By regulating the IP3R/GRP75/VDAC1 complex to restore mitochondrial dynamic balance, selenomethionine reduces lipopolysaccharide-induced neuronal apoptosis.

Selenium (Se), as one of the essential trace elements, plays an anti-inflammatory, antioxidation, and immune-enhancing effect in the body. In addition, Se can also improve nervous system damage induced by various factors. Earlier studies have described the important role of mitochondrial dynamic imbalance in lipopolysaccharide (LPS)-induced nerve injury. The inositol 1,4,5-triphosphate receptor (IP3R)/glucose-regulated protein 75 (GRP75)/voltage-dependent anion channel 1 (VDAC1) complex is considered to be the key to regulating mitochondrial dynamics. However, it is not clear whether Selenomethionine (SeMet) has any influence on the IP3R/GRP75/VDAC1 complex. Therefore, the aim of this investigation was to determine whether SeMet can alleviate LPS-induced brain damage and to elucidate the function of the IP3R/GRP75/VDAC1 complex in it. We established SeMet and/or LPS exposure models in vivo and in vitro using laying hens and primary chicken nerve cells. We noticed that SeMet reversed endoplasmic reticulum stress (ERS) and the imbalance in mitochondrial dynamics and significantly prevented the occurrence of neuronal apoptosis. We made this finding by morphological observation of the brain tissue of laying hens and the detection of related genes such as ERS, the IP3R/GRP75/VDAC1 complex, calcium signal (Ca2+), mitochondrial dynamics, and apoptosis. Other than that, we also discovered that the IP3R/GRP75/VDAC1 complex was crucial in controlling Ca2+ transport between the endoplasmic reticulum and the mitochondrion when SeMet functions as a neuroprotective agent. In summary, our results revealed the specific mechanism by which SeMet alleviated LPS-induced neuronal apoptosis for the first time. As a consequence, SeMet has great potential in the treatment and prevention of neurological illnesses (like neurodegenerative diseases).

Activation of ß2-adrenergic receptors prevents AD-type synaptotoxicity via epigenetic mechanisms.

We previously reported that prolonged exposure to an enriched environment (EE) enhances hippocampal synaptic plasticity, with one of the significant mechanistic pathways being activation of ß2-adrenergic receptor (ß2-AR) signaling, thereby mitigating the synaptotoxic effects of soluble oligomers of amyloid ß-protein (oAß). However, the detailed mechanism remained elusive. In this work, we recorded field excitatory postsynaptic potentials (fEPSP) in the CA1 region of mouse hippocampal slices treated with or without toxic Aß-species. We found that pharmacological activation of ß2-AR, but not ß1-AR, selectively mimicked the effects of EE in enhancing LTP and preventing oAß-induced synaptic dysfunction. Mechanistic analyses showed that certain histone deacetylase (HDAC) inhibitors mimicked the benefits of EE, but this was not seen in ß2-AR knockout mice, suggesting that activating ß2-AR prevents oAß-mediated synaptic dysfunction via changes in histone acetylation. EE or activation of ß-ARs each decreased HDAC2, whereas Aß oligomers increased HDAC2 levels in the hippocampus. Further, oAß-induced inflammatory effects and neurite degeneration were prevented by either ß2-AR agonists or certain specific HDAC inhibitors. These preclinical results suggest that activation of ß2-AR is a novel potential therapeutic strategy to mitigate oAß-mediated features of AD.

The Laparoscopic Right-lower Quadrant Approach for the Treatment of Right-sided Colon Cancer Offers Advantages Such as Shorter Surgical Time and Less Blood Loss.

