Baricitinib and tofacitinib off-target profile, with a focus on Alzheimer's disease.

Introduction: Janus kinase (JAK) inhibitors were recently identified as promising drug candidates for repurposing in Alzheimer's disease (AD) due to their capacity to suppress inflammation via modulation of JAK/STAT signaling pathways. Besides interaction with primary therapeutic targets, JAK inhibitor drugs frequently interact with unintended, often unknown, biological off-targets, leading to associated effects. Nevertheless, the relevance of JAK inhibitors' off-target interactions in the context of AD remains unclear.

Anterolateral augmentation procedures during anterior cruciate ligament reconstructions in skeletally immature patients: Scoping review of surgical techniques and outcomes.

Purpose: Graft failure rates after anterior cruciate ligament reconstruction (ACLR) in children and adolescents are higher compared to adults. Anterolateral augmentation procedures have recently generated increased focus regarding their ability to reduce graft failure rates. Concerns in skeletally immatures are potential growth disturbances and overconstraint after anterolateral augmentation.

Bioluminescent detection of viral surface proteins using branched multivalent protein switches.

Fast and reliable virus diagnostics is key to prevent the spread of viruses in populations. A hallmark of viruses is the presence of multivalent surface proteins, a property that can be harnessed to control conformational switching in sensor proteins. Here, we introduce a new sensor platform (dark-LUX) for the detection of viral surface proteins consisting of a general bioluminescent framework that can be post-translationally functionalized with separately expressed binding domains.

Microvascular Dysfunction and Whole-Brain White Matter Connectivity: The Maastricht Study.

Background: Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole-brain white matter connectivity.

Orthotopic equine study confirms the pivotal importance of structural reinforcement over the pre-culture of cartilage implants.

In articular cartilage (AC), the collagen arcades provide the tissue with its extraordinary mechanical properties. As these structures cannot be restored once damaged, functional restoration of AC defects remains a major challenge. We report that the use of a converged bioprinted, osteochondral implant, based on a gelatin methacryloyl cartilage phase, reinforced with precisely patterned melt electrowritten polycaprolactone micrometer-scale fibers in a zonal fashion, inspired by native collagen architecture, can provide long-term mechanically stable neo-tissue in an orthotopic large animal model.

Artificial cells with viscoadaptive behavior based on hydrogel-loaded giant unilamellar vesicles.

Viscoadaptation is an essential process in natural cells, where supramolecular interactions between cytosolic components drive adaptation of the cellular mechanical features to regulate metabolic function. This important relationship between mechanical properties and function has until now been underexplored in artificial cell research. Here, we have created an artificial cell platform that exploits internal supramolecular interactions to display viscoadaptive behavior.

Effect of temperature on the CO splitting rate in a DBD microreactor.

A novel plate-to-plate dielectric barrier discharge microreactor (micro DBD) has been demonstrated in CO splitting. In this design, the ground electrode has a cooling microchannel to maintain the electrode temperature in the 263-298 K range during plasma operation. A small gap size between the electrodes of 0.

Discovery of lead quinone cathode materials for Li-ion batteries.

Organic cathode materials are attractive candidates for the development of high-performance Li-ion batteries (LIBs). The chemical space of candidate molecules is too vast to be explored solely by experiments; however, it can be systematically explored by a high-throughput computational search that incorporates a spectrum of screening techniques. Here, we present a time- and resource-efficient computational scheme that incorporates machine learning and semi-empirical quantum mechanical methods to study the chemical space of approximately 200 000 quinone-based molecules for use as cathode materials in LIBs.

Plasma ceramides relate to mild cognitive impairment in middle-aged men: The Maastricht Study.

Introduction: There is an urgent need for biomarkers identifying individuals at risk of early-stage cognitive impairment. Using cross-sectional data from The Maastricht Study, this study included 197 individuals with mild cognitive impairment (MCI) and 200 cognitively unimpaired individuals aged 40 to 75, matched by age, sex, and educational level.

Methods: We assessed the association of plasma sphingolipid and ceramide transfer protein (CERT) levels with MCI and adjusted for potentially confounding risk factors.

Recent advances in permeable polymersomes: fabrication, responsiveness, and applications.

Polymersomes are vesicular nanostructures enclosed by a bilayer-membrane self-assembled from amphiphilic block copolymers, which exhibit higher stability compared with their biological analogues ( liposomes). Due to their versatility, polymersomes have found various applications in different research fields such as drug delivery, nanomedicine, biological nanoreactors, and artificial cells. However, polymersomes prepared with high molecular weight components typically display low permeability to molecules and ions.

Biomechanical evaluation of a novel biomimetic artificial intervertebral disc in canine cervical cadaveric spines.

Background Context: Cervical disc replacement (CDR) aims to restore motion of the treated level to reduce the risk of adjacent segment disease (ASD) compared with spinal fusion. However, first-generation articulating devices are unable to mimic the complex deformation kinematics of a natural disc. Thus, a biomimetic artificial intervertebral CDR (bioAID), containing a hydroxyethylmethacrylate (HEMA)-sodium methacrylate (NaMA) hydrogel core representing the nucleus pulposus, an ultra-high-molecular-weight-polyethylene fiber jacket as annulus fibrosus, and titanium endplates with pins for primary mechanical fixation, was developed.

Tracking the mechanism of covalent molecular glue stabilization using native mass spectrometry.

Molecular glues are powerful tools for the control of protein-protein interactions. Yet, the mechanisms underlying multi-component protein complex formation remain poorly understood. Native mass spectrometry (MS) detects multiple protein species simultaneously, providing an entry to elucidate these mechanisms.

Virtual screening of organic quinones as cathode materials for sodium-ion batteries.

