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Abstract Allergic rhinitis (AR) threatens patient survival. CD4+ T cells play key roles in AR progression. Long non‐coding RNAs (lncRNAs) are key regulators of cell differentiation. Therefore, we investigated the molecular mechanism of the lncRNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) in AR. Expression levels of MALAT1, microRNA (miR)‐135b‐5p, interleukin‐4 (IL‐4), and GATA‐binding protein 3 (GATA‐3) in the nasal mucosa of AR patients were quantified. CD4+ T cells were isolated from the peripheral blood of healthy volunteers and treated with ovalbumin (OVA) and Th2 inducers. After MALAT1 and miR‐135b‐5p levels changed in CD4+ T cells, the proportion of IL‐4‐expressing cells and the levels of IL‐4 and GATA‐3 in OVA‐induced CD4+ T cells were determined. Binding relationships among MALAT1, miR‐135b‐5p, and GATA‐3 were predicted and verified. Rescue experiments were performed to confirm the role of the MALAT1/miR‐135b‐5p/GATA‐3 axis in Th2 differentiation of CD4+ T cells. MALAT1, IL‐4, and GATA‐3 expression was upregulated, whereas miR‐135b‐5p expression was downregulated, in patients with AR. MALAT1 knockdown or miR‐135b‐5p overexpression in CD4+ T cells notably decreased the proportion of IL‐4‐expressing cells and downregulated GATA‐3 and IL‐4 expression in OVA‐induced CD4+ T cells. MALAT1 and GATA‐3 exhibited competitive binding toward miR‐135b‐5p. MALAT1 facilitated CD4+ T cell Th2 differentiation via the miR‐135b‐5p/GATA‐3 axis. MALAT1 facilitated AR development by facilitating CD4+ T cell Th2 differentiation via the miR‐135b‐5p/GATA‐3 axis. This study may provide guidance for clinical treatment of AR.

Objective: This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE).Methods: This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups.Results: One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children’s Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%–87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups.Conclusion: PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE.Clinical Trial Registration: Identifier ChiCTR2300074696

BackgroundSocial interaction is a fundamental human need. Social isolation (SI) can have negative effects on both emotional and cognitive function. However, it is currently unclear how age and the duration of SI affect emotion and recognition function. In addition, there is no specific treatment for the effects of SI.MethodsThe adolescence or adult mice were individually housed in cages for 1, 6 or 12 months and for 2 months to estabolish SI mouse model. We investigated the effects of SI on behavior in mice at different ages and under distinct durations of SI, and we explored the possible underlying mechanisms. Then we performed deep brain stimulation (DBS) to evaluate its influences on SI induced behavioral abnormalities.ResultsWe found that social recognition was affected in the short term, while social preference was damaged by extremely long periods of SI. In addition to affecting social memory, SI also affects emotion, short-term spatial ability and learning willingness in mice. Myelin was decreased significantly in the medial prefrontal cortex (mPFC) and dorsal hippocampus of socially isolated mice. Cellular activity in response to social stimulation in both areas was impaired by social isolation. By stimulating the mPFC using DBS, we found that DBS alleviated cellular activation disorders in the mPFC after long-term SI and improved social preference in mice.ConclusionOur results suggest that the therapeutic potential of stimulating the mPFC with DBS in individuals with social preference deficits caused by long-term social isolation, as well as the effects of DBS on the cellular activity and density of OPCs.

The effects of endogenous lipids and protein in sorghum flour on starch digestion were studied following the depletion of lipids and/or protein and after the reconstitution of separated fractions. The removal of protein or lipids moderately increases the digestibility of starch in raw (uncooked) sorghum flour to values close to those for purified starch. Rapid Visco Analyzer data (as a model for the cooking process) show that cooked sorghum flours with lipids have a lower starch digestibility than those without lipids after RVA processing, due to the formation of starch–lipid complexes as evidenced by their higher final viscosity and larger enthalpy changes. Additionally, the formation of a starch–lipid–protein ternary complex was identified in cooked sorghum flour, rather than in a reconstituted ternary mixture, according to the unique cooling stage viscosity peak and a greater enthalpy of lipid complexes. After heating, the sorghum flour showed a lower digestibility than the depleted flours and the reconstituted flours. The results indicate that the natural organization of components in sorghum flour is an important factor in facilitating the interactions between starch, lipids, and protein during RVA processing and, in turn, reducing the starch digestion.

