Chanoclavine synthase operates by an NADPH-independent superoxide mechanism.

More than ten ergot alkaloids comprising both natural and semi-synthetic products are used to treat various diseases. The central C ring forms the core pharmacophore for ergot alkaloids, giving them structural similarity to neurotransmitters, thus enabling their modulation of neurotransmitter receptors. The haem catalase chanoclavine synthase (EasC) catalyses the construction of this ring through complex radical oxidative cyclization.

How does a preference-based generic health-related quality of life measure perform in patients with a rare disease? Measurement properties of the EQ-5D-Y proxy version among underage patients with neurofibromatosis type 1.

Background: EQ-5D-Y is a pediatric preference-based health-related quality of life (HRQL) measure that is recommended in health economic evaluation according to China's guidelines. However, there is limited evidence regarding how the EQ-5D-Y perform in patients with rare diseases in the country. Neurofibromatosis type 1 (NF1) is a rare disease that affects the growth and development of underage patients.

A bio-based alginate hydrogel with considerable thermoelectric performance, mechanical strength and flame retardancy for ultra-fast and sustained early fire-alarm system.

Recently, the widespread utilization of combustible materials has increased the risks associated with building fires. Early fire-warning systems represent a pivotal strategy in mitigating losses incurred from fire incidents and offer considerable potential for the enhancement of fire safety management. This study focuses on the synthesis of bio-based ionic hydrogels, specifically calcium alginate/polyacrylamide/glycerol/lithium bromide (CPG-L), as a novel fire sensor.

Assessing Susceptibility of Grapevine Cultivars to Latent Infections Using Molecular Disease Index.

Traditional assessments of grapevine susceptibility to grapevine downy mildew (GDM) caused by rely on the visual evaluation of leaf symptoms. In this study, we used a well-established quantitative real-time PCR TaqMan assay (real-time PCR) to quantify the number of infecting 12 grapevine cultivars under controlled conditions. The molecular disease index (MDI), derived from molecular detection methods, reflects the relative abundance of pathogens in plant tissues during the latent infection phase.

Multi-crosslinked gelatin-based composite hydrogel featuring high thermoelectric performance and excellent flame retardancy for intelligent fire-warning system.

The frequency occurrence of building fires necessitates response materials with high flame retardancy and temperature sensitivity. Herein, we synthesized a gelatin/poly(acrylamide-co-acrylic acid)/lithium bromide/sodium phytate/glycerol hydrogel (Gly-GAPL) using in situ radical polymerization and solvent exchange techniques. Gly-GAPL exhibits notable thermoelectric performance (the Seebeck coefficient: 8.

New Sulfurated Butyrolactones from the Fungus Penicillium janthinellum.

Deep-sea derived fungi are considered as significant resources to discovery structurally diverse and biologically active natural compounds. In this study, four new sulfurated butyrolactones, penijanthiones A-D (1-4), together with four known analogues (5-8), were isolated from a Mariana Trench-derived fungus Penicillium janthinellum SH0301. Compounds 1-4 were the undescribed examples for natural butyrolactones coupling with a mercaptolactate moiety.

Long-term distress throughout one's life: health-related quality of life, economic and caregiver burden of patients with neurofibromatosis type 1 in China.

Introduction: Neurofibromatosis type 1 (NF1) is a rare genetic disorder, with lack of evidence of disease burden in China. We aimed to describe the economic burden, health-related quality of life (HRQL), and caregiver burden of NF1 patients in China.

Methods: We conducted an online cross-sectional survey employing the China Cloud Platform for Rare Diseases, with 223 caregivers of NF1 pediatric patients (patients under 18), and 226 adult patients.

Substrate specificity of a branch of aromatic dioxygenases determined by three distinct motifs.

The inversion of substrate size specificity is an evolutionary roadblock for proteins. The Duf4243 dioxygenases GedK and BTG13 are known to catalyze the aromatic cleavage of bulky tricyclic hydroquinone. In this study, we discover a Duf4243 dioxygenase PaD that favors small monocyclic hydroquinones from the penicillic-acid biosynthetic pathway.

Coronary heart disease increases the risk of perioperative ischemic stroke after noncardiac surgery: A retrospective cohort study.

Objective: To investigate the association between coronary heart disease (CHD) and the risk of perioperative ischemic stroke in patients undergoing noncardiac surgery.

Methods: This retrospective study evaluated the incidence of ischemic stroke within 30 days after a noncardiac surgery. A cohort of 221,541 patients who underwent noncardiac surgery between January 2008 and August 2019 was segregated according to whether they were diagnosed with CHD.

Synthetic Nicotinamide Cofactors as Alternatives to NADPH in Imine Reductase-Catalyzed Reactions.

This study demonstrates the effectiveness of synthetic nicotinamide cofactors as cost-effective alternatives to NADPH in imine reductase (IRED) catalysis. The synthetic cofactors maintained catalytic activity and stereoselectivity, achieving high conversion rates. Molecular docking studies revealed key structural interactions influencing performance.

Theoretical study of the substituent effects on the ESIPT mechanism of salicylideneaniline and the TICT photochemistry reactions.

The study of salicylideneaniline (SA) and its derivatives is critical due to their special photophysical properties and environmental sensitivity. In this work, the density time-dependent functional theory (TDDFT) and complete-active-space self-consistent-field (CASSCF) methods were carried out to calculate the substituent effect on excited-state properties and dynamics of SA derivatives. We found the para-substitution triggers the excited-state intramolecular proton transfer (ESIPT) reaction, exhibiting the dual-fluorescent phenomena.

Distribution of the active components from Xianglian Pill in tissues of healthy and antibiotic-associated diarrhea model mice and the mechanism study.

