Structural and thermodynamic framework for PIEZO1 modulation by small molecules.

Mechanosensitive PIEZO channels constitute potential pharmacological targets for multiple clinical conditions, spurring the search for potent chemical PIEZO modulators. Among them is Yoda1, a widely used synthetic small molecule PIEZO1 activator discovered through cell-based high-throughput screening. Yoda1 is thought to bind to PIEZO1's mechanosensory arm domain, sandwiched between two transmembrane regions near the channel pore. However, how the binding of Yoda1 to this region promotes channel activation remains elusive. Here, we first demonstrate that cross-linking PIEZO1 repeats A and B with disulfide bridges reduces the effects of Yoda1 in a redox-dependent manner, suggesting that Yoda1 acts by perturbing the contact between these repeats. Using molecular dynamics-based absolute binding free energy simulations, we next show that Yoda1 preferentially occupies a deeper, amphipathic binding site with higher affinity in PIEZO1 open state. Using Yoda1's binding poses in open and closed states, relative binding free energy simulations were conducted in the membrane environment, recapitulating structure-activity relationships of known Yoda1 analogs. Through virtual screening of an 8 million-compound library using computed fragment maps of the Yoda1 binding site, we subsequently identified two chemical scaffolds with agonist activity toward PIEZO1. This study supports a pharmacological model in which Yoda1 activates PIEZO1 by wedging repeats A and B, providing a structural and thermodynamic framework for the rational design of PIEZO1 modulators. Beyond PIEZO channels, the three orthogonal computational approaches employed here represent a promising path toward drug discovery in highly heterogeneous membrane protein systems.

Predicting subsolid pulmonary nodules before percutaneous needle biopsy: a comparison of artificial neural network and biopsy results.

AIM: To establish an artificial neural network (ANN) model to predict subsolid nodules (SSNs) before percutaneous core-needle biopsy (PCNB). The results of the two methods were compared to provide guidance on the treatment of SSNs. MATERIALS AND METHODS: This was a single-centre retrospective study using data from 1,459 SSNs between 2013 and 2021. The ANN was developed using data from patients who underwent surgery following computed tomography (CT) (SFC) and validated using data from patients who underwent surgery following biopsy (SFB). The prediction results of the ANN for the PCNB group and the histopathological results obtained after biopsy were compared with the histopathological results of lung nodules in the same group after surgery. Additionally, the choice of predictors for PCNB was analysed using multivariate analysis. RESULTS: There was no significant difference between the accuracies of the ANN and PCNB in the SFB group (p=0.086). The sensitivity of PCNB was lower than that of the ANN (p=0.000), but the specificity was higher (p=0.001). PCNB had better diagnostic ability than the ANN. The incidence of precursor lesions and non-neoplastic lesions in the SFB group was lower than that in the SFC group (p=0.000). A history of malignant tumours, size (2-3 cm), volume (>400 cm3) and mean CT value (≥-450 HU) are important factors for selecting PCNB. CONCLUSIONS: Both ANN and PCNB have comparable accuracy in diagnosing SSNs; however, PCNB has a slightly higher diagnostic ability than ANN. Selecting appropriate patients for PCNB is important for maximising the benefit to SSN patients.

In silico prediction of ARB resistance: A first step in creating personalized ARB therapy.

Angiotensin II type 1 receptor (AT1R) blockers (ARBs) are among the most prescribed drugs. However, ARB effectiveness varies widely, which may be due to non-synonymous single nucleotide polymorphisms (nsSNPs) within the AT1R gene. The AT1R coding sequence contains over 100 nsSNPs; therefore, this study embarked on determining which nsSNPs may abrogate the binding of selective ARBs. The crystal structure of olmesartan-bound human AT1R (PDB:4ZUD) served as a template to create an inactive apo-AT1R via molecular dynamics simulation (n = 3). All simulations resulted in a water accessible ligand-binding pocket that lacked sodium ions. The model remained inactive displaying little movement in the receptor core; however, helix 8 showed considerable flexibility. A single frame representing the average stable AT1R was used as a template to dock Olmesartan via AutoDock 4.2, MOE, and AutoDock Vina to obtain predicted binding poses and mean Boltzmann weighted average affinity. The docking results did not match the known pose and affinity of Olmesartan. Thus, an optimization protocol was initiated using AutoDock 4.2 that provided more accurate poses and affinity for Olmesartan (n = 6). Atomic models of 103 of the known human AT1R polymorphisms were constructed using the molecular dynamics equilibrated apo-AT1R. Each of the eight ARBs was then docked, using ARB-optimized parameters, to each polymorphic AT1R (n = 6). Although each nsSNP has a negligible effect on the global AT1R structure, most nsSNPs drastically alter a sub-set of ARBs affinity to the AT1R. Alterations within N298 -L314 strongly effected predicted ARB affinity, which aligns with early mutagenesis studies. The current study demonstrates the potential of utilizing in silico approaches towards personalized ARB therapy. The results presented here will guide further biochemical studies and refinement of the model to increase the accuracy of the prediction of ARB resistance in order to increase overall ARB effectiveness.

