Mediated Reactions Research Articles

Flushing in children with cutaneous mastocytosis

Introduction. Flushing is a subjective feeling of warmth that is accompanied by redness of the skin on any part of the body, but mainly on the face, neck and upper trunk. Episodic flushing with other symptoms associated with mast cell mediators can be observed in 30–50% of children with cutaneous mastocytosis (CM).Aim. To analyze the frequency of flushing in children with various clinical forms of cutaneous mastocytosis. To study serum tryptase levels in children with flushing.Materials and methods. The study included data from 275 children aged from 6 months to 17 years inclusive, who were undergoing outpatient treatment and observation at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology from March 2022 until January 2024. The concentration of tryptase in the blood was determined by immunofluo-rescence on a three-dimensional porous solid phase (ImmunoCAP technology, Pharmacia Diagnostics AB, Sweden). Polarization and immersion dermatoscopy with 20x magnification were performed.Results. Flushings were observed in 17.5% of patients out of 275 observed children with CM. The level of tryptase more than 15 µg/l was determined in 20.8% of children with flushing, above 11.0 µg/l – in 37.5%. Tryptase levels were higher than 8.0 µg/L in 22 (45.8%) patients. In 25.0% of patients with flushing, tryptase levels did not exceed 5 µg/L. The severity of the vascular pattern in lesions and apparently healthy skin was characteristic of patients with frequent or prolonged flushing and tryptase levels above 8.0 µg/L.Conclusion. This study was the first in the Russian Federation to demonstrate the prevalence of flushing in children with various clinical forms of cutaneous mastocytosis. The results showed that the assessment of serum tryptase levels should be performed in all children with flushing, regardless of the clinical form of mastocytosis, including those with isolated and multiple skin mastocytomas. Clinical laboratory and dermatoscopic monitoring are important for the development of individual therapeutic tactics and prevention of mediator reactions and anaphylaxis.

Light-Induced Reactivity Switch at O2-Activating Bioinspired Copper(I) Complexes.

Using light to unveil unexplored reactivities of earth-abundant metal-oxygen intermediates is a formidable challenge, given the already remarkable oxidation ability of these species in the ground state. However, the light-induced reactivity of Cu-O2 intermediates still remains unexplored, due to the photoejection of O2 under irradiation. Herein, we describe a photoinduced reactivity switch of bioinspired O2-activating CuI complexes, based on the archetypal tris(2-pyridyl-methyl)amine (TPA) ligand. This report represents a key precedent for light-induced reactivity switch in Cu-O2 chemistry, obtained by positioning C-H substrates in close proximity of the active site. Open and caged CuI complexes displaying an internal aryl ether substrate were evaluated. Under light, a Cu-O2 mediated reaction takes place that induces a selective conversion of the internal aryl ether unit to a phenolate-CH2- moiety with excellent yields. This light-induced transformation displays high selectivity and allows easy postfunctionalization of TPA-based ligands for straightforward preparation of challenging heteroleptic structures. In the absence of light, O2 activation results in the standard oxidative cleavage of the covalently attached substrate. A reaction mechanism that supports a monomeric cupric-superoxide-dependent reactivity promoted by light is proposed on the basis of reactivity studies combined with (TD-) DFT calculations.

Colorimetric and fluorometric determination of uric acid by a suspension-based assay using enzyme-immobilized micro-sized particles.

Daily monitoring of serum uric acid levels is very important to provide appropriate treatment according to the constitution and lifestyle of individual hyperuricemic patients. We have developed a suspension-based assay to measure uric acid by adding a sample solution to the suspension containing micro-sized particles immobilized on uricase and horseradish peroxidase (HRP). In the proposed method, the mediator reaction of uricase, HRP, and uric acid produces resorufin from Amplex red. This resorufin is adsorbed onto enzyme-immobilized micro-sized particles simultaneously with its production, resulting in the red color of the micro-sized particles. The concentration of resorufin on the small surface area of the microscopic particles achieves a colorimetric analysis of uric acid with superior visibility. In addition, ethanol-induced desorption of resorufin allowed quantitative measurement of uric acid using a 96-well fluorescent microplate reader. The limit of detection (3σ) and RSD (n = 3) were estimated to be 2.2 × 10-2μg/mL and ≤ 12.1%, respectively. This approach could also be applied to a portable fluorometer.

