A study of the pharmacokinetics of clozapine and its metabolites by the dynamics of its distribution in the oral fluid of healthy volunteers.

Clozapine (CLZ) -related accidents or crimes are common in the world. Oral fluid drug detection is a convenient measure of dealing with things like that. There has not been any literature reported detailedly the representation rule of clozapine and its metabolites in oral fluid so far. The study aimed to describe the pharmacokinetics of CLZ and its metabolites N-desmethylclozapine and clozapine-N-oxide in human oral fluid after a single 12.5 mg oral dose of CLZ. Twenty-nine volunteers, including 20 males and 9 females, were recruited, and 2 mL oral fluid was collected from each participant at post-consumption time-points of prior (zero), 0.5, 1.5, 3, 5, 8, 12, 24, 36, 51, 82, and 130 h, respectively. Analytes of interest were extracted with solid-phase extraction and analyzed with liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters were calculated using the pharmacokinetic software DAS according to the non-compartment model. The maximum concentration, the time of maximum concentration, oral clearance, and the elimination half-life of clozapine were 16.57 ± 9.63 ng/mL, 4.53 ± 3.61 h, 57.65 ± 23.77 L/h and 53.58 ± 52.28 h, respectively. The maximum concentration, the time of maximum concentration, and the elimination half-life of the metabolite N-desmethylclozapine were 3.08 ± 1.19 ng/mL, 9.38 ± 9.33 h and 62.67 ± 82.57 h, respectively; of clozapine-N-oxide were 1.15 ± 0.36 ng/mL, 4.53 ± 2.19 h and 19.15 ± 23.11 h, respectively. It was the first study on the pharmacokinetics of CLZ and its metabolites in the oral fluid of Chinese healthy volunteers, and it provided a basis for the therapeutic drug monitoring and toxicological interpretation in clozapine-related cases.

Modified Ileal Conduit for Pelvic Lipomatosis: Technique Description and Outcome.

INTRODUCTION: The aim of this study was to present the surgical technique and clinical outcomes of modified ileal conduit for pelvic lipomatosis (PL). METHODS: From 2020 to 2022, we prospectively enrolled 9 patients with PL undergoing modified ileal conduit. The patient characteristics, perioperative variables, and follow-up outcomes as well as the description of surgical technique were reported. RESULTS: All 9 patients successfully completed the operation. Two patients had perioperative complications of Clavien-Dindo grade I. The mean operation time and bleeding volumes were 253 ± 51.4 min and 238.9 ± 196.9 mL, with a mean postoperative follow-up time of 13.0 ± 5.6 months. The postoperative 3-month and 1-year creatinine values were significantly decreased versus the preoperative (p = 0.006 and p = 0.024). The postoperative 3-month and 1-year estimated glomerular filtration rate values were significantly increased compared with those before operation (p = 0.0002 and p = 0.018). The separation value of left renal pelvis collection system after operation was significantly reduced compared with preoperative evaluation (p = 0.023 at 3 months and p = 0.042 at 1 year) and so was the right side (p = 0.019 and p = 0.023). CONCLUSION: Modified ileal conduit is safe and feasible for PL. A large sample cohort with long-term follow-up is needed to evaluate the clinical outcomes of PL.

The neuroprotective effects of caffeic acid phenethyl ester against methamphetamine-induced neurotoxicity.

