Positional multi-length and mutual-attention network for epileptic seizure classification.

The automatic classification of epilepsy electroencephalogram (EEG) signals plays a crucial role in diagnosing neurological diseases. Although promising results have been achieved by deep learning methods in this task, capturing the minute abnormal characteristics, contextual information, and long dependencies of EEG signals remains a challenge. To address this challenge, a positional multi-length and mutual-attention (PMM) network is proposed for the automatic classification of epilepsy EEG signals. The PMM network incorporates a positional feature encoding process that extracts minute abnormal characteristics from the EEG signal and utilizes a multi-length feature learning process with a hierarchy residual dilated LSTM (RDLSTM) to capture long contextual dependencies. Furthermore, a mutual-attention feature reinforcement process is employed to learn the global and relative feature dependencies and enhance the discriminative abilities of the network. To validate the effectiveness PMM network, we conduct extensive experiments on the public dataset and the experimental results demonstrate the superior performance of the PMM network compared to state-of-the-art methods.

Associations between Alzheimer's disease biomarkers and postoperative delirium or cognitive dysfunction: A meta-analysis and trial sequential analysis of prospective clinical trials.

BACKGROUND: The relationship between Alzheimer's disease biomarkers and postoperative complications, such as postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), remains a subject of ongoing debate. OBJECTIVE: This meta-analysis aimed to determine whether there is an association between perioperative Alzheimer's disease biomarkers and postoperative complications. DESIGN: We conducted a meta-analysis of observational clinical studies that explored the correlation between Alzheimer's disease biomarkers and POD or POCD in patients who have undergone surgery, following PRISMA guidelines. The protocol was previously published (INPLASY: INPLASY202350001). DATA SOURCES: A comprehensive search was conducted across PubMed, Embase, Web of Science, and Cochrane databases until March 2023. ELIGIBILITY CRITERIA: Surgical patients aged at least 18 years, studies focusing on POD or POCD, research involving Alzheimer's disease biomarkers, including Aß or tau in blood or cerebrospinal fluid (CSF), and availability of the full text. RESULTS: Our meta-analysis included 15 studies: six focusing on POD and nine on POCD. The findings revealed a negative correlation between preoperative CSF ß-amyloid 42 (Aß42) levels and the onset of POD [mean difference -86.1, 95% confidence interval (CI), -114.15 to -58.05, I2 : 47%]; this association was strongly supported by trial sequential analysis (TSA). A similar negative correlation was discerned between preoperative CSF Aß42 levels and the incidence of POCD (-165.01, 95% CI, -261.48 to -68.53, I2 : 95%). The TSA also provided robust evidence for this finding; however, the evidence remains insufficient to confirm a relationship between other Alzheimer's disease biomarkers [ß-amyloid 40 (Aß40), total tau (T-tau), phosphorylated tau (P-tau), and Aß42/T-tau ratio] and POD or POCD. CONCLUSION: The study results indicate a negative correlation between preoperative CSF Aß42 levels and the occurrence of both POD and POCD. Future investigations are warranted to identify the predictive cutoff value of preoperative CSF Aß42 for POD and POCD.

Establishing a Device for Sleep Deprivation in Mice.

Circadian rhythm disruption refers to the desynchronization between the external environment or behavior and the endogenous molecular clock, which significantly impairs health. Sleep deprivation is one of the most common causes of circadian rhythm disruption. Various modalities (e.g., platforms on the water, gentle handling, sliding bar chambers, rotating drums, orbital shakers, etc.) have been reported for inducing sleep deprivation in mice to investigate its effects on health. The current study introduces an alternative method for sleep deprivation in mice. An automated rocker platform-based device was designed that is cost-effective and efficiently disrupts sleep in group-housed mice at adjustable time intervals. This device induces characteristic changes of sleep deprivation with minimal stress response. Consequently, this method may prove useful for investigators interested in studying the effects and underlying mechanisms of sleep deprivation on the pathogenesis of multiple diseases. Moreover, it offers a cost-effective solution, particularly when multiple sleep deprivation devices are required to run in parallel.

IgNAR characterization and gene loci identification in whitespotted bamboo shark (Chiloscyllium plagiosum) genome.

