The quantum twisting microscope.

The invention of scanning probe microscopy revolutionized the way electronic phenomena are visualized1. Whereas present-day probes can access a variety of electronic properties at a single location in space2, a scanning microscope that can directly probe the quantum mechanical existence of an electron at several locations would provide direct access to key quantum properties of electronic systems, so far unreachable. Here, we demonstrate a conceptually new type of scanning probe microscope-the quantum twisting microscope (QTM)-capable of performing local interference experiments at its tip. The QTM is based on a unique van der Waals tip, allowing the creation of pristine two-dimensional junctions, which provide a multitude of coherently interfering paths for an electron to tunnel into a sample. With the addition of a continuously scanned twist angle between the tip and sample, this microscope probes electrons along a line in momentum space similar to how a scanning tunnelling microscope probes electrons along a line in real space. Through a series of experiments, we demonstrate room-temperature quantum coherence at the tip, study the twist angle evolution of twisted bilayer graphene, directly image the energy bands of monolayer and twisted bilayer graphene and, finally, apply large local pressures while visualizing the gradual flattening of the low-energy band of twisted bilayer graphene. The QTM opens the way for new classes of experiments on quantum materials.

Direct observation of vortices in an electron fluid.

Vortices are the hallmarks of hydrodynamic flow. Strongly interacting electrons in ultrapure conductors can display signatures of hydrodynamic behaviour, including negative non-local resistance1-4, higher-than-ballistic conduction5-7, Poiseuille flow in narrow channels8-10 and violation of the Wiedemann-Franz law11. Here we provide a visualization of whirlpools in an electron fluid. By using a nanoscale scanning superconducting quantum interference device on a tip12, we image the current distribution in a circular chamber connected through a small aperture to a current-carrying strip in the high-purity type II Weyl semimetal WTe2. In this geometry, the Gurzhi momentum diffusion length and the size of the aperture determine the vortex stability phase diagram. We find that vortices are present for only small apertures, whereas the flow is laminar (non-vortical) for larger apertures. Near the vortical-to-laminar transition, we observe the single vortex in the chamber splitting into two vortices; this behaviour is expected only in the hydrodynamic regime and is not anticipated for ballistic transport. These findings suggest a new mechanism of hydrodynamic flow in thin pure crystals such that the spatial diffusion of electron momenta is enabled by small-angle scattering at the surfaces instead of the routinely invoked electron-electron scattering, which becomes extremely weak at low temperatures. This surface-induced para-hydrodynamics, which mimics many aspects of conventional hydrodynamics including vortices, opens new possibilities for exploring and using electron fluidics in high-mobility electron systems.

Solvation Shifts the Band-Edge Position of Colloidal Quantum Dots by Nearly 1 eV.

The optoelectronic properties of colloidal quantum dots (cQDs) depend critically on the absolute energy of the conduction and valence band edges. It is well known these band-edge energies are sensitive to the ligands on the cQD surface, but it is much less clear how they depend on other experimental conditions, like solvation. Here, we experimentally determine the band-edge positions of thin films of PbS and ZnO cQDs via spectroelectrochemical measurements. To achieve this, we first carefully evaluate and optimize the electrochemical injection of electrons and holes into PbS cQDs. This results in electrochemically fully reversible electron injection with >8 electrons per PbS cQDs, allowing the quantitative determination of the conduction band energy for PbS cQDs with various diameters and surface compositions. Surprisingly, we find that the band-edge energies shift by nearly 1 eV in the presence of different solvents, a result that also holds true for ZnO cQDs. We argue that complexation and partial charge transfer between solvent and surface ions are responsible for this large effect of the solvent on the band-edge energy. The trend in the energy shift matches the results of density functional theory (DFT) calculations in explicit solvents and scales with the energy of complexation between surface cations and solvents. As a first approximation, the solvent Lewis basicity can be used as a good descriptor to predict the shift of the conduction and valence band edges of solvated cQDs.

Radiomics nomogram in aiding preoperatively dilatation and curettage in differentiating type II and type I endometrial cancer.