High-throughput virtual screening (HTVS) has been increasingly applied as an effective approach to find candidate materials for energy applications. We performed a HTVS study, which is powered by: (i) automated virtual screening library generation, (ii) automated search on a readily purchasable chemical space of quinone-based compounds, and (iii) computed physicochemical descriptors for the prediction of key battery-related features of compounds, including the reduction potential, gravimetric energy density, gravimetric charge capacity, and molecular stability. From the initial virtual library of approximately 450k molecules, a total of 326 compounds have been identified as commercially available.

Review of the Scalable Core-Shell Synthesis Methods: The Improvements of Li-Ion Battery Electrochemistry and Cycling Stability.

The demand for lithium-ion batteries has significantly increased due to the increasing adoption of electric vehicles (EVs). However, these batteries have a limited lifespan, which needs to be improved for the long-term use needs of EVs expected to be in service for 20 years or more. In addition, the capacity of lithium-ion batteries is often insufficient for long-range travel, posing challenges for EV drivers.

On design of plasma jet reactor for non-oxidative methane conversion.

Non-oxidative methane coupling in an atmospheric pressure plasma jet reactor with an internal diameter of 3.0 mm has been studied. The jet reactor consisted of a quartz tube surrounded by a copper ring and a stainless-steel tube, which were separated by a variable distance.

Dynamic loading leads to increased metabolic activity and spatial redistribution of viable cell density in nucleus pulposus tissue.

Background: Nucleus pulposus (NP) cell density is orchestrated by an interplay between nutrient supply and metabolite accumulation. Physiological loading is essential for tissue homeostasis. However, dynamic loading is also believed to increase metabolic activity and could thereby interfere with cell density regulation and regenerative strategies.

Harmonization and standardization of nucleus pulposus cell extraction and culture methods.

Background: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources.

Multivalent effect of peptide functionalized polymeric nanoparticles towards selective prostate cancer targeting.

The concept of selective tumor targeting using nanomedicines has been around for decades; however, no targeted nanoparticle has yet reached the clinic. A key bottleneck is the non-selectivity of targeted nanomedicines , which is attributed to the lack of characterization of their surface properties, especially the ligand number, thereby calling for robust techniques that allow quantifiable outcomes for an optimal design. Multivalent interactions comprise multiple copies of ligands attached to scaffolds, allowing simultaneous binding to receptors, and they play an important role in targeting.

L-type Voltage-Gated calcium channels partly mediate Mechanotransduction in the intervertebral disc.

Background: Intervertebral disc (IVD) degeneration continues to be a major global health challenge, with strong links to lower back pain, while the pathogenesis of this disease is poorly understood. In cartilage, much more is known about mechanotransduction pathways involving the strain-generated potential (SGP) and function of voltage-gated ion channels (VGICs) in health and disease. This evidence implicates a similar important role for VGICs in IVD matrix turnover.

Temporal Trends in Incidence of Premature Cardiovascular Disease Over the Past 7 Decades: The Framingham Heart Study.

Background Premature onset of cardiovascular disease (CVD) imposes a significant societal burden and challenges prevention efforts. Methods and Results Trends in the incidence of premature CVD (before age 55, 60, or 65 years, separate analysis for each threshold) were evaluated in 14 464 Framingham Heart Study participants over 7 decades of observation (1950-2019). The change in the incidence of premature CVD (per decade) in men and women was assessed using overdispersed Poisson regression (accounting for cohort effects), adjusting for age at entry and age at onset of premature CVD within each decade.

LPV modeling of nonlinear systems: A multi-path feedback linearization approach.

This article introduces a systematic approach to synthesize linear parameter-varying (LPV) representations of nonlinear (NL) systems which are described by input affine state-space (SS) representations. The conversion approach results in LPV-SS representations in the observable canonical form. Based on the relative degree concept, first the SS description of a given NL representation is transformed to a normal form.

Marker-Independent Monitoring of and Degradation of Supramolecular Polymers Applied in Cardiovascular Tissue Engineering.

The equilibrium between scaffold degradation and neotissue formation, is highly essential for tissue engineering. Herein, biodegradable grafts function as temporal roadmap to guide regeneration. The ability to monitor and understand the dynamics of degradation and tissue deposition in cardiovascular graft materials is therefore of great value to accelerate the implementation of safe and sustainable tissue-engineered vascular grafts (TEVGs) as a substitute for conventional prosthetic grafts.

Can super-resolution microscopy become a standard characterization technique for materials chemistry?

The characterization of newly synthesized materials is a cornerstone of all chemistry and nanotechnology laboratories. For this purpose, a wide array of analytical techniques have been standardized and are used routinely by laboratories across the globe. With these methods we can understand the structure, dynamics and function of novel molecular architectures and their relations with the desired performance, guiding the development of the next generation of materials.

Buyers' role in innovation procurement: Evidence from US military R&D contracts.

This study provides the first quantification of buyers' role in the outcome of R&D procurement contracts. We combine together four data sources on US federal R&D contracts, follow-on patented inventions, federal public workforce characteristics, and perception of their work environment. By exploiting the observability of deaths of federal employees, we find that managers' death events negatively affect innovation outcomes: a 1% increase in the share of relevant public officer deaths causes a decline of 32.

Identification of molecular glues of the SLP76/14-3-3 protein-protein interaction.

The stabilisation of protein-protein interactions (PPIs) through molecular glues is a novel and promising approach in drug discovery. In stark contrast to research in protein-protein inhibition the field of stabilisation remains underdeveloped with comparatively few examples of small-molecule stabilisers of PPIs reported to date. At the same time identifying molecular glues has received recent sustained interest, especially in the fields of targeted protein degradation and 14-3-3 PPIs.