Single domain antibodies (sdAb) are promising candidates in cancer and anti-virus biotherapies for their unique structure characters. Though VHH and IgNAR have been discovered in camelidae and nurse shark (Ginlymostoma cirratum) respectively serval decades ago, expense of these large animals still limits the studies and applications of sdAb. Recently, IgNAR has been found in whitespotted bamboo shark (Chiloscyllium plagiosum), a small-sized sharks, while how to characterize and achieved the IgNAR of whitespotted bamboo shark is still unclear. In our research, we identified four IgNAR coding gene loci in whitespotted bamboo shark chromosome 44 (NC_057753.1), and primers were designed for single domain variable regions of IgNAR (VNAR) libraries preparation. Following sequencing results revealed that all plasmids constructed with our predicted VNAR libraries contained VNAR coding sequences, which confirmed the specificities of our primers in VNAR amplification. To our surprise, ≥90% VNAR sequences were encoded by IgNAR1, which suggests IgNAR1 is the most active IgNAR transcription locus in whitespotted bamboo shark. Interestingly, we found IgNAR(ΔC2-C3) were encoded by IgNAR3. Our findings gave a new sight of whitespotted bamboo shark IgNAR, which would broad the way of IgNAR studies and applications in biotherapies.

The transcription factor PbrbZIP52 positively affects pear pollen tube longevity by promoting callose synthesis.

In pear (Pyrus bretschneideri), pollen tube growth is critical for the double fertilization associated with seed setting, which in turn affects fruit yield. The normal deposition of callose mediates the polar growth of pollen tubes. However, the mechanism regulating callose synthesis in pollen tubes remains relatively uncharacterized. In this study, we revealed that the typical pear pollen tube lifecycle has a semi-growth duration (GD50) of 16.16 h under in vitro culture conditions. Moreover, callose plugs were deposited throughout the pollen tube lifecycle. The formation of callose plugs was inhibited by 2-deoxy-D-glucose, which also accelerated the senescence of pear pollen tubes. Additionally, PbrCalS1B.1, which encodes a plasma membrane-localized callose synthase, was expressed specifically in pollen tubes and restored the fertility of the Arabidopsis (Arabidopsis thaliana) cals5 mutant, in which callose synthesis is inhibited. However, this restoration of fertility was impaired by the transient silencing of PbrCalS1B.1, which restricts callose plug formation and shortens the pear pollen tube lifecycle. More specifically, PbrbZIP52 regulated PbrCalS1B.1 transcription by binding to promoter A-box elements to maintain the periodic formation of callose plugs and normal pollen tube growth, ultimately leading to double fertilization. This study confirmed that PbrbZIP52 positively affects pear pollen tube longevity by promoting callose synthesis. This finding may be useful for breeding high-yielding pear cultivars and stabilizing fruit setting in commercial orchards.

Silencing of OGDHL promotes liver cancer metastasis by enhancing hypoxia inducible factor 1 α protein stability.

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases associated with a high rate of mortality. Frequent intrahepatic spread, extrahepatic metastasis, and tumor invasiveness are the main factors responsible for the poor prognosis of patients with HCC. Hypoxia-inducible factor 1 (HIF-1) has been verified to play a critical role in the metastasis of HCC. HIFs are also known to be modulated by small molecular metabolites, thus highlighting the need to understand the complexity of their cellular regulation in tumor metastasis. In this study, lower expression levels of oxoglutarate dehydrogenase-like (OGDHL) were strongly correlated with aggressive clinicopathologic characteristics, such as metastasis and invasion in three independent cohorts featuring a total of 281 postoperative HCC patients. The aberrant expression of OGDHL reduced cell invasiveness and migration in vitro and HCC metastasis in vivo, whereas the silencing of OGDHL promoted these processes in HCC cells. The pro-metastatic role of OGDHL downregulation is most likely attributed to its upregulation of HIF-1α transactivation activity and the protein stabilization by promoting the accumulation of L-2-HG to prevent the activity of HIF-1α prolyl hydroxylases, which subsequently causes an epithelial-mesenchymal transition process in HCC cells. These results demonstrate that OGDHL is a dominant factor that modulates the metastasis of HCC.

