Room temperature optically detected magnetic resonance of single spins in GaN.

High-contrast optically detected magnetic resonance is a valuable property for reading out the spin of isolated defect colour centres at room temperature. Spin-active single defect centres have been studied in wide bandgap materials including diamond, SiC and hexagonal boron nitride, each with associated advantages for applications. We report the discovery of optically detected magnetic resonance in two distinct species of bright, isolated defect centres hosted in GaN. In one group, we find negative optically detected magnetic resonance of a few percent associated with a metastable electronic state, whereas in the other, we find positive optically detected magnetic resonance of up to 30% associated with the ground and optically excited electronic states. We examine the spin symmetry axis of each defect species and establish coherent control over a single defect's ground-state spin. Given the maturity of the semiconductor host, these results are promising for scalable and integrated quantum sensing applications.

Discovery and biological evaluation of novel CARM1/HDAC2 dual-targeting inhibitors with anti-prostate cancer agents.

Prostate cancer (PCa) is a clinically heterogeneous disease with a progressively increasing incidence. Concurrent inhibition of coactivator-associated arginine methyltransferase 1 (CARM1) and histone deacetylase 2 (HDAC2) could potentially be a novel strategy against PCa. Herein, we identified seven compounds simultaneously targeting CARM1 and HDAC2 through structure-based virtual screening. These compounds possessed potent inhibitory activities at the nanomolar level in vitro. Among them, CH-1 was the most active inhibitor which exhibited excellent and balanced inhibitory effects against both CARM1 (IC50 = 3.71 ± 0.11 nM) and HDAC2 (IC50 = 4.07 ± 0.25 nM). MD simulations presented that CH-1 could stably bind the active pockets of CARM1 and HDAC2. Notably, CH-1 exhibited strong anti-proliferative activity against multiple prostate-related tumour cells (IC50 < 1 µM). In vivo, assessment indicated that CH-1 significantly inhibited tumour growth in a DU145 xenograft model. Collectively, CH-1 could be a promising drug candidate for PCa treatment.

Extensive therapeutic effects, underlying molecular mechanisms and disease treatment prediction of Metformin: a systematic review.

Metformin (Met), a first-line management for type 2 diabetes mellitus, has been expansively employed and studied with results indicating its therapeutic potential extending beyond glycemic control. Beyond its established role, this therapeutic drug demonstrates a broad spectrum of action encompassing over 60 disorders, encompassing metabolic conditions, inflammatory disorders, carcinomas, cardiovascular diseases, and cerebrovascular pathologies. There is clear evidence of Met's action targeting specific nodes in the molecular pathways of these diseases and, intriguingly, interactions with the intestinal microbiota and epigenetic processes have been explored. Furthermore, novel Met derivatives with structural modifications tailored to diverse diseases have been synthesized and assessed. This manuscript proffers a comprehensive thematic review of the diseases amenable to Met treatment, elucidates their molecular mechanisms, and employs informatics technology to prospect future therapeutic applications of Met. These data and insights gleaned considerably contribute to enriching our understanding and appreciation of Met's far-reaching clinical potential and therapeutic applicability.

Identification and validation of platelet-related diagnostic markers and potential drug screening in ischemic stroke by integrating comprehensive bioinformatics analysis and machine learning.

Background: Ischemic stroke (IS), caused by blood and oxygen deprivation due to cerebral thrombosis, has links to activated and aggregated platelets. Discovering platelet-related biomarkers, developing diagnostic models, and screening antiplatelet drugs are crucial for IS diagnosis and treatment. Methods and results: Combining and normalizing GSE16561 and GSE22255 datasets identified 1,753 upregulated and 1,187 downregulated genes. Fifty-one genes in the platelet-related module were isolated using weighted gene co-expression network analysis (WGCNA) and other analyses, including 50 upregulated and one downregulated gene. Subsequent enrichment and network analyses resulted in 25 platelet-associated genes and six diagnostic markers for a risk assessment model. This model's area under the ROC curve outperformed single genes, and in the peripheral blood of the high-risk group, immune infiltration indicated a higher proportion of CD4, resting CD4 memory, and activated CD4 memory T cells, along with a lower proportion of CD8 T cells in comparison to the low-risk group. Utilizing the gene expression matrix and the CMap database, we identified two potential drugs for IS. Finally, a rat MACO/R model was used to validate the diagnostic markers' expression and the drugs' predicted anticoagulant effects. Conclusion: We identified six IS platelet-related biomarkers (APP, THBS1, F13A1, SRC, PPBP, and VCL) for a robust diagnostic model. The drugs alpha-linolenic acid and ciprofibrate have potential antiplatelet effects in IS. This study advances early IS diagnosis and treatment.

Discovery of a Dual Tubulin and Neuropilin-1 (NRP1) Inhibitor with Potent In Vivo Anti-Tumor Activity via Pharmacophore-based Docking Screening, Structure Optimization, and Biological Evaluation.

Dual inhibition of tubulin and neuropilin-1 (NRP1) may become an effective method for cancer treatment by simultaneously killing tumor cells and inhibiting tumor angiogenesis. Herein, we identified dual tubulin/NRP1-targeting inhibitor TN-2, which exhibited good inhibitory activity against both tubulin polymerization (IC50 = 0.71 ± 0.03 µM) and NRP1 (IC50 = 0.85 ± 0.04 µM). Importantly, it significantly inhibited the viability of several human prostate tumor cell lines. Further mechanism studies indicated that TN-2 could inhibit tubulin polymerization and cause G2/M arrest, thereby inducing cell apoptosis. It could also suppress cell tube formation, migration, and invasion. Moreover, TN-2 showed obvious antitumor effects on the PC-3 cell-derived xenograft model with negligible side effects and good pharmacokinetic profiles. These data demonstrate that TN-2 could be a promising dual-target chemotherapeutic agent for the treatment of prostate cancer.

