Elucidating the Functional Mechanism of PTK7 in Cancer Development through Spatial Assembly Analysis Using Super Resolution Imaging.

Protein tyrosine kinase-7 (PTK7) has been reported as a vital participant in the Wnt signaling pathway, influencing tumorigenesis and metastasis. However, their specific roles in the mechanisms underlying cancer development and progression remain elusive. Here, using direct stochastic optical reconstruction microscopy (dSTORM) with aptamer-probe labeling, we first revealed that a weakening clustering distribution of PTK7 on the basal membranes happened as cellular migration increased during cancer progression. This correspondence was further supported by a diminished aggregated state of PTK7 caused by direct enhancement of cell migration. By comparing the alterations in PTK7 distribution with activation or inhibition of specific Wnt signaling pathway, we speculated that PTK7 could modulate cell migration by participating in the interplay between canonical Wnt (in MCF7 cells) and noncanonical Wnt signals (in MDA-MB-231 cells). Furthermore, we discovered that the spatial distribution morphology of PTK7 was also subject to the hydrolysis ability and activation state of the related hydrolase Matrix metallopeptidase14 (MMP14). This function-related specific assembly of PTK7 reveals a clear relationship between PTK7 and cancer. Meanwhile, potential molecular interactions predicted by the apparent assembly morphology can promote a deep understanding of the functional mechanism of PTK7 in cancer progress.

Noncanonical regulation of HOIL-1 on cancer stemness and sorafenib resistance identifies pixantrone as a novel therapeutic agent for HCC.

BACKGROUND AND AIMS: Cancer stem cells (CSCs) contribute to therapy resistance in HCC. Linear ubiquitin chain assembly complex (LUBAC) has been reported to accelerate the progression of cancers, yet its role in the sorafenib response of HCC is poorly defined. Herein, we investigated the impact of LUBAC on sorafenib resistance and the CSC properties of HCC, and explored the potential targeted drugs. APPROACH AND RESULTS: We found that HOIL-1, but not the other components of LUBAC, played a contributing role in LUBAC-mediated HCC sorafenib resistance, independent of its ubiquitin ligase activity. Both in vitro and in vivo assays revealed that the upregulated HOIL-1 expression enhanced the CSC properties of HCC. Mechanistically, HOIL-1 promoted sorafenib resistance and the CSC properties of HCC through Notch1 signaling. Mass spectrometry, co-immunoprecipitation, western blot, and immunofluorescence were used to determine that the A64/Q65 residues of HOIL-1 bound with the K78 residue of Numb, resulting in impaired Numb-mediated Notch1 lysosomal degradation. Notably, pixantrone was screened out by Autodock Vina, which was validated to disrupt HOIL-1/Numb interaction to inhibit Notch1 signaling and CSC properties by targeting the Q65 residue of HOIL-1. Moreover, pixantrone exerted synergistic effects with sorafenib for the treatment of HCC in different HCC mouse models. CONCLUSIONS: HOIL-1 is critical in promoting sorafenib resistance and CSC properties of HCC through Notch1 signaling. Pixantrone targeting HOIL-1 restrains the sorafenib resistance and provides a potential therapeutic intervention for HCC.

Brain tissue heterotopic in the adrenal gland in a child: a scarce case report.

Heterotopic brain tissue is rare and has not been reported. Our center made the first report. 4 years and 2 months old Girl presented with a cystic mass in the right adrenal gland 2 weeks after right upper abdominal pain. The operation was successful, and the diagnosis was confirmed by postoperative pathology. 6 months after the procedure, the incision healed well without recurrence. This case report has a detailed diagnosis and treatment process and satisfactory examination results. It can provide a reference for diagnosing and treating clinical HBT and reduce the risk of misdiagnosis and mistreatment.

Assembly Characterization of Human Equilibrium Nucleoside Transporter 1 (hENT1) by Inhibitor Probe-Based dSTORM Imaging.

