The changes of Treg and Th17 cells relate to serum 25(OH)D in patients with initial-onset childhood systemic lupus erythematosus

BackgroundT helper 17 (Th17) cells and regulatory T cells (Treg) are known to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). Improving the balance between Treg and Th17 cells can be a promising new therapeutic target in SLE patients. Vitamin D has a significant impact on the immune inflammatory process and the immune cells involved in this process. The purpose of this study is to investigate the relationship between Th17, Treg, cytokines, and serum 25 hydroxyvitamin D [25(OH)D] in patients with initial-onset childhood SLE.MethodsA total of 82 children aged <18 years with initial-onset SLE were included, as well as 60 healthy subjects during the same period at the Pediatrics Department of the Second Hospital of Hebei Medical University. The chemiluminescence method was performed to detect serum 25(OH)D levels. Flow cytometry was used to evaluate Treg and Th17 cells. An enzyme-linked immunosorbent assay kit was used to evaluate plasma interleukin (IL)-23, IL-17, IL-10, IL-6, and tumor necrosis factor alpha (TNF-α) concentrations.ResultThe serum 25(OH)D levels in patients with initial-onset childhood SLE were significantly lower than those in the healthy controls. The proportion of lupus nephritis (LN) was higher in the vitamin D insufficiency group (71.4%) compared with the vitamin D sufficiency group (30.3%) (p < 0.05). The SLE disease activity index (SLEDAI) was higher in the vitamin D insufficiency group (median = 14) than that in the vitamin D sufficiency group (median = 9) (p < 0.05).The 25(OH)D level was positively correlated with the Treg ratio (r = 0.337, p = 0.002), and it was negatively correlated with the Th17 cell ratio (r = −0.370, p = 0.001). The serum 25(OH)D level had a negative correlation with IL-23 (r = −0.589, p < 0.001), IL-17(r = −0.351, p = 0.001), TNF-α (r = −0.283, p = 0.01), IL-6 (r = −0.392, p < 0.001), and IL-10 (r = −0.313, p = 0.004) levels.ConclusionThe serum 25(OH)D levels decreased in patients with initial-onset childhood SLE. There was a negative correlation between the serum 25(OH)D levels and SLEDAI. The serum 25(OH)D levels in patients with initial-onset childhood SLE were negatively correlated with the Th17 ratio and related cytokines, while positively correlated with the Treg ratio

A regression method for EEG-based cross-dataset fatigue detection

Introduction: Fatigue is dangerous for certain jobs requiring continuous concentration. When faced with new datasets, the existing fatigue detection model needs a large amount of electroencephalogram (EEG) data for training, which is resource-consuming and impractical. Although the cross-dataset fatigue detection model does not need to be retrained, no one has studied this problem previously. Therefore, this study will focus on the design of the cross-dataset fatigue detection model.Methods: This study proposes a regression method for EEG-based cross-dataset fatigue detection. This method is similar to self-supervised learning and can be divided into two steps: pre-training and the domain-specific adaptive step. To extract specific features for different datasets, a pretext task is proposed to distinguish data on different datasets in the pre-training step. Then, in the domain-specific adaptation stage, these specific features are projected into a shared subspace. Moreover, the maximum mean discrepancy (MMD) is exploited to continuously narrow the differences in the subspace so that an inherent connection can be built between datasets. In addition, the attention mechanism is introduced to extract continuous information on spatial features, and the gated recurrent unit (GRU) is used to capture time series information.Results: The accuracy and root mean square error (RMSE) achieved by the proposed method are 59.10% and 0.27, respectively, which significantly outperforms state-of-the-art domain adaptation methods.Discussion: In addition, this study discusses the effect of labeled samples. When the number of labeled samples is 10% of the total number, the accuracy of the proposed model can reach 66.21%. This study fills a vacancy in the field of fatigue detection. In addition, the EEG-based cross-dataset fatigue detection method can be used for reference by other EEG-based deep learning research practices

Extracellular RNA in melanoma: Advances, challenges, and opportunities

Melanoma, a malignant mass lesion that originates in melanocytes and has a high rate of malignancy, metastasis, and mortality, is defined by these characteristics. Malignant melanoma is a kind of highly malignant tumor that produces melanin and has a high mortality rate. Its incidence accounts for 1%–3% of all malignant tumors and shows an obvious upward trend. The discovery of biomolecules for the diagnosis and treatment of malignant melanoma has important application value. So far, the exact molecular mechanism of melanoma development relevant signal pathway still remains unclear. According to previous studies, extracellular RNAs (exRNAs) have been implicated in tumorigenesis and spread of melanoma. They can influence the proliferation, invasion and metastasis of melanoma by controlling the expression of target genes and can also influence tumor progression by participating in signal transduction mechanisms. Therefore, understanding the relationship between exRNA and malignant melanoma and targeting therapy is of positive significance for its prevention and treatment. In this review, we did an analysis of extracellular vesicles of melanoma which focused on the role of exRNAs (lncRNAs, miRNAs, and mRNAs) and identifies several potential therapeutic targets. In addition, we discuss the typical signaling pathways involved in exRNAs, advances in exRNA detection and how they affect the tumor immune microenvironment in melanoma

Autophagy protein NRBF2 has reduced expression in Alzheimer\u27s brains and modulates memory and amyloid-beta homeostasis in mice

Background Dysfunctional autophagy is implicated in Alzheimer\u27s Disease (AD) pathogenesis. The alterations in the expression of many autophagy related genes (ATGs) have been reported in AD brains; however, the disparity of the changes confounds the role of autophagy in AD. Methods To further understand the autophagy alteration in AD brains, we analyzed transcriptomic (RNAseq) datasets of several brain regions (BA10, BA22, BA36 and BA44 in 223 patients compared to 59 healthy controls) and measured the expression of 130 ATGs. We used autophagy-deficient mouse models to assess the impact of the identified ATGs depletion on memory, autophagic activity and amyloid-beta (A beta) production. Results We observed significant downregulation of multiple components of two autophagy kinase complexes BECN1-PIK3C3 and ULK1/2-FIP200 specifically in the parahippocampal gyrus (BA36). Most importantly, we demonstrated that deletion of NRBF2, a component of the BECN1-PIK3C3 complex, which also associates with ULK1/2-FIP200 complex, impairs memory in mice, alters long-term potentiation (LTP), reduces autophagy in mouse hippocampus, and promotes A beta accumulation. Furthermore, AAV-mediated NRBF2 overexpression in the hippocampus not only rescues the impaired autophagy and memory deficits in NRBF2-depleted mice, but also reduces beta-amyloid levels and improves memory in an AD mouse model. Conclusions Our data not only implicates NRBF2 deficiency as a risk factor for cognitive impairment associated with AD, but also support the idea of NRBF2 as a potential therapeutic target for AD

The Chinese pine genome and methylome unveil key features of conifer evolution

Conifers dominate the world's forest ecosystems and are the most widely planted tree species. Their giant and complex genomes present great challenges for assembling a complete reference genome for evolutionary and genomic studies. We present a 25.4-Gb chromosome-level assembly of Chinese pine (Pinus tabuliformis) and revealed that its genome size is mostly attributable to huge intergenic regions and long introns with high transposable element (TE) content. Large genes with long introns exhibited higher expressions levels. Despite a lack of recent whole-genome duplication, 91.2% of genes were duplicated through dispersed duplication, and expanded gene families are mainly related to stress responses, which may underpin conifers' adaptation, particularly in cold and/or arid conditions. The reproductive regulation network is distinct compared with angiosperms. Slow removal of TEs with high-level methylation may have contributed to genomic expansion. This study provides insights into conifer evolution and resources for advancing research on conifer adaptation and development

The phylogenetically-related pattern recognition receptors EFR and XA21 recruit similar immune signaling components in monocots and dicots

