Reconstructing historic and modern potato late blight outbreaks using text analytics.

In 1843, a hitherto unknown plant pathogen entered the US and spread to potato fields in the northeast. By 1845, the pathogen had reached Ireland leading to devastating famine. Questions arose immediately about the source of the outbreaks and how the disease should be managed. The pathogen, now known as Phytophthora infestans, still continues to threaten food security globally. A wealth of untapped knowledge exists in both archival and modern documents, but is not readily available because the details are hidden in descriptive text. In this work, we (1) used text analytics of unstructured historical reports (1843-1845) to map US late blight outbreaks; (2) characterized theories on the source of the pathogen and remedies for control; and (3) created modern late blight intensity maps using Twitter feeds. The disease spread from 5 to 17 states and provinces in the US and Canada between 1843 and 1845. Crop losses, Andean sources of the pathogen, possible causes and potential treatments were discussed. Modern disease discussion on Twitter included near-global coverage and local disease observations. Topic modeling revealed general disease information, published research, and outbreak locations. The tools described will help researchers explore and map unstructured text to track and visualize pandemics.

The chromosome-level genome assembly of Fraxinus americana provides insights into the evolution of Oleaceae plants.

White ash (Fraxinus americana linn.) originates from the southeastern United States. It is a tall and fast-growing tree species with strong salt-alkali resistance and cold tolerance, making it an important reforestation species and widely planted worldwide. Here, we completed the chromosome-level reference genome assembly of F. americana based on Illumina, PacBio, and Hi-C reads, with a genome size of 878.98 Mb, an N50 of 3.27 Mb, and a heterozygosity rate of 0.3 %. Based on de novo prediction, transcriptome prediction, and homology-based protein prediction, we obtained 39,538 genes. Approximately 843.21 Mb of the assembly genome was composed of 37,928 annotated protein-coding genes, with a gene function annotation rate of 95.93 %. 99.94 % of the overlap clusters (877.44 Mb) were anchored to 23 chromosomes. Synteny analysis of F. americana and other Oleaceae plants showed that F. americana underwent frequent chromosome rearrangements. The amplification of the Ale transposons effectively promoted the genome size of F. americana. Compared with other Oleaceae plants, the Glutathione S-transferase (GST) gene family in the F. americana genome has undergone significant expansion, which may help F. americana cope with adverse natural environments. Furthermore, we found that key enzyme-coding gene families related to lignin biosynthesis were expanded and highly expressed in F. americana leaves. These key genes drive lignin synthesis and benefit F. americana in fast-growing, as well as resisting biotic and abiotic stress. Overall, the F. americana genome assembly provides insights into the evolution of Oleaceae plants and provides abundant resources for breeding and germplasm conservation of white ash.

[Research status of dural injury types and repair].

Objective: To evaluate the current status of classification and repair methods for dural injury caused by spinal surgery or trauma, providing new strategies and ideas for the clinical repair of dural injury and the development of related materials. Methods: The literature related to dural injury both at home and abroad in recent years was thoroughly reviewed and analyzed in order to draw meaningful conclusions. Results: There have been numerous retrospective studies on dural injury, but there is a scarcity of prospective and multi-center studies, resulting in a low level of evidence-based research. The incidence and risk factors of dural injury have primarily been studied in relation to common degenerative spinal diseases of the cervical and lumbar spine, with insufficient research on thoracic spine-related diseases. Currently, a universally recognized method for grading and classifying dural injury has not been established, which hampers the development of clinical guidelines for their repair. Furthermore, although there are repair materials and surgical strategies available to address clinical issues such as suture leakage and surgical repair of dural injury in complex locations, there is a lack of comprehensive clinical research and evidence-based data to validate their scientificity and reliability. Conclusion: Regardless of the classification of dural injury, suture remains the most important repair method. It is important to further develop new patches or sealants that can meet clinical needs and reduce the difficulty of repair.

Improving the Microstructural and Rheological Properties of Frozen Unfermented Wheat Dough with Laccase and Ferulic Acid.

