39.1% of patients, but only one germline inactivating mutation was found. Other cancer-related mutations identified in more than one case were MAF (2/23), NEB (6/23), NCOR1 (2/23), TTK (2/23), GRIN3A (4/23), TRIO (2/23), MAP1B (2/23), TJP2 (2/23) and FAM20A (2/23). In the seven wild-type CDC73 samples, the mutated genes were enriched in pathways involving antigen presentation, allograft rejection or autoimmune disease. More copy number variants were found in patients with cancer recurrence (P = .006) and CDC73 mutations (P = .022) than in those without these characteristics. PIK3CA loss was found in one sample, which also harboured a CDC73 mutation. Gene alterations in the PI3K/AKT/mTOR pathway were found in 78.3% (18/23) of tumours. The most prominent cancer-predisposing mutations were PDE4DIP (15/23), MAP3K1 (13/23) and CDC42EP1 (10/23). In conclusion, the PI3K/AKT/mTOR pathway may be pivotal in PC. CDC73 mutation correlated with an increased mutational burden and tumour relapse. PC patients with wild-type CDC73 harboured mutations relevant to antigen presentation and autoimmune diseases. A molecular classification based on the CDC73 mutation may help to manage follow-up and therapy for PC patients., (© 2020 UICC.)

CDHR5 has been reported to play key roles in carcinogenesis of various cancers, but its roles in pancreatic cancer have not been reported. The present study was designed to investigate its clinical value in pancreatic ductal adenocarcinoma (PDAC). Tissue microarray-based immunohistochemistry was performed to analyse the correlation between CDHR5 expression and clinical and pathological features of PDAC, as well as the CDHR5 expression during tumour progression. Cell function assays were performed to investigate CDHR5's effects on PDAC cells. Moreover, qRT-PCR was applied to investigate the expression of CDHR5 isoforms in PDAC cells. Expression of CDHR5 was higher on the membrane of PDAC cells. This high expression level was associated with shorter overall survival of PDAC patients and was identified as an independent prognostic factor for overall survival by multivariate Cox regression analysis. In addition, expression level of CDHR5 presented an increased trend in the occurrence and progression of PDAC. Cell experiment suggested that CDHR5 could notably promote invasion and migration of PDAC cells. Moreover, analysis of CDHR5 isoforms indicated CDHR5-L was the major isoform expressed in PDAC cell lines. CDHR5 appears to be a promising and novel prognostic factor for PDAC, and its promotion in PDAC metastasis might be ascribed to the isoform CDHR5-L., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Purpose: To develop an automated classification system using a machine learning classifier to distinguish clinically unaffected eyes in patients with keratoconus from a normal control population based on a combination of Scheimpflug camera images and ultra-high-resolution optical coherence tomography (UHR-OCT) imaging data., Methods: A total of 121 eyes from 121 participants were classified by 2 cornea experts into 3 groups: normal (50 eyes), with keratoconus (38 eyes) or with subclinical keratoconus (33 eyes). All eyes were imaged with a Scheimpflug camera and UHR-OCT. Corneal morphological features were extracted from the imaging data. A neural network was used to train a model based on these features to distinguish the eyes with subclinical keratoconus from normal eyes. Fisher's score was used to rank the differentiable power of each feature. The receiver operating characteristic (ROC) curves were calculated to obtain the area under the ROC curves (AUCs)., Results: The developed classification model used to combine all features from the Scheimpflug camera and UHR-OCT dramatically improved the differentiable power to discriminate between normal eyes and eyes with subclinical keratoconus (AUC = 0.93). The variation in the thickness profile within each individual in the corneal epithelium extracted from UHR-OCT imaging ranked the highest in differentiating eyes with subclinical keratoconus from normal eyes., Conclusion: The automated classification system using machine learning based on the combination of Scheimpflug camera data and UHR-OCT imaging data showed excellent performance in discriminating eyes with subclinical keratoconus from normal eyes. The epithelial features extracted from the OCT images were the most valuable in the discrimination process. This classification system has the potential to improve the differentiable power of subclinical keratoconus and the efficiency of keratoconus screening., Competing Interests: Competing interestsAll authors of the manuscript have no proprietary interest in any materials or methods described within this article., (© The Author(s) 2020.)

Muscle atrophy occurs in many pathological states, including cancer, diabetes and sepsis, whose results primarily from accelerated protein degradation and activation of the ubiquitin-proteasome pathway. Expression of Muscle RING finger 1 (MuRF1), an E3 ubiquitin ligase, was increased to induce the loss of muscle mass in diabetic condition. However, hydrogen sulphide (H 2 S) plays a crucial role in the variety of physiological functions, including antihypertension, antiproliferation and antioxidant. In this study, db/db mice and C2C12 myoblasts treated by high glucose and palmitate and oleate were chose as animal and cellular models. We explored how exogenous H 2 S attenuated the degradation of skeletal muscle via the modification of MuRF1 S-sulfhydration in db/db mice. Our results show cystathionine-r-lyase expression, and H 2 S level in skeletal muscle of db/db mice was reduced. Simultaneously, exogenous H 2 S could alleviate ROS production and reverse expression of ER stress protein markers. Exogenous H 2 S could decrease the ubiquitination level of MYOM1 and MYH4 in db/db mice. In addition, exogenous H 2 S reduced the interaction between MuRF1 with MYOM1 and MYH4 via MuRF1 S-sulfhydration. Based on these results, we establish that H 2 S prevented the degradation of skeletal muscle via MuRF1 S-sulfhydration at the site of Cys44 in db/db mice., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: To quantitatively assess anterior chamber angle (ACA) structure by anterior segment optical coherence tomography (AS-OCT) and develop a model to evaluate angle width as defined by gonioscopy., Methods: The ACAs of each quadrant were evaluated by gonioscopy, classified by the Scheie grading system, and assigned into one of the three grades: small angle (SA), moderate angle (MA), and large angle (LA). The eyes were imaged by AS-OCT, and ACA structural parameters including angle opening distance at the scleral spur (AODSS) and at 750 μm anterior to the scleral spur (AOD750), trabecular-iris space area at 750 μm anterior to the scleral spur (TISA750), and a newly defined parameter "light intersection distance" (LID), were measured. The ACA structural data were used to construct an ordered logistic regression model for assignment of ACAs to one of the three angle grades. The validity of the model was then tested., Results: A total of 169 quadrants from 53 subjects were included in the analysis, of which 111 quadrants were included in the modeling data and 58 in the testing data. In pairwise comparisons of SA, MA, and LA by ANOVA, the measured parameters were as follows: AOD750 (0.174 ± 0.060 vs. 0.249 ± 0.068 vs. 0.376 ± 0.114 mm; P  < 0.001), TISA750 (0.075 ± 0.035 vs. 0.117 ± 0.036 vs. 0.181 ± 0.062 mm 2 ; P  < 0.001), and LID (- 0.300 ± 0.187 vs. -0.085 ± 0.170 vs. 0.122 ± 0.156 mm; P  < 0.001). The ACA grading model based on LID showed a relatively high correction rate of 72.4%, and the model efficiency, calculated using the receiver operating characteristic, showed an area under the curve of 0.740. Weighted kappa statistics showed a good agreement for multiple ACA grades (0.772)., Conclusions: The AS-OCT-based multiple ACA grades model was demonstrated as a non-contact approach for ACA assessment with high speed and high spatial resolution, providing guidance for diagnosis of angle closure., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer-related death in young women. Several prognostic and predictive transcription factor (TF) markers have been reported for BC; however, they are inconsistent due to small datasets, the heterogeneity of BC, and variation in data pre-processing approaches. This study aimed to identify an effective predictive TF signature for the prognosis of patients with BC. We analyzed the TF data of 868 patients with BC in The Cancer Genome Atlas (TCGA) database to investigate TF biomarkers relevant to recurrence-free survival (RFS). These patients were separated into training and internal validation datasets, with GSE2034 and GSE42568 used as external validation sets. A nine-TF signature was identified as crucially related to the RFS of patients with BC by univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and multivariate Cox proportional hazard analysis in the training dataset. Kaplan-Meier analysis revealed that the nine-TF signature could significantly distinguish high- and low-risk patients in both the internal validation dataset and the two external validation sets. Receiver operating characteristic (ROC) analysis further verified that the nine-TF signature showed a good performance for predicting the RFS of patients with BC. In addition, we developed a nomogram based on risk score and lymph node status, with C-index, ROC, and calibration plot analysis, suggesting that it displays good performance and clinical value. In summary, we used integrated bioinformatics approaches to identify an effective predictive nine-TF signature which may be a potential biomarker for BC prognosis., (Copyright © 2020 Chen, Ma, Yang, Wang, Li and Huang.)

Purpose: The purpose of this study was to measure alterations of inner retinal microvascular density and outer retinal sublayer thicknesses in pathological myopia, and to correlate the measured parameters with best corrected visual acuity (BCVA)., Methods: Optical coherence tomography (OCT) and OCT angiography (OCTA) images of 21 control, 48 simple high myopia, and 22 pathological myopia eyes were analyzed to quantify the thicknesses of the outer retinal sublayers and the density of the inner retinal microvascular network that includes the superficial retinal capillary plexus (SRCP) and deep retinal capillary plexus (DRCP). Retinal sublayer thicknesses and microvascular densities were compared among the three groups, and correlations of sublayer thicknesses and microvascular densities with BCVA were determined., Results: In pathological myopia, density of the DRCP, thicknesses of myoid and ellipsoid zone (MEZ), interdigitation zone and retinal pigment epithelium/Bruch complex (IZ + RPE), and choroid were lower than in simple high myopia (P < 0.05). The decreased DRCP density was correlated with thinner MEZ and IZ+RPE in pathological myopia (P < 0.05), but not in simple high myopia (P > 0.05). Simple linear regression showed that axial length, female, thicknesses of outer plexiform layer (OPL), MEZ, IZ + RPE, choroid, and density of the SRCP and DRCP were correlated with BCVA. In multiple regression analysis, worse BCVA was associated only with thinner MEZ, thinner choroid, and decreased DRCP (P < 0.05)., Conclusions: Alteration of inner retinal microvascular density and outer retinal sublayer thicknesses occurred in pathological myopia, especially decreased DRCP and thinner MEZ, which were significantly associated with worse BCVA.

Background : C-X-C motif chemokine 5 (CXCL5) is an important attractant for immune cell accumulation in tumor tissues. Recent evidence has shown that CXCL5 could promote carcinogenesis and cancer progression in a variety of cancer types. However, the relationships between CXCL5, immune cell infiltration and pancreatic ductal adenocarcinoma (PDAC) remain largely unknown. This study aimed to explore the role and regulative mechanism of CXCL5 in PDAC carcinogenesis. Materials and Methods : The expression of CXCL5 in PDAC was analyzed based on online databases and tissue microarray staining, and Western blotting of CXCL5 in PDAC cell lines and patient samples. The correlation between CXCL5 expression and clinicopathological features, prognosis and immune cell infiltration in tumor tissues was analyzed. Results : High expression of CXCL5 was observed both in PDAC tumor tissue and PDAC cell lines, compared to normal pancreas tissues and normal ductal epithelium cells. High CXCL5 expression in tumor tissues was positively correlated with an advanced T stage (p=0.036), a positive tumor lymph node metastasis (p=0.014), a poor differentiation status (p=0.003) and a poor prognosis (p=0.001). Combination of CA242 and CXCL5 expression (p<0.0001) served as a better prognostic factor than CA242 alone (p=0.006). In addition, PDAC patients with high CXCL5 expression had more intratumoral M2 polarized macrophages (p=0.0248), neutrophils (p=0.0068) and IgG + plasma cells (p=0.0133) than patients with low CXCL5 expression. Conclusions : The expression of CXCL5 is elevated in pancreatic cancer cells. High CXCL5 expression is positively correlated with poor survival and the increased infiltration of several types of immune suppressive cells. Thus, CXCL5 could be a promising therapeutic target for PDAC immunotherapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Tumor-associated macrophages (TAMs) are versatile immune cells that promote a variety of malignant behaviors of pancreatic cancer. CD59 is a GPI-anchored membrane protein that prevents complement activation by inhibiting the formation of the membrane attack complex, which may protect cancer cells from complement-dependent cytotoxicity (CDC). The interactions between CD59, TAMs and pancreatic cancer remain largely unknown. A tissue microarray of pancreatic cancer patients was used to evaluate the interrelationship of CD59 and TAMs and their survival impacts were analyzed. In a coculture system, THP-1 cells were used as a model to study the function of TAMs and the roles of pancreatic cancer-educated macrophages in regulating the expression of CD59 in pancreatic cancer cells were demonstrated by real-time PCR, western blot and immunofluorescence staining. The effects of macrophages on regulating CDC in pancreatic cancer cells were demonstrated by an in vitro study. To explore the potential mechanisms, RNA sequencing of pancreatic cancer cells with or without co-culture of THP-1 macrophages was performed, and the results showed that the IL-6R/STAT3 signaling pathway might participate in the regulation, which was further demonstrated by target-siRNA transfection, antibody neutralization and STAT3 inhibitors. Our data revealed that the infiltration of TAMs and the expression of CD59 of pancreatic cancer were paralleled, and higher infiltration of TAMs and higher expression of CD59 predicted worse survival of pancreatic cancer patients. Pancreatic cancer-educated macrophages could protect cancer cells from CDC by up-regulating CD59 via the IL-6R/STAT3 signaling pathway. These findings uncovered the novel mechanisms between TAMs and CD59, and contribute to providing a new promising target for the immunotherapy of pancreatic cancer.