Nucleoside transporters (NTs) play an important role in the metabolism of nucleoside substances and the efficacy of nucleoside drugs. Its spatial information related to biofunctions at the single-molecule level remains unclear, owing to the limitation of the existing labeling methods and traditional imaging methods. Therefore, we synthesize the inhibitor-based fluorescent probe SAENTA-Cy5 and apply direct stochastic optical reconstruction microscopy (dSTORM) to conduct refined observation of human equilibrative nucleoside transporter 1 (hENT1), the most important and famous member of NTs. We first demonstrate the labeling specificity and superiority of SAENTA-Cy5 to the antibody probe. Then, we found different assembly patterns of hENT1 on the apical and basal membranes, which are further investigated to be caused by varying associations of membrane carbohydrates, membrane classical functional domains (lipid rafts), and associated membrane proteins (EpCAM). Our work provides an efficient method for labeling hENT1, which contributes to realize fine observation of NTs. The findings on the assembly features and potential assembly mechanism of hENT1 promote a better understanding of its biofunction, which facilitates further investigations on how NTs work in the metabolism of nucleoside and nucleoside analogues.

Causal associations between chronic hepatitis B and COVID-19 in East Asian populations.

BACKGROUND: The relationship between chronic hepatitis B (CHB) and Coronavirus disease 2019 (COVID-19) has been inconsistent in traditional observational studies. METHODS: We explored the total causal and direct causal associations between CHB and the three COVID-19 outcomes using univariate and multivariate Mendelian randomization (MR) analyses, respectively. Genome-wide association study datasets for CHB and COVID-19 were obtained from the Japan Biobank and the COVID-19 Host Genetics Initiative, respectively. RESULTS: Univariate MR analysis showed that CHB increased the risk of SARS-CoV-2 infection (OR = 1.04, 95% CI 1.01-1.07, P = 3.39E-03), hospitalized COVID-19 (OR = 1.10, 95% CI 1.06-1.13, P = 7.31E-08), and severe COVID-19 (OR = 1.16, 95%CI 1.08-1.26, P = 1.43E-04). A series of subsequent sensitivity analyses ensured the stability and reliability of these results. In multivariable MR analyses adjusting for type 2 diabetes, body mass index, basophil count, and smoking, genetically related CHB is still positively associated with increased risk of SARS-CoV-2 infection (OR = 1.06, 95% CI 1.02-1.11, P = 1.44E-03) and hospitalized COVID-19 (OR = 1.12, 95% CI 1.07-1.16, P = 5.13E-07). However, the causal link between CHB and severe COVID-19 was attenuated after adjustment for the above variables. In addition, the MR analysis did not support the causal effect of COVID-19 on CHB. CONCLUSIONS: This study provides evidence that CHB increases COVID-19 susceptibility and severity among individuals of East Asian ancestry.

Chaotropic Effect Stabilized Radical-Containing Supramolecular Organic Frameworks for Photothermal Therapy.

Radical-containing frameworks (RCFs) have emerged as promising functional materials in various fields due to the combination of the highly ordered frame structure and the fascinating property of organic radicals. Here, the first example of radical-containing supramolecular organic frameworks (SOFs) fabricated by the chaotropic effect between closo-dodecaborate cluster (B12 H122- ) and 2,4,6-tri(4-pyridyl)-1,3,5-triazine (TPT3+ ) is presented. The SOFs can be easily synthesized by stirring the B12 H122- and the TPT3+ in aqueous solution through self-assembly. Upon 435 nm light irradiation, the SOFs exhibits photochromic behavior from slight yellow (SOF-1) to dark purple (SOF-2). Electron paramagnetic resonance spectroscopy also reveals that stable radicals are generated in situ after light irradiation. Powder X-ray diffraction demonstrates the SOFs maintain their structural stabilities upon light irradiation. More interestingly, the radical-containing SOFs exhibit efficient photothermal effect under 660 nm light irradiation, which can be applied as photothermal agent for antibacterial application both in vitro and in vivo. This work highlights the construction of RCFs through supramolecular self-assembly, which may arouse applications in energy, catalysis, photoluminescence, and biomedical fields.

Organization of Protein Tyrosine Kinase-7 on Cell Membranes Characterized by Aptamer Probe-Based STORM Imaging.