The quality deterioration that is induced by freezing treatment limits the development of frozen dough technology for standardized and delayed baking. In this study, laccase (LAC) and ferulic acid (FA) were employed to improve the rheological properties and microstructure of frozen unfermented dough. The results showed that the dough with LAC + FA had a lower softening degree than the dough with FA alone. Correspondingly, LAC + FA incorporation enhanced the viscoelastic behavior of frozen unfermented dough with better stability. Furthermore, a more uniform and homogeneous gluten network was observed in the LAC + FA-supplemented dough after 21 d of storage. The structural stability of the frozen gluten sample increased after LAC + FA treatment, possibly owing to an increase in the oxidation degree of FA. Moreover, LAC + FA treatment promoted the oxidation of the sulfhydryl groups to some extent, resulting in more extensive cross-linking. LAC + FA treatment hindered the protein conformational changes typically induced by frozen storage compared with LAC alone. Overall, LAC + FA treatment has a synergistic effect on enhancing the viscoelastic behaviors of frozen unfermented dough and inhibiting the conformational variation in frozen gluten; thus, it shows promise for improving frozen dough.

A novel surgical technique for cervical laminoplasty in patients with multilevel cervical spondylotic myelopathy: A case report and literature review.

Cervical laminoplasty is a posterior-based surgical decompression technique for the treatment of multilevel cervical spondylotic myelopathy (CSM) that may improve the preservation of cervical mobility, spinal canal structure, and natural lordosis. Although this procedure is considered to be comparatively safe, with fewer complications than those seen with laminectomy, several postoperative problems have been noted, including axial neck pain, C5 nerve palsy, and failed resolution of radiculopathy. Hence, various modifications have been made to improve the safety and effectiveness of this technique. Here, we report the case of a 74-year-old man with multilevel CSM who underwent posterior cervical laminoplasty in the C3-C7 segments using a novel surgical technique, termed alternating-side cervical laminoplasty. Preoperative and postoperative assessments, including visual analog scale, modified Japanese Orthopaedic Association, neck disability index scores, and imaging data, were collected and analyzed. The results of a 5-year follow-up indicated that the patient recovered well, with no development of axial neck pain. This is the first report of this modified open-door laminoplasty, which we propose may be a better surgical option for preventing postoperative axial neck pain in patients with multilevel CSM. Additionally, opening the laminae on the alternating sides during laminoplasty could provide a flexible approach to complete decompression on different radiculopathy sides.

Recent Research Progress of Ionic Liquid Dissolving Silks for Biomedicine and Tissue Engineering Applications.

Ionic liquids (ILs) show a bright application prospect in the field of biomedicine and energy materials due to their unique recyclable, modifiability, structure of cation and anion adjustability, as well as excellent physical and chemical properties. Dissolving silk fibroin (SF), from different species silkworm cocoons, with ILs is considered an effective new way to obtain biomaterials with highly enhanced/tailored properties, which can significantly overcome the shortcomings of traditional preparation methods, such as the cumbersome, time-consuming and the organic toxicity caused by manufacture. In this paper, the basic structure and properties of SF and the preparation methods of traditional regenerated SF solution are first introduced. Then, the dissolving mechanism and main influencing factors of ILs for SF are expounded, and the fabrication methods, material structure and properties of SF blending with natural biological protein, inorganic matter, synthetic polymer, carbon nanotube and graphene oxide in the ILs solution system are introduced. Additionally, our work summarizes the biomedicine and tissue engineering applications of silk-based materials dissolved through various ILs. Finally, according to the deficiency of ILs for dissolving SF at a high melting point and expensive cost, their further study and future development trend are prospected.

Laminoplasty and simultaneous C2 semi-laminectomy with internal fixation in treating ossification of the posterior longitudinal ligament in cervical discs at C2 segment.

