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Molecular strain can be introduced to influence the outcome of chemical reactions. Once a thermodynamic product is formed, however, reversing the course of a strain-promoted reaction is challenging. Here, a reversible, strain-promoted polymerization in cyclic DNA is reported. The use of nonhybridizing, single-stranded spacers as short as a single nucleotide in length can promote DNA cyclization. Molecular strain is generated by duplexing the spacers, leading to ring opening and subsequent polymerization. Then, removal of the strain-generating duplexers triggers depolymerization and cyclic dimer recovery via enthalpy-driven cyclization and entropy-mediated ring contraction. This reversibility is retained even when a protein is conjugated to the DNA strands, and the architecture of the protein assemblies can be modulated between bivalent and polyvalent states. This work underscores the utility of using DNA not only as a programmable ligand for assembly but also as a route to access restorable bonds, thus providing a molecular basis for DNA-based materials with shape-memory, self-healing, and stimuli-responsive properties. [ABSTRACT FROM AUTHOR]

The structural and functional diversity of materials in nature depends on the controlled assembly of discrete building blocks into complex architectures via specific, multistep, hierarchical assembly pathways. Achieving similar complexity in synthetic materials through hierarchical assembly is challenging due to difficulties with defining multiple recognition areas on synthetic building blocks and controlling the sequence through which those recognition sites direct assembly. Here, we show that we can exploit the chemical anisotropy of proteins and the programmability of DNA ligands to deliberately control the hierarchical assembly of protein–DNA materials. Through DNA sequence design, we introduce orthogonal DNA interactions with disparate interaction strengths (“strong” and “weak”) onto specific geometric regions of a model protein, stable protein 1 (Sp1). We show that the spatial encoding of DNA ligands leads to highly directional assembly via strong interactions and that, by design, the first stage of assembly increases the multivalency of weak DNA–DNA interactions that give rise to an emergent second stage of assembly. Furthermore, we demonstrate that judicious DNA design not only directs assembly along a given pathway but can also direct distinct structural outcomes from a single pathway. This combination of protein surface and DNA sequence design allows us to encode the structural and chemical information necessary into building blocks to program their multistep hierarchical assembly. Our findings represent a strategy for controlling the hierarchical assembly of proteins to realize a diverse set of protein– DNA materials by design. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic foot ulcers (DFU) are one of the leading long-term complications experienced by patients with diabetes. Dipeptidyl Peptidase 4 inhibitors (DPP4is) are a class of antihyperglycemic medications prescribed to patients with diabetes to manage glycaemic control. DPP4is may also have a beneficial effect on DFU healing. This study aimed to determine vildagliptin's effect on inflammatory markers and wound healing. Trial design: Prospective, randomized, double-blind, placebo-controlled, single-center study. Methods: Equal number of participants were randomized into the treatment and placebo groups. The treatment was for 12 weeks, during which the participants had regular visits to the podiatrist, who monitored their DFU sizes using 3D camera, and blood samples were taken at baseline, six weeks, and 12 weeks during the study for measurement of inflammatory markers. In addition, demographic characteristics, co-morbidities, DFU risk factors, and DFU wound parameters were recorded. Results: 50 participants were recruited for the study, with 25 assigned to placebo and 25 to treatment group. Vildagliptin treatment resulted in a statistically significant reduction of HBA1c (p < 0.02) and hematocrit (p < 0.04), total cholesterol (p < 0.02), LDL cholesterol (p < 0.04), and total/HDL cholesterol ratio (P < 0.03) compared to the placebo group. Also, vildagliptin had a protective effect on DFU wound healing, evidenced by the odds ratio (OR) favoring the intervention of 11.2 (95% CI 1.1–113.5; p < 0.04) and the average treatment effect on the treated (ATET) for vildagliptin treatment group showed increased healing by 35% (95%CI; 10–60, p = 0.01) compared to placebo with the model adjusted for microvascular complications, smoking, amputation, dyslipidemia, peripheral vascular disease (PVD) and duration of diabetes. Conclusions: Vildagliptin treatment was effective in healing DFU in addition to controlling the diabetes. Our findings support the use of DPP4is as a preferred option for treating ulcers in patients with diabetes. Further studies on a larger population are warranted to confirm our findings and understand how DPP4is could affect inflammation and DFU healing. [ABSTRACT FROM AUTHOR]

Background and Objectives The increasing number of people with dementia requires transparency and quality dementia education, training, and care. This scoping review aimed to determine the key elements of national or state-wide standards on dementia education and training that could underpin the development of international standards for dementia workforce training and education. Research Design and Methods The English-language peer-reviewed and gray literature were searched (2010–20). Key search domains were training, workforce, standards/frameworks, and dementia. Results Thirteen standards were identified from the United Kingdom (n = 5), the United States (n = 4), Australia (n = 3), and Ireland (n = 1). Most standards focused on training health care professionals with some including people in customer-centric settings, people living with dementia, and informal carers or the general community. Seventeen training topics were identified in 10 or more of the 13 standards. Cultural safety, rural issues, health care professional self-care, digital literacy, and health promotion topics were less commonly reported. The barriers to standards implementation were lack of organizational support, lack of access to relevant training, low staff literacy, lack of funding, high staff turnover, ineffective past program cycles, and inconsistent service delivery. Enablers included a strong implementation plan, funding, strength of partnerships, and building on previous work. Discussion and Implications The U.K. Dementia Skills and Core Training Standard, the Irish Department of Health Dementia Together, and the National Health Services Scotland Standard are the recommended strongest standards for underpinning the development of international standards. It is essential that training standards are tailored to the needs of the consumer, worker, and regions. [ABSTRACT FROM AUTHOR]