Microdosimetric Analysis for Boron Neutron Capture Therapy via Monte Carlo Track Structure Simulation with Modified Lithium Cross-sections.

Boron neutron capture therapy (BNCT) is a cellular-level hadron therapy achieving therapeutic effects via the synergistic action of multiple particles, including Lithium, alpha, proton, and photon. However, evaluating the relative biological effectiveness (RBE) in BNCT remains challenging. In this research, we performed a microdosimetric calculation for BNCT using the Monte Carlo track structure (MCTS) simulation toolkit, TOPAS-nBio. This paper reports the first attempt to derive the ionization cross-sections of low-energy (>0.025 MeV/u) Lithium for MCTS simulation based on the effective charge cross-section scalation method and phenomenological double-parameter modification. The fitting parameters λ1=1.101,λ2=3.486 were determined to reproduce the range and stopping power data from the ICRU report 73. Besides, the lineal energy spectra of charged particles in BNCT were calculated, and the influence of sensitive volume (SV) size was discussed. Condensed history simulation obtained similar results with MCTS when using Micron-SV while overestimating the lineal energy when using Nano-SV. Furthermore, we found that the microscopic boron distribution can significantly affect the lineal energy for Lithium, while the effect for alpha is minimal. Similar results to the published data by PHITS simulation were observed for the compound particles and monoenergetic protons when using micron-SV. Spectra with nano-SV reflected that the different track densities and absorbed doses in the nucleus together result in the dramatic difference in the macroscopic biological response of BPA and BSH. This work and the developed methodology could impact the research fields in BNCT where understanding radiation effects is crucial, such as the treatment planning system, source evaluation, and new boron drug development

Brain Cell-Type Shifts in Alzheimer’s Disease, Autism, and Schizophrenia Interrogated Using Methylomics and Genetics

Few neuropsychiatric disorders have replicable biomarkers, prompting high-resolution and large-scale molecular studies. However, we still lack consensus on a more foundational question: whether quantitative shifts in cell types-the functional unit of life-contribute to neuropsychiatric disorders. Leveraging advances in human brain single-cell methylomics, we deconvolve seven major cell types using bulk DNA methylation profiling across 1270 postmortem brains, including from individuals diagnosed with Alzheimer\u27s disease, schizophrenia, and autism. We observe and replicate cell-type compositional shifts for Alzheimer\u27s disease (endothelial cell loss), autism (increased microglia), and schizophrenia (decreased oligodendrocytes), and find age- and sex-related changes. Multiple layers of evidence indicate that endothelial cell loss contributes to Alzheimer\u27s disease, with comparable effect size to APOE genotype among older people. Genome-wide association identified five genetic loci related to cell-type composition, involving plausible genes for the neurovascular unit (P2RX5 and TRPV3) and excitatory neurons (DPY30 and MEMO1). These results implicate specific cell-type shifts in the pathophysiology of neuropsychiatric disorders

Co-assembling living material as an in vitro lung epithelial infection model

Biofilms are robust living 3D materials that play key roles in nature but also cause major problems, such as tolerance to antibiotic treatment. Recreation of these living structures in vitro is critical to understand their biology and develop solutions to the problems they cause. However, growing 3D biofilms in vitro is difficult primarily because of the limitations in developing matrices that mimic the inherent structural and compositional complexity of their extracellular milieu. Here, we report a living material based on the co-assembly of artificial sputum medium with bioactive peptide amphiphiles. We demonstrate its capacity to support the growth of 3D polymicrobial biofilms and build an interkingdom infected lung epithelial model to study the impact of the antibiotic ciprofloxacin. Our study offers a living material capable of growing functional 3D biofilms that simulate in vitro the nutritional and mechanical properties of these systems in vivo

Large-Scale Roll-to-Roll Fabrication of Ordered Mesoporous Materials using Resol-Assisted Cooperative Assembly

Roll-to-roll (R2R) processing enables the rapid fabrication of large-area sheets of cooperatively assembled materials for production of mesoporous materials. Evaporation induced self-assembly of a nonionic surfactant (Pluronic F127) with sol–gel precursors and phenolic resin oligomers (resol) produce highly ordered mesostructures for a variety of chemistries including silica, titania, and tin oxide. The cast thick (\u3e200 μm) film can be easily delaminated from the carrier substrate (polyethylene terephthalate, PET) after cross-linking the resol to produce meter-long self-assembled sheets. The surface areas of these mesoporous materials range from 240 m2/g to \u3e1650 m2/g with these areas for each material comparing favorably with prior reports in the literature. These R2R methods provide a facile route to the scalable production of kilograms of a wide variety of ordered mesoporous materials that have shown potential for a wide variety of applications with small-batch syntheses