OBJECTIVE: To explore the effect of open-door laminoplasty and simultaneous C2 semi-laminectomy with lateral mass screw fixation (LSLF) in treating ossification of the posterior longitudinal ligament (OPLL) in cervical discs at C2 segment. METHODS: In this retrospective study, 76 patients diagnosed with OPLL in cervical discs at C2 segment from November 2016 to May 2019 were included. These patients were assigned into a LSLF group (n=41, LSLF surgery) and LF group (n=35, laminectomy and lateral mass screw fixation) according to the treatment they received. The surgery time and intraoperative blood loss were recorded. Improvements in neurological function (JOA score), cervical curvature index (CCI), spinal cord drift distance, cross-sectional area (CSA) of the posterior muscles from cervical spine, occurrence of C5 palsy, and severity of axial symptoms were evaluated between LSLF group and LF group. RESULTS: Compared with LF group, the operative time was longer and blood loss volume was higher in LSLF group (P<0.05). No statistical difference was found in decompression width between LSLF group and LF group, while the drift distance of spinal cord in LSLF group was larger than that in LF group (P<0.05). No obvious differences were observed in anteroposterior dural sac diameter after the surgery between LSLF group and LF group. CSA in LF group decreased more than that in LSLF group (P<0.05). No remarkable difference was obtained in CCI at the final follow-up between LSLF group and LF group. The NDI score after surgery in the LSLF group was significantly decreased compared to LF group (P<0.05), while no differences were observed in JOA scores or the neurological recovery rate between LSLF group and LF group. The occurrence of C5 palsy in the LSLF group was 4.9%, which was less than that of LF group (20.0%). In contrast to LF group, postoperative axial symptoms in LSLF group were decreased (P<0.05). CONCLUSION: Compared to LF, LSLF could better improve neck functions, and reduce the severity of axial symptoms and the occurrence of C5 palsy for patients with OPLL at C2 segment.

Varied thyroid disrupting effects of perfluorooctanoic acid (PFOA) and its novel alternatives hexafluoropropylene-oxide-dimer-acid (GenX) and ammonium 4,8-dioxa-3H-perfluorononanoate (ADONA) in vitro.

Due to its potential adverse effects on human health, perfluorooctanoic acid (PFOA), one of the once widely used legacy per- and polyfluoroalkyl substances (PFASs), has been recently replaced by its novel alternatives including hexafluoropropylene-oxide-dimer-acid (GenX) and ammonium 4,8-dioxa-3H-perfluorononanoate (ADONA). These alternative PFASs are detected in water and exposed workers. PFASs can enter organs like thyroids, however, it is yet unknown whether the new alternatives are safer than PFOA. In the current study, we compared the thyroid disrupting effects of PFOA and its alternatives GenX and ADONA in vitro with both rat thyroid cell line FRTL5 and primary normal human thyroid (NHT) cells. Cells were exposed to ascendant doses of PFOA, GenX or ADONA for various incubation time and cell viability was assessed by WST-1 assay and LDH assay. The proliferation rate of survived cells was determined by crystal violet-based cell proliferation assay and MTT assay. The gene expression of thyroid hormone regulation-related genes in thyroid cells after exposure was quantified by RT-PCR and Western blot. Our data showed that both PFOA and GenX reduced thyroid cell viability in both dose and time dependent manner, with GenX being more toxic than PFOA at the same condition. Similarly, the proliferation rate of cells survived exposure to PFOA and GenX was considerably impaired, with GenX showing more profound adverse effect than PFOA. Unlike PFOA and GenX, ADONA showed no apparent adverse effects on the viability and proliferation of both thyroid cell types. Gene expression data revealed that all three PFASs altered gene expression in both thyroid cells and the altered gene expression seemed to be PFAS and cell type dependent. Taken together, our data reveal that the thyroid disrupting effects is increased in the order of GenX > PFOA > ADONA. Our findings will be beneficial for the guidance of the future usage of PFASs and development of better alternatives.

Effects of acid ionization on the formation mechanism of bimodal mesoporous Al-MCM-41s from coal gasification fine residue and evaluation of adsorption capabilities.

The development of synthetic methods to obtain high value-added mesoporous Al-MCM-41 from a low-cost silicon-aluminum source with low toxicity is an active research topic in solid waste resource utilization. In particular, the controlled synthesis of MCM-41 with a two-level pore distribution is a challenging task. In this work, the synthesis of unimodal and bimodal mesoporous Al-MCM-41s was achieved using acids with different degrees of ionization from coal gasification fine residue (CGFR) as bulk solid waste generated by the coal gasification process. We determined that the degree of acid ionization affected the self-assembly of inorganic/organic species as well as condensation processes, resulting in some changes of the hexagonal mesoscopic structure. The unimodal mesoporous Al-MCM-41 with acetic acid HAc and bimodal mesoporous Al-MCM-41s with an inorganic acid environment (HCl, HNO3 or H2SO4) could be effectively prepared in a controllable manner by the silicon and aluminum source obtained at alkali dissolution time 6 h and crystallization conditions at pH 10.5 and 383 K in 72 h. Moreover, the synthesis of Al-MCM-41-HAc with different SiO2/Al2O3 molar ratios (18-89) could also be realized by different alkali dissolution times. And alkali dissolution time (2-24 h) and the crystallization conditions (pH 4.5-11.5, temperatures 373-393 K, and time 48-96 h) also affected the formation of unimodal and bimodal mesoporous Al-MCM-41-HAc. In addition, the maximum adsorption amount onto bimodal mesoporous Al-MCM-41-H2SO4 (476.19 mg g-1 at 308 K) was larger than that onto unimodal mesoporous Al-MCM-41-HAc (243.90 mg g-1 at 303 K). The mesoporous Al-MCM-41s showed good stability.

Hepatitis B virus induces sorafenib resistance in liver cancer via upregulation of cIAP2 expression.

BACKGROUND: HBV promotes cell survival by upregulating the expression of the cellular inhibitor of apoptosis protein 2 (cIAP2), however whether it is involved in HBV-induced sorafenib resistance in liver cancer remains unclear. METHODS: cIAP2 overexpression and knockdown was adopted to assess the involvement of cIAP2 in HBV-induced sorafenib resistance. Anti-HBV drug lamivudine and Akt inhibitor were used to investigate the impact of HBV replication on cIAP2 expression and sorafenib resistance. Xenotransplantation mouse model was used to confirm the data on cell lines in vitro. RESULTS: Liver cancer cell line HepG2.215 showed increased cIAP2 expression and enhanced resistance to sorafenib. Upon sorafenib treatment, overexpression of cIAP2 in HepG2 lead to decreased cleaved caspase 3 level and increased cell viability, while knockdown of cIAP2 in HepG2.215 resulted in increased level of cleaved caspase 3 and decreased cell viability, suggesting the involvement of cIAP2 in HBV-induced sorafenib resistance. Furthermore, anti-HBV treatment reduced cIAP2 expression and partially restored sorafenib sensitivity in HepG2.215 cells. Xenotransplantation mouse model further confirmed that co-treatment with lamivudine and sorafenib could reduce sorafenib-resistant HepG2.215 tumor cell growth. CONCLUSION: cIAP2 is involved in HBV-induced sorafenib resistance in liver cancer and anti-HBV treatments reduce cIAP2 expression and partially restore sorafenib sensibility.

Simultaneous or staged operation for tandem spinal stenosis: surgical strategy and efficacy comparison.

BACKGROUND: Tandem spinal stenosis (TSS) has a complex clinical presentation, and there is no consensus on the optimal surgical strategy. This study retrospectively compared the efficacy of different staged operations and simultaneous decompression for patients with TSS. METHODS: We reviewed data from 132 patients with TSS who received surgical procedures from January 2011 to June 2018. Patients were classified into three groups according to the most symptomatic area of compression (group C: first-stage surgery for cervical compression; group L: first-stage surgery for lumbar compression; group CL: simultaneous surgery for both). Medical records were reviewed for age, gender, comorbidities, operation time, combined estimated blood loss, and time of hospitalization. The JOA-C, JOA-L, NDI, and ODI scores, and complications were also examined. RESULTS: Postoperative outcomes were followed for 32.1 ± 5.4 months. There were significant differences in the re-operation rate and the interval time between the two types of staged operations (p = 0.005 and p = 0.001, respectively). There were no significant differences in gender (p = 0.639), operation time (p = 0.138), combined estimated blood loss (p = 0.116), or complications (p = 0.652) among the three groups, while the simultaneous group was significantly younger (p = 0.027), with fewer comorbidities (p < 0.001) and a shorter hospitalization time (p < 0.001). At the final follow-up, the JOA-C and JOA-L scores were increased, while the NDI and ODI scores were decreased, compared with the preoperative scores. CONCLUSIONS: TSS can be effectively managed by either simultaneous or staged decompressions. First-stage surgery for cervical stenosis significantly lowers the requirement for second-stage lumbar surgery. One-stage simultaneous decompression is safe and effective with the advantage of reduce hospitalization time, without an increase in operative time or bleeding. However, the surgical indications should be strictly controlled and is recommended for younger patients with fewer comorbidities.

