Wnt/β-Catenin Signaling in Liver Pathobiology.

The liver has a critical role in regulating host metabolism, immunity, detoxification, and homeostasis. Proper liver function is essential for host health, and dysregulation of hepatic signaling pathways can lead to the onset of disease. The Wnt/β-catenin signaling pathway is an important regulator of liver homeostasis and function.

Northwestern University resource and education development initiatives to advance collaborative artificial intelligence across the learning health system.

Introduction: The rapid development of artificial intelligence (AI) in healthcare has exposed the unmet need for growing a multidisciplinary workforce that can collaborate effectively in the learning health systems. Maximizing the synergy among multiple teams is critical for Collaborative AI in Healthcare.

Methods: We have developed a series of data, tools, and educational resources for cultivating the next generation of multidisciplinary workforce for Collaborative AI in Healthcare.

Loss of β-catenin reveals a role for glutathione in regulating oxidative stress during cholestatic liver disease.

Background: Cholestasis is an intractable liver disorder that results from impaired bile flow. We have previously shown that the Wnt/β-catenin signaling pathway regulates the progression of cholestatic liver disease through multiple mechanisms, including bile acid metabolism and hepatocyte proliferation. To further explore the impact of these functions during intrahepatic cholestasis, we exposed mice to a xenobiotic that causes selective biliary injury.

Synthesis of Phenol-Pyridinium Salts Enabled by Tandem Electron Donor-Acceptor Complexation and Iridium Photocatalysis.

Herein, we describe a dual photocatalytic system to synthesize phenol-pyridinium salts using visible light. Utilizing both electron donor-acceptor (EDA) complex and iridium(III) photocatalytic cycles, the C-N cross-coupling of unprotected phenols and pyridines proceeds in the presence of oxygen to furnish pyridinium salts. Photocatalytic generation of phenoxyl radical cations also enabled a nucleophilic aromatic substitution (SAr) of a fluorophenol with an electron-poor pyridine.

Adolescence and the Microbiome: Implications for Healthy Growth and Maturation.

The gut microbiota was initially thought to develop into a stable, adult-like profile during early postnatal life. The formation of the gut microbiota during early life has been shown to contribute to healthy growth and has lifelong implications for host health. Adolescence, the developmental period between childhood and adulthood, is a critical window for healthy growth and maturation.

Antibiotic prophylaxis dysregulates dental implant placement surgery-induced osteoimmune wound healing and attenuates the alveolar bone-implant interface in mice.

Aim: Antimicrobial-induced shifts in commensal oral microbiota can dysregulate helper T-cell oral immunity to affect osteoclast-osteoblast actions in alveolar bone. Antibiotic prophylaxis is commonly performed with dental implant placement surgery to prevent post-surgical complications. However, antibiotic prophylaxis effects on osteoimmune processes supporting dental implant osseointegration are unknown.

Commensal Microbiota Effects on Craniofacial Skeletal Growth and Morphology.

Microbes colonize anatomical sites in health to form commensal microbial communities (e.g., commensal gut microbiota, commensal skin microbiota, commensal oral microbiota).

Inhibiting Wnt Signaling Reduces Cholestatic Injury by Disrupting the Inflammatory Axis.

Background & Aims: β-Catenin, the effector molecule of the Wnt signaling pathway, has been shown to play a crucial role in bile acid homeostasis through direct inhibition of farnesoid X receptor (FXR), which has pleiotropic effects on bile acid homeostasis. We hypothesize that simultaneous suppression of β-catenin signaling and activation of FXR in a mouse model of cholestasis will reduce injury and biliary fibrosis through inhibition of bile acid synthesis.

Methods: To induce cholestasis, we performed bile duct ligation (BDL) on wild-type male mice.

Recent advances in oxidative phenol coupling for the total synthesis of natural products.

Covering: 2008 to 2023This review will describe oxidative phenol coupling as applied in the total synthesis of natural products. This review covers catalytic and electrochemical methods with a brief comparison to stoichiometric and enzymatic systems assessing their practicality, atom economy, and other measures. Natural products forged by C-C and C-O oxidative phenol couplings as well as from alkenyl phenol couplings will be addressed.

Bridging the gap: A library-based collaboration to enhance data skills for clinical researchers.

Introduction: Enterprise data warehouses (EDWs) serve as foundational infrastructure in a modern learning health system, housing clinical and other system-wide data and making it available for research, strategic, and quality improvement purposes. Building on a longstanding partnership between Northwestern University's Galter Health Sciences Library and the Northwestern Medicine Enterprise Data Warehouse (NMEDW), an end-to-end clinical research data management (cRDM) program was created to enhance clinical data workforce capacity and further expand related library-based services for the campus.

Methods: The training program covers topics such as clinical database architecture, clinical coding standards, and translation of research questions into queries for proper data extraction.

Large field-of-view short-wave infrared metalens for scanning fiber endoscopy.

Significance: The scanning fiber endoscope (SFE), an ultrasmall optical imaging device with a large field-of-view (FOV) for having a clear forward view into the interior of blood vessels, has great potential in the cardiovascular disease diagnosis and surgery assistance, which is one of the key applications for short-wave infrared biomedical imaging. The state-of-the-art SFE system uses a miniaturized refractive spherical lens doublet for beam projection. A metalens is a promising alternative that can be made much thinner and has fewer off-axis aberrations than its refractive counterpart.