During plant immunity, surface-localized pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs). The transfer of PRRs between plant species is a promising strategy for engineering broad-spectrum disease resistance. Thus, there is a great interest in understanding the mechanisms of PRR-mediated resistance across different plant species. Two well-characterized plant PRRs are the leucine-rich repeat receptor kinases (LRR-RKs) EFR and XA21 from Arabidopsis thaliana (Arabidopsis) and rice, respectively. Interestingly, despite being evolutionary distant, EFR and XA21 are phylogenetically closely related and are both members of the sub-family XII of LRR-RKs that contains numerous potential PRRs. Here, we compared the ability of these related PRRs to engage immune signaling across the monocots-dicots taxonomic divide. Using chimera between Arabidopsis EFR and rice XA21, we show that the kinase domain of the rice XA21 is functional in triggering elf18-induced signaling and quantitative immunity to the bacteria Pseudomonas syringae pv. tomato (Pto) DC3000 and Agrobacterium tumefaciens in Arabidopsis. Furthermore, the EFR:XA21 chimera associates dynamically in a ligand-dependent manner with known components of the EFR complex. Conversely, EFR associates with Arabidopsis orthologues of rice XA21-interacting proteins, which appear to be involved in EFR-mediated signaling and immunity in Arabidopsis. Our work indicates the overall functional conservation of immune components acting downstream of distinct LRR-RK-type PRRs between monocots and dicots

Outcomes of Microendoscopic Discectomy and Percutaneous Transforaminal Endoscopic Discectomy for the Treatment of Lumbar Disc Herniation: A Comparative Retrospective Study

Study DesignRetrospective, case control evaluation of 86 patients who underwent microendoscopic discectomy (MED) and percutaneous transforaminal endoscopic discectomy (PTED) for the treatment of lumbar disc herniation (LDH).PurposeTo evaluate the safety and the outcomes of MED and PTED for the treatment of LDH.Overview of LiteratureMED and PTED are minimally invasive surgical techniques for lower back pain. Studies to date have shown that MED and PTED are safe and effective treatment modalities for LDH.MethodsA retrospective study was performed in patients with LDH treated with MED (n=50) and transforaminal endoscopic discectomy (PTED; n=36) in our hospital. All patients were followed-up with self-evaluation questionnaires, Oswestry disability index (ODI), medical outcomes study 36-item short form health survey and MacNab criteria. All the patients in both groups were followed up to 12 months after the operation.ResultsODI questionnaire responses were not statistically different between the MED and PTED groups (53.00 vs. 48.72) before treatment. Average scores and minimal disability after 5 days to 12 months of follow-up were 4.96 in the MED group and 3.61 in the PTED group. According to MacNab criteria, 92.0% of the MED group and 94.4% of the PTED group had excellent or good results with no significant difference.ConclusionsThere was no significant difference between MED and PTED outcomes. Further large-scale, randomized studies with long-term follow-up are needed

Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes

Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers’ tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates

Chemotherapy-induced nausea and vomiting among cancer patients in Shanghai: a cross-sectional study

Background and purpose: Chemotherapy-induced nausea and vomiting (CINV) can cause severe damage to body functions and even lead to death. The prevention of CINV is critically important in patients receiving emetogenic chemotherapy regimen. This study aimed to investigate the prevalence and treatment of CINV in Grade-A tertiary hospitals in Shanghai and explore risk factors of CINV to improve its management. Methods: The clinical data of 376 cancer patients in Grade-A tertiary hospitals in Shanghai from October 2022 to December 2022 were collected retrospectively. The questionnaire was used to conduct a cross-sectional study. The univariate and multivariable logistic regression models were used to evaluate the influencing factors of CINV. Results: The management and coincidence of the guideline in 2022 significantly improved compared to five years ago. For patients receiving high-emetic-risk chemotherapy regimen, the coincidence of the guideline increased from 21.6% to 67.0%. For patients receiving moderate-emetic-risk chemotherapy regimen, the neurokinin-1 (NK-1) receptor antagonist was not significantly associated with CINV. Multivariable analysis showed that the chemotherapy regimen was the only risk factor for CINV during the whole period (P<0.05). Conclusion: The chemotherapy regimen is the main risk factor for CINV. To control CINV better, clinical practitioners should focus on the intrinsic risk of chemotherapy regimens preferentially, estimate the risk and adhere better to guidelines