Methamphetamine (METH) is a highly abused substance on a global scale and has the capacity to elicit toxicity within the central nervous system. The neurotoxicity induced by METH encompasses neuronal degeneration and cellular demise within the substantia nigra-striatum and hippocampus. Caffeic acid phenethyl ester (CAPE), a constituent of propolis, is a diminutive compound that demonstrates antioxidative and anti-inflammatory characteristics. Numerous investigations have demonstrated the safeguarding effects of CAPE in various neurodegenerative ailments. Our hypothesis posits that CAPE may exert a neuroprotective influence on METH-induced neurotoxicity via specific mechanisms. In order to validate the hypothesis, a series of experimental techniques including behavioral tests, immunofluorescence labeling, RNA sequencing, and western blotting were employed to investigate the neurotoxic effects of METH and the potential protective effects of CAPE. The results of our study demonstrate that CAPE effectively ameliorates cognitive memory deficits and anxiety symptoms induced by METH in mice. Furthermore, CAPE has been observed to attenuate the upregulation of neurotoxicity-associated proteins that are induced by METH exposure and also reduced the loss of hippocampal neurons in mice. Moreover, transcriptomics analysis was conducted to determine alterations in gene expression within the hippocampus of mice. Subsequently, bioinformatics analysis was employed to investigate the divergent outcomes and identify potential key genes. Interferon-stimulated gene 15 (ISG15) was successfully identified and confirmed through RT-qPCR, western blotting, and immunofluorescence techniques. Our research findings unequivocally demonstrated the neuroprotective effect of CAPE against METH-induced neurotoxicity, with ISG15 may have an important role in the underlying protective mechanism. These results offer novel perspectives on the treatment of METH-induced neurotoxicity.

Extracellular vesicles derived from human Sertoli cells: characterizations, proteomic analysis, and miRNA profiling.

BACKGROUND: Extracellular vesicles (EVs) contain thousands of proteins and nucleic acids, playing an important role in cell-cell communications. Sertoli cells have been essential in the testis as a "nurse cell". However, EVs derived from human Sertoli cells (HSerCs) have not been well investigated. METHODS: EVs were isolated from HSerCs via ultracentrifugation and characterized by transmission electron microscopy, tunable resistive pulse sensing, and Western blotting. The cargo carried by HSerCs-EVs was measured via liquid chromatography-mass spectrometry and GeneChip miRNA Arrays. Bioinformatic analysis was performed to reveal potential functions of HSerCs-EVs. RESULTS: A total of 860 proteins with no less than 2 unique peptides and 88 microRNAs with high signal values were identified in HSerCs-EVs. Biological processes related to molecular binding, enzyme activity, and regulation of cell cycle were significantly enriched. Specifically, many proteins in HSerCs-EVs were associated with spermatogenesis and regulation of immune system, including Septins, Large proline-rich protein BAG6, Clusterin, and Galectin-1. Moreover, abundant microRNAs within HSerCs-EVs (miR-638, miR-149-3p, miR-1246, etc.) had a possible impact on male reproductive disorders such as asthenozoospermia and oligozoospermia. CONCLUSIONS: Our study has shown that HSerCs-EVs contain diverse components such as proteins and microRNAs. Further research is required to evaluate HSerCs-EVs in spermatogenesis, which are underutilized but highly potent resources with particular promise for male infertility.

Improving results management processes in an acute hospital using a multi-faceted approach.

BACKGROUND: Radiological examinations and laboratory tests are routinely ordered by hospital physicians as part of the care plan to diagnose and treat patients. However, the failure to actively review and follow-up on these results pose a significant problem to patient safety. A study team was formed to mitigate the clinical risks of poor results management, which was identified as a top clinical risk in our organization, in order to make improvements to the results management process and to ensure the timely review, acknowledgement and follow-up of test results. OBJECTIVE: This study was carried out to improve results management processes and ensure the timely review, acknowledgment, and follow-up of test results, in order to mitigate the clinical risks posed to patient safety. METHODS: The institutional expectations of results management were set and published as a hospital policy, which was communicated to all clinical departments for compliance. Improvements to the electronic medical records system were made to facilitate the results acknowledgement process, and physicians were engaged to educate them on the importance of results management. RESULTS: The study team observed a decrease in unacknowledged results from approximately 16 000 in March 2017 to 2673 in December 2020. The compliance rate for acknowledgement results increased from a monthly average of 83.7% (from March to December 2017) to a monthly average of 99.3% (in 2020). The risk score for results management decreased from 16 to 6.5 and was excluded from the organization's top clinical risks. CONCLUSION: This study showed the importance of both system improvements and culture changes that are required to improve the process of results management and provides a step forward for the hospital to safeguard patient safety and mitigate clinical risk.