Hierarchical Electrospun and Cooperatively Assembled Nanoporous Ni/NiO/MnO_<i>x</i>/Carbon Nanofiber Composites for Lithium Ion Battery Anodes

A facile method to fabricate hierarchically structured fiber composites is described based on the electrospinning of a dope containing nickel and manganese nitrate salts, citric acid, phenolic resin, and an amphiphilic block copolymer. Carbonization of these fiber mats at 800 °C generates metallic Ni-encapsulated NiO/MnO_<i>x</i>/carbon composite fibers with average BET surface area (150 m²/g) almost 3 times higher than those reported for nonporous metal oxide nanofibers. The average diameter (∼900 nm) of these fiber composites is nearly invariant of chemical composition and can be easily tuned by the dope concentration and electrospinning conditions. The metallic Ni nanoparticle encapsulation of NiO/MnO_<i>x</i>/C fibers leads to enhanced electrical conductivity of the fibers, while the block copolymers template an internal nanoporous morphology and the carbon in these composite fibers helps to accommodate volumetric changes during charging. These attributes can lead to lithium ion battery anodes with decent rate performance and long-term cycle stability, but performance strongly depends on the composition of the composite fibers. The composite fibers produced from a dope where the metal nitrate is 66% Ni generates the anode that exhibits the highest reversible specific capacity at high rate for any composition, even when including the mass of the nonactive carbon and Ni⁰ in the calculation of the capacity. On the basis of the active oxides alone, near-theoretical capacity and excellent cycling stability are achieved for this composition. These cooperatively assembled hierarchical composites provide a platform for fundamentally assessing compositional dependencies for electrochemical performance. Moreover, this electrospinning strategy is readily scalable for the fabrication of a wide variety of nanoporous transition metal oxide fibers

Large-Scale Roll-to-Roll Fabrication of Ordered Mesoporous Materials using Resol-Assisted Cooperative Assembly

Roll-to-roll (R2R) processing enables the rapid fabrication of large-area sheets of cooperatively assembled materials for production of mesoporous materials. Evaporation induced self-assembly of a nonionic surfactant (Pluronic F127) with sol–gel precursors and phenolic resin oligomers (resol) produce highly ordered mesostructures for a variety of chemistries including silica, titania, and tin oxide. The cast thick (>200 μm) film can be easily delaminated from the carrier substrate (polyethylene terephthalate, PET) after cross-linking the resol to produce meter-long self-assembled sheets. The surface areas of these mesoporous materials range from 240 m²/g to >1650 m²/g with these areas for each material comparing favorably with prior reports in the literature. These R2R methods provide a facile route to the scalable production of kilograms of a wide variety of ordered mesoporous materials that have shown potential for a wide variety of applications with small-batch syntheses

Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection

<div><p>In order to assess potential associations between autism spectrum disorder (ASD) phenotype, functional GI disorders and fecal microbiota, we recruited simplex families, which had only a single ASD proband and neurotypical (NT) siblings, through the Simons Simplex Community at the Interactive Autism Network (SSC@IAN). Fecal samples and metadata related to functional GI disorders and diet were collected from ASD probands and NT siblings of ASD probands (age 7–14). Functional gastrointestinal disorders (FGID) were assessed using the parent-completed ROME III questionnaire for pediatric FGIDs, and problem behaviors were assessed using the Child Behavior Check List (CBCL). Targeted quantitative polymerase chain reaction (qPCR) assays were conducted on selected taxa implicated in ASD, including <i>Sutterella spp</i>., <i>Bacteroidetes spp</i>. and <u><i>Prevotella spp</i></u>. Illumina sequencing of the V1V2 and the V1V3 regions of the bacterial 16S rRNA genes from fecal DNA was performed to an average depth of 208,000 and 107,000 high-quality reads respectively. Twenty-five of 59 ASD children and 13 of 44 NT siblings met ROME III criteria for at least one FGID. Functional constipation was more prevalent in ASD (17 of 59) compared to NT siblings (6 of 44, P = 0.035). The mean CBCL scores in NT siblings with FGID, ASD children with FGID and ASD without FGID were comparably higher (58–62 vs. 44, P < 0.0001) when compared to NT children without FGID. There was no significant difference in macronutrient intake between ASD and NT siblings. There was no significant difference in ASD severity scores between ASD children with and without FGID. No significant difference in diversity or overall microbial composition was detected between ASD children with NT siblings. Exploratory analysis of the 16S rRNA sequencing data, however, identified several low abundance taxa binned at the genus level that were associated with ASD and/or first order ASD*FGID interactions (FDR <0.1).</p></div