Evidence of Selection in Mineral Mediated Polymerization Reactions Executed in a Robotic Chemputer System

AbstractIt has long been thought that abiogenesis requires a process of selection and evolution at the molecular level, but this process is hard to explore experimentally. One solution could be the use of automation in experiments which could allow for traceability and the ability to explore a larger reaction space. We report a fully programmable and automated platform to explore the reactions of amino acids in the presence of mineral environments. The robotic system is based upon the Chemputer system which has well defined modules, software, and a chemical programming language to orchestrate the chemical processes, including analysis. The reaction mixtures were analysed with tandem mass spectrometry and a peptide sequencing algorithm. Each experiment was screened for 1,398,100 possible unique sequences, and more than 550 specifically defined sequences were confirmed experimentally. This work aimed to develop a new understanding of selection in repeated cycles of polymerisation reactions to explore the emergence of well‐defined amino acid sequences. We found that the outcome of oligomerisation was significantly influenced by the presence of different minerals, and that a serpentine environment selects glycine and phenylalanine rich fragments that enable the formation of longer oligomers with well‐defined sequences as a function of cycle number.

Continuous Flow Synthesis of Benzotriazin-4(3H)-ones via Visible Light Mediated Nitrogen-Centered Norrish Reaction.

We report a new protocol for the synthesis of substituted benzotriazin-4(3H)-ones which are underrepresented heterocyclic scaffolds with important pharmacological properties. Our method exploits acyclic aryl triazine precursors that undergo a photocyclization reaction upon exposure to violet light (420 nm). Continuous flow reactor technology is exploited to afford excellent yields in only 10 min residence time with no additives or photocatalysts needed. The underlying reaction mechanism appears to be based on an unprecedented variation of the classical Norrish type II reaction with concomitant fragmentation and formation of N-N bonds. Scalability, process robustness, and green credentials of this intriguing transformation are highlighted.

Visible-Light Mediated Reaction of Indole with Aryl Halides Using Porphyrin Photocatalyst: A Feasible Technique to Afford N-Functionalized Indoles

Visible-Light Mediated Reaction of Indole with Aryl Halides Using Porphyrin Photocatalyst: A Feasible Technique to Afford N-Functionalized Indoles

Insight into the Role of NH3/NH4+ and NOx/NO3- in the Formation of Nitrogen-Containing Brown Carbon in Chinese Megacities.

Particulate brown carbon (BrC) plays a crucial role in the global radiative balance due to its ability to absorb light. However, the effect of molecular formation on the light absorption properties of BrC remains poorly understood. In this study, atmospheric BrC samples collected from six Chinese megacities in winter and summer were characterized through ultrahigh-performance liquid chromatography coupled with Orbitrap mass spectrometry (UHPLC-Orbitrap MS) and light absorption measurements. The average values of BrC light absorption coefficient at a wavelength of 365 nm (babs365) in winter were approximately 4.0 times higher than those in summer. Nitrogen-containing organic molecules (CHNO) were identified as critical components of light-absorbing substances in both seasons, underscoring the importance of N-addition in BrC. These nitrogen-containing BrC chromophores were more closely related to nitro-containing compounds originating from biomass burning and nitrogen oxides (NOx)/nitrate (NO3-) reactions in winter. In summer, they were related to reduced N-containing compounds formed in ammonia (NH3)/ammonium (NH4+) reactions. The NH3/NH4+-mediated reactions contributed more to secondary BrC in summer than winter, particularly in southern cities. Compared with winter, the higher O/Cw, lower molecule conjugation indicator (double bond equivalent, DBE), and reduced BrC babs365 in summer suggest a possible bleaching mechanism during the oxidation process. These findings strengthen the connection between molecular composition and the light-absorbing properties of BrC, providing insights into the formation mechanisms of BrC chromophores across northern and southern Chinese cities in different seasons.

Biodegradable Ferric Phosphate Nanocarriers with Tumor‐Specific Activation and Glutathione Depletion for Tumor Self‐Enhanced Ferroptosis and Chemotherapy