Protein tyrosine kinase-7 (PTK7), as an important membrane receptor, regulates various cellular activities, including cell polarity, movement, migration, and invasion. Although lots of research studies focused on revealing its functions from the aspect of the expression of the gene and protein are present, the relationship between the spatial distribution at the single-molecule level and the function remains unclear. Through combining aptamer probe labeling and super-resolution imaging technology, after verifying the specificity and superiority of the aptamer probe, a more significant clustering distribution of PTK7 is found on the MCF10A cell basal membrane than on the apical membrane, which is thought to be related to their specific functions on different membranes. By exploring the relationship between the assembly of PTK7 and lipid rafts, actin cytoskeleton, and carbohydrate chains on the membrane, the unique distribution of PTK7 on disparate membranes is revealed to be probably because of the varied dominant position of these three factors. These findings present the detailed spatial information of PTK7 and the related potential organization mechanism on the cell membrane, which will facilitate a better understanding of the relationship between the molecular assembly and its function, as well as the overall structure of the cell membrane.

Immediate versus delayed frozen embryo transfer in patients following a stimulated IVF cycle: a randomised controlled trial.

STUDY QUESTION: Is there any difference in the ongoing pregnancy rate after immediate versus delayed frozen embryo transfer (FET) following a stimulated IVF cycle? SUMMARY ANSWER: Immediate FET following a stimulated IVF cycle produced significantly higher ongoing pregnancy and live birth rate than did delayed FET. WHAT IS KNOWN ALREADY: Embryo cryopreservation is an increasingly important part of IVF, but there is still no good evidence to advise when to perform FET following a stimulated IVF cycle. All published studies are retrospective, and the findings are contradictory. STUDY DESIGN, SIZE, DURATION: This was a randomised controlled non-inferiority trial of 724 infertile women carried out in two fertility centres in China between 9 August 2017 and 5 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile women having their first FET cycle after a stimulated IVF cycle were randomly assigned to either (1) the immediate group in which FET was performed in the first menstrual cycle following the stimulated IVF cycle (n = 362) or (2) the delayed group in which FET was performed in the second or later menstrual cycle following the stimulated IVF cycle (n = 362). All FET cycles were performed in hormone replacement cycles. The randomisation sequence was generated using an online randomisation program with block sizes of four. The primary outcome was the ongoing pregnancy rate, defined as a viable pregnancy beyond 12 weeks of gestation. The non-inferiority margin was -10%. Analysis was performed by both per-protocol and intention-to-treat approaches. MAIN RESULTS AND THE ROLE OF CHANCE: Women in the immediate group were slightly younger than those in the delayed group (30.0 (27.7-33.5) versus 31.0 (28.5-34.2), respectively, P = 0.006), but the proportion of women ≤35 years was comparable between the two groups (308/362, 85.1% in the immediate group versus 303/362, 83.7% in the delayed group). The ongoing pregnancy rate was 49.6% (171/345) in the immediate group and 41.5% (142/342) in the delayed group (odds ratios 0.72, 95% CI 0.53-0.98, P = 0.034). The live birth rate was 47.2% (163/345) in the immediate group and 37.7% (129/342) in the delayed group (odds ratios 0.68, 95% CI 0.50-0.92, P = 0.012). The miscarriage rate was 13.2% (26 of 197 women) in the immediate group and 24.2% (43 of 178 women) in the delayed group (odds ratios 2.10; 95% CI 1.23-3.58, P = 0.006). The multivariable logistic regression, which adjusted for potential confounding factors including maternal age, number of oocytes retrieved, embryo stage at transfer, number of transferred embryos/blastocysts, reasons for FET, ovarian stimulation protocol and trigger type, demonstrated that the ongoing pregnancy rate was still higher in the immediate group. LIMITATIONS, REASON FOR CAUTION: Despite randomisation, the two groups still differed slightly in the age of the women at IVF. The study was powered to consider the ongoing pregnancy rate, but the live birth rate may be of greater clinical interest. Conclusions relating to the observed differences between the treatment groups in terms of live birth rate should, therefore, be made with caution. WIDER IMPLICATIONS OF THE FINDINGS: Immediate FET following a stimulated IVF cycle had a significantly higher ongoing pregnancy and live birth rate than delayed FET. The findings of this study support immediate FET after a stimulated IVF cycle. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used and no competing interests were declared. TRIAL REGISTRATION NUMBER: ClinicalTials.gov identifier: NCT03201783. TRIAL REGISTRATION DATE: 28 June 2017. DATE OF FIRST PATIENT'S ENROLMENT: 9 August 2017.