Objective: This study aims to compare the therapeutic efficacy of laparoscopic right-lower quadrant and midline approaches for the treatment of right-sided colon cancer and evaluate the analgesic effect of parecoxib sodium. Methods: Sixty patients with right-sided colon cancer admitted to Hospital of Lin 'an District between January 2019 and November 2022 were selected. They were divided into the study group A (n=30) with a right-lower quadrant approach and the study group B (n=30) with a midline approach. All patients received parecoxib sodium. Surgical time, blood loss, postoperative complications, and other relevant indicators were recorded and compared between the two groups. Additionally, a control group of 60 right-sided colon cancer patients who underwent conventional non-exclusive analgesic laparoscopic surgery during the same period was included to compare the analgesic effects between the study and control groups. Results: The surgical time (RR = 0.608, 95%CI 0.51, 1.53, P = .042), blood loss (RR = 0.798, 95%CI 0.52, 1.02, P < .001), time for bowel function recovery (RR = 0.808, 95%CI 0.50, 1.77, P = .007), and length of hospital stay (RR = 0.766, 95%CI 0.56, 1.72, P =.052) were significantly lower in group A than in group B, while the number of lymph node dissections was higher in group A (RR = 0.803, 95%CI 0.62, 1.52, P = .047). The postoperative levels of tumor-specific growth factor (TSGF) (RR = 0.710, 95%CI 0.50, 1.55, P < .001) and carcinoembryonic antigen (CEA) (RR = 0.803, 95%CI 0.62, 1.52, P < .001) were significantly decreased in both groups A and B, with no significant difference between the groups (P > .05). The incidence of complications in group A was significantly lower than in group B (RR = 0.167, 95%CI 0.17, 0.63, P = .044). The VAS scores of the study group at 2/4/6/8 hours postoperatively were significantly lower than those of the control group (RR = 0.702, 95%CI 0.52, 1.62, P < .001). The SF-36 scores of the study group were significantly higher than those of the control group (RR = 0.753, 95%CI 0.56, 1.82, P < .001). Conclusions: The Laparoscopic right-lower quadrant approach for the treatment of right-sided colon cancer offers advantages such as shorter surgical time and less blood loss. It demonstrates significant clinical efficacy and reduces the incidence of postoperative complications. Parecoxib sodium enhances postoperative analgesic effect, effectively alleviating patient pain, promoting recovery, and improving quality of life. It is worth promoting in clinical practice.

Insight into the mechanism of melatonin in attenuating PCB126-induced liver injury: Resistance to ROS-dependent NETs formation to alleviate inflammation and lipid metabolism dysfunction.

3,3',4',4',5-Polychlorinated biphenyls (PCB126) is classified as a persistent organic environmental pollutant that can cause liver damage by producing excessive reactive oxygen species (ROS). ROS also can stimulate neutrophil extracellular traps (NETs) formation, which cause damage to organism if NETs are produced in excess. Melatonin is generally considered to possess strong antioxidant and anti-inflammation prosperities, but it is unclear whether it can alleviate PCB126-induced injury. To explore whether PCB126-induced liver injury is related to the formation of NETs and whether melatonin has a potent protective effect, we established PCB126 exposure/ PCB126 and melatonin co-treatment mouse models by gavage. To further clarify the specific mechanism, we also cultured neutrophils and AML12 cells to replicate in vivo model. Here, we found PCB126 exposure resulted in an elevation in the activities of MDA, LPO, PCO, and 8-OHdG, and a reduction in the activities of CAT, GSH-PX and SOD. We found that PCB126 exposure led to an elevation in the expression levels of chemokines (CCL2, CCL3, CCL4, CXCL12, and CXCL8) and marker factors for NETs formation (MPO, NE, NOX2, PKCα, and PKCζ) in the PCB126 group. IF, SYTOX staining, and SEM results also revealed that PCB126 could stimulate NETs formation. In addition, results of a co-culture system of PBNs and AML12 cells revealed that the expression levels of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) significantly decreased and the expression levels of metabolism factors (Fas, Acc, and Srebp) slightly decreased for scavenging NETs, indicating NETs formation aggravated PCB126-induced hepatic damages. Noteworthy, treatment with melatonin reversed these results. In summary, our findings revealed that melatonin alleviated hepatic damage aggravated by PCB126-induced ROS-dependent NETs formation through suppressing excessive ROS production. This finding not only enriches toxicological mechanism of PCB126, but more importantly extends biological effects of melatonin and its potential application values.

Stent-to-vessel diameter ratio is associated with in-stent stenosis after flow-diversion treatment of intracranial aneurysms.