AbstractFerroptosis is a regulatory cell death that is dependent on iron‐mediated lipid peroxidation and cell membrane damage. The use of iron‐based nanocarriers to activate ferroptosis is of great significance in oncotherapy. However, the limited endogenous hydrogen peroxide (H2O2) and high expression of glutathione (GSH) in tumor cells restrict the efficiency of iron‐based nanocarriers in inducing ferroptosis. Herein, a ferric phosphate nanotherapeutic system (denoted as FeP@HCPT‐HA) is reported with H2O2‐supply and GSH‐elimination properties for tumor self‐enhanced ferroptosis and chemotherapy. FeP@HCPT‐HA is obtained by a coprecipitation method with the in situ loading of 10‐hydroxycamptothecin (HCPT), followed by the modification of hyaluronic acid (HA). FeP@HCPT‐HA actively targets CD44‐overexpressed tumor cells and degrades in acidic tumor microenvironment to release HCPT, Fe2+ and Fe3+. As a chemotherapy drug, HCPT not only induces tumor cell apoptosis but also supplies H2O2 for Fe2+‐mediated Fenton reaction to enhance ferroptosis. The released Fe3+ depletes GSH by the redox reaction between Fe3+ and GSH, which down‐regulates the expression of glutathione peroxidase 4 (GPX4) and enhances lipid peroxidation, resulting in enhanced ferroptosis. The integration of tumor targeting and tumor‐specific activation, as well as H2O2‐supply and GSH‐elimination, endow the FeP@HCPT‐HA with effective tumor growth inhibition by the enhanced ferroptosis and chemotherapy.

Evaluation of Antibiotic Allergy in the Ambulatory Setting Using a Standardized Questionnaire

Patients are sometimes mislabeled as having an immune-mediated antibiotic allergy in their medical records. Therefore, the aim of this study was to investigate the prevalence of subjects with non-immune mediated reactions to antibiotics using a standardized questionnaire. Subjects aged 18 years and older with a documented antibiotic allergy were identified and recruited from 2 outpatient clinics in the greater Chicago area. Subjects completed a standardized questionnaire during a single visit regarding their previous adverse reaction to an antibiotic. For subjects with multiple documented antibiotic allergies, 1 questionnaire was filled out for each antibiotic allergy. Investigators subsequently evaluated the questionnaire responses to determine whether the adverse reaction was a true immune-mediated allergic reaction or an adverse drug reaction. A total of 98 subjects were recruited with completion of 159 questionnaires. Eighteen subjects (18.37%, 95% CI: 10.7%, 26.3%) had antibiotic allergy labels with no corresponding immune-mediated reaction history. There were 35 allergy labels (22.0%, 95% CI: 14.7%, 29.4%) that were unlikely to be immune-mediated. Antibiotics with the highest percentage of clinical histories that were unlikely to be immune-mediated were macrolides (8 of 11 subjects), nitrofurantoin (1 of 2 subjects), and amoxicillin/clavulanate (2 of 8 subjects). The most common antibiotic allergy labels were penicillin (43 of 159 subjects), sulfonamides (25 of 159 subjects), and fluoroquinolones (21 of 159 subjects). Identification of adverse reactions to antibiotics that are unlikely to be immune-mediated can be accomplished using a standardized questionnaire in the outpatient setting. Improved identification of low-risk antibiotic allergy labels can guide de-labeling initiatives to improve antibiotic prescribing.

Pollen food allergy syndrome secondary to molds and raw mushroom cross-reactivity: a case report

BackgroundPollen food allergy syndrome (PFAS) is an immunoglobulin E (IgE) mediated reaction that causes oropharyngeal pruritus or angioedema due to homologous proteins present in the culprit food as well as a sensitizing aeroallergen. This cross-reactivity has been well established between pollen and fruits/vegetables. Given the evolutionary similarity between all fungi; cross-reactivity between spore forming microfungi and edible macrofungi have been suggested, however only a limited number of case reports have ever been published on this phenomenon. We present a case of a patient who experiences pollen food allergy syndrome-like symptoms following lightly cooked mushroom ingestion who otherwise was able to tolerate cooked mushrooms. We then review the literature to highlight the limited studies of an underrecognized PFAS cross-reactivity between molds and mushrooms.Case presentationA 15-year-old male presents with symptoms of seasonal and perennial allergic rhinitis was found to have multiple environmental sensitizations to molds via skin prick testing (C.gramineum, A.Pullulans and B.cinerea) and ImmunoCAP serum-specific IgE (A.alternata, C. herbarum, and P. notatum). He developed throat pruritus and subjective throat tightness following ingestion of mushroom containing pizza. ImmunoCAP serum specific IgE to whole mushroom was negative but fresh food prick testing to fresh portobello mushroom and cremini mushroom were both positive with a negative test to canned mushroom. The patient then underwent a graded oral challenge and successfully tolerated canned mushrooms.ConclusionThis case highlights the potential cross-reactivity between microfungi aeroallergens and edible fungi, leading to PFAS-like reactions in susceptible individuals. The patient’s ability to tolerate canned mushrooms suggests a possible heat-labile protein as the cause of the reaction, similar to PFAS patients tolerating cooked but not raw fruits/vegetables. Positive skin prick test to both spore-forming fungi and edible fungi with negative and whole mushroom IgE results further support the hypothesis of cross-reactivity and sensitization. Further research is needed to identify the specific allergenic proteins involved in these cross-reactions and the susceptible species of mold and mushroom. Understanding these components will contribute to improved diagnosis and management of mold and mushroom allergies, and enhance our knowledge of allergenic cross-reactivity in general.

