Mechanistic study of quercetin in the treatment of hepatocellular carcinoma with diabetes via MEK/ERK pathway.

Hepatocellular carcinoma (HCC) is a complex disease, further exacerbated by coexisting diabetes. With the rising incidence of HCC-diabetes cases, alternative treatment strategies are urgently needed. Traditional Chinese Medicine (TCM) offers promising options, and quercetin, a bioactive flavonoid, has shown significant antitumor and antidiabetic effects. This study aimed to investigate the efficacy of quercetin in treating HCC with diabetes using bioinformatics and network pharmacology. We constructed a prognostic model for HCC-diabetes using multivariate Cox proportional hazards regression and identified potential targets for quercetin by intersecting quercetin target genes with HCC-diabetes genes. Molecular docking and molecular dynamics simulations screened these potential targets, and in vitro experiments verified quercetin's targets and pathways. The results revealed a prediction model with four essential genes that effectively predict HCC prognosis in diabetic patients. IL6 and MMP9 were identified as potential targets of quercetin through molecular docking and dynamics simulations. In vitro experiments revealed that quercetin promotes apoptosis, inhibits cell proliferation, and suppresses epithelial-mesenchymal transition (EMT) in HepG2 cells under high-glucose conditions by reducing IL6 expression and inhibiting the MEK/ERK pathway. In summary, quercetin may delay the progression of HCC-diabetes by modulating IL6 to inhibit the MEK/ERK signaling pathway, thereby promoting apoptosis and inhibiting the proliferation and EMT of HepG2 cells.

Influence of Postoperative Insulin Resistance on Short-Term Outcomes of Radical Gastrectomy for Gastric Cancer: A Microbiome and Metabolome-Based Prospective Cohort Study.

BACKGROUND: Gastrectomy is one of the main treatment modalities for gastric cancer (GC) and induces pathophysiological changes that significantly affect patients' postoperative recovery. In this study, we investigated the relationships between altered insulin resistance (IR), inflammation, and gut microbiota associated with gastrectomy. PATIENTS AND METHODS: This study was a single-center prospective cohort investigation involving 60 patients with GC who underwent gastrectomy between May 2023 and April 2024. Monitoring encompassed IR, inflammation, and nutrition-related markers via blood assays, while gut microbiota analysis employed high-throughput sequencing, and short-chain fatty acids (SCFAs) were examined through targeted metabolomics. The study is registered under the number ChiCTR2300075653. RESULTS: The patients exhibited a significant increase in post-gastrectomy IR markers (P < 0.001), accompanied by elevated inflammation markers (P < 0.001), and also showed decreased nutrition-related indicators (P < 0.001). Notable alterations were observed in the gut microbiota, including reductions in Bifidobacterium and Faecalibacterium, an increase in Streptococcus, and a noteworthy decrease in fecal butyrate. Patients with postoperative IR exhibited poorer inflammation markers (P < 0.05), nutritional indicators (P < 0.05), and postoperative recovery parameters (P < 0.05). Furthermore, significant negative correlations were observed between IR and Bifidobacterium, Faecalibacterium, as well as butyrate. CONCLUSIONS: Patients with GC post-gastrectomy displayed heightened IR, exacerbated inflammation, and compromised nutritional status. Disturbed gut microbiota and reduced fecal butyrate were observed. Gut microbiota and metabolite butyrate production may be predictors of postoperative IR and short-term outcomes in patients with GC.

Prunus persica (L.) Batsch blossom soluble dietary fiber synergia polyphenol improving loperamide-induced constipation in mice via regulating stem cell factor/C-kit, NF-κB signaling pathway and gut microbiota.