Assessment of circulating HISLA as a potential biomarker for breast cancer diagnosis and prognosis.

Breast cancer (BC) is the most frequently encountered and aggressive type of malignant tumor and affects the health of females across the globe. Approximately 30% of patients that are newly diagnosed have a high risk of subsequent metastasis and relapse. HIF-1α-stabilizing long noncoding RNA (HISLA) packaged in exosome has been recently identified and revealed as an important oncogenic gene in promoting BC progress. Thus, we sought to investigate whether serum circulating HISLA was involved in dynamics underlying its applicability for the diagnosis and prognosis of BC. We assessed serum HISLA expression in 40 patients with BC and 20 healthy controls to investigate its roles in BC using quantitative real-time polymerase chain reaction (qRT-PCR). We also assessed measures of correlation of clinical and pathological parameters with prognoses of BC patients. Our findings suggested that serum HISLA expression in BC patients was significantly higher than in healthy controls. Furthermore, high expression of serum HISLA was positively associated with advanced stage lymph node metastasis. Expression of HISLA was reduced in postoperative BC patients' serum samples, compared with preoperative serum samples. Pearson correlation assessments indicated significant correlation between serum HISLA expression and the tissue sample HISLA expression in BC patients. Our findings suggested that serum HISLA may serve as newfound biomarker which could help to improve diagnoses and prognoses for BC-afflicted patients.

Comparison between repeat anterior and posterior decompression and fusion in the treatment of two-level symptomatic adjacent segment disease after anterior cervical arthrodesis.

BACKGROUND: Two-level symptomatic adjacent segment disease (ASD) is rarely reported, but remains a challenge after anterior cervical arthrodesis. The purpose of this study was to compare the clinical and radiological outcomes of repeat anterior and posterior decompression and fusion procedures for two-level symptomatic ASD. METHODS: Thirty-two patients with two-level symptomatic ASD were retrospectively reviewed and underwent repeat anterior cervical discectomy and fusion (ACDF) or posterior decompression and fusion (PDF). Clinical outcomes (JOA, NDI, and VAS scores), perioperative parameters (blood loss, operation time, and length of hospital stay), radiological parameters (cervical lordosis and ROM), and complications were compared. RESULTS: Eighteen patients underwent ACDF, and 14 patients underwent PDF. Patients who underwent PDF were older, more frequently presented with myelopathic deficits, and were fused at more levels. Patients who underwent ACDF experienced significantly shorter surgery time (p < 0.001), lower blood loss (p < 0.001), and reduced hospital stay (p = 0.002). Both groups exhibited significant increases in JOA scores and decreases in NDI and both neck pain and arm pain VAS scores (p < 0.05), but patients who underwent PDF had significantly higher NDI scores (p = 0.012), neck pain VAS scores (p = 0.019), loss of cervical lordosis (p < 0.001), and loss of ROM (p = 0.001). Three patients developed dysphagia in the ACDF group, and two patients had C5 root palsy and one had hematoma in the PDF group. Recurrent ASD after the second operation occurred in two patients in the ACDF group but no patients in the PDF group. CONCLUSIONS: For patients with two-level symptomatic ASD, both anterior and posterior decompression and fusion were effective for improving the neurological function. For patients with radicular symptoms, ACDF had less surgical trauma, better restoration of lordosis, and less postoperative neck pain, but higher chance of recurrent ASD. PDF was an effective surgical option for older patients with myelopathy developing in adjacent segments.

Insight into the Mechanism of Reduced IgG/IgE Binding Capacity in Ovalbumin as Induced by Glycation with Monose Epimers through Liquid Chromatography and High-Resolution Mass Spectrometry.

Ovalbumin (OVA) is one of the major food allergens in hen eggs. In this work, it was demonstrated that glycation with d-glucose and its epimers, including d-mannose, d-allose, d-galactose, and l-idose, could effectively attenuate the IgG/IgE binding of OVA, which was attributed to the covalent masking by sugars and to its structural changes. The glycation sites were determined, and their average degree of substitution was found using liquid chromatography coupled with high-resolution mass spectrometry. Fluctuations in OVA conformation were monitored by conventional spectrometry. Compared to those of OVA-Man and OVA-Glu, OVA-All, OVA-Gal, and OVA-Ido showed a higher glycation extent, and the alterations on their steric layouts were more drastic, suggesting that the configuration of hydroxyl groups at positions C-3, C-4, and C-5 in sugars might be important for the glycation reactivity; as such, their capabilities in binding with IgG/IgE decreased more significantly. Attempts were made to provide valuable information for in-depth understanding of the differences in biochemical functionality among epimeric sugars. These insights would be helpful for designing sweetened food products with a desirable level of safety.