Mesozoic origin and 'out-of-India' radiation of ricefishes (Adrianichthyidae).

The Indian subcontinent has an origin geologically different from Eurasia, but many terrestrial animal and plant species on it have congeneric or sister species in other parts of Asia, especially in the Southeast. This faunal and floral similarity between India and Southeast Asia is explained by either of the two biogeographic scenarios, 'into-India' or 'out-of-India'. Phylogenies based on complete mitochondrial genomes and five nuclear genes were undertaken for ricefishes (Adrianichthyidae) to examine which of these two biogeographic scenarios fits better. We found that Oryzias setnai, the only adrianichthyid distributed in and endemic to the Western Ghats, a mountain range running parallel to the western coast of the Indian subcontinent, is sister to all other adrianichthyids from eastern India and Southeast-East Asia. Divergence time estimates and ancestral area reconstructions reveal that this western Indian species diverged in the late Mesozoic during the northward drift of the Indian subcontinent. These findings indicate that adrianichthyids dispersed eastward 'out-of-India' after the collision of the Indian subcontinent with Eurasia, and subsequently diversified in Southeast-East Asia. A review of geographic distributions of 'out-of-India' taxa reveals that they may have largely fuelled or modified the biodiversity of Eurasia.

[Comparative transcriptomics analysis of Citrus medica var. sarcodactylis at different developmental stages].

In order to study the transcriptional differences of Citrus medica var. sarcodactylis at different developmental stages, we explored the genes regulating the biosynthesis of the effective components. In this study, Illumina Hiseq 4 000 high-throughput sequencing technology was used to sequence the transcriptome of C. medica var. sarcodactylis at different developmental stages, 121 235 unigenes were obtained with an average length of 2 434 bp, 3 379 different genes were obtained using DESeq screening, which mainly connected to biological processes such as signal transmission, biological regulation, and metabolic processes, and enriched in metabolic pathways such as starch, sucrose metabolism, phenylpropanoid biosynthesis, and flavonoid biosynthesis. Further dynamic comparison of biosynthesis related genes of active ingredients: the expression levels of PAL, CHI, CYP75B1, ZDS, 4CL and FLS gradually increased as the fruit turned from green to yellow; the expressions of COMT, F3H and CYP73A increased at first and then decreased; CCR, HCT and HRP were down-regulated whereas up-regulated. This study provides references for further excavation of key genes in the biosynthesis of active components, as well as biopathway analysis of active components for C. medica var. sarcodactylis.

[Mechanism of "Scutellaria barbata-Hedyotis diffusa" against breast cancer based on network pharmacology].