This study aimed to investigate the ameliorating effects of peach blossom soluble dietary fiber (PBSDF) and polyphenol (PBP) combinations on loperamide (Lop)-induced constipation in mice, together with the possible mechanism of action. The results demonstrated that the combined use of PBSDF and PBP could synergistically accelerate the gastrointestinal transit rate and gastric emptying rate, shorten first red fecal defecation time, accelerate the frequency of defecation, regulate the abnormal secretion of gastrointestinal neurotransmitters and pro-inflammatory cytokines, and down-regulate the expressions of AQP3 and AQP8. Western blotting and RT-qPCR analysis confirmed that PBSDF + PBP up-regulated the protein and mRNA expressions of SCF and C-kit in SCF/C-kit signaling pathway, and down-regulated pro-inflammatory mediator expressions in NF-κB signaling pathway. 16S rRNA sequencing showed that the diversity of gut microbiota and the relative abundance of specific strains, including Akkermansia, Bacteroides, Ruminococcus, Lachnospiraceae_NK4A136_group, and Turicibacter, rehabilitated after PBSDF + PBP intervention. These findings suggested that the combination of a certain dose of PBSDF and PBP had a synergistic effect on attenuating Lop-induced constipation, and the synergistic mechanism in improving constipation might associated with the regulating NF-κB and SCF/C-kit signaling pathway, and modulating the specific gut strains on constipation-related systemic types. The present study provided a novel strategy via dietary fiber and polyphenol interactions for the treatment of constipation.

Who can Benefit From Volunteer Participation? Analysis of Wellbeing Heterogeneity in Volunteer Participation of Older People.

The basic premise of this study is that the traditional method to treating all older people as coming from the same distribution misspecifies the true model and ignores potentially important information in wellbeing outcomes of social participation. Using data from the China Longitudinal Aging Social Survey (CLASS), this paper proposes a finite mixture model (FMM) to identify the heterogeneous relationship between volunteer participation and older people's subjective well-being (SWB) and then explore the determinants of wellbeing heterogeneity in volunteer participation. The results reveal that older people can be classified into two latent subgroups, that is the volunteering beneficiary group (accounting for about 42%) and the volunteering non-beneficiary group (accounting for about 58%). The FMM is therefore more appropriate in estimating the complex impact of volunteering. Rural older people with poorer health, weaker social networks, better economic status, and better community environments are more likely to benefit from volunteer participation. Our findings have suggested some practical implications to increase the probability of benefit from volunteer participation.

Continual learning for seizure prediction via memory projection strategy.

Despite extensive algorithms for epilepsy prediction via machine learning, most models are tailored for offline scenarios and cannot handle actual scenarios where data changes over time. Catastrophic forgetting(CF) for learned electroencephalogram(EEG) data occurs when EEG changes dynamically in the clinical setting. This paper implements a continual learning(CL) strategy Memory Projection(MP) for epilepsy prediction, which can be combined with other algorithms to avoid CF. Such a strategy enables the model to learn EEG data from each patient in dynamic subspaces with weak correlation layer by layer to minimize interference and promote knowledge transfer. Regularization Loss Reconstruction Algorithm and Matrix Dimensionality Reduction Algorithm are introduced into the core of MP. Experimental results show that MP exhibits excellent performance and low forgetting rates in sequential learning of seizure prediction. The forgetting rate of accuracy and sensitivity under multiple experiments are below 5%. When learning from multi-center datasets, the forgetting rates for accuracy and sensitivity decrease to 0.65% and 1.86%, making it comparable to state-of-the-art CL strategies. Through ablation experiments, we have analyzed that MP can operate with minimal storage and computational cost, which demonstrates practical potential for seizure prediction in clinical scenarios.

Acidification state and interannual variability in marginal sea: A case study of the Bohai and the Yellow Seas surface waters in April 2023.

The acidification of the marginal seawater was a more intricate process than the ocean. Although some studies have been done on seasonal acidification in the bottom water of Chinese marginal seas, research on surface water acidification has still been insufficient. We analyzed the acidification properties and controlling factors in the Bohai Sea (BS) and Yellow Sea (YS) surface water during April 2023. The observation showed that the average surface water pH of the BS, North Yellow Sea (NYS), and South Yellow Sea (SYS) were 8.09 ± 0.06, 8.13 ± 0.05, and 8.15 ± 0.05. Phytoplankton significantly impacted pH and Ωarag, while riverine inputs and biological activity played a vital role in controlling DIC and TA. The Yellow River significantly impacted the BS. The North Yellow Sea Cold Water Mass had a limited impact on acidification, while the South Yellow Sea Cold Water Mass significantly affected the SYS. Regarding seasonal fluctuations, Ωarag was significantly higher in summer than in other seasons. DIC and TA showed different patterns in both the BS and YS, with a minimal fluctuation in pH. Over the last two decades, the pH in the BS showed a slight annual decline, and the rate of change was (-1.45 ± 2.19) × 10-5 yr-1. In contrast, the NYS and SYS have slightly risen, with rates of change of (2.39 ± 1.24) × 10-5 and (1.23 ± 0.76) × 10-5 yr-1. We believed that surface water acidification in the BS and YS did not follow the expected trend of significant acidification observed in open oceanic regions. Instead, the acidification process in these marginal seas was dominated by local factors such as riverine inputs, biological activity, and cold water masses, resulting in minimal pH changes over the last two decades.

