Discovery of Therapeutic Candidates for Diabetic Retinopathy Based on Molecular Switch Analysis: Application of a Systematic Process

The pathogenesis of diabetic retinopathy (DR) is complicated, and there is no effective drug. Oxidative stress-induced human retinal microvascular endothelial cells (HRMECs) injury is one of the pathogenic factors for DR. Molecular switches are considered high-risk targets in disease progression. Identification of molecular switch is crucial to interpret the pathogenesis of disease and screen effective ingredients. In this study, a systematic process was executed to discover therapeutic candidates for DR based on HRMECs injury. First of all, the molecular mechanism of HRMECs oxidative stress injury was revealed by transcriptomics and network pharmacology. We found that oxidative stress was one of the pivotal pathogenic factors, which interfered with vascular system development, inflammation, cell adhesion, and cytoskeleton damaged HRMECs through crosstalk. Then, network topology analysis was used to recognize molecular switches. The results indicated that the Keap1-Nrf2-ARE signaling pathway was the molecular switch in HRMECs oxidative stress injury. On this basis, the HEK293-ARE overexpression cell line was applied to obtain 18 active traditional Chinese medicine (TCM) ingredients. Furthermore, andrographolide, one of the 18 candidates, was applied in the HRMECs oxidative stress model to evaluate the accuracy of the systematic process. The efficacy evaluation results showed that andrographolide could regulate oxidative stress, vascular system development, inflammation, adhesion, and skeleton tissue to inhibit HRMECs injury cooperatively. And its mechanism was related to the Nrf2 signaling pathway. Overall, our data suggest that the Nrf2 signaling pathway is the molecular switch in the HRMECs oxidative stress injury. 18 potential Nrf2 agonists are likely to be promising DR candidates.

Servant and Shepherd Leadership in Higher Education

To lead, you must serve, mentor, and teach others. Servant leadership is the systematic process of developing the needs of servants ahead of those leaders found within private or public institutions. Shepherd leadership individually provides others with empowerment and achievement to perform well. The principle behind effective leadership is based on the interplay of responsibility, respect, care, and working with people, not against people. Ultimately, leadership is about character and substance. Using the distinct characteristics of servant leadership and shepherd leadership is to promote and foster the development of successful individuals and relating well with individuals through care and a strong commitment. Honest and caring concern for others leads to empowerment and emotional support, which inspires the members to embrace the needs of the organization. This creates a mentoring and learning environment in higher education that is conducive to producing optimal performance from their faculty, staff, and students.

Development of an Offsite Construction Typology: A Delphi Study

Offsite construction (OSC) delivers multiple products that vary in design and building complexity. Considering the growing prevalence of OSC, a systematic categorization of OSC types can offer operational and macroeconomic benefits to the construction industry. The purpose of this study is to develop an OSC typology through a systematic process, as existing studies do not present a rigorously evaluated typology that suits the modern OSC context. The research addresses the following research question: what are the distinct characteristics of unique OSC types that have emerged through the adoption of Industry 4.0-based technological advancements? Due to the rapid advancement of production and construction technologies, the existing OSC classifications are becoming outdated. As such, a detailed review of OSC technologies was conducted which enabled the identification of OSC categories: components, panels, pods, modules, complete buildings, and flat-pack (foldable structure). A series of case studies was then reviewed to explore and analyze the relevance of these OSC types in practice. It was then subjected to a Delphi-based multi-level expert forum to develop a modern and future-proof OSC typology. The rigorous process validated, defined, and delineated the boundaries between the OSC types. The research confirmed that OSC types can be broadly categorized as volumetric (pods, modules, complete buildings) and non-volumetric (components, panels, foldable structure). The results indicated that OSC skills vary with the complexity of OSC types, and that lightweight steel and timber are the most common materials.

Using Implementation Science Strategy Mapping on the Age-Friendly Health System's 4Ms Journey

Background Implementation science is the study of methods to promote the adoption and integration of evidence-based practices into routine health care to improve the quality of care. The purpose of this study was to use Implementation Mapping to guide the implementation of The John A. Hartford evidence-based Age-Friendly Health Systems (AFHS) 4Ms Framework: What Matters, Medications, Mentation, and Mobility. Methods Implementation Mapping, a systematic process for planning implementation strategies, guided the 9-month integration of the 4Ms Framework in the 1,100 MinuteClinics across the US. Implementation Mapping includes five tasks: (1) conduct an implementation needs assessment and identify program adopters and implementers; (2) state adoption and implementation outcomes and performance objectives, identify determinants, and create matrices of change objectives; (3) choose theoretical methods (mechanisms of change) and select or design implementation strategies; (4) produce implementation protocols and materials; and (5) evaluate implementation outcomes. Results The implementation plan, developed by the implementation mapping method, was carried out over 9-months. Seven implementation strategies were identified from the Expert Recommendations for Implementing Change (ERIC) project including the provision of education, electronic health record integration, internal champion facilitation, cues to action, and a dashboard to monitor progress. To date, the implementation mapping has resulted in the adoption of the 4Ms by 1145 providers (37%). Monitoring of the adoption of the 4Ms Framework and consideration of future implementation strategies is ongoing. Conclusions Implementation Mapping provided a systematic process to develop strategies to improve the adoption, implementation, sustainment, and scale-up of the evidence-based 4Ms Framework.

Desglose y sistematización de ítems para las labores de supervisión formal de proyectos de edificación

Graduates of technical architecture and construction have several work possibilities ahead of them. One is to join firms that carry out supervisory work of construction design projects, and their role in such firms is to perform an in-depth and formal verification of the content of design documents. This paper presents a number of results obtained in practical activities with students, the objective of which was to understand how they would carry out the management of such supervisory tasks by means of a systematic process of item verification. It is thus intended to hold an exercise of how they will eventually organise their professional duties. The results are grouped into five fully systematised checklist tables, one for each of the component elements of design projects (description, attachments, plans, measurements and budgets, and terms and conditions). A total of 108 testing and control checks were envisaged, each of which is well suited to be used, as-is, in a real professional context.