PEPPI-MS: gel-based sample pre-fractionation for deep top-down and middle-down proteomics.

Top-down analysis of intact proteins and middle-down analysis of proteins subjected to limited digestion require efficient detection of traces of proteoforms in samples, necessitating the reduction of sample complexity by thorough pre-fractionation of the proteome components in the sample. SDS-PAGE is a simple and inexpensive high-resolution protein-separation technique widely used in biochemical and molecular biology experiments. Although its effectiveness for sample preparation in bottom-up proteomics has been proven, establishing a method for highly efficient recovery of intact proteins from the gel matrix has long been a challenge for its implementation in top-down and middle-down proteomics.

Discovery of bicyclic borane molecule BH.

The discovery of fullerene following the synthesis of graphene marked a paradigm shift in chemistry. Here, we report the discovery of biycycloborane, arising from the synthesis of borophane (hydrogen boride). Uniquely, this synthesis method involves a decomposition mechanism rather than traditional atom-by-atom assembly, marking an unique approach to constructing complex borane structures.

Evaluating and Enhancing Japanese Large Language Models for Genetic Counseling Support: Comparative Study of Domain Adaptation and the Development of an Expert-Evaluated Dataset.

Background: Advances in genetics have underscored a strong association between genetic factors and health outcomes, leading to an increased demand for genetic counseling services. However, a shortage of qualified genetic counselors poses a significant challenge. Large language models (LLMs) have emerged as a potential solution for augmenting support in genetic counseling tasks.

The preference for surprise in reinforcement learning underlies the differences in developmental changes in risk preference between autistic and neurotypical youth.

Background: Risk preference changes nonlinearly across development. Although extensive developmental research on the neurotypical (NTP) population has shown that risk preference is highest during adolescence, developmental changes in risk preference in autistic (AUT) people, who tend to prefer predictable behaviors, have not been investigated. Here, we aimed to investigate these changes and underlying computational mechanisms.

Multicentric Cross-Sectional Survey to Assess the Variation of Fractionation Strategies Used in the Management of Head and Neck Cancers in the Asian Region (INNOCENCE-ASIA).

Purpose: Head and neck cancers (HNCs) are in general treated with conventional fractionation regimen of 1.8-2 Gy per fraction. Altered fractionation (ALFT) strategies such as hypofractionation radiotherapy (HYPO-RT), accelerated fractionation radiotherapy (AFRT), and hyperfractionation radiotherapy (HFRT) have not been practiced uniformly across centers in different parts of the world.

Associations of Cardiorespiratory Fitness with Cerebral Cortical Thickness and Gray Matter Volume Across the Adult Lifespan.

High cardiorespiratory fitness (CRF) is associated with reduced cortical thinning and gray matter (GM) shrinkage in older adults. We investigated associations of CRF measured with peak oxygen consumption (V̇ O) with cortical thickness and GM volume across the adult lifespan. We hypothesized that higher CRF is associated with less cortical thinning and GM shrinkage across the adult lifespan, which is associated with better cognitive performance.

Identification of Key Amino Acids in the A Domains of Polymyxin Synthetase Responsible for 2,4-Diaminobutyric Acid Adenylation in NBRC3020 Strain.

Developing novel nonribosomal peptides (NRPs) requires a comprehensive understanding of the enzymes involved in their biosynthesis, particularly the substrate amino acid recognition mechanisms in the adenylation (A) domain. This study focused on the A domain responsible for adenylating l-2,4-diaminobutyric acid (l-Dab) within the synthetase of polymyxin, an NRP produced by NBRC3020. To date, investigations into recombinant proteins that selectively adenylate l-Dab─exploring substrate specificity and enzymatic activity parameters─have been limited to reports on A domains found in enzymes synthesizing l-Dab homopolymers (pldA from USE31 and pddA from NBRC15115), which remain exceedingly rare.

FilmArray® Effectively Detects All Clades of F41 but Encounters Challenges with Other Adenovirus Species.

The BioFire FilmArray® Gastrointestinal (GI) Panel, a widely used diagnostic tool, is designed to detect the genetic material of 22 common pathogens responsible for gastroenteritis, including viruses, bacteria, and parasites. It can detect human adenovirus (HAdV) species F, particularly serotypes F40 and F41, which are the major causes of diarrhea and mortality in children. However, its potential shortcomings in detecting other HAdV species limit its effectiveness in broader HAdV detection in clinical settings and outbreak investigations.

Endothelial cell (EC)-specific CTGF/CCN2 Expression Increases EC Reprogramming and Atherosclerosis.

Arterial endothelial cells (ECs) reside in a complex biomechanical environment. ECs sense and respond to wall shear stress. Low and oscillatory wall shear stress is characteristic of disturbed flow and commonly found at arterial bifurcations and around atherosclerotic plaques.

Factors affecting 1-year persistence with vedolizumab for ulcerative colitis: a multicenter, retrospective real-world study.

Background/aims: The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response.

Methods: In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled.

Results: Persistence with vedolizumab was 64.

The impact of colloid-solvent dynamic coupling on the coarsening rate of colloidal phase separation.

Phase separation, a fundamental phenomenon in both natural and industrial settings, involves the coarsening of domains over time t to reduce interfacial energy. While well-understood for simple viscous liquid mixtures, the physical laws governing coarsening dynamics in complex fluids, such as colloidal suspensions, remain unclear. Here, we investigate colloidal phase separation through particle-based simulations with and without hydrodynamic interactions (HIs).

Emerging Trends and Future Opportunities for Battery Recycling.