This study uses two different carbon emission factor methods to analyze the differences in carbon emissions from trucks under different types and times. The analysis is based on the Xinjiang Expressway Database and other data, with the G30 Yandun Toll Station as an example. The study aims to provide insight into the environmental impact of trucking and inform future policy decisions. The study indicates that heavy-duty trucks are responsible for 90% and 97% of the total carbon emissions from all trucks, respectively. The number of vehicles and the type of trucks are the main factors contributing to these emissions. Additionally, the second quarter shows the highest carbon emissions, while the first quarter exhibits the most considerable difference between the results of the two methods. In March, carbon emissions were at their highest. Additionally, the fuel consumption of trucks with GVW ⩾ 31000kg was the highest, with a significant difference between the results of the two methods. It is worth noting that the fuel consumption of trucks with GVW ⩾ 31000kg was also measured. This study provides data to support the implementation of policies related to transportation carbon emissions in Xinjiang. The paper is significant for promoting green travel.

Streptococcus suis (S. suis) is a zoonotic pathogen with multiple serotypes, and thus, multivalent vaccines generating cross-protection against S. suis infections are urgently needed to improve animal welfare and reduce antibiotic abuse. In this study, we established a systematic and comprehensive epitope prediction pipeline based on immunoinformatics. Ten candidate epitopes were ultimately selected for building the multi-epitope vaccine (MVSS) against S. suis infections. The ten epitopes of MVSS were all derived from highly conserved, immunogenic, and virulence-associated surface proteins in S. suis. In silico analyses revealed that MVSS was structurally stable and affixed with immune receptors, indicating that it would likely trigger strong immunological reactions in the host. Furthermore, mice models demonstrated that MVSS elicited high titer antibodies and diminished damages in S. suis serotype 2 and Chz infection, significantly reduced sequelae, induced cytokine transcription, and decreased organ bacterial burdens after triple vaccination. Meanwhile, anti-rMVSS serum inhibited five important S. suis serotypes in vitro, exerted beneficial protective effects against S. suis infections and significantly reduced histopathological damage in mice. Given the above, it is possible to develop MVSS as a universal subunit vaccine against multiple serotypes of S. suis infections.

A 2D imine-linked COF with a hitherto unreported htb type topology was synthesized from a linear diamine linker and a judiciously designed tetra-aldehyde building block. This work opens the door to the development of COFs with unprecedented topologies and may broaden the scope of COF functional materials by pore size and pore surface engineering.

A detailed understanding of abiotic stress tolerance in plants is essential to provide food security in the face of increasingly harsh climatic conditions. Glucosinolates (GLSs) are secondary metabolites found in the Brassicaceae that protect plants from herbivory and pathogen attack. Here we report that in Arabidopsis, aliphatic GLS levels are regulated by the auxin-sensitive Aux/IAA repressors IAA5, IAA6, and IAA19. These proteins act in a transcriptional cascade that maintains expression of GLS levels when plants are exposed to drought conditions. Loss of IAA5/6/19 results in reduced GLS levels and decreased drought tolerance. Further, we show that this phenotype is associated with a defect in stomatal regulation. Application of GLS to the iaa5,6,19 mutants restores stomatal regulation and normal drought tolerance. GLS action is dependent on the receptor kinase GHR1, suggesting that GLS may signal via reactive oxygen species. These results provide a novel connection between auxin signaling, GLS levels and drought response.