Many bacteria and some archaea produce the second messenger cyclic diadenosine monophosphate (c-di-AMP). c-di-AMP controls the uptake of osmolytes in Firmicutes, including the human pathogen Listeria monocytogenes , making it essential for growth. c-di-AMP is known to directly regulate several potassium channels involved in osmolyte transport in species such as Bacillus subtilis and Streptococcus pneumoniae , but whether this same mechanism is involved in L. monocytogenes , or even whether similar ion channels were present, was not known. Here, we have identified and characterized the putative L. monocytogenes' potassium transporters KimA, KtrCD, and KdpABC. We demonstrate that Escherichia coli expressing KimA and KtrCD, but not KdpABC, transport potassium into the cell, and both KimA and KtrCD are inhibited by c-di-AMP in vivo For KimA, c-di-AMP-dependent regulation requires the C-terminal domain. In vitro assays demonstrated that the dinucleotide binds to the cytoplasmic regulatory subunit KtrC and to the KdpD sensor kinase of the KdpDE two-component system, which in Staphylococcus aureus regulates the corresponding KdpABC transporter. Finally, we also show that S. aureus contains a homolog of KimA, which mediates potassium transport. Thus, the c-di-AMP-dependent control of systems involved in potassium homeostasis seems to be conserved in phylogenetically related bacteria. Surprisingly, the growth of an L. monocytogenes mutant lacking the c-di-AMP-synthesizing enzyme cdaA is only weakly inhibited by potassium. Thus, the physiological impact of the c-di-AMP-dependent control of potassium uptake seems to be less pronounced in L. monocytogenes than in other Firmicutes., (© 2019 Gibhardt et al.)

To develop low-cost, high-capacity and long-life anode materials for lithium-ion batteries, glucose-C and F-doped C coated SiO composites with adjustable pore structure (p-SiO@gl-C@F-doped C) are synthesized by facile and scalable methods. The combination of the heterogeneous dual-carbon shells and porous structure significantly promotes the reaction kinetics of the electrode, effectively suppresses and buffers the volume expansion of SiO, and largely enhances the stability of solid electrolyte interface of the electrode. In a half cell, the optimized p-SiO@gl-C@F-doped C (7:3) composite shows a stable discharge capacity of 785 mAh g -1 at a current density of 200 mA g -1 . The discharge capacity is maintained at 772 mAh g -1 after 200 cycles. At a current density of 400 mA g -1 , the electrode shows a discharge capacity of 633 mAh g -1 after 500 cycles, with a capacity degradation of ∼0.0096% per cycle from the 2nd cycle to the 500th cycle. The full cell which is composed of the commercial LiFePO 4 as a cathode and the optimized composite as an anode, exhibits high capacity and good cycling stability., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Parathyroid carcinoma (PC) is a rare endocrine malignancy with a poor prognosis. The optimal surgical procedure and prognostic factors for PC remain controversial. Methods: Clinical information and parafibromin staining results from 53 patients with PC were reviewed retrospectively from 1997 to 2018. Immunohistochemical staining for parafibromin was performed on formalin-fixed, paraffin-embedded tissue samples. The influence of clinical parameters, surgical procedure, and parafibromin staining of tumor tissues on prognosis were evaluated. Results: A total of 53 patients with PC were enrolled in this study. The male to female ratio was 1.94:1. En bloc resection was performed as initial surgery for 18 patients (34.0%), and 35 patients (66.0%) underwent local resection. Parafibromin staining was negative in the tumor tissues of 24 PC patients (45.3%). Thirty-three patients suffered from local recurrence or distant metastasis, and overall mortality was 16/53 at a median follow-up time of 80 months (range, 7 to 282 months). Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio [HR], 4.13; 95% confidence interval [CI], 1.73 to 9.87; P = .001) was related to recurrence or metastasis and that age >50 years (HR, 5.66; 95% CI, 1.58 to 20.31; P = .008) was related to mortality. The extent of resection was not related to recurrence or overall survival. Conclusion: The majority of PC patients have a relatively long survival with multiple recurrences. Absence of parafibromin staining was a factor that influenced PC recurrence. The main factor influencing PC outcomes may be the biological characteristics rather than surgical extent. Abbreviations: CI = confidence interval; DFS = disease-free survival; HR = hazard ratio; OS = overall survival; PC = parathyroid carcinoma; WHO = World Health Organization.

Parathyroid carcinoma (PCa) is a rare endocrine neoplasia that typically has unfavourable outcomes. The contribution of long non-coding RNAs (lncRNAs) to the development of malignant and benign parathyroid tumours remains largely unknown. In this study, we explored transcriptomic profiling of lncRNA and mRNA expression in 6 PCa, 6 parathyroid adenoma (PAd) and 4 normal parathyroid (PaN) tissues. In total, 2641 lncRNA transcripts and 2165 mRNA transcripts were differentially expressed between PCa and PAd. Enrichment analysis demonstrated that dysregulated transcripts were involved mainly in the extracellular matrix (ECM)-receptor interaction and energy metabolism pathways. Bioinformatics analysis suggested that ATF3, ID1, FOXM1, EZH2 and MITF may be crucial to parathyroid carcinogenesis. Series test of cluster analysis segregated differentially expressed lncRNAs and mRNAs into several expression profile models, among which the 'plateau' profile representing components specific to parathyroid carcinogenesis was selected to build a co-expression network. Seven lncRNAs and three mRNAs were selected for quantitative RT-PCR validation in 16 PCa, 41 PAd and 4 PaN samples. Receiver-operator characteristic curves analysis showed that lncRNA PVT1 and GLIS2-AS1 yielded the area under the curve values of 0.871 and 0.860, respectively. Higher hybridization signals were observed in PCa for PVT1 and PAd for GLIS2-AS1. In conclusion, the current evidence indicates that PAd and PCa partially share common signalling molecules and pathways, but have independent transcriptional events. Differentially expressed lncRNAs and mRNAs have intricate interactions and are involved in parathyroid tumourigenesis. The lncRNA PVT1 and GLIS2-AS1 may be new potential markers for the diagnosis of PCa.

Enzymes have evolved to facilitate challenging reactions at ambient conditions with specificity seldom matched by other catalysts. Computational modeling provides valuable insight into catalytic mechanism, and the large size of enzymes mandates multi-scale, quantum mechanical-molecular mechanical (QM/MM) simulations. Although QM/MM plays an essential role in balancing simulation cost to enable sampling with full QM treatment needed to understand electronic structure in enzyme active sites, the relative importance of these two strategies for understanding enzyme mechanism is not well known. We explore challenges in QM/MM for studying the reactivity and stability of three diverse enzymes: i) Mg 2+ -dependent catechol O -methyltransferase (COMT), ii) radical enzyme choline trimethylamine lyase (CutC), and iii) DNA methyltransferase (DNMT1), which has structural Zn 2+ binding sites. In COMT, strong non-covalent interactions lead to long range coupling of electronic structure properties across the active site, but the more isolated nature of the metallocofactor in DNMT1 leads to faster convergence of some properties. We quantify these effects in COMT by computing covariance matrices of by-residue electronic structure properties during dynamics and along the reaction coordinate. In CutC, we observe spontaneous bond cleavage following initiation events, highlighting the importance of sampling and dynamics. We use electronic structure analysis to quantify the relative importance of CHO and OHO non-covalent interactions in imparting reactivity. These three diverse cases enable us to provide some general recommendations regarding QM/MM simulation of enzymes., Competing Interests: The authors declare no competing financial interest.