BACKGROUND AND PURPOSE: Flow-diversion treatment for intracranial aneurysms has been associated with the development of in-stent stenosis (ISS) for unclear reasons. We assess whether the size of the stent relative to that of the vessel (the stent-to-vessel diameter ratio, or SVR) may be predictive of the development of ISS after treatment with flow diverters. METHODS: We retrospectively reviewed patients with unruptured intracranial aneurysms who underwent flow-diversion treatment using either the Pipeline or Tubridge embolization device from September 2018 to September 2022. The relationship between SVR and ISS was analyzed. Multiple logistic regression models were used to determine the significant predictors. RESULTS: A total of 458 patients with 481 aneurysms were included. In a mean angiographic follow-up of 10.73 ± 3.97 months, ISS was detected in 68 cases (14.1 %). After adjusting for candidate variables, a higher distal SVR (DSVR) was associated with an increased risk of ISS (adjusted odds ratio [aOR] = 3.420, 95 % confidence interval [CI] = 1.182 - 9.889, p = 0.023). We conducted a subgroup analysis of the two different flow diverters to assess the effects of their individual characteristics. Our results showed a significant association between the DSVR and the incidence of ISS in both the Pipeline (aOR = 4.033, 95 % CI = 1.156-14.072, p = 0.029) and Tubridge groups (aOR = 11.981, 95 % CI=1.005-142.774, p = 0.049). CONCLUSION: A higher DSVR was associated with an increased risk of ISS. This may help neurointerventionalists select an appropriate stent size when conducting flow-diversion treatment for intracranial aneurysms.

webSCST: an interactive web application for single-cell RNA-sequencing data and spatial transcriptomic data integration.

SUMMARY: Integrative analysis of single-cell RNA-sequencing (scRNA-seq) data with spatial data for the same species and organ would provide each cell sample with a predictive spatial location, which would facilitate biological study. However, publicly available spatial sequencing datasets for specific species and organs are rare and are often displayed in different formats. In this study, we introduce a new web-based scRNA-seq analysis tool, webSCST, that integrates well-organized spatial transcriptome sequencing datasets categorized by species and organs, provides a user-friendly interface for raw single-cell processing with popular integration methods and allows users to submit their raw scRNA-seq data once to obtain predicted spatial locations for each cell type. AVAILABILITY AND IMPLEMENTATION: webSCST implemented in shiny with all major browsers supported is available at http://www.webscst.com. webSCST is also freely available as an R package at https://github.com/swsoyee/webSCST.

Deep learning for ultra-widefield imaging: a scoping review.

PURPOSE: This article is a scoping review of published and peer-reviewed articles using deep-learning (DL) applied to ultra-widefield (UWF) imaging. This study provides an overview of the published uses of DL and UWF imaging for the detection of ophthalmic and systemic diseases, generative image synthesis, quality assessment of images, and segmentation and localization of ophthalmic image features. METHODS: A literature search was performed up to August 31st, 2021 using PubMed, Embase, Cochrane Library, and Google Scholar. The inclusion criteria were as follows: (1) deep learning, (2) ultra-widefield imaging. The exclusion criteria were as follows: (1) articles published in any language other than English, (2) articles not peer-reviewed (usually preprints), (3) no full-text availability, (4) articles using machine learning algorithms other than deep learning. No study design was excluded from consideration. RESULTS: A total of 36 studies were included. Twenty-three studies discussed ophthalmic disease detection and classification, 5 discussed segmentation and localization of ultra-widefield images (UWFIs), 3 discussed generative image synthesis, 3 discussed ophthalmic image quality assessment, and 2 discussed detecting systemic diseases via UWF imaging. CONCLUSION: The application of DL to UWF imaging has demonstrated significant effectiveness in the diagnosis and detection of ophthalmic diseases including diabetic retinopathy, retinal detachment, and glaucoma. DL has also been applied in the generation of synthetic ophthalmic images. This scoping review highlights and discusses the current uses of DL with UWF imaging, and the future of DL applications in this field.

Post-focus compression in Brahvi and Balochi.

Previous research has shown that post-focus compression (PFC) - the reduction of pitch range and intensity after a focused word in an utterance, is a robust means of marking focus, but it is present only in some languages. The presence of PFC appears to follow language family lines. The present study is a further exploration of the distribution of PFC by investigating Brahvi, a Dravidian language, and Balochi, an Indo-Iranian language. Balochi is predicted to show PFC given its presence in other Iranian languages. Dravidian languages have not been studied for prosodic focus before and they are not related to any languages with PFC. We recorded twenty native speakers from each language producing declarative sentences in different focus conditions. Acoustic analyses showed that, in both languages, post-focus f0 and other correlates were significantly reduced relative to baseline neutral-focus sentences, but post-focus lowering of f0, and intensity was greater in magnitude in Balochi than in Brahvi. The Balochi results confirm our prediction, while the Brahvi results offer the first evidence of PFC in a Dravidian language. The finding of PFC in a Dravidian language is relevant to a postulated origin of PFC, which is related to the controversial Nostratic Macrofamily hypothesis.

