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Triple-negative breast cancer (TNBC) has a high propensity for organ-specific metastasis. However, the underlying mechanisms are not well understood. Here, we show that the primary TNBC tumor-derived C-X-C motif chemokines 1/2/8 (CXCL1/2/8) stimulate lung resident fibroblasts to produce C-C motif chemokines 2/7 (CCL2/7), which in turn activate cholesterol synthesis in lung-colonizing TNBC cells and induce angiogenesis at lung metastatic sites. Inhibiting cholesterol synthesis in lung-colonizing breast tumor cells by the pulmonary administration of simvastatin-carrying HER3-targeting nanoparticles reduces the angiogenesis and growth of lung metastases in a syngeneic TNBC mouse model. Our findings reveal a novel, chemokine-regulated mechanism for the cholesterol synthesis pathway and a critical role of metastatic site-specific cholesterol synthesis in the pulmonary tropism of TNBC metastasis. The study has implications for the unresolved epidemiological observation that the use of cholesterol-lowering drugs has no effect on breast cancer incidence but can unexpectedly reduce breast cancer mortality, suggesting interventions of cholesterol synthesis in lung metastases as an effective treatment to improve survival in TNBC patients.Exercise training benefits the heart. The knowledge of post-transcription regulation, especially RNA editing, in the hearts remain rare. ADAR2 is an enzyme that edits adenosine to inosine nucleotides in double strand RNA, and RNA editing is associated with many human diseases. We found that ADAR2 was up-regulated in the hearts during exercise training. AAV9-mediated cardiac specific ADAR2 overexpression attenuated acute myocardial infarction (AMI), MI remodeling and doxorubicin-induced cardiotoxicity. In vitro, overexpression of ADAR2 inhibited doxorubicin-induced cardiomyocyte apoptosis but could also induce neonatal rat cardiomyocyte proliferation. Mechanistically, ADAR2 could regulate the abundance of mature miR-34a in cardiomyocytes. Regulations of miR-34a or its target genes (Sirt1, Cyclin D1, and Bcl2) could affect the pro-proliferation and anti-apoptosis effects of ADAR2 on cardiomyocyte. These data demonstrated that exercise-induced ADAR2 protects the heart from MI and doxorubicin-induced cardiotoxicity. Our work suggests that ADAR2 overexpression or a post-transcriptional associated RNA editing via ADAR2 might be a promising therapeutic strategy for heart diseases.Pelvic fixation is becoming an increasingly important caudal anchor point for long lumbar constructs, high-grade spondylolisthesis, fixation of sacral fractures, and support for 3-column osteotomies, by adding lumbosacral fixation anterior to the McCord pivot point. Iliac bolts were once common but have become less favorable due to screw head irritation and complications associated with connecting rods. S2-alar-iliac (S2AI) screws have been shown to achieve equivalent anchoring strength of constructs to the pelvis, while being lower profile and in line with the lumbar instrumentation. More recently, surgeons have noted the potential for S2AI screws to toggle and loosen, commonly in the softer sacrum, leading to caudal anchor failure and possible pseudarthrosis. The addition of triangular titanium implants to augment S2AI screws (bedrock technique) is a relatively new adaptation to reduce toggling on the S2AI screw and improve the overall stability of the pelvic fixation. read more Video 1 shows the placement of an S2AI screw and triangular titanium implant for pelvic fixation. The patient is a 68-year-old woman who presented with flat back syndrome, spinal stenosis, degenerative spondylolisthesis, pseudarthrosis of previously instrumented levels, and bilateral sacroiliitis. She underwent posterior instrumentation and fusion of L1 to S1 with pelvic fixation, open bilateral sacroiliac joint fusion, and multilevel Smith-Peterson osteotomies and transforaminal lumbar interbody fusions.Optic nerve head (ONH) biomechanics is centrally involved in the pathogenesis of glaucoma, a blinding ocular condition often characterized by elevation and fluctuation of the intraocular pressure and resulting loads on the ONH. Further, tissue viscoelasticity is expected to strongly influence the mechanical response of the ONH to mechanical loading, yet the viscoelastic mechanical properties of the ONH remain unknown. To determine these properties, we conducted micromechanical testing on porcine ONH tissue samples, coupled with finite element modeling based on a mixture model consisting of a biphasic material with a viscoelastic solid matrix. Our results provide a detailed description of the viscoelastic properties of the porcine ONH at each of its four anatomical quadrants (i.e., nasal, superior, temporal, and inferior). We showed that the ONH’s viscoelastic mechanical response can be explained by a dual mechanism of fluid flow and solid matrix viscoelasticity, as is common in other soft tissues. We obtained also be used to design and fabricate ex vivo 3D cultures to study glaucoma pathophysiology in a physiologically relevant environment, enabling the discovery of new generations of glaucoma medications focusing on neuroprotection.Prostate cancer (PC) is second-leading cancer in men, with limited treatment options available for men with advanced and metastatic PC. Prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) have been exploited as therapeutic targets in PC due to their upregulation in the advanced stages of the disease. To date, several PSA- and PSMA-activatable prodrugs have been developed to reduce the systemic toxicity of existing chemotherapeutics. Bioinspired nanovesicles have been exploited in drug delivery, offering prolonged drug blood circulation and higher tumour accumulation. For the first time, this study describes the engineering of dually targeted PSA/PSMA nanovesicles for advanced PC. PSMA-targeted bioinspired hybrids were prepared by hydrating a lipid film with anti-PSMA-U937 cell membranes and DOX-PSA prodrug, followed by extrusion. The bioinspired hybrids were characterised using dynamic light scattering, transmission electron microscopy, Dot blot, flow cytometry and Western blot. Cellular binding and toxicity studies in PC cancer cell lines were carried out using flow cytometry, confocal microscopy, and resazurin assay.