Predicting ion mobility collision cross sections using projection approximation with ROSIE-PARCS webserver.

Ion mobility coupled to mass spectrometry informs on the shape and size of protein structures in the form of a collision cross section (CCSIM). Although there are several computational methods for predicting CCSIM based on protein structures, including our previously developed projection approximation using rough circular shapes (PARCS), the process usually requires prior experience with the command-line interface. To overcome this challenge, here we present a web application on the Rosetta Online Server that Includes Everyone (ROSIE) webserver to predict CCSIM from protein structure using projection approximation with PARCS. In this web interface, the user is only required to provide one or more PDB files as input. Results from our case studies suggest that CCSIM predictions (with ROSIE-PARCS) are highly accurate with an average error of 6.12%. Furthermore, the absolute difference between CCSIM and CCSPARCS can help in distinguishing accurate from inaccurate AlphaFold2 protein structure predictions. ROSIE-PARCS is designed with a user-friendly interface, is available publicly and is free to use. The ROSIE-PARCS web interface is supported by all major web browsers and can be accessed via this link (https://rosie.graylab.jhu.edu).

Defect Density and Atomic Defect Recognition in the Middle Layer of a Trilayer MoS2 Stack.

Molybdenum disulfide (MoS2) is one of the most intriguing two-dimensional materials, and moreover, its single atomic defects can significantly alter the properties. These defects can be both imaged and engineered using spherical and chromatic aberration-corrected high-resolution transmission electron microscopy (CC/CS-corrected HRTEM). In a few-layer stack, several atoms are vertically aligned in one atomic column. Therefore, it is challenging to determine the positions of missing atoms and the damage cross-section, particularly in the not directly accessible middle layers. In this study, we introduce a technique for extracting subtle intensity differences in CC/CS-corrected HRTEM images. By exploiting the crystal structure of the material, our method discerns chalcogen vacancies even in the middle layer of trilayer MoS2. We found that in trilayer MoS2 the middle layer's damage cross-section is about ten times lower than that in the monolayer. Our findings could be essential for the application of few-layer MoS2 in nanodevices.

In-Brain Multiphoton Imaging of Vaterite Cargoes Loaded with Carbon Dots.

Biocompatible fluorescent agents are key contributors to the theranostic paradigm by enabling real-time in vivo imaging. This study explores the optical properties of phenylenediamine carbon dots (CDs) and demonstrates their potential for fluorescence imaging in cells and brain blood vessels. The nonlinear absorption cross-section of the CDs was measured and achieved values near 50 Goeppert-Mayer (GM) units with efficient excitation in the 775-895 nm spectral range. Mesoporous vaterite nanoparticles were loaded with CDs to examine the possibility of a biocompatible imaging platform. Efficient one- and two-photon imaging of the CD-vaterite composites uptaken by diverse cells was demonstrated. For an in vivo scenario, CD-vaterite composites were injected into the bloodstream of a mouse, and their flow was monitored within the blood vessels of the brain through a cranial window. These results show the potential of the platform for high-brightness biocompatible imaging with the potential for both sensing and simultaneous drug delivery.

Re-understanding of SERS for General and Standardized Quantitative Analysis.

We proposed two physical concepts, i.e., an intramolecular relative cross section (RCS) and an intermolecular relative scattering ability (RSA), to re-understand and re-describe surface-enhanced Raman scattering (SERS) and established a general SERS quantification theory. Interestingly, RCS and RSA are intrinsic factors and are experimentally measurable to form datasheets of molecules, namely, SERS cards, with which a standard SERS quantification procedure was established. The validity of the theory and quantification procedure was confirmed by experiments. Surprisingly, RCS and RSA are also valid for complex systems being considered as virtual molecules and are experimentally measurable. This simplifies complex systems into analyte-virtual molecule binary systems. With this consideration, trace-level mitoxantrone (a typical cancer drug metabolite) in artificial urine was accurately predicted. The theory, the SERS cards, the standard quantification procedure, and the virtual molecule concept pave a way toward quantitative and standardized SERS spectroscopy in dealing with real-world problems and complex samples.

Computational tools and algorithms for ion mobility spectrometry-mass spectrometry.