To explore the mechanism of Scutellaria barbata-Hedyotis diffusa against breast cancer based on network pharmacological methods. The active components and corresponding target proteins of S. barbata and H. diffusa were screened by using Traditional Chinese Medicine Systems Pharmacology Database(TCMSP), and the targets of breast cancer were screened through the Genecards and OMIM databases. Venn online software was used to obtain the common targets of drugs and the disease, and then the "compound-target-disease" network diagram was constructed by using Cytoscape 3.7.2 software. The STRING database was used to draw the protein-protein interaction(PPI) network, and the David database was used to perform GO function and KEGG pathway enrichment analysis on effective targets. The results showed that 29 S. barbata compounds, 7 H. diffusa compounds, and 109 effective targets were screened. The 59 common targets for drugs and disease were obtained through Venn diagrams. The PPI network showed that MYC, CCND1, EGFR, ESR1, CASP3, VEGFA, etc. might be the key targets for "S. barbata-H. diffusa" in the treatment of breast cancer. In the GO function analysis, 88 entries were found, involving the regulation of transcription factor activity, receptor activity, cytokine activity, enzyme activity, and biosynthetic processes. In KEGG pathway analysis, 37 entries related to cancer, cell cycle, apoptosis, angioge-nesis and other pathways were found, including p53 signaling pathway, ErbB signaling pathway, nod like receptor signaling pathway, MAPK signaling pathway, VEGF signaling pathway, Wnt signaling pathway and mTOR signaling pathway and other classic signaling pathways. This study preliminarily revealed the key targets, biological processes and signal pathway of "S. barbata-H. diffusa" against breast cancer. It was found that its function was in a multi-target and multi-channel manner, which laid a foundation for future molecular biological experiments.

LncRNAs in Secondary Hair Follicle of Cashmere Goat: Identification, Expression, and Their Regulatory Network in Wnt Signaling Pathway.

Long noncoding RNAs (lncRNAs) are a novel class of eukaryotic transcripts. They are thought to act as a critical regulator of protein-coding gene expression. Herein, we identified and characterized 13 putative lncRNAs from the expressed sequence tags from secondary hair follicle of Cashmere goat. Furthermore, we investigated their transcriptional pattern in secondary hair follicle of Liaoning Cashmere goat during telogen and anagen phases. Also, we generated intracellular regulatory networks of upregulated lncRNAs at anagen in Wnt signaling pathway based on bioinformatics analysis. The relative expression of six putative lncRNAs (lncRNA-599618, -599556, -599554, -599547, -599531, and -599509) at the anagen phase is significantly higher than that at telogen. Compared with anagen, the relative expression of four putative lncRNAs (lncRNA-599528, -599518, -599511, and -599497) was found to be significantly upregulated at telogen phase. The network generated showed that a rich and complex regulatory relationship of the putative lncRNAs and related miRNAs with their target genes in Wnt signaling pathway. Our results from the present study provided a foundation for further elucidating the functional and regulatory mechanisms of these putative lncRNAs in the development of secondary hair follicle and cashmere fiber growth of Cashmere goat.

Smad4 SUMOylation is essential for memory formation through upregulation of the skeletal myopathy gene TPM2.

BACKGROUND: Smad4 is a critical effector of TGF-ß signaling that regulates a variety of cellular functions. However, its role in the brain has rarely been studied. Here, we examined the molecular mechanisms underlying the post-translational regulation of Smad4 function by SUMOylation, and its role in spatial memory formation. RESULTS: In the hippocampus, Smad4 is SUMOylated by the E3 ligase PIAS1 at Lys-113 and Lys-159. Both spatial training and NMDA injection enhanced Smad4 SUMOylation. Inhibition of Smad4 SUMOylation impaired spatial learning and memory in rats by downregulating TPM2, a gene associated with skeletal myopathies. Similarly, knockdown of TPM2 expression impaired spatial learning and memory, while TPM2 mRNA and protein expression increased after spatial training. Among the TPM2 mutations associated with skeletal myopathies, the TPM2E122K mutation was found to reduce TPM2 expression and impair spatial learning and memory in rats. CONCLUSIONS: We have identified a novel role of Smad4 SUMOylation and TPM2 in learning and memory formation. These results suggest that patients with skeletal myopathies who carry the TPM2E122K mutation may also have deficits in learning and memory functions.

Degradation of dye wastewater with a photoelectric integration process (MPEC): Microbial fuel cells-assisted dual electrodes thin-film photoelectrocatalytic.