Consonantal F0 perturbation in American English involves multiple mechanisms.

In this study, we revisit consonantal perturbation of F0 in English, taking into particular consideration the effect of alignment of F0 contours to segments and the F0 extraction method in the acoustic analysis. We recorded words differing in consonant voicing, manner of articulation, and position in syllable, spoken by native speakers of American English in both statements and questions. In the analysis, we compared methods of F0 alignment and found that the highest F0 consistency occurred when F0 contours were time-normalized to the entire syllable. Applying this method, along with using syllables with nasal consonants as the baseline and a fine-detailed F0 extraction procedure, we identified three distinct consonantal effects: a large but brief (10-40 ms) F0 raising at voice onset regardless of consonant voicing, a smaller but longer-lasting F0 raising effect by voiceless consonants throughout a large proportion of the following vowels, and a small lowering effect of around 6 Hz by voiced consonants, which was not found in previous studies. Additionally, a brief anticipatory effect was observed before a coda consonant. These effects are imposed on a continuously changing F0 curve that is either rising-falling or falling-rising, depending on whether the carrier sentence is a statement or a question.

Modelling microprosodic effects can lead to an audible improvement in articulatory synthesis.

When pitch is explicitly modelled for parametric speech synthesis, microprosodic variations of the fundamental frequency f0 are usually disregarded by current intonation models. While there are numerous studies dealing with the nature and the origin of microprosody, little research has been done on its audibility and its effect on the naturalness of synthetic speech. In this work, the influence of obstruent-related microprosodic variations on the perceived naturalness of articulatory speech synthesis was studied. A small corpus of 20 German words and sentences was re-synthesized using the state-of-the-art articulatory synthesizer VocalTractLab. The pitch contours of the real utterances were extracted and fitted with the Target-Approximation-Model. After the real microprosodic variations were removed from the obtained pitch contours, synthetic variations were applied based on a microprosody model. Subsequently, multiple stimuli with different microprosody amplitudes were synthesized and evaluated in a listening experiment. The results indicate that microprosodic variations are barely audible, but can lead to a greater perceived naturalness of the synthesized speech in certain cases.

The effect of physical exercise on rheumatoid arthritis: An overview of systematic reviews and meta-analysis.

AIMS: To determine which outcomes will be improved by different exercise interventions and the evidence quality for each intervention. DESIGN: Overview of systematic reviews and meta-analysis. DATA SOURCES: PubMed, Cochrane, Web of Science, CINAHL, and Embase. Published from the establishment of the database to 3 September 2019. REVIEW METHODS: AMSTAR 2 and PRISMA were used to evaluate methodological and reporting quality. Evidence quality of the effect of each intervention was assessed according to GRADE guidelines. Meta-analysis of original studies was conducted for comparison of systematic reviews and to explore the effect of different exercise interventions on the same outcome. RESULTS: Ten systematic reviews were included in the overview. A significant improvement was seen in: aerobic exercise for aerobic capacity; strength training for erythrocyte sedimentation rate and 50-foot walking time; aerobic exercise combined with strength training for aerobic capacity, physical function, and fatigue; hand exercise for hand function. CONCLUSIONS: For the maximum benefit of rheumatoid arthritis (RA) patients, different exercise methods should be selected according to the symptoms. For RA patients, any exercise is better than no exercise, but the intensity, frequency, and period of exercise for better results are not determined. IMPACT: What problem did the study address is which outcomes will be improved by different exercise interventions. For maximum benefit for RA patients, different exercise methods should be selected according to symptoms. The research summarized the evidence of exercise rehabilitation of RA and will help RA patients or their caregivers choose the appropriate type of exercise, which will play a positive role on the rehabilitation of patients with RA.

MiR-4310 induced by SP1 targets PTEN to promote glioma progression.

