The Synthesis of Hydroquinolines from Nitroaldehydes and Ketones by Hydrogenation Sequences and Condensations.

Catalytic reaction discovery or methodology development is preferably performed with homogeneous catalysts, but heterogeneous catalysts allow the design of complex multistep syntheses based on their reusability. We introduce here the catalytic synthesis of hydroquinolines starting from nitroaldehydes, ketones and hydrogen. The reaction is complex and proceeds via multiple selective hydrogenation and condensation steps.

Continuous spectroscopic monitoring of urinary catheter output: advancements and clinical implications.

Urine diagnostics are crucial for identifying urological disorders and systemic diseases. Monitoring bladder catheters for urine output and early signs of urinary tract infections (UTIs) is essential but labor-intensive and prone to documentation errors. Recent advances in electronic monitoring and spectroscopy offer potential improvement in this process.

Characterization of the two-dimensional length and diameter distributions of gold nanorods by size exclusion chromatography.

Access to complex multidimensional property distributions of nanoparticle systems is indispensable for the understanding of their synthesis, processing and application in modern production technologies. Plasmonic gold nanorods are a system of particular interest due to their shape-dependent localized surface plasmon resonance. In this study, we show how the optical back coupling technique, previously developed for the analysis of sedimentation coefficient-resolved extinction spectra derived from analytical ultracentrifugation experiments, can be transferred to standard laboratory equipment, namely size exclusion chromatography.

TBK1 is involved in programmed cell death and ALS-related pathways in novel zebrafish models.

Pathogenic mutations within the TBK1 gene leading to haploinsufficiency are causative of amyotrophic lateral sclerosis (ALS). This gene is linked to autophagy and inflammation, two cellular mechanisms reported to be dysregulated in ALS patients, although its functional role in the pathogenesis could involve other players. We targeted the TBK1 ortholog in zebrafish, an optimal vertebrate model for investigating genetic defects in neurological disorders.

Structure and function of the geldanamycin amide synthase from Streptomyces hygroscopicus.

Amide synthases catalyze the formation of macrolactam rings from aniline-containing polyketide-derived seco-acids as found in the important class of ansamycin antibiotics. One of these amide synthases is the geldanamycin amide synthase GdmF, which we recombinantly expressed, purified and studied in detail both functionally as well as structurally. Here we show that purified GdmF catalyzes the amide formation using synthetically derived substrates.

β-catenin-driven endomesoderm specification is a Bilateria-specific novelty.

Endomesoderm specification by a maternal β-catenin signal and body axis patterning by interpreting a gradient of zygotic Wnt/β-catenin signalling was suggested to predate the split between Bilateria and their sister clade Cnidaria. However, in Cnidaria, the roles of β-catenin signalling in these processes have not been demonstrated directly. Here, by tagging the endogenous β-catenin in the cnidarian Nematostella vectensis, we confirm that its oral-aboral axis is indeed patterned by a gradient of β-catenin signalling.

Mapping variants in thyroid hormone transporter MCT8 to disease severity by genomic, phenotypic, functional, structural and deep learning integration.

Predicting and quantifying phenotypic consequences of genetic variants in rare disorders is a major challenge, particularly pertinent for 'actionable' genes such as thyroid hormone transporter MCT8 (encoded by the X-linked SLC16A2 gene), where loss-of-function (LoF) variants cause a rare neurodevelopmental and (treatable) metabolic disorder in males. The combination of deep phenotyping data with functional and computational tests and with outcomes in population cohorts, enabled us to: (i) identify the genetic aetiology of divergent clinical phenotypes of MCT8 deficiency with genotype-phenotype relationships present across survival and 24 out of 32 disease features; (ii) demonstrate a mild phenocopy in ~400,000 individuals with common genetic variants in MCT8; (iii) assess therapeutic effectiveness, which did not differ among LoF-categories; (iv) advance structural insights in normal and mutated MCT8 by delineating seven critical functional domains; (v) create a pathogenicity-severity MCT8 variant classifier that accurately predicted pathogenicity (AUC:0.91) and severity (AUC:0.

The translation inhibitors kasugamycin, edeine and GE81112 target distinct steps during 30S initiation complex formation.

