Search

Objective·To determine the levels of nasally exhaled nitric oxide (FnNO) combined with fractional concentration of exhaled nitric oxide (FeNO) in children with asthma (AS) complicated with allergic rhinitis (AR), and analyze the levels of FnNO and FeNO in different clinical stages of AS with different severities of AR, so as to provide basis for guiding clinical diagnosis and treatment.Methods·Children diagnosed with AR with AS in the Department of Respiratory and Otolaryngology of Children's Hospital of Soochow University from April 2021 to November 2021 were included, and healthy children who visited the Department of Pediatrics for normal physical examination during the same period were enrolled as the control group. FeNO and FnNO were measured in all children to assess the severity of the children's diseases. The levels of FeNO and FnNO in children with AR and AS at different clinical stages of AS and their correlation with pulmonary function were compared and analyzed.Results·The proportion of persistent moderate-to-severe rhinitis was higher in the acute exacerbation stage of AS, and the proportion of intermittent mild rhinitis was higher in the clinical remission stage of AS. The FeNO level in the acute exacerbation stage were higher than that in the chronic persistent stage and clinical remission stage of AS (adjusted P=0.022, 0.000), and higher in the chronic persistent stage than that in the clinical remission stage of AS (adjusted P=0.002). The FnNO level in the acute exacerbation stage was higher than that in the clinical remission stage of AS (adjusted P=0.044). In the chronic persistent stage of AS, the FnNO levels in the persistent mild group and persistent moderate-to-severe control group were higher than those in the intermittent mild group (adjusted P=0.001, 0.000). In the clinical remission stage of AS, the FnNO levels in the persistent mild group and persistent moderate to severe control group were higher than those in the intermittent mild group (adjusted P=0.001, 0.007). In the intermittent mild group of AR, the FnNO levels in the acute exacerbation stage were higher than those in the chronic persistent stage and clinical remission stage of AS (adjusted P=0.010, 0.019). Part of pulmonary functions in the acute exacerbation stage of AS children were negatively correlated with the FeNO and FnNO levels (all P

This study focuses on investigating the prevalence of various airborne pollens and their correlation with clinical characteristics of childhood respiratory allergic diseases in southeastern China. Methods: From November 2020 to October 2021, this research employed Durham monitoring samplers to collect airborne pollen. Simultaneously, skin prick tests (SPTs) were performed on children with respiratory allergic conditions at the Children's Hospital of Soochow University and standardised questionnaires are also administered to assess children's symptoms. Results: Over the course of November 2020 to October 2021, the study identified more than 36 pollen species. Notably, the spring season (March to May) exhibited the highest pollen concentrations, with Broussonetia accounting for 30.04% and Pinus for 26.38%. Similarly, the autumn months (September to October) saw prominent taxa like Humulus scandens (47.55%) and Gramineae (35.93%). Among the patients, a significant 92.7% exhibited positive reactions, with 81.7% showing sensitization to house dust mites (HMD), 17.8% to pollen, and 3.7% to Cockroach. Noteworthy the five most common pollens were observed for Bermuda (6.0%), Elm pollen (6.0%), Birch pollen (4.6%), and Mugwort (4.6%). The study indicated a substantial multisensitized ratio among pollen-sensitized patients in comparison to non-pollen-sensitized ones (97.4% vs 1.6%, P < 0.001). Moreover, weekly total airborne pollen concentrations showed positive correlations with weekly admissions due to allergic rhinitis(AR)(r=0.642, P < 0.001), bronchial asthma (BA) (r= 0.472, P< 0.001), and the coexistence of AR and BA (r=0.485, P < 0.001). Conclusion: The findings found that there were two peaks of pollen count in a year during March-May and September-October. The findings emphasize the critical role of specific airborne pollens in driving sensitization and exacerbating respiratory allergic diseases in children. [ABSTRACT FROM AUTHOR]

The PAK (p21-activated kinases) family is a class of intracellular signal transduction protein kinases that regulate various cellular functions, mainly through their interactions with small GTP enzymes. PAK1 and PAK2 in the PAK kinase family are key signal transduction molecules that play important roles in various biological processes, including morphological changes, migration, proliferation, and apoptosis, and are involved in the progression of many diseases. Abnormal expression or dysregulation of PAK1 and PAK2 may be associated with several diseases, including cancer, neurological diseases, etc. The current research mainly focuses on studying the role of PAK and PAK inhibitors in the regulation of cancer progression, but relatively few reports are available that explore their potential role in cardiovascular diseases. Vascular injury and repair are complex processes involved in many cardiovascular conditions, including atherosclerosis, restenosis, and hypertension. Emerging research suggests that PAK1 and PAK2 have pivotal roles in vascular endothelial cell functions, including migration, proliferation, and angiogenesis. These kinases also modulate vascular smooth muscle relaxation, vascular permeability, and structural alterations, which are critical in the development of atherosclerosis and vascular inflammation. By targeting these activities, PAK proteins are essential for both normal vascular physiology and the pathogenesis of vascular diseases, highlighting their potential as therapeutic targets for vascular health. This review focuses on recent studies that offer experimental insights into the mechanisms by which PAK1 and PAK2 regulate the biological processes of vascular injury and repair and the therapeutic potential of the current existing PAK inhibitors in vascular-related diseases. The limitations of treatment with some PAK inhibitors and the ways that future development can overcome these challenges are also discussed. [ABSTRACT FROM AUTHOR]