Dephasing by optical phonons in GaN defect single-photon emitters.

Single-photon defect emitters (SPEs), especially those with magnetically and optically addressable spin states, in technologically mature wide bandgap semiconductors are attractive for realizing integrated platforms for quantum applications. Broadening of the zero phonon line (ZPL) caused by dephasing in solid state SPEs limits the indistinguishability of the emitted photons. Dephasing also limits the use of defect states in quantum information processing, sensing, and metrology. In most defect emitters, such as those in SiC and diamond, interaction with low-energy acoustic phonons determines the temperature dependence of the dephasing rate and the resulting broadening of the ZPL with the temperature obeys a power law. GaN hosts bright and stable single-photon emitters in the 600-700 nm wavelength range with strong ZPLs even at room temperature. In this work, we study the temperature dependence of the ZPL spectra of GaN SPEs integrated with solid immersion lenses with the goal of understanding the relevant dephasing mechanisms. At temperatures below ~ 50 K, the ZPL lineshape is found to be Gaussian and the ZPL linewidth is temperature independent and dominated by spectral diffusion. Above ~ 50 K, the linewidth increases monotonically with the temperature and the lineshape evolves into a Lorentzian. Quite remarkably, the temperature dependence of the linewidth does not follow a power law. We propose a model in which dephasing caused by absorption/emission of optical phonons in an elastic Raman process determines the temperature dependence of the lineshape and the linewidth. Our model explains the temperature dependence of the ZPL linewidth and lineshape in the entire 10-270 K temperature range explored in this work. The ~ 19 meV optical phonon energy extracted by fitting the model to the data matches remarkably well the ~ 18 meV zone center energy of the lowest optical phonon band ([Formula: see text]) in GaN. Our work sheds light on the mechanisms responsible for linewidth broadening in GaN SPEs. Since a low energy optical phonon band ([Formula: see text]) is a feature of most group III-V nitrides with a wurtzite crystal structure, including hBN and AlN, we expect our proposed mechanism to play an important role in defect emitters in these materials as well.

A Bioinformatics Research on Novel Mechanism of Compound Kushen Injection for Treating Breast Cancer by Network Pharmacology and Molecular Docking Verification.

Compound Kushen injection (CKI) has been extensively used in treating breast cancer (BC). However, the molecular mechanism remains unclear. In this study, 16 active compounds of CKI were obtained from 3 articles for target prediction. Then, a compound-predicted target network and a compound-BC target network were conducted by Cytoscape 3.6.1. The gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the DAVID database. The binding energy between the key targets of CKI and the active compounds was studied by molecular docking. As a result, 16 active compounds of CKI were identified, corresponding to 285 putative targets. The key targets of CKI for BC are HSD11B1, DPP4, MMP9, CDK1, MMP2, PTGS2, and CA14. The function enrichment analysis obtained 13 GO entries and 6 KEGG pathways, including bladder cancer, cancer pathways, chemical carcinogenesis, estrogen signaling pathway, TNF signaling pathway, and leukocyte transendothelial migration. The result of molecular docking indicated that DPP4 had strong binding activity with matrine, alicyclic protein, and sophoridine, and MMP9 had strong binding activity with adenine and sophoridine. In conclusion, the therapeutic effect of CKI on BC is based on the overall pharmacological effect formed by the combined effects of multiple components, multiple targets, and multiple pathways. This study provides a theoretical basis for further experimental research in the future.

Comparative Efficacy and Safety of Chinese Herbal Injections Combined With Cyclophosphamide and 5-Fluorouracil Chemotherapies in Treatment of Breast Cancer: A Bayesian Network Meta-Analysis.

Background: Given the limitations of chemotherapy for the treatment of breast cancer (BC) and the wide exploration of Chinese herbal injections (CHIs), this network meta-analysis (NMA) was conducted to analyze the comparative efficacy and safety of nine CHIs combined with CF (Cyclophosphamide and 5-Fluorouracil) chemotherapy regimens in the treatment of BC. Methods: Several electronic databases were searched to identify randomized controlled trials (RCTs) from inception to January 6, 2020. RCTs were screened by pre-established eligibility criteria, and the quality of which was assessed using the Cochrane risk of bias tool. Outcomes such as the clinical effectiveness rate, performance status, peripheral hemogram, and detection of T-lymphocyte subsets were analyzed using the Winbugs 1.4.3 and Stata 13.0 software. Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Cluster analysis was performed to compare the effect of CHIs between two or three different outcomes. Results: A total of 84 RCTs involving 7855 patients and nine CHIs were included. The results showed that compared to CF chemotherapy regimens alone, the ones injected along with Aidi, Shenmai, Shenqi Fuzheng, Kangai, Kanglaite, or Shengmai combined with CF can improve the clinical effectiveness rate. Aidi, Shenmai, Shenqi Fuzheng, Compound Kushen, Kangai, and Kanglaite injection combined with CF can improve the performance status. Shenqi Fuzheng injection was considered as a favorable choice for relieving adverse reactions. According to the results of cluster analysis, Aidi injection and Compound Kushen injection plus CF were more favorable for the clinical effectiveness rate and performance status. Conclusion: In conclusion, Shenqi Fuzheng, Compound Kushen, Aidi, and Kangai injection combined with CF chemotherapy regimen have more significant effects for patients with BC. However, more high-quality clinical RCTs, especialy which correctly use blinding and allocation concealment, are required to support the conclusions.