BACKGROUND: miRNAs have been reported to be involved in multiple biological processes of gliomas. Here, we aimed to analyze miR-4310 and its correlation genes involved in the progression of human glioma. METHODS: miR-4310 expression levels were examined in glioma and non-tumor brain (NB) tissues. The molecular mechanisms of miR-4310 expression and its effects on cell proliferation, migration, and invasion were explored using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide, Transwell chamber, Boyden chamber, and western blot analyses, as well as its effect on tumorigenesis was explored in vivo in nude mice. The relationships between miR-4310, SP1, phosphatase, and tensin homolog (PTEN) were explored using chromatin immunoprecipitation, agarose gel electrophoresis, electrophoresis mobility shift, and dual-luciferase reporter gene assays. RESULTS: miR-4310 expression was upregulated in glioma tissues compared to that in NB tissues. Overexpressed miR-4310 promoted glioma cell proliferation, migration, and invasion in vitro, as well as tumorigenesis in vivo. The inhibition of miR-4310 expression was sufficient to reverse these results. Mechanistic analyses revealed that miR-4310 promoted glioma progression through the PI3K/AKT pathway by targeting PTEN. Additionally, SP1 induced the expression of miR-4310 by binding to its promoter region. CONCLUSION: miR-4310 promotes the progression of glioma by targeting PTEN and activating the PI3K/AKT pathway; meanwhile, the expression of miR-4310 was induced by SP1.

Interaction of prosody and syntax-semantics in Mandarin wh-indeterminates.

This paper reports on two speech-production experiments focused on Putonghua and Taiwan Mandarin sentence-final particles and wh-phrases that have interrogative or indefinite readings in three contexts: yes/no questions, wh-questions, and statements. Sentence-final particles were found to influence focus-prosody through right-edge shortening and lowering of F0 and intensity of wh-phrases, thus distinguishing wh-interrogatives from indefinites and questions from statements. Speakers adopt multidimensional acoustic strategies to shape intonation: while maintaining the lexical tones, prosody interacts with the organization imposed by syntax, semantics, and focus. The two varieties of Mandarin differ in the extent to which their prosodic differences represent such syntactic-semantic information.

SKA1 promotes malignant phenotype and progression of glioma via multiple signaling pathways.

BACKGROUND: Spindle and kinetochore associated protein 1 (SKA1) is a protein involved in chromosome congression and mitosis. It has been found to be upregulated and oncogenic in several human cancers. Herein, we investigated the precise role of SKA1 in the progression and malignant phenotype of human glioma. METHODS: Bioinformatic analysis was carried out based on the RNA-seq data and corresponding clinical data from GEO, TCGA and CGGA databases. Western blot was performed to analyze the expression of SKA1 in clinical samples and signaling pathway proteins in glioma cells, respectively. CCK8 assay, colony forming assay and EdU assay were performed to assess the cell viability. Cell migration and invasion assays were also performed. Moreover, xenograft model was established and the expression of SKA1 was assessed in the xenograft by immunohistochemistry. RESULTS: SKA1 expression is positively correlated with glioma grade and could be a promising biomarker for GBM. Moreover, overexpression of SKA1 may lead to poor prognosis in glioma. Downregulation of SKA1 attenuated cell viability, migration, and invasion in U251, U87, LN229 and T98 cells. Furthermore, GSEA analysis demonstrated that SKA1 was involved in the cell cycle, EMT pathway as well as Wnt/ß-catenin signaling pathway, which were then confirmed with Western blot analysis. CONCLUSION: SKA1 promotes malignant phenotype and progression of glioma via multiple pathways, including cell cycle, EMT, Wnt/ß-catenin signaling pathway. Therefore, SKA1 could be a promising therapeutic target for the treatment of human gliomas.

Effectiveness of e-health based self-management to improve cancer-related fatigue, self-efficacy and quality of life in cancer patients: Systematic review and meta-analysis.

AIMS: To integrate the overall effect of e-health based self-management on cancer-related fatigue (CRF), self-efficacy, and quality of life (QOL) among adult cancer patients. DESIGN: A systematic review and meta-analysis of randomized controlled trials. DATA SOURCES: We researched PubMed, Cumulative Index Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Web of Science and Embase up to 14 July 2019. REVIEW METHODS: We conducted the review with the Cochrane Handbook (version 5.1.0) and measured the quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation criteria. RESULTS: Literature searching identified 15 trials with a total of 2,337 participants. Integrated results analysis of e-health based self-management demonstrated a statistically significant but small effect on CRF and self-efficacy, but no statistically significant improvement on the QOL. Meanwhile, subgroup analysis indicated that e-health based self-management had a larger effect on fatigue compared with usual care/waiting list control. CONCLUSION: E-health based self-management is effective for CRF and self-efficacy, but not the QOL. More high-quality randomized control trials are warranted to confirm these conclusions. IMPACT: Results showed e-health could improve fatigue and self-efficacy but not the QOL. Health providers could take into the various factors of e-health interventions when providing telehealth service. Other researchers might be inspired by the current review before they begin a study about e-health.