Global daily mask use estimation in the pandemic and its post environmental health risks: Analysis based on a validated dynamic mathematical model.

The outbreak of the COVID-19 pandemic led to a sharp increase in disposable surgical mask usage. Discarded masks can release microplastic and cause environmental pollution. Since masks have become a daily necessity for protection against virus infections, it is necessary to review the usage and disposal of masks during the pandemic for future management. In this study, we constructed a dynamic model by introducing related parameters to estimate daily mask usage in 214 countries from January 22, 2020 to July 31, 2022. And we validated the accuracy of our model by establishing a dataset based on published survey data. Our results show that the cumulative mask usage has reached 800 billion worldwide, and the microplastics released from discarded masks due to mismanagement account for 3.27% of global marine microplastic emissions in this period. Furthermore, we illustrated the response relationship between mask usage and the infection rates. We found a marginally significant negative correlation existing between the mean daily per capita mask usage and the rate of cumulative confirmed cases within the range of 25% to 50%. This indicates that if the rate reaches the specified threshold, the preventive effect of masks may become evident.

Probiotic Compounds Enhanced Recovery after Surgery for Patients with Distal Gastric Cancer: A Prospective, Controlled Clinical Trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) for radical distal gastrectomy needs to be improved urgently. We investigated the effects of probiotic compounds (including Lactobacillus plantarum, L. rhamnosus, L. acidophilus, and Bifidobacterium animalis subsp.lactis) on enhance recovery after gastrectomy. METHODS: The patients in this prospective study were divided into probiotic group (PG group, n = 36) and placebo group (CG group, n = 38), taking corresponding capsule according to the protocol during the perioperative period. We compared the trends in perioperative hematologic findings and the postoperative outcomes. Patients' feces were collected for bacterial 16S rRNA sequencing. Patients were followed up at 1 month postoperatively. RESULTS: After the application of probiotics, the patients' postoperative inflammatory response level was reduced, and the trend of postoperative NLR decrease was significantly faster in the patients of the PG group than in the CG group (P = 0.047, partial η2 = 0.054). The trend of postoperative increase in serum albumin concentration in the patients of the PG group was significantly better than that in the CG group (P = 0.016, partial η2 = 0.078). In addition, patients in the PG group met discharge criteria earlier postoperatively and had fewer medical expenses. The quality of life of PG group was improved postoperatively. Postoperative inflammation-related markers, including the ratio of Firmicutes/Bacteroidetes, were increasing in untreated patients. In addition, the postoperative microbial diversity and abundance in the PG group remained stable. CONCLUSIONS: Probiotic compounds can reduce the inflammatory response after gastrectomy and enhance the recovery of the DGC patients by maintaining the stability of the gut microbiota.

A multi-constituent model for assessing the effect of impeller shroud on the thrombosis potential of a centrifugal blood pump.

Centrifugal blood pumps can be used for treating heart failure patients. However, pump thrombosis has remained one of the complications that trouble clinical treatment. This study analyzed the effect of impeller shroud on the thrombosis risk of the blood pump, and predicted areas prone to thrombosis. Multi-constituent transport equations were presented, considering mechanical activation and biochemical activation. It was found that activated platelets concentration can increase with shear stress and adenosine diphosphate(ADP) concentration increasing, and the highest risk of thrombosis inside the blood pump was under extracorporeal membrane oxygenation (ECMO) mode. Under the same condition, ADP concentration and thrombosis index of semi-shroud impeller can increase by 7.3% and 7.2% compared to the closed-shroud impeller. The main reason for the increase in thrombosis risk was owing to elevated scalar shear stress and more coagulation promoting factor-ADP released. The regions with higher thrombosis potential were in the center hole, top and bottom clearance. As a novelty, the findings revealed that impeller shroud can influence mechanical and biochemical activation factors. It is useful for identifying potential risk regions of thrombus formation based on relative comparisons.

Mechanism of miR-98-5p in gastric cancer cell proliferation, migration, and invasion through the USP44/CTCFL axis.

