Summary
Background
Atopic dermatitis is a systemic disorder characterized by abnormal barrier function across multiple organ sites. Causes of epidermal barrier breakdown are complex and driven by a ...combination of structural, genetic, environmental and immunological factors. In addition, alteration in microflora diversity can influence disease severity, duration, and response to treatment. Clinically, atopic dermatitis can progress from skin disease to food allergy, allergic rhinitis, and later asthma, a phenomenon commonly known as the atopic march. The mechanism by which atopic dermatitis progresses towards gastrointestinal or airway disease remains to be elucidated.
Objectives
This review addresses how epithelial dysfunction linking microbiome alteration and immune dysregulation can predispose to the development of the atopic march.
Methods
A literature search was conducted using the PubMed database for relevant articles with the keywords ‘atopic dermatitis’, ‘epithelial barrier’, ‘skin’, ‘gut’, ‘lung’, ‘microbiome’ and ‘immune dysregulation’.
Results
Initial disruption in the skin epidermal barrier permits allergen sensitization and colonization by pathogens. This induces a T helper 2 inflammatory response and a thymic stromal lymphopoietin‐mediated pathway that further promotes barrier breakdown at distant sites, including the intestinal and respiratory tract.
Conclusions
As there are no immediate cures for food allergy or asthma, early intervention aimed at protecting the skin barrier and effective control of local and systemic inflammation may improve long‐term outcomes and reduce allergen sensitization in the airway and gut.
What's already known about this topic?
The atopic march is a phenomenon characterized by sequential development of atopic dermatitis, food allergy, allergic rhinitis and later asthma; however, the mechanism by which atopic dermatitis progresses towards gastrointestinal or airway disease remains to be elucidated.
What does this study add?
This review addresses how epithelial dysfunction linking microbiome alteration and immune dysregulation can predispose to development of the atopic march.
We examine the factors contributing to the pathogenesis of the atopic march and propose strategies for intervention and targeted therapy.
Gradient structures have evolved over millions of years through natural selection and optimization in many biological systems such as bones and plant stems, where the structures change gradually from ...the surface to interior. The advantage of gradient structures is their maximization of physical and mechanical performance while minimizing material cost. Here we report that the gradient structure in engineering materials such as metals renders a unique extra strain hardening, which leads to high ductility. The grain-size gradient under uniaxial tension induces a macroscopic strain gradient and converts the applied uniaxial stress to multiaxial stresses due to the evolution of incompatible deformation along the gradient depth. Thereby the accumulation and interaction of dislocations are promoted, resulting in an extra strain hardening and an obvious strain hardening rate up-turn. Such extraordinary strain hardening, which is inherent to gradient structures and does not exist in homogeneous materials, provides a hitherto unknown strategy to develop strong and ductile materials by architecting heterogeneous nanostructures.
Although gully development is frequently observed to be associated with piping and tunnel erosion in many parts of the world, there is a lack of detailed studies on their spatial interactions. Such ...studies not only contribute to developing geomorphic theories on the evolution of both hillslopes and drainage networks but also are useful to design effective control measures of erosion. The present study aims to examine the interactions between gully development and tunnel erosion in the hilly Loess Plateau region of northern China. Firstly, gullies, tunnel inlets and mass movements in the 9.1km2 Wangjiagou watershed were mapped through aerial photo interpretation and reconnaissance surveys. Secondly, detailed field studies were carried out to investigate the interactions between gully development and tunnel formation processes in the selected gullies. Thirdly, the physiographic variables of gullies, derived from GIS and field measurements, were analyzed to identify differences between tunneled and untunneled gullies.
A total of 704 channels, 967 tunnel inlets and 547 mass movements were identified in the study watershed. On the basis of their location and morphology, all the channels were classified into four types: headwater gullies, hillside gullies, valleyside gullies and ephemeral river channels. Tunnels are associated with 79% of headwater gullies, 48% of hillside gullies, 3% of valleyside gullies and none of ephemeral river channels. Mass movements are dominated by falls in headwater gullies, falls and slides in hillside gullies, and soil creeps in ephemeral stream channels. Statistical tests indicate that there are significant differences in physiographic variables between tunneled and untunneled gullies. Tunnel formation in gullies is intricately affected by topographic conditions, land uses, knickpoint distribution, soil materials and mass movements.
► Distribution of gullies, tunnels, and mass movement in a semi-arid watershed. ► Tunnel erosion is active in the development of headwater and hillslope gullies. ► Tunnel erosion is largely absent in hanging gullies and ephemeral river channels. ► The frequency and types of mass movements vary according to types of gullies.
Nanocrystalline (nc) materials can be defined as solids with grain sizes in the range of 1aAA"100nm. Contrary to coarse-grained metals, which become more difficult to twin with decreasing grain size, ...nanocrystalline face-centered-cubic (fcc) metals become easier to twin with decreasing grain size, reaching a maximum twinning probability, and then become more difficult to twin when the grain size decreases further, i.e. exhibiting an inverse grain-size effect on twinning. Molecular dynamics simulations and experimental observations have revealed that the mechanisms of deformation twinning in nanocrystalline metals are different from those in their coarse-grained counterparts. Consequently, there are several types of deformation twins that are observed in nanocrystalline materials, but not in coarse-grained metals. It has also been reported that deformation twinning can be utilized to enhance the strength and ductility of nanocrystalline materials. This paper reviews all aspects of deformation twinning in nanocrystalline metals, including deformation twins observed by molecular dynamics simulations and experiments, twinning mechanisms, factors affecting the twinning, analytical models on the nucleation and growth of deformation twins, interactions between twins and dislocations, and the effects of twins on mechanical and other properties. It is the authorsaAAtm intention for this review paper to serve not only as a valuable reference for researchers in the field of nanocrystalline metals and alloys, but also as a textbook for the education of graduate students.
as a representative work focused on health preservation in the Song Dynasty, a period of highly-developed health preservation culture. It was written by Liu Ci, following the theory of "food is the ...basis of life" and recorded a great number of principles and methods of diet health preservation. It demonstrated the relationship between diet and the five organs of the human body, diet and disease prevention, diet and time adjusting and diet and risk factors. It provided significant reference for diet health preservation currently.
A model is developed to study the stress generation in a spherical particle subjected to lithium insertion. The model accounts for both the plastic deformation and the coexistence of lithium-poor and ...lithium-rich phases with a sharp and curved phase boundary. Such two-phase and inelastic deformation characteristics often arise during lithiation of crystalline particles with high capacity. A flexible sigmoid function is used to create the lithium profile with a step-like change in lithium concentration, mimicking a sharp phase boundary that separates a pristine core and a lithiated shell in the particle. The mechanics results, obtained by an analytic formulation and finite difference calculations, show the development of tensile hoop stress in the surface layer of the lithiated shell. This hoop tension provides the driving force of surface cracking, as observed by in situ transmission electron microscopy. The two-phase lithiation model is further compared with the single-phase one, which assumes a gradual and smooth variation in radial lithium distributions, and thus predicts only hoop compression in the surface layer of the particle. Furthermore, the effect of dilatational vs. unidirectional lithiation strains in the two-phase model is studied, thereby underscoring the critical role of anisotropy of lithiation strain in controlling stress generation in high-capacity electrodes for lithium ion batteries.
Abstract
Introduction
Xylazine, an α2-adrenoceptor agonist sedative commonly used in veterinary medicine, is not approved for human use. Nevertheless, xylazine-involved overdose rates have surged in ...recent years, fueled by an increasingly toxic and synthetic illicit drug supply in North America.
Methods
This narrative review assessed major epidemiological trends in xylazine-involved overdoses in North America, aiming to identify harm reduction priorities. A literature search was conducted using four bibliographic databases (PubMed, Scopus, Embase, and ScienceDirect) and three preprint servers (medRxiv, bioRxiv, and Europe PMC) on May 28, 2023, to capture articles related to combinations of keywords such as “xylazine”, “opioid”, and “harm reduction”.
Results
Xylazine emerged as an adulterant in Puerto Rico in 2001, likely diverted from veterinary supplies. By the mid-2010s, it began proliferating across unregulated US drug markets, often contemporaneously with illicitly manufactured fentanyl (IMF), displaying characteristics of a syndemic. Initially concentrated in Northeastern regions (e.g., Philadelphia, Connecticut, Maryland), xylazine-involved overdoses later extended to the Rust Belt, Southern, and Western regions of the USA in the late 2010s and early 2020s. During this time, xylazine-involved overdoses also surged in Canada, particularly in Western provinces (British Columbia and Alberta) and Ontario with established IMF-dominated unregulated drug markets.
Discussion
Over the past two decades, xylazine-involved overdoses have been rapidly rising in North America and exhibit few signs of slowing down, representing a serious public health epidemic. Numerous factors may have contributed to this, including limited epidemiological surveillance and drug checking for xylazine and emerging novel adulterants; further, barriers to comprehensive, trauma-informed, non-stigmatizing treatment and social services have also exacerbated this issue. While several epidemiological and ethnographic studies have assessed these factors in the USA, limited evidence is available in Canada where xylazine emerged more recently. This underscores the need for additional research and harm reduction measures.
Conclusion
Harm reduction-informed public health guidelines and programs are urgently needed to promote a safer supply, strengthen the healthcare system capacity to prevent and respond to xylazine-involved overdoses, and address social and structural disparities in health outcomes.
A modeling method for flapwise and chordwise bending vibration analysis of rotating pre-twisted Timoshenko beams is introduced. In the present modeling method, the shear and the rotary inertia ...effects on the modal characteristics are correctly included based on the Timoshenko beam theory. The kinetic and potential energy expressions of this model are derived from the Rayleigh–Ritz method, using a set of hybrid deformation variables. The equations of motion of the rotating beam are derived from the kinetic and potential energy expressions introduced in the present study. The equations thus derived are transmitted into dimensionless forms in which main dimensionless parameters are identified. The effects of dimensionless parameters such as the hub radius ratio, slenderness ration, etc. on the natural frequencies and modal characteristics of rotating pre-twisted beams are successfully examined through numerical studies. Finally the resonance frequency of the rotating beam is evaluated.
On 15 January 2022, the submarine Hunga Tonga volcanic eruption lofted materials high into the upper stratosphere, reaching a record-breaking altitude of ~58 km, unprecedented in the satellite ...observations era. Within two weeks, the bulk of the injected material circulated the globe between 20 – 30 km altitude, as observed by satellite instruments. We estimate that the stratospheric aerosol optical depth (sAOD) is the largest since the Pinatubo eruption and is at least twice as great as the sAOD after the 2015 Calbubo eruption despite the similar SO2 injection from that eruption. We use space-based observations to monitor the Hunga-Tonga volcanic plume evolution and transport at different altitudes as it circulates the globe. While the main aerosol layer remains trapped in the tropical pipe, small parts have already made it to both the northern and southern hemisphere poles by April, which is almost certain to influence this year's ozone hole.
The brain endothelium is an important therapeutic target for the inhibition of cerebrovascular dysfunction in ischemic stroke. Previously, we documented the important regulatory roles of microRNAs in ...the cerebral vasculature, in particular the cerebral vascular endothelium. However, the functional significance and molecular mechanisms of other classes of non-coding RNAs in the regulation of cerebrovascular endothelial pathophysiology after stroke are completely unknown.
Using RNA sequencing (RNA-seq) technology, we profiled long non-coding RNA (lncRNA) expressional signatures in primary brain microvascular endothelial cells (BMECs) after oxygen–glucose deprivation (OGD), an in vitro mimic of ischemic stroke conditions. After 16h of OGD exposure, the expression levels for 362 of the 10,677 lncRNAs analyzed changed significantly, including a total of 147 lncRNAs increased and 70 lncRNAs decreased by more than 2-fold. Among them, the most highly upregulated lncRNAs include Snhg12, Malat1, and lnc-OGD 1006, whereas the most highly downregulated lncRNAs include 281008D09Rik, Peg13, and lnc-OGD 3916. Alteration of the most highly upregulated/downregulated ODG-responsive lncRNAs was further confirmed in cultured BMECs after OGD as well as isolated cerebral microvessels in mice following transient middle cerebral artery occlusion (MCAO) and 24h reperfusion by the quantitative real-time PCR approach. Moreover, promoter analysis of altered ODG-responsive endothelial lncRNA genes by bioinformatics showed substantial transcription factor binding sites on lncRNAs, implying potential transcriptional regulation of those lncRNAs. These findings are the first to identify OGD-responsive brain endothelial lncRNAs, which suggest potential pathological roles for these lncRNAs in mediating endothelial responses to ischemic stimuli. Endothelial-selective lncRNAs may function as a class of novel master regulators in cerebrovascular endothelial pathologies after ischemic stroke.
•A first study to profile ischemic-responsive brain endothelial long non-coding RNAs•Total 217 lncRNAs were classified as ischemic-responsive endothelial lncRNAs.•The most highly altered lncRNAs were confirmed in brain microvessels after stroke.•Identified key transcription factors that regulate ischemic-responsive lncRNAs
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