In superconductors, electrons are paired and condensed into the ground state. An impurity can break the electron pairs into quasiparticles with energy states inside the superconducting gap. The ...characteristics of such in-gap states reflect accordingly the properties of the superconducting ground state. A zero-energy in-gap state is particularly noteworthy, because it can be the consequence of non-trivial pairing symmetry or topology. Here we use scanning tunnelling microscopy/spectroscopy to demonstrate that an isotropic zero-energy bound state with a decay length of ∼10 Å emerges at each interstitial iron impurity in superconducting Fe(Te,Se). More noticeably, this zero-energy bound state is robust against a magnetic field up to 8 T, as well as perturbations by neighbouring impurities. Such a spectroscopic feature has no natural explanation in terms of impurity states in superconductors with s-wave symmetry, but bears all the characteristics of the Majorana bound state proposed for topological superconductors, indicating that the superconducting state and the scattering mechanism of the interstitial iron impurities in Fe(Te,Se) are highly unconventional.
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IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UL, UM, UPUK
Background
Exposure to environmental pollutants promotes Th2 cell responses. Aryl hydrocarbon receptor (AhR) activation aggravates allergic responses. Epithelium‐derived thymic stromal lymphopoietin ...(TSLP), interleukin (IL)‐25, and IL‐33 are implicated in the dysregulation of Th2 immune responses in severe allergic asthma.
Methods
Bronchial biopsies of 28 allergic severe asthma and 6 mild asthma subjects from highly polluted areas were analyzed for AhR nuclear translocation (NT), cytokine expression, and gene activation. Cultured primary epithelial cells were stimulated with diesel exhausted particles (DEP) to determine AhR‐mediated IL‐33, Il‐25, and TSLP synthesis and release.
Results
Primary bronchial epithelial cells exposed to DEP showed upregulation of IL‐33, IL‐25, and TSLP. These effects were abolished by knockdown of AhR by siRNA. Increased AhR/ARNT binding to promoters of IL‐33, IL‐25, and TSLP was found using chromatin immunoprecipitation (ChIP) assay. Allergic severe asthma with high AhR NT had higher bronchial gene and protein expression of IL‐33, IL‐25, and TSLP. These patients derived clinical benefit from anti‐IgE treatment.
Conclusion
Aryl hydrocarbon receptor activation by DEP mediates upregulation of IL‐33, IL‐25, and TSLP with Th2 activation, potentially linking environmental pollution and allergic severe asthma.
Environmental diesel exhaust particles (DEP) exposed to airway epithelium ligate cytoplasmic aryl hydrocarbon receptor (AhR), translocate to the nucleus with aryl hydrocarbon receptor nuclear translocator (ARNT), and then transactivate IL‐33, Il‐25, and TSLP gene expression. Patients with high AhR nucleus translocation overexpressed IL‐33, Il‐25, and TSLP cytokines compared to those with low. Patients with high AhR nucleus translocation are more response to anti‐IgE therapy compared to those with low.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Combined esophageal high‐resolution impedance manometry (HRIM) measures multiple pressures and bolus transit simultaneously, facilitating detailed assessment of esophageal motility. ...Currently, normative values for water‐perfused HRIM systems for Chinese populations are lacking.
Methods
Healthy volunteers were enrolled for comprehensive anthropometric measures, blood biochemistry tests, and an HRIM study using 22 water‐perfused pressure sensors and 12 impedance channels. Ten 5‐mL liquid swallows of saline at 30‐second intervals were conducted. The following parameters were calculated: distal contractile integral (DCI), distal latency (DL), lower esophageal sphincter (LES) basal pressure, 4‐second integrated relaxation pressure (IRP‐4s), and complete bolus transit percentage. Normal values were established based on the 5th and 95th percentiles.
