A theoretical screening of phytochemical constituents from Millettia brandisiana as inhibitors against acetylcholinesterase.

Alzheimer's disease is one of the causes associated with the early stages of dementia. Nowadays, the main treatment available is to inhibit the actions of the acetylcholinesterase (AChE) enzyme, which has been identified as responsible for the disease. In this study, computational methods were used to examine the structure and therapeutic ability of chemical compounds extracted from Millettia brandisiana natural products against AChE. This plant is commonly known as a traditional medicine in Vietnam and Thailand for the treatment of several diseases. Furthermore, machine learning helped us narrow down the choice of 85 substances for further studies by molecular docking and molecular dynamics simulations to gain deeper insights into the interactions between inhibitors and disease proteins. Of the five top-choice substances, γ-dimethylallyloxy-5,7,2,5-tetramethoxyisoflavone emerges as a promising substance due to its large free binding energy to AChE and the high thermodynamic stability of the resulting complex.

Unusual reaction of (E)-2-[(benzo[d]thia-zol-2-yl-imino)-meth-yl]-5-(di-ethyl-amino)-phenol with tri-phenyl-borane: crystal structures and optical properties.

The mol-ecular and crystal structure of (E)-2-[(benzo[d]thia-zol-2-yl-imino)-meth-yl]-5-(di-ethyl-amino)-phenol (C18H19N3O2S, Et2N-Bz) and its unexpected reaction product with tri-phenyl-borane, 2,2-diphenyl-1,3-dioxa-2-borata-1,2-di-hydro-naphthalene [systematic name: N,N-diethyl-2,2-diphenyl-2H-1,3λ3,2λ4-ben-zodioxaborinin-7-amine, C23H24BNO2, (I)] are described. For Et2N-Bz, the hydroxyl group is involved in an intra-molecular hydrogen bond with the imino nitro-gen atom and the C=N bond displays an E configuration. The crystal packing is characterized by layers of inversion dimers parallel to the (10) plane and chains of mol-ecule in the a-axis direction formed through C-H⋯O inter-actions. Complex (I) crystallizes with two mol-ecules (A and B) in the asymmetric unit, which differ in the orientation of the ethyl groups. The 1,3-dioxa-2-borata-1,2,3,4-tetra-hydro-naphthalene ring displays a slight envelope conformation with the boron atom as the flap. In the crystal packing, chains of alternating A and B mol-ecules formed by C-H⋯O hydrogen bonds run in the b-axis direction. The UV-vis absorption and emission properties of the compounds are discussed and their aggregation-induced emission properties are further investigated.

Diagnostic and prognostic value of miR-200 family in breast cancer: A meta-analysis and systematic review.

BACKGROUND: Breast cancer (BC) is the most common cancer for women all over the world. Great interests have been paid to discover accurate and noninvasive methods for breast cancer diagnosis and prognosis. Although the diagnostic and prognostic value of microRNA-200 (miRNA- 200, miR-200) family has been revealed in many studies, the results were inconsistent. Thus, this meta-analysis aims to assess the overall value of miRNA-200 family in breast cancer diagnosis and prognosis. METHOD: Relevant studies were searched from the following databases: PubMed, PMC, EMBASE, and ScienceDirect using key words: ("miRNA-200 family" or "miR-141" or "miR-200a" or "miR-200b" or "miR-200c" or "miR-429") and ("HER2" or "Luminal A" or "Luminal B" or "TNBC") and ("breast cancers" or "breast carcinoma" or "breast malignancy" or "breast tumor"). The sensitivity, specificity, AUC were then calculated to estimate the diagnostic accuracy of the miR-200 family. As for the prognostic value of the miR-200 family, the pooled hazard ratio (HR) was assessed. Heterogeneity among individual studies was also examined by subgroup analyses. RESULT: A total of 24 articles were included in the meta-analysis. The diagnostic value of miR-200s in BC was presented by the pooled sensitivity was 0.86 (95% CI: 0.83-0.88); the pooled specificity was 0.82 (95% CI: 0.72-0.89); the pooled AUC was 0.931 (95% CI: 0.919-0.942). Besides, expression of miR-200s in metastatic breast cancer has sensitivity, specificity and AUC of 0.70 (95%CI: 0.56-0.81), 0.72 (95%CI: 0.61-0.81), and 0.814 (95%CI: 0.741-0.903), respectively. The meta-analysis then revealed that high expression of miR-200 family corresponded to poor OS (HR: 1.63, 95% CI: 1.03-2.52), poor DFS (HR: 1.55, 95% CI: 0.95-2.56) in BC patients while downregulation of miRNA-200s corresponded to poor OS (HR= 0.84, 95%CI: 0.46-1.63) in TNBC patients and poor OS (HR=0.49; 95%CI: 0.27-0.88) in luminal BC patient. CONCLUSION: The MiR-200 family has high diagnostic accuracy and can be used as an important biomarker to prognosticate breast cancer.

Capturing the clinical decision-making processes of expert and novice diabetic retinal graders using a 'think-aloud' approach.

BACKGROUND: Diabetic eye screening programmes have been developed worldwide based on evidence that early detection and treatment of diabetic retinopathy are crucial to preventing sight loss. However, little is known about the decision-making processes and training needs of diabetic retinal graders, particularly in low- and middle-income countries. OBJECTIVES: To provide data for improving evidence-based diabetic retinopathy training to help novice graders process fundus images more like experts. SUBJECTS/METHODS: This is a mixed-methods qualitative study conducted in southern Vietnam and Northern Ireland. Novice diabetic retinal graders in Vietnam (n = 18) and expert graders in Northern Ireland (n = 5) were selected through a purposive sampling technique. Data were collected from 21st February to 3rd September 2019. The interviewer used neutral prompts during think-aloud sessions to encourage participants to verbalise their thought processes while grading fundus images from anonymised patients, followed by semi-structured interviews. Thematic framework analysis was used to identify themes, supported by illustrative quotes from interviews. Mann-Whitney U tests were used to compare graders' performance. RESULTS: Expert graders used a more systematic approach when grading images, considered all four images per patient and used available software tools such as red-free filters prior to making a decision on management. The most challenging features for novice graders were intra-retinal microvascular abnormalities and new vessels, which were more accurately identified by experts. CONCLUSION: Taking more time to grade fundus images and adopting a protocol-driven "checklist" approach may help novice graders to function more like experts.

The sporulation control gene spo0M of Bacillus subtilis is a target of the FtsH metalloprotease.

In an attempt to identify substrate proteins of the FtsH metalloprotease involved in stage 0 of sporulation in Bacillus subtilis, the proteome of an ftsH wild-type strain was compared to that of an ftsH null mutant by the 2D gel technique. One of the most abundant proteins identified in the absence of ftsH turned out to be Spo0M, a sporulation control protein of stage 0. Using transcriptional fusion between the spo0M promoter and the bgaB reporter gene, expression analysis did not reveal any influence of FtsH on spo0M transcription, suggesting that FtsH might have a negative effect on the stability of Spo0M due to its proteolytic activity on Spo0M. Indeed, in vitro incubation of purified components demonstrated that Spo0M was degraded by FtsH, indicating that it serves as a substrate for the FtsH protease. These results are discussed.