Mohamed Aly Saad Aly, Ph.D., P.Eng on LinkedIn: A single infusion of engineered long-lived and multifunctional T cells… (2024)

I am excited to share a link to my most recent research in the Journal of Chemosphere. It is a result of my fruitful international collaboration with the goal of using an AI algorithm to predict the biological properties of a group of indoloquinoline derivatives.Boosting Sinh Cosh Optimizer and Arithmetic Optimization Algorithm for Improved Prediction of Biological Activities for Indoloquinoline Derivatives.Quantitative Structure Activity Relation (QSAR) models are mathematical techniques used to link structural characteristics with biological activities, thus considered a useful tool in drug discovery, hazard evaluation, and identifying potentially lethal molecules. The QSAR regulations are determined by the Organization for Economic Cooperation and Development (OECD). QSAR models are helpful in discovering new drugs and chemicals to treat severe diseases.In order to improve the QSAR model's predictive power for the biological activities of naturally occurring indoloquinoline derivatives against different cancer cell lines, a modified machine learning (ML) technique is presented in this paper. The Arithmetic Optimization Algorithm (AOA) operators are used in the suggested model to enhance the performance of the Sinh Cosh Optimizer (SCHO). Moreover, this improvement functions as a feature selection method that eliminates superfluous descriptors. An actual dataset gathered from previously published research is utilized to evaluate the performance of the suggested model. Moreover, a comparison is made between the outcomes of the suggested model and other established methodologies. In terms of pIC50 values for different indoloquinoline derivatives against human MV4-11 (leukemia), human HCT116 (colon cancer), and human A549 (lung cancer) cell lines, the suggested model achieves a root mean square error (RMSE) of 0.6822, 0.6787, 0.4411, and 0.4477, respectively. The biological application of indoloquinoline derivatives as possible anticancer medicines is predicted with a high degree of accuracy by the suggested model, as evidenced by these findings.https://lnkd.in/gY6brUPw

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Fabrication of bioactive silk composite meshes for hernia repair and guided soft tissue remodeling:In silico, in vitroandin vivomodels.Post-operative complications stemming from incompatible meshes often lead to delayed wound healing, seroma, infections, inappropriate tissue infiltration, and pain. The present study was outlined to develop biocompatible composite hand-knitted silk meshes modified with polymers and natural extracts. This study introduced hand-knittedB. morisilk fibroin as the primary mesh material, offering superior mechanical strength and biocompatibility. The spin-assisted dip coating achieved desirable morphology, internal structures, thickness, and surface roughness. In this study, 9 silk-based composite meshes (modified with polymeric-extract blends through spin-assisted dip coating) were successfully developed. Experimental variants were then subjected to various characterizations, including SEM, DMA and chemical analysis (FTIR and GC-MS). Modified meshes were evaluated for their physiological characteristics and biological responses (the basic criterion for the selection of composite silk mesh). The biological testing included (antimicrobial susceptibility testing, in vitro cell viability assay, cell attachment assays (NIH3T3 and hUc-MSCs), in vitro cell migration, in vitro gene expression analysis with NIH3T3, in silico molecular docking with bioactive ligands of HE extract and in vivo analysis with PHBV-HE and PHBV-Control composite meshes in rat models.Results showed that all variants exhibited a multi-fiber morphology with significant surface coating, allowing for optimal drug release up to 72 h. This release facilitated antibacterial properties and biocompatibility, as evidenced by in vitro cell viability, migration assays and gene expression analysis. Among the variants, the PHBV-HE composite mesh demonstrated superior results. In the case of PHBV-coated polymeric controls, the SEM analysis concluded that the presence of coating reduced the pore size up to 39.62%, whereas, fiber diameter was increased by up to 19.89 % as compared to the control. The presence of a coating on the mesh improved the mechanical strength/modulus by 165.89 %, UTS by 185.38 % and reduced the % strain by 64.67 %. The fast release of HE from PHBV-HE composite mesh was 90.7% up to 72h, confirming that it can induce antibacterial activity against surgical infections.PHBV-HE showed the highest cell viability, wound healing and gene expression. Based on appreciable biological evaluation results shown by PHBV-HE, in rat hernia models, only the PHBV-HE variant was tested for in-vivo analysis. Results confirmed its non-toxic nature and wound-healing abilities. Enhanced cell proliferation and wound healing observed bothin vitroandin vivoindicated that PHBV-HE holds promise as a biomedical implant suggesting its potential for effective hernia and soft tissue repair and regeneration.https://lnkd.in/gDQqAGxN