Self-assembled micelle derived from pterostilbene ameliorate acute inflammatory bowel disease.

PEGylated pterostilbene micelle (PTENPs) with higher bioavailability, biocompatibility, and water solubility were prepared. Then we detected the therapeutic effects in the treatment of inflammatory bowel disease (IBD), together with its potential mechanisms. The anti-oxidant effects and anti-inflammatory effects of PTENPs were determined under in vitro and in vivo conditions. Besides, the cellular toxicity of the PTENPs was determined in vitro, and biocompatibility testing was performed on a colitis mice model to determine its safety. The self-assembled PTENPs showed potency in treating IBD, which was featured by effectively anti-oxidant capacity, inhibition of cellular damages, and an anti-inflammatory role. In addition, PTENPs could inhibit the activation of TLR4, thereby inhibiting the NF-κB and MAPK signaling pathways. Meanwhile, it could protect colonic tissues from oxidative damage, which promoted the remission of colonic inflammation with low toxicity. Compared with free PTE, PTENPs could effectively ameliorate acute IBD with low toxicity, which may be related to the inactivation of TLR4, and inhibition of NF-κB and MAPK signaling pathways.

An Effective Chromatography Process for Simultaneous Purification and Separation of Total Lignans and Flavonoids from Valeriana amurensis.

An effective chromatography process was developed and validated for simultaneous purification and separation of total lignans and flavonoids from Valeriana amurensis. The total lignans and flavonoids in Valeriana amurensis extract were prepurified with macroporous resin column chromatography, and the conditions were optimized as follows: 40 mg/mL Valeriana amurensis extract (2.0 g) solution was loaded onto an AB-8 resin column with a diameter-to-height ratio of 1:7, followed by adsorption for 6 h; then, the column was eluted successively with 5 BV water and 10% and 50% ethanol at a flow rate 2 BV/h. The obtained 50% ethanol fraction was further repurified and separated by polyamide resin column chromatography to obtain the total lignans and flavonoids, respectively. The chromatography conditions were optimized as follows: a 50% ethanol fraction (1.0 g) was mixed with 1.0 g polyamide resin and loaded onto a polyamide resin (60-100 mesh) column with a diameter-to-height ratio of 1:3; then, the column was eluted successively with 6 BV water and 40% and 80% ethanol at a flow rate of 4 BV/h. The total lignans and flavonoids were obtained from water and 80% ethanol fraction, respectively. The content and recovery of standard compounds in total lignans and flavonoids were analyzed with HPLC-PDA, and the feasibility of the process was confirmed.

Preparing Thick Gradient Surface Layer in Cu-Zn Alloy via Ultrasonic Severe Surface Rolling for Strength-Ductility Balance.

A gradient structure (GS) design is a prominent strategy for strength-ductility balance in metallic materials, including Cu alloys. However, producing a thick GS surface layer without surface damage is still a challenging task limited by the available processing technology. In this work, a gradient structure (GS) surface layer with a thickness at the millimeter scale is produced in the Cu-38 wt.% Zn alloy using ultrasonic severe surface rolling technology at room temperature. The GS surface layer is as thick as 1.1 mm and involves the gradient distribution of grain size and dislocation density. The grain size is refined to 153.5 nm in the topmost surface layer and gradually increases with increasing depth. Tensile tests indicate that the single-sided USSR processed alloy exhibits balanced strength (467.5 MPa in yield strength) and ductility (10.7% in uniform elongation). Tailoring the volume fraction of the GS surface layer can tune the combination of strength and ductility in a certain range. The high strength of GS surface layer mainly stems from the high density of grain boundaries, dislocations and dislocation structures, deformation twins, and GS-induced synergistic strengthening effect. Our study elucidates the effect of the thick GS surface layer on strength and ductility, and provides a novel pathway for optimizing the strength-ductility combination of Cu alloys.

Synthetic augmentation for semantic segmentation of class imbalanced biomedical images: A data pair generative adversarial network approach.

In recent years, deep learning (DL) has been recognized very useful in the semantic segmentation of biomedical images. Such an application, however, is significantly hindered by the lack of pixel-wise annotations. In this work, we propose a data pair generative adversarial network (DPGAN) for the purpose of synthesizing concurrently the diverse biomedical images and the segmentation labels from random latent vectors. First, a hierarchical structure is constructed consisting of three variational auto-encoder generative adversarial networks (VAEGANs) with an extra discriminator. Subsequently, to alleviate the influence from the imbalance between lesions and non-lesions areas in biomedical segmentation data sets, we divide the DPGAN into three stages, namely, background stage, mask stage and advanced stage, with each stage deploying a VAEGAN. In such a way, a large number of new segmentation data pairs are generated from random latent vectors and then used to augment the original data sets. Finally, to validate the effectiveness of the proposed DPGAN, experiments are carried out on a vestibular schwannoma data set, a kidney tumor data set and a skin cancer data set. The results indicate that, in comparison to other state-of-the-art GAN-based methods, the proposed DPGAN shows better performance in the generative quality, and meanwhile, gains an effective boost on semantic segmentation of class imbalanced biomedical images.

Erratum: MicroRNA-506-3p targets SIRT1 and suppresses AMPK pathway activation to promote hepatic steatosis.

[This corrects the article DOI: 10.3892/etm.2021.10865.].

The Effect of a Combined Modified Pectoral and Stellate Ganglion Block on Stress and Inflammatory Response in Patients Undergoing Modified Radical Mastectomy.

Background and Aims: Regional anaesthesia reports to attenuate stress and inflammatory responses associated with surgical resection; however, the effectiveness of combined nerve blocks is less often investigated. We evaluated whether a combination of a pectoral nerve block (PNB) and stellate ganglion block (SGB) is more effective than a PNB alone in reducing these responses in women undergoing modified radical mastectomy (MRM). Methods: This is a prospective randomized controlled trial. Fifty patients with breast cancer were randomly allocated to receive an ultrasound-guided PNB (n = 25, PNB only group) or ultrasound-guided PNB combined with SGB (n = 25, combined blockade group). The primary outcome was perioperative plasma level of interleukin- (IL-) 6. Secondary outcomes included perioperative plasma levels of cortisol, glucose, IL-8, and tumour necrosis factor- (TNF-) α, pain scores, haemodynamic variables, sleep quality, and complications postsurgery. Results: The combined blockade group exhibited significantly lower IL-6 and TNF-α levels 24 h postsurgery. Cortisol levels were significantly lower in the combined blockade group at the end of the surgery. Glucose levels at the time of incision were lower in the combined blockade group. Pain scores up to 12 h postsurgery were significantly lower in the combined blockade group, which also exhibited better perioperative haemodynamic stability. Patients in the combined blockade group reported better sleep quality on the night of surgery. Conclusion: In patients undergoing MRM, PNB combined with SGB block effectively blunted perioperative inflammatory response than PNB alone. A combined block approach can also alleviate stress response and postoperative acute pain with stable perioperative haemodynamics and better postoperative sleep quality.

Rapid titration of recombinant baculoviruses based on NanoLuc secretion in early infection.

The baculovirus expression vector system has become a powerful tool for recombinant protein production and gene delivery. However, existing titration methods for baculovirus are not economical in terms of test time and cost. A titration method based on NanoLuc secretion that allows for titration of recombinant baculoviruses at 4 h post infection (hpi) is described. In the assay, the envelop protein GP64 signal peptide-guided NanoLuc was secreted into the culture medium in proportion to the virus amount during early infection under combined control by the homologous region 5 (hr5) enhancer and the promoter of immediate early gene 1 (ie1) plus L21. Two timepoint standard curves of luciferase activity to virus titers of 5-9 logs were established with excellent linearity and correlation coefficients (slope = 1.050, R2 ≥ 0.9969) using a secretory Nanoluc (secrNluc) - inserted standard baculovirus. Through the assay, the titers of three recombinant viruses prepared independently were calculated by directly measuring luciferase activity in the supernatant at 4 and 6 hpi, with greater accuracy compared to the endpoint dilution assay. These results show the efficacy of this proposed method as a streamlined assay for rapidly titrating recombinant baculoviruses.

Factors Affecting Adenoma Risk Level in Patients with Intestinal Polyp and Association Analysis.