AIM: To established a radiomics nomogram for improving the dilatation and curettage (D&C) result in differentiating type II from type I endometrial cancer (EC) preoperatively. MATERIAL AND METHODS: EC patients (n=875) were enrolled retrospectively and divided randomly into a training cohort (n=437) and a test cohort (n=438), according to the ratio of 1:1. Radiomics signatures were extracted and selected from apparent diffusion coefficient (ADC) maps. A multivariate logistic regression analysis was used to identify the independent clinical risk factors. An ADC based-radiomics nomogram was built by integrating the selected radiomics signatures and the independent clinical risk factors. Decision curve analysis (DCA) was conducted to determine the clinical usefulness of the radiomics nomogram. The net reclassification index (NRI) and total integrated discrimination index (IDI) were calculated to compare the discrimination performances between the radiomics nomogram and the D&C result. RESULTS: Receiver operating characteristic (ROC) curves showed that the clinical risk factors, the D&C, and the ADC based-radiomics nomogram yielded areas under the ROC curves (AUCs) of 0.70 (95% CI: 0.64-0.76), 0.85 (95% CI: 0.80-0.89), and 0.93 (95% CI: 0.90-0.96) in the training cohort and 0.64 (95% CI: 0.57-0.71), 0.82 (95% CI: 0.77-0.87) and 0.91 (95% CI: 0.87-0.95) in the test cohort, respectively. The DCA, NRI, and IDI demonstrated the clinically usefulness of the ADC based-radiomics nomogram. CONCLUSION: The ADC-based radiomics nomogram could be used to improve the D&C result in differentiating type II from type I EC preoperatively.

[Persistence follow-up of immune memory to hepatitis B vaccine among infants with non- and low-response to primary vaccination after revaccination with three doses].

This study followed up the immune memory after 3-dose revaccination among infants with non-and low-response following primary hepatitis B (HepB) vaccination. About 120 children without self-booster doses were finally included who had anti-HBs<10 mIU/ml (anti-HBs negative) at the time of follow-up, of whom 86 children completed blood sampling and anti-HBs testing. Before the challenge dose, all 86 children were negative for anti-HBs, and the GMC of anti-HBs was<10 mIU/ml. The seropositive conversion rate of anti-HBs was 100% and the GMC of anti-HBs was 886.11 (95%CI: 678.15-1 157.84) mIU/ml after the challenge dose. Compared with those with GMC<7 mIU/ml before the challenge dose, infants with GMC>7 mIU/ml had a higher anti-HBs level after the challenge dose. The ß value (95%CI) was 0.82 (0.18-1.46) (P=0.012). Compared with those with GMC<1 000 mIU/ml at primary vaccination, infants with GMC≥1 000 mIU/ml had a higher anti-HBs level after the challenge dose. The ß value (95%CI) was 0.78 (0.18-1.38)(P=0.012). The results showed a stronger immune memory was found at 9 years after revaccination among infants with non-and low-response to HepB.

Visualization of Chiral Electronic Structure and Anomalous Optical Response in a Material with Chiral Charge Density Waves.

Chiral materials have attracted significant research interests as they exhibit intriguing physical properties, such as chiral optical response, spin-momentum locking, and chiral induced spin selectivity. Recently, layered transition metal dichalcogenide 1T-TaS_{2} has been found to host a chiral charge density wave (CDW) order. Nevertheless, the physical consequences of the chiral order, for example, in electronic structures and the optical properties, are yet to be explored. Here, we report the spectroscopic visualization of an emergent chiral electronic band structure in the CDW phase, characterized by windmill-shaped Fermi surfaces. We uncover a remarkable chirality-dependent circularly polarized Raman response due to the salient in-plane chiral symmetry of CDW, although the ordinary circular dichroism vanishes. Chiral Fermi surfaces and anomalous Raman responses coincide with the CDW transition, proving their lattice origin. Our Letter paves a path to manipulate the chiral electronic and optical properties in two-dimensional materials and explore applications in polarization optics and spintronics.

Limonitum Ameliorates Castor Oil-Induced Diarrhoea in Mice by Modulating Gut Microbiota.