Integration of transcriptome and machine learning to identify the potential key genes and regulatory networks affecting drip loss in pork.

Low level of drip loss is an important quality characteristic of meat with high economic value. However, the key genes and regulatory networks contributing to drip loss in pork remain largely unknown. To accurately identify the key genes affecting drip loss in muscles postmortem, 12 Duroc × (Landrace × Yorkshire) pigs with extremely high (n ＝ 6, H group) and low (n ＝ 6, L group) drip loss at both 24h and 48h postmortem were selected for transcriptome sequencing. The analysis of differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were performed to find the overlapping genes using the transcriptome data, and functional enrichment and protein-protein interaction (PPI) network analysis were conducted using the overlapping genes. Moreover, we used machine learning to identify the key genes and regulatory networks related to drip loss based on the interactive genes of the PPI network. Finally, nine potential key genes (IRS1, ESR1, HSPA6, INSR, SPOP, MSTN, LGALS4, MYLK2, and FRMD4B) mainly associated with the MAPK signaling pathway, the insulin signaling pathway, and the calcium signaling pathway were identified, and a single-gene set enrichment analysis (GSEA) was performed to further annotate the functions of these potential key genes. The GSEA results showed that these genes are mainly related to ubiquitin mediated proteolysis and oxidative reactions. Taken together, our results indicate that the potential key genes influencing drip loss are mainly related to insulin signaling mediated differences in glycolysis and ubiquitin mediated changes in muscle structure and improves the understanding of gene expression and regulation related to drip loss and contributes to future molecular breeding for improving pork quality.

Oxone® Mediated Regioselective C(sp2)−H Selenylation and Thiocyanation of Pyrazolo[1,5‐a]pyrimidines at Room Temperature

AbstractA mild Oxone® mediated reaction for direct regioselective C−H selenylation and thiocyanation of pyrazolo[1,5‐a]pyrimidines is established at ambient temperature. This practical and efficient methodology employs Oxone® as a user friendly, green, non‐toxic and cheap reagent to facilitate selenylation and thiocyanation at room temperature. The present method offers high regioselectivity, broad substrate scope, mild conditions and excellent yields. Further, this eco‐friendly approach could easily be extended for mild C−H selenylation and thiocyanation of other heterocycles. Mechanistic studies indicate that the reaction occurs through electrophilic substitution mechanism via generation of an electrophilic chalcogen species.

Operando investigations of the solid electrolyte interphase in the lithium mediated nitrogen reduction reaction

Operando GI-WAXS showed that the SEI layer formed by LiBF4 enhances Li-NRR performance by limiting proton transport to the electrode. Intermediate LiNxHy species give insight into the mechanism of Li-NRR.

Loss of Lipocalin2 confers cisplatin vulnerability through modulating NF-ĸB mediated ferroptosis via ferroportin.

Cisplatin is a widely used anti-cancer drug. Unfortunately, many cancers often develop resistance, which contributes to tumor recurrence and poorly prognosis. Growing knowledge has suggested the therapeutic potential of ferroptosis in cancer. Lipocalin2 (LCN2) is demonstrated to be a critical iron metabolic factor and implies in ferroptosis. Here, we aim to explore its role in chemotherapy resistance. The influence of LCN2 on colorectal cancer (CRC) cell chemoresistance and ferroptosis were evaluated by in vitro and in vivo approaches. The interaction between LCN2, NF-ĸB and ferroportin (FPN) was assessed by western blots, immunohistochemistry and dual luciferase reporter assays. Results showed that LCN2 was highly expressed in tumor regression grade 1 (TRG1) cases than that in TRG3 specimens. Loss of LCN2 contributed to resistance to cisplatin-induced ferroptosis. Mechanistically, loss of LCN2 inhibited cisplatin sensitivity and cisplatin-induced ferroptosis through elevating FPN expression which was regulated by NF-ĸB, subsequently reducing Fe2+ mediated Fenton reaction. Furthermore, FPN expression rate was much lower in TRG1 cases, and negative correlation between LCN2 and FPN expression was observed in clinical specimens. Collectively, low LCN2 expression enhances insensitivity of cisplatin to CRC cells via Fenton reaction mediated ferroptosis. LCN2/NF-ĸB/FPN pathway might be potentially utilized for chemoresistance strategy. LCN2 and FPN expression might be a promising biomarker of chemotherapy effect for CRC patients.

