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The gastrointestinal (GI) tract is a site of replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans, which commensal bacteria that bathe the human mucosa are known to modify. To explore human gut HS-modifying bacterial abundances and how their presence may impact SARS-CoV-2 infection, we developed a task-based analysis of proteoglycan degradation on large-scale shotgun metagenomic data. We observed that gut bacteria with high predicted catabolic capacity for HS differ by age and sex, factors associated with coronavirus disease 2019 (COVID-19) severity, and directly by disease severity during/after infection, but do not vary between subjects with COVID-19 comorbidities or by diet. Gut commensal bacterial HS-modifying enzymes reduce spike protein binding and infection of authentic SARS-CoV-2, suggesting that bacterial grooming of the GI mucosa may impact viral susceptibility.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019, can infect the gastrointestinal (GI) tract, and individuals who exhibit GI symptoms often have more severe disease. The GI tract's glycocalyx, a component of the mucosa covering the large intestine, plays a key role in viral entry by binding SARS-CoV-2's spike protein via heparan sulfate (HS). Here, using metabolic task analysis of multiple large microbiome sequencing data sets of the human gut microbiome, we identify a key commensal human intestinal bacteria capable of grooming glycocalyx HS and modulating SARS-CoV-2 infectivity in vitro . Moreover, we engineered the common probiotic Escherichia coli Nissle 1917 (EcN) to effectively block SARS-CoV-2 binding and infection of human cell cultures. Understanding these microbial interactions could lead to better risk assessments and novel therapies targeting viral entry mechanisms.

Background: The Flow Re-Direction Endoluminal Device X (FRED X) offers several benefits over other flow-diverter devices including an antithrombotic coating, optimized in-vessel stability, and increased flexibility for easier device placement. We present a to-date experience of the safety and utility of the FRED X device in the repair of posterior and anterior circulation aneurysms., Methods: A retrospective review was conducted on all endovascular procedures that utilized the FRED X device at our center from May 2022 to November 2023., Results: 77 patients (72.7% women, mean age 58.9), underwent a total of 85 procedures using the FRED X device. Indications included treatment of incidentally discovered aneurysms, acute dissections, aneurysm rupture, repair of residual filling following prior intervention, and use of FRED X for recanalization of non-aneurysmal extracranial stroke. 31.3% of the aneurysms were in the posterior circulation, 68.7% were in the anterior circulation. 9.4% of patients presented with SAH due to acute aneurysm rupture. Patients treated with FRED X were separated into OFF-Label (40.0%) or ON-label (60.0%) indications. Occlusion rate at 6-month follow-up were 72.2% in the OFF-label group, 66.7% in the ON-label group, and 68.4% overall. Rate of major periprocedural complications was 1.2% and the cumulative rate of postprocedural complication at follow-up was 5.3%., Conclusion: This study shows that FRED X treatment of intracranial aneurysms is safe in both OFF-label and ON-label indications. Continued follow-up of our patient population will further establish the safety, efficacy, and long-term stability of this device., Competing Interests: Declaration of conflicting interestsThe authors declared the following conflict of interest: Y.J.Z, F.H., and S.T serve as consultants for microvention (Aliso Viejo, CA, USA) and Stryker (Portage, MI, USA).

We introduce a protocol for generating 3D organoids from circulating tumor cells (CTCs), enabling longitudinal functional and molecular analyses in pancreatic cancer patients, including those with unresectable disease, which constitutes the majority of cases. We outline the process for isolating and characterizing CTCs from the blood of pancreatic cancer patients and provide detailed instructions for initiating, passaging, and phenotyping CTC-derived organoids. Additionally, we describe techniques for utilizing these organoids in drug screening with a focus on stemness-related pathways. For complete details on the use and execution of this protocol, please refer to Tang et al. 1 ., Competing Interests: Declaration of interests M.Ø.A., T.M.C., T.G.T., and A. Salanti are shareholders of VAR2 Pharmaceuticals ApS, hold a patent on utilizing rVAR2 for diagnosing cancer, and were not involved in the data analysis., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)