Fucoidan from Laminaria japonica Inhibits Expression of GLUT9 and URAT1 via PI3K/Akt, JNK and NF-κB Pathways in Uric Acid-Exposed HK-2 Cells.

This work aimed to investigate the effect of fucoidan (FPS) on urate transporters induced by uric acid (UA). The results showed that UA stimulated the expression of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) in HK-2 cells, and FPS could reverse the effect. Moreover, UA could activate NF-κB, JNK and PI3K/Akt pathways, but both pathway inhibitors and FPS inhibited the UA-induced activation of these three pathways. These data suggested that FPS effectively inhibited the expression induction of reabsorption transporters URAT1 and GLUT9 by UA, through repressing the activation of NF-κB, JNK and PI3K/Akt signal pathways in HK-2 cells. The in vitro research findings support the in vivo results that FPS reduces serum uric acid content in hyperuricemia mice and rats through inhibiting the expression of URAT1 and GLUT9 in renal tubular epithelial cells. This study provides a theoretical basis for the application of FPS in the treatment of hyperuricemia.

Rarely fatal bilateral re-expansion pulmonary edema after inserting a chest tube for unilateral spontaneous pneumothorax: a case report.

We describe a case of a 32-year-old man who died due to bilateral re-expansion pulmonary edema (RPE) following the insertion a chest tube for unilateral spontaneous pneumothorax. Fifteen minutes after inserting the chest tube, the patient with right spontaneous pneumothorax was diagnosed with right re-expansion edema by chest radiograph. Although multiple treatments were administered, the patient died. However, the findings from autopsy showed bilateral RPE existed in the decedent but not unilateral RPE. Autopsy, microscopic examination, and clinical records concluded that the cause of death was acute cardiac and respiratory failure due to bilateral re-expansion pulmonary edema following unilateral spontaneous pneumothorax. Bilateral RPE due to a unilateral pneumothorax is quite rare in clinical and forensic practice. To the best of our knowledge, this is the first time that the pathological changes of RPE have been described by gross and microscopic examinations. This case is reported to provide histopathologic references for diagnosis of RPE and indicate that combining death investigation, pathological findings and clinical courses plays a vital role in diagnosis of RPE in forensic pathology.

Transcriptomic Changes of Astrocytes in the Brain of Rats with Subacute METH Exposure.

OBJECTIVES: To study the transcriptomic changes of astrocytes in the brain of rats exposed to methamphetamine (METH) and its possible mechanism in neurotoxicity. METHODS: The rats were intraperitoneally injected with METH (15 mg/kg) every 12 h for 8 times in total to establish the subacute rat model of METH. After the model was successfully established, the striatum was extracted, and astrocytes were separated by the magnetic bead method. Transcriptome sequencing was performed on selected astrocytes, and the differentially expressed genes were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. RESULTS: A total of 876 differentially expressed genes were obtained by transcriptome sequencing, including 321 up-regulated genes and 555 down-regulated genes. GO analysis revealed that differentially expressed genes were mainly concentrated in cell structure, biological process regulation, extracellular matrix and organelle functions. KEGG pathway enrichment analysis showed that steroids biosynthesis, fatty acid biosynthesis, peroxisome proliferators-activated receptor (PPAR), adenosine 5'-monophosphate-activated protein kinase (AMPK) and other signaling pathways were significantly changed. CONCLUSIONS: METH can cause structural changes of astrocytes through multiple targets, among which cellular structure, steroids biosynthesis and fatty acid biosynthesis may play an important role in nerve injury, providing a new idea for forensic identification of METH related death.

Molecular Targets and Related Biologic Activities of Fucoidan: A Review.