Objectives: Gastric cancer (GC) is the leading digestive malignancy with high incidence and mortality rate. microRNAs (miRs) play an important role in GC progresssion. This study aimed to investigate the effect of miR-98-5p on proliferation, migration, and invasion of GC cells. Methods: The expression levels of miR-98-5p, ubiquitin specific peptidase 44 (USP44), and CCCTCbinding factor-like (CTCFL) in GC tissues and cells were identified using reversetranscription quantitative polymerase chain reaction and Western blot assay. The relationship between miR-98-5p expression/USP44 and the clinicopathological features in GC patients was analyzed. GC cell proliferation, invasion, and migration were evaluated by cell counting kit-8 and clone formation assays and Transwell assays. The bindings of miR-98-5p to USP44 and USP44 to CTCFL were examined using dualluciferase assay and co-immunoprecipitation. GC cells were treated with MG132 and the ubiquitination level of CTCFL was examined using ubiquitination assay. Rescue experiments were performed to verify the roles of USP44 and CTCFL in GC cells. Results: miR-98-5p was downregulated in GC. miR-98-5p overexpression inhibited the proliferation, migration, and invasion of GC cells. miR-98-5p inhibited USP44 expression. USP44 bound to CTCFL and limited ubiquitination degradation of CTCFL. Overexpression of USP44 and CTCFL attenuated the inhibitory effects of miR-98-5p overexpression on GC cell progression. Conclusion: miR-98-5p overexpression limited USP44-mediated CTCFL deubiquitination, and suppressed CTCFL expression, mitigating GC cell proliferation, migration, and invasion.

Structure-aware contrastive hashing for unsupervised cross-modal retrieval.

Cross-modal hashing has attracted a lot of attention and achieved remarkable success in large-scale cross-media similarity retrieval applications because of its superior computational efficiency and low storage overhead. However, constructing similarity relationship among samples in cross-modal unsupervised hashing is challenging because of the lack of manual annotation. Most existing unsupervised methods directly use the representations extracted from the backbone of their respective modality to construct instance similarity matrices, leading to inaccurate similarity matrices and resulting in suboptimal hash codes. To address this issue, a novel unsupervised hashing model, named Structure-aware Contrastive Hashing for Unsupervised Cross-modal Retrieval (SACH), is proposed in this paper. Specifically, we concurrently employ both high-dimensional representations and discriminative representations learned by the network to construct a more informative semantic correlative matrix across modalities. Moreover, we design a multimodal structure-aware alignment network to minimize heterogeneous gap in the high-order semantic space of each modality, effectively reducing disparities within heterogeneous data sources and enhancing the consistency of semantic information across modalities. Extensive experimental results on two widely utilized datasets demonstrate the superiority of our proposed SACH method in cross-modal retrieval tasks over existing state-of-the-art methods.

Development and external validation of a nomogram predicting overall survival for Gastric adenocarcinoma patients with radical gastrectomy.

PURPOSE: The aim of this study was to develop and externally validate a nomogram to accurately predict the overall survival (OS) of patients with gastric adenocarcinoma who underwent radical gastrectomy. MATERIALS AND METHODS: A total of 3492 patients with gastric adenocarcinoma who underwent radical gastrectomy from 2012 to 2017 were included as the training cohort. Survival analysis was performed via Kaplan Meier method and log-rank test. Independent postoperative prognostic factors in patients with gastric adenocarcinoma were analyzed using univariate and multifactorial COX analysis methods. The prognosis nomogram was established in the training cohort and verified externally in the Surveillance, Epidemiology and End Results (SEER) database. RESULTS: According to the univariate and multifactorial COX analyses, metastatic lymph node ratio (MLNR) and five other independent prognostic factors (age at surgery, type of gastrectomy, tumor size, T stage, and pathological grade) were included in the prognostic nomogram. The nomogram had better prognostic predictive ability than the American Joint Committee on Cancer (AJCC) TNM staging in both the training (C-index: 0.736 VS. 0.668) and external validation cohort (C-index: 0.712 VS. 0.627). The calibration plots showed that the predicted survival rate was in good agreement with the actual survival rate. And the decision curve analysis (DCA) curves revealed that nomogram showed stronger ability in predicting 1-year, 3-year, and 5-year OS. CONCLUSION: This study estimated the excellent prognostic predictive power and clinical application potential of the MLNR-based nomogram, which may be used to facilitate postoperative clinical treatment decisions and potentially improve patient survival outcomes.