As a new and popular medium, bullet comments are popular among young people, and the presence of bullet comments is particularly indispensable in bilibili auto-tune remix-themed content video. The pop-ups themselves have not been a one-day success, but there are many political, economic and social and cultural influences, and the culture of the bullet comments, which originated in Japan, has fused with the culture of Chinese subtitling groups in China, making our bullet comment culture more locally. In fact, many of the internet buzzwords come from online pop-ups, and the auto-tune remix-themed content area, as a gathering place for very talented uploaders, is naturally not short of inspired viewers, and the classic bullet comments from them are gradually becoming visible in many mainstream cultures, and are also used by many influential celebrities or a significant portion of the public, causing a wider spread.From these cultural phenomena, it is easy to see that the producers of auto-tune remix-themed bullet comments have a strong secondary production capacity for specific cultures and a vigorous vitality for cultural products. Therefore, the study of the language of auto-tune remix-themed bullet comments has great significance and reference value for the diversification of cultural industries in the era of online culture and new media.This paper uses literature research, participant observation and inductive analysis to analyse the characteristics and significance of the language of bullet comments in bilibili auto-tune remix-themed content video.

Although significant efforts have been undertaken to explore the toughening of epoxy resins, it remains challenges to establish a simple and effective toughening technique which does not compromise its strength, thermal stability and processing performance. In this paper, toluene‐diisocyanate‐trimer (TDI‐T) was utilized to manufacture a novel epoxy‐terminated dendritic modifier TDI‐T glycol diglycidyl ether (TDI‐T GLDE). When the addition of TDI‐T GLDE reaches 20% of the resin mass, the tensile strength, tensile elongation, compressive strength and impact strength were increased by 28.1%, 75%, 24.8%, and 138.0% respectively, compared to E‐51. The thermal properties of the samples have been improved, including an increased glass transition temperature (Tg) from 68.2 to 73.2°C, as well as an increase in the initial decomposition temperature from 240.6 to 257.7°C. The toughening mechanism of TDI‐T GLDE was studied through a combination of mechanical performance tests, thermal performance tests, and resin fracture surface morphology analysis. [ABSTRACT FROM AUTHOR]

Covalent adaptable networks (CANs), leveraging the dynamic exchange of covalent bonds, emerge as a promising material to address the challenge of irreversible cross‐linking in thermosetting polymers. In this work, we explore the introduction of a catalyst‐free and associative C=C/C=N metathesis reaction into thermosetting polyurethanes, creating CANs with superior stability, solvent resistance, and thermal/mechanical properties. By incorporating this dynamic exchange reaction, stress‐relaxation is significantly accelerated compared to imine‐bond‐only networks, with the rate adjustable by modifying substituents in the ortho position of the dynamic double bonds. The obtained plasticity enables recycle without altering the chemical structure or mechanical properties, and is also found to be vital for achieving shape memory functions with complex spatial structures. This metathesis reaction as a new dynamic crosslinker of polymer networks has the potential to accelerate the ongoing exploration of malleable and functional thermoset polymers. [ABSTRACT FROM AUTHOR]

Shock is characterized with vascular hyporesponsiveness to vasoconstrictors, thereby to cause refractory hypotension, insufficient tissue perfusion, and multiple organ dysfunction. The vascular hyporeactivity persisted even though norepinephrine and fluid resuscitation were administrated, it is of critical importance to find new potential target. Ion channels are crucial in the regulation of cell membrane potential and affect vasoconstriction and vasodilation. It has been demonstrated that many types of ion channels including K+ channels, Ca2+ permeable channels, and Na+ channels exist in vascular smooth muscle cells and endothelial cells, contributing to the regulation of vascular homeostasis and vasomotor function. An increasing number of studies suggested that the structural and functional alterations of ion channels located in arteries contribute to vascular hyporesponsiveness during shock, but the underlying mechanisms remained to be fully clarified. Therefore, the expression and functional changes in ion channels in arteries associated with shock are reviewed, to pave the way for further exploring the potential of ion channel‐targeted compounds in treating refractory hypotension in shock. [ABSTRACT FROM AUTHOR]

