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In order to investigate the effects of task switching under different modal transitions on the attenuation phenomenon of monitor alertness, event related potential (EEG) experimental method was used to design tasks such as hazardous action recognition, hazardous scene recognition for comprehensive analysis combined with behavioral data and ERP technology; through the empirical study of the coal mine monitoring and dispatching personnel, we reveal the effect of the modal difference of switching task on the alertness of the monitoring personnel and its internal mechanism. The experiment focuses on the specific effects of task switching between different modes on the alertness of supervisors. The results show that the main reason for the decrease of work performance when switching between the same stimulus tasks is the distraction caused by the switching cost, which is reflected in the increase of the average amplitude of P300 and P200 after task switching. However, when the task was switched between different stimuli, especially when the task was switched to auditory stimuli, the participants’ alertness level was improved to some extent.

Abstract The unfolded protein response (UPR) is a conserved and adaptive intracellular pathway that relieves the endoplasmic reticulum (ER) stress by activating ER transmembrane stress sensors. As a consequence of ER stress, the inhibition of nonsense-mediated mRNA decay (NMD) is due to an increase in the phosphorylation of eIF2α, which has the effect of inhibiting translation. However, the role of NMD in maintaining ER homeostasis remains unclear. In this study, we found that the three NMD factors, up-frameshift (UPF)1, UPF2, or UPF3B, were required to negate the UPR. Among these three NMD factors, only UPF3B interacted with inositol-requiring enzyme-1α (IRE1α). This interaction inhibited the kinase activity of IRE1α, abolished autophosphorylation, and reduced IRE1α clustering for ER stress. BiP and UPF3B jointly control the activation of IRE1α on both sides of the ER membrane. Under stress conditions, the phosphorylation of UPF3B was increased and the phosphorylated sites were identified. Both the UPF3BY160D genetic mutation and phosphorylation at Thr169 of UPF3B abolished its interaction with IRE1α and UPF2, respectively, leading to activation of ER stress and NMD dysfunction. Our study reveals a key physiological role for UPF3B in the reciprocal regulatory relationship between NMD and ER stress.

ABSTRACT Background Early detection of bladder cancer (BCa) can have a positive impact on patients' prognosis. However, there is currently no widely accepted method for early screening of BCa. We aimed to develop an efficient, clinically applicable, and noninvasive method for the early screening of BCa by detecting specific serum miRNA levels. Methods A mixed‐cohort (including BCa, 12 different other cancers, benign disease patients, and health population) study was conducted using a sample size of 16,189. Five machine learning algorithms were utilized to develop screening models for BCa using the training dataset. The performance of the model was evaluated using receiver operating characteristic curve and decision curve analysis on the testing dataset, and subsequently, the model with the best predictive power was selected. Furthermore, the selected model's screening performance was evaluated using both the validation set and external set. Results The BCaS3miR model, utilizing only three serum miRNAs (miR‐6087, miR‐1343‐3p, and miR‐5100) and based on the KNN algorithm, is the superior screening model chosen for BCa. BCaS3miR consistently performed well in both the testing, validation, and external sets, exceeding 90% sensitivity and specificity levels. The area under the curve was 0.990 (95% CI: 0.984–0.991), 0.964 (95% CI: 0.936–0.984), and 0.917 (95% CI: 0.836–0.953) in the testing, validation, and external set. The subgroup analysis revealed that the BCaS3miR model demonstrated outstanding screening accuracy in various clinical subgroups of BCa. In addition, we developed a BCa screening scoring model (BCaSS) based on the levels of miR‐1343‐3p/miR‐6087 and miR‐5100/miR‐6087. The screening effect of BCaSS is investigated and the findings indicate that it has predictability and distinct advantages. Conclusions Using a mixed cohort with the largest known sample size to date, we have developed effective screening models for BCa, namely BCaS3miR and BCaSS. The models demonstrated remarkable screening accuracy, indicating potential for the early detection of BCa.