ST-SCGNN: A Spatio-Temporal Self-Constructing Graph Neural Network for Cross-Subject EEG-Based Emotion Recognition and Consciousness Detection.

In this paper, a novel spatio-temporal self-constructing graph neural network (ST-SCGNN) is proposed for cross-subject emotion recognition and consciousness detection. For spatio-temporal feature generation, activation and connection pattern features are first extracted and then combined to leverage their complementary emotion-related information. Next, a self-constructing graph neural network with a spatio-temporal model is presented. Specifically, the graph structure of the neural network is dynamically updated by the self-constructing module of the input signal. Experiments based on the SEED and SEED-IV datasets showed that the model achieved average accuracies of 85.90% and 76.37%, respectively. Both values exceed the state-of-the-art metrics with the same protocol. In clinical besides, patients with disorders of consciousness (DOC) suffer severe brain injuries, and sufficient training data for EEG-based emotion recognition cannot be collected. Our proposed ST-SCGNN method for cross-subject emotion recognition was first attempted in training in ten healthy subjects and testing in eight patients with DOC. We found that two patients obtained accuracies significantly higher than chance level and showed similar neural patterns with healthy subjects. Covert consciousness and emotion-related abilities were thus demonstrated in these two patients. Our proposed ST-SCGNN for cross-subject emotion recognition could be a promising tool for consciousness detection in DOC patients.

Tangeretin attenuates acute lung injury in septic mice by inhibiting ROS-mediated NLRP3 inflammasome activation via regulating PLK1/AMPK/DRP1 signaling axis.

OBJECTIVE: NLRP3 inflammasome-mediated pyroptosis of macrophage acts essential roles in the progression of sepsis-induced acute lung injury (ALI). Tangeretin (TAN), enriched in citrus fruit peel, presents anti-oxidative and anti-inflammatory effects. Here, we aimed to explore the potentially protective effect of TAN on sepsis-induced ALI, and the underlying mechanism of TAN in regulating NLRP3 inflammasome. MATERIAL AND METHODS: The effect of TAN on sepsis-induced ALI and NLRP3 inflammasome-mediated pyroptosis of macrophage were examined in vivo and in vitro using a LPS-treated mice model and LPS-induced murine macrophages, respectively. The mechanism of TAN regulating the activation of NLRP3 inflammasome in sepsis-induced ALI was investigated with HE staining, Masson staining, immunofluorescent staining, ELISA, molecular docking, transmission electron microscope detection, qRT-PCR, and western blot. RESULTS: TAN could evidently attenuate sepsis-induced ALI in mice, evidenced by reducing pulmonary edema, pulmonary congestion and lung interstitial fibrosis, and inhibiting macrophage infiltration in the lung tissue. Besides, TAN significantly suppressed inflammatory cytokine IL-1ß and IL-18 expression in the serum or bronchoalveolar lavage fluid (BALF) samples of mice with LPS-induced ALI, and inhibited NLRP3 inflammasome-mediated pyroptosis of macrophages. Furthermore, we found TAN inhibited ROS production, preserved mitochondrial morphology, and alleviated excessive mitochondrial fission in LPS-induced ALI in mice. Through bioinformatic analysis and molecular docking, Polo-like kinase 1 (PLK1) was identified as a potential target of TAN for treating sepsis-induced ALI. Moreover, TAN significantly inhibited the reduction of PLK1 expression, AMP-activated protein kinase (AMPK) phosphorylation, and Dynamin related protein 1 (Drp1) phosphorylation (S637) in LPS-induced ALI in mice. In addition, Volasertib, a specific inhibitor of PLK1, abolished the protective effects of TAN against NLRP3 inflammasome-mediated pyroptosis of macrophage and lung injury in the cell and mice septic models. CONCLUSION: TAN attenuates sepsis-induced ALI by inhibiting ROS-mediated NLRP3 inflammasome activation via regulating PLK1/AMPK/DRP1 signaling axis, and TAN is a potentially therapeutic candidate against ALI through inhibiting pyroptosis.

A glutathione-responsive PEGylated nanogel with doxorubicin-conjugation for cancer therapy.