Mechanistic insights into GLUT1 activation and clustering revealed by super-resolution imaging.

The glucose transporter GLUT1, a plasma membrane protein that mediates glucose homeostasis in mammalian cells, is responsible for constitutive uptake of glucose into many tissues and organs. Many studies have focused on its vital physiological functions and close relationship with diseases. However, the molecular mechanisms of its activation and transport are not clear, and its detailed distribution pattern on cell membranes also remains unknown. To address these, we first investigated the distribution and assembly of GLUT1 at a nanometer resolution by super-resolution imaging. On HeLa cell membranes, the transporter formed clusters with an average diameter of ∼250 nm, the majority of which were regulated by lipid rafts, as well as being restricted in size by both the cytoskeleton and glycosylation. More importantly, we found that the activation of GLUT1 by azide or MßCD did not increase its membrane expression but induced the decrease of the large clusters. The results suggested that sporadic distribution of GLUT1 may facilitate the transport of glucose, implying a potential association between the distribution and activation. Collectively, our work characterized the clustering distribution of GLUT1 and linked its spatial structural organization to the functions, which would provide insights into the activation mechanism of the transporter.

Structural Mechanism Analysis of Orderly and Efficient Vesicle Transport by High-Resolution Imaging and Fluorescence Tracking.

The orderly organelle interaction network is essential for normal biological activity of cells. However, the mechanism of orderly organelle interaction remains elusive. In this report, we analyzed the structure characteristics of the cell membrane, endocytic vesicles, and the Golgi membrane through a high-resolution imaging technique and further comprehensively investigated the vesicle-transport process via epidermal growth factor receptor endocytosis and a recycling pathway using a real-time fluorescence tracing method. Our data suggest that orderly vesicle transport is due to protein protrusion from the outer surface of endocytic vesicles and that full membrane fusion between homotypic endocytic vesicles is a result of the rough outer surface. Finally, the kiss-and-run method, which is utilized by endocytic vesicles to communicate with the trans-Golgi network (TGN) is attributed to a dense protein layer at the outer surface of the TGN. In summary, by combining static structural analysis with dynamic tracing, we elucidate the mechanism of orderly vesicle transport from the overall structural features of the membrane. This work provides insight into the structural mechanisms underlying vital biological processes involving organelle interactions at the molecular level.

Quantitatively Mapping the Assembly Pattern of EpCAM on Cell Membranes with Peptide Probes.

Epithelial cell adhesion molecule (EpCAM) is an important type I transmembrane protein that is overexpressed on the surfaces of most cancer cells and involved in various biological processes such as cell adhesion and cell signaling. Although it plays crucial roles in cell functions and tumorigenesis, questions concerning the detailed morphology, molecular stoichiometry, and the assembly mechanisms of EpCAM on cell membranes have not been fully elucidated. Here, we used direct stochastic optical reconstruction microscopy (dSTORM) and relied on fluorophore-conjugated peptides to quantitatively analyze the assembly pattern of EpCAM with single-molecule precision. EpCAM was found to organize heterogeneous clusters with different sizes, which contain different numbers of EpCAM molecules on MCF-7 cell membranes. Moreover, dual-color dSTORM imaging revealed a significant correlation between EpCAM and tetraspanin CD9, and part of the EpCAM clusters could be disrupted by knockdown of CD9, which indicated that EpCAM might localize in tetraspanin-enriched microdomains (TEMs) and function cooperatively with CD9 on cell membranes. In addition, the assembly of the membrane EpCAM was found to be limited by both cytoskeleton and glycosylation. Overall, our work clarified the clustered distribution of EpCAM and revealed the potential mechanisms of its clustering at the molecular level, promoting a deeper understanding of the nano-organization of membrane proteins.