Diarrhoea is a common clinical condition; its pathogenesis is strongly associated with gut microbiota dysbiosis. Limonitum is a well-known traditional Chinese medicine that exerts appreciable benefits regarding the amelioration of diarrhoea. However, the mechanism through which Limonitum ameliorates diarrhoea remains unclear. Here, the efficacy and underlying mechanism of Limonitum decoction (LD) regarding diarrhoea were explored from the aspect of gut microbiota. Castor oil (CO) was used to induce diarrhoea in mice, which were then used to evaluate the effects of LD regarding the timing of the first defecation, diarrhoea stool rate, degree of diarrhoea, diarrhoea score, intestinal propulsive rate, and weight of intestinal contents. The concentrations of short-chain fatty acids (SCFAs), including acetic, propionic, isobutyric, butyric and valeric acids, were analysed by gas chromatography-mass spectrometry (GC-MS). The 16S rRNA high-throughput sequencing technology was applied to evaluate changes in the gut microbiota under exposure to LD. LD was found to effectively ameliorate the symptoms of diarrhoea, and the diversity and relative abundance of gut microbiota were restored to normal levels following LD treatment. Additionally, LD significantly restored the observed reductions in SCFAs. These results provide strong evidence that LD can sufficiently ameliorate diarrhoea in mice by regulating their gut microbiota. The findings presented here highlight that Limonitum may constitute a prospective remedy for diarrhoea.

[Preclinical study of T cell receptor specifically reactive with KRAS G12V mutation in the treatment of malignant tumors].

OBJECTIVE: KRAS gene is one of the most common mutations of proto-oncogenes in human tumors, G12V is one of the most common mutation types for KRAS. It's challenging to chemically acquire the targeted drug for this mutation. Recent studies reported that this mutation peptides can form a neoepitope for T cell recognition. Our study aims to clone the T cell receptor (TCR) which specifically recognizes the neoepitope for KRAS G12V mutation and constructs TCR engineered T cells (TCR-T), and to investigate if TCR-Ts have strong antitumor response ability. METHODS: In this study, tumor infiltrating lymphocytes were obtained from one colorectal cancer patient carrying KRAS G12V mutation. Tumor-reactive TCR was obtained by single-cell RT-5' rapid-amplification of cDNA ends PCR analysis and introduced into peripheral blood lymphocytes to generate TCR-Ts. RESULTS: We obtained a high-affinity TCR sequence that specifically recognized the HLA-A*11:01-restricted KRAS G12V8-16 epitope: KVA11-01. KVA11-01 TCR-T could significantly kill various tumor cells such as PANC-1, SW480 and HeLa (overexpressing HLA-A*11:01 and KRAS G12V), and secreting high levels of interferon-γ (IFN-γ). Non-specific killing experiments suggested KVA11-01 specifically recognized tumor cells expressing both mutant KRAS G12V and HLA-A*11:01. In vivo assay, tumor inhibition experiments demonstrated that infusion of approximately 1E7 KVA11-01 TCR-T could significantly inhibit the growth of subcuta-neously transplanted tumors of PANC-1 and HeLa (overexpressing HLA-A*11:01 and KRAS G12V) cells in nude mice. No destruction of the morphologies of the liver, spleen and brain were observed. We also found that KVA11-01 TCR-T could significantly infiltrate into tumor tissue and had a better homing ability. CONCLUSION: KVA11-01 TCR-T cells can effectively target a variety of malignant tumor cells carrying KRAS G12V mutation through in vitro and in vivo assay. KVA11-01 TCR-T cells have excellent biological activity, high specificity of target antigen and homing ability into solid tumor tissue. KVA11-01 TCR-T is expected to be an effective treatment for patients with KRAS G12V mutant solid malignancies.

[Anti-HBs persistence after primary vaccination with three doses of 5 µg recombinant hepatitis B vaccine among normal and high-responder infants: 10-year of follow-up].

Objective: Assess the 10-year Immune persistence and the predictors after primary vaccination hepatitis B vaccine (HepB) among normal and high-responder infants. Methods: A total of 1 838 Infants of 7-12 months old located in Jinan, Weifang, Yantai and Weihai of Shandong Province who were induced normal or high antibody response (anti-HBs titer ≥ 100 mIU/ml) after primary vaccination (three dose with 0-1-6 procedure) with 5 µg recombinant HepB among newborns were included in the study, in 2009. 3 ml of venous blood samples were collected at baseline survey (T0) and antibodies against hepatitis B surface antigen (anti-HBs), antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected using chemiluminescence microparticle immunoassay (CMIA) method. A self-designed questionnaire was used to collect information including the infant's age, sex, birth weight, premature birth, birth number, delivery location and mother's HBV infection status. In 2014 (followed up for 5 years) and in 2019 (followed up for 10 years) (T1), 2 ml of venous blood samples were collected. Anti HBS and anti HBC were detected by CMIA method. Those with anti HBS<10 mIU/ml were detected by CMIA method. Multivariate unconditional logistic and linear regression models were used to analyze the influencing factors of anti-HBs positive rate and geometric mean concentration (GMC) at T1. Results: After 10 years follow-up, 73.94% of the subjects (1 359/1 835) finished the follow-up. 51.15% of the subjects, a total of 625 were boys. The positive rate of anti-HBs was 100% at T0 and decreased to 53.44% (95%CI: 50.59%-56.26%) at T1. The average annual decline rate of anti-HBs positive rate from T0 to T1 was 6.07%. The GMC of anti-HBs decreased from 607.89 (95%CI: 579.01-642.62) mIU/ml to 16.44 (95%CI: 15.06-18.00) mIU/ml. The average annual decline rate of anti-HBs GMC in 10-year follow-up was 30.30%. Multivariate logistic analysis showed that the positive rate of anti-HBs at T1 was lower in those who did not vaccinate the first dose in time (OR=0.25, 95%CI:0.07-0.71). Compared with those with GMC<1 000 mIU/ml at T0, those with GMC ≥ 1 000 mIU/ml had a higher positive rate of anti-HBs at T1 (OR=2.29, 95%CI:1.76-2.97). Multivariate regression analysis showed that the GMC of anti-HBs at T1 was lower in those who did not vaccinate the first dose in time (ß=-0.50, 95%CI:-1.24-0.24). Compared with those with GMC<1 000 mIU/ml at T0, those with GMC ≥ 1 000 mIU/ml had a higher GMC of anti-HBs at T1 (ß=0.81, 95%CI: 0.62-1.05). Conclusion: Anti-HBs GMC decreased in 10 years after primary vaccination of 5 µg recombinant hepatitis B vaccine among normal and high-responders. The anti-HBs persistence was mainly associated with whether the first dose was vaccinated in time and the level of anti-HBs at the end of primary vaccination.

Common Background Signals in Voltammograms of Crystalline Silicon Electrodes are Reversible Silica-Silicon Redox Chemistry at Highly Conductive Surface Sites.

The electrochemical reduction of bulk silica, due to its high electrical resistance, is of limited viability, namely, requiring temperatures in excess of 850 °C. By means of electrochemical and electrical measurements in atomic force microscopy, we demonstrate that at a buried interface, where silica has grown on highly conductive Si(110) crystal facets, the silica-silicon conversion becomes reversible at room temperature and accessible within a narrow potential window. We conclude that parasitic signals commonly observed in voltammograms of silicon electrodes originate from silica-silicon redox chemistry. While these findings do not remove the requirement of high temperature toward bulk silica electrochemical reduction, they redefine for silicon the potential window free from parasitic signals and, as such, significantly restrict the conditions where electroanalytical methods can be applied to the study of silicon surface reactivity.

CNN-based qualitative detection of bone mineral density via diagnostic CT slices for osteoporosis screening.

The features extracted from diagnostic computed tomography (CT) slices were used to qualitatively detect bone mineral density (BMD) through neural network models, and the evaluation results indicated that it may be a promising approach to perform osteoporosis screening in clinical practice. INTRODUCTION: The purpose of this study is to design a novelty diagnostic method for osteoporosis screening by using the convolutional neural network (CNN), which can be incorporated into the procedure of routine CT diagnostic in medical examination thereby improving the osteoporosis diagnosis and reducing the patient burden. METHODS: The proposed CNN-based method mainly comprises two functional modules to perform qualitative detection of BMD by analyzing the diagnostic 2D CT slice. The first functional module aims to locate and segment the ROI of diagnostic 2D CT slice, called Mark-Segmentation-Network (MS-Net). The second functional module is used to determine the category of BMD by the features of ROI, called BMD-Classification-Network (BMDC-Net). The diagnostic 2D CT slice of pedicle level in lumbar vertebrae (L1) was selected from 3D CT image in our experiments firstly. Then, the trained MS-Net can get the mark image of input original 2D CT slice, thereby obtain the segmentation image. Finally, the trained BMDC-Net can obtain the probability value of normal bone mass, low bone mass, and osteoporosis by inputting the segmentation image. On the basis of network results, the radiologists can provide preliminary qualitative diagnosis results of BMD. RESULTS: Training of the network was performed on diagnostic 2D CT slices of 150 patients. The network was tested on 63 patients. Each patient corresponds to a 2D CT slice. The proposed MS-Net has an excellent segmentation precision on the shape preservation of different lumbar vertebra. The dice index (DI), pixel accuracy (PA), and intersection over union (IOU) of segmentation results are greater than 0.8. The proposed BMDC-Net achieved an accuracy of 76.65% and an area under the receiver operating characteristic curve of 0.9167. CONCLUSIONS: This study proposed a novel method for qualitative detection of BMD via diagnostic CT slices and it has great potential in clinical applications for osteoporosis screening. The method can potentially reduce the manual burden to radiologists and diagnostic cost to patients.