Parathyroid carcinoma (PC) is a rare endocrine malignancy. Surgical resection is curative for local lesions, while effective therapies are lacking for recurrent or metastatic PCs. To study whether targeted therapies could be applied in recurrent or metastatic PCs, potential therapeutic targets were identified with next-generation sequencing (NGS). DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) sections from 19 recurrent or metastatic PC samples. A panel of 560 genes was sequenced with NGS to identify genomic alterations at an average sequencing depth of 581×. In total, 190 genomic alterations were identified. Nine PC samples (47%) harbored at least one potentially actionable genomic alteration including in the after genes: ROS1 (5/19; 26%), PTEN (3/19; 16%), TSC1 (2/19; 11%), PIK3CA (1/19; 5%), AKT1 (1/19; 5%), MTOR (1/19; 5%), ERBB2 (1/19; 5%), NTRK1 (1/19; 5%), IDH1 (1/19; 5%) and FGFR3 (1/19; 5%). CDC73 mutations were detected in 9/19 (47%) PC samples. Additional recurrent genomic alterations were identified in MSH2 (15/19; 79%), AR (9/19; 47%), BCR (8/19; 42%), SLC45A3 (6/19; 32%), MAGI1 (5/19; 26%), ZNF521 (4/19; 21%), KMT2C (4/19; 21%) and NOTCH4 (4/19; 21%). Our study identified a relatively high frequency of potentially actionable genomic alterations in PC patients in a Chinese population for the first time. A series of recurrent mutant genes was detected as well. Our study contributes to both the selection of novel targeted therapies for PC and further molecular understanding of this refractory malignancy., (© 2018 UICC.)

Oxide glasses are typically described as having a random, disordered skeleton of network-forming polyhedra that are depolymerized by network-modifying cations. However, the existence of local heterogeneity or clustering within the network-forming and network-modifying species remains unclear. Here, based on molecular dynamics simulations, we investigate the atomic structure of a series of borosilicate glasses. We show that the network-modifying cations exhibit some level of clustering that depends on composition-in agreement with Greaves' modified random network model. In addition, we demonstrate the existence of some mutual avoidance among network-forming atoms, which echoes the Loewenstein avoidance principle typically observed in aluminosilicate phases. Importantly, we demonstrate that the degree of heterogeneity in the spatial distribution of the network modifiers is controlled by the level of ordering in the interconnectivity of the network formers. Specifically, the mutual avoidance of network formers is found to decrease the propensity for modifier clustering.

Purpose: Parathyroid carcinoma (PCa) is a rare endocrine malignancy with poor prognosis and is often difficult to accurately diagnose both before and after surgery. Dysregulated microRNA (miRNA) levels have been identified in PCa using a limited number of samples. The aim of the present study was to verify a group of miRNA markers in a new series of samples to explore their potential significance in PCa diagnosis., Methods: A total of 58 tissue samples, including 17 PCa lesions and 41 sporadic parathyroid adenomas (PAds), were obtained from 56 primary hyperparathyroidism (pHPT) patients. Candidate miRNAs (miR-139-5p, miR-155-5p, miR-222-3p, miR-26b-5p, miR-296-5p, miR-30b-5p, miR-372-3p, miR-503-5p, miR-517c-3p, miR-7-5p, and miR-126-5p) were quantified by TaqMan real-time quantitative PCR assays., Results: Up-regulated miR-222 (p = 0.041) levels and down-regulated miR-139 (p = 0.003), miR-30b (p < 0.001), miR-517c (p = 0.038), and miR-126* (p = 0.002) levels were found in PCa relative to PAd. Binary logistic regression analysis showed that miR-139 and miR-30b were the best diagnostic markers. The combination of miR-139 and miR-30b yielded an area under the receiver operating characteristic curve of 0.888. Additionally, serum calcium (r s  = -0.518, p < 0.001), intact parathyroid hormone (iPTH) (r s  = -0.495, p < 0.001), and alkaline phosphatase (ALP) (r s  = -0.523, p < 0.001) levels were negatively correlated with miR-30b levels., Conclusions: miR-139, miR-222, miR-30b, miR-517c, and miR-126* were differentially expressed between PCa and PAd. The combined analysis of miR-139 and miR-30b may be used as a potential diagnostic strategy for distinguishing PCa from PAd.

An alternatively spliced transcription factor that participates in the unfolded protein response, XBP1 is a novel protein involved in cancer progression and outcome. This study aimed to investigate the relationship of spliced XBP1 (XBP1s) with the clinicopathological characteristics and prognosis of breast cancer by using tissue-microarray analysis. A consecutive series of 170 patients with breast cancer diagnosed between 2001 and 2004 in hospitals in eastern and southern China were included. Immunohistochemical staining for XBP1s was performed, and the expression of XBP1s was separately examined in nuclei and cytoplasm. We found that a higher expression of XBP1s in nuclei strongly correlated with poorer survival (46.7% versus 75%, P =0.018); however, the expression of XBP1s in the cytoplasm had no relationship with survival. Multivariate Cox regression analysis indicated that the expression of XBP1s was not an independent prognostic factor (RR 2.074, 95% CI 0.909-4.736; P =0.083). None of the other clinicopathological characteristics - age, pathology grade, T stage, N stage, TNM stage, estrogen receptor, progesterone receptor, or HER2 status - was found to be correlated with XBP1s expression in the nuclei. In conclusion, independently of other clinicopathological factors, the nuclear expression of XBP1s is correlated with shorter breast cancer survival; however, whether nuclear XBP1s is an independent prognostic biomarker needs to be confirmed by further studies with larger samples and detailed sample stratification., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Wireless sensor networks are widely used to acquire environmental parameters to support agricultural production. However, data variation and noise caused by actuators often produce complex measurement conditions. These factors can lead to nonconformity in reporting samples from different nodes and cause errors when making a final decision. Data fusion is well suited to reduce the influence of actuator-based noise and improve automation accuracy. A key step is to identify the sensor nodes disturbed by actuator noise and reduce their degree of participation in the data fusion results. A smoothing value is introduced and a searching method based on Prim's algorithm is designed to help obtain stable sensing data. A voting mechanism with dynamic weights is then proposed to obtain the data fusion result. The dynamic weighting process can sharply reduce the influence of actuator noise in data fusion and gradually condition the data to normal levels over time. To shorten the data fusion time in large networks, an acceleration method with prediction is also presented to reduce the data collection time. A real-time system is implemented on STMicroelectronics STM32F103 and NORDIC nRF24L01 platforms and the experimental results verify the improvement provided by these new algorithms.