Mechanism of the effect of 2, 2'-azobis (2-amidinopropane) dihydrochloride simulated lipid oxidation on the IgG/IgE binding ability of ovalbumin.

In this work, the mechanism of the effect of lipid oxidation on the IgG/IgE binding ability of ovalbumin (OVA) was investigated via the peroxyl radicals produced by 2, 2'-azobis (2-amidinopropane) dihydrochloride to simulate lipid oxidation. Results showed that the structure of OVA unfolded partially with an increase in oxidation degree, leading to the exposure of the allergenic epitopes and increasing the IgG/IgE binding ability of OVA. Nine oxidation sites were found on the α-helix, and these sites may unwind the α-helix and expose the allergenic epitopes on the OVA surface, leading to antibody recognition and combination. Consequently, the IgG/IgE binding ability of OVA was increased. In conclusion, the allergenic capacity of OVA can be promoted by modifying peroxyl radical oxidation in processing egg products.

A SINS/DVL Integrated Positioning System through Filtering Gain Compensation Adaptive Filtering.

Because of the complex task environment, long working distance, and random drift of the gyro, the positioning error gradually diverges with time in the design of a strapdown inertial navigation system (SINS)/Doppler velocity log (DVL) integrated positioning system. The use of velocity information in the DVL system cannot completely suppress the divergence of the SINS navigation error, which will result in low positioning accuracy and instability. To address this problem, this paper proposes a SINS/DVL integrated positioning system based on a filtering gain compensation adaptive filtering technology that considers the source of error in SINS and the mechanism that influences the positioning results. In the integrated positioning system, an organic combination of a filtering gain compensation adaptive filter and a filtering gain compensation strong tracking filter is explored to fuse position information to obtain higher accuracy and a more stable positioning result. Firstly, the system selects the indirect filtering method and uses the integrated positioning error to model the navigation parameters of the system. Then, a filtering gain compensation adaptive filtering method is developed by using the filtering gain compensation algorithm based on the error statistics of the positioning parameters. The positioning parameters of the system are filtered and information on errors in the navigation parameters is obtained. Finally, integrated with the positioning parameter error information, the positioning parameters of the system are solved, and high-precision positioning results are obtained to accurately position autonomous underwater vehicles (AUVs). The simulation results show that the SINS/DVL integrated positioning method, based on the filtering gain compensation adaptive filtering technology, can effectively enhance the positioning accuracy.

Plasma extracellular vesicle­packaged microRNAs as candidate diagnostic biomarkers for early­stage breast cancer.

Extracellular vesicle­packaged microRNAs (miRNAs) are a class of circulating miRNAs located in the plasma that are packaged into extracellular vesicles. The present study examined the expression profiles of extracellular vesicles and tissue miRNAs with the aim of investigating the miRNA signatures in early­stage breast cancer. The present study identified and compared the extracellular vesicle­packaged miRNA expression signature and tissue miRNA expression signature from healthy individuals (n=10) and patients with early­stage breast cancer (n=12). A total of five miRNAs, including miRNA­375, miRNA­24­2­5p, miRNA­548b­5p, miRNA­655­3P and miRNA­376b­5p, were synchronized in extracellular vesicles and tissues of the breast cancer group when compared with the healthy group. The highest area under the curve (AUC) for a single miRNA was achieved with miRNA­548b­5p [AUC=0.785; 95% confidence interval (CI)=0.585­0.984; P=0.022]. The highest overall AUC was achieved by the combination of miRNA­375, miRNA­655­3p, miRNA­548b­5p and miRNA­24­2­5p (AUC=0.808; 95% CI=0.629­0.986; P=0.013). The Kaplan­Meier curves and log test analysis results of these five miRNAs, especially those for miRNA­548b­5p, were partly consistent with the hypothesis. Two miRNAs (miRNA­548b­5p and miRNA­376b­5p) were positively associated with patient survival, while two miRNAs (miRNA­375 and miRNA­24­2­5p) were negatively associated with patient survival. The present study provided a set of plasma extracellular vesicle­packaged miRNA­based biomarkers for the diagnosis of early­stage breast cancer.