ObjectiveAnterior cervical discectomy and fusion (ACDF) is an established treatment for cervical degenerative disc disease, but cervical spine surgery may affect sagittal alignment parameters and induce adjacent segment degeneration (ASD). This study aimed to determine the risk factors for developing ASD following anterior cervical plate and cage (ACPC) compared with the use of zero-profile anchored spacer (ROI-C).MethodsA retrospective contrastive study included 105 patients who underwent ACPC or ROI-C between January 2014 and October 2019 at our treatment centre. There were 50 cases in the ROI-C group and 55 patients in the ACPC group. Clinical and radiological results and the incidence of ASD were assessed after surgery. All patients were further divided into the ASD and non-ASD groups for subgroup analysis.ResultsAt each follow-up time, there was no statistically significant in radiographic parameters between the two groups. The overall ASD rate was higher in the ACPC group than in the ROI-C group (65.5% vs. 44.0%, p = 0.027). The low preoperative Cobb angle, low preoperative segment angle (SA), and loss of Cobb (ΔCobb) were significantly correlated with ASD. However, clinical outcomes were not associated with ASD at any postoperative follow-up visit.ConclusionEqually good therapeutic effects were achieved with both the ROI-C and ACPC. The occurrence of ASD was considerably higher in the ACPC group than in the ROI-C group. The preoperative Cobb angle, preoperative SA, and ΔCobb were the most associated with an increase in the risk of ASD.

Abstract Osteoarthritis (OA) is one of the most prevalent chronic musculoskeletal diseases among the elderly population. In this study, macrophage-derived exosomes were isolated and identified. Exosomes were subjected to microRNA (miRNA) sequencing and bioinformatic analysis, and differentially expressed miRNAs were verified. miR-26b-5p target genes were confirmed through target-site mutation combined with a dual-luciferase reporter assay. The effects of miR-26b-5p on macrophage polarization and chondrocyte hypertrophy were assessed in vitro. miR-26b-5p agomir was applied to mice with OA induced by anterior cruciate ligament transection (ACLT). The therapeutic effects of miR-26b-5p were evaluated via pain behavior experiments and histological observations. In vitro, miR-26b-5p repolarized M1 macrophages to an anti-inflammatory M2 type by targeting the TLR3 signaling pathway. miR-26b-5p could target COL10A1, further inhibiting chondrocyte hypertrophy induced by M1 macrophage-conditioned medium (M1-CM). In vivo, miR-26b-5p agomir ameliorated gait abnormalities and mechanical allodynia in OA mice. miR-26b-5p treatment attenuated synovitis and cartilage degeneration, thereby delaying OA progression. In conclusion, M2 macrophage-derived exosomal miR-26b-5p could protect articular cartilage and ameliorate gait abnormalities in OA mice by targeting TLR3 and COL10A1. miR-26b-5p further affected macrophage polarization and chondrocyte hypertrophy. Thus, this exosomal miR-26b-5p-based strategy might be a potential method for OA treatment. Graphical Abstract

Abstract Objective The primary aim of this study was to create a nomogram for predicting survival outcomes in penile cancer patients, utilizing data from the Surveillance, Epidemiology, and End Results (SEER) and a Chinese organization. Methods Our study involved a cohort of 5744 patients diagnosed with penile cancer from the SEER database, spanning from 2004 to 2019. In addition, 103 patients with penile cancer from Sun Yat‐sen Memorial Hospital of Sun Yat‐sen University were included during the same period. Based on the results of regression analysis, a nomogram is constructed and validated internally and externally. The predictive performance of the model was evaluated by concordance index (c‐index), area under the curve, decision curve analysis, and calibration curve, in internal and external datasets. Finally, the prediction efficiency is compared with the TNM staging model. Results A total of 3154 penile patients were randomly divided into the training group and the internal validation group at a ratio of 2:1. Nine independent risk factors were identified, including age, race, marital status, tumor grade, histology, TNM stage, and the surgical approach. Based on these factors, a nomogram was constructed to predict OS. The nomogram demonstrated relatively better consistency, predictive accuracy, and clinical relevance, with a c‐index over 0.73 (in the training cohort, the validation cohort, and externally validation cohort.) These evaluation indexes are far better than the TNM staging system. Conclusion Penile cancer, often overlooked in research, has lacked detailed investigative focus and guidelines. This study stands as the first to validate penile cancer prognosis using extensive data from the SEER database, supplemented by data from our own institution. Our findings equip surgeons with an essential tool to predict the prognosis of penile cancer better suited than TNM, thereby enhancing clinical decision‐making processes.