Asiatic Acid Induces Mitochondrial Apoptosis via Inhibition of JAK2/STAT3 Signalling Pathway in Human Osteosarcoma.

Osteosarcoma (OS), a severe malignant bone tumour, usually occurs in adolescents and children and has a poor prognosis. Asiatic acid (AA), an active component isolated from Centella asiatica (L.) Urb., exhibits appreciable anti-oxidant and anti-tumour activities. So far, the effects and underlying mechanisms of AA against OS have not been clarified. Here, we explored the anti-tumour effects of AA against human OS and the involved mechanism mediating its actions. To evaluate effects of AA on the cell proliferation of human OS cells, cell viability and colony formation assays were performed. Flow cytometry was used to evaluate apoptosis in OS cells exposed to AA and mitochondrial membrane potential. Western blotting and RT-PCR were applied to determine expression of the relevant proteins and their mRNA levels. Our explorations showed that AA inhibits proliferation of human OS cells in a concentration- and time-dependent manner, and induces apoptosis of OS cells by the intrinsic (mitochondrial) pathway. Importantly, we found that inhibition of the AA-induced phosphorylation of JAK2/STAT3 signalling molecules and the decrease in MCL-1 contributed to the anti-tumour efficacy of AA. Collectively, our results suggest that AA could evoke mitochondrial- induced apoptosis in human OS cells by suppression of the JAK2/STAT3 pathway and MCL-1 expression. These results strongly demonstrate that AA could be a potential anti-tumour agent for OS treatment.

Effects of pill splitting training on drug physiochemical properties, compliance, and clinical outcomes in the elderly population: a randomised trial.

INTRODUCTION: This study aimed to provide information about the clinical and physiochemical effects of pill splitting training in elderly cardiac patients in Hong Kong. METHODS: A parallel study design was adopted. Patients taking lisinopril, amlodipine, simvastatin, metformin, or perindopril who needed to split pills were recruited from the Prince of Wales Hospital. Patients were divided into two groups at their first visit. Patients in group A split drugs using their own technique, whereas patients in group B used pill cutters after relevant training until their next follow-up visit. The primary outcome was the change in drug content between before and after the pill splitting training. Assays were performed to determine the drug content. Secondary outcomes were the changes in clinical outcomes, patients' attitudes and acceptance towards pill splitting, and patients' knowledge about pill splitting. RESULTS: A total of 193 patients were recruited, and 101 returned for the follow-up visit. The percentage of split tablets falling within the assay limits increased from 39.13% to 47.82% (P=0.523) in group A and from 48.94% to 51.06% (P=1.000) in group B. The changes did not reach statistical significance. As for clinical outcomes, the mean triglyceride level decreased from 1.62±1.05 to 1.36±0.80 (P=0.049), whereas the mean heart rate increased significantly from 73.97±11.01 to 77.92±12.72 (P=0.026). Changes in other parameters were not significant. CONCLUSION: This study highlights the high variability of drug content after pill splitting. Pills with dosages that do not require splitting would be preferable, considering patients' preference. Patients should be educated to use pill cutters properly if pill splitting is unavoidable.

[Effects of normobaric hyperoxia intervention on renal ischemia-reperfusion injury in rats].