17ß-estradiol promotes bone marrow mesenchymal stem cell migration mediated by chemokine upregulation.

Bone marrow-derived cells engraft to the uterine endometrium and contribute to endometriosis. This study sought to further confirm that estrogen can promote the migration of bone marrow mesenchymal stem cells (BMSCs) and to investigate the function of estrogen on the secretion of chemokines during BMSC migration. BMSCs were treated with or without 17ß-estradiol, cultured with or without endometrial stromal cells (ESCs), or pretreated with or without AMD 3100 (an antagonist of the SDF-1α receptor) before co-culture. A migration assay was used to investigate the changes in the migration of BMSCs. The secretion of chemokines in the co-culture medium was detected by chemokine analysis, and the mRNA expression of SDF-1α in cells was tested using quantitative real-time PCR. The results revealed that the migration of BMSCs was promoted by ESC, and the migration ability of BMSCs was enhanced after treatment with 17ß-estradiol (p < 0.05). Through chemokine analysis, we further showed that 17ß-estradiol promoted the secretion of chemokines especially for SDF-1α (p < 0.05). Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these chemokines were mainly linked to the cytokine signaling pathway and interaction with cytokines receptors. Furthermore, the expression of SDF-1α mRNA was significantly increased in the 17ß-estradiol treatment group (p < 0.001), and the migration of BMSCs was blocked by the use of our SDF-1α antagonist (p < 0.01). Our results indicate that 17ß-estradiol could promote the chemotaxis and migration of BMSCs by up-regulating the secretion of chemokines, especially SDF-1α. Our study provides additional evidence to support and supplement the stem cell theory of endometriosis.

Super-resolution microscopy reveals the insulin-resistance-regulated reorganization of GLUT4 on plasma membranes.

GLUT4 (also known as SLC2A4) is essential for glucose uptake in skeletal muscles and adipocytes, which play central roles in whole-body glucose metabolism. Here, using direct stochastic optical reconstruction microscopy (dSTORM) to investigate the characteristics of plasma-membrane-fused GLUT4 at the single-molecule level, we have demonstrated that insulin and insulin resistance regulate the spatial organization of GLUT4 in adipocytes. Stimulation with insulin shifted the balance of GLUT4 on the plasma membrane toward a more dispersed configuration. In contrast, insulin resistance induced a more clustered distribution of GLUT4 and increased the mean number of molecules per cluster. Furthermore, our data demonstrate that the F5QQI motif and lipid rafts mediate the maintenance of GLUT4 clusters on the plasma membrane. Mutation of F5QQI (F5QQA-GLUT4) induced a more clustered distribution of GLUT4; moreover, destruction of lipid rafts in adipocytes expressing F5QQA-GLUT4 dramatically decreased the percentage of large clusters and the mean number of molecules per cluster. In conclusion, our data clarify the effects of insulin stimulation or insulin resistance on GLUT4 reorganization on the plasma membrane and reveal new pathogenic mechanisms of insulin resistance.

Mutations in TUBB8 and Human Oocyte Meiotic Arrest.

Background Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown. Methods We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other ß-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells, and several somatic tissues by means of a quantitative reverse-transcriptase-polymerase-chain-reaction assay. We evaluated the effect of the TUBB8 mutations on the assembly of the heterodimer consisting of one α-tubulin polypeptide and one ß-tubulin polypeptide (α/ß-tubulin heterodimer) in vitro, on microtubule architecture in HeLa cells, on microtubule dynamics in yeast cells, and on spindle assembly in mouse and human oocytes. Results We identified seven mutations in the primate-specific gene TUBB8 that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed ß-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/ß-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes. Conclusions TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. (Funded by the National Basic Research Program of China and others.).

Alpha-glucosidase inhibitor 1-Deoxynojirimycin promotes beige remodeling of 3T3-L1 preadipocytes via activating AMPK.

