作者:
Wu, YouXie, LeiCUNY
Grad Ctr PhD Program Comp Sci New York NY 10016 USA CUNY
Grad Ctr PhD Program Biol & Biochem New York NY USA CUNY
Hunter Coll Dept Comp Sci New York NY USA Cornell Univ
Weill Cornell Med Helen & Robert Appel Alzheimers Dis Res Inst Feil Family Brain & Mind Res Inst New York NY USA
Despite the wealth of single-cell multi-omics data, it remains challenging to predict the consequences of novel genetic and chemical perturbations in the human body. It requires knowledge of molecular interactions at ...
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Despite the wealth of single-cell multi-omics data, it remains challenging to predict the consequences of novel genetic and chemical perturbations in the human body. It requires knowledge of molecular interactions at all biological levels, encompassing disease models and humans. Current machine learning methods primarily establish statistical correlations between genotypes and phenotypes but struggle to identify physiologically significant causal factors, limiting their predictive power. Key challenges in predictive modeling include scarcity of labeled data, generalization across different domains, and disentangling causation from correlation. In light of recent advances in multi-omics data integration, we propose a new artificial intelligence (AI)-powered biologyinspired multi-scale modeling framework to tackle these issues. This framework will integrate multi-omics data across biological levels, organism hierarchies, and species to predict genotype-environment-phenotype relationships under various conditions. AI models inspired by biology may identify novel molecular targets, biomarkers, pharmaceutical agents, and personalized medicines for presently unmet medical needs.
This study evaluated the microshear bond strength (mu SBS) of resin cement to a 3D-printed ceramic-containing resin composite (PriZma 3D Bio Crown, Makertech) subjected to different adhesive protocols (surface pretrea...
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This study evaluated the microshear bond strength (mu SBS) of resin cement to a 3D-printed ceramic-containing resin composite (PriZma 3D Bio Crown, Makertech) subjected to different adhesive protocols (surface pretreatments and adhesive systems), in both baseline and aging conditions. For this, 3D-printed resin composite slices were fabricated and divided into groups based on adhesive protocols, considering three surface pretreatments: alumina grit-blasting (AlOx), 37 % phosphoric acid (PA), and a combination of both (AlOx + PA);and two adhesive systems: conventional (Adper Single Bond 2, 3M) and universal (Single Bond Universal, 3M). The resin cement (RelyX Ultimate, 3M) cylinder specimens (n = 18) underwent mu SBS testing before and after thermocycling (12,000 cycles, 5-55 degrees C). Surface roughness (R-a and R-z), SEM topography, and failure modes were analyzed. Statistical analysis included One- and Two-Way ANOVA with Tukey tests for roughness and mu SBS, respectively, and paired t-test to compare baseline and aging conditions considering the same adhesive protocol (alpha = 0.05). AlOx + PA with the universal adhesive demonstrated the highest bond strength in both baseline and aged conditions, with a minimal reduction after aging (11.68 %, p = 0.294). The PA-conventional adhesive group had the greatest reduction post-aging (50.32 %, p < 0.001). After aging, AlOx and PA with universal adhesive showed intermediate bond strengths, similar to AlOx + PA-universal, while the use of conventional adhesive resulted in lower bonding performance. In Baseline, AlOx + PA-universal exhibited the highest Weibull modulus, while AlOx + PA-conventional had the lowest. After aging, AlOx + PA-universal remained the highest, differing from the other groups but similar to AlOx + PA-conventional, whereas PA-universal had the lowest modulus. The other groups showed intermediate values without significant differences. The combination of alumina grit-blasting and phosphoric acid with a
作者:
Marciano, Yarondel Solar, VirginiaNayeem, NaziaDave, DhwanitSon, JiyeContel, MariaUlijn, Rein, VCUNY
Adv Sci Res Ctr Nanosci Initiat Grad Ctr New York NY 10031 USA CUNY
Brooklyn Coll Dept Chem Brooklyn NY 11210 USA Guys Hosp
Cell & Gene Therapy Catapult 12th Floor Tower Wing London SE1 9RT England CUNY
PhD Program Chem Grad Ctr New York NY 10016 USA CUNY
Hunter Coll Dept Chem New York NY 10065 USA CUNY
PhD Program Biochem PhD Program Chem Grad Ctr New York NY 10016 USA CUNY
PhD Program Biochem Grad Ctr New York NY 10016 USA
We investigated the use of amphiphilic, protease-cleavable peptides as encapsulation moieties for hydrophobic metallodrugs, in order to enhance their bioavailability and consequent activity. Two hydrophobic, gold-cont...