Objective: To investigate the effects of normobaric hyperoxia intervention on renal ischemia-reperfusion injury in rats and its possible mechanism. Methods: Twenty-one adult male SD rats were enrolled and their right kidneys were excised. After two weeks, they were randomly assigned to 3 groups, with 7 rats in each group, namely sham-operated group (Group S), ischemia-reperfusion group (Group I/R), and normobaric hyperoxia+ischemia-reperfusion group (Group NBHO+I/R). In group S, only the left renal pedicle was isolated, but no ischemic treatment was performed. However, in group I/R and group NBHO+I/R, left renal pedicles were separated and left renal ischemia was induced by noninvasive arterial clamp for 45 min, and after 24 h of reperfusion, rats in group S and group I/R inhaled regular concentration of oxygen (21%), while rats in group NBHO+I/R inhaled high concentration of oxygen (60%), 2 h at each time, once a day for 7 days. On the 7th day after surgery, blood urea nitrogen (BUN) and creatinine (Cr) levels were measured by taking blood from the orbital veins of rats. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) was detected from the left kidney tissues. The mRNA and protein contents of Keap1 and Nrf2 gene in kidney tissues were determined by qPCR and Western Blotting, respectively. Hematoxylin-eosin staining (HE) was employed to observe the pathological changes of kidney tissue. Immunohistochemical staining was used to measure the protein expression of Keap1 and Nrf2 in kidney tissues. Results: Compared with group S, the serum BUN [(10.7±1.7) mmol/L, (8.4±1.0) mmol/L vs (6.1±1.3) mmol/L, both P<0.05] and Cr [(81.0±3.7) µmol/L, (62.9±3.4) µmol/L vs (48.3±2.9) µmol/L, both P<0.05] levels of rats in the group I/R and group NBHO+I/R increased, and the I/R group had the most significant increase. Compared with group S, the MDA content of kidney tissue in the rats of group I/R and NBHO+I/R increased [(10.5±1.0) µmol/L, (8.6±0.8) µmol/L vs (6.5±0.5) µmol/L, both P<0.05], but the MDA content in group NBHO+I/R was lower than that of group I/R (P<0.05). Compared with group S, the SOD content in the kidney tissues of rats in both group I/R and group NBHO+I/R decreased. However, the SOD content of group NBHO+I/R was higher than that of group I/R (P<0.05). Compared with group S, the mRNA and protein contents of Keap1 gene in kidney tissues of group I/R and group NBHO+I/R decreased, and group NBHO+I/R had the most significant decrease (P<0.05). However, compared with group S, mRNA and protein expressions of Nrf2 gene increased in kidney tissues of group I/R and group NBHO+I/R, and NBHO+I/R group had the most significant increase (P<0.05). Postoperative pathological results suggested that compared with group S, the pathological damage of kidney tissues in group I/R and group NBHO+I/R increased, but the degree of damage in group NBHO+I/R was lower than that in group I/R. Conclusion: Normobaric hyperoxia intervention may have protective effects on renal ischemia-reperfusion injury in rats by activating Keap1-Nrf2 signaling pathway.

[Analysis of capability to pertussis etiology and serological diagnosis for Gradeâ ¡ and â ¢medical institutions in Shandong Province in 2018].

Objective: Investigate and analyze the etiology and serological diagnosis capabilities of pertussis in medical institutions in Shandong Province in 2018. Methods: Using the census method, a questionnaire survey was conducted among 603 second and above level medical institutions in Shandong Province. The deadline for the survey was December 2018, and a total of 543 questionnaires have been recovered, and the validity rate of the questionnaires was 90%. Surveyed the pertussis etiology and serology test items (pertussis IgM and IgG, pertussis nucleic acid and pertussis bacterial culture) and the start time of each test item by questionnaire. The reported cases (confirmed cases and clinically diagnosed cases) between January 1, 2012 and December 31, 2018 were derived from the Chinese Disease Control and Prevention Information System according to the onset date. We used indicators such as fixed-base development speed, chain development speed, and chain growth speed for analysis. The chi test was used to analyze the differences in the composition ratio of medical institutions with detection ability in different levels and regions, and analyze the changes in the number of reported cases before and after the development of pertussis etiology and serology testing. Results: A total of 543 medical institutions accounted for 90.0% (543/603) of all secondary and above level medical institutions in the province, 356 secondary medical institutions (65.6%), and 187 tertiary medical institutions (34.4%). There were 10 medical institutions that carry out pertussis IgM, IgG and nucleic acid testing, accounting for 1.8% (10/543) of the surveyed medical institutions respectively. 2 medical institutions that carried out bacterial culture, accounting for 0.4% of the surveyed medical institutions (2/543). 20 medical institutions have carried out the above tests (8 secondary medical institutions and 12 tertiary medical institutions), accounting for 3.7% (20/543). The proportion of tertiary medical institutions with pertussis IgM, IgG detection and nucleic acid detection capabilities [6.42% (12/187)] was significantly higher than that of secondary medical institutions [2.25% (8/356)] (χ²=6.01, P=0.014). From 2012 to 2018, the fixed base ratio development speed of reported cases was 3 834.69% in Shandong Province, among which medical institutions with etiology and serological testing capabilities reached 4 533.33%. In 13 medical institutions, the average annual number of reported cases after pertussis etiology and serological testing were higher than that of reported cases before testing. Conclusion: The ability of pertussis etiology and serology diagnosis of secondary and above medical institutions in Shandong Province needs to be improved.

