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Mitochondria are indispensable organelles for maintaining cell energy metabolism, and also are necessary to retain cell biological function by transmitting information as signal organelles. Hypoxia, one of the important cellular stresses, can directly regulates mitochondrial metabolites and mitochondrial reactive oxygen species (mROS), which affects the nuclear gene expression through mitochondrial retrograde signal pathways, and also promotes the delivery of signal components into cytoplasm, causing cellular injury. In addition, mitochondria can also trigger adaptive mechanisms to maintain mitochondrial function in response to hypoxia. Extracellular vesicles (EVs), as a medium of information transmission between cells, can change the biological effects of receptor cells by the release of cargo, including nucleic acids, proteins, lipids, mitochondria, and their compositions. The secretion of EVs increases in cells under hypoxia, which indirectly changes the mitochondrial function through the uptake of contents by the receptor cells. In this review, we focus on the mitochondrial regulation indirectly through EVs under hypoxia, and the possible mechanisms that EVs cause the changes in mitochondrial function. Finally, we discuss the significance of this EV-mitochondria axis in hypoxic diseases.

Background Alzheimer's disease (AD) is the most common neurodegenerative disease. Mitochondrial dysfunction and immune responses are important factors in the pathogenesis of AD, but their crosstalk in AD has not been studied. In this study, the independent role and interaction of mitochondria-related genes and immune cell infiltration in AD were investigated using bioinformatics methods. Methods The datasets of AD were obtained from NCBI Gene Expression Omnibus (GEO), and the data of mitochondrial genes was from MitoCarta3.0 database. Subsequently, differential expression genes (DEGs) screening and GSEA functional enrichment analysis were performed. The intersection of DEGs and mitochondrial related genes was used to obtain MitoDEGs. The MitoDEGs most relevant to AD were determined by Least absolute shrinkage and selection operator and multiple support vector machine recursive feature elimination, as well as protein–protein interactions (PPI) network and random forest. The infiltration of 28 kinds of immune cells in AD was analyzed by ssGSEA, and the relationship between hub MitoDEGs and the proportion of immune infiltration was studied. The expression levels of hub MitoDEGs were verified in cell models and AD mice, and the role of OPA1 in mitochondrial damage and neuronal apoptosis was investigated. Results The functions and pathways of DEGs were significantly enriched in AD, including immune response activation, IL1R pathway, mitochondrial metabolism, oxidative damage response and electron transport chain-oxphos system in mitochondria. Hub MitoDEGs closely related to AD were obtained based on PPI network, random forest and two machine learning algorithms. Five hub MitoDEGs associated with neurological disorders were identified by biological function examination. The hub MitoDEGs were found to be correlated with memory B cell, effector memory CD8 T cell, activated dendritic cell, natural killer T cell, type 17 T helper cell, Neutrophil, MDSC, plasmacytoid dendritic cell. These genes can also be used to predict the risk of AD and have good diagnostic efficacy. In addition, the mRNA expression levels of BDH1, TRAP1, OPA1, DLD in cell models and AD mice were consistent with the results of bioinformatics analysis, and expression levels of SPG7 showed a downward trend. Meanwhile, OPA1 overexpression alleviated mitochondrial damage and neuronal apoptosis induced by Aβ1-42. Conclusions Five potential hub MitoDEGs most associated with AD were identified. Their interaction with immune microenvironment may play a crucial role in the occurrