Enhancing Cytoplasmic Expression of Exogenous mRNA Through Dynamic Mechanical Stimulation.

Ionizable lipid nanoparticles (LNPs) are pivotal in combating COVID-19, and numerous preclinical and clinical studies have highlighted their potential in nucleic acid-based therapies and vaccines. However, the effectiveness of endosomal escape for the nucleic acid cargos encapsulated in LNPs is still low, leading to suboptimal treatment outcomes and side effects. Hence, improving endosomal escape is crucial for enhancing the efficacy of nucleic acid delivery using LNPs.

Enhancing Cytoplasmic Expression of Exogenous mRNA through Dynamic Mechanical Stimulation.

Ionizable lipid nanoparticles (LNPs) have been pivotal in combating COVID-19, and numerous preclinical and clinical studies have highlighted their potential in nucleic acid-based therapies and vaccines. However, the effectiveness of endosomal escape for the nucleic acid cargos encapsulated in LNPs is still low, leading to suboptimal treatment outcomes and side effects. Hence, improving endosomal escape is crucial for enhancing the efficacy of nucleic acid delivery using LNPs.

Lung-Mimetic Hydrofoam Sealant to Treat Pulmonary Air Leak.

Pulmonary air leak is the most common complication of lung surgery, contributing to post-operative morbidity in up to 60% of patients; yet, there is no reliable treatment. Available surgical sealants do not match the demanding deformation mechanics of lung tissue; and therefore, fail to seal air leak. To address this therapeutic gap, a sealant with structural and mechanical similarity to subpleural lung is designed, developed, and systematically evaluated.

Recovery of extracorporeal lungs using cross-circulation with injured recipient swine.

Objective: Lung transplantation remains limited by the shortage of healthy organs. Cross-circulation with a healthy swine recipient provides a durable physiologic environment to recover injured donor lungs. In a clinical application, a recipient awaiting lung transplantation could be placed on cross-circulation to recover damaged donor lungs, enabling eventual transplantation.

Future trends in incidence and long-term survival of metastatic cancer in the United States.

Background: Previous studies have demonstrated epidemiological trends in individual metastatic cancer subtypes; however, research forecasting long-term incidence trends and projected survivorship of metastatic cancers is lacking. We assess the burden of metastatic cancer to 2040 by (1) characterizing past, current, and forecasted incidence trends, and (2) estimating odds of long-term (5-year) survivorship.

Methods: This retrospective, serial cross-sectional, population-based study used registry data from the Surveillance, Epidemiology, and End Results (SEER 9) database.

Emerging Imaging Modalities for Functional Assessment of Donor Lungs .

The severe shortage of functional donor lungs that can be offered to recipients has been a major challenge in lung transplantation. Innovative lung perfusion (EVLP) and tissue engineering methodologies are now being developed to repair damaged donor lungs that are deemed unsuitable for transplantation. To assess the efficacy of donor lung reconditioning methods intended to rehabilitate rejected donor lungs, monitoring of lung function with improved spatiotemporal resolution is needed.

Opto-electromechanical quantification of epithelial barrier function in injured and healthy airway tissues.

The airway epithelium lining the luminal surface of the respiratory tract creates a protective barrier that ensures maintenance of tissue homeostasis and prevention of respiratory diseases. The airway epithelium, unfortunately, is frequently injured by inhaled toxic materials, trauma, or medical procedures. Substantial or repeated airway epithelial injury can lead to dysregulated intrinsic repair pathways and aberrant tissue remodeling that can lead to dysfunctional airway epithelium.

A clinically relevant model of acute respiratory distress syndrome in human-size swine.

Despite over 30 years of intensive research for targeted therapies, treatment of acute respiratory distress syndrome (ARDS) remains supportive in nature. With mortality upwards of 30%, a high-fidelity pre-clinical model of ARDS, on which to test novel therapeutics, is urgently needed. We used the Yorkshire breed of swine to induce a reproducible model of ARDS in human-sized swine to allow the study of new therapeutics, from both mechanistic and clinical standpoints.

Pathological remodeling of distal lung matrix in end-stage cystic fibrosis patients.

Background: Manifestations of cystic fibrosis, although well-characterized in the proximal airways, are understudied in the distal lung. Characterization of the cystic fibrosis lung 'matrisome' (matrix proteome) has not been previously described, and could help identify biomarkers and inform therapeutic strategies.

Methods: We performed liquid chromatography-mass spectrometry, gene ontology analysis, and multi-modal imaging, including histology, immunofluorescence, and electron microscopy for a comprehensive evaluation of distal human lung extracellular matrix (matrix) structure and composition in end-stage cystic fibrosis.

Citrate-based materials fuel human stem cells by metabonegenic regulation.

A comprehensive understanding of the key microenvironmental signals regulating bone regeneration is pivotal for the effective design of bioinspired orthopedic materials. Here, we identified citrate as an osteopromotive factor and revealed its metabonegenic role in mediating citrate metabolism and its downstream effects on the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our studies show that extracellular citrate uptake through solute carrier family 13, member 5 (SLC13a5) supports osteogenic differentiation via regulation of energy-producing metabolic pathways, leading to elevated cell energy status that fuels the high metabolic demands of hMSC osteodifferentiation.