Monodisperse Polyaspartic Acid Derivative Microspheres for Potential Tumor Embolization Therapy.

Polyaspartic acid derivatives are a well-known kind of polypeptide with good biocompatibility and biodegradability, and thus have been widely used as biomedical materials, including drug-loaded nano-scale micelles or macroscopic hydrogels. In this work, for the first time, monodisperse polyaspartic acid derivative microspheres with diameter ranging from 120 to 350 µm for potential tumor embolization therapy are successfully prepared by single emulsion droplet microfluidic technique. The obtained microsphere shows fast cationic anticancer drug doxorubicin hydrochloride loading kinetics with high loading capacity, which is much better than those of the commercial ones. Additionally, drug release behaviors of the drug-loaded microspheres with different diameters in different media are also studied and discussed in detail. These results provide some new insights for the preparation and potential application of polyaspartic acid derivative-based monodisperse microspheres, especially for their potential application as embolic agent.

MECOM: A Meta-Completion Network for Fine-Grained Recognition With Incomplete Multi-Modalities.

Our work focuses on tackling the problem of fine-grained recognition with incomplete multi-modal data, which is overlooked by previous work in the literature. It is desirable to not only capture fine-grained patterns of objects but also alleviate the challenges of missing modalities for such a practical problem. In this paper, we propose to leverage a meta-learning strategy to learn model abilities of both fast modal adaptation and more importantly missing modality completion across a variety of incomplete multi-modality learning tasks. Based on that, we develop a meta-completion method, termed as MECOM, to perform multimodal fusion and explicit missing modality completion by our proposals of cross-modal attention and decoupling reconstruction. To further improve fine-grained recognition accuracy, an additional partial stream (as a counterpart of the main stream of MECOM, i.e., holistic) and the part-level features (corresponding to fine-grained objects' parts) selection are designed, which are tailored for fine-grained nature to capture discriminative but subtle part-level patterns. Comprehensive experiments from quantitative and qualitative aspects, as well as various ablation studies, on two fine-grained multimodal datasets and one generic multimodal dataset show our superiority over competing methods. Our code is open-source and available at https://github.com/SEU-VIPGroup/MECOM.

Correlation Between C4/IgG with Macroproteinuria in Chronic Kidney Disease: A Pilot Study.

Background and Objectives: Loss of immunoglobulin G (IgG) is accompanied with proteinuria, especially macroproteinuria. The complement system participates kidney disease resulting in proteinuria. Whether the ratio of complement and IgG is associated with macroproteinuria remains unknown. Design Setting Participants and Measurements: A total of 1013 non-dialysis chronic kidney disease (CKD) patients were recruited according to the electrical case records system with 268 patients who endured kidney biopsy. Patients were grouped via the estimated glomerular filtration rate or the levels of proteinuria determination. Biomarkers in different CKD groups or proteinuria groups were compared by one-way ANOVA or independent samples t-test. Pearson or spearman analysis was employed to analyze correlation between clinical indexes. Further, influence factor of macroproteinuria was studied by using binary logistic regression. The ROC curve was performed to explore probable predictive biomarker for macroproteinuria. Results: No significant difference of complement C3 and C4 among CKD1 to CKD5 stages, while higher level of complement C4 in patients with macroproteinuria. Further, C4 had a positive correlation with proteinuria (r=0.255, p=0.006). After adjusted for age, IgA, IgM, triglyceride and HDL, a binary logistic regression model showed lnC4/IgG (OR=3.561, 95% CI 2.196-5.773, p<0.01), gender (OR=1.737, 95% CI 1.116-2.702, p=0.014), age (OR=0.983, 95% CI 0.969-0.997, p=0.014), and history of diabetes (OR=0.405, 95% CI 0.235-0.699, p<0.01) were independent influence factors of macroproteinuria. The area under the ROC curve was 0.77 (95% CI: 0.75-0.82, p<0.001) for C4/IgG. The analysis of ROC curves revealed a best cut-off for complement C4 was 0.024 and yielded a sensitivity of 71% and a specificity of 71%. The area under the ROC curve was 0.841 (95% CI: 0.735-0.946, p < 0.001) for C4/IgG in IgA nephropathy patients. The analysis of ROC curves revealed a best cut-off for complement C4/IgG was 0.026 and yielded a sensitivity of 75% and a specificity of 81.2%. The area under the ROC curve for C4/IgG in CKD1-5 stages were 0.772, 0.811, 0.785, 0.835, 0.674. Conclusion: Complement C4/IgG could be used to predict macroproteinuria.

Expression of microRNAs during apheresis platelet storage up to day 14 in a blood bank in China.

BACKGROUND: Storage affects platelet microRNAs (miRNAs); discussing miRNA expression differences in apheresis platelets after varied storage periods is important for developing platelet quality measurement tools and identifying platelet storage lesion biomarkers. To our knowledge, the difference of MicroRNA expression profile in up to 14-day storage apheresis platelets has less relevant reports. STUDY DESIGN AND METHODS: Apheresis platelet bags from three donors were collected, divided into six groups, and stored for 1, 3, 5, 7, 9, and 14 days. miRNA expression was determined using quantitative reverse transcription polymerase chain reaction. Differentially expressed miRNAs were screened using RNA sequencing. RESULTS: MiRNA expression profiles showed that the six treatment groups generally highly expressed hsa-let-7 family, hsa-miR-26a-5p, hsa-miR-92a-3p, hsa-miR-199, and hsa-miR-103a-3p. A total of 15 miRNAs in the top 10 known miRNAs of the six groups were highly expressed. Time series analyses for the trend classification of 944 differentially expressed miRNAs indicated 43 genes with 14 trend changes. Hsa-miR-223-3p, hsa-miR-181a-5p, hsa-miR-4433b-5p, hsa-miR-22-3p, and hsa-miR-30c-5p were selected, and the qRT-PCR results also showed that they were significantly reduced under standard blood bank condition. DISCUSSION: Expression of microRNAs lays the foundation for further research on apheresis platelet storage lesions. Based on our results from information analysis and miRNA target gene prediction, we suggest hsa-miR-30c-5p as a biomarker of the quality and viability of apheresis platelets during storage in blood banks.

Dietary selenomethionine reduced oxidative stress by resisting METTL3-mediated m6A methylation level of Nrf2 to ameliorate LPS-induced liver necroptosis in laying hens.

Selenomethionine (SeMet) as the main form of daily dietary selenium, occupies essential roles in providing antioxidant and anti-inflammatory properties, which alleviates inflammatory liver damage. N6-methyladenosine (m6A) is one of the most prevalent and abundant internal transcriptional modifications that regulate gene expression. To investigate the protective mechanism of SeMet on liver injury and the regulatory effect of m6A methylation modification, we established the model by supplementing dietary SeMet, and LPS as stimulus in laying hens. LMH cells were intervened with SeMet (0.075 µM) and/or LPS (60 µg/mL). Subsequently, histopathology and ultrastructure of liver were observed. Western Blot, qRT-PCR, colorimetry, MeRIP-qPCR, fluorescent probe staining and AO/EB were used to detect total m6A methylation level, m6A methylation level of Nrf2, ROS, inflammatory and necroptosis factors. Studies showed that SeMet suppressed LPS-induced upregulation of total m6A methylation levels and METTL3 expression. Interestingly, SeMet reduced the m6A methylation level of Nrf2, activated antioxidant pathways and alleviated oxidative stress. LMH cells were transfected with 50 µm siMETTL3. SeMet/SiMETTL3 reversed the LPS-induced reduction in Nrf2 mRNA stability, slowed down its degradation rate. Moreover, LPS induced oxidative stress, led to necroptosis and activated NF-κB to promote the expression of inflammatory factors. SeMet/SiMETTL3 alleviated LPS-induced necroptosis and inflammation. Altogether, SeMet enhanced antioxidant and anti-inflammatory capacity by reducing METTL3-mediated m6A methylation levels of Nrf2, ultimately alleviating liver damage. Our findings provided new insights and therapeutic target for the practical application of dietary SeMet in the treatment and prevention of liver inflammation, and supplied a reference for comparative medicine.