Ion mobility spectrometry-mass spectrometry (IMS-MS or IM-MS) is a powerful analytical technique that combines the gas-phase separation capabilities of IM with the identification and quantification capabilities of MS. IM-MS can differentiate molecules with indistinguishable masses but different structures (e.g., isomers, isobars, molecular classes, and contaminant ions). The importance of this analytical technique is reflected by a staged increase in the number of applications for molecular characterization across a variety of fields, from different MS-based omics (proteomics, metabolomics, lipidomics, etc.) to the structural characterization of glycans, organic matter, proteins, and macromolecular complexes. With the increasing application of IM-MS there is a pressing need for effective and accessible computational tools. This article presents an overview of the most recent free and open-source software tools specifically tailored for the analysis and interpretation of data derived from IM-MS instrumentation. This review enumerates these tools and outlines their main algorithmic approaches, while highlighting representative applications across different fields. Finally, a discussion of current limitations and expectable improvements is presented.

Vaccine efficacy at a point in time.

Vaccine trials are generally designed to assess efficacy on clinical disease. The vaccine effect on infection, while important both as a proxy for transmission and to describe a vaccine's entire effects, requires frequent (e.g., twice a week) longitudinal sampling to capture all infections. Such sampling may not always be feasible. A logistically easy approach is to collect a sample to test for infection at a regularly scheduled visit. Such point or cross-sectional sampling does not permit estimation of classic vaccine efficacy on infection, as long duration infections are sampled with higher probability. Building on work by Rinta-Kokko and others (2009) and Lipsitch and Kahn (2021), we evaluate proxies of the vaccine effect on transmission at a point in time; the vaccine efficacy on prevalent infection and on prevalent viral load, VE$_{\rm PI}$ and VE$_{\rm PVL}$, respectively. Longer infections with higher viral loads should have more transmission potential and prevalent vaccine efficacy naturally captures this aspect. We demonstrate how these parameters obtain from an underlying proportional hazards model for infection and allow for waning efficacy on infection, duration, and viral load. We estimate these parameters based on regression models with either repeated cross-sectional sampling or frequent longitudinal sampling. We evaluate the methods by simulation and analyze a phase III vaccine trial with polymerase chain reaction (PCR) cross-sectional sampling for subclinical infection.

Lightweight, Flexible, and Thermal Insulating Carbon/SiO2@CNTs Composite Aerogel for High-Efficiency Microwave Absorption.

A complex electromagnetic environment is a formidable challenge in national defense areas. Microwave-absorbing materials are considered as a strategy to tackle this challenge. In this work, lightweight, flexible, and thermal insulating Carbon/SiO2@CNTs (CSC) aerogel is successfully prepared coupled with outstanding microwave absorbing performance, through freeze-drying and high-temperature annealing techniques. The CSC aerogel shows a strong reflection loss (-55.16 dB) as well as wide effective absorbing bandwidth (8.5 GHz) in 2-18 GHz. It also retains good microwave absorption properties under tension and compression. Radar cross-sectional (RCS) simulation result demonstrates the CSC processing a strong reduction ability of RCS compared with a metal plate. Further exploration shows amazing flexibility and good thermal insulation properties of CSC. The successful preparation of this composite aerogel provides a broad prospect for the design of microwave-absorbing materials.

Population trends in human rib cross-sectional shapes.

Rib fractures remain the most frequent thoracic injury in motor vehicle crashes. Computational human body models (HBMs) can be used to simulate these injuries and design mitigation strategies, but they require adequately detailed geometry to replicate such fractures. Due to a lack of rib cross-sectional shape data availability, most commercial HBMs use highly simplified rib sections extracted from a single individual during original HBM development. This study provides human rib shape data collected from chest CT scans of 240 females and males across the full adult age range. A cortical bone mapping algorithm extracted cross-sectional geometry from scans in terms of local periosteal position with respect to the central rib axis and local cortex thickness. Principal component analysis was used to reduce the dimensionality of these cross-sectional shape data. Linear regression found significant associations between principal component scores and subject demographics (sex, age, height, and weight) at all rib levels, and predicted scores were used to explore the expected rib cross-sectional shapes across a wide range of subject demographics. The resulting detailed rib cross-sectional shapes were quantified in terms of their total cross-sectional area and their cortical bone cross-sectional area. Average-sized female ribs were smaller in total cross-sectional area than average-sized male ribs by between 20% and 36% across the rib cage, with the greatest differences seen in the central portions of rib 6. This trend persisted although to smaller differences of 14%-29% when comparing females and males of equal intermediate weight and stature. Cortical bone cross-sectional areas were up to 18% smaller in females than males of equivalent height and weight but also reached parity in certain regions of the rib cage. Increased age from 25 to 80 years was associated with reductions in cortical bone cross-sectional area (up to 37% in females and 26% in males at mid-rib levels). Total cross-sectional area was also seen to reduce with age in females but to a lesser degree (of up to 17% in mid-rib regions). Similar regions saw marginal increases in total cross-sectional area for male ribs, indicating age affects rib cortex thickness moreso than overall rib cross-sectional size. Increased subject height was associated with increased rib total and cortical bone cross-sectional areas by approximately 25% and 15% increases, respectively, in mid-rib sections for a given 30 cm increase in height, although the magnitudes of these associations varied by sex and rib location. Increased weight was associated with approximately equal changes in both cortical bone and total cross-sectional areas in males. These effects were most prominent (around 25% increases for an addition of 50 kg) toward lower ribs in the rib cage and had only modest effects (less than 12% change) in ribs 2-4. Females saw greater increases with weight in total rib area compared to cortical bone area, of up to 21% at the eighth rib level. Results from this study show the expected shapes of rib cross-sections across the adult rib cage and across a broad range of demographics. This detailed geometry can be used to produce accurate rib models representing widely varying populations.

