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Durymanov, M.

Publications and source records attributed to Durymanov, M..

4 recordsLinked to original sources

DORA AI Scientist: Multi-agent Virtual Research Team for Scientific Exploration Discovery and Automated Report Generation

Modern goal-oriented scientific research process involves hierarchical teams of researchers of diverse backgrounds performing generalist and domain-specific tasks. Many of these tasks include hypothesis generation, literature review, data collection, cleanup, processing and analysis, experimental design, virtual and physical experiments, research report and academic paper writing, reference management, bibliography and quality control. Most of these tasks can be performed automatically or in a co-pilot mode by the generative reinforcement learning systems. In this paper, we introduce a versatile multi-agent scientific exploration and draft outline research assistant (DORA), which provides multiple templates and workflows for automated or semi-automated research studies and report generation. Under user guidance, it employs hierarchical teams of AI agents based on the plug-and-play generalist and domain-specific large language models (LLMs) exploiting a variety of specialized research tools and open data repositories and generates high-quality research outputs publication drafts with maximally-accurate references. DORA is designed to minimize the time and effort required for manuscript preparation, thereby enabling researchers to devote more attention to high-value discovery tasks. The system is constantly evolving with user feedback with regular feature and resource updates. The platform is available at https://dora.insilico.com.

bioinformatics↗

Yttrium-90-doped metal-organic frameworks (MOFs) for low-dose rate intratumoral radiotherapy

Brachytherapy, or intratumoral radiation therapy, is a highly effective treatment option for localized tumors. Herein, we engineered injectable and biodegradable metal-organic frameworks (MOFs) to deliver the therapeutic radioisotope yttrium-90 (90Y). Particles of bimetallic MIL-100(Fe,Y) and Y-BTC, doped with 90Y and 88Y, were synthesized in a single step and retained radioyttrium in various buffer solutions. Tumor injectability and radioisotope retention were evaluated using tumor-bearing mice. In vivo analysis and calculations showed that radiolabeled MIL-100(Fe,Y) emitted more than 38% of its radioactivity, while Y-BTC emitted greater than 75% of its radioactivity, through 7 days at the tumor site upon intratumoral injection, without significant yttrium accumulation in off-target tissues. The anticancer effects of MIL-100(Fe,Y,90Y) and 90Y,Y-BTC particles were assessed using 3D multicellular tumor spheroids and a tumor-bearing mouse model, respectively. 90Y-doped MIL-100(Fe,Y) particles penetrated A549 tumor spheroids and caused superior cytotoxic effects compared to non-radioactive particles or 90YCl3, added at the same dose. Brachytherapy with 90Y-doped Y-BTC MOFs induced inhibition of B16F1 melanoma tumor growth and resulted in an increased median survival of 8.5 days compared to 4.5 days in untreated mice. This study exhibits the feasibility to prepare radioactive 90Y-containing biodegradable, non-toxic MOF particles that are advantageous for low-dose rate internal radiotherapy.

biophysics↗

Retrovirus-Like Gag Protein Arc/Arg3.1 is Involved in Extracellular-Vesicle-Mediated mRNA Transfer between Glioma Cells

Activity-regulated cytoskeleton-associated (Arc) protein is expressed in neural tissue of vertebrates, where it plays a pivotal role in modulation of synaptic communication. In addition, Arc protein forms capsid-like particles, which can encapsulate and transfer mRNA in extracellular vesicles (EVs) between neurons, that could modulate synaptic function and plasticity. Glioma cell networks actively interact with neurons via paracrine signaling and formation of neurogliomal glutamatergic synapses that contribute to cancer cell survival, proliferation, and invasion. Here, we revealed that Arc is expressed in human glioma cell lines, which can produce EVs containing Arc protein and Arc mRNA (or "Arc EVs"). Recombinant Arc protein binds to Arc mRNA with 1.5-fold higher affinity as compared with control mCherry mRNA. Arc EVs from U87 glioma cells internalize and deliver Arc mRNA to recipient U87 cells, where it is translated into a protein. Arc overexpression significantly increases EV production, alters EV morphology, and enhances intercellular transfer of highly expressed mRNA in glioma cell culture. These findings indicate involvement of Arc EVs into mRNA transfer between glioma cells that could contribute to tumor progression and affect synaptic plasticity in cancer patients.

cancer biology↗

NanoMOFs with Encapsulated Photosensitizer: Accumulation in Chlamydia trachomatis Inclusions and Antimicrobial Effects

Metal-organic framework nanoparticles (nanoMOFs) are a promising class of hybrid nanomaterials for biomedical applications. Some of them, including biodegradable porous iron carboxylates are proposed for encapsulation and delivery of antibiotics. Due to the high drug loading capacity and fast internalization kinetics nanoMOFs are more beneficial for the treatment of intracellular bacterial infections compared to free antibacterial drugs, which poorly accumulate inside the cells because of the inability to cross membrane barriers or have low intracellular retention. However, nanoparticle internalization does not ensure their accumulation in the cell compartment that shelters a pathogen. This study shows the availability of MIL-100(Fe) MOF nanoparticles to co-localize with Chlamydia trachomatis, an obligate intracellular bacterium, in the infected RAW264.7 macrophages. Furthermore, nanoMOFs loaded with photosensitizer methylene blue (MB) exhibit complete photodynamic inactivation of Chlamydia trachomatis growth. Simultaneous infection and treatment of RAW264.7 cells with empty nanoMOFs resulted in a 3-fold decrease in bacterial load that indicates an intrinsic anti-chlamydial effect of this iron-containing nanomaterial. Thus, our findings suggest the use of iron-based nanoMOFs as a promising drug delivery platform, which contributes to antibacterial effect, for the treatment of chlamydial infections.

biophysics↗