Dithioacetals are heavily used in organic, material and medical chemistries, and exhibit huge potential to synthesize degradable or recyclable polymers. However, the current synthetic approaches of dithioacetals and polydithioacetals are overwhelmingly dependent on external catalysts and organic solvents. Herein, we disclose a catalyst‐ and solvent‐free acetal‐thiol click‐like reaction for synthesizing dithioacetals and polydithioacetals. High conversion, higher than acid catalytic acetal‐thiol reaction, can be achieved. High universality was confirmed by monitoring the reactions of linear and cyclic acetals (including renewable bio‐sourced furan‐acetal) with aliphatic and aromatic thiols, and the reaction mechanism of monomolecular nucleophilic substitution (SN1) and auto‐protonation (activation) by thiol was clarified by combining experiments and density functional theory computation. Subsequently, we utilize this reaction to synthesize readily recyclable polydithioacetals. By simple heating and stirring, linear polydithioacetals with M‾ ${\bar M}$ w of ~110 kDa were synthesized from acetal and dithiol, and depolymerization into macrocyclic dithioacetal and repolymerization into polydithioacetal can be achieved; through reactive extrusion, a semi‐interpenetrating polymer dynamic network with excellent mechanical properties and continuous reprocessability was prepared from poly(vinyl butyral) and pentaerythritol tetrakis(3‐mercaptopropionate). This green and high‐efficient synthesis method for dithioacetals and polydithioacetals is beneficial to the sustainable development of chemistry. [ABSTRACT FROM AUTHOR]

BACKGROUND: High blood pressure has been suggested to accelerate vascular injury-induced neointimal formation and progression. However, little is known about the intricate relationships between vascular injury and hypertension in the context of arterial remodeling. METHODS: Single-cell RNA-sequencing analysis was used to depict the cell atlas of carotid arteries of Wistar Kyoto rats and spontaneously hypertensive rats with or without balloon injury. RESULTS: We found that hypertension significantly aggravated balloon injury-induced arterial stenosis. A total of 36 202 cells from carotid arteries with or without balloon injury were included in single-cell RNA-sequencing analysis. Cell composition analysis showed that vascular injury and hypertension independently induced distinct aortic cell phenotypic alterations including immune cells, endothelial cells (ECs), and smooth muscle cells. Specifically, our data showed that injury and hypertension-induced specific EC phenotypic alterations, and revealed a transition from functional ECs to hypermetabolic, and eventually dysfunctional ECs in hypertensive rats upon balloon injury. Importantly, our data also showed that vascular injury and hypertension-induced different smooth muscle cell phenotypic alterations, characterized by deferential expression of synthetic signatures. Interestingly, pathway analysis showed that dysregulated metabolic pathways were a common feature in monocytes/macrophages, ECs, and smooth muscle cells in response to injury and hypertension. Functionally, we demonstrate that inhibition of mitochondrial respiration significantly ameliorated injury-induced neointimal formation in spontaneously hypertensive rats. CONCLUSIONS: This study provides the cell landscape changes of the main aortic cell phenotypic alterations in response to injury and hypertension. Our findings suggest that targeting cellular mitochondrial respiration could be a novel therapeutic for patients with hypertension undergoing vascular angioplasty. [ABSTRACT FROM AUTHOR]

The α2A adrenergic receptor (α2A-AR) serves as a critical molecular target for sedatives and analgesics. However, α2A-AR ligands with an imidazole ring also interact with an imidazoline receptor as well as other proteins and lead to undesirable effects, motivating us to develop more novel scaffold α2A-AR ligands. For this purpose, we employed an ensemble-based ligand discovery strategy, integrating long-term molecular dynamics (MD) simulations and virtual screening, to identify new potential α2A-AR agonists with novel scaffold. Our results showed that compounds SY-15 and SY-17 exhibited significant biological effects in the preliminary evaluation of protein kinase A (PKA) redistribution assays. They also reduced levels of intracellular cyclic adenosine monophosphate (cAMP) in a dose-dependent manner. Upon treatment of the cells with 100 μM concentrations of SY-15 and SY-17, there was a respective decrease in the intracellular cAMP levels by 63.43% and 53.83%. Subsequent computational analysis was conducted to elucidate the binding interactions of SY-15 and SY-17 with the α2A-AR. The binding free energies of SY-15 and SY-17 calculated by MD simulations were −45.93 and −71.97 kcal/mol. MD simulations also revealed that both compounds act as bitopic agonists, occupying the orthosteric site and a novel exosite of the receptor simultaneously. Our findings of integrative computational and experimental approaches could offer the potential to enhance ligand affinity and selectivity through dual-site occupancy and provide a novel direction for the rational design of sedatives and analgesics. [ABSTRACT FROM AUTHOR]

Rare-earth perovskite oxides have become a research hotspot in the fields of environment and energy owing to their structural tunability, excellent redox properties, high stability and high catalytic activity. Researchers have designed and developed different rare-earth perovskite catalysts for tackling environmental pollutants in recent years. This review summarizes recent research progress on rare-earth perovskite catalysts in the catalytic oxidation and photocatalytic degradation of pollutants, gas sensing of volatile organic compounds and photocatalytic water splitting for hydrogen production and carbon dioxide reduction and conversion, and summarizes the mechanism of these reactions. It also discusses in detail the relationship between structural modification, synthesis process and the physical–chemical properties of the catalysts. Finally, the challenges with rare-earth chalcocite catalysts in the field of environment and energy are discussed. This paper reviews recent progress in rare-earth perovskite oxide materials, explores the effects of capacity factors, lattice defects, different metal active centers and perovskite modifications on crystal structure and applied properties, discusses the effects of synthesis processes (sol-gel, co-precipitation, microemulsion, hydrothermal, high-temperature) on their physical and chemical properties, and summarizes their applications in pollutant catalytic oxidation and photocatalytic degradation, VOCs gas sensing, and photocatalytic splitting of water for hydrogen production and carbon dioxide reduction and conversion. (Image credit: P. Li.) [ABSTRACT FROM AUTHOR]

Background: The OTUD5 gene encodes a deubiquitinating enzyme (DUB) of the OTU family. Variants of OTUD5 are associated with X‐linked multiple congenital anomalies‐neurodevelopmental syndrome (MCAND). The case described in this study expands the clinical and molecular spectrum of OTUD5. Methods: Trio‐based clinical exome sequencing (trio‐CES) was performed on a Chinese boy with a clinical phenotype and both of his parents. Sanger sequencing was employed for validation of the variant detected. Results: The patient presented with characteristic facial features, intellectual disability, motor/language/cognitive, and global developmental delays, limb contractures, and kidney abnormalities, and trio‐CES identified a de novo missense variant, c.1305T>A, of the OTUD5 gene. Discussion: We describe OTUD5 gene variation in the Chinese population, with the first report of this variant. Additionally, we provide a comprehensive summary of all published cases of MCAND to date, in order to elucidate the primary clinical features of the syndrome and the variability in phenotype severity. This case expands the genetic and clinical phenotypic spectrum of OTUD5‐associated MCAND. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders that poses a global threat to human health. It can lead to complications in multiple organs and tissues, owing to its wide-ranging impact on the human body. Diabetic cardiomyopathy (DCM) is a specific cardiac manifestation of DM, which is characterized by heart failure in the absence of coronary heart disease, hypertension and valvular heart disease. Given that oxidative stress is a key factor in the pathogenesis of DCM, intervening to mitigate oxidative stress may serve as a therapeutic strategy for managing DCM. Naringenin is a natural product with anti-oxidative stress properties that can suppress oxidative damage by regulating various oxidative stress signaling pathways. In this review, we address the relationship between oxidative stress and its primary signaling pathways implicated in DCM, and explores the therapeutic potential of naringenin in DCM. [ABSTRACT FROM AUTHOR]

Aims: Vascular resident stem cells expressing stem cell antigen-1 (Sca-1+ cells) promote vascular regeneration and remodelling following injury through migration, proliferation and differentiation. The aim of this study was to examine the contributions of ATP signalling through purinergic receptor type 2 (P2R) isoforms in promoting Sca-1+ cell migration and proliferation after vascular injury and to elucidate the main downstream signalling pathways. Methods and results: ATP-evoked changes in isolated Sca-1+ cell migration were examined by transwell assays, proliferation by viable cell counting assays and intracellular Ca2+ signalling by fluorometry, while receptor subtype contributions and downstream signals were examined by pharmacological or genetic inhibition, immunofluorescence, Western blotting and quantitative RT-PCR. These mechanisms were further examined in mice harbouring TdTomato-labelled Sca-1+ cells with and without Sca-1+-targeted P2R knockout following femoral artery guidewire injury. Stimulation with ATP promoted cultured Sca-1+ cell migration, induced intracellular free calcium elevations primarily via P2Y2R stimulation and accelerated proliferation mainly via P2Y6R stimulation. Enhanced migration was inhibited by the ERK blocker PD98059 or P2Y2R-shRNA, while enhanced proliferation was inhibited by the P38 inhibitor SB203580. Femoral artery guidewire injury of the neointima increased the number of TdTomato-labelled Sca-1+ cells, neointimal area and the ratio of neointimal area to media area at 3 weeks post-injury, and all of these responses were reduced by P2Y2R knockdown. Conclusions: ATP induces Sca-1+ cell migration through the P2Y2R–Ca2+–ERK signalling pathway, and enhances proliferation through the P2Y6R–P38-MAPK signalling pathway. Both pathways are essential for vascular remodelling following injury. 1ojmKs4RKbR9szmL_ViEmx Video Abstract [ABSTRACT FROM AUTHOR]