Fucoidan-a marine natural active polysaccharide derived from brown algae with a variety of medicinal activities and low toxicity-has been used as clinical drug for renal diseases for nearly 20 years. The pharmacological mechanism of fucoidan has been well-investigated, based on target molecules and downstream signaling pathways. This review summarizes some important molecular targets of fucoidan and its related biologic activities, including scavenger receptor (SR), Toll-like receptors (TLRs), C-type lectin (CLEC) and some newly found target molecules, which may be beneficial for further understanding the pharmacological mechanism of fucoidan and discovering its new functions, as well as developing related clinical or adjuvant drugs and functional preparations.

Preventive Effects of Three Polysaccharides on the Oxidative Stress Induced by Acrylamide in a Saccharomyces cerevisiae Model.

Saccharomyces cerevisiae was used as a model to explore the preventive effect of two marine polysaccharides separately derived from Sepia esculenta ink (SIP) and Laminaria japonica (FL) as well as one terrestrial polysaccharides from Eleocharis tuberosa peel (WCPP) on toxic injury induced by acrylamide (AA). The growth of yeast was evaluated by kinetics indexes including doubling time, lag phase and maximum proliferation density. Meanwhile, intracellular redox state was determined by contents of MDA and GSH, and SOD activity. The results showed that AA inhibited yeast growth and destroyed the antioxidant defense system. Supplement with polysaccharides, the oxidative damage of cells was alleviated. According to the growth recovery of yeast, FL and WCPP had similar degree of capacity against AA associated cytotoxicity, while SIP was 1.5~2 folds as strong as FL and WCPP. SIP and FL significantly reduced production of MDA by AA administration. Moreover, SIP, FL and WCPP increased SOD activity and repressed GSH depletion caused by AA.

Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer.

BACKGROUND: Understanding the molecular alterations associated with breast cancer (BC) progression may lead to more effective strategies for both prevention and management. The current model of BC progression suggests a linear, multistep process from normal epithelial to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS), and then invasive ductal carcinoma (IDC). Up to 20% ADH and 40% DCIS lesions progress to invasive BC if left untreated. Deciphering the molecular mechanisms during BC progression is therefore crucial to prevent over- or under-treatment. Our previous work demonstrated that miR-671-5p serves as a tumor suppressor by targeting Forkhead box protein M1 (FOXM1)-mediated epithelial-to-mesenchymal transition (EMT) in BC. Here, we aim to explore the role of miR-671-5p in the progression of BC oncogenic transformation and treatment. METHODS: The 21T series cell lines, which were originally derived from the same patient with metastatic BC, including normal epithelia (H16N2), ADH (21PT), primary DCIS (21NT), and cells derived from pleural effusion of lung metastasis (21MT), and human BC specimens were used. Microdissection, miRNA transfection, dual-luciferase, radio- and chemosensitivity, and host-cell reactivation (HCR) assays were performed. RESULTS: Expression of miR-671-5p displays a gradual dynamic decrease from ADH, to DCIS, and to IDC. Interestingly, the decreased expression of miR-671-5p detected in ADH coexisted with advanced lesions, such as DCIS and/or IDC (cADH), but not in simple ADH (sADH). Ectopic transfection of miR-671-5p significantly inhibited cell proliferation in 21NT (DCIS) and 21MT (IDC), but not in H16N2 (normal) and 21PT (ADH) cell lines. At the same time, the effect exhibited in time- and dose-dependent manner. Interestingly, miR-671-5p significantly suppressed invasion in 21PT, 21NT, and 21MT cell lines. Furthermore, miR-671-5p suppressed FOXM1-mediated EMT in all 21T cell lines. In addition, miR-671-5p sensitizes these cell lines to UV and chemotherapeutic exposure by reducing the DNA repair capability. CONCLUSIONS: miR-671-5p displays a dynamic decrease expression during the oncogenic transition of BC by suppressing FOXM1-mediated EMT and DNA repair. Therefore, miR-671-5p may serve as a novel biomarker for early BC detection as well as a therapeutic target for BC management.