Two stable crystalline hydrazone-linked covalent organic frameworks (COFs) (Bth-Dha and Bth-Dma) containing functional O,N,O'-chelating sites have been designed and successfully synthesized by the Schiff-base condensation reactions between benzene-1,3,5-tricarbohydrazide (Bth) and 2,5-dihydroxyterephthalaldehyde (Dha) or 2,5-dimethoxyterephthal-aldehyde (Dma), respectively. Bth-Dma exhibits strong fluorescence in the solid state and in an aqueous dispersion, while no fluorescence can be observed for Bth-Dha. Interestingly, the as-synthesized Bth-Dma can be used as a turn-off fluorescence sensor for the Fe(III) ion in aqueous solution with outstanding selectivity and sensitivity. The recognition process can be attributed to the coordination interaction between Fe(III) ion and the O,N,O'-chelating sites in the pore wall of Bth-Dma COF, as verified by X-ray photoelectron spectroscopy and 1H NMR spectroscopy. To the best of our knowledge, this is the first report on the rational design of luminescent COF with predesigned O,N,O'-chelating sites as a fluorescence sensor for highly selective and sensitive metal ion detection. This work may pave the way for designing luminescent COF sensors with functional binding sites for detecting specific metal ions.

A key remit of the NSF-funded Arabidopsis Research and Training for the 21st Century (ART-21) Research Coordination Network has been to convene a series of workshops with community members to explore issues concerning research and training in plant biology, including the role that research using Arabidopsis thaliana can play in addressing those issues. A first workshop focused on training needs for bioinformatic and computational approaches in plant biology was held in 2016, and recommendations from that workshop have been published (Friesner et al., Plant Physiology, 175, 2017, 1499). In this white paper, we provide a summary of the discussions and insights arising from the second ART-21 workshop. The second workshop focused on experimental aspects of omics data acquisition and analysis and involved a broad spectrum of participants from academics and industry, ranging from graduate students through post-doctorates, early career and established investigators. Our hope is that this article will inspire beginning and established scientists, corporations, and funding agencies to pursue directions in research and training identified by this workshop, capitalizing on the reference species Arabidopsis thaliana and other valuable plant systems.

Transcranial ultrasound stimulation is a neurostimulation technique that has gradually attracted the attention of researchers, especially as a potential therapy for neurological disorders, because of its high spatial resolution, its good penetration depth, and its non-invasiveness. Ultrasound can be categorized as high-intensity and low-intensity based on the intensity of its acoustic wave. High-intensity ultrasound can be used for thermal ablation by taking advantage of its high-energy characteristics. Low-intensity ultrasound, which produces low energy, can be used as a means to regulate the nervous system. The present review describes the current status of research on low-intensity transcranial ultrasound stimulation (LITUS) in the treatment of neurological disorders, such as epilepsy, essential tremor, depression, Parkinson's disease (PD), and Alzheimer's disease (AD). This review summarizes preclinical and clinical studies using LITUS to treat the aforementioned neurological disorders and discusses their underlying mechanisms.