Antibiotic-associated diarrhea (AAD) is a common side effect of antibiotic therapy, characterized by intestinal inflammation which reduces the quality of life of patients. Xianglian Pill (XLP) has long been used to treat abdominal pain, diarrhea, bacillary dysentery and enteritis. Studies found that XLP has curative effect on AAD; however, the chemical constituents and mechanism of XLP have not been fully elucidated because of the lack of in vitro and in vivo studies.

Comparative transcriptomic insights into molecular mechanisms of the susceptibility wheat variety MX169 response to f. sp. () infection.

Unlabelled: Stripe rust of wheat is caused by the fungal pathogen f. sp. ().

Structural Optimization of Marine Natural Product Pretrichodermamide B for the Treatment of Colon Cancer by Targeting the JAK/STAT3 Signaling Pathway.

Marine natural product (MNP) pretrichodermamide B (Pre B, ) was identified as a novel STAT3 inhibitor in our previous work, while its metabolic instability hindered its further development. To address this drawback, ligand structure-based drug design was adopted leading to a series of Pre B derivatives. Among them, MNP trichodermamide B (tri B, ) obtained by skeletal rearrangement exhibited more potent antiproliferative activity with an IC value of 0.

Prelimbic cortical pyramidal neurons to ventral tegmental area projections promotes arousal from sevoflurane anesthesia.

Aims: General anesthesia has been used in surgical procedures for approximately 180 years, yet the precise mechanism of anesthetic drugs remains elusive. There is significant anatomical connectivity between the ventral tegmental area (VTA) and the prelimbic cortex (PrL). Projections from VTA dopaminergic neurons (VTA ) to the PrL play a role in the transition from sevoflurane anesthesia to arousal.

Resolving syntactic-semantic conflicts: comprehension and processing patterns by deaf Chinese readers.

The current study combined sentence plausibility judgment and self-paced reading tasks to examine the comprehension strategies and processing patterns of Chinese deaf individuals when comprehending written Chinese sentences with syntactic-semantic cue conflicts. Similar to findings from previous crosslinguistic studies on deaf readers, the Chinese deaf readers showed great variability in their comprehension strategies, with only 38% robustly relying on syntactic cues. Regardless of their overall comprehension preferences, the deaf readers all showed additional processing efforts as reflected by longer reading time at the verb regions when they relied on the syntactic cues.

Sevoflurane exerts antidepressant-like effects via the BDNF-TrkB pathway.

Depression has emerged as the predominant psychiatric affliction affecting individuals. Prior research has substantiated the antidepressant properties exhibited by numerous anesthetics. Sevoflurane, a widely utilized inhalant anesthetic in clinical practice, remains relatively uncharted in terms of its specific antidepressant effects.

A flame-retardant and conductive fabric-based triboelectric nanogenerator: Application in fire alarm and emergency evacuation.

The fabrics commonly used in architectural decorative materials pose significant fire hazards due to their flammability and rapid fire spread. Moreover, the traditional fire-alarm systems may fail to function properly in complex fire environments owing to power supply disruptions. In this study, we developed a low-cost and eco-friendly flame-retardant conductive fabric-based triboelectric nanogenerator (FCF-TENG) by integrating flame-retardant conductive nylon fabric and polytetrafluoroethylene soaked cotton fabric.

A deep lung cell atlas reveals cytokine-mediated lineage switching of a rare cell progenitor of the human airway epithelium.

The human airway contains specialized rare epithelial cells whose roles in respiratory disease are not well understood. Ionocytes express the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), while chemosensory tuft cells express asthma-associated alarmins. However, surprisingly, exceedingly few mature tuft cells have been identified in human lung cell atlases despite the ready identification of rare ionocytes and neuroendocrine cells.

Host-parasite interactions: a study on the pathogenicity of different Mesanophrys sp. densities and hemocytes-mediated parasitic resistance of swimming crabs (Portunus trituberculatus).

Mesanophrys sp. is a parasitic ciliate that invades and destroys the hemocytes of the swimming crab (Portunus trituberculatus). In the present study, we employed an in vitro model to elucidate how Mesanophrys sp.

Economic and Humanistic Burden of Osteoarthritis: An Updated Systematic Review of Large Sample Studies.

Objective: A previous systematic literature review demonstrated a significant economic and humanistic burden on patients with osteoarthritis (OA). The aim of this study was to systematically review and update the burden of OA reported by large sample studies since 2016.

Methods: We searched Medline (via Ovid) and Embase using the updated search strategy based on the previous review.

Semi-rational design of an imine reductase for asymmetric synthesis of alkylated -4-azepanamines.

Although imine reductase (IRED)-catalyzed reductive amination is promising for the synthesis of alkylated chiral amines, precisely regulating the stereoselectivity of IRED remains a great challenge. Herein, focusing on the residues directly in contact with the ketone moiety, we applied structure-guided semi-rational design to obtain the triple-mutant I149Y/L200H/W234K. This mutant showed high stereoselectivity, of up to >99% (), toward reductive amination of -Boc-4-oxo-azepane and different amines, and to the best of our knowledge is the first biocatalyst developed for asymmetric synthesis of chiral azepane-4-amines.

Identification of marine natural product Pretrichodermamide B as a STAT3 inhibitor for efficient anticancer therapy.

Unlabelled: The Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) regulates the expression of various critical mediators of cancer and is considered as one of the central communication nodes in cell growth and survival. Marine natural products (MNP) represent great resources for discovery of bioactive lead compounds, especially anti-cancer agents. Through the medium-throughput screening of our in-house MNP library, Pretrichodermamide B, an epidithiodiketopiperazine, was identified as a JAK/STAT3 signaling inhibitor.