OBJECTIVE: To explore the factors affecting the adenoma risk level in patients with intestinal polyp and association. METHODS: The clinical data of 3,911 patients with intestinal polyp treated in our hospital from January 2018 to January 2021 were retrospectively analyzed, all patients accepted the histopathological examination, their risk of suffering from adenoma was evaluated according to the results of pathological diagnosis, and relevant hazard factors affecting adenoma risk level in them were analyzed by multifactor logistic regression analysis. RESULTS: The results of multifactor logistic analysis showed that male gender, age ≥60 years, number of polyps >3, diameter ≥2 cm, onset at colon, and physiologically tubulovillous adenoma were the hazard factors causing high-grade adenoma risk in patients with intestinal polyp. CONCLUSION: There are many risk factors causing high-grade adenoma in patients with intestinal polyp, and therefore, the screening for high-risk population shall be enhanced to reduce the potential of carcinomatous change in such patients.

Development of nomograms predictive of anastomotic leakage in patients before minimally invasive McKeown esophagectomy.

Purpose: The present study aims to identify factors related to anastomotic leakage before esophagectomy and to construct a prediction model. Methods: A retrospective analysis of 285 patients who underwent minimally invasive esophagectomy (MIE). An absolute shrinkage and selection operator was applied to screen the variables, and predictive models were developed using binary logistic regression. Results: A total of 28 variables were collected in this study. LASSO regression analysis, combined with previous literature and clinical experience, finally screened out four variables, including aortic calcification, heart disease, BMI, and FEV1. A binary logistic regression was conducted on the four predictors, and a prediction model was established. The prediction model showed good discrimination and calibration, with a C-statistic of 0.67 (95% CI, 0.593-0.743), a calibration curve fitting a 45° slope, and a Brier score of 0.179. The DCA demonstrated that the prediction nomogram was clinically useful. In the internal validation, the C-statistic still reaches 0.66, and the calibration curve has a good effect. Conclusions: When patients have aortic calcification, heart disease, obesity, and a low FEV1, the risk of anastomotic leakage is higher, and relevant surgical techniques can be used to prevent it. Therefore, the clinical prediction model is a practical tool to guide surgeons in the primary prevention of anastomotic leakage.

The transcription factor zinc fingers and homeoboxes 2 alleviates NASH by transcriptional activation of phosphatase and tensin homolog.

BACKGROUND AND AIMS: NASH, which is a common clinical condition predisposing to advanced liver diseases, has become a worldwide epidemic. A large and growing unmet therapeutic need for this condition reflects incomplete understanding of its pathogenesis. In the current study, we identified a transcription factor, zinc fingers and homeoboxes 2 (ZHX2), in hepatocytes as a protective factor against steatohepatitis. APPROACH AND RESULTS: We found that hepatic ZHX2 was significantly suppressed in NASH models and steatotic hepatic cells. Hepatocyte-specific ablation of ZHX2 exacerbated NASH-related phenotypes in mice, including lipid accumulation, enhanced inflammation, and hepatic fibrosis. Conversely, hepatocyte-specific overexpression of ZHX2 significantly alleviated the progression of NASH in an experimental setting. Integrated analysis of transcriptomic profiling and chromatin immunoprecipitation sequencing data demonstrated that the phosphatase and tensin homolog (PTEN) was a target gene of ZHX2 in hepatocyte. ZHX2 bound to the promoter of PTEN gene and subsequently promoted the transcription of PTEN, which mediated the beneficial role of ZHX2 against NASH. CONCLUSIONS: The current findings demonstrate a protective role of ZHX2 against NASH progression by transcriptionally activating PTEN. These findings shed light on the therapeutic potential of targeting ZHX2 for treating NASH and related metabolic disorders.

Naringenin protects swine testis cells from bisphenol A-induced apoptosis via Keap1/Nrf2 signaling pathway.