Retrospective analysis to determine outcomes of patients with bilateral Wilms tumor undergoing nephron sparing surgery: 15-year tertiary single-institution experience.

PURPOSE: To describe our clinical experience with nephron sparing surgery (NSS) for bilateral Wilms tumor and evaluate the outcomes of patients treated at one of the largest pediatric medical centers in China. METHODS: Medical records of children with bilateral Wilms tumor undergoing NSS in the Children's Hospital of Chongqing Medical University during a 15-year period were retrospectively analyzed. Data collected were composed of age at surgery, tumor response, tumor rupture during resection, final pathologic margins, use of radiation therapy, pathology reports, renal function, and patient survival. RESULTS: A total of 18 eligible patients (10 males, 8 females) with bilateral Wilms tumor at a mean age of 2.28 ± 1.12 years were identified. The administration of preoperative chemotherapy did not result in universally successful outcomes. All children underwent successfully unilateral or bilateral NSS, of which one had positive pathologic margins and five received radiation therapy postoperatively. The rates of tumor rupture and positive lymph nodes involvement were 11.1 and 19.4%, respectively. The pathological study showed favorable histology and unfavorable histology in 32 and 4 kidneys, respectively. The 4-year event-free survival and overall survival rates were 68.18 and 85.56%. In univariable analysis, tumor histology (p = 0.0028) and disease stage (p = 0.0303) appeared significantly associated with overall survival. After a median follow-up period of 41.5 months (range 10-89), three of the surviving patients were diagnosed with hypertension and one had renal insufficiency. CONCLUSIONS: Our experience suggests that NSS has become a feasible and effective option with good oncologic outcomes. Further research, ideally in a multicenter randomized manner, is warranted to better assess the role of NSS in this challenging clinical scenario.

Molecular pathology of cerebral TNF-α, IL-1ß, iNOS and Nrf2 in forensic autopsy cases with special regard to deaths due to environmental hazards and intoxication.

Deaths involved with environmental hazards and intoxication might present with minimal or nonspecific morphological features, which are insufficient to establish a diagnosis. The present study investigated the postmortem brain mRNA and immunohistochemical expressions of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS) and nuclear factor erythroid-2-related factor-2 (Nrf2) in forensic cases. Relative mRNA quantification using Taqman real-time PCR assay demonstrated higher expression of IL-1ß, TNF-α and iNOS, and lower expression of Nrf2 in methamphetamine intoxication and hyperthermia cases, higher expression of iNOS in phenobarbital intoxication cases, and higher expression of Nrf2 in phenobarbital intoxication and hypothermia cases. Immunostaining results showed substantial inter-individual variations in each group, showing no evident differences in distribution or intensity. These findings suggest that different inflammatory and antioxidant responses were involved in deaths from different etiologies, and these markers may be useful for evaluating brain damage and responses.

Characterization of the archaeal community fouling a membrane bioreactor.

Biofilm formation, one of the primary causes of biofouling, results in reduced membrane flux or increased transmembrane pressure and thus represents a major impediment to the wider implementation of membrane bioreactor (MBR) technologies for water purification. Most studies have focused on the role of bacteria in membrane fouling as they are the most dominant and best studied organisms present in the MBR. In contrast, there is limited information on the role of the archaeal community in biofilm formation in MBRs. This study investigated the composition of the archaeal community during the process of biofouling in an MBR. The archaeal community was observed to have lower richness and diversity in the biofilm than the sludge during the establishment of biofilms at low transmembrane pressure (TMP). Clustering of the communities based on the Bray-Curtis similarity matrix indicated that a subset of the sludge archaeal community formed the initial biofilms. The archaeal community in the biofilm was mainly composed of Thermoprotei, Thermoplasmata, Thermococci, Methanopyri, Methanomicrobia and Halobacteria. Among them, the Thermoprotei and Thermoplasmata were present at higher relative proportions in the biofilms than they were in the sludge. Additionally, the Thermoprotei, Thermoplasmata and Thermococci were the dominant organisms detected in the initial biofilms at low TMP, while as the TMP increased, the Methanopyri, Methanomicrobia, Aciduliprofundum and Halobacteria were present at higher abundances in the biofilms at high TMP.

miR-638 mediated regulation of BRCA1 affects DNA repair and sensitivity to UV and cisplatin in triple-negative breast cancer.