Key Results
All 66 participants (34 male, 32 female, aged 21‐64 years) completed the study and tolerated the HRIM procedure well. The upper normal limit (95th percentile) of IRP‐4 second was 20 mmHg. The 5th‐95th percentile range for DCI, DL, and complete bolus transit was 99‐2186 mmHg●s●cm, 6.2‐11.3 second, and 50%‐100%, respectively. Age was negatively correlated with DL. Females had significantly higher upper limits for IRP‐4s and median DCI than males. Multivariate analyses confirmed that IRP‐4s was higher in females, and that higher body mass index and waist circumference were associated with reduced DL and better bolus transit, respectively.
Conclusions and Inferences
We established normative values for the water‐perfused HRIM system for a Chinese population. Gender and anthropometric factors may affect various major HRIM parameters and should be taken into account when interpreting HRIM results in clinical practice.
The present study provides the first normative dataset for water‐perfused HRIM systems for the Chinese population, and confirms the importance of establishing respective normative datasets for different HRM/HRIM systems and populations. Moreover, we show that various demographic factors, especially gender, may affect the major parameters of esophageal motility that are obtained using HRIM. These factors may need to be accounted for when interpreting HRIM results in clinical practice.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Mechanisms of the development of abnormal metabolic phenotypes among obese population are not yet clear. In this study, we aimed to screen metabolomes of both healthy and subjects with abnormal ...obesity to identify potential metabolic pathways that may regulate the different metabolic characteristics of obesity.
We recruited subjects with body mass index (BMI) over 25 from the weight-loss clinic of a central hospital in Taiwan. Metabolic healthy obesity (MHO) is defined as without having any form of hyperglycemia, hypertension and dyslipidemia, while metabolic abnormal obesity (MAO) is defined as having one or more abnormal metabolic indexes. Serum-based metabolomic profiling using both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry of 34 MHO and MAO individuals with matching age, sex and BMI was performed. Conditional logistic regression and partial least squares discriminant analysis were applied to identify significant metabolites between the two groups. Pathway enrichment and topology analyses were conducted to evaluate the regulated pathways.
A differential metabolite panel was identified to be significantly differed in MHO and MAO groups, including L-kynurenine, glycerophosphocholine (GPC), glycerol 1-phosphate, glycolic acid, tagatose, methyl palmitate and uric acid. Moreover, several metabolic pathways were relevant in distinguishing MHO from MAO groups, including fatty acid biosynthesis, phenylalanine metabolism, propanoate metabolism, and valine, leucine and isoleucine degradation.
Different metabolomic profiles and metabolic pathways are important for distinguishing between MHO and MAO groups. We have identified and discussed the key metabolites and pathways that may prove important in the regulation of metabolic traits among the obese, which could provide useful clues to study the underlying mechanisms of the development of abnormal metabolic phenotypes.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Hepatocellular carcinoma (HCC)-the most common form of liver cancer-is an aggressive malignancy with few effective treatment options
. Lenvatinib is a small-molecule inhibitor of multiple receptor ...tyrosine kinases that is used for the treatment of patients with advanced HCC, but this drug has only limited clinical benefit
. Here, using a kinome-centred CRISPR-Cas9 genetic screen, we show that inhibition of epidermal growth factor receptor (EGFR) is synthetic lethal with lenvatinib in liver cancer. The combination of the EGFR inhibitor gefitinib and lenvatinib displays potent anti-proliferative effects in vitro in liver cancer cell lines that express EGFR and in vivo in xenografted liver cancer cell lines, immunocompetent mouse models and patient-derived HCC tumours in mice. Mechanistically, inhibition of fibroblast growth factor receptor (FGFR) by lenvatinib treatment leads to feedback activation of the EGFR-PAK2-ERK5 signalling axis, which is blocked by EGFR inhibition. Treatment of 12 patients with advanced HCC who were unresponsive to lenvatinib treatment with the combination of lenvatinib plus gefitinib (trial identifier NCT04642547) resulted in meaningful clinical responses. The combination therapy identified here may represent a promising strategy for the approximately 50% of patients with advanced HCC who have high levels of EGFR.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
The quest for materials capable of realizing the next generation of electronic and photonic devices continues to fuel research on the electronic, optical and vibrational properties of graphene. ...Few-layer graphene (FLG) flakes with less than ten layers each show a distinctive band structure. Thus, there is an increasing interest in the physics and applications of FLGs. Raman spectroscopy is one of the most useful and versatile tools to probe graphene samples. Here, we uncover the interlayer shear mode of FLGs, ranging from bilayer graphene (BLG) to bulk graphite, and suggest that the corresponding Raman peak measures the interlayer coupling. This peak scales from ~43 cm(-1) in bulk graphite to ~31 cm(-1) in BLG. Its low energy makes it sensitive to near-Dirac point quasiparticles. Similar shear modes are expected in all layered materials, providing a direct probe of interlayer interactions.