Bisphenol A (BPA) has caused serious pathologies in varying organs of humans and animals, especially reproductive organs. Naringenin (NRG) is a flavanone compound that has shown protective effects against several environmental chemicals through suppression of oxidative stress and activation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Herein, we described the discovery path of NRG inhibition on apoptosis in BPA exposed swine testis (ST) cells through targeting Kelch-like ech-associated protein (Keap1). We found that NRG could specifically bound to the active residues of DGR domain in Keap1, thereby activating Nrf2 signaling pathway, and then increasing the levels of SOD, GPx and CAT, and finally inhibiting oxidative stress and mitochondrial apoptosis induced by BPA in ST cells. Altogether, our results showed that NRG inhibits oxidative stress and mitochondrial apoptosis induced by BPA in ST cells by targeting Keap1/Nrf2 signaling pathway, indicating that NRG could serve as an antagonistic therapy against BPA.

A Modified Simple Method for Induction of Myocardial Infarction in Mice.

Myocardial infarction (MI) represents one of the leading causes of death. MI models are widely used for investigating the pathomechanisms of post-MI remodeling and evaluation of novel therapeutics. Different methods (e.g., isoproterenol treatment, cryoinjury, coronary artery ligation, etc.) have been used to induce MI. Compared with isoproterenol treatment and cryoinjury, coronary artery ligation may better reflect the ischemic response and chronic remodeling after MI. However, traditional methods for coronary ligation in mice are technically challenging and require commercially available apparatus. The current study describes a simple and efficient process for induction of MI in mice with readily available materials. The mouse chest skin was cut open under stable anesthesia with a simplified anesthesia device made of centrifuge tubes. The heart was immediately externalized through the intercostal space after blunt separation of the pectoralis major and pectoralis minor. The left anterior descending branch (LAD) was ligated with a 6-0 suture 3 mm from its origin. Following LAD ligation, staining with 2,3,5-Triphenyltetrazolium chloride (TTC) indicated successful induction of MI and temporal changes of post-MI scar size. Meanwhile, survival analysis results showed overt mortality within 7 days after MI, mainly due to cardiac rupture. Moreover, post-MI echocardiographic assessment demonstrated successful induction of contractile dysfunction and ventricular remodeling. Once mastered, an MI model can be established in mice within 2-3 min with readily available materials.

A duodenal ampullary tumor with malignant transformation of papillary polyps: a case report and literature review.

Periampullary carcinoma refers to a malignant tumor within 2 cm of the duodenal ampulla. Primary ampullary carcinoma is very rare, accounting for only 0.2% of malignant gastrointestinal tumors. The small intestine accounts for 75% of the length of the gastrointestinal tract, and primary tumors in the small intestine account for only 2% of all gastrointestinal tumors. Here, we report the case of a duodenal ampullary tumor with malignant transformation of parapapillary polyps. The patient had both a primary ampullary tumor and high-grade intraepithelial neoplasia of juxtapapillary adenomatous duodenal polyps.

M6A-mediated up-regulation of LncRNA LIFR-AS1 enhances the progression of pancreatic cancer via miRNA-150-5p/ VEGFA/Akt signaling.

N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. There is extensive evidence indicating that long non-coding RNAs (lncRNAs) serve as key regulators of oncogenesis and tumor progression in humans. Through prior study has assessed that LIFR-AS1 plays a key role in various kinds of malignant tumors. However, the exact role of m6A induced LIFR-AS1 in pancreatic cancer (PC) and its potential molecular mechanisms remain largely unknown. In this study, we determined that PC cell lines and tumors exhibit increased LIFR-AS1 expression that correlates with larger tumor size, lymph node metastasis, and more advanced TNM stage. Functionally, loss-of-function studies indicated that LIFR-AS1 knockdown decreased the proliferation, migration, and invasion of PC cells in vitro. Mechanistically, we found that METTL3 induced m6A hyper-methylation on the 3' UTR of LIFR-AS1 to enhance its mRNA stability and LIFR-AS1 could directly interact with miR-150-5p, thereby indirectly up-regulating VEGFA expressions within cells. Through rescue experiments, we were able to confirm that the unfavorable impact of LIFR-AS1 knockdown on VEGFA /PI3K/Akt Signaling could be reversed via the inhibition of miR-150-5p expression. Together, these findings indicate that a noval m6A-LIFR-AS1 axis promotes PC progression at least in part via regulation of the miR-150-5p/VEGFA axis, indicating that this regulatory axis may be a viable clinical target for the treatment of PC.