Abstract Accumulating evidence suggests that osteoclastogenesis and angiogenesis in subchondral bone are critical destructive factors in the initiation and progression of osteoarthritis (OA). Herein, methoxypolyethylene glycol amine (mPEG-NH2) modified polydopamine nanoparticles (PDA-PEG NPs) were synthesized for treating early OA. The cytotoxicity and reactive oxygen species (ROS) scavenging ability of PDA-PEG NPs were evaluated. The effects of PDA-PEG NPs on osteoclast differentiation and vessel formation were then evaluated. Further, PDA-PEG NPs were administrated to anterior cruciate ligament transection (ACLT)-induced OA mice. Results demonstrated that PDA-PEG NPs had low toxicity both in vitro and in vivo. PDA-PEG NPs could inhibit osteoclastogenesis via regulating nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, PDA-PEG NPs suppressed osteoclast-related angiogenesis via down-regulating platelet-derived growth factor-BB (PDGF-BB). In vivo, PDA-PEG NPs inhibited subchondral bone resorption and angiogenesis, further rescuing cartilage degradation in OA mice. In conclusion, we demonstrated that PDA-PEG NPs deployment could be a potential therapy for OA. Graphical Abstract

ABSTRACT: Fumonisin B1 (FB1), a worldwide contaminating mycotoxin produced by Fusarium, poses a great threat to the poultry industry. It was reported that extracellular traps could be induced by FB1 efficiently in chickens. However, the relevance of autophagy and glycolysis in FB1-triggered heterophil extracellular trap (HET) formation is unclear. In this study, immunostaining revealed that FB1-induced HETs structures were composed of DNA coated with histones H3, and elastase, and that heterophils underwent LC3B-related autophagosome formation assembly driven by FB1. Western blotting showed that FB1 downregulated the phosphorylated phosphoinositide 3-kinase3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin complex 1 (mTORC1) axis and raised the AMP-activated kinase α (AMPKα) activation protein. Furthermore, rapamycin- and 3-Methyladenine (3-MA)-treatments modulated FB1-triggered HET formation according to the pharmacological analysis. Further studies on energy metabolism showed that glucose/lactate transport and glycolysis inhibitors abated FB1-induced HETs. These results showed that FB1-induced HET formation might interact with the autophagy process and relied on glucose/monocarboxylic acid transporter 1 (MCT1) and glycolysis, reflecting chicken's early innate immune responses against FB1 intake.

ObjectiveTo compare the clinical efficacy and radiological outcomes of 3-level anterior cervical discectomy and fusion (ACDF) and open-door laminoplasty (LP).MethodsA total of 74 patients from January 2017 to January 2020 were enrolled in this retrospective study. There were two groups. Group A (30 cases) received 3-level ACDF, while Group B (44 cases) received open-door LP. Clinical evaluation included perioperative parameters, Neck Disability Index (NDI), and Japanese Orthopaedic Association (JOA) scores. Radiological evaluation included cervical curve depth (CCD), C2–7 angle, C2–7 sagittal vertical axis (cSVA), C7 slope (C7S), and T1 slope (T1S).ResultsPerioperative parameters such as blood loss, drainage volume after surgery, and hospital stay of patients in Group A were significantly less than those in Group B (P

