Bioinformatics analysis of the potential receptor and therapeutic drugs for Alzheimer's disease with comorbid Parkinson's disease.

Background: Now, there are no sensitive biomarkers for improving Alzheimer's disease (AD) and comorbid Parkinson's disease (PD). The aim of the present study was to analyze differentially expressed genes (DEGs) in brain tissue from AD and PD patients via bioinformatics analysis, as well as to explore precise diagnostic and therapeutic targets for AD and comorbid PD. Methods: GFE122063 and GSE7621 data sets from GEO in NCBI, were used to screen differentially expressed genes (DEGs) for AD and PD, and identify the intersected genes, respectively. Intersected genes were analyzed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, STRING site and Cytoscape were used to construct a protein-protein interaction (PPI) network, CytoNCA algorithm to analyze and evaluate centrality, Mcode plug-in to analyze module, and Cytohubba to screen key genes. Combined GO-KEGG enrichment analysis with Cytoscape algorithm to screen the key gene in AD complicated with PD. Then, the DEGs for AD and PD were imported into the Association Map (CMap) online platform to screen out the top 10 small molecule drugs, and using molecular docking techniques to evaluate the interactions between small molecule drugs and key genes receptors. Results: In total, 231 upregulated genes and 300 downregulated genes were identified. GO analysis revealed that the DEGs were highly enriched in signal transduction, and KEGG analysis revealed that the DEGs were associated with the MAPK and PI3K-Akt signaling pathways. Epidermal growth factor receptor (EGFR) was identified as a potential receptor gene in AD and comorbid PD. EGFR was upregulated in both AD and PD, and the proteins that interact with EGFR were enriched in the Ras/Raf/MAPK and PI3K/Akt signaling pathways. Semagacestat was identified as a drug with therapeutic potential for treating AD complicated with PD. There was a high binding affinity between semagacestat and EGFRNTD, with seven hydrogen bonds and one hydrophobic bond. Discussion: Semagacestat may improve the health of patients with AD complicated with PD through the regulation of the Ras/Raf/MAPK and PI3K/Akt signaling pathways by EGFR, providing evidence supporting the structural modification of semagacestat to develop a more effective drug for treating AD complicated with PD.

Melatonin as an add-on treatment for epilepsy: A systematic review and meta-analysis.

PURPOSE: Epilepsy, one severe prevalent brain disorder, primarily relies on drug treatment. However, approximately one-third of patients with epilepsy do not achieve effective control with current medications, underscoring the need for more innovative treatment approaches. Notably, melatonin has gained attention for its anti-seizure properties and favourable safety profile. This systematic review aimed to evaluate the efficacy and safety of melatonin as an add-on treatment for epilepsy. METHODS: We searched for articles published before June 2023 in Web of Science, Cochrane Library, and PubMed. We used RevMan 5.4 software to compute relative risks (RRs) and 95 % confidence intervals (CIs). Key outcomes included total sleep time, wakefulness after sleep onset, sleep latency, seizure frequency, seizure severity, and safety. The quality of randomised controlled studies (RCTs) was assessed using the Cochrane Risk of Bias tool. RESULTS: Of the 264 publications retrieved, 10 RCTs were included in the meta-analysis. Add-on melatonin treatment improved sleep latency (RR: 0.56; 95 %CI: 0.10-1.02; P = 0.02) and seizure severity (RR: 0.33; 95 %CI: 0.04-0.62; P = 0.03) compared with placebo treatment. Adverse events (increased headache severity in children with a history of migraines, bronchitis, ear infections, agitation, and urinary frequency) were reported in only one trial. CONCLUSION: This systematic review found that add-on melatonin therapy improved sleep latency and seizure severity in patients with epilepsy. However, several of the included studies did not systematically assess sleep quality, seizures, and safety and lacked long-term follow-up data. Further RCTs with extended follow-up periods are required to definitively determine the efficacy and safety of melatonin.

Near-Infrared Light Regulation of Capture and Release of ctDNA Platforms Based on the DNA Assembly System.

Despite recent progress, a challenge remains on how to gently release and recover viable ctDNA captured on DNA probe-based devices. Here, a reusable detector was successfully manufactured for the capture and release of ctDNA by means of an UCNPs@SiO2-Azo/CD-probe. Biocompatible NIR light is used to excite UCNPs and convert into local UV light. Continuous irradiation induces a rapid release of the entire ctDNA-probe-CD complex from the functionalized surface via the trans-cis isomerization of azo units without disrupting the ctDNA-structure receptor. Specifically, these composite chips allow reloading DNA probes for reusable ctDNA detection with no obvious influence on their efficiency. The results of our study demonstrated the potential application of this platform for the quantitative detection of ctDNA and the individualized analysis of cancer patients.

A valproic acid-modified platinum diimine complex as potential photosensitizer for photodynamic therapy.

Histone deacetylase inhibitors have often been used in combination treatment of various types of cancers due to their non-genotoxic epigenetic potential. Valproic acid (VPA) is a well-known histone deacetylase inhibitor. Conjugate of VPA with a phtoactive platinum diimine complex through an ester bond has been fabricated to potentiate the photocytotoxicity of the photosensitizer. Its capability to generate singlet oxygen, behavior in the presence of esterase, and photocytotoxicity in tumor cells have also been studied. The results revealed that the novel VPA-modified platinum diimine complex could produce singlet oxygen efficiently and release VPA in the presence of porcine liver esterase. The results also suggested that incorporation of VPA moiety into the platinum diimine complex might significantly enhance the cytotoxicity of the complex.

Micromirror array allocation algorithm based on deconvolution.

Freeform illumination is one of the necessary techniques in 28 nm technology nodes and beyond. The micromirror array (MMA) has been widely used in lithography freeform illumination systems due to its programmability and high free degree. The MMA allocation algorithm is the key to generate the target freeform illumination source. Its computational speed and precision affect the generation speed and precision of the target illumination source as well as the process window size of the generated illumination pupil directly. In this paper, an MMA allocation method based on deconvolution is proposed. The target freeform illumination source can be obtained directly with the deconvolution and quantization processes. Without the iterative optimization process, the computational speed of the proposed method is much faster than that of the traditional method. The numerical simulation results show that the difference between the target source and the MMA source generated using the proposed method is less than 0.2%. Compared with the process window loss of the target source, the process window loss of the MMA source generated by the proposed deconvolution method is less than 0.5%. Compared with the traditional allocation method, the runtime of the proposed method is less than 0.05 s and has improved by 1463 times.