Obesity is a serious health challenge in the world, and searching effective drugs to cure obesity is of great importance. 1-Deoxynojirimycin (DNJ) is extracted from mulberry leaves and acts as an α-glucosidase inhibitor to lower blood glucose. Recent studies demonstrated that it also has anti-obesity effect, but the mechanisms remain unknown. In our present study, we mainly examined the effects of DNJ on beige remodeling of 3T3-L1 preadipocytes. We observed that DNJ didn't affect the mRNA levels of fatty acid binding protein 4 (aP2), peroxisome proliferator-activated receptor γ (PPARγ), preadipocyte factor-1 (Pref-1) as well as the mitochondrial uncoupling protein 1 (UCP1), PR domain containing protein 16 (PRDM16), transmembrane protein 26 (TMEM26) in undifferentiated preadipocytes. But after inducing 3T3-L1 preadipocytes to differentiation with white or beige adipogenic medium, DNJ significantly reduced aP2, PPARγ and Pref-1 expressions, while up-regulated the expressions of UCP1, PRDM16 and TMEM26, accompanying with decreased lipid deposition. The ratio of p-AMPK/AMPK was up-regulated by DNJ (10 µM) treatment for 10 days, and the effects of DNJ on p-AMPK/AMPK, UCP1 and PRDM16 could be blocked by AMPK inhibitor Compound C. These results demonstrated that hypoglycemic agent DNJ could suppress the adipogenesis during the differentiation of white preadipocytes, and promote the switch of white preadipocytes to beige adipocytes via activating AMPK, which provided new mechanisms for explaining the benefits of DNJ on obesity-related disorders.

Strong damping of the localized surface plasmon resonance of Ag nanoparticles by Ag2O.

By studying oxidation of AgNPs (Ag nanoparticles) and decomposition of the produced silver oxide, we demonstrate that the localized surface plasmon resonance (LSPR) of AgNPs was damped by Ag2O produced during oxygen plasma irradiation (OPI). The AgNPs were fabricated by evaporation of high pure silver under high vacuum. The oxidation was conducted in oxygen plasma generated by radio frequency glow discharging in vacuum, and the decomposition was performed by annealing the silver oxide in nitrogen ambient at temperatures ranging from room temperature to 450 °C. Samples were characterized by color, absorption spectra, surface enhanced Raman scattering, x-ray photoelectron spectroscopy, and field emission scanning electron microscopy. The bandgap of the silver oxide was calculated. We propose that AgNPs are only partially oxidized into silver oxide during OPI, and the LSPR of the AgNPs left without being oxidation is strongly damped by the produced silver oxide. This LSPR damping is responsible for the transparency of the sample after OPI for 2 s.

Expression of ENPP3 in human cyclic endometrium: a novel molecule involved in embryo implantation.

Ectonucleotide pyrophosphatase-phosphodiesterase 3 (ENPP3), a protein detected in the human uterus, has been found to play an important role in the development and invasion of tumours. It was recently discovered that ENPP3 was upregulated during the window of implantation in the human endometrium but its functional relevance remains elusive. The objective was to determine ENPP3 expression in human endometrium and its roles in endometrial receptivity and embryo implantation. ENPP3 expression was analysed using immunohistochemistry and western blot assay. The effects of ENPP3 on embryo implantation were evaluated using a BeWo cell (a human choriocarcinoma cell line) spheroid attachment assay and BeWo cells were dual cultured with Ishikawa cells transfected with lentiviral vectors (LV5-NC or LV5-ENPP3) to mimic embryo implantation in a Transwell model. The effects of endometrial ENPP3 on factors related to endometrial receptivity were also determined. The results showed that ENPP3 was expressed in human endometrial epithelial cells and its expression levels changed during the menstrual cycle, peaking in the mid-secretory phase, corresponding to the time of embryo implantation. The overexpression of endometrial ENPP3 not only increased the embryo implantation rate but also had positive effects on the expression of factors related to endometrial receptivity in human endometrial cells. The results indicate that ENPP3 levels undergo cyclic changes in the endometrium and affect embryo adhesion and invasion via altering the expression of implantation factors in the human endometrium. Therefore, ENPP3 may play an important role in embryo implantation and may be a unique biomarker of endometrial receptivity.