The global lithium-ion battery recycling capacity needs to increase by a factor of 50 in the next decade to meet the projected adoption of electric vehicles. During this expansion of recycling capacity, it is unclear which technologies are most appropriate to reduce costs and environmental impacts. Here, we describe the current and future recycling capacity situation and summarize methods for quantifying costs and environmental impacts of battery recycling methods with a focus on cathode active materials.

Design concepts for advanced-technology intraocular lenses [Invited].

An intraocular lens (IOL) replaces the natural crystalline lens during cataract surgery, and although the vast majority of implants have simple optics, "advanced technology" IOLs have multifocal and extended depth of focus (EDOF) properties. Optical concepts are evaluated here, with image contrast, focal range, and unwanted visual phenomena being the primary concerns. Visual phenomena with earlier bifocal diffractive lenses led to alternative diffractive designs (trifocals, etc.

Availability and Key Characteristics of National Early Warning Systems for Emerging Profiles of Antimicrobial Resistance in High-Income Countries: Systematic Review.

Background: The World Health Organization (WHO) recently advocated an urgent need for implementing national surveillance systems for the timely detection and reporting of emerging antimicrobial resistance (AMR). However, public information on the existing national early warning systems (EWSs) is often incomplete, and a comprehensive overview on this topic is currently lacking.

Objective: This review aimed to map the availability of EWSs for emerging AMR in high-income countries and describe their main characteristics.

Sucrose and Gibberellic Acid Binding Stabilize the Inward-Open Conformation of AtSWEET13: A Molecular Dynamics Study.

In plants, sugar will eventually be exported transporters (SWEETs) facilitate the translocation of mono- and disaccharides across membranes and play a critical role in modulating responses to gibberellin (GA3), a key growth hormone. However, the dynamic mechanisms underlying sucrose and GA3 binding and transport remain elusive. Here, we employed microsecond-scale molecular dynamics (MD) simulations to investigate the influence of sucrose and GA3 binding on SWEET13 transporter motions.

Updates on neonatal cell and novel therapeutics: Proceedings of the Second Neonatal Cell Therapies Symposium (2024).

Cell therapies as treatments for neonatal conditions have attracted significant research and parent interest over the last two decades. Mesenchymal stromal cells, umbilical cord blood cells and neural stem cells translate from lab, to preclinical and into clinical trials, with contributions being made from all over the world. Effective and timely translation involves frequent reflection and consultation from research-adjacent fields (i.

Ferroelectricity with concomitant Coulomb screening in van der Waals heterostructures.

Interfacial ferroelectricity emerges in non-centrosymmetric heterostructures consisting of non-polar van der Waals (vdW) layers. Ferroelectricity with concomitant Coulomb screening can switch topological currents or superconductivity and simulate synaptic response. So far, it has only been realized in bilayer graphene moiré superlattices, posing stringent requirements to constituent materials and twist angles.

G-quadruplex-forming small RNA inhibits coronavirus and influenza A virus replication.

Future pandemic threats may be caused by novel coronaviruses and influenza A viruses. Here we show that when directly added to a cell culture, 12mer guanine RNA (G12) and its phosphorothioate-linked derivatives (G12(S)), rapidly entered cytoplasm and suppressed the propagation of human coronaviruses and influenza A viruses to between 1/100 and nearly 1/1000 of normal virus infectivity without cellular toxicity and induction of innate immunity. Moreover, G12(S) alleviated the weight loss caused by coronavirus infection in mice.

Massively parallel characterization of transcriptional regulatory elements.

The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.

Diversity of TCR repertoire predicts recurrence after CRT followed by durvalumab in patients with NSCLC.

Chemoradiotherapy (CRT) followed by durvalumab is standard for unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). This study assesses how CRT alters the T-cell receptor (TCR) repertoire in CD8 + PD-1 + T-cells and its impact on clinical outcomes. This prospective study, conducted from November 2019 to May 2021 at three institutions in Japan, evaluated the diversity of TCR repertoire (DE50) in PD-1 + CD8 + T-cells and CD8 + T-cell phenotypes in peripheral blood before and after CRT.

Two-layer homolog network approach for PFAS nontarget screening and retrospective data mining.

The rapid increase of novel per- and polyfluoroalkyl substances (PFAS) raises concerns, while their identification remains challenging. Here, we develop a two-layer homolog network approach for PFAS nontarget screening using mass spectrometry. The first layer constructs networks between homologs, with evaluation showing that it filters 94% of false candidates.

Optical Fresnel zone plate flat lenses made entirely of colored photoresist through an i-line stepper.

Light manipulation and control are essential in various contemporary technologies, and as these technologies evolve, the demand for miniaturized optical components increases. Planar-lens technologies, such as metasurfaces and diffractive optical elements, have gained attention in recent years for their potential to dramatically reduce the thickness of traditional refractive optical systems. However, their fabrication, particularly for visible wavelengths, involves complex and costly processes, such as high-resolution lithography and dry-etching, which has limited their availability.

Cutting through the noise: A narrative review of Alzheimer's disease plasma biomarkers for routine clinical use.

As novel, anti-amyloid therapies have become more widely available, access to timely and accurate diagnosis has become integral to ensuring optimal treatment of patients with early-stage Alzheimer's disease (AD). Plasma biomarkers are a promising tool for identifying AD pathology; however, several technical and clinical factors need to be considered prior to their implementation in routine clinical use. Given the rapid pace of advancements in the field and the wide array of available biomarkers and tests, this review aims to summarize these considerations, evaluate available platforms, and discuss the steps needed to bring plasma biomarker testing to the clinic.