Catalytic Enantioselective Synthesis of 1,4-(Hetero) Dicarbonyl Compounds through α-Carbonyl Umpolung.

The enantioselective synthesis of 1,4-dicarbonyl compounds continues to pose a significant challenge in organic synthesis, and a catalytic process which generates two adjacent stereogenic centers with full stereochemical control is lacking until now. The 1,4-relationship of the functional groups requires an Umpolung strategy as one of the α-carbonyl positions has to be inverted into an electrophilic center to react with a normal enolate. We report herein the highly enantio- and diastereoselective addition of silyl ketene acetals toward electrophilic 1-azaallyl cations to furnish chiral 4-hydrazonoesters, which are masked 1,4-dicarbonyl compounds.

Pharmacovigilance Pregnancy Data in a Population of Japanese Patients With Chronic Inflammatory Disease Exposed to Certolizumab Pegol.

Aim: Uncontrolled chronic inflammatory diseases (CIDs) before, during, and after pregnancy, as well as some CID medications, can increase the risk of impaired fertility in addition to adverse maternal/pregnancy outcomes in women of childbearing age. We report pregnancy outcomes from prospectively reported pregnancies in Japanese women treated with certolizumab pegol (CZP).

Methods: Data from July 2001 to November 2020 on CZP-exposed pregnancies from the CZP Pharmacovigilance safety database were reviewed.

Deep Learning and Multidisciplinary Imaging in Pediatric Surgical Oncology: A Scoping Review.

Background: Medical images play an important role in diagnosis and treatment of pediatric solid tumors. The field of radiology, pathology, and other image-based diagnostics are getting increasingly important and advanced. This indicates a need for advanced image processing technology such as Deep Learning (DL).

Mass Spectrometry Analysis of Chemically and Collisionally Dissociated Molecular Glue- and PROTAC-Mediated Protein Complexes Informs on Disassembly Pathways.

Molecular glues (MGs) and proteolysis-targeting chimeras (PROTACs) are used to modulate protein-protein interactions (PPIs), via induced proximity between compounds that have little or no affinity for each other naturally. They promote either reversible inhibition or selective degradation of a target protein, including ones deemed undruggable by traditional therapeutics. Though native MS (nMS) is capable of analyzing multiprotein complexes, the behavior of these artificially induced compounds in the gas phase is still not fully understood, and the number of publications over the past few years is still rather limited.

Subacute thyroiditis - Is it really linked to viral infection? Retrospective hospital patient registry study.

Objective: Subacute thyroiditis (SAT) is a painful inflammatory disorder of the thyroid gland, which - after a phase of thyrotoxicosis - leads to transient, or less frequently permanent hypothyroidism. Apart from a strong association with specific HLA alleles, the causes are uncertain. Viral disease has been hypothesised as a trigger, with Enteroviruses, namely Echoviruses and Coxsackieviruses, showing a seasonal distribution that coincides with the incidence of SAT.

Development of Lentiviral Packaging Cells and Scale Up of Production to Meet the Growing Demand in Cell and Gene Therapy.

Gamma-Retroviral (RVVs) and lentiviral vectors (LVVs) represent indispensable tools in somatic gene therapy, mediating the efficient, stable transfer of therapeutic genes into a variety of human target cells. LVVs, in contrast to RVVs, are capable of stably genetically modifying non-proliferating target cells, making them the superior instrument in cell and gene therapy. To date, the LVV manufacturing process employs human embryonic kidney cells (HEK293) and derivatives thereof transiently transfected with multiple plasmids encoding the required viral vector components.

Unlocking Platelet Mechanisms through Multi-Omics Integration: A Brief Review.

Platelets, tiny cell fragments measuring 2-4 μm in diameter without a nucleus, play a crucial role in blood clotting and maintaining vascular integrity. Abnormalities in platelets, whether genetic or acquired, are linked to bleeding disorders, increased risk of blood clots, and cardiovascular diseases. Advanced proteomic techniques offer profound insights into the roles of platelets in hemostasis and their involvement in processes such as inflammation, metastasis, and thrombosis.

Ionic Strength-Induced Compartmentalization for Nanogel-in-Microgel Colloids.

Compartmentalization is crucial for control over complex biological cascade reactions. In microgels, the formation of discrete compartments allows for simultaneous uptake and orthogonal release of physicochemically distinct drugs, among others. However, many state-of-the-art approaches yielding compartmentalized microgels require the use of specific, though not always biocompatible, components and temperatures well above the physiological range, which may damage possible biological cargo.

HOMAc: A Parameterization of the Harmonic Oscillator Model of Aromaticity (HOMA) That Includes Antiaromaticity.

The harmonic oscillator model of aromaticity (HOMA) offers a straightforward route to quantifying aromaticity that requires no other information than the bond lengths of the conjugated ring in question. Given that such information is often readily obtainable from quantum-chemical calculations, it is pertinent to improve this parametrized model as much as possible. Here, a new version of HOMA is presented where, atypically, the corresponding parameters are derived from the actual bond lengths of both aromatic and antiaromatic (rather than nonaromatic) reference compounds, as calculated with a high-level method.

Binding Kinetics of Self-Assembled Monolayers of Fluorinated Phosphate Ester on Metal Oxides for Underwater Aerophilicity.

