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Psoriasis, an immune-mediated inflammatory skin disorder characterized by a chronically relapsing-remitting course, continues to be primarily managed through topical therapy. While oral administration of tyrosine kinase 2 inhibitors (TYK2i) stands as an effective approach for psoriasis treatment, the potential efficacy of topical application of TYK2i remains unexplored. Herein, the carbomer/alginic acid hydrogel is embedded with borneol (BO) as a new topical carrier of TYK2i for achieving enhanced transdermal permeation and anti-psoriasis efficacy. The hydrogel system, i.e., TYK2i-BO-gel, exhibits significantly improved preventative and therapeutic effects in mice models of psoriasiform dermatitis, as evidenced by phenotypical images, psoriasis severity score index (PSI), histology, immunohistochemical staining, and PCR analysis. Remarkably, TYK2i-BO-gel outperforms conventional topical corticosteroid therapy by significantly preventing psoriatic lesion recurrence as measured by a nearly 50 % reduction in ear thickness changes (p

Abstract Background Ischemic stroke (IS) is known for its high morbidity, disability and mortality rates, and studies designed to explore its pathophysiological mechanisms and identify novel therapeutic strategies are urgently needed. We aimed to probe the effects of the deubiquitinase OTUD3-IRP2-p53/PTGS2 pathway on cerebral ischemia‒reperfusion (I/R) injury and hippocampal neuron ferroptosis. Methods A cerebral I/R mouse model was established. Furthermore, lentiviral vectors that overexpressed OTUD3 and knocked down IRP2 were constructed, and a series of assays were performed to probe the OTUD3/IRP2/p53/PTGS2 mechanism. An oxygen‒glucose deprivation and reoxygenation (OGD/R) model of mouse hippocampal neurons was constructed. Then, OTUD3 and IRP2 were knocked down and overexpressed, and p53 was overexpressed to explore the mechanism of the OTUD3/IRP2/p53/PTGS2 pathway. Results OTUD3 and IRP2 were expressed at low levels in cerebral I/R models. OTUD3 promoted IRP2 expression to protect damaged hippocampal neurons. Moreover, IRP2 affected ferroptosis in hippocampal neurons. In addition, IRP2 inhibited p53. After IRP2 and p53 were overexpressed, IRP2 regulated the p53/PTGS2 pathway and affected ferroptosis in hippocampal neurons. In vivo, after overexpressing OTUD3 and knocking down IRP2, we found that overexpression of OTUD3 promoted IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway. Conclusions The deubiquitinase OTUD3 stabilized IRP2 expression to reduce hippocampal neuron ferroptosis via the p53/PTGS2 pathway to subsequently ameliorate cerebral I/R injury.

Abstract Metabolic dysfunction-associated steatohepatitis (MASH) is a common but frequently unrecognized complication of obesity and type 2 diabetes. The association between these conditions is multifaceted and involves complex interactions between metabolic, inflammatory, and genetic factors. Here we assess the underlying structural and molecular processes focusing on the immunological phase of MASH in the nonobese inflammation and fibrosis (NIF) mouse model and compare it to the human disease as well as other murine models. Histopathology together with synchrotron-radiation-based x-ray micro-computed tomography (SRµCT) was used to investigate structural changes within the hepatic sinusoids network in the NIF mouse in comparison to patients with different severities of MASH. A time-course, bulk RNA-sequencing analysis of liver tissue from NIF mice was performed to identify the dynamics of key processes associated with the pathogenesis. Transcriptomics profiling of the NIF mouse revealed a gradual transition from an initially reactive inflammatory response to a regenerative, pro-fibrotic inflammatory response suggesting new avenues for treatment strategies that focus on immunological targets. Despite the lack of metabolic stress induced liver phenotype, a large similarity between the NIF mouse and the immunological phase of human MASH was detected. The translational value was further supported by the comparative analyses with MASH patients and additional animal models. Finally, the impact of diets known to induce metabolic stress, was explored in the NIF mouse. An obesogenic diet was found to induce key physiological, metabolic, and histologic changes akin to those observed in human MASH.

Abstract Background The Medium and Long-Term Plan for the Prevention and Treatment of Chronic Diseases (2017–2025) in China has highlighted the importance of reducing fat, sodium, and sugar in foods. However, front-of-pack labeling, which enables consumers to assess the health levels of prepackaged foods, is lacking in China. In response to the Zhejiang Provincial Health Commission’s request, we sought to develop a method for efficiently evaluating the health level of prepackaged foods. Methods Through a comprehensive literature review, we established a systematic framework: the Prepackaged Foods Healthiness Ranking Index (PHRI). We determined specific threshold values and grading criteria and conducted two rounds of Delphi survey to refine the index. Using a measurement dataset, we aimed to determine the optimal limit values for assessing the health level of prepackaged foods in real-world settings. Results After two rounds of Delphi surveys, the PHRI underwent multiple revisions until consensus among experts was reached. The final decision regarding the upper limit values set 30% Nutrient Reference Values as the limit for solid foods and 15% Nutrient Reference Values for liquid foods. The calculation of PHRI values was successfully implemented with the dataset, in accord with current nutrition awareness and real-world conditions. Conclusions The PHRI provides a valuable tool for assessing the healthiness of prepackaged foods. This front-of-pack labeling system provides a convenient method for evaluating the nutritional quality of prepackaged foods. Ultimately, the PHRI has the potential to contribute to advancements in health policy, practice, and education in China.

Abstract Background Although clinical substance use disorder (SUD) care is multidisciplinary there are few opportunities to collaborate for quality improvement or systems change. In Oregon, the Project ECHO (Extension for Community Healthcare Outcomes) model was adapted to create a novel multidisciplinary SUD Leadership ECHO. The objective of this study was to understand the unique effects of the adapted ECHO model, determine if the SUD Leadership ECHO could promote systems change, and identify elements that enabled participant-leaders to make changes. Methods Four focus groups were conducted between August and September of 2022 with a purposive sample of participants from the second cohort of the Oregon ECHO Network’s SUD Leadership ECHO that ran January to June 2022. Focus group domains addressed the benefits of the adapted ECHO model, whether and why participants were able to make systems change following participation in the ECHO, and recommendations for improvement. Thematic analysis developed emergent themes. Results 16 of the 53 ECHO participants participated in the focus groups. We found that the SUD Leadership ECHO built a multi-disciplinary community of practice among leaders and reduced isolation and burnout. Three participants reported making organizational changes following participation in the ECHO. Those who successfully made changes heard best practices and how other organizations approached problems. Barriers to initiating practice and policy changes included lack of formal leadership authority, time constraints, and higher-level systemic issues. Participants desired for future iterations of the ECHO more focused presentations on a singular topic, and asked for a greater focus on solutions, advocacy, and next steps. Conclusions The adapted ECHO model was well received by focus group participants, with mixed reports on whether participation equipped them to initiate organizational or policy changes. Our findings suggest that the SUD Leadership ECHO model, with fine-tuning, is a promising avenue to support SUD leaders in promoting systems change and reducing isolation among SUD leaders.

As concerns about personal health continue to escalate, there is an urgent need to innovate the development and production of photopolymeric 3D printing thermoset materials with inherent antibacterial properties and high elongation, paving the way for significant advances in 3D printing technology. In this work, two acrylate compounds (CMA and CAMA)with inherent antibacterial properties were synthesized using renewable monomers derived from citronellol and cinnamyl alcohol. The chemical structures of the two acrylate compounds were verified via Fourier transform infrared spectroscopy(FT-IR) and 1H NMR. The addition of these compounds to the photopolymeric 3D printing resin system can facilitate the production of 3D printed thermoset materials with inherent antibacterial properties. The mechanical and antibacterial properties of photopolymeric 3D printing thermosets were assessed utilizing tensile tests and oscillation methods. The results show that the addition of CMA and CAMA can significantly improve the fracture elongation and antibacterial performance of photopolymeric 3D printing thermosets. The improved systems exhibited the highest antibacterial rate (94.2 % and 98.9 %, respectively), and fracture productivities (47 % and 50 %, respectively). These results highlight the significant impact of integrating CMA and CAMA to enhance the toughness and antibacterial effects of photopolymeric 3D printing systems.

Summary: Background: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID. Methods: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.). Findings: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events. Interpretation: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions. Funding: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.

A novel type of tailless FBG smart bolt with good performance is developed. Owe to the innovative design of an integrated FBG sensor comprising a strain measured FBG and a temperature-compensated FBG, the tailless FBG smart bolt serves the purpose of torque monitoring or bolt looseness monitoring. We use a theoretical approach to establish the linear correlation between the applied torque and the central wavelength of the tailless FBG smart bolt. Additionally, a newly designed M24 bolt with a nominal strength has been integrated as a crucial component of the tailless FBG smart bolt. To enable the experimental study, the tailless FBG smart bolt is newly designed, fabricated and tested. The experimental results show a strong linear correlation between the applied torque and the central wavelength of the tailless FBG smart bolt, showing good agreement with the theory.