The innate and adaptive immune cells have complex signaling pathways for sensing and initiating immune responses against disease. These pathways are interrupted at different levels to occur immune ...evasion, including by N6-methyladenosine (m6A) modification. In this review, we discuss studies revealing the immune evasion mechanism by m6A modification, which underlies the retouching of these signaling networks and the rapid tolerance of innate and adaptive immune molecules during disease. We also focus on the functions of m6A in main chemokines regulation, and their roles in promotive and suppressive immune cell recruitment. We then discuss some of the current challenges in the field and describe future directions for the immunological mechanisms of m6A modification.
Objective
There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to ...verify the reliability and validity of the developed scale.
Methods
The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38).
Results
A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient ICC = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92).
Interpretation
CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352–358.
We investigated the therapeutic potential of the interleukin‐6 receptor inhibitor tocilizumab in 7 patients with new onset refractory status epilepticus (NORSE) who remained refractory to ...conventional immunotherapy with rituximab (n = 5) or without rituximab (n = 2). Status epilepticus (SE) was terminated after 1 or 2 doses of tocilizumab in 6 patients with a median interval of 3 days from the initiation. They had no recurrence of SE during the observation. However, 2 patients experienced severe adverse events related to infection during the tocilizumab therapy. Further prospective controlled studies are warranted to validate the efficacy and safety of tocilizumab in patients with NORSE. Ann Neurol 2018;84:940–945
The conversion of body heat into electrical energy using a thermoelectric (TE) power generator is useful for wearable self-powered mobile electronic systems such as medical sensors or smart watches. ...We herein demonstrate a glass fabric-based flexible TE generator using a screen printing technique and the self-sustaining structure of a TE device without top and bottom substrates. With this technique it is possible to make the device thin ( similar to 500 mu m), lightweight ( similar to 0.13 g cm super(-2)), and flexible. In addition, the developed TE generator achieved an unprecedentedly large output power density which is several tens of times higher than that of flexible TE generators reported to date. The developed TE generator shows an allowable bending radius of as low as 20 mm and no change in performance by repeated bending for 120 cycles. This work can expedite the development of wearable self-powered mobile devices.
Summary
Lignocellulosic biomass was used for thousands of years as animal feed and is now considered a great sugar source for biofuels production. It is composed mostly of secondary cell walls built ...with polysaccharide polymers that are embedded in lignin to reinforce the cell wall structure and maintain its integrity. Lignin is the primary material responsible for biomass recalcitrance to enzymatic hydrolysis. During plant development, deep reductions of lignin cause growth defects and often correlate with the loss of vessel integrity that adversely affects water and nutrient transport in plants. The work presented here describes a new approach to decrease lignin content while preventing vessel collapse and introduces a new strategy to boost transcription factor expression in native tissues. We used synthetic biology tools in Arabidopsis to rewire the secondary cell network by changing promoter‐coding sequence associations. The result was a reduction in lignin and an increase in polysaccharide depositions in fibre cells. The promoter of a key lignin gene, C4H, was replaced by the vessel‐specific promoter of transcription factor VND6. This rewired lignin biosynthesis specifically for vessel formation while disconnecting C4H expression from the fibre regulatory network. Secondly, the promoter of the IRX8 gene, secondary cell wall glycosyltransferase, was used to express a new copy of the fibre transcription factor NST1, and as the IRX8 promoter is induced by NST1, this also created an artificial positive feedback loop (APFL). The combination of strategies—lignin rewiring with APFL insertion—enhances polysaccharide deposition in stems without over‐lignifying them, resulting in higher sugar yields after enzymatic hydrolysis.
Recent work suggests that the stereotype associating brilliance with men may underpin women's underrepresentation in prestigious careers, yet little is known about its development and consequences in ...non‐Western contexts. The present research examined the onset of this stereotype and its relation to children's motivation in 5‐ to 7‐year‐old Korean children (N = 272, 50% girls, tested 2021 to 2022). At age 7, children attributed brilliance to men when evaluating Asians and Whites, and girls became less interested in participating in intellectually challenging tasks than boys. Notably, this gender difference in interest was mediated by children's endorsement of the stereotype. The generalizable early emergence of the gender brilliance stereotype and its detrimental implications press the need to tackle gender imbalance in early childhood.
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•Polystyrene microplastics (PS-MPs) cause pulmonary cytotoxicity by inducing ROS.•PS-MPs is associated with impaired pulmonary barrier by depleting ZO proteins.•PS-MPs inhalation ...increases the risk for chronic obstructive pulmonary disease.
Microplastics (MPs) have become a global environmental concern. Recent studies have shown that MPs, of which the predominant type is often polystyrene (PS; known as PS-MPs), can extend to and affect remote, sparsely inhabited areas via atmospheric transport. Although exposure to inhaled MPs may induce lung dysfunction, further experimental verification of the pulmonary toxic potential of MPs and the mechanism underlying the toxicity is needed. Here we used normal human lung epithelial BEAS-2B cells to clarify the association between pulmonary toxicity and PS-MPs. Results revealed that PS-MPs can cause cytotoxic and inflammatory effects in BEAS-2B cells by inducing reactive oxygen species formation. PS-MPs can decrease transepithelial electrical resistance by depleting zonula occludens proteins. Indeed, decreased α1-antitrypsin levels in BEAS-2B cells suggest that exposure to PS-MPs increases the risk for chronic obstructive pulmonary disease, and high concentrations of PS-MPs can induce these adverse responses. While low PS-MP levels can only disrupt the protective pulmonary barrier, they may also increase the risk for lung disease. Collectively, our findings indicate that PS-MP inhalation may influence human respiratory health.
Highlights • Recent trends in prodrug-based nanocarriers for cancer therapy are provided. • Stimuli-sensitive nanoparticulate drug delivery systems (Nano-DDS) facilitates the spatio-temporally ...controlled release of drugs. • Hybrid Nano-DDS is a potent multifunctional platform to deliver anticancer drugs. • Combination therapy can improve the therapeutic effects of prodrug-based Nano-DDS.
We propose a unifying rheological framework for dense suspensions of non-Brownian spheres, predicting the onsets of particle friction and particle inertia as distinct shear thickening mechanisms, ...while capturing quasistatic and soft particle rheology at high volume fractions and shear rates respectively. Discrete element method simulations that take suitable account of hydrodynamic and particle-contact interactions corroborate the model predictions, demonstrating both mechanisms of shear thickening, and showing that they can occur concurrently with carefully selected particle surface properties under certain flow conditions. Microstructural transitions associated with frictional shear thickening are presented. We find very distinctive divergences of both microstructural and dynamic variables with respect to volume fraction in the thickened and non-thickened states.
A flow regime map for suspended particles that unifies aspects of colloidal, granular and soft-particle rheology across remarkably diverse scales.
Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered adipose tissue, adipokines, ...play critical roles in the development of metabolic syndrome. Although the adipokines leptin and adiponectin improve insulin sensitivity, others contribute to the development of glucose intolerance, including visfatin, fetuin-A, resistin, and plasminogen activator inhibitor-1 (PAI-1). Leptin and adiponectin increase fatty acid oxidation, prevent foam cell formation, and improve lipid metabolism, while visfatin, fetuin-A, PAI-1, and resistin have pro-atherogenic properties. In this review, we briefly summarize the role of various adipokines in the development of metabolic syndrome, focusing on glucose homeostasis and lipid metabolism.
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