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IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Treatment with effective antibiotics is one important strategy for syphilis control in China. This study aimed to evaluate the prevalence of azithromycin resistance to T. pallidum in China. A ...cross-sectional study was conducted among 391 patients with early syphilis recruited from STD clinics in eight cities during October 2008 and October 2011. The swabs were obtained from the moist lesions of the participating patients. A touchdown/nested PCR of the 23S ribosomal RNA (rRNA) gene was performed on DNA samples extracted from these specimens. The presence or absence of the A2058G point mutation, conferring resistance to azithromycin, was determined by restriction enzyme digestion analysis of the PCR amplicon by MboII. Two hundred and eleven patients with primary or secondary syphilis were found to have T. pallidum DNA in their moist lesions by PCR assays. The A2058G mutation was present in 91.9% (194/211, 95% CI, 87.2–95.1%) of these patients, with no significant differences noted between patients from the eastern part (93.8%), southern part (88.6%) and northern part (95.2%) of China (v2 = 2.303, p 0.316). Compared with patients who had not taken macrolides in previous years before study entry, the patients who had taken the antibiotics had a significantly higher prevalence of azithromycin resistance (97.0% vs. 62.5%), with an odds ratio of 19.65 (95% CI, 5.77–66.93). It can be concluded that prevalence of azithromycin resistance is substantial in China and consequently that the macrolides should not be used as a treatment option for early or incubating syphilis in China.
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BFBNIB, DOBA, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UKNU, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Micromotors are an emerging class of micromachines that could find potential applications in biomedicine, environmental remediation, and microscale self-assembly. Understanding their propulsion ...mechanisms holds the key to their future development. This is especially true for a popular category of micromotors that are driven by asymmetric surface photochemical reactions. Many of these micromotors release ionic species and are propelled via a mechanism termed “ionic self-diffusiophoresis”. However, exactly how it operates remains vague. To address this fundamental yet important issue, we have developed a dielectric-AgCl Janus micromotor that clearly moves away from the AgCl side when exposed to UV or strong visible light. Taking advantage of numerical simulations and acoustic levitation techniques, we have provided tentative explanations for its speed decay over time as well as its directionality. In addition, photoactive AgCl micromotors demonstrate interesting gravitactic behaviors that hint at three-dimensional transport or sensing applications. The current work presents a well-controlled and easily fabricated model system to understand chemically powered micromotors, highlighting the usefulness of acoustic levitation for studying active matter free from the effect of boundaries.
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IJS, KILJ, NUK, PNG, UL, UM
Implementing on-chip non-volatile photonic memories has been a long-term, yet elusive goal. Photonic data storage would dramatically improve performance in existing computing architectures by ...reducing the latencies associated with electrical memories and potentially eliminating optoelectronic conversions. Furthermore, multi-level photonic memories with random access would allow for leveraging even greater computational capability. However, photonic memories have thus far been volatile. Here, we demonstrate a robust, non-volatile, all-photonic memory based on phase-change materials. By using optical near-field effects, we realize bit storage of up to eight levels in a single device that readily switches between intermediate states. Our on-chip memory cells feature single-shot readout and switching energies as low as 13.4pJ at speeds approaching 1GHz. We show that individual memory elements can be addressed using a wavelength multiplexing scheme. Our multi-level, multi-bit devices provide a pathway towards eliminating the von Neumann bottleneck and portend a new paradigm in all-photonic memory and non-conventional computing.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UL, UM, UPUK
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