Search Results (243,207)

Acetylsalicylic acid (ASA) represents a cornerstone of antiplatelet therapy for the treatment of atherosclerotic coronary artery disease (CAD). ASA is in fact indicated in case of an acute coronary syndrome or after a percutaneous coronary intervention with stent implantation. Aspirin hypersensitivity is frequently reported by patients, and this challenging situation requires a careful evaluation of the true nature of the presumed sensitivity and of its mechanisms, as well as to differentiate it from a more frequent (and more easily manageable) aspirin intolerance. Two main strategies are available to allow ASA administration for patients with CAD and suspected ASA hypersensitivity: a low-dose ASA challenge, aimed at assessing the tolerability of ASA at the antiplatelet dose of 100 mg, and desensitization, a therapeutic procedure which aims to induce tolerance to ASA. For those patients who cannot undergo ASA challenge and desensitization due to previous serious adverse reactions, or for those in whom desensitization was unsuccessful, a number of further alternative strategies are available, even if these have not been validated and approved by guidelines. The aim of this state-of-the-art review is therefore to summarize the established evidence regarding pathophysiology, clinical presentation, diagnosis, and management of aspirin hypersensitivity and to provide a practical guide for cardiologists (and clinicians) who have to face the not uncommon situation of a patient with concomitant coronary artery disease and aspirin hypersensitivity. Full article

Findings accumulated over time show that neurophysiological, neuropathological, and molecular alterations are present in CMT1A and support the dysmyelinating rather than demyelinating nature of this neuropathy. Moreover, uniform slowing of nerve conduction velocity is already manifest in CMT1A children and does not improve throughout their life. This evidence and our previous studies displaying aberrant myelin composition and structure in adult CMT1A rats prompt us to hypothesize a myelin and axon developmental defect in the CMT1A peripheral nervous system. Peripheral myelination begins during the early stages of development in mammals and, during this process, chemical and structural features of myelinated fibers (MFs) evolve towards a mature phenotype; deficiencies within this self-modulating circuit can cause its blockage. Therefore, to shed light on pathophysiological mechanisms that occur during development, and to investigate the relationship among axonal, myelin, and lipidome deficiencies in CMT1A, we extensively analyzed the evolution of both myelin lipid profile and MF structure in WT and CMT1A rats. Lipidomic analysis revealed a delayed maturation of CMT1A myelin already detectable at P10 characterized by a deprivation of sphingolipid species such as hexosylceramides and long-chain sphingomyelins, whose concentration physiologically increases in WT, and an increase in lipids typical of unspecialized plasma membranes, including phosphatidylcholines and phosphatidylethanolamines. Consistently, advanced morphometric analysis on more than 130,000 MFs revealed a delay in the evolution of CMT1A axon and myelin geometric parameters, appearing concomitantly with lipid impairment. We here demonstrate that, during normal development, MFs undergo a continuous maturation process in both chemical composition and physical structure, but these processes are delayed in CMT1A. Full article

Black spot caused by Alternaria alternata is one of the most common postharvest diseases in fruit and vegetables. A comprehensive investigation into its pathogenicity mechanism is imperative in order to propose a targeted and effective control strategy. The effect of nitric oxide (NO) on the pathogenicity of A. alternata and its underlying mechanism was studied. The results showed that treatment with 0.5 mM L⁻¹ of sodium nitroprusside (SNP) (NO donor) increased the lesion diameter of A. alternata in vivo and in vitro, which was 22.8% and 13.2% higher than that of the control, respectively. Exogenous NO treatment also induced endogenous NO accumulation by activating nitric oxide synthase (NOS). In addition, NO triggered an increase in reactive oxygen species (ROS) levels. NO enhanced activities and gene expression levels of NADPH oxidase (NOX), superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione peroxidase (GPX), and glutathione reductase (GR). Moreover, NO stimulated cell wall degrading enzymes by activating the corresponding gene expression in vivo and in vitro. These results suggested that exogenous NO promoted the pathogenicity of A. alternata by inducing ROS accumulation and activating antioxidants and cell wall degrading enzymes. The present results could establish a theoretical foundation for the targeted control of the black spot disease in pear fruit. Full article

Confocal laser scanning microscopy is one of the most widely used tools for high-resolution imaging of biological cells. However, the imaging resolution of conventional confocal technology is limited by diffraction, and more complex optical principles and expensive optical-mechanical structures are usually required to improve the resolution. This study proposed a deep residual neural network algorithm that can effectively improve the imaging resolution of the confocal microscopy in real time. The reliability and real-time performance of the algorithm were verified through imaging experiments on different biological structures, and an imaging resolution of less than 120 nm was achieved in a more cost-effective manner. This study contributes to the real-time improvement of the imaging resolution of confocal microscopy and expands the application scenarios of confocal microscopy in biological imaging. Full article

The friction stir welding (FSW) process is a unique combination of deformation and high temperature, which provides opportunities to modify microstructures through the adjustment of the processing parameters and is an ideal way to join non-weldable aluminum alloys by avoiding the formation of a molten pool. The 7xxx series heat-treatable aluminum alloys are widely used in the aerospace field as high-performance structural materials. The microstructure evolution and mechanical performance of these alloys are affected by the effects of thermomechanical processing, which provides opportunities to optimize the material properties by controlling microstructural features such as intermetallic constituent particles, dispersoids and nanoscale precipitates. This paper focuses on the basic principles of the thermal and mechanical effects generated during FSW on the evolution of second-phase particles in different zones of the weld. Full article

Traumatic brain injury (TBI), a major cause of death and disability among young people, leads to significant public health and economic challenges. Despite its frequency, treatment options remain largely unsuitable. However, examination of the blood–brain barrier (BBB) can assist with understanding the mechanisms and dynamics of brain dysfunction, which affects TBI sufferers secondarily to the injury. Here, we present a rat model of TBI focused on two standard BBB assessment markers, high- and low-molecular-weight complexes, in order to understand BBB disruption. In addition, we tested a new technique to evaluate BBB disruption on a single brain set, comparing the new technique with neuroimaging. A total of 100 Sprague–Dawley rats were separated into the following five groups: naive rats (n = 20 rats), control rats with administration (n = 20 rats), and TBI rats (n = 60 rats). Rats were assessed at different time points after the injury to measure BBB disruption using low- and high-molecular-weight complexes. Neurological severity score was evaluated at baseline and at 24 h following TBI. During the neurological exam after TBI, the rats were scanned with magnetic resonance imaging and euthanized for assessment of the BBB permeability. We found that the two markers displayed different examples of BBB disruption in the same set of brain tissues over the period of a week. Our innovative protocol for assessing BBB permeability using high- and low-molecular-weight complexes markers in a single brain set showed appropriate results. Additionally, we determined the lower limit of sensitivity, therefore demonstrating the accuracy of this method. Full article

Objectives: The COVID-19 pandemic has had a profound effect on the pediatric population worldwide. The consequences of the lockdown and the reallocation of hospital resources have caused notable changes in the presentation of pediatric orthopedic injuries. Through our use of patient records, we were able to display the epidemiological trends, as well as analyze the changes in the type and mechanism of various injuries. Our purpose is to further understand the considerable effects of the COVID-19 pandemic on pediatric orthopedic trauma and help guide the allocation of future healthcare resources. Methods: We conducted a retrospective cohort study on pediatric patients admitted for any orthopedic injury over a 3-year period (September 2018 to August 2021) at a Midwest level 1 trauma center. Cases were stratified into two groups based on the United States’ COVID-19 lockdown (19 March 2020): Pre-COVID-19 cases were any cases prior to the lockdown and Intra-COVID-19 which are cases following the lockdown. Numerical data and categorical variables were summarized and differences between the case groups were examined using either two-Proportion Z-Test, Independent Two-Sample t-test, Pearson’s chi-squared, or Fisher’s exact tests. Results: A total of 3179 pediatric orthopedic referrals occurred between the Pre-COVID-19 and Intra-COVID-19 study periods. We observed a general decrease in orthopedic injuries following the COVID-19 lockdowns with 1235 injuries compared to 1606 Pre-COVID-19. Patterns in the locations of injuries changed; notably, fractures of the humerus, tibia, and fibula decreased significantly (p < 0.05). Several mechanisms of injuries decreased significantly following the onset of COVID-19 including injuries caused by monkey bars, basketball, and automobiles (p < 0.01). There was a significant increase in the overall injury severity during the Intra-COVID-19 period (p < 0.05). Conclusions: Although there was a reduction in acute orthopedic trauma referrals, many injury mechanisms displayed similar trends regardless of restrictions. We clinically observed an overall increase in the severity of pediatric orthopedic injuries during the COVID-19 pandemic. Full article

One of the key conditions for achieving superior regional growth is ensuring the harmonious development of both the layout and functions of territorial space. Territorial space, which includes production space, living space, and ecological space, serves as a critical system and venue for economic, cultural, and social activities in a region. The harmonized growth of production–living–ecological space (PLES) is essential for attaining sustainable development goals. Research on PLES offers a fresh perspective on promoting sustainable development of the spatial domain and the sustainable use of resources. However, studies on PLE functions in ecologically fragile areas are lacking. Therefore, in this study, which adopts a PLES perspective, land-use data are used to classify land according to the dominant functions of production, ecology, and living. Integration of point-of-interest (POI) data with socio-economic data was established to spatially describe indicators at the grid level and create a scoring system for PLES indicators in ecologically fragile areas. Finally, the entropy weight method, holistic assessment methods, coupling coordination degree model (CCDM), and geodetector were employed to explore the coupling coordination relationships and factors influencing PLESs in the Turpan–Hami Basin from 2010 to 2020. The results indicate that the Turpan–Hami Basin consists predominantly of potential ecological space, mainly in the central and northern regions, which are characterized by the Gobi Desert and bare rock landforms. Over the past decade, the PLES framework has seen a notable rise in the allocation of residential and ecological areas, whereas the portion dedicated to production spaces has diminished. The overall coupling coordination degree (CCD) of PLES in the Turpan–Hami Basin is at a coordinated level and gradually increasing. The most significant impact on the degree of PLES coupling coordination is exerted by population and natural factors. The research findings provide theoretical support for the sustainable utilization of resources in the Turpan–Hami Basin and other ecologically fragile areas while also offering scientific evidence to promote the coupling coordination of PLES, thereby contributing to high-quality regional development. Full article

This review examines the impact of recycled aggregates (RAs) on the fresh and mechanical properties of high-strength concrete (HSC). The results revealed that incorporating RAs can reduce the compressive strength of HSC by up to 25%, with strength values ranging from 40 to 70 MPa depending on the RA content. The addition of supplementary materials like silica fume, fly ash, and polycarboxylate ether significantly mitigated these negative effects, enhancing the compressive strength by approximately 15–20% compared with the control mixes without additives. Furthermore, the tensile strength was observed to decrease by up to 18% with increasing RA content, but fiber reinforcement improved this by 10%, demonstrating the potential of additives to offset mechanical weaknesses. The modulus of elasticity also declined by up to 30% with higher RA dosages, highlighting the critical impact of the adhered mortar quality on the overall stiffness of the concrete. According to the literature, it was noticed that, when the dosage of RCAs is increased, there is a drop in the strength activity index (SAI). When the substitute dosage exceeded 50%, the SAI decreased. These findings underscore the importance of using optimized additive combinations to improve the mechanical performance of RA concrete, making it a viable option for sustainable construction. Overall, the findings suggest that, although RAs may negatively affect certain physical traits of HSC, the use of appropriate additives can optimize its performance, making it a viable option for sustainable construction practices. Full article

Track decay rate (TDR), meaning the rate of attenuation of bending waves through the rail, is the most important indicator of a track’s dynamic characteristic impacting the rail noise emission. TDR depends on various parameters related to the construction of the track, and it can be increased using rail dampers. These are mechanical devices working on the principle of dynamic absorbers and are attached to the rail. This paper addresses the track with light rails needing improvements to reduce the rail noise emission using a particular rail damper with a mixed damping system (rubber–oil). The bending waves that propagate through the rail, the frequency response function of the rail, and TDR are investigated considering different scenarios regarding the parameters of the track: soft/stiff rail pad, tampered/settled ballast, and sleeper bay. To this end, an analytic model of the track featuring rail dampers consisting of an infinite Timoshenko beam with discrete attached oscillators is used. Numerical results show the possibility to increase TDR of railway track with light rails for both soft/stiff rail pads from 4 to 500 Hz up to 1250–1600 Hz using rail dampers with a mixed damping system. Full article

Weizmannia coagulans has been shown to have anticancer properties. However, there is limited research on the effects of postbiotic W. coagulans on colorectal cancer cell proliferation. Additionally, the exact mechanisms through which it influences apoptosis- and autophagy-related signaling pathways are yet to be thoroughly elucidated. This study explored the role of W. coagulans MZY531 as a postbiotic in inhibiting tumor growth by modulating apoptosis and autophagy in tumor cells. During the experimental period in the model group, tumors proliferated, tumor markers increased significantly, and immunofluorescence results showed that caspase-3 and terminal deoxynucleotidyl transferase dUTP nick-end labeling were significantly decreased. Conversely, supplementation with W. coagulans MZY531 postbiotics significantly reduced the levels of tumor markers carcinoembryonic antigen, colon cancer antigen, and extracellular protein kinase A and promoted cell apoptosis by increasing the caspase-3-positive count and terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in tumor tissue. Mechanistically, W. coagulans MZY531 postbiotics inhibit tumor growth through the modulation of the Bax/Bcl-2/caspase-3 and JAK2/STAT3 apoptosis pathways and PI3K/AKT/mTOR and TGF-β/SMAD4 cell autophagy pathways. W. coagulans MZY531 postbiotics had a more significant effect than that of W. coagulans MZY531 alone. Probiotics are expected to become effective natural functional foods for the treatment of colorectal cancer. Full article

The solubilization behavior of medroxyprogesterone (MP) within gemini surfactant micelles (14-6-14,2Br⁻) was investigated and compared with that of progesterone to uncover distinct solubilization mechanisms. We employed ¹H-NMR and 2D ROESY spectroscopy to elucidate the spatial positioning of MP within the micelle, revealing that MP integrates more deeply into the micellar core. This behavior is linked to the unique structural features of MP, particularly its 17β-acetyl group, which promotes enhanced interactions with the hydrophobic regions of the micelle, while the 6α-methyl group interacts with the hydrophilic regions of the micelle. The 2D ROESY correlations specifically highlighted interactions between the hydrophobic chains of the surfactant and two protons of MP, H22 and H19. Complementary machine learning and electron density analyses supported these spectroscopic findings, underscoring the pivotal role of the molecular characteristics of MP in its solubilization behavior. These insights into the solubilization dynamics of MP not only advance our understanding of hydrophobic compound incorporation in gemini surfactant micelles but also indicate the potential of 14-6-14,2Br⁻ micelles for diverse drug delivery applications. Full article

Plants encounter various stresses in their natural environments and can effectively respond to only one stress at a time. Through a complex gene network, transcription factors (TFs) such as WRKY TFs regulate a diverse array of stress responses. The clarification of the structural characteristics of WRKY proteins, along with recent advancements in molecular dynamics simulations, has shed light on the formation, stability, and interactions of DNA–protein complexes. This has provided a novel viewpoint regarding the control of WRKY TFs. The investigation of superfamilies, encompassing their historical development, diversity, and evolutionary patterns, has become feasible due to the transcriptome approach’s capacity to provide extensive and comprehensive transcripts. The significance of WRKY TFs lies in their pivotal role within several signaling cascades and regulatory networks that influence plant defense responses. The present review summarizes the functional aspects of the high-volume sequence data of WRKY TFs from different species studied to date. Moreover, a comparative analysis approach was utilized to determine the functions of the identified WRKY TFs in response to both abiotic and biotic stresses, as revealed through numerous studies on different plant species. The results of this review will be pivotal in understanding evolutionary events and the significance of WRKY TFs in the context of climate change, incorporating new scientific evidence to propose an innovative viewpoint. Full article

Myocarditis after the COVID-19 vaccine is one of the important adverse events following immunization, observed mainly after mRNA-based vaccines. Importantly, post-vaccination myocarditis was less common than myocarditis after SARS-CoV-2 infection, as it was scored at 19.7 per 1,000,000 doses and 2.76 per 1000 infections. Predominantly, its course was benign and, compared with the myocarditis after COVID-19 infection, significantly fewer patients developed heart failure or died among patients with post-vaccination myocarditis. The group at highest risk of myocarditis related to COVID-19 vaccination were young males who received a second dose of an mRNA vaccine. It was observed that, among mRNA vaccines, specifically mRNA-1273 was associated with a higher risk of myocarditis. The mechanism underlying myocarditis after COVID-19 vaccination is still under investigation and certain processes are being considered. Currently, some follow-up assessments of patients who developed vaccine-induced myocarditis are available and suggest a favorable prognosis. The aim of this review is to discuss the most recent data on myocarditis after COVID-19 vaccination considering its epidemiology, clinical presentation, diagnosis, management, relative risk of myocarditis compared with SARS-CoV-2 infection, potential underlying mechanism, and follow-up data of patients who developed post-vaccination myocarditis. Full article

The small brown planthopper (SBPH), Laodelphax striatellus (Fallén) (Hemiptera: Delphacidae), is an increasing threat to Gramineae crops, posing significant risks to both the environment and food safety. β-asarone, as a promising green alternative to chemical insecticides, possesses wide application prospects in the crop protection field. To enhance the insecticidal activity of β-asarone, a series of derivatives were prepared through an active substructure splicing strategy, and their insecticidal activities against SBPH were evaluated. Among the 7 commercial compounds with chemical structures similar to β-asarone and 12 structural derivatives of β-asarone, compound 10, which incorporates the 2-chloropyridine functional group from flupyrimin, exhibited the most potent insecticidal activity against SBPH, with an 8.31-fold increase in insecticidal activity compared to β-asarone. Furthermore, transcriptome analysis showed that among the selected genes that may play important roles in insecticidal activity, an ABC transporter gene, MDR49, was most significantly down-regulated. MDR49 was highly expressed in the 4th-instar nymphs, with the highest expression level in the fat body, midgut, and abdomen. RNA interference (RNAi) against MDR49 significantly reduced susceptibility to compound 10 in SBPH, which revealed that MDR49 may be the candidate insecticidal target of compound 10. Additionally, the insecticidal spectrum revealed that compound 10 showed excellent efficacy against Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) and Tetranychus cinnabarinus (Boisduval) (Acarina: Tetranychidae). This study indicates that compound 10 could be further developed as a novel eco-friendly pesticide. Full article