Background Osteoporotic vertebral compression fracture (OVCF) has become a health issue of worldwide concern. Percutaneous kyphoplasty (PKP) is one of the main surgical methods for OVCFs. This study aimed to evaluate and compare the clinical efficacy and safety of PKP with high- and low-viscosity bone cement for OVCFs. Methods Totally 62 patients with single-level OVCF were enrolled in this study from December 2018 to April 2021. Among them, 32 cases underwent PKP with high-viscosity bone cement, while 30 cases underwent PKP with low-viscosity bone cement. Visual analog scale (VAS) scores and Oswestry disability index (ODI) scores were used in the pre- and post-operative period to assess patients’ rehabilitation. Compression rates of anterior vertebra height (AVH) and posterior vertebra height (PVH) were analyzed to evaluate the restoration of vertebra height. Leakage rates and locations were recorded to show clinical safety. Results VAS and ODI scores both significantly improved in 2 groups at 1 day, 1 month, and 3 months after surgery. Compression rates of AVH and PVH at 1 day and 3 months after PKP were lower than those before surgery. However, there was no significant difference in VAS scores, ODI scores, and compression rates between both groups. However, PKP with high-viscosity bone cement achieved a lower bone cement leakage rate significantly, which showed the safety of high-viscosity bone cement in PKP. Conclusions PKP with high- and low-viscosity bone cement both improved the recovery of patients and restored vertebra heights. Notably, PKP with high-viscosity bone cement can achieve favorable clinical outcomes as well as lower bone cement leakage rate.

Fumonisin B1 (FB1) is a common mycotoxin contamination in agricultural commodities being considered as a significant risk to human and livestock health, while the mechanism of FB1 immunotoxicity are less understood, especially in chicken. Given that extracellular traps as a novel defense mechanism of leukocytes play an important role against foreign matters, in this study we aimed to investigate the effects of FB1 on chicken heterophil extracellular traps (HETs) formation. Our result showed that FB1 induced HETs release in chicken heterophils observed via immunostaining, and it was concentration-dependent during 10 to 40 μM. Moreover, in 40 μM FB1-exposed chicken heterophils, reactive oxygen species (ROS) level was increased, while catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity and glutathione (GSH) content were decreased. Simultaneously, FB1 (40 μM) activated ERK and p38 MAPK signaling pathways via increasing the phosphorylation level of ERK and p38 proteins. However, pretreatment of SB202190, U0126, and diphenyleneiodonium chloride (DPI) did not change FB1-triggered ROS production and HETs formation, suggesting FB1-induced HETs was a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, p38, and extracellular regulated protein kinases (ERK) signaling pathways-independent process. Inhibition of peptidyl arginine deiminase 4 (PAD4) enzyme and P2 × 1 receptor showed their vital role in 40 μM FB1-triggered HETs. This study reported for the first time that 40 μM FB1 induced the release of HETs in heterophils, and it was related to ROS production, PAD4, and P2 × 1, but was independent of NADPH oxidase, p38 and ERK signaling pathways, which might provide a whole novel perspective of perceiving and understanding the role of FB1 in immunotoxicity.

Acute liver injury (ALI), posing a serious threaten to our life, has emerged as a public health issue around the world. β-carotene has plenty of pharmacologic effects, such as anti-inflammatory, antioxidant, and antitumor activities. In this study, we focused on studying the protective role and potential molecular mechanisms of β-carotene against D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced ALI. Our results indicated that β-carotene pretreatment effectively hindered abnormal changes induced by LPS/ D-GalN in liver histopathology. Meanwhile, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were downgraded with β-carotene pretreatment. β-carotene pretreatment also decreased malondialdehyde content and myeloperoxidase activity, increased glutathione peroxidase and superoxide dismutase levels, and reduced the levels of tumor necrosis factor-a (TNF-α) and interleukin 6 (IL-6) in liver tissues. Further investigations found that β-carotene mediated multiple signaling pathways in LPS/D-GalN-induced ALI, inhibiting NF-κB and MAPK signaling and upregulating the expression of Nrf2 and HO-1 proteins. All findings indicate that β-carotene appears to protect mice against LPS/D-GalN induced ALI by reducing oxidative stress and inflammation, possibly via regulating NF-κB, MAPK, and Nrf2 signaling. [ABSTRACT FROM AUTHOR]