A novel photoelectric integration process (MPEC) was developed to degrade Amaranth. In the MPEC, the output voltage of the microbial fuel cells (MFCs) was used to assist the dual slant-placed electrodes thin-film photocatalytic (PC). With two MFCs connected in series, the MPEC process realized the highest decolorization efficiency. It is close to that of the external bias photoelectrocatalytic (PEC), and 7% higher than that of the self-generated electric field-assisted photoelectrocatalytic (SPEC). The feasibility of MPEC pre-treatment and MFC post-treatment of Amaranth was investigated. The results demonstrated that MPEC pre-treatment of Amaranth could improve its biodegradability. The higher MPEC decolorization efficiency indicated the stronger biodegradability of the obtained intermediates and the higher MFC output voltage. When the MPEC decolorization efficiency was gradually increased to 50%, the removal efficiencies of total Chemical Oxygen Demand (COD) by the MPEC and MFC increased; when the decolorization efficiency was increased above 50%, the removal efficiencies became stable. MPEC enhanced the biodegradability efficiently and was applicable to pre-treat textile wastewater.

Molecular characterization of HOXC8 gene and methylation status analysis of its exon 1 associated with the length of cashmere fiber in Liaoning cashmere goat.

Homeobox protein Hox-C8 (HOXC8) is a member of Hox family. It is expressed in the dermal papilla of the skin and is thought to be associated with the hair inductive capacity of dermal papilla cells. In the present study, we isolated and characterized a full-length open reading frame of HOXC8 cDNA from the skin tissue of Liaoning cashmere goat, as well as, established a phylogenetic relationship of goat HOXC8 with that of other species. Also, we investigated the effect of methylation status of HOXC8 exon 1 at anagen secondary hair follicle on the cashmere fiber traits in Liaoning cashmere goat. The sequence analysis indicated that the obtained cDNA was 1134-bp in length containing a complete ORF of 729-bp. It encoded a peptide of 242 amino acid residues in length. The structural analysis indicated that goat HOXC8 contained a typical homeobox domain. The phylogenetic analysis revealed that Capra hircus HOXC8 had a closer genetic relationship with that of Ovis aries, followed by Bos Taurus and Bubalus bubalis. The methylation analysis suggested that the methylation degree of HOXC8 exon 1 in anagen secondary hair follicle might be involved in regulating the growth of cashmere fiber in Liaoning cashmere goat. Our results provide new evidence for understanding the molecular structural and evolutionary characteristics of HOXC8 in Liaoning cashmere goat, as well as, for further insight into the role of methylation degree of HOXC8 exon 1 regulates the growth of cashmere fiber in goat.

A centrally generated primary care physician audit report does not improve colonoscopy uptake after a positive result on a fecal occult blood test in Ontario's ColonCancerCheck program.

BACKGROUND: Timely follow-up of fecal occult blood screening with colonoscopy is essential for achieving colorectal cancer mortality reduction. In the present study, we evaluated the effectiveness of centrally generated, physician-targeted audit and feedback to improve colonoscopy uptake after a positive fecal occult blood test (fobt) result within Ontario's population-wide ColonCancerCheck Program. METHODS: This prospective cohort study used data sets from Ontario's ColonCancerCheck Program (2008-2011) that were linked to provincial administrative health databases. Cox proportional hazards regression was used to estimate the effect of centralized, physician-targeted audit and feedback on colonoscopy uptake in an Ontario-wide fobt-positive cohort. RESULTS: A mailed physician audit and feedback report identifying individuals outstanding for colonoscopy for 3 or more months after a positive fobt result did not increase the likelihood of colonoscopy uptake (hazard ratio: 0.95; 95% confidence interval: 0.79 to 1.13). Duration of positive fobt status was strongly inversely associated with the hazard of follow-up colonoscopy (p for linear trend: <0.001). CONCLUSIONS: In a large population-wide setting, centralized tracking in the form of physician-targeted mailed audit and feedback reports does not improve colonoscopy uptake for screening participants with a positive fobt result outstanding for 3 or more months. Mailed physician-targeted screening audit and feedback reports alone are unlikely to improve compliance with follow-up colonoscopy in Ontario. Other interventions such as physician audits or automatic referrals, demonstrated to be effective in other jurisdictions, might be warranted.

A population-based assessment of primary care visits during adjuvant chemotherapy for breast cancer.