The complexity, degradability, and stability of drug delivery systems are crucial factors for clinical application. Herein, a glutathione (GSH)-responsive polyethylene glycol (PEG)ylated nanogel conjugated with doxorubicin (Dox) was prepared based on a linker with disulfide bonds, PEG, and Dox using a one-pot method. FT-IR and UV-vis analyses confirmed that all raw materials were incorporated in the Dox-conjugated nanogel structure. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results showed that the particle size of the Dox-conjugated nanogel was at the nanoscale and could be responsively disrupted in high GSH concentration. The in vitro accumulative Dox release rate from the nanogel reached 88% in PBS with 5 mg mL-1 GSH on day 4. Moreover, H22 cell viability and apoptosis experiments revealed that the nanogel effectively inhibited tumor cell growth. In vivo tracking and cell uptake experiments demonstrated that the nanogel accumulated and persisted in tumor tissues for 5 days and was distributed into cell nuclei at 6 h. Furthermore, H22-bearing mice experiments showed that the tumor size of the Dox-conjugated nanogel group was the smallest (287 mm3) compared to that of the free Dox (558 mm3) and 0.9% NaCl (2700 mm3) groups. Meanwhile, the body weight of mice as well as the H&E and TUNEL tissue section staining of organs and tumor tissues from the mice illustrated that the nanogel could significantly prevent side effects and induce tumor cell apoptosis. Taken together, compared with free Dox, the Dox-conjugated nanogel exhibited higher therapeutic efficacy and lower side effects in normal tissues, making it a potential novel nanomedicine for cancer.

Comparison of surgical and endovascular left subclavian artery revascularization during thoracic aortic endovascular repair: a systematic review and meta-analysis.

Objective: The purpose of this systematic review and meta-analysis was to incorporate data from the latest clinical studies and compare the safety and efficacy of surgical left subclavian artery (LSA) revascularization and endovascular LSA revascularization during thoracic endovascular aortic repair (TEVAR). Methods: This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with the PROSPERO database on 16 April 2023 (CRD42023414579). The Embase, MEDLINE (PubMed), and the Cochrane Library databases were searched from January 2000 to May 2023. Results: A total of 14 retrospective cohort studies with a total of 1,695 patients, were included for review. The peri-operative stroke rates of the surgical and endovascular LSA revascularization groups were 3.8% and 2.6%, respectively (P = 0.97). The peri-operative technical success rates for the surgical and endovascular LSA revascularization groups were 95.6% and 93.0%, respectively (P = 0.24). The peri-operative spinal cord ischemia rates were 1.6% (n = 18) and 1.9% (n = 7) in the surgical and endovascular LSA revascularization groups, respectively (P = 0.90). The peri-operative type Ⅰ endoleak rates for the surgical and endovascular LSA revascularization groups were 6.6% and 23.2%, respectively (P = 0.25). The subgroup analysis showed that the incidence of peri-operative type I endoleak in the parallel stent group was significantly higher than that in the surgical LSA revascularization group (P < 0.0001). The peri-operative left upper limb ischemia rates for the surgical and endovascular LSA revascularization groups were 1.2% and 0.6%, respectively (P = 0.96). The peri-operative mortality rates of the surgical and endovascular LSA revascularization groups were 2.0% and 2.0%, respectively (P = 0.88). Conclusion: There was no significant difference in the terms of short-term outcomes when comparing the two revascularization techniques. The quality of evidence assessed by GRADE scale was low to very-low. Surgical and endovascular LSA revascularization during TEVAR were both safe and effective. Compared with surgical LSA revascularization techniques, parallel stent revascularization of LSA significantly increased the rate of type I endoleak.

Covalent Peptide LSD1 Inhibitor Specifically Recognizes Cys360 in the Enzyme-Active Region.

Lysine-specific demethylase 1 (LSD1) is a promising therapeutic target, especially in cancer treatment. Despite several LSD1 inhibitors being discovered for the cofactor pocket, none are FDA-approved. We aimed to develop stabilized peptides for irreversible LSD1 binding, focusing on unique cysteine residue Cys360 in LSD1 and SNAIL1. We created LSD1 C360-targeting peptides, like cyclic peptide S9-CMC1, using our Cysteine-Methionine cyclization strategy. S9-CMC1 effectively inhibited LSD1 at the protein level, as confirmed by MS analysis showing covalent bonding to Cys360. In cells, S9-CMC1 inhibited LSD1 activity, increasing H3K4me1 and H3K4me2 levels, leading to G1 cell cycle arrest and apoptosis and inhibiting cell proliferation. Remarkably, S9-CMC1 showed therapeutic potential in A549 xenograft animal models, regulating LSD1 activity and significantly inhibiting tumor growth with minimal organ damage. These findings suggest LSD1 C360 as a promising site for covalent LSD1 inhibitors' development.