The term "aerophilic surface" is used to describe superhydrophobic surfaces in the Cassie-Baxter wetting state that can trap air underwater. To create aerophilic surfaces, it is essential to achieve a synergy between a low surface energy coating and substrate surface roughness. While a variety of techniques have been established to create surface roughness, the development of rapid, scalable, low-cost, waste-free, efficient, and substrate-geometry-independent processes for depositing low surface energy coatings remains a challenge.

Supramolecular Gelation Based on Native Amino Acid Tyrosine and Its Charge-Transfer Complex Formation.

Self-assembly of amino acids and short-peptide derivatives attracted significant curiosity worldwide due to their unique self-assembly process and wide variety of applications. Amino acid is considered one of the important synthons in supramolecular chemistry. Self-assembly processes and applications of unfunctionalized native amino acids have been less reported in the literature.

Structural and Dynamic Assessment of Disease-Causing Mutations for the Carnitine Transporter OCTN2.

Primary carnitine deficiency (PCD) is a rare autosomal recessive genetic disorder caused by missense mutations in the SLC22A5 gene encoding the organic carnitine transporter novel type 2 (OCTN2). This study investigates the structural consequences of PCD-causing mutations, focusing on the N32S variant. Using an alpha-fold model, molecular dynamics simulations reveal altered interactions and dynamics suggesting potential mechanistic changes in carnitine transport.

Molecular docking to investigate HLA-associated idiosyncratic drug reactions.

Idiosyncratic drug reactions (IDRs) pose severe threats to patient health. Unlike conventionally dose-dependent side effects, they are unpredictable and frequently manifest as life-threatening conditions, such as severe cutaneous adverse reactions (SCARs) and drug-induced liver injury (DILI). Some HLA alleles, such as , , and , are known risk factors for adverse reactions induced by multiple drugs.

Genotoxicity testing of the anthraquinone dye Alizarin Red S.

The anthraquinone dye Alizarin Red S (ARS) is used for marking live animals, specifically as a tool for monitoring the stock of the endangered European eel by marking caught fish with ARS before releasing the eels back into the wild. As ARS can be found in recaptured eels even years later, knowledge of potential health hazards of ARS is essential for assessing the food safety of eels marked with ARS. As the compound class of anthraquinones is known for their genotoxic and carcinogenic properties, concerns were raised regarding the food safety of marked eels.

Impact of disease-modifying therapies on pregnancy outcomes in multiple sclerosis: a prospective cohort study from the German multiple sclerosis and pregnancy registry.

Background: In recent decades, relapsing remitting multiple sclerosis (MS) became more treatable through new disease-modifying therapies (DMTs). Identifying safe treatments with minimal fetal risks for family planning is needed.

Methods: In this prospective cohort from the German MS and Pregnancy Registry (DMSKW), we analyzed pregnancy and neonatal outcomes in MS-patients using descriptive statistics and logistic/linear regression models to compare DMT-exposed pregnancies to DMT-unexposed pregnancies.

Determination of spin Hall effect and spin diffusion length of Pt from self-consistent fitting of damping enhancement and inverse spin-orbit torque measurements.

Understanding the evolution of spin-orbit torque (SOT) with increasing heavy-metal thickness in ferromagnet/normal metal (FM/NM) bilayers is critical for the development of magnetic memory based on SOT. However, several experiments have revealed an apparent discrepancy between damping enhancement and damping-like SOT regarding their dependence on NM thickness. Here, using linewidth and phase-resolved amplitude analysis of vector network analyzer ferromagnetic resonance (VNA-FMR) measurements, we simultaneously extract damping enhancement and both field-like and damping-like inverse SOT in NiFe/Pt bilayers as a function of Pt thickness.

Weekly Intraperitoneal Injection of Tamoxifen in an Inducible In Vivo Model of Junctional Epidermolysis Bullosa Generates Early and Advanced Disease Phenotypes.

Junctional epidermolysis bullosa caused by loss-of-function variants in genes encoding the skin basement membrane proteins laminin 332, type XVII collagen, or integrin α6β4 affects patients from birth with severe blistering, eventually leading to scarring and early lethality. In this study, we have optimized a previously published junctional epidermolysis bullosa-knockout mouse model with weekly tamoxifen intraperitoneal injections, resulting in a more controllable and severe model. Owing to the titratable dosing, this model now recapitulates both early and advanced stages of the human disease, strengthening its use in therapeutic studies.

Endovascular therapy for iatrogenic occlusion of the popliteal artery after complex total knee arthroplasty: A case report.

Iatrogenic arterial injury is an infrequent but limb-threatening complication of total knee arthroplasty (TKA). Open surgical reconstruction may not always be feasible or optimal, particularly in patients who have recently just undergone complex TKA procedures. In this report, we describe the treatment of a patient who developed popliteal artery occlusion following a complex TKA procedure performed the previous day.

Combining Cre-LoxP and single-cell sequencing technologies: insights into the extracellular vesicle cargo transfer.

The recent study from the Pogge von Strandmann group published in , by Alashkar Alhamwe ., combined for the first time the Cre-LoxP recombination system with single-cell sequencing. The group monitored the tumor-derived extracellular vesicle (EV) uptake and the EV functions in the recipient non-malignant cells in a pancreatic ductal adenocarcinoma mouse model.