During bacterial translation initiation, the 30S ribosomal subunit, initiation factors, and initiator tRNA define the reading frame of the mRNA. This process is inhibited by kasugamycin, edeine and GE81112, however, their mechanisms of action have not been fully elucidated. Here we present cryo-electron microscopy structures of 30S initiation intermediate complexes formed in the presence of kasugamycin, edeine and GE81112 at resolutions of 2.

Chromosome-level genome assembly of a specialist walnut pest Atrijuglans aristata.

Gelechioidea represents the most diverse superfamily of tiny boring pests in Lepidoptera that pose a serious threat to agricultural and forestry economic crops. However, the lack of high-quality genome of highly specialized species makes it difficult to draw general conclusions about the mechanism of the close binding relationship between pests and crops. In this study, based on second- and third-generation sequencing reads, we constructed a chromosome-level genome for the Atrijuglans aristata, a specialized boring pest, that specifically harms the green husk of cultivated walnuts.

New recommendations for reversal of high-dose methotrexate cytotoxicity with folinic acid.

Purpose: Folinic acid (FA) rescue protocols to counter the adverse effects of high-dose methotrexate (HDMTX) vary widely, and the risk of over-rescue and potential adverse effects of excessive FA (e.g., hypercalcemia) are under-recognized issues when providing augmented rescue in cases of delayed methotrexate elimination (DME).

First-Line Tislelizumab Plus Chemotherapy for Advanced Gastric Cancer with Programmed Death-Ligand 1 Expression ≥ 1%: A Retrospective Analysis of RATIONALE-305.

Introduction: Tislelizumab plus investigator-chosen chemotherapy (ICC) demonstrated a statistically significant improvement in overall survival (OS) versus placebo plus ICC in RATIONALE-305 in patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer/gastroesophageal junction cancer (GC/GEJC) in the intent-to-treat population and in patients with programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score ≥ 5%. The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against first-line treatment with programmed cell death protein-1 inhibitors in this setting in patients with a PD-L1 combined positive score < 1 or TAP score < 1%, due to an unfavorable benefit-risk profile. Thus, we retrospectively analyzed data from RATIONALE-305 in patients with a PD-L1 TAP score ≥ 1%.

Geographic Atrophy Secondary to Subclinical Angioid Streaks in Age-Related Macular Degeneration: Progression of the Disease at 2-Year Follow-Up.

Introduction: The purpose of the study is to characterize the rate of progression of geographic atrophy (GA) areas in patients with age-related macular degeneration (AMD) with subclinical angioid streaks (AS), compared to patients with AMD without subclinical AS.

Methods: This is a retrospective, longitudinal, case-control study. Among a cohort of patients with AMD, we selected patients with GA with subclinical AS and followed them for a 2-year follow-up.

CAG Repeat Instability and Region-Specific Gene Expression Changes in the SCA12 Brain.

Spinocerebellar ataxia type 12 (SCA12), an autosomal dominant cerebellar ataxia, caused by an expansion of (CAG) in the 5' of the PPP2R2B gene on chr5q32, is common in India. The illness often manifests late in life, with diverse neurological and psychiatric symptoms, suggesting involvement of different brain regions. Prominent neuronal loss and atrophy of the cerebellum have been noted earlier.

Update on the Treatment of Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is a mast cell-mediated skin disease that presents with wheals, angioedema, or both for more than 6 weeks. Less than 10% of patients have complete control of their CSU (the main goal of CSU treatment) with second generation H1-antihistamines, the first-line treatment. About 70% of patients with antihistamine-refractory CSU do not reach complete control with omalizumab, the second-line treatment.

Safety and complications of antimicrobial coated compared to conventional intramedullary femoral nails in proximal femoral fractures.

Purpose: The aim of this study was to compare one-year mortality and the incidence of complications, particularly fracture-related infections, between patients with proximal femur fractures treated with novel noble metal-coated implants and those treated with uncoated implants, to detect possible effects of the coating on these endpoints.

Methods: Design: Retrospective cohort observational study.

Setting: Level 1 trauma centre.