Integrins ß1 and ß3 are biomarkers of uterine condition for embryo transfer.

BACKGROUND: Clinical ovulation induction induces blood estrogen (E2) in excess of physiological levels, which can hinder uterine receptivity. In contrast, progesterone produces the opposite clinical effect, suggesting that it might be capable of recovering the lost receptivity resulting from exposure to high estrogen levels. Integrins are the most widely used biological markers for monitoring uterine conditions. We studied progesterone-induced changes in integrin ß expression patterns as biomarkers for changes in uterine receptivity in response to increased estrogen levels. METHODS: Endometrial biopsy samples from patients were screened for their estrogen (E2) and progesterone (P4) content and expressing levels of integrin ß1 and ß3. Uterine receptivity was evaluated using human endometrial adenocarcinoma cells in an embryo attachment model. The respective and concatenated effects of embryo attachment and changes in the integrin ß1 and ß3 expression patterns on the adenocarcinoma cell plasma membranes in response to 100 nM concentrations of E2 and P4 were evaluated. RESULTS: Increased blood E2 concentrations were associated with significantly decreased the levels of integrin ß3 expression in uterine biopsy samples. In vitro experiments revealed that a 100 nM E2 concentration inhibited the distribution of integrin ß3 on the plasma membranes of human endometrial adenocarcinoma cells used in the embryo attachment model, and resulted in decreased rates of embryo attachment. In contrast, P4 enhanced the expression of integrin ß1 and promoted its distribution on the plasma membranes. Furthermore, P4 recovered the embryo attachment efficiency that was lost by exposure to 100 nM E2. CONCLUSIONS: Blood E2 and P4 levels and integrin ß3 and ß1 expression levels in uterine biopsy samples should be considered as biomarkers for evaluating uterine receptivity and determining the optimal time for embryo transfer. Trial registration Trial number: ChiCTR-TRC-13003777; Name of registry: Chinese Clinical Trial Registry; Date of registration: 4 September 2013; Date of enrollment of the first study participant: 15 October 2013.

Ar plasma irradiation improved optical and electrical properties of TiO2/Ag/TiO2 multilayer thin film.

Embedding a thin metal layer between two thin dielectric or semiconductor layers [dielectric/metal/dielectric (DMD)] leads to a kind of transparent electrode that is promising as a substitute for the currently widely applied indium tin oxide electrode. However, the optical and electrical properties of DMD still wait for further improvement. In this study, Ar plasma irradiation (API) was, for the first time to our knowledge, applied to improve the optical and electrical properties of a TiO2/Ag/TiO2 electrode that was fabricated by electron-beam evaporation of TiO2 and electric-resistance heating of high purity Ag under vacuum. Ar plasma was produced by radio frequency glow discharge. The Ag layer was bombarded before the second layer of TiO2 was deposited. The electrode with configuration of TiO2 (24 nm)/Ag(14 nm)/TiO2 (24 nm) after API for 10 s shows excellent performance. The mean transmittance between 370 and 800 nm reaches 94% and the sheet resistance is as low as 6 Ω/sq, while Haacke's figure of merit is as high as 112×10(-3) Ω(-1). The improvement mechanism is discussed based on field emission scanning electron microscope images and absorption spectra. The improvement is attributed to the fact that API reduces the localized surface plasmon resonance of Ag nanoparticles and makes the Ag film thinner and denser.

Magnetic-field-enabled resolution enhancement in super-resolution imaging.

A novel strategy for modulating the photophysics of organic dyes in super-resolution fluorescence imaging using an external magnetic field was reported. The magnetic field induced increase in fluorescence intensity, localization number of probe molecules, and the number of photons emitted per molecule as compared to those acquired without a magnetic field were experimentally confirmed. Improved dSTORM localization precision and imaging resolution were consequently achieved.