INTRODUCTION: Triple-negative breast cancer (TNBC) represents 15 to 20% of all types of breast cancer; however, it accounts for a large number of metastatic cases and deaths, and there is still no effective treatment. The deregulation of microRNAs (miRNAs) in breast cancer has been widely reported. We previously identified that miR-638 was one of the most deregulated miRNAs in breast cancer progression. Bioinformatics analysis revealed that miR-638 directly targets BRCA1. The aim of this study was to investigate the role of miR-638 in breast cancer prognosis and treatment. METHODS: Formalin-fixed, paraffin-embedded (FFPE) breast cancer samples were microdissected into normal epithelial and invasive ductal carcinoma (IDC) cells, and total RNA was isolated. Several breast cancer cell lines were used for the functional analysis. miR-638 target genes were identified by TARGETSCAN-VERT 6.2 and miRanda. The expression of miR-638 and its target genes was analyzed by real-time qRT-PCR and Western blotting. Dual-luciferase reporter assay was employed to confirm the specificity of miR-638 target genes. The biological function of miR-638 was analyzed by MTT chemosensitivity, matrigel invasion and host cell reactivation assays. RESULTS: The expression of miR-638 was decreased in IDC tissue samples compared to their adjacent normal controls. The decreased miR-638 expression was more prevalent in non-TNBC compared with TNBC cases. miR-638 expression was significantly downregulated in breast cancer cell lines compared to the immortalized MCF-10A epithelial cells. BRCA1 was predicted as one of the direct targets of miR-638, which was subsequently confirmed by dual-luciferase reporter assay. Forced expression of miR-638 resulted in a significantly reduced proliferation rate as well as decreased invasive ability in TNBC cells. Furthermore, miR-638 overexpression increased sensitivity to DNA-damaging agents, ultraviolet (UV) and cisplatin, but not to 5-fluorouracil (5-FU) and epirubicin exposure in TNBC cells. Host cell reactivation assays showed that miR-638 reduced DNA repair capability in post UV/cisplatin-exposed TNBC cells. The reduced proliferation, invasive ability, and DNA repair capabilities are associated with downregulated BRCA1 expression. CONCLUSIONS: Our findings suggest that miR-638 plays an important role in TNBC progression via BRCA1 deregulation. Therefore, miR-638 might serve as a potential prognostic biomarker and therapeutic target for breast cancer.

Silver nanowire composite thin films as transparent electrodes for Cu(In,Ga)Se2/ZnS thin film solar cells.

Solution processed silver nanowire indium-tin oxide nanoparticle (AgNW-ITONP) composite thin films were successfully applied as the transparent electrodes for Cu(In,Ga)Se2 (CIGS) thin film solar cells with ZnS buffer layers. Properties of the AgNW-ITONP thin film and its effects on performance of CIGS/ZnS thin film solar cells were studied. Compared with the traditional sputtered ITO electrodes, the AgNW-ITONP thin films show comparable optical transmittance and electrical conductivity. Furthermore, the AgNW-ITONP thin film causes no physical damage to the adjacent surface layer and does not need high temperature annealing, which makes it very suitable to use as transparent conductive layers for heat or sputtering damage-sensitive optoelectronic devices. By using AgNW-ITONP electrodes, the required thickness of the ZnS buffer layers for CIGS thin film solar cells was greatly decreased.

The correlation between biofilm biopolymer composition and membrane fouling in submerged membrane bioreactors.