Covalent Linkages of Molecules and Proteins to Si-H Surfaces Formed by Disulfide Reduction.

Thiols and disulfide contacts have been, for decades, key for connecting organic molecules to surfaces and nanoclusters as they form self-assembled monolayers (SAMs) on metals such as gold (Au) under mild conditions. In contrast, they have not been similarly deployed on Si owing to the harsh conditions required for monolayer formation. Here, we show that SAMs can be simply formed by dipping Si-H surfaces into dilute solutions of organic molecules or proteins comprising disulfide bonds. We demonstrate that S-S bonds can be spontaneously reduced on Si-H, forming covalent Si-S bonds in the presence of traces of water, and that this grafting can be catalyzed by electrochemical potential. Cyclic disulfide can be spontaneously reduced to form complete monolayers in 1 h, and the reduction can be catalyzed electrochemically to form full surface coverages within 15 min. In contrast, the kinetics of SAM formation of the cyclic disulfide molecule on Au was found to be three-fold slower than that on Si. It is also demonstrated that dilute thiol solutions can form monolayers on Si-H following oxidation to disulfides under ambient conditions; the supply of too much oxygen, however, inhibits SAM formation. The electron transfer kinetics of the Si-S-enabled SAMs on Si-H is comparable to that on Au, suggesting that Si-S contacts are electrically transmissive. We further demonstrate the prospect of this spontaneous disulfide reduction by forming a monolayer of protein azurin on a Si-H surface within 1 h. The direct reduction of disulfides on Si electrodes presents new capabilities for a range of fields, including molecular electronics, for which highly conducting SAM-electrode contacts are necessary and for emerging fields such as biomolecular electronics as disulfide linkages could be exploited to wire proteins between Si electrodes, within the context of the current Si-based technologies.

Association of daytime napping with incident stroke in middle-aged and older adults: a large community-based study.

BACKGROUND AND PURPOSE: There are conflicting reports on the association between daytime napping and incident stroke. This study was designed to investigate the relationship between daytime napping and stroke within a community-based cohort. METHODS: The present prospective study was based on the Sleep Heart Health Study. Napping habits were assessed with a self-reported Sleep Habits Questionnaire. Participants with napping habits of different durations and frequencies were followed up until the first stroke occurred or the final censoring date. Cox proportional hazards models were used to estimate the relationship between napping habits and stroke. RESULTS: A total of 4757 participants (2219 men, mean age 63.6 ± 11.1 years) were enrolled in this study. Compared with those taking no naps, multivariate proportional hazards models analysis indicated that individuals taking naps with a duration of >60 min [hazard ratio (HR), 2.460; 95% confidence interval (CI), 1.538-3.934] had a higher risk of stroke. There was also an increased risk of stroke among participants taking naps daily (HR, 1.563; 95% CI, 1.059-2.307) or five to six times/week (HR, 1.548; 95% CI, 1.026-2.335). After combining napping durations and frequencies, regular long naps (HR, 1.903; 95% CI, 1.182-3.065) and regular short naps (HR, 1.451; 95% CI, 1.010-2.084) were independent risk factors for incident stroke. CONCLUSION: Daytime napping with a long duration (>30 min) or a high frequency (≥5 times/week) may increase the risk of stroke.

Predictive significance of Charcot-Leyden Crystal mRNA levels in nasal brushing for nasal polyp recurrence.