Tuft cell IL-17RB restrains IL-25 bioavailability and reveals context-dependent ILC2 hypoproliferation.

The tuft cell-group 2 innate lymphoid cell (ILC2) circuit orchestrates rapid type 2 responses upon detecting microbially derived succinate and luminal helminths. Our findings delineate key mechanistic steps involving IP3R2 engagement and Ca flux, governing interleukin-25 (IL-25) production by tuft cells triggered by succinate detection. While IL-17RB has a pivotal intrinsic role in ILC2 activation, it exerts a regulatory function in tuft cells.

Infectious diseases, cardio-cerebrovascular health and vaccines: pathways to prevention.

Cardiovascular and infectious diseases both feature among the leading causes of death among men and women in the world. The pathophysiological pathways of infection and cardiovascular disease intersect, and there is a bidirectional relationship between the two. Vaccines are available for the most common infectious diseases affecting older adults, such as influenza, pertussis, pneumococcal disease, herpes zoster, COVID and respiratory syncytial virus (RSV).

Dual antiplatelet pre-treatment with aspirin and ticagrelor in ACS patients undergoing unplanned aortocoronary bypass surgery.

Background: Major bleedings following coronary artery bypass grafting (CABG) have significant implications on outcomes in acute coronary syndrome (ACS) patients. Owing fears of fatal bleedings in case of urgent CABG, current guidelines recommend a cessation of P2Y receptor antagonists (P2Y-RA) before cardiac surgery and opt against routine pre-treatment with a P2Y-RA before coronary angiography (CA). However, sparse information exists outside randomized trials on the frequency of urgent CABG and the consequences of inappropriately long cessation of P2Y-RA treatment in patients presenting with ACS.

Biochar application using recycled annual self straw reduces long-term greenhouse gas emissions from paddy fields with economic benefits.

Paddy fields are major contributors to agricultural greenhouse gas emissions. Applying ~1% biochar by topsoil weight (high single, HS) effectively reduces greenhouse gas emissions from paddy fields, but long-term impacts are unclear. Here we present 8-year field experiments showing HS reduces CO equivalent per hectare by 59% and yields a net benefit of US$1,810 per hectare.

MYC ecDNA promotes intratumour heterogeneity and plasticity in PDAC.

Intratumour heterogeneity and phenotypic plasticity drive tumour progression and therapy resistance. Oncogene dosage variation contributes to cell-state transitions and phenotypic heterogeneity, thereby providing a substrate for somatic evolution. Nonetheless, the genetic mechanisms underlying phenotypic heterogeneity are still poorly understood.

Large recoverable elastic energy in chiral metamaterials via twist buckling.

Mechanical metamaterials with high recoverable elastic energy density, which we refer to as high-enthalpy elastic metamaterials, can offer many enhanced properties, including efficient mechanical energy storage, load-bearing capability, impact resistance and motion agility. These qualities make them ideal for lightweight, miniaturized and multi-functional structures. However, achieving high enthalpy is challenging, as it requires combining conflicting properties: high stiffness, high strength and large recoverable strain.

TGFβ links EBV to multisystem inflammatory syndrome in children.

In a subset of children and adolescents, SARS-CoV-2 infection induces a severe acute hyperinflammatory shock termed multisystem inflammatory syndrome in children (MIS-C) at four to eight weeks after infection. MIS-C is characterized by a specific T cell expansion and systemic hyperinflammation. The pathogenesis of MIS-C remains largely unknown.

High continuity of forager ancestry in the Neolithic period of the eastern Maghreb.

Ancient DNA from the Mediterranean region has revealed long-range connections and population transformations associated with the spread of food-producing economies. However, in contrast to Europe, genetic data from this key transition in northern Africa are limited, and have only been available from the far western Maghreb (Morocco). Here we present genome-wide data for nine individuals from the Later Stone Age through the Neolithic period from Algeria and Tunisia.

Genomic determinants of antigen expression hierarchy in African trypanosomes.

Antigenic variation is an immune evasion strategy used by many different pathogens. It involves the periodic, non-random switch in the expression of different antigens throughout an infection. How the observed hierarchy in antigen expression is achieved has remained a mystery.