Biofouling, the combined effect of microorganism and biopolymer accumulation, significantly reduces the process efficiency of membrane bioreactors (MBRs). Here, four biofilm components, alpha-polysaccharides, beta-polysaccharides, proteins and microorganisms, were quantified in MBRs. The biomass of each component was positively correlated with the transmembrane pressure increase in MBRs. Proteins were the most abundant biopolymer in biofilms and showed the fastest rate of increase. The spatial distribution and co-localization analysis of the biofouling components indicated at least 60% of the extracellular polysaccharide (EPS) components were associated with the microbial cells when the transmembrane pressure (TMP) entered the jump phase, suggesting that the EPS components were either secreted by the biofilm cells or that the deposition of these components facilitated biofilm formation. It is suggested that biofilm formation and the accumulation of EPS are intrinsically coupled, resulting in biofouling and loss of system performance. Therefore, strategies that control biofilm formation on membranes may result in a significant improvement of MBR performance.

Multiclass motor imagery classification with Riemannian geometry and temporal-spectral selection.

Motor imagery (MI) based brain-computer interfaces (BCIs) decode the users' intentions from electroencephalography (EEG) to achieve information control and interaction between the brain and external devices. In this paper, firstly, we apply Riemannian geometry to the covariance matrix extracted by spatial filtering to obtain robust and distinct features. Then, a multiscale temporal-spectral segmentation scheme is developed to enrich the feature dimensionality. In order to determine the optimal feature configurations, we utilize a linear learning-based temporal window and spectral band (TWSB) selection method to evaluate the feature contributions, which efficiently reduces the redundant features and improves the decoding efficiency without excessive loss of accuracy. Finally, support vector machines are used to predict the classification labels based on the selected MI features. To evaluate the performance of our model, we test it on the publicly available BCI Competition IV dataset 2a and 2b. The results show that the method has an average accuracy of 79.1% and 83.1%, which outperforms other existing methods. Using TWSB feature selection instead of selecting all features improves the accuracy by up to about 6%. Moreover, the TWSB selection method can effectively reduce the computational burden. We believe that the framework reveals more interpretable feature information of motor imagery EEG signals, provides neural responses discriminative with high accuracy, and facilitates the performance of real-time MI-BCI.

Fucoidan from Laminaria japonica protects renal tubular epithelial cells from uric acid induced NLRP3-mediated pyroptosis through inhibition of NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperuricemia is a common metabolic disease with prominent morbidity, it can lead to many adverse effects and complications, such as chronic nephrosis. Fucoidan has been used as natural drug for acute and chronic kidney disease for over 20 years in China, but the precise mechanisms underlying the renal protective function are still indefinable. PURPOSE: This study is conducted to explore alleviation of fucoidan (FPS) from Laminaria japonica on urate-induced NOD-like receptor family, pyrin domain-containing 3 (NLRP3)-mediated pyroptosis in renal tubular epithelial cells HK-2, as well as the mechanism of nuclear factor κB (NF-κB) signaling pathway involved. MATERIALS AND METHODS: HK-2 cells were treated with FPS, uric acid (UA), and inhibitor of NF-κB signaling pathway. Nitric oxide (NO) content and inducible nitric oxide synthase (iNOS) activity were determined with detection kits. Activation of intercellular NLRP3 inflammasome and NF-κB signaling pathway, gasdermin D (GSDMD) expression level were evaluated with western blot and quantitative reverse transcription-PCR (qRT-PCR), and immunofluorescent analysis. RESULTS: Data showed that UA induced cellular inflammatory response demonstrated by elevated NO content, iNOS activity and expression level of NLRP3 inflammasome-mediated pyroptosis associated molecules including NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), Caspase-1, interleukin 18 (IL-18) and GSDMD, moreover the NF-κB signaling pathway was activated by UA. However, FPS exposure inhibited efficiently the UA induced adverse effect. CONCLUSION: It can be concluded that FPS inhibited UA-induced NLRP3-mediated pyroptosis in HK-2 cells through repressing NF-κB signaling pathway.