The association between triglyceride-glucose index and the likelihood of cardiovascular disease in the U.S. population of older adults aged ≥ 60 years: a population-based study.

BACKGROUND: The association between the triglyceride-glucose (TyG) index and the likelihood of developing cardiovascular disease (CVD) in the general elderly population in the United States aged 60 and above is not well understood. The objective of our study was to examine the relationship between the TyG index and CVD likelihood in the general elderly population over 60 years of age in the United States. METHODS: Data for this cross-sectional study were sourced from the 2003-2018 National Health and Nutrition Examination Survey. Weighted multivariable regression analysis and subgroup analysis were conducted to estimate the independent relationship between the TyG index and the likelihood of CVD. Non-linear correlations were explored using restricted cubic splines. RESULTS: A total of 6502 participants were included, with a mean TyG index of 8.75 ± 0.01. The average prevalence of CVD was 24.31% overall. Participants in the higher TyG quartiles showed high rates of CVD (Quartile 1: 19.91%; Quartile 2: 21.65%; Quartile 3: 23.82%; Quartile 4: 32.43%). For CVD, a possible association between the TyG index and the odds of CVD was observed. Our findings suggest a nonlinear association between the TyG index and the odds of CVD. The threshold of 8.73 for the likelihood of CVD. Interaction terms were employed to assess heterogeneities among each subgroup, revealing a significant difference specifically in alcohol consumption. This suggests that the positive association between the TyG index and the likelihood of CVD is dependent on the drinking status of the participants. CONCLUSION: A higher TyG index is linked to an increased likelihood of CVD in US adults aged ≥ 60 years. TyG index is anticipated to emerge as a more effective metric for identifying populations at early likelihood of CVD.

Increased Secreted Frizzled-Related Protein 2 in Hypertension-Induced Left Ventricular Remodeling.

Background: Secreted frizzled-related protein 2 (sFRP2) is involved in various cardiovascular diseases. However, its relevance in left ventricular (LV) remodeling in patients with hypertension (HTN) is obscure. Methods: In this study, 196 patients with HTN were included, 59 with echocardiographic LV remodeling. A total of 100 healthy subjects served as normal controls. The serum-sFRP2 level was measured by enzyme-linked immunosorbent assay (ELISA). Data were collected from medical records for baseline characteristics, biochemistry tests, and echocardiography. Receiver operating characteristic (ROC) curves were used to assess the distinguishing value of sFRP2 for LV remodeling in patients with HTN. Spearman rank correlation analysis was utilized to identify factors correlated with sFRP2. Cardiac sFRP2 was determined by Western blot and quantitative polymerase chain reaction (qPCR). Results: The level of serum-sFRP2 was higher in HTN patients with echocardiographic LV remodeling than their non-remodeling counterparts. ROC analysis showed that the area under the curve (AUC) for sFRP2 in distinguishing echocardiographic LV remodeling in HTN patients was 0.791 (95% confidence interval (CI): 0.714-0.869). The sFRP2 was negatively correlated with LV dimension and positively correlated with relative wall thickness (RWT). The expression of sFRP2 was higher in hypertrophic hearts, which could be reversed by myricetin. Conclusions: The serum level and cardiac sFRP2 increased in the setting of LV remodeling and decreased by myricetin. Serum sFRP2 may be a promising distinguishing factor for LV remodeling in HTN patients.