BACKGROUND: We used administrative health data to explore the impact of primary care physician (pcp) visits on acute-care service utilization by women receiving adjuvant chemotherapy for early-stage breast cancer (ebc). METHODS: Our population-based retrospective cohort study examined pcp visits and acute-care use [defined as an emergency room (er) visit or hospitalization] by women diagnosed with ebc between 2007 and 2009 and treated with adjuvant chemotherapy. Multivariate regression analysis was used to identify the effect of pcp visits on the likelihood of experiencing an acute-care visit. RESULTS: Patients receiving chemotherapy visited a pcp significantly more frequently than they had before their diagnosis [relative risk (rr): 1.48; 95% confidence interval (ci): 1.44 to 1.53; p < 0.001] and significantly more frequently than control subjects without cancer (rr: 1.51; 95% ci: 1.46 to 1.57; p < 0.001). More than one third of pcp visits by chemotherapy patients were related to breast cancer or chemotherapy-related side effects. In adjusted multivariate analyses, the likelihood of experiencing an er visit or hospitalization increased in the days immediately after a pcp visit (rr: 1.92; 95% ci: 1.76 to 2.10; p < 0.001). CONCLUSIONS: During chemotherapy treatment, patients visited their pcp more frequently than control subjects did, and they visited for reasons related to their breast cancer or to chemotherapy-related side effects. Visits to a pcp by patients receiving chemotherapy were associated with an increased frequency of er visits or hospitalizations in the days immediately after the pcp visit. Those results suggest an opportunity to institute measures for early detection and intervention in chemotherapy side effects.

[Current Status of Forensic Identification for Blunt Injuries of Internal Carotid Arterial System].

Internal carotid arterial system is the main source of blood supply in brain. In forensic identification practice, blunt injures of internal carotid arterial system usually cause complications such as thrombus, aneurysm and arteriovenous fistula, etc. The deaths following delayed cerebral infarction or intracranial haemorrhage are not rare. At present, literature of deaths caused by blunt injuries of internal carotid arterial system mainly consist of case reports in China. This paper reviews related literature and case reports at home and abroad, and summarizes forensic medical features and identification method of the deaths caused by such injuries. The results show that blunt injures of internal carotid arterial system are related to the direct or indirect force on head and neck, which can result in exceed physiological range traction of head and neck, incision following basicranial fracture, etc. Such injuries are common in the cases as mechanical asphyxia, cervical manipulation, traffic accident and fall, etc. The artery should be examined carefully, and the relationship among injury, disease and death should be analysed correctly when no cause of infarction and hemorrhage was found in routine examination of such cases in forensic pratice. Because of the difficulty for exposing the artery completely in autopsy, angiography can be used to infer the location when necessary for improving the scientificity and reliability of the appraisal conclusion.

Molecular characterization, expression and methylation status analysis of BMP4 gene in skin tissue of Liaoning cashmere goat during hair follicle cycle.

Bone morphogenetic protein 4 (BMP4) is a member of the bone morphogenetic protein family (BMPs). It is involved in the development and cycle of hair follicle, as well as, is thought to be a potential candidate gene for cashmere traits in goats. In the present study, we isolated and characterized a full-length open reading frame (ORF) of BMP4 cDNA from the skin tissue of Liaoning cashmere goat, and investigated the transcriptional pattern and methylation status of BMP4 gene in skin tissue of this breed during different stages of hair follicle cycle. The sequence analysis indicated that the isolated cDNA was 1264-bp in length containing a complete ORF of 1230-bp. It encoded a precursor peptide of 409 amino acids with a signal peptide of 19 amino acids. The structural analysis indicated that goat BMP4 contains typical TGF-ß propeptide and TGF-ß domains. In skin tissue, BMP4 is generally transcribed in an ascendant pattern from anagen to telogen. The methylation level of 5' flanking regulatory region of BMP4 gene might be involved in its mRNA expression in skin tissue: a higher BMP4 methylation level in skin coincides with a lower expression of BMP4 mRNA. These results from the present work provided a foundation for further insight into the functional and regulatory characteristics of BMP4 in the development and cycle of hair follicle in Liaoning Cashmere goat.

Differential Expression of microRNAs and their Regulatory Networks in Skin Tissue of Liaoning Cashmere Goat during Hair Follicle Cycles.

MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules that negatively regulate gene expression. Herein, we investigated a selective number of miRNAs for their expression in skin tissue of Liaoning Cashmere goat during hair follicle cycles, and their intracellular regulatory networks were constructed based on bioinformatics analysis. The relative expression of six miRNAs (mir-103-3p, -15b-5p, 17-5p, -200b, -25-3p, and -30c-5p) at anagen phase is significantly higher than that at catagen and/or telogen phases. In comparison to anagen, the relative expression of seven miRNAs (mir-148a-3p, -199a-3p, -199a-5p, -24-3p, -30a-5p, -30e-5p, and -29a-3p) was revealed to be significantly up-regulated at catagen and/or telogen stages. The network analyses of miRNAs indicated those miRNAs investigated might be directly or indirectly involved in several signaling pathways through their target genes. These results provided a foundation for further insight into the roles of these miRNAs in skin tissue of Liaoning Cashmere goat during hair follicle cycles.

Novel role and mechanism of protein inhibitor of activated STAT1 in spatial learning.

By using differential display PCR, we have previously identified 98 cDNA fragments from rat dorsal hippocampus, which are expressed differentially between the fast learners and slow learners from water-maze learning task. One cDNA fragment, which showed a higher expression level in fast learners, encodes the rat protein inhibitor of activated STAT1 (pias1) gene. Spatial training induced a significant increase in PIAS1 expression in rat hippocampus. Transient transfection of the wild-type (WT) PIAS1 plasmid to CA1 neurons facilitated, whereas transfection of PIAS1 siRNA impaired spatial learning in rats. Meanwhile, PIAS1WT increased STAT1 sumoylation, decreased STAT1 DNA binding and decreased STAT1 phosphorylation at Tyr-701 associated with spatial learning facilitation. But PIAS1 siRNA transfection produced an opposite effect on these measures associated with spatial learning impairment. Further, transfection of STAT1 sumoylation mutant impaired spatial acquisition, whereas transfection of STAT1 phosphorylation mutant blocked the impairing effect of PIAS1 siRNA on spatial learning. In this study, we first demonstrate the role of PIAS1 in spatial learning. Both posttranslational modifications (increased sumoylation and decreased phosphorylation) mediate the effect of PIAS1 on spatial learning facilitation.

Acute effects of kinesio taping on knee extensor peak torque and electromyographic activity after exhaustive isometric knee extension in healthy young adults.

OBJECTIVE: To evaluate the effect of Kinesio Tex tape and its method of application, Kinesio Taping (KT) on knee extensor performance before and after an exhaustive isometric knee extension exercise. DESIGN: Single-blinded, randomized control trial. SETTING: Centre for Sports Training and Rehabilitation at The Hong Kong Polytechnic University. PARTICIPANTS: Twenty-six healthy volunteers with no history of knee injuries. INTERVENTIONS: Subjects were randomized to either the KT or sham taping group. MAIN OUTCOME MEASURES: The effects of KT on the neuromuscular performance of the knee extensors were measured before and after KT application, and immediately and 5 and 10 minutes after an exhaustive isometric knee extension exercise. RESULTS: Within-group analyses revealed a significant effect of time on the peak torque in isometric knee extension (F2.73,65.44 = 24.5, P < 0.001), but no significant group (F2.73,65.44 = 2.13, P = 0.11) or interaction (F1,24 = 0.59, P = 0.45) effect. A significant time effect (F2.52,60.14 = 3.75, P = 0.02) and a significant time × group interaction (F1,24 = 4.59, P = 0.04) was found for the rate of peak torque development. Post hoc comparisons revealed significantly higher rates in the intervention group (F1,24 = 4.594, P = 0.04) over all 5 tests. No significant effects of time (F4,96 = 0.88, P = 0.48; F2.56,61.35 = 2.75, P = 0.06), group (F4,96 = 0.56, P = 0.69; F2.56,61.35 = 1.16, P = 0.33), or time × group interaction (F1,24 = 2.77, P = 0.11; F1,24 = 0.20, P = 0.66) were found for either the electromechanical delay or electromyographic results, respectively. CONCLUSIONS: The present study suggests that KT shortens the time required to generate peak torque during isometric knee extension, which has important implications for sports performances that require the rapid generation of peak muscular force. CLINICAL RELEVANCE: Kinesio taping is commonly seen in the sports arena. The popularity is presumably due to the general belief in its injury prevention and enhancement of muscle performance. The results of the present findings suggested that KT shortens the time to reach peak torque generation. Aside from this, there is no other significant positive effect on muscle performance. Further investigation on the effects of KT on muscle performance is warranted.

