pH-Responsive Polyethylene Glycol Engagers for Enhanced Brain Delivery of PEGylated Nanomedicine to Treat Glioblastoma.

The blood-brain barrier (BBB) remains a major obstacle for effective delivery of therapeutics to treat central nervous system (CNS) disorders. Although transferrin receptor (TfR)-mediated transcytosis is widely employed for brain drug delivery, the inefficient release of therapeutic payload hinders their efficacy from crossing the BBB. Here, we developed a pH-responsive anti-polyethylene glycol (PEG) × anti-TfR bispecific antibody (pH-PEG engager) that can complex with PEGylated nanomedicine at physiological pH to trigger TfR-mediated transcytosis in the brain microvascular endothelial cells, while rapidly dissociating from PEGylated nanomedicine at acidic endosomes for efficient release of PEGylated nanomedicine to cross the BBB.

An acidophilic fungus promotes prey digestion in a carnivorous plant.

Leaves of the carnivorous sundew plants (Drosera spp.) secrete mucilage that hosts microorganisms, but whether this microbiota contributes to prey digestion is unclear. We identified the acidophilic fungus Acrodontium crateriforme as the dominant species in the mucilage microbial communities, thriving in multiple sundew species across the global range.

Development of a high-throughput kinase activity platform using nanoLC-MS/MS with DIA approach for studying the anti-cancer mechanism of Taxol in ovarian cancer.

Background: Protein phosphorylation by protein kinases plays a pivotal role in increasing protein diversity, thereby influencing various cellular functions. However, due to the relatively low abundance of phosphopeptides in a mixture of peptides and the ion-suppression effect of non-phosphorylated peptides, the detection of phosphopeptides is not straightforward.

Results: Herein, a quantitative high-throughput platform was developed for assessing multikinase activity using nano-LC-MS/MS with a data-independent acquisition (DIA) approach.

Tracking alternative versions of the galactose gene network in the genus and their expansion after domestication.

When grows on mixtures of glucose and galactose, galactose utilization is repressed by glucose, and induction of the gene network only occurs when glucose is exhausted. Contrary to reference alleles, alternative alleles support faster growth on galactose, thus enabling distinct galactose utilization strategies maintained by balancing selection. Here, we report on new wild populations of harboring alternative versions and, for the first time, of alternative alleles.

Single-worm long-read sequencing reveals genome diversity in free-living nematodes.

Obtaining sufficient genetic material from a limited biological source is currently the primary operational bottleneck in studies investigating biodiversity and genome evolution. In this study, we employed multiple displacement amplification (MDA) and Smartseq2 to amplify nanograms of genomic DNA and mRNA, respectively, from individual Caenorhabditis elegans. Although reduced genome coverage was observed in repetitive regions, we produced assemblies covering 98% of the reference genome using long-read sequences generated with Oxford Nanopore Technologies (ONT).

Online 2D High-pH and Low-pH Reversed-Phase Nano-LC-MS/MS System for Deep Proteome Analysis.

In bottom-up proteomic profiling, the complexity of proteome composition and wide dynamic range has created challenges on the limited number of protein identification and proteome coverage, especially in sample input-limited nanoflow (nano) LC-MS/MS analysis. Herein, we developed a fully automatic online 2D nano-LC-MS/MS system using both high-pH and low-pH reverse phase (RP) LCs on a single LC instrument toward comprehensive proteomics analysis. Compared to conventional microflow 2D-LC, the high-pH RP trapping column demonstrated a low sample requirement of cellular protein digest at the μg level with good fractionation resolution of >90% peptides in a single fraction.

A Comprehensive Secondary Prevention Benchmark (2PBM) Score Identifying Differences in Secondary Prevention Care in Patients After Acute Coronary Syndrome.

Purpose: The objective of this study was to quantify secondary prevention care by creating a secondary prevention benchmark (2PBM) score for patients undergoing ambulatory cardiac rehabilitation (CR) after acute coronary syndrome (ACS).

Methods: In this observational cohort study, 472 consecutive ACS patients who completed the ambulatory CR program between 2017 and 2019 were included. Benchmarks for secondary prevention medication and clinical and lifestyle targets were predefined and combined in the comprehensive 2PBM score with maximum 10 points.

The Aphelenchoides genomes reveal substantial horizontal gene transfers in the last common ancestor of free-living and major plant-parasitic nematodes.

Aphelenchoides besseyi is a plant-parasitic nematode (PPN) in the family Aphelenchoididae capable of infecting more than 200 plant species. A. besseyi is also a species complex with strains exhibiting varying pathogenicity to plants.

Achievement of Low-Density Lipoprotein Cholesterol Targets in Cardiac Rehabilitation: Impact of the 2019 ESC/EAS Dyslipidaemia Guidelines.

In 2019 the European Society of Cardiology (ESC) lowered the target values for low-density lipoprotein cholesterol (LDL-C) from <1.8 mmol/L to <1.4 mmol/L for secondary prevention of cardiovascular disease (CVD).

A Comparison of Cooking Conditions of Pulp as a Substitute for Wood Pulp.

The green macroalga was cooked with 5%, 10%, and 20% sodium hydroxide (NaOH) for 4 h (5-N, 10-N, and 20-N groups, respectively); with 5%, 10%, and 20% sodium sulfite (NaSO) for 4 h (5-NS, 10-NS, and 20-NS groups, respectively); and with 5%, 10%, and 20% NaOH for 2 h and 1% hydrogen peroxide (HO) for 2 h (5-NH, 10-NH, and 20-NH groups, respectively). The 5-NH handsheet showed the best mechanical properties; however, the 10-NH pulp was easier to separate than 5-NH during handsheet making, and 10-NH was more suitable for the industrial process. Thus, the 10-NH group showed the optimal production conditions with an optimal length/width ratio, crystallinity index (CI%), three-dimensional (3D) configuration, and mechanical strength.

Bond strength of self-adhesive resin cements to a high transparency zirconia crown and dentin.

Background/purpose: The bond strength and durability of highly translucent zirconia ceramics to dentin is still unclear. The purpose of this study was to investigate the effect of various surface treatments on the bond strength of self-adhesive resin cements to high-translucent zirconia crowns and dentin.

Materials And Methods: A high-transparent zirconia and three self-adhesive resin cements (G-CEM LinkAce (GCL), RelyX U200 (RXU) and TotalCem (TTC)) were used.

Extensive sampling of in Taiwan reveals ecology and evolution of predomesticated lineages.

The ecology and genetic diversity of the model yeast before human domestication remain poorly understood. Taiwan is regarded as part of this yeast's geographic birthplace, where the most divergent natural lineage was discovered. Here, we extensively sampled the broadleaf forests across this continental island to probe the ancestral species' diversity.

Rapid Identification of Methicillin-Resistant Staphylococcus aureus Using MALDI-TOF MS and Machine Learning from over 20,000 Clinical Isolates.

Rapidly identifying methicillin-resistant Staphylococcus aureus (MRSA) with high integration in the current workflow is critical in clinical practices. We proposed a matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS)-based machine learning model for rapid MRSA prediction. The model was evaluated on a prospective test and four external clinical sites.

Development of a high-pH reversed-phase well plate for peptide fractionation and deep proteome analysis of cells and exosomes.

The complexity of the proteome often limits the number of identified proteins in the nanoflow LC-MS (nanoLC-MS) analysis of samples. Therefore, peptide fractionation is essential for reducing the sample complexity and improving the proteome coverage. In this study, to achieve high-pH reversed-phase (RP)-well plate fractionation for high-throughput proteomics analysis, C18 particles were coated on a 96-well plate, and the sample-loading processes were optimized for high-pH fractionation.

Optical properties evaluation of rapid sintered translucent zirconia with two dental colorimeters.

Background/purpose: The efficient rapid sintering technique has employed to dental zirconia ceramics for shortening the fabrication time of zirconia restorations. The purpose was to compare the optical properties of two generations of rapid sintered translucent zirconia using two dental colorimeters.

Materials And Methods: Two generations of translucent zirconia ceramics, 3 mol% yttria-tetragonal zirconia polycrystal (3Y-TZP): Copran Zr-i Ultra-T (UT) and Cercon HT (HT), and 5 mol% yttria-tetragonal zirconia polycrystal (5Y-TZP): Cercon xt (XT), of different thicknesses (0.

Pleural cytokines MIF and MIP-3α as novel biomarkers for complicated parapneumonic effusions and empyema.

Patients with complicated parapneumonic effusion (CPPE)/empyema have high morbidity and mortality, particularly when adequate management is delayed. We aimed to investigate novel dysregulated cytokines that can be used as biomarkers for infectious pleural effusions, especially for CPPE/empyema. Expression of 40 cytokines in parapneumonic effusions (PPE) was screened in the discovery phase, involving 63 patients, using a multiplex immunobead-based assay.

genomes resolve the evolution of fungal bioluminescence.

Mushroom-forming fungi in the order Agaricales represent an independent origin of bioluminescence in the tree of life; yet the diversity, evolutionary history, and timing of the origin of fungal luciferases remain elusive. We sequenced the genomes and transcriptomes of five bonnet mushroom species ( spp.), a diverse lineage comprising the majority of bioluminescent fungi.

Protein Biomarker Discovery for Methicillin-Sensitive, Heterogeneous Vancomycin-Intermediate and Vancomycin-Intermediate Strains Using Label-Free Data-Independent Acquisition Proteomics.

Rapid identification of methicillin-sensitive (MSSA), heterogeneous vancomycin-intermediate (hVISA), and vancomycin-intermediate (VISA) is important for accurate treatment, timely intervention, and prevention of outbreaks. Here, 90 isolates were analyzed for protein biomarker discovery, including MSSA, vancomycin-susceptible (VSSA), hVISA, and VISA strains. Label-free data-independent acquisition proteomics was used to identify protein biomarkers that allow for discrimination among MSSA, hVISA, and VISA strains.

SUMO E3 ligase PIAS1 is a potential biomarker indicating stress susceptibility.

Prior studies suggest that individual differences in stress responses contribute to the pathogenesis of neuropsychiatric disorders. In the present study, we investigated the role of small ubiquitin-like modifier (SUMO) E3 ligase protein inhibitor of activated STAT1 (PIAS1) in mediating stress responses to chronic social defeat stress (CSDS). We found that mRNA and protein levels of PIAS 1 were decreased in the hippocampus of high-susceptibility (HS) mice but not in low-susceptibility (LS) mice after CSDS.

Novel human models for elucidating mechanisms of rate-sensitive H-reflex depression.

Background: This study used novel human neurophysiologic models to investigate whether the mechanism of rate-sensitive H-reflex depression lies in the pre-synaptic or post-synaptic locus in humans. We hypothesized that pre-synaptic inhibition would suppress Ia afferents and H-reflexes without suppressing alpha motor neurons or motor evoked potentials (MEPs). In contrast, post-synaptic inhibition would suppress alpha motor neurons, thereby reducing H-reflexes and MEPs.

A rapid, multiplexed kinase activity assay using 8-plex iTRAQ labeling, SPE, and MALDI-TOF/TOF MS.

Synthesized peptide substrates have been used for in vitro phosphorylation using purified kinases or cell lysates. For screening assays, a direct readout and comparison among different experimental conditions without using an internal standard would be preferred. In this study, we developed a rapid, quantitative measurement method of multikinase activity based on MALDI-TOF/TOF MS.

Combined serum biomarkers in the noninvasive diagnosis of complicated parapneumonic effusions and empyema.

Background: We previously demonstrated that the pleural levels of proteins (neutrophil gelatinase-associated lipocalin/NGAL, calprotectin, bactericidal permeability-increasing/BPI, azurocidin 1/AZU-1) were valuable markers for identifying complicated PPE (CPPE). Herein, this study was performed to evaluate whether these proteins are useful as serological markers for identifying CPPE and empyema.

Methods: A total of 137 participates were enrolled in this study.

Bond strength of ceramics heat-pressed onto three dental alloys.

Statement Of Problem: The press-on-metal (PoM) technique has been used as an alternative fabrication method for metal-ceramic restorations. However, how the PoM technique compares with the conventional porcelain layering (CPL) technique under a variety of conditions is unclear.

Purpose: The purpose of this in vitro study was to compare the bond strength of 3 alloy substrates with heat-pressed ceramics or conventionally layered porcelain before and after thermocycling.

Stout camphor tree genome fills gaps in understanding of flowering plant genome evolution.

We present reference-quality genome assembly and annotation for the stout camphor tree (Cinnamomum kanehirae (Laurales, Lauraceae)), the first sequenced member of the Magnoliidae comprising four orders (Laurales, Magnoliales, Canellales and Piperales) and over 9,000 species. Phylogenomic analysis of 13 representative seed plant genomes indicates that magnoliid and eudicot lineages share more recent common ancestry than monocots. Two whole-genome duplication events were inferred within the magnoliid lineage: one before divergence of Laurales and Magnoliales and the other within the Lauraceae.

Targeted Ubiquitin-Proteasomal Proteolysis Pathway in Chronic Social Defeat Stress.

Stressful events promote psychopathogenic changes that might contribute to the development of mental illnesses. Some individuals tend to recover from the stress response, while some do not. However, the molecular mechanisms of stress resilience during stress are not well-characterized.