Age-related difference in acute type B aortic dissection.

OBJECTIVE: The objective is to compare the characteristics of clinical data, imaging data, and treatment methods of young and old patients with acute type B aortic dissection (ABAD). METHODS: ABAD patients admitted to the Department of Vascular Surgery of the First Affiliated Hospital of Anhui Medical University from January 2012 to December 2018 were retrospectively reviewed. Patient demographics, such as gender, age, diabetes, hypertension, presenting symptoms, imaging characteristics, laboratory data on admission, hemodynamics on admission and in-hospital management, and mortality of different age groups were compared and analyzed. Categorical variables were compared using χ2 tests or Fisher's exact test. Continuous variables were compared using Student's t-test or Mann-Whitney U-test. RESULTS: A total of 141 ABAD patients were included in this study. Old ABAD patients were more likely to have a prior history of hypertension (88.6% vs 70.4%, p = 0.037) and atherosclerosis (29.8% vs 7.4%, p = 0.016). In the young group, Marfan syndrome was significantly higher (14.8% vs 0.9%; p = 0.005). Compared with the old group, the number of distal tears in the young group was significantly higher (62.3% vs 39.5%, p = 0.027). The proportion of patients with malperfusion of lower limbs in the young group was significantly higher than that in the old group (22.2% vs 6.1%, p = 0.026). There was no significant difference in the treatment methods and in-hospital mortality between the two groups. CONCLUSION: Compared with old ABAD patients, young ABAD patients had more distal tears and a higher proportion of lower limbs malperfusion.

Numerical investigation on the effect of impeller axial position on hemodynamics of an extracorporeal centrifugal blood pump.

Extracorporeal centrifugal blood pumps are used to treat cardiogenic shock. Owing to the imbalanced excitation or initial assembly configurations, the variation in the impeller axial position has the potential to affect the blood pump performance. This study compared the hydrodynamics and hemolysis outcomes at different impeller axial positions via numerical simulations. The result shows that pressure difference of the blood pump decreased with increasing impeller axial position, with decreasing by 4.5% at a flow rate of 2 L/min. Under axial impeller motion close to the top pump casing, average wall shear stress and scalar shear stress reached their maximum values (64.2 and 29.1 Pa, respectively). The residence time in the impeller center hole and bottom clearance were extended to 0.5 s by increasing impeller axial position. Compared to the baseline blood pump, hemolysis index increased by 12.3% and 24.3% when impeller axial position is 2.5 and 4.0 mm, respectively. As a novelty, the findings reveal that the impeller axial position adversely affects hemolysis performance when the impeller is close to the pump casing. Therefore, in the development process of centrifugal blood pumps, the optimal axial position of the impeller must be defined to ensure hemodynamic performance.

Combining temporal and spatial attention for seizure prediction.

Purpose: Approximately 1% of the world population is currently suffering from epilepsy. Successful seizure prediction is necessary for those patients. Influenced by neurons in their own and surrounding locations, the electroencephalogram (EEG) signals collected by scalp electrodes carry information of spatiotemporal interactions. Therefore, it is a great challenge to exploit the spatiotemporal information of EEG signals fully. Methods: In this paper, a new seizure prediction model called Gatformer is proposed by fusing the graph attention network (GAT) and the Transformer. The temporal and spatial attention are combined to extract EEG information from the perspective of spatiotemporal interactions. The model aims to explore the temporal dependence of single-channel EEG signals and the spatial correlations among multi-channel EEG signals. It can automatically identify the most noteworthy interaction in brain regions and achieve accurate seizure prediction. Results: Compared with the baseline models, the performance of our model is significantly improved. The false prediction rate (FPR) on the private dataset is 0.0064/h. The average accuracy, specificity and sensitivity are 98.25%, 99.36% and 97.65%. Conclusion: The proposed model is comparable to the state of the arts. Experiments on different datasets show that it has good robustness and generalization performance. The high sensitivity and low FPR prove that this model has great potential to realize clinical assistance for diagnosis and treatment.