Simultaneous picosecond and femtosecond solitons delivered from a nanotube-mode-locked all-fiber laser.

We propose a compact nanotube-mode-locked all-fiber laser that can simultaneously generate picosecond and femtosecond solitons at different wavelengths. The pulse durations of picosecond and femtosecond solitons are measured to be ∼10.6 ps and ∼466 fs, respectively. Numerical results agree well with the experimental observations and clearly reveal that the dynamic evolutions of the picosecond and femtosecond solitons are qualitatively distinct in the intracavity. Our study presents a simple, stable, low-cost, and dual-scale ultrafast-pulsed laser source suitable for practical applications in optical communications.

Impact of socio-economic status on breast cancer screening in women with diabetes: a population-based study.

AIMS: There is evidence to suggest that mammography rates are decreased in women with diabetes and in women of lower socio-economic status. Given the strong association between low socio-economic status and diabetes, we explored the extent to which differences in socio-economic status explain lower mammography rates in women with diabetes. METHODS: A population-based retrospective cohort study in Ontario, Canada, of women aged 50 to 69 years with diabetes between 1999 and 2010 age matched 1:2 to women without diabetes. Main outcome measure is the likelihood of at least one screening mammogram in women with diabetes within a 36-month period, starting as of either 1 January 1999, their 50th birthday, or 2 years after diabetes diagnosis--whichever came last. Outcomes were compared with those in women without diabetes during the same period as their matched counterparts, adjusting for socio-economic status based on neighbourhood income and other demographic and clinical variables. RESULTS: Of 504,288 women studied (188,759 with diabetes, 315,529 with no diabetes), 63.8% had a screening mammogram. Women with diabetes were significantly less likely to have a mammogram after adjustment for socio-economic status and other factors (odds ratio 0.79, 95% CI 0.78-0.80). Diabetes was associated with lower mammogram use even in women from the highest socio-economic status quintile (odds ratio 0.79, 95% CI 0.75-0.83). CONCLUSIONS: The presence of diabetes was an independent barrier to breast cancer screening, which was not explained by differences in socio-economic status. Interventions that target patient, provider, and health system factors are needed to improve cancer screening in this population.

MTTP polymorphisms and susceptibility to non-alcoholic fatty liver disease in a Han Chinese population.

BACKGROUND: The microsomal triglyceride transfer protein (MTP) is required for the assembly and secretion of apolipoprotein B (ApoB)-containing lipoproteins from the liver and intestine. Previous studies showed that functional polymorphisms in the MTTP gene correspond to lower LDL levels and protect against other traits of the metabolic syndrome. AIMS: Here, we aimed to investigate whether MTTP single nucleotide polymorphisms (SNPs) and their predicted haplotypes of linkage disequilibrium blocks contribute to non-alcoholic fatty liver disease (NAFLD) susceptibility in a Han Chinese population. METHODS: Seven tag SNPs in the MTTP gene were selected and genotyped in a frequency-matched case-control study in a population from Fuzhou City, China. We enrolled 580 patients with NAFLD and 580 healthy controls. RESULTS: In the multivariate logistic regression analysis, the rs1800804 (-164 T/C) was associated with an increased risk of NAFLD, while the rs1057613 A/G and rs3805335 C/T SNPs were associated with a decreased risk of NAFLD. The cumulative effect of the rs1800804 (-164 T/C), rs1057613 and rs3805335 was estimated, and a significant increased trend in the risk of NAFLD with increasing genetic risk score was observed (adjusted P(trend) = 0.014). Furthermore, the results of haplotype analysis suggested that the haplotype GC in block 1 containing the -164 C allele was associated with an increased risk of NAFLD, while haplotype TGTTC in block 2 was associated with a decreased risk of NAFLD. CONCLUSIONS: Our data show that MTTP genetic polymorphisms influence the susceptibility to developing NAFLD independently or jointly in the Han Chinese population.