How We Prevented an anti-P1 Mediated Hemolytic Transfusion Reaction.

How We Prevented an anti-P1 Mediated Hemolytic Transfusion Reaction.

Kidneys and commonly used medications: how to reduce a risk of acute kidney injury in everyday practice?

Medications are a common cause of acute kidney injury (AKI). There are various mechanisms in which medications can induce AKI, and better understanding of their pathophysiology can aid in clinical recognition, treatment, and prevention of this condition. Hemodynamic‑mediated AKI is often associated with drugs that alter renal perfusion and its autoregulation. Acute tubular injury is a result of direct renal tubular cell toxicity. Acute interstitial nephritis is a T‑cell-mediated immune hypersensitivity reaction to drugs leading to tubule‑interstitial inflammation and AKI. Crystalline nephropathy can be caused by crystallization of medications or by altered urinary chemistry caused by medications. Some medications can evoke AKI through uncommon mechanisms, such as glomerulonephritis and thrombotic microangiopathy. Notably, some medications may cause a phenomenon called "pseudo‑AKI," where serum creatinine is elevated without actual reduction in kidney function. Medications commonly used in clinical practice are reviewed with a focus on their mechanisms of injury, diagnosis, treatment, and prevention. Recognizing common medications associated with AKI is an important first step in reducing the risk of this condition. For each medication, understanding general and specific risk factors for AKI allows for early identification and timely discontinuation of offending agents. These measures can help mitigate the risk of AKI and promote renal recovery.

Design, synthesis, and applications of plasmonic semiconductor WO3−x photocatalyst

Different synthesis and characterization techniques for WO3−x photocatalysts and recent developments in the application of visible-NIR mediated transformation reactions.

Bio-chemical Ferrous ions (Fe2+) Mediated Fenton Reaction: A Biological Prodigy for Curing and Developing Autoimmune Rheumatoid Arthritis and Cancer

Bio-chemical Ferrous ions (Fe2+) Mediated Fenton Reaction: A Biological Prodigy for Curing and Developing Autoimmune Rheumatoid Arthritis and Cancer

Going for gold - the chemistry of structurally authenticated gold(I)-ethylene complexes.

Gold coordination chemistry and catalysis involving unsaturated hydrocarbons such as olefins have experienced a remarkable growth during the last few decades. Despite the importance, isolable and well-characterized molecules with ethylene, the simplest and the most widely produced olefin, on gold are still limited. This review aims to cover features of, and strategies utilized to stabilize, gold-ethylene complexes and their diverse use in chemical transformations and homogeneous catalytic processes. Isolable and well-authenticated gold-ethylene complexes are important not only for structural, spectroscopic, and bonding studies but also as models for likely intermediates in gold mediated reactions of alkenes and gold-alkene species observed in the gas phase. There has also been development on AuI/III catalytic cycles. Nitrogen based ligands have been the most widely utilized ligand supports thus far for the successful stabilization of gold-ethylene adducts. Gold has a bright future in olefin chemistry and with ethylene.

A transaminase-mediated aldol reaction and applications in cascades to styryl pyridines.

Transaminase enzymes are well established biocatalysts that are used in chemical synthesis due to their beneficial sustainability profile, regio- and stereoselectivity and substrate specificity. Here, the use of a wild-type Chromobacterium violaceum transaminase (CvTAm) in enzyme cascades revealed the formation of a novel hydroxystyryl pyridine product. Subsequent studies established it was a transaminase mediated reaction where it was exhibiting apparent aldolase reactivity. This promiscuous enzyme reaction mechanism was then explored using other wild-type transaminases and via the formation of CvTAm mutants. Application of one pot multi-step enzyme cascades was subsequently developed to produce a range of hydroxystyryl pyridines.