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@#Abstract: The new generation of artificial intelligence technology, represented by deep learning, has emerged as a crucial driving force in the advancement of new drug research and development. This article creatively proposes a workflow named “Molecular Factory” for the design and optimization of drug molecules based on artificial intelligence technology. This workflow integrates intelligent molecular generation models, high-performance molecular docking algorithms, and accurate protein-ligand binding affinity prediction methods. It has been integrated as a core module into DrugFlow, a one-stop drug design software platform, providing a comprehensive set of mature solutions for the discovery and optimization of lead compounds. Utilizing the “Molecular Factory” module, we conducted the research of second-generation inhibitors against Menin that can combat drug resistance. Through the integration of computational and experimental approaches, we rapidly identified multiple promising compounds. Among them, compound RG-10 exhibited the IC50 values of 9.681 nmol/L, 233.2 nmol/L, and 40.09 nmol/L against the wild-type Menin, M327I mutant, and T349M mutant, respectively. Compared to the positive reference molecule SNDX-5613, which has entered Phase II clinical trials, RG-10 demonstrated significantly enhanced inhibitory activity against the M327I and T349M mutants. These findings fully demonstrate the unique advantages of the "Molecular Factory" technology in practical drug design and development scenarios. It can rapidly and efficiently generate high-quality active molecules targeting specific protein structures, holding significant value and profound implications for advancing new drug discovery.
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ObjectiveTo study the effect of upper limb robot-assisted therapy on upper limb function and cerebral cortex activation in stroke patients using functional near-infrared spectroscopy (fNIRS). MethodsFrom January, 2022 to January, 2023, 32 stroke patients in Zhejiang Rehabilitation Medical Center were randomly divided into control group (n = 16) and experimental group (n = 16). Both groups received routine neurological medication and routine rehabilitation. The control group received routine upper limb exercises, the experimental group received upper limb robot-assisted therapy. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and fNIRS (oxyhemoglobin, deoxyhemoglobin, and total hemoglobin) before and four weeks after treatment. NIRS_SPM was used for activation analysis, Homer2 was used for blood oxygen concentration analysis. ResultsAfter treatment, the score of FMA-UE increased in both groups (|t| > 5.910, P < 0.001), and was higher in the experimental group than in the control group (t = -2.348, P < 0.05). fNIRS activation results showed that, the activation increased in the experimental group after treatment in channel 17 (F = 9.354, P < 0.01), and it was more than that in the control group (F = 5.217, P < 0.05). fNIRS blood oxygen concentration results showed that, the blood oxygen concentration increased in the experimental group after treatment in channel 17 (F = 12.179, P < 0.01), and it was more than that in the control group (F = 4.883, P < 0.05). ConclusionThe upper limb robot-assisted therapy can improve the upper limb motor function and cerebral cortex activation of stroke patients.
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Objective To explore the characteristics and biological functions of epigenetic treatment to DNMT1 expression in NSCLC cell lines. Methods Lung cancer cells were divided into 4 groups , and drugs with different concentrations. The effect of epigenetic treatment on NSCLC cell line was detected by CCK-8 and MTT. The effect of epigenetic treatment on the expression of DNMT1 in NSCLC cell line was detected by Western blot. Results CCK-8 and MTT assay showed that treatment with 5-Aza-CdR and MS-275 inhibited the proliferation of NSCLC cells. Western blot showed that treatment with 5-Aza-CdR and MS-275 inhibited the DNMT1 expression in NSCLC cells. Conclusion The expression of DNMT1 gene in the NSCLC cell lines may be suppressed effectively by epigenetic treatment , and the gene may inhibit the proliferation and growth of NSCLC cell lines.
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@#Contracture and spasticity of ankle joints were major sources of disability in neurological impairment including stroke and cerebral palsy, etc. The manual stretching used in physical therapy might be laborious and time-consuming to the therapists and the outcome was dependent on the experience and the subjectiveend feelingof the therapists. A device was developed that could safely stretch the an-kle joint to its extreme positions with quantitative control of the resistance torque and stretching velocity. Furthermore, it could satisfy a strong need for quantitative and objective measures of the impairment and rehabilitation outcome. This was just the meaning intelligent stretching referred to. This article described the origin of the concept of intelligent stretching and its definition, operational principle, and su-periority and weakness, as well as its application in ankle joint spasticity and contracture in patients with stroke and cerebral palsy.
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BACKGROUND: Our former studies have shown that bone marrow mesenchymal stem cells (BMMSCs) can be induced differentiation to vascular smooth muscle-like cells (VSMLCs) and vascular endothelium-like cells (VELCs), which are compatible with collagen-embedded polyglycolic acid scaffolds. OBJECTIVE: To investigate the possibility of constructing small diameter tissue-engineered blood vessels via subcutaneous implantation. METHODS: The cells-scaffold complex was produced by separately seeding VSMLCs and VELCs derived from BMMSCs on polyglycolic acid collagen scaffolds. The two layers were separated by ECMgel. The cells-scaffold complex was subcutaneous implanted into small diameter tissue-engineered blood vessels.RESULTS AND CONCLUSION: Histological analysis of the small diameter tissue-engineered blood vessel walls revealed a typical artery structure, which was similar to natural vessels. The tissue-engineered blood vessels were not broken down under a force of 26.6 kPa. Eight weeks after implantation, the Brdu-labeled seed cells were found in the three layers of the vessel walls. The results revealed that the subcutaneous tissue was a good bioreactor to construct small diameter tissue-engineered blood vessels.