Investigation of the Mechanism of Conformational Alteration in Ovalbumin as Induced by Glycation with Different Monoses through Conventional Spectrometry and Liquid Chromatography High-Resolution Mass Spectrometry.

Glycation between ovalbumin (OVA) and different monoses under mild dry heating at 37 °C was studied. The content of free amino groups decreased dramatically, and the conformational changes based on fluorescence and circular dichroism spectra were evident in glycated OVA. The glycated sites and the average degree of substitution per peptide molecule per site were determined using liquid chromatography high-resolution mass spectrometry. Lysine and arginine were the predominant glyaction sites, in which Lys207 was a relatively reactive site for glycation in all of the conjugates. In general, the extent of glycation of aldose was higher, and its alterations on the steric layouts of protein were more drastic than those of ketose. The configuration of hydroxyl groups at C-4 in sugar epimers might be important for the glycation reactivity and conformational modification in the glycated proteins. These insights would have important implications for the creation of sweetened food products with desirable structures and excellent quality control.

Upregulation of PAG1/Cbp contributes to adipose-derived mesenchymal stem cells promoted tumor progression and chemoresistance in breast cancer.

C-terminal Src kinase (Csk)-binding protein (Cbp) is a ubiquitously expressed transmembrane adaptor protein which regulating Src family kinase (SFK) activities. Although SFKs are well known for their involvement in breast cancer, the function of Cbp in breast carcinogenesis upon the adipose-tumor microenvironment has not been investigated. Here, we reported that adipose-derived mesenchymal stem cells (ASCs) induced increased expression of Cbp accompanied by enhanced cell proliferation and chemotherapy resistance in breast cancer cell MCF-7/ADR. Depletion of Cbp in breast cancer cell by RNA interference led to remarkable inhibition of cell proliferation, invasion as well as synergy with adriamycin hydrochloride to suppress the tumor growth. Furthermore, silencing of Cbp concomitantly inhibited the expression of phosphoryl of Src, AKT and mTOR signals. Our study highlights the underlying mechanism of cross interaction between ASCs and breast cancer cells, and indicates that PAG1/Cbp in breast cancer cell may modulate tumor progression and acquired chemoresistance in the ASCs-associated breast cancer microenvironment through Src and AKT/mTOR pathways.

Melatonin prevents sleep deprivation-associated anxiety-like behavior in rats: role of oxidative stress and balance between GABAergic and glutamatergic transmission.

Sleep deprivation (SD) has been shown to induce anxiety-like behavior. Melatonin, an endogenous potent antioxidant, protects neurons from oxidative stress in many disease models. Here we investigated the effect of melatonin against SD-induced anxiety-like behavior and attempted to define the possible mechanisms involved. SD was induced in rats using modified multiple platform model. Melatonin (15 mg/kg) was administered to the rats via intraperitoneal injection. The elevated plus maze test, open field test and light-dark exploration were used to evaluate anxiety-like behavior. Serum corticosterone was measured to determine stress level. Malondialdehyde (MDA) level and superoxide dismutase (SOD) enzyme activity of amygdala and serum were performed to determine the level of oxidative stress. Levels of protein were detected by means of Western blot. The results showed that SD induces anxiety-like behavior, while melatonin treatment prevented these changes. Serum corticosterone also increased with SD but its levels were normalized by melatonin. In addition, melatonin reversed SD-induced changes in MDA and SOD in both of amygdala and serum. The results of Western blot showed that melatonin attenuated the up-regulation of NR2B-containing N-methyl-D-aspartate receptors, GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor as well as phosphorylation of GluR1 at Ser831, and Ca2+/calmodulin-dependent protein kinase II-alpha in SD rats. Meanwhile, melatonin blocked the down-regulation of γ-aminobutyric acid A-alpha-2 receptor. In conclusion, our results suggest that melatonin prevents anxiety-like behavior induced by SD. The possible mechanism may be attributed to its ability to reduce oxidative stress and maintain balance between GABAergic and glutamatergic transmission.