Background
The aim of this study was to investigate the prevalence of epidemiologic and physician‐diagnosed pollen‐induced AR (PiAR) in the grasslands of northern China and to study the impact of the ...intensity and time of pollen exposure on PiAR prevalence.
Methods
A multistage, clustered and proportionately stratified random sampling with a field interviewer‐administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count.
Results
A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05).
Conclusion
Pollen‐induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.
This article explores the conceptual and practical gap existing between the developed and developing countries in relation to corporate social responsibility (CSR), or the North-South ' CSR Divide', ...through the analysis of possible impact on the competitiveness of developing countries' and economies' SMEs and MNEs in globalization. To do so, this article first reviewed the traditional wisdom on the concept of strategic CSR developed in the North and the role that CSR engagement can play in corporate competitiveness, and compare with the impact on the competitive advantage of the South through the supply chains. It points out that among the many factors that could explain the ' CSR Divide', the negative impact of CSR on comparative advantage is the final resort where developing countries are reluctant and defensive toward western-style CSR. It did point out that developing countries are changing their approaches to make CSR work in favor of their competitive position in global trade, such as China who has started to adopt proactive approach by becoming CSR standards-setter. This article concludes with two policy proposals that aim to bridge the CSR gap, the first is to improve CSR standard-setting participation from both sides, and the second to search for solutions in the international investment legal framework which will define corporate obligations in relating to CSR in a more explicit way.
Mesenchymal stem cells (MSCs) can be isolated from almost all tissues and effectively expanded in vitro. Although their true in situ properties and biological functions remain to be elucidated, these ...in vitro expanded cells have been shown to possess potential to differentiate into specific cell lineages. It is speculated that MSCs in situ have important roles in tissue cellular homeostasis by replacing dead or dysfunctional cells. Recent studies have demonstrated that in vitro expanded MSCs of various origins have great capacity to modulate immune responses and change the progression of different inflammatory diseases. As tissue injuries are often accompanied by inflammation, inflammatory factors may provide cues to mobilize MSCs to tissue sites with damage. Before carrying out tissue repair functions, MSCs first prepare the microenvironment by modulating inflammatory processes and releasing various growth factors in response to the inflammation status. In this review, we focus on the crosstalk between MSCs and immune responses and their potential clinical applications, especially in inflammatory diseases.
Modeling hydraulic fracture propagation in rock mass within the extended finite element method (XFEM) is presented in this paper. The XFEM framework is integrated by fully coupling the model with ...fluid flow and rock deformation in the proposed algorithm. The fluid within the fracture is considered as an incompressible Newtonian fluid. In the proposed formulation, the first-order generalized shape functions for the nodes around the cracks are used, and the augmented Lagrange method combined with the mortar method (segment to segment) is used to treat the contact of the two cracks faces. The crack width, the crack length, and the pressure in the crack in the presence of a natural fracture are studied.
Epileptic encephalopathies are severe epilepsy disorders with strong genetic bases. We performed targeted next‐generation sequencing (NGS) in 70 patients with epileptic encephalopathies. The likely ...pathogenicity of variants in candidate genes was evaluated by American College of Medical Genetics and Genomics (ACMG) scoring taken together with the accepted clinical presentation. Thirty‐three candidate variants were detected after population filtration and computational prediction. According to ACMG, 21 candidate variants, including 18 de novo variants, were assessed to be pathogenic/likely pathogenic with clinical concordance. Twelve variants were initially assessed as uncertain significance by ACMG, among which 3 were considered causative and 3 others were considered possibly causative after analysis of clinical concordance. In total, 24 variants were identified as putatively causative, among which 19 were novel findings. SCN1A mutations were identified in 50% of patients with Dravet syndrome. TSC1/TSC2 mutations were detected in 66.7% of patients with tuberous sclerosis. STXBP1 mutations were the main findings in patients with West syndrome. Mutations in SCN2A, KCNT1, KCNQ2 and CLCN4 were identified in patients with epileptic infantile with migrating focal seizures; among them, KCNQ2 and CLCN4 were first identified as potential causative genes. Only one CHD2 mutation was detected in patients with Lennox‐Gastaut syndrome. This study highlighted the utility of targeted NGS in genetic diagnoses of epileptic encephalopathies and a comprehensive evaluation of the pathogenicity of variants based on ACMG scoring and assessment of clinical concordance. Epileptic encephalopathies differ in genetic causes, and the genotype‐phenotype correlations would provide insights into the underlying pathogenic mechanisms.
We identified 24 causative mutations (19 novel) in a cohort of 70 EE patients and delineated new phenotype associated with CLCN4 and KCNQ2.
Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions ...in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer's theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.
The frequency of human being suffering from cancer is increasing annually throughout the world, but treatment of cancer is becoming more complex in recent years due to the multidrug resistance, ...creating an urgent demand for novel chemotherapeutics. Betulin and betulinic acid as lupane-type pentacyclic triterpenes distributed ubiquitously in the plant kingdom. Betulin and betulinic acid derivatives could hold the anticancer effects through different mechanisms, inclusive of induction of apoptosis and autophagy, antiangiogenesis, inhibition of invasion and migration, cell cycle arrest and multidrug resistance reversal. Notably, betulin and betulinic acid hybrids have been recently identified as promising candidates to explore novel anticancer chemotherapeutics since these derivatives could circumvent multidrug resistance, reduce the toxicity, and improve the efficacy. This review outlines the research progress regarding the anticancer potential of betulin and betulinic acid hybrids from 2012 to 2022, and the structure–activity relationship and mechanisms of action were also discussed.
Apoptosome refers to the adaptor protein complex that mediates the activation of an initiator caspase at the onset of apoptosis. In mammalian cells, caspase-9, caspase-8, and caspase-2 rely on the ...apoptotic protease-activating factor 1 (Apaf-1)-apoptosome, death-inducing signaling complex (DISC), and PIDDosome, respectively, for activation. In Drosophila, activation of the caspase-9 homolog Dronc requires assembly of an apoptosome comprised of Dark/Hac-1/Dapaf-1. In Caenorhabditis elegans, activation of the caspase CED-3 is facilitated by the CED-4-apoptosome. Recent biochemical and structural investigation revealed significant insights into the assembly and function of the various apoptosomes. Nonetheless, conclusive mechanisms by which the initiator caspases are activated by the apoptosomes remain elusive. Several models have been proposed to explain the activation process. The induced proximity model summarizes the general process of initiator caspase activation. The proximity-driven dimerization model describes how initiator caspases respond to induced proximity and offers an explanation for their activation. Regardless of how initiator caspases are activated, enhanced activity must be correlated with altered active site conformation. The induced conformation model posits that the activated conformation for the active site of a given initiator caspase is attained through direct interaction with the apoptosome or through homo-oligomerization facilitated by the apoptosome.
Hepatocellular carcinoma (HCC) is linked to inflammation and immunosuppression. Chemerin is highly expressed in the liver and implicated in the regulation of inflammation. However, the role of ...chemerin in HCC remains unclear. In this study, we aimed to investigate whether chemerin is able to influence HCC progression by regulating tumor-associated inflammation. Here we demonstrated that chemerin significantly decreased in blood and tumor tissues of HCC patients, and tumor chemerin levels were inversely associated with the prognosis. In an orthotopic mouse model of HCC, Rarres2
mice exhibited aggressive tumor growth and lung metastasis, whereas chemerin overexpression greatly inhibited tumor growth. The tumor-inhibitory effect of chemerin was accompanied by a shift in tumor-infiltrating immune cells from myeloid-derived suppressive cells (MDSCs) to interferon-γ
T cells and decreased tumor angiogenesis. Furthermore, we demonstrated that the tumor-inhibitory effect of chemerin was partly dependent on T cells, as chemerin overexpression could inhibit tumor growth, albeit to a lesser extent, in Rag1
mice when compared with wild-type controls. Mechanistically, chemerin inhibited nuclear factor-κB activation and the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-6) by tumor cells and tumor-associated endothelial cell, respectively, via its receptors, and consequently, MDSC induction was impaired, leading to restoration of antitumor T-cell response and decreased tumor angiogenesis. Clinically, systemic and tumor levels of chemerin were found to inversely correlate with circulating concentrations of GM-CSF or IL-6 and tumor-infiltrating myeloid cells, respectively, in HCC patients. Moreover, neutralization of GM-CSF and IL-6 abrogated HCC progression and MDSC accumulation in Rarres2
mice. In conclusion, our study reveals the tumor-inhibitory effect of chemerin by suppressing inflammatory tumor microenvironment with therapeutic implications for inflammation-associated cancer-like HCC.
Chiral ketones have been shown to be effective organocatalysts for asymmetric epoxidation of olefins with broad substrate scope. High enantioselectivity has been obtained for a wide variety of trans ...and trisubstituted olefins, as well as a number of cis olefins, with encouragingly high ee's for some terminal olefins. The stereochemical outcome of the reaction can be rationalized by a spiro transition state model.
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