Nanoscale Label-free Bioprobes to Detect Intracellular Proteins in Single Living Cells

Fluorescent labeling techniques have been widely used in live cell studies; however, the labeling processes can be laborious and challenging for use in non-transfectable cells, and labels can interfere with protein functions. While label-free biosensors have been realized by nanofabrication, a method to track intracellular protein dynamics in real-time, in situ and in living cells has not been found. Here we present the first demonstration of label-free detection of intracellular p53 protein dynamics through a nanoscale surface plasmon-polariton fiber-tip-probe (FTP)

Roadmap on optical sensors

Optical sensors and sensing technologies are playing a more and more important role in our modern world. From micro-probes to large devices used in such diverse areas like medical diagnosis, defence, monitoring of industrial and environmental conditions, optics can be used in a variety of ways to achieve compact, low cost, stand-off sensing with extreme sensitivity and selectivity. Actually, the challenges to the design and functioning of an optical sensor for a particular application requires intimate knowledge of the optical, material, and environmental properties that can affect its performance. This roadmap on optical sensors addresses different technologies and application areas. It is constituted by twelve contributions authored by world-leading experts, providing insight into the current state-of-the-art and the challenges their respective fields face. Two articles address the area of optical fibre sensors, encompassing both conventional and specialty optical fibres. Several other articles are dedicated to laser-based sensors, micro- and nano-engineered sensors, whispering-gallery mode and plasmonic sensors. The use of optical sensors in chemical, biological and biomedical areas is discussed in some other papers. Different approaches required to satisfy applications at visible, infrared and THz spectral regions are also discussed

Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Detecting Single Gold Nanoparticles (1.8 nm) with Ultrahigh‑<i>Q</i> Air-Mode Photonic Crystal Nanobeam Cavities

The growing applications of nanoparticles in energy and healthcare demand new metrology techniques with improved sensitivity, lower sample concentration, and affordable instrument cost. Here we demonstrate the first air-mode photonic crystal nanobeam cavity with ultrahigh <i>Q</i>-factor (<i>Q</i> = 2.5 × 10⁵) and ultrasmall mode volume (<i>V</i> = 0.01λ³) at telecom wavelength. The air-mode cavity has strong field localization outside of its high-index material, thus significantly improving the sensitivity to detect nanoparticles. The strong field gradient attracts the nanoparticles to its field maximum, improving the detection efficiency. Combining these advantages, we report detecting and sizing single gold nanoparticles down to 1.8 nm in diameter (equivalently single polystyrene nanoparticle of 3 nm in diameter) with significantly reduced sample concentration (∼fM) than traditional optical techniques. In addition, the air-mode ultrahigh <i>Q</i>, ultrasmall <i>V</i> photonic crystal nanobeam cavity will be a useful platform to study strong light–matter interactions, nonlinear processes, and cavity quantum electrodynamics

Development and Validation of Prognostic Nomograms for Lung Squamous Cell Carcinoma With Brain Metastasis in Patients Aged 45 Years or Older: A Population-Based Study

Purpose We aimed to establish nomograms to predict the survival in patients aged ≥45  years with lung squamous cell carcinoma and brain metastasis. Methods We collected patients diagnosed as lung squamous cell carcinoma with brain metastasis aged ≥45 years between 2010 and 2019 from the Surveillance, Epidemiology, and End Results database. Prognostic factors were determined by the univariate and multivariate Cox regression analysis, and then the nomogram was constructed to predict cancer-specific survival and overall survival. Nomograms were evaluated by decision curve analysis, the area under the receiver operating characteristic curve, calibration plot, concordance index, and risk group stratification. Results In total, 2437 patients were included, with 1706 and 731 in the cohorts of training and validation, respectively. The age, N stage, T stage, liver metastasis, chemotherapy, bone metastasis, along with radiotherapy were significant in predicting the survival, and adopted for the establishment of nomograms. In the training and validation sets, the concordance index were .713(95%CI:0.699–.728) & .700(95%CI:0.677–.722) in predicting cancer-specific survival and .715(95%CI:0.701–.729) & .712(95%CI:0.690–.735) in predicting overall survival, respectively. Besides, the area under the receiver operating characteristic curve for predicting cancer-specific survival and overall survival in the training set were all >.7 at 1-, 2-, and 3- years. Calibration plots proved the survival predicted by nomograms were consistent with the actual values. decision curve analysis revealed better clinical validity of the nomogram in predicting cancer-specific survival and overall survival at 1-year than TNM staging. Patients were stratified into the high-/low-risk groups according to the optimal cutoff value of 100.21 for cancer-specific survival and 91.98 for overall survival. A web-based probability calculator was constructed finally. Conclusion Two nomograms were developed for the prognostic prediction of lung squamous cell carcinoma patients with brain metastasis aged ≥45 years, providing guidance for decision-making in clinical practice

Hyperspectral and Multispectral Remote Sensing Image Fusion Based on Endmember Spatial Information

Hyperspectral (HS) images usually have high spectral resolution and low spatial resolution (LSR). However, multispectral (MS) images have high spatial resolution (HSR) and low spectral resolution. HS&ndash;MS image fusion technology can combine both advantages, which is beneficial for accurate feature classification. Nevertheless, heterogeneous sensors always have temporal differences between LSR-HS and HSR-MS images in the real cases, which means that the classical fusion methods cannot get effective results. For this problem, we present a fusion method via spectral unmixing and image mask. Considering the difference between the two images, we firstly extracted the endmembers and their corresponding positions from the invariant regions of LSR-HS images. Then we can get the endmembers of HSR-MS images based on the theory that HSR-MS images and LSR-HS images are the spectral and spatial degradation from HSR-HS images, respectively. The fusion image is obtained by two result matrices. Series experimental results on simulated and real datasets substantiated the effectiveness of our method both quantitatively and visually

Additional file 1 of Effect of neuromuscular electrical stimulation in critically ill adults with mechanical ventilation: a systematic review and network meta-analysis

Additional file 1:. Supplementary Tables and Figure