Prolonged Antibiotic Exposure during Adolescence Dysregulates Liver Metabolism and Promotes Adiposity in Mice.

Antibiotic administration during early life has been shown to have lasting effects on the gut microbiota, which have been linked to sustained alterations in liver metabolism and adiposity. Recent investigations have discerned that the gut microbiota continues to develop toward an adult-like profile during adolescence. However, the impact of antibiotic exposure during adolescence on metabolism and adiposity is unclear.

C3a-C3aR signaling is a novel modulator of skeletal homeostasis.

Osteoimmune studies have identified complement signaling as an important regulator of the skeleton. Specifically, complement anaphylatoxin receptors (i.e.

Minocycline-induced disruption of the intestinal FXR/FGF15 axis impairs osteogenesis in mice.

Antibiotic-induced shifts in the indigenous gut microbiota influence normal skeletal maturation. Current theory implies that gut microbiota actions on bone occur through a direct gut/bone signaling axis. However, our prior work supports that a gut/liver signaling axis contributes to gut microbiota effects on bone.

Photocatalytic Synthesis of -Peroxyquinols: Total Synthesis of (±)-Stemenone B and (±)-Parvistilbine B.

A photocatalytic method to selectively synthesize 4-hydroperoxy-2,5-cyclohexadienones from -alkyl phenols is disclosed. This photosensitized singlet oxygen approach functionalized a variety of electronically diverse -alkyl phenols in 27-99% isolated yields. Utilizing this dearomative oxidation, (±)-stemenone B and (±)-parvistilbine B were synthesized in 9 and 11 steps, respectively, from commercially available starting materials.

Ten simple rules for maximizing the recommendations of the NIH data management and sharing plan.

The National Institutes of Health (NIH) Policy for Data Management and Sharing (DMS Policy) recognizes the NIH's role as a key steward of United States biomedical research and information and seeks to enhance that stewardship through systematic recommendations for the preservation and sharing of research data generated by funded projects. The policy is effective as of January 2023. The recommendations include a requirement for the submission of a Data Management and Sharing Plan (DMSP) with funding applications, and while no strict template was provided, the NIH has released supplemental draft guidance on elements to consider when developing a plan.

Exploring the prevalence, impact and experience of cardiac cachexia in patients with advanced heart failure and their caregivers: A sequential phased study.

Background: Cardiac Cachexia is a wasting syndrome that has a significant impact on patient mortality and quality of life world-wide, although it is poorly understood in clinical practice.

Aim: Identify the prevalence of cardiac cachexia in patients with advanced New York Heart Association (NYHA) functional class and explore its impact on patients and caregivers.

Design: An exploratory cross-sectional study.

O-pH: Optical pH Monitor to Measure Dental Biofilm Acidity and Assist in Enamel Health Monitoring.

Objective: Bacteria in the dental biofilm produceacid after consumption of carbohydrates which if left unmonitored leads to caries formation. We present O-pH, a device that can measure dental biofilm acidity and provide quantitative feedback to assist in oral health monitoring.

Method: O-pH utilizes a ratiometric pH sensing method by capturing fluorescence of Sodium Fluorescein, an FDA approved chemical dye.

Commensal gut bacterium critically regulates alveolar bone homeostasis.

The alveolar bone is a unique osseous tissue due to the presence of the teeth and the proximity of commensal oral microbes. Commensal microbe effects on alveolar bone homeostasis have been attributed to the oral microbiota, yet the impact of commensal gut microbes is unknown. Study purpose was to elucidate whether commensal gut microbes regulate osteoimmune mechanisms and skeletal homeostasis in alveolar bone.

Antimicrobial-induced oral dysbiosis exacerbates naturally occurring alveolar bone loss.

Periodontitis-mediated alveolar bone loss is caused by dysbiotic shifts in the commensal oral microbiota that upregulate proinflammatory osteoimmune responses. The study purpose was to determine whether antimicrobial-induced disruption of the commensal microbiota has deleterious effects on alveolar bone. We administered an antibiotic cocktail, minocycline, or vehicle-control to sex-matched C57BL/6T mice from age 6- to 12 weeks.

The varied role, scope of practice, and education of cardiovascular nurses in ESC-affiliated countries: an ACNAP survey.

Aims: Cardiovascular disease burden is increasing globally, pressuring nursing staff to deliver high-quality care across a diverse range of treatment areas. As such, an evaluation of the educational preparation of nurses is needed. To determine the current role, scope of practice, education level, and needs of cardiovascular nurses working across the European Society of Cardiology (ESC)-affiliated countries.

Branched-chain α-ketoacids are preferentially reaminated and activate protein synthesis in the heart.

Branched-chain amino acids (BCAA) and their cognate α-ketoacids (BCKA) are elevated in an array of cardiometabolic diseases. Here we demonstrate that the major metabolic fate of uniformly-C-labeled α-ketoisovalerate ([U-C]KIV) in the heart is reamination to valine. Activation of cardiac branched-chain α-ketoacid dehydrogenase (BCKDH) by treatment with the BCKDH kinase inhibitor, BT2, does not impede the strong flux of [U-C]KIV to valine.