Abstract Background Lung adenocarcinoma is the leading cause of cancer death worldwide. Recently, ubiquitin C-terminal hydrolase L1 (UCHL1) has been demonstrated to be highly expressed in many tumors and plays the role of an oncogene. However, the functional mechanism of UCHL1 is unclear in lung adenocarcinoma progression. Methods We analyzed the differential expression of the UCHL1 gene in lung adenocarcinoma and normal lung tissues, and the correlation between the UCHL1 gene and prognosis was also analyzed by the bioinformatics database TCGA. Meanwhile, we detected and analyzed the expression of UCHL1 and Ki-67 protein in a tissue microarray (TMA) containing 150 patients with lung adenocarcinoma by immunohistochemistry (IHC) and clinicopathological characteristics by TCGA database. In vitro experiments, we knocked down the UCHL1 gene of A549 cells and detected the changes in cell migration, invasion, and apoptosis. At the same time, we analyzed the effect of UCHL1 on anti-tumor drug sensitivity of lung adenocarcinoma by a bioinformatics database. In terms of the detection rate of lung adenocarcinoma indicators, we analyzed the impact of UCHL1 combined with common clinical indicators on the detection rate of lung adenocarcinoma through a bioinformatics database. Results In this study, the analysis of UCHL1 protein expression in lung adenocarcinoma proved that obviously higher UCHL1 protein level was discovered in lung adenocarcinoma tissues. The expression of UCHL1 was closely related to poor clinical outcomes. Interestingly, a significantly positive correlation between the expression of UCHL1 and Ki-67-indicated UCHL1 was associated with tumor migration and invasion. Through executing loss of function tests, we affirmed that silencing of UCHL1 expression significantly inhibited migration and invasion of lung adenocarcinoma cells in vitro. Furthermore, lung adenocarcinoma cells with silenced UCHL1 showed a higher probability of apoptosis. In terms of the detection rate of lung adenocarcinoma indicators, we discovered UCHL1 could improve the detection rate of clinical lung adenocarcinoma and affect drug sensitivity. Conclusion In lung adenocarcinoma, UCHL1 promotes tumor migration, invasion, and metastasis by inhibiting apoptosis and has an important impact on the clinical drug treatment of lung adenocarcinoma. In addition, UCHL1 can improve the detection rate of clinical lung adenocarcinoma. Above all, UCHL1 may be a new marker for the diagnosis of lung adenocarcinoma and provide a new target for the treatment of clinical diseases.

Abstract At present, the treatment of esophageal cancer (EC) is mainly surgical and drug treatment. However, due to drug resistance, these therapies can not effectively improve the prognosis of patients with the EC. Therefore, a multigene prognostic risk scoring system was constructed by bioinformatics analysis method to provide a theoretical basis for the prognosis and treatment decision of EC. The gene expression profiles and clinical data of esophageal cancer patients were gathered from the Cancer Genome Atlas TCGA database, and the differentially expressed genes (DEGs) were screened by R software. Genes with prognostic value were screened by Kaplan Meier analysis, followed by functional enrichment analysis. A cox regression model was used to construct the prognostic risk score model of DEGs. ROC curve and survival curve were utilized to evaluate the performance of the model. Univariate and multivariate Cox regression analysis was used to evaluate whether the model has an independent prognostic value. Network tool mirdip was used to find miRNAs that may regulate risk genes, and Cytoscape software was used to construct gene miRNA regulatory network. GSCA platform is used to analyze the relationship between gene expression and drug sensitivity. 41 DEGs related to prognosis were pre-liminarily screened by survival analysis. A prognostic risk scoring model composed of 8 DEGs (APOA2, COX6A2, CLCNKB, BHLHA15, HIST1H1E, FABP3, UBE2C and ERO1B) was built by Cox regression analysis. In this model, the prognosis of the high-risk score group was poor (P

This research presents a rigorous comparative analysis of high‐pressure homogenization (HPH) and microfluidization (MF) for the production of krill oil (KO) emulsions, scrutinizing their impact on oxidative stability, bioaccessibility, and the behavior under in vitro simulated digestion. Our findings revealed that MF emulsions possessed a distinct advantage, with a droplet size and distribution that promoted exceptional oxidative stability, evidenced by a sustained reduction in oxidative markers and enhanced retention of bioactive components, including EPA and DHA, and the potent antioxidant astaxanthin. In contrast, HPH yielded larger and less uniform particles, correlating with diminished stability. The in vitro digestion studies underscored the superior bioaccessibility of MF emulsions, with a pronounced release of free fatty acids during the intestinal phase, indicative of an optimized digestion and absorption process due to the smaller droplet size of the emulsions. The study's insights advocate for the adoption of microfluidization in the food industry for the development of advanced delivery systems for n‐3 fatty acids, particularly in the context of KO‐based products. The technique shows promise in enhancing the quality, stability, and bioavailability of these products, which are rich in health‐promoting lipids. The microfluidization technique emerges as a promising avenue for the fortification of a diverse range of commercial food, beverage, and pharmaceutical products with lipids that contribute to health and wellness. [ABSTRACT FROM AUTHOR]