BACKGROUND: Tissue eosinophils have been shown to be associated with polyp recurrence in chronic rhinosinusitis with nasal polyps (CRSwNP). We addressed whether the mRNA levels of Charcot-Leyden Crystal (CLC) in nasal brushing samples, a molecule mainly released from activated eosinophils, could serve as an effective non-invasive biomarker to predict polyp recurrence. METHODS: A total of 51 patients with CRSwNP completing the postoperative follow-up over a period of 12-18 months were enrolled. Baseline CLC mRNA levels of the nasal brushings collected prior to endoscopic sinus surgery were quantified by quantitative real-time polymerase chain reaction (qRT-PCR). Polyp specimens were collected during surgery and were evaluated for inflammatory cells by histopathologic staining. The patients' baseline characteristics were reviewed and analyzed for associations with recurrence. Logistic regression analysis was performed to determine the predictive factors for polyp recurrence, and receiver operating characteristic (ROC) curves were performed to determine their predictive values. RESULTS: Overall, 25/51(49.02%) patients experienced polyp recurrence during the 12-18 months follow-up. The baseline relative CLC mRNA level in nasal brushing samples was significantly increased in patients with recurrence compared to those without recurrence (p.

Light-addressable electrochemistry at semiconductor electrodes: redox imaging, mask-free lithography and spatially resolved chemical and biological sensing.

Spatial confinement of electrochemical reactions at solid/liquid interfaces is a mature area of research, and a central theme from cell biology to analytical chemistry. Monitoring or manipulating the kinetics of a charge transfer reaction in 2D is generally achieved using scanning electrochemical microscopy or multielectrode arrays, techniques that rely on moving physical probes or on a network of electrical connections. This tutorial is introducing concepts and instruments to confine faradaic electrochemical reactions in 2D without resorting to the mechanical movement of a probe, and with the simple design of one semiconducting electrode, one electrical lead and a single-channel potentiostat. We provide a theoretical background of semiconductor electrochemistry, and describe the use of localised visible light stimuli on photoconductor/liquid and semiconductor/liquid interfaces to address electrical conductivity - hence chemical reactivity - only at one specific site defined by the experimentalist. This enables shifting of the tenet of one electrode/one wire towards one wire/many electrodes. We discuss the applications of this emerging platform in the context of surface chemistry patterning, redox imaging, chemical and biological sensing, generating chemical gradients, electrocatalysis, nanotechnology and cell biology.

[Association between single nucleotide polymorphism in promoter region of SIRT1 gene and senile degenerative heart valvular disease].

Objective: To investigate the correlation between single nucleotide polymorphisms (SNPs) of SIRT1 gene promoter sequence and senile degenerative heart valvular disease (SDHVD). Methods: A total of 236 SDHVD patients and 285 healthy controls who visited the Affiliated Hospital of Jining Medical University between February 2012 and October 2016 were enrolled. SNPs of SIRT1 gene promoter were detected by Sanger sequencing. Typing and correlation were analyzed by χ(2) test and Logistic regression analysis. Haplotype and linkage disequilibrium were analyzed by Haploview4.2 software and SHEsis online software. The effect of SNPs on the binding of transcription factors to SIRT1 gene promoter was analyzed by electrophoretic mobility shift assay(EMSA). The transcription factors affected by SNPs were predicted by Transfac online software. Results: The frequency distribution of GG genotype of rs3740051 in the SDHVD group was significantly higher than that in the control group (χ(2)=4.855, P=0.028). There was a correlation between GG genotype of the rs3740051 and SDHVD. After adjusting for age, the risk of SDHVD in the carrier of GG genotype was 3.079 times higher than that of AA genotype(OR=3.079, 95%CI: 1.156-8.201, P=0.024). The five SNPs (rs3740051, rs932658, rs35995735, rs3740053 and rs2394443) showed strong linkage disequilibrium(D'>0.8). The haplotype analysis of the five SNPs (haplotype frequency<0 was ignored in the analysis) showed that 11 haplotypes (P<0.05) were formed, and the frequency of *A**C, AA**C, *AG*C, AAG*C, AA*AC, *AGAC and AAGAC in SDHVD group were significantly higher than that in control group (P<0.05, OR>1, 95%CI does not contains 1). EMSA showed that the color of the binding bands incubated by wild type probe and nucleoprotein was darker than that incubated by DNA sequence variation probe and nucleoprotein. Conclusion: The GG genotype of rs3740051 is associated with SDHVD and may be a risk genotype for SDHVD. The haplotype AC (across rs932658 and rs2394443) may be a dangerous haplotype of SDHVD. rs3740051 may affect the occurrence and development of SDHVD by interfering with the binding of FOXC protein to SIRT1 gene promoter.