Despite the dramatic increase of viscosity as temperature decreases, some glasses are known to feature room-temperature relaxation. However, the structural origin of this phenomenon-known as the "thermometer effect"-remains unclear. Here, based on accelerated molecular dynamics simulations of alkali silicate glasses, we show that both enthalpy and volume follow stretched exponential decay functions upon relaxation. However, we observe a bifurcation of their stretching exponents, with β=3/5 and 3/7 for enthalpy and volume relaxation, respectively, in agreement with Phillips's topological diffusion-trap model. Based on these results, we demonstrate that the thermometer effect is a manifestation of the mixed alkali effect. We show that relaxation is driven by the existence of stressed local structural instabilities in mixed alkali glasses. This driving force is found to be at a maximum when the concentrations of each alkali atom equal each other, which arises from a balance between the concentration of each alkali atom and the magnitude of the local stress that they experience.

Upon loading, atomic networks can feature delayed irreversible relaxation. However, the effect of composition and structure on relaxation remains poorly understood. Herein, relying on accelerated molecular dynamics simulations and topological constraint theory, we investigate the relationship between atomic topology and stress-induced structural relaxation, by taking the example of creep deformations in calcium silicate hydrates (C─S─H), the binding phase of concrete. Under constant shear stress, C─S─H is found to feature delayed logarithmic shear deformations. We demonstrate that the propensity for relaxation is minimum for isostatic atomic networks, which are characterized by the simultaneous absence of floppy internal modes of relaxation and eigenstress. This suggests that topological nanoengineering could lead to the discovery of nonaging materials.

Objective To summarize our experiences in the diagnosis and prognosis of different subtypes of primary thyroid lymphoma (PTL). Methods The clinical data of 27 PTL patients who were treated in our hospital from January 1998 to December 2014 were retrospectively analyzed. The pathological types of these patients included B cell lymphoma unclassifiable (BCLU) (n=5),mucosa-associated lymphiod tissue lymphoma (MALT) (n=9),diffuse large B cell lymphoma (DLBCL) (n=12),and T cell lymphoma (n=1). Results Of all these 27 cases,the most common clinical symptom was painless swelling of the neck (n=21,77.8%). Of 7 patients who had received preoperative fine needle biopsy,lymphoma was suspected in 2 cases (28.6%). Among these 7 cases,the positive rate of suspicious lymphoma was 66.7% in 3 DLBCL patients,0 in 3 MALT patients,and 0 in 1 BCLU paitent. Also,25 patients underwent intraoperative frozen pathological examination,which revealed lymphoma or suspicious lymphoma in 16 cases (64.0%); in these patients,the positive rate was 66.7% for BCLU,77.8% for MALT,58.3% for DLBCL,and 0 for T-cell lymphomas. The overall survival was (89.3±12.4) months,and the overall 5-year survival rate was 61.6%. The estimated survival in symptomatic group was 31.6 months,which was significantly shorter than that in asymptomatic group (97.9 months) (P=0.032). Other factors including age,sex,tumor size,tumor stage,international prognostic index,tracheal compression,lactate dehydrogenase,residual tumor,and pathological type showed no significant effect on survival(all P>0.05). Conclusions DLBCL has the highest fine needle biopsy positive rate,MALT has the highest frozen pathological positive rate,and intraoperative frozen pathology has more malignant results than the preoperative fine needle biopsy in the diagnosis. The accompanying lymphoma symptoms may be an adverse prognostic factor.

Riemerella anatipestifer is an important bacterial pathogen in ducks and causes heavy economic losses in the duck industry. However, the pathogensis of this bacterium is poorly understood. In this study, a putative outer membrane hemin receptor gene B739&#95;1208 in R. anatipestifer CH-1 was deleted to determine the relationship between iron uptake and virulence. The R. anatipestifer CH-1ΔB739&#95;1208 mutants grew significantly more slowly than the wild-type bacteria in TSB liquid medium. Further characterization revealed that the R. anatipestifer CH-1ΔB739&#95;1208 mutants were deficient in iron uptake. Animal experiments indicated that the median lethal dose of the wild-type RA-CH-1 in ducklings was 3.89×10 8 , whereas the median lethal dose of the R. anatipestifer CH-1ΔB739&#95;1208 mutant in ducklings was 5.68×10 9 . The median lethal dose of the complementation strain in ducklings was 9.84×10 8 . Additional analysis indicated that bacterial loads in the blood, liver, and brain tissues in the R. anatipestifer CH-1ΔB739&#95;1208-infected ducklings were significantly decreased compared to those in the wild-type R. anatipestifer CH-1 infected ducklings. In a duck co-infection model with R. anatipestifer CH-1 and R. anatipestifer CH-1ΔB739&#95;1208, the R. anatipestifer CH-1B739&#95;1208 mutant was outcompeted by the wild-type R. anatipestifer CH-1 in the blood (P<0.002), livers (P<0.001) and brains (P<0.001) of infected ducks, indicating that B739&#95;1208 gene expression provided a competitive advantage in these organs. Our results demonstrate that the B739&#95;1208 gene is a virulence factor in R. anatipestifer CH-1., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Pancreatic cancer is characterized as inflammatory malignancy with a dismal prognosis. There is abundant intratumoral infiltration of macrophages, and most of these tumor associated macrophages (TAM) are induced to be M2 phenotype. The M2 polarized TAM has been demonstrated to promote progression and induce chemo-resistance of pancreatic cancer. Interleukin (IL)-27 is a novel member of IL-12 cytokine family and its roles in regulation of phenotypes and functions of TAM remain largely unknown. In this study, we demonstrated IL-27 significantly inhibited the M2 macrophages polarization and dampened the proliferation, migration and metastasis of pancreatic cancer cells and as well enhanced the efficacy of gemcitabine. IL-27 could be potential to improve the treatment of pancreatic cancer by targeting M2 polarized TAMs., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Garlic has the charisma of a potent remedy and holds its repute of a therapeutic panacea since the dawn of civilization. An integrated approach was adopted to evaluate the genetic diversity among Chinese garlic cultivars for their antifungal potency as well as allicin content distribution and, furthermore; a bioassay was performed to study the bio-stimulation mechanism of aqueous garlic extracts (AGE) in the growth and physiology of cucumber (Cucumis sativus). Initially, 28 garlic cultivars were evaluated against four kinds of phytopathogenic fungi; Fusarium oxysporum, Botrytis cinerea, Verticillium dahliae and Phytophthora capsici, respectively. A capricious antifungal potential among the selected garlic cultivars was observed. HPLC fingerprinting and quantification confirmed diversity in allicin abundance among the selected cultivars. Cultivar G025, G064, and G074 had the highest allicin content of 3.98, 3.7, and 3.66 mg g(-1), respectively, whereas G110 was found to have lowest allicin content of 0.66 mg g(-1). Cluster analysis revealed three groups on the basis of antifungal activity and allicin content among the garlic cultivars. Cultivar G025, G2011-4, and G110 were further evaluated to authenticate the findings through different solvents and shelf life duration and G025 had the strongest antifungal activity in all conditions. minimum inhibitory concentration and minimum fungicidal concentration of Allicin aqueous standard (AAS) and AGE showed significant role of allicin as primary antifungal substance of AGE. Leaf disk bioassay against P. capsici and V. dahliae to comparatively study direct action of AGE and AAS during infection process employing eggplant and pepper leaves showed a significant reduction in infection percentage. To study the bioactivity of AGE, a bioassay was performed using cucumber seedlings and results revealed that AGE is biologically active inside cucumber seedlings and alters the defense mechanism of the plant probably activating reactive oxygen species at mild concentrations. However, at higher concentrations, it might cause lipid peroxidation and membrane damage which temper the growth of cucumber seedlings. At the outcome of the study, an argument is advanced that current research findings provide bases for cultivar selection in antifungal effectivity as well as genetic variability of the cultivars. Allicin containing AGE can be used in specialized horticultural situations such as plastic tunnel and organic farming as a bio-stimulant to enhance cucumber growth and attenuate fungal degradation of agricultural produce.