Vaccine design via antigen reorientation.A major challenge in creating universal influenza vaccines is to focus immune responses away from the immunodominant, variable head region of hemagglutinin (HA-head) and toward the evolutionarily conserved stem region (HA-stem). Here, an approach to control antigen orientation via site-specific insertion of aspartate residues that facilitates antigen binding to alum is introduced. The generalizability of this approach with antigens from Ebola, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses is demonstrated, and further enhanced neutralizing antibody responses are observed in all cases. An H2 HA in an ‘upside-down’ configuration is then reoriented to increase the exposure and immunogenicity of the HA-stem. The reoriented H2 HA (reoH2HA) on alum-induced stem-directed antibodies that cross-react with both group 1 and group 2 influenza A subtypes. Electron microscopy polyclonal epitope mapping (EMPEM) revealed that reoH2HA (group 1) elicits cross-reactive antibodies targeting group 2 HA-stems. These results highlight antigen reorientation as a generalizable approach for designing epitope-focused vaccines.https://lnkd.in/gf*ckAtYR

Antiviral drug recognition and elevator-type transport motions of CNT3.Nucleoside analogs have broad clinical utility as antiviral drugs. Key to their systemic distribution and cellular entry are human nucleoside transporters. Here, it is established that the human concentrative nucleoside transporter 3 (CNT3) interacts with antiviral drugs used in the treatment of coronavirus infections. High-resolution single-particle cryo-electron microscopy structures of bovine CNT3 complexed with the antiviral nucleosidesN4-hydroxycytidine, PSI-6206, GS-441524 and ribavirin, all in inward-facing states, are reported. Notably, it was found that the orally bioavailable antiviral molnupiravir arrests CNT3 in four distinct conformations, allowing us to capture cryo-electron microscopy structures of drug-loaded outward-facing and drug-loaded intermediate states. These studies uncover the conformational trajectory of CNT3 during membrane transport of a nucleoside analog antiviral drug, yield new insights into the role of interactions between the transport and the scaffold domains in elevator-like domain movements during drug translocation, and provide insights into the design of nucleoside analog antiviral prodrugs with improved oral bioavailability.https://lnkd.in/gkX5KdZu

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Intelligent wearable olfactory interface for latency-free mixed reality and fast olfactory enhancement.Olfaction feedback systems could be utilized to stimulate human emotion, increase alertness, provide clinical therapy, and establish immersive virtual environments. Currently, the reported olfaction feedback technologies still face a host of formidable challenges, including human perceivable delay in odor manipulation, unwieldy dimensions, and a limited number of odor supplies. Herein, a general strategy to solve these problems isreported, which is associated with a wearable, high-performance olfactory interface based on miniaturized odor generators (OGs) with advanced artificial intelligence (AI) algorithms. The OGs serve as the core technology of the intelligent olfactory interface, which exhibits milestone advances in millisecond-level response time, milliwatt-scale power consumption, and miniaturized size. Empowered by robust AI algorithms, the olfactory interface shows its great potential in latency-free mixed reality (MR) and fast olfaction enhancement, thereby establishing a bridge between electronics and users for broad applications ranging from entertainment, education, medical treatment, and human machine interfaces.https://lnkd.in/gD77EywD

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Electrochemical Paper-Based Microfluidics: Harnessing Capillary Flow for Advanced Diagnostics.Electrochemical paper-based microfluidics has attracted much attention due to the promise of transforming point-of-care diagnostics by facilitating quantitative analysis with low-cost and portable analyzers. Such devices harness capillary flow to transport samples and reagents, enabling bioassays to be executed passively. Despite exciting demonstrations of capillary-driven electrochemical tests, conventional methods for fabricating electrodes on paper impede capillary flow, limit fluidic pathways, and constrain accessible device architectures. This account reviews recent developments in paper-based electroanalytical devices and offers perspective by revisiting key milestones in lateral flow tests and paper-based microfluidics engineering. The study highlights the benefits associated with electrochemical sensing and discusses how the detection modality can be leveraged to unlock novel functionalities. Particular focus is given to electrofluidic platforms that embed electrodes into paper for enhanced biosensing applications. Together, these innovations pave the way for diagnostic technologies that offer portability, quantitative analysis, and seamless integration with digital healthcare, all without compromising the simplicity of commercially available rapid diagnostic tests.https://lnkd.in/gWzGsWTN

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