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).

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.

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.

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.

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.

A review: simulation tools for genome-wide interaction studies.

Genome-wide association study (GWAS) is essential for investigating the genetic basis of complex diseases; nevertheless, it usually ignores the interaction of multiple single nucleotide polymorphisms (SNPs). Genome-wide interaction studies provide crucial means for exploring complex genetic interactions that GWAS may miss. Although many interaction methods have been proposed, challenges still persist, including the lack of epistasis models and the inconsistency of benchmark datasets. SNP data simulation is a pivotal intermediary between interaction methods and real applications. Therefore, it is important to obtain epistasis models and benchmark datasets by simulation tools, which is helpful for further improving interaction methods. At present, many simulation tools have been widely employed in the field of population genetics. According to their basic principles, these existing tools can be divided into four categories: coalescent simulation, forward-time simulation, resampling simulation, and other simulation frameworks. In this paper, their basic principles and representative simulation tools are compared and analyzed in detail. Additionally, this paper provides a discussion and summary of the advantages and disadvantages of these frameworks and tools, offering technical insights for the design of new methods, and serving as valuable reference tools for researchers to comprehensively understand GWAS and genome-wide interaction studies.

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.

Machine learning-based prediction model for distant metastasis of breast cancer.

BACKGROUND: Breast cancer is the most prevalent malignancy in women. Advanced breast cancer can develop distant metastases, posing a severe threat to the life of patients. Because the clinical warning signs of distant metastasis are manifested in the late stage of the disease, there is a need for better methods of predicting metastasis. METHODS: First, we screened breast cancer distant metastasis target genes by performing difference analysis and weighted gene co-expression network analysis (WGCNA) on the selected datasets, and performed analyses such as GO enrichment analysis on these target genes. Secondly, we screened breast cancer distant metastasis target genes by LASSO regression analysis and performed correlation analysis and other analyses on these biomarkers. Finally, we constructed several breast cancer distant metastasis prediction models based on Logistic Regression (LR) model, Random Forest (RF) model, Support Vector Machine (SVM) model, Gradient Boosting Decision Tree (GBDT) model and eXtreme Gradient Boosting (XGBoost) model, and selected the optimal model from them. RESULTS: Several 21-gene breast cancer distant metastasis prediction models were constructed, with the best performance of the model constructed based on the random forest model. This model accurately predicted the emergence of distant metastases from breast cancer, with an accuracy of 93.6 %, an F1-score of 88.9 % and an AUC value of 91.3 % on the validation set. CONCLUSION: Our findings have the potential to be translated into a point-of-care prognostic analysis to reduce breast cancer mortality.

Effect of high NEFA concentration on lipid metabolism disorders in hepatocytes based on lipidomics.

Introduction: High concentrations of nonesterified fatty acids (NEFA) is the key of characteristic of fatty liver in dairy cows. Therefore, the aim of this study was to investigate the effect of high concentration of NEFA on lipid metabolism in hepatocytes through the lipidomic approach and molecular biology techniques. Methods: Stimulate AML-12 cells with different concentrations of NEFA, observe the cellular lipid accumulation, and select 0.6 mM NEFA stimulation concentration for subsequent experiments. Collect cells for lipidomics analysis. Results: High concentration of NEFA (0.6-2.4 mM) significantly reduced the cell viability in a concentration-dependent manner, indicating that high concentrations of NEFA have lipotoxicity on hepatocytes. In addition, NEFA promoted triglycerides (TAG) accumulation, increased the mRNA expression of the lipogenic molecules SREBP1c and FASN, and decreased the mRNA expression of lipolytic molecules CPT1A and HSL in hepatocytes. Mechanistically, high concentration of NEFA induced lipid metabolism disorders in hepatocytes by regulating metabolic pathways such as glycerol phospholipid metabolism, glycosyl phosphatidylinositol anchored biosynthesis, triglyceride metabolism, sphingolipid metabolism, and inositol phosphate metabolism. Discussion: High concentration of NEFA is lipotoxic to cells, promoting lipid accumulation. LPE (18:2), LPE (18:3), LPE (18:1) via glycerophospholipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, glycerolipid metabolism, sphingolipid metabolism, and inositol phosphate metabolism, indicating their potential regulation role in the pathogenesis of fatty liver.

Comparison of Pipeline embolization device versus Tubridge embolization device in unruptured intracranial aneurysms: a multicenter, propensity score matched study.

BACKGROUND: Flow diverter devices (FDs) are increasingly used for treating unruptured intracranial aneurysms (UIAs), but limited studies compared different FDs. OBJECTIVE: To conduct a propensity score matched analysis comparing the Pipeline embolization device (PED) and Tubridge embolization device (TED) for UIAs. METHODS: Patients with UIAs treated with either PED or TED between July 2016 and July 2022 were included. Propensity score matching was performed to adjust for age, sex, comorbidities, smoking, drinking, aneurysm size, morphology, neck, location, parent artery diameter, adjunctive coiling, and angiographic follow-up duration. Perioperative complications and clinical and angiographic outcomes were compared after matching. RESULTS: 735 patients treated by PED and 290 patients treated by TED were enrolled. Compared with the PED group, patients in the TED group had a greater number of women and patients with ischemia, a smaller proportion of vertebrobasilar and non-saccular aneurysms, a smaller size and neck, and fewer adjunctive coils and overlapping stents, but a larger parent artery diameter and lumen disparities. After adjusting for these differences, 275 pairs were matched. No differences were found in perioperative complications (4.4% vs 2.5%, P=0.350), in-stent stenosis (16.0% vs 15.6%, P>0.999), or favorable prognosis (98.9% vs 98.5%, P>0.999). However, PED showed a trend towards better complete occlusion over a median 8-month angiographic follow-up (81.8% vs 75.3%, P=0.077). CONCLUSION: Compared with PED, TED provides a comparable rate of perioperative and short-term outcomes. Nevertheless, a better occlusion status in the PED group needs to be further verified over a longer follow-up period.