Selection of the optimal chemotherapy regimen for an individual cancer patient is challenging. The existing chemosensitivity tests are costly, time-consuming, and not amenable to wide utilization within a clinic. This limitation might be addressed by the recently proposed use of circulating tumor cells (CTCs), which provide an opportunity to noninvasively monitor response to therapy. Over the past few decades, various techniques were developed to capture and recover CTCs, but these techniques were often limited by a capture and recovery performance tradeoff between high viability and high efficiency. In this work, we used anti-epithelial cell adhesion molecule coated aptamer-poly (N-isopropylacrylamide) functionalized silicon nanowire substrates to capture and release epithelial cell adhesion molecule-positive CTCs at 32°C and 4°C, respectively. Then, we applied the nuclease to digest the aptamer to release the captured CTCs (near or at the end of the polymer brush), which cannot be released by heating/cooling process. High viability and purity CTCs could be achieved by decreasing the heating/cooling cycles and enzymatic treatment rounds. Furthermore, the time-saving process is helpful to maintain the morphology and enhance vitality of the recovered CTCs and is beneficial to the subsequent cell culture in vitro. We validated the feasibility of chemosensitivity testing based on the recovered HCC827 cells using an adenosine triphosphate-tumor chemosensitivity assay, and the results suggested that our method can determine which agent and what concentration have the best chemosensitivity for the culturing recovered CTCs. So, the novel method capable of a highly effective capture and recovery of high viability CTCs will pave the way for chemosensitivity testing.

This research was conducted to evaluate the effect of temperature and photoperiod treatments on the bolting and bulb formation of three local garlic cultivars (cvs) in two consecutive years. Naturally vernalized plants of cvs G107, G025 and G064 were transplanted into growth chambers and subjected to various combinations of temperature [T15/10, 15°C/10°C; T20/15, 20°C/15°C and T25/18, 25°C/18°C (day/night)] and photoperiod (L8, 8 h and L14,14 h) treatments. Plant growth, endogenous phytohormone and methyl jasmonate (MeJA) levels, along with the bolting and yield of garlic were evaluated. The experimental results from two consecutive years indicated that higher temperature (20°C or 25°C) and longer photoperiod (14 h) treatments significantly enhanced the garlic bolting, bulbing and cloving with a shorter growth period and a higher bulb weight. Moreover, the endogenous phytohormone and MeJA levels in the test plants were significantly increased by the higher temperature (25°C for the phytohormone level; 20°C for the MeJA level) and longer photoperiod [14 h, except for abscisic acid (ABA), which had the highest level at 8 h] conditions and were decreased by the lowest test temperature (15°C) and shorter photoperiod (8 h, except for ABA) conditions. This response coincided with that of the bulbing index, bolting rate, growth period and bulb weight. In addition, plants treated under the conditions of 20°C/15°C-14 h and 25°C/18°C-14 h produced the highest phytohormone levels (except for ABA) for cvs G025 and G064, respectively, and showed the best bolting and bulbing behavior. It is reasonable to assume that endogenous phytohormone (especially gibberellic acid) and MeJA levels are highly related to garlic bolting and bulbing, which might lead to the different responses of the three studied cultivars to the combination of temperature and photoperiod treatments. Furthermore, cvs G107 and G025 bolt well and have better bulb formation under 20°C-14 h conditions, while the conditions of 25°C-14 h are critical for the bolting and bulbing of cv. G064., (© 2016. Published by The Company of Biologists Ltd.)

In this work, for the first time, magnetic binary metal oxides nanocomposites which integrated Zr and Ti into one entity on an atomic scale on polydopamine coated magnetic graphene (magG/PD/(Zr-Ti)O4 ) was designed and synthesized, and applied to the enrichment of phosphopeptides. The newly prepared magG/PD/(Zr-Ti)O4 composites gathered the advantages of large surface area, superparamagnetism, biocompatibility and the enhanced affinity properties to phosphopeptides. MagG/PD/ZrO2 , magG/PD/TiO2 , as well as the simple physical mixture of them were introduced to compare with magG/PD/(Zr-Ti)O4 composites. High sensitivity (1 pg/μL or 4.0 × 10(-11) M) and selectivity (weight ratio of β-casein and BSA reached up to 1:8000) toward phosphopeptides were also presented for magG/PD/(Zr-Ti)O4 composites. Additionally, mouse brain tissue was chose as the real samples to further investigate the phosphopeptides enrichment ability of this new material., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Interactions of inflammatory cells with pancreatic cancer cells play crucial roles in pancreatic cancer, however the dynamic changes of inflammatory cell populations in pancreatic cancerogensis and after chemotherapy have not been well eclucidated. The combinational use of aspirin and atrovastatin (Lipitor) have been widely prescribled for cardio-cerebral vascular diseases mainly by regulation of inflammations, and they have been also reported to have plausible anti-tumor effects, however their potential roles in pancreatic cancerogenesis and chemotherapeutic effects have been seldom investigated. We scanned the dynamic changes of pan-inflammatory cell populations in pancreatic cancerogensis and after chemotherapy and found the potential target cell populations. Then we tested the roles of aspirin and Lipitor to regulate these inflammatory cell populations and their effects on pancreatic cancerogenesis and chemotherapeutic effects., Methods: Cancerogen, dimethylbenzanthracene (DMBA), was used to induce pancreatic cancerogenesis and subcatunous implantation of syngenic murine Panc02 pancreatic cancer cells was adopted as well. Gemcitabine was used for chemotherapy. The peripheral blood, pancreatic lesions and tumor samples were harvested and analyzed to search for the potential target cell populations. The roles of aspirin and Lipitor to regulate these cell populations and their potential effects on pancreatic cancerogenesis and chemotherapeutic efficacy were investigated both in vitro and in vivo., Results: We found progressive accumulations of myeloid-derived suppressor cells (MDSC) and M2-polarzied tumor associated macrophages(M2) in pancreatic lesions accompanied with dynamic reducations of cytotoxic T cells(CTL) and helper T cells(Th) in the progression of pancreatic cancerogenesis. After gemcitabine treatment, the MDSC significantly reduced, however M2 soared up unexpectedly. Aspirin could significantly inhibit the MDSC and M2 to prevent pancreatic cancerogenesis and improve chemotherapeutic effects of gemcitabine, however Lipitor did not significantly affect MDSC, instead it could promote M2 to attenuate the postive effects of aspirin and gemcitabine., Conclusions: MDSC and M2 accumulate in progression of pancreatic cancerogenesis and gemcitabine can induce M2. Aspirin could prevent pancreatic cancerogenesis and improve efficacy of gemcitabine partially by inhibiting MDSC and M2, however when used in combination, Lipitor could weaken the efficacy of aspirin and gemcitabine partially by promoting M2.

