Applications of Graphene Family Nanomaterials in Regenerative Medicine: Recent Advances, Challenges, and Future Perspectives.

Graphene family nanomaterials (GFNs) have attracted considerable attention in diverse fields from engineering and electronics to biomedical applications because of their distinctive physicochemical properties such as large specific surface area, high mechanical strength, and favorable hydrophilic nature. Moreover, GFNs have demonstrated the ability to create an anti-inflammatory environment and exhibit antibacterial effects. Consequently, these materials hold immense potential in facilitating cell adhesion, proliferation, and differentiation, further promoting the repair and regeneration of various tissues, including bone, nerve, oral, myocardial, and vascular tissues. Note that challenges still persist in current applications, including concerns regarding biosecurity risks, inadequate adhesion performance, and unsuitable degradability as matrix materials. This review provides a comprehensive overview of current advancements in the utilization of GFNs in regenerative medicine, as well as their molecular mechanism and signaling targets in facilitating tissue repair and regeneration. Future research prospects for GFNs, such as potential in promoting ocular tissue regeneration, are also discussed in details. We hope to offer a valuable reference for the clinical application of GFNs in the treatment of bone defects, nerve damage, periodontitis, and atherosclerosis.

An automated ICU agitation monitoring system for video streaming using deep learning classification.

OBJECTIVE: To address the challenge of assessing sedation status in critically ill patients in the intensive care unit (ICU), we aimed to develop a non-contact automatic classifier of agitation using artificial intelligence and deep learning. METHODS: We collected the video recordings of ICU patients and cut them into 30-second (30-s) and 2-second (2-s) segments. All of the segments were annotated with the status of agitation as "Attention" and "Non-attention". After transforming the video segments into movement quantification, we constructed the models of agitation classifiers with Threshold, Random Forest, and LSTM and evaluated their performances. RESULTS: The video recording segmentation yielded 427 30-s and 6405 2-s segments from 61 patients for model construction. The LSTM model achieved remarkable accuracy (ACC 0.92, AUC 0.91), outperforming other methods. CONCLUSION: Our study proposes an advanced monitoring system combining LSTM and image processing to ensure mild patient sedation in ICU care. LSTM proves to be the optimal choice for accurate monitoring. Future efforts should prioritize expanding data collection and enhancing system integration for practical application.

Arbitrary trapezoidal illumination generation method based on variable slits for optical lithography.

Trapezoidal illumination is an effective approach to improve the integrated uniformity of light intensity in a step-and-scan lithographic system. When different laser pulses are utilized, the optimal trapezoidal illumination varies. In addition, if the coherence factor takes different values, the outline of the trapezoidal illumination varies as well, directly affecting the integrated uniformity of light intensity. To reduce the impact of variations in trapezoidal illumination, a newly designed method for generating arbitrary trapezoidal illuminations using variable slits is proposed. The performance of our method after adjusting the trapezoidal outline for different coherence factors in different illumination modes was verified through optical simulations. Compared to the traditional method, the proposed strategy to realize arbitrary trapezoidal illuminations based on variable slits can obtain the best outlines for illumination, calculated by balancing pulse quantization error and energy losses. Furthermore, when different coherence factors are applied, the outline of the generated trapezoidal illumination can always be maintained by simply moving the blades an appropriate distance.

Securinine enhances SMN2 exon 7 inclusion in spinal muscular atrophy cells.

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by the degeneration of motor neurons in the spinal cord, leading to muscular atrophy. SMA is caused by deletions or mutations in the survival motor neuron gene (SMN1) on chromosome 5q13. A second copy of the SMN gene (SMN2) also exists on chromosome 5, and both genes can produce functional protein. However, due to alternative splicing of the exon 7, the majority of SMN protein produced by SMN2 is truncated and unable to compensate for the loss of SMN1. Increasing full-length SMN protein production by promoting the exon 7 inclusion in SMN2 mRNA or increasing SMN2 gene transcription could be a therapeutic approach for SMA. In this study, we screened for the compounds that enhance SMN2 exon 7 inclusion by using SMN2 minigene-luciferase reporter system. We found that securinine can increase luciferase activity, indicating that securinine promoted SMN2 exon 7 inclusion. In addition, securinine increased full-length SMN2 mRNA and SMN protein expression in SMA patient-derived lymphoid cell lines. To investigate the mechanism of securinine effect on SMN2 splicing, we compared the protein levels of relevant splicing factors between securinine-treated and untreated cells. We found that securinine downregulated hnRNP A1 and Sam68 and upregulated Tra2-ß1 expression. However, securinine, unlike HDAC inhibitors, did not enhance tra2-ß1 gene transcription, indicating a post-transcriptional mechanism for Tra2-ß1 upregulation. Furthermore, we treated SMA-like mice with securinine by i.p. injection and found that securinine treatment increased SMN2 exon 7 inclusion and SMN protein expression in the brain and spinal cord. According to our results, securinine might have the potential to become a therapeutic drug for SMA disease.

Synthesis and evaluation of 4-(2-hydroxypropyl)piperazin-1-yl) derivatives as Hsp90 inhibitors.

We previously reported 4-(3-((6-bromonaphthalen-2-yl)oxy)-2-hydroxypropyl)-N,N-dimethylpiperazine-1-sulfonamide (1) as a novel heat shock protein 90 inhibitor with moderate activity. In our ongoing efforts for the discovery of Hsp90 modulators we undertake structural investigations on 1. Series of the titled compound were designed, synthesized and evaluated. We have found that compounds with a hydroxyl group at C-4 of the aryl ring on the piperazine moiety possess Hsp90 inhibition properties. Compound 6f with improved activity could be further developed and optimized as Hsp90 inhibitor.