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We investigated the use of amphiphilic, protease-cleavable peptides as encapsulation moieties for hydrophobic metallodrugs, in order to enhance their bioavailability and consequent activity. Two hydrophobic, gold-containing anticancer agents varying in aromatic ligand distribution (Au(I)-N-heterocyclic carbene compounds 1 and 2) were investigated. These were encapsulated into amphiphilic decapeptides that form soluble filamentous structures with hydrophobic cores, varying supramolecular packing arrangements and surface charge. Peptide sequence strongly dictates the supramolecular packing within the aromatic core, which in turn dictates drug loading. Anionic peptide filaments can effectively load 1, and to a lesser extent 2, while their cationic counterparts could not, collectively demonstrating that loading efficiency is dictated by both aromatic and electrostatic (mis)matching between drug and peptide. Peptide nanofilaments were nontoxic to cancerous and noncancerous cells. By contrast, those loaded with 1 and 2 displayed enhanced cytotoxicity in comparison to 1 and 2 alone, when exposed to Caki-1 and MDA-MB-231 cancerous cell lines, while no cytotoxicity was observed in noncancerous lung fibroblasts, IMR-90. We propose that the enhanced in vitro activity results from the enhanced proteolytic activity in the vicinity of the cancer cells, thereby breaking the filaments into drug-bound peptide fragments that are taken up by these cells, resulting in enhanced cytotoxicity toward cancer cells.
Cancer cells exploit mechanisms to evade immune detection triggered by aberrant self-nucleic acids (NA). PARP7, a key player in this immune evasion strategy, has emerged as a potential target for cancer therapy. PARP7...
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Cancer cells exploit mechanisms to evade immune detection triggered by aberrant self-nucleic acids (NA). PARP7, a key player in this immune evasion strategy, has emerged as a potential target for cancer therapy. PARP7 inhibitors reactivate NA sensing, resulting in type I interferon (IFN) signaling, programmed cell death, anti-tumor immunity, and tumor regression. Cancer cells with elevated IFN-stimulated gene (ISG) scores, representing a viral mimicry-primed state, are particularly sensitive to PARP7 inhibition. This review focuses on the endogenous sources of NA in cancer and the potential to exploit elevated aberrant self-NA in cancer therapy. We describe strategies to increase cytoplamic NA levels, including targeting epigenetic control, DNA damage response, and mitochondrial function. We also discuss targeting RNA processing pathways, such as splicing and RNA editing, to enhance the immunostimulatory potential of existing NA. Combining PARP7 inhibitors with NA elevating strategies may improve cancer immunotherapy, especially for tumors with high ISG scores.
Overactive or dysregulated cytokine expression is a hallmark of many acute and chronic inflammatory diseases. This is true for acute or chronic infections, neurodegenerative diseases, autoimmune diseases, cardiovascul...
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Overactive or dysregulated cytokine expression is a hallmark of many acute and chronic inflammatory diseases. This is true for acute or chronic infections, neurodegenerative diseases, autoimmune diseases, cardiovascular diseases, cancer, and others. Cytokines such as interleukin-6 (IL-6) are known therapeutic targets and biomarkers for such inflammatory diseases. Platforms for cytokine detection are, therefore, desirable tools for both research and clinical applications. Single-walled carbon nanotubes (SWCNT) are versatile nanomaterials with near-infrared fluorescence that can serve as transducers for optical sensors. When functionalized with an analyte-specific recognition element, SWCNT emission may become sensitive and selective toward the desired target. SWCNT-aptamer sensors are easily assembled, inexpensive, and biocompatible. In this work, we introduced a nanosensor design based on SWCNT and a DNA aptamer specific to IL-6. We first evaluated several SWCNT-aptamer constructs based on this simple direct complexation method, wherein the aptamer both solubilizes the SWCNT and confers sensitivity to IL-6. The sensor limit of detection, 105 ng/mL, lies in the relevant range for pathological IL-6 levels. Upon investigation of sensor kinetics, we found rapid response within seconds of antigen addition which continued over the course of 3 h. We found that this sensor construct is stable and the aptamer is not displaced from the nanotube surface during IL-6 detection. Finally, we investigated the ability of this sensor construct to detect macrophage activation caused by bacterial lipopolysaccharides (LPS) in an in vitro model of disease, finding rapid and sensitive detection of macrophage-expressed IL-6. We are confident that further development of this sensor will have novel implications for diagnosis of acute and chronic inflammatory diseases, in addition to contributing to the understanding of the role of cytokines in these diseases.
Previous studies have demonstrated an increasing trend of the number of authors across various fields over the years. This trend has been attributed to the necessity for larger collaborations and, at times, to ethical...
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Previous studies have demonstrated an increasing trend of the number of authors across various fields over the years. This trend has been attributed to the necessity for larger collaborations and, at times, to ethical issues regarding authorship attribution. Our study focuses on the evolution of authorship trends in the field of Neuroscience. We conducted our analysis based on a dataset containing 580,782 neuroscience publications produced from 2000 to 2022, focusing on the publications within the Group of ten (G10) countries. Using a matrix-based methodology, we extracted and analyzed the average number of authors per country. Our findings reveal a consistent rise in authorship across all G10 countries over the past two decades. Italy emerged with the highest average number of authors, while France stood out for experiencing the most significant increase, particularly in the last decade. The countries with the lowest number of authors per publication were the USA, UK and Canada. Differences between countries could result from variations in the size of collaboration between researchers in different countries. Additionally, these differences may depend on utilitarian considerations aimed at receiving higher scores in the individual evaluation of their own work. We propose that a normalization procedure for the number of authors should be implemented to ensure a fair evaluation of researchers.
Pre-vetting inspection, enhanced with onsite training, is a critical process to improve safety and environmental compliance onboard tanker ships. As a part of pre-vetting services, this study develops a maritime gamif...
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Pre-vetting inspection, enhanced with onsite training, is a critical process to improve safety and environmental compliance onboard tanker ships. As a part of pre-vetting services, this study develops a maritime gamified mentoring platform, namely Maritime Gamentor, to manage crew upskilling in tanker vetting requirements. In this stage, the study considers the recently updated requirements of the Ship Inspection Report (SIRE 2.0) programme of Oil Companies International Marine Forum (OCIMF) to conceptualise a holistic serious game-based training solution. Then, a step-by-step approach to the preliminary design, development and prototyping of maritime serious games is provided in detail. Particular to the SIRE 2.0 Clause# 5.1.4, the study conducts a case study on Maritime Gamentor Module-01 illustrated with a task-based risk assessment (TBRA) on enclosed space entry operation. Consequently, the Maritime Gamentor is conceptualised as a powerful training and mentorship platform for global shipping companies.
Untargeted lipidomics, with its ability to take a snapshot of the lipidome landscape, is an important tool to highlight lipid changes in pathology or drug treatment models. One of the shortcomings of most untargeted l...
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Untargeted lipidomics, with its ability to take a snapshot of the lipidome landscape, is an important tool to highlight lipid changes in pathology or drug treatment models. One of the shortcomings of most untargeted lipidomics based on UHPLC-HRMS is the low throughput, which is not compatible with large-scale screening. In this contribution, we evaluate the application of a sub-5-min high-throughput four-dimensional trapped ion mobility mass spectrometry (HT-4D-TIMS) platform for the fast profiling of multiple complex biological matrices. Human AC-16 cells and mouse brain, liver, sclera, and feces were used as samples. By using a fast 4-min RP gradient, the implementation of TIMS allows us to differentiate coeluting isomeric and isobaric lipids, with correct precursor ion isolation, avoiding co-fragmentation and chimeric MS/MS spectra. Globally, the HT-4D-TIMS allowed us to annotate 1910 different lipid species, 1308 at the molecular level and 602 at the sum composition level, covering 58 lipid subclasses, together with quantitation capability covering more than three orders of magnitude. Notably, TIMS values were highly comparable with respect to longer LC gradients (CV% = 0.39%). These results highlight how HT-4D-TIMS-based untargeted lipidomics possess high coverage and accuracy, halving the analysis time with respect to conventional UHPLC methods, and can be used for fast and accurate untargeted analysis of complex matrices to rapidly evaluate changes of lipid metabolism in disease models or drug discovery campaigns.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by the presence of extracellular amyloid plaques consisting of beta-amyloid peptides (A beta) and intracellular neurofibrillary t...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by the presence of extracellular amyloid plaques consisting of beta-amyloid peptides (A beta) and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau (pTau) protein in the brain. Genetic and animal studies strongly indicate that A beta, tau and neuroinflammation play important roles in the pathogenesis of AD. Several staging models showed that NFTs correlated well with the disease progression. Positron emission tomography (PET) imaging has become a widely used non-invasive technique to image NFTs for early diagnosis of AD. Despite the remarkable progress made over the past few years, tau PET imaging is still challenging due to the nature of tau pathology and the technical aspects of PET imaging. Tau pathology often coexists with other proteinopathies, such as A beta plaques and alpha-synuclein aggregates. Distinguishing tau-specific signals from other overlapping pathologies is difficult, especially in the context of AD, where multiple protein aggregates are present, as well as the spectrum of different tau isoforms (3R and 4R) and conformations. Moreover, tracers should ideally have optimal pharmacokinetic properties to penetrate the blood-brain barrier (BBB) while maintaining specificity, low toxicity, low non-specific binding, rapid uptake and clearance from the brain, and formation of no radiolabeled metabolites in the brain. On the other hand, Parkinson's disease (PD) is a progressive neurodegenerative movement disorder characterized by the abnormal accumulations of alpha-synuclein in neurons. Heterogeneity and the unclear pathogenesis of PD hinder early and accurate diagnosis of the disease for therapeutic development in clinical use. In this review, while referring to existing reviews, we focus on the design strategies and current progress in tau (NFTs) targeting new PET tracers for AD;evolution of non-AD tau targeting PET tracers for applications
microRNA-210 (miRNA), a well-documented miRNA, has been implicated in a myriad of biological processes, including responses to hypoxia, angiogenesis, cell proliferation, and male infertility in humans. However, a comp...
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microRNA-210 (miRNA), a well-documented miRNA, has been implicated in a myriad of biological processes, including responses to hypoxia, angiogenesis, cell proliferation, and male infertility in humans. However, a comprehensive understanding of its functions in fish requires further investigation. This study pursued to elucidate the downstream effect of dre-miR-210-5p on primary ovarian cell culture in zebrafish (Danio rerio), an animal model. A protocol was settled down by incubations with either an miR-210 mimic or a scrambled miRNA in the isolated ovaries. RNA-sequencing analysis identified similar to 6000 differentially expressed target genes revealing that downregulated genes were associated with reproduction-related pathways while immune-related pathways displayed an upregulated pattern. To identify molecular markers, predicted target genes were classified into reproduction and immune cell types. These findings underscore the existence of a profound interplay between the reproductive and immune systems, with miR-210 emerging as a pivotal player in orchestrating transcriptomic alterations within fish ovaries.
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