Objective: To evaluate the effect and safety of enucleation of insulinoma under the Da Vinci robotic surgical system combination with intraoperative ultrasonography(IOUS) for the localization., Methods: The clinical materials of 50 insulinoma cases which underwent IOUS and assisted by the robotic surgical system from September 2012 to September 2014 in Peking Union Medical College Hospital were reviewed retrospectively. The patients were followed up by outpatient review and telephone until October 2014. The diagnostic accuracy rate, operation time, blood loss, complications and cure rate were analyzed by t-test., Results: The locations of tumors were 13 in the head, 21 in the body and 13 in the tail of pancreas, 2 were multiple insulinoma, 1 was ectopic to mesenterium.The average operation time was 142 minutes; the average blood loss was 165 ml.Three(6.0%) patients were transformed to open.One patient experienced postoperative bleeding about 300 ml on the 7(th) day after operation and no infection and perioperative death.Thirty-five cases were of class A and 14 of class B according to the clinical grading of postoperative pancreatic fistula.The blood glucose 60 minutes after tumor dissection was significantly elevated than that before operation ((6.2±1.8)mmol/L vs.(3.7±1.2)mmol/L)(t=-6.89, P<0.01). The cure rate was 100% as all the patients' symptoms were disappeared during follow-up time., Conclusions: Combination IOUS is a highly sensitive method for the localization of insulinoma, which is helpful in localizing tumors precisely in insulinoma cases assisted by robotic surgical system and shortening operation time.It is safe and effective for insulinoma enucleation.

Recent studies show that the unfolded protein response (UPR) within the endoplasmic reticulum is correlated with breast cancer drug resistance. In particular, human X-box binding protein-1(XBP1), a transcription factor which participates in UPR stress signaling, is reported to correlate with poor clinical responsiveness to tamoxifen. In this study, we develop a tamoxifen-resistant MCF-7 cell line by treating the cell line with low concentration of tamoxifen, and we find that XBP1 is indeed up-regulated at both the mRNA and protein levels compared to normal MCF-7 cells. STF-083010, a novel inhibitor which specifically blocks the XBP1 splicing, reestablishes tamoxifen sensitivity to resistant MCF-7 cells. Moreover, co-treatment with STF-083010 and tamoxifen can significantly delay breast cancer progression in a xenograft mammary tumor model. We next investigate the expression of XBP1s in over 170 breast cancer patients' samples and the results demonstrate that XBP1s expression level is highly correlated with overall survival in the ER+ subgroup, but not in the ER- subgroup, suggesting a potential therapeutic application of XBP1 inhibitors in ER+breast cancer treatment.

The question of whether glass continues to relax at low temperature is of fundamental and practical interest. Here, we report a novel atomistic simulation method allowing us to directly access the long-term dynamics of glass relaxation at room temperature. We find that the potential energy relaxation follows a stretched exponential decay, with a stretching exponent β=3/5, as predicted by Phillips's diffusion-trap model. Interestingly, volume relaxation is also found. However, it is not correlated to the energy relaxation, but it is rather a manifestation of the mixed alkali effect.

Epstein-Barr virus (EBV) can infect both susceptible B lymphocytes and non-susceptible epithelial cells (ECs). Viral tropism analyses have revealed two intriguing means of EBV infection, either by a receptor-mediated infection of B cells or by a cell-to-cell contact-mediated infection of non-susceptible ECs. Herein, we report a novel "in-cell infection" mechanism for EBV infection of non-susceptible ECs through the formation of cell-in-cell structures. Epithelial CNE-2 cells were invaded by EBV-infected Akata B cells to form cell-in-cell structures in vitro. Such unique cellular structures could be readily observed in the specimens of nasopharyngeal carcinoma. Importantly, the formation of cell-in-cell structures led to the autonomous activation of EBV within Akata cells and subsequent viral transmission to CNE-2 cells, as evidenced by the expression of viral genes and the presence of virion particles in CNE-2 cells. Significantly, EBV generated from in-cell infected ECs displayed altered tropism with higher infection efficacy to both B cells and ECs. In addition to CNE-2 tumor cells, cell-in-cell structure formation could also mediate EBV infection of NPEC1-Bmi1 cells, an immortalized nasopharyngeal epithelial cell line. Furthermore, efficient infection by this mechanism involved the activation of the PI3K/AKT signaling pathway. Thus, our study identified "in-cell infection" as a novel mechanism for EBV infection. Given the diversity of virus-infected cells and the prevalence of cell-in-cell structures during chronic infection, we speculate that "in-cell infection" is likely a general mechanism for EBV and other viruses to infect non-susceptible ECs.

In this work, the composites of magnetic Fe3 O4 @SiO2 @poly (styrene-co-4-vinylbenzene-boronic acid) microspheres with well-defined core-shell-shell structure were facilely synthesized and applied to selectively enrich glycopeptides. Due to the relatively large amount of vinyl groups introduced by 3-methacryloxy-propyl-trimethoxysilane on the core-shell surface, the poly(styrene-co-4-vinylbenzeneboronic acid) (PSV) was coated with high efficiency, resulting in a large amount of boronic acid on the outermost polymer shell of the Fe3 O4 @SiO2 @PSV microspheres, which is of great importance to improve the enrichment efficiency for glycopeptides. The obtained Fe3 O4 @SiO2 @PSV microspheres were successfully applied to the enrichment of glycopeptides with strong specificity and high selectivity, evaluated by capturing glycopeptides from tryptic digestion of model glycoprotein HRP diluted to 0.05 ng/μL (1.25 × 10(-13) mol, 100 μL), tryptic digest of HRP and nonglycosylated BSA up to the ratio of 1:120 w/w and the real complex sample human serum with 103 unique N-glycosylation peptides of 46 different glycoproteins enriched., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Relay intercropping represents an alternative for sustainable production of vegetables, but the changes of internally antioxidant defense combined with the growth and yield are not clear. Field experiment was carried out to investigate the malondialdehyde (MDA) content and activity levels of superoxide dismutase (SOD), peroxidase (POD), polyphenol oxidase (PPO), and phenylalanine ammonia-lyase (PAL) in eggplant (Solanum melongena L.) and plant height, stem diameter, maximal leaf area, and yield of eggplant grown under successive cropping in the year 2011 and 2012 to see if relay intercropping with garlic (Allium sativum L.) could benefit to eggplant growth and yield. Three experimental treatments with three repeats in each were carried out (completely randomized block design): eggplant monoculture (CK), eggplant relay intercropping with normal garlic (NG), and eggplant relay intercropping with green garlic (GG). In both years, the MDA content was significantly lower and SOD and POD activities were generally lower in NG and GG compared with CK in most sampling dates. PPO activity trends were generally opposite to those of POD. The general trend of PAL activity was similar to MDA. The plant height and stem of eggplant was lower, but the maximal leaf area was larger in NG and GG in 2011; in 2012 the plant growth was stronger in relay intercropping treatments. For eggplant yield in 2011, NG was 2.85% higher than CK; after the time for the green garlic pulled out was moved forward in 2012, the yield was increased by 6.26 and 7.80%, respectively, in NG and GG. The lower MDA content and enzyme activities in relay intercropping treatments showed that the eggplant suffered less damage from environment and continuous cropping obstacles, which promoted healthier plant. Thus from both the growth and physiological perspective, it was concluded that eggplant/garlic relay intercropping is a beneficial cultivation practice maintaining stronger plant growth and higher yield.

We aimed to explore the optimal follow-up time for benign gastric Schwannoma. Benign gastric Schwannoma is an uncommon type of gastric neoplasias. Most of the studies are case reports and case series. Although it is generally considered to be benign, the optimal follow-up time and the chance of recurrence have not yet been investigated fully. We presented a case of benign gastric Schwannoma and systematically reviewed published case series with follow-up data. Eight studies were included, totaling 137 patients (44 male and 93 female) with the median follow-up time ranging from 22-132 months across different studies. No recurrence had been recorded during the follow-up period. Benign gastric Schwannoma rarely recurs after complete surgical resection. Long-term survival will be expected in most patients.

Soil sickness is a critical problem for eggplant (Solanum melongena L.) under continuous cropping that affects sustainable eggplant production. Relay intercropping is a significant technique on promoting soil quality, improving eco-environment, and raising output. Field experiments were conducted from September 2010 to November 2012 in northwest China to determine the effects of relay intercropping eggplant with garlic (Allium sativum L.) on soil enzyme activities, available nutrient contents, and pH value under a plastic tunnel. Three treatments were in triplicate using randomized block design: eggplant monoculture (CK), eggplant relay intercropping with normal garlic (NG) and eggplant relay intercropping with green garlic (GG). The major results are as follows: (1) the activities of soil invertase, urease, and alkaline phosphatase were generally enhanced in NG and GG treatments; (2) relay intercropping significantly increased the soil available nutrient contents, and they were mostly higher in GG than NG. On April 11, 2011, the eggplant/garlic co-growth stage, the available nitrogen content in GG was 76.30 mg·kg(-1), significantly higher than 61.95 mg·kg(-1) in NG. For available potassium on April 17, 2012, they were 398.48 and 387.97 mg·kg(-1) in NG and GG, both were significantly higher than 314.84 mg·kg(-1) in CK; (3) the soil pH showed a significantly higher level in NG treatment, but lower in GG treatment compared with CK. For the last samples in 2012, soil pH in NG and GG were 7.70 and 7.46, the highest and lowest one among them; (4) the alkaline phosphatase activity and pH displayed a similar decreasing trend with continuous cropping. These findings indicate that relay intercropping eggplant with garlic could be an ideal farming system to effectively improve soil nutrient content, increase soil fertility, and alleviate soil sickness to some extent. These findings are important in helping to develop sustainable eggplant production.

Non-small cell lung cancer (NSCLC) is the major cause of cancer death worldwide. Increasing evidence shows that microRNAs (miRNAs), evolutionally conserved non-coding RNAs, are widely involved in the development and progression of NSCLC. Aberrant alteration of miRNAs expression has been implicated in NSCLC initiation and progression. Herein, we studied the role of miR-27b in NSCLC cells. We found that miR-27b was significantly decreased in several NSCLC cell lines. Forced overexpression of miR-27 inhibited both the growth and invasion of NSCLC cells. Furthermore, we identified Sp1 transcription factor (Sp1) as a target of miR-27b in NSCLC cells. Moreover, we found that miR-27 suppressed growth and invasion of NSCLC cells partially by targeting Sp1. Our data indicate that miR-27b may play a critical role in the development of NSCLC.

In this work, for the first time, binary metal oxides ((Ti-Sn)O4) were integrated into one entity on an atomic scale on magnetic graphene as affinity probe for highly selective enrichment of phosphopeptides. The newly prepared Fe3O4/graphene/(Ti-Sn)O4 (magG/(Ti-Sn)O4) composites gathered the advantages of large specific surface area of graphene, superparamagnetism, and biocompatibility of iron oxide, and enhanced affinity properties of binary metal oxides. The phosphopeptide enrichment efficiency of the magG/(Ti-Sn)O4 composite was investigated, and the results indicated an ultralow detection limit (1 pg/μL or 4.0 × 10(-11) M) and an ultrahigh selectivity (weight ratio of β-casein and BSA reached up to 1:1500). Compared with magnetic affinity probes with single metal oxide (magG/TiO2, magG/SnO2) or the simple physical mixture of magG/TiO2 and magG/SnO2, the magG/(Ti-Sn)O4 composite possessed stronger specificity, higher selectivity and better efficiency; and more importantly, it possessed the ability to enrich both the mono- and multi- phosophorylated peptides, demonstrating the notable features of the novel binary metal oxides affinity probe in the specific and selective enrichment of phosphopeptides. Additionally, by utilizing the magG/(Ti-Sn)O4 composites, a total number of 349 phosphorylation sites on 170 phosphopeptides including 66 monophosphopeptides and 104 multiphosphopeptides were captured and identified from mouse brain, indicating the great potential for their application in phosphoproteomics analysis in the future.

Protein phosphorylation is one of the most important post-translational modifications. Due to the dynamic nature and low stoichiometry of the protein phosphorylation, enrichment of phosphopeptides from proteolytic mixtures is necessary prior to their characterization by mass spectrometry. In this work, we synthesized Fe3O4@mesoporous TiO2 magnetic microspheres with core-shell structure and large surface area for selective enrichment of phosphopeptides. To demonstrate its ability for selective enrichment of phosphopeptides, we applied Fe3O4@mesoporous TiO2 magnetic microspheres to isolation and enrichment of the phosphopeptides from tryptic digestion of standard proteins and real samples, and then the enriched peptides were analyzed by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) or liquid chromatography coupled to electrospray ionization mass spectrometry (LC-ESI-MS). Due to that the as-made Fe3O4@mesoporous TiO2 microspheres have large surface area, good dispersivity and biocompatibility, they have been demonstrated as a powerful tool for phosphoproteomics research., (Copyright © 2012 Elsevier B.V. All rights reserved.)

TiO(2)/graphene composites were synthesized through a simple one-step hydrothermal reaction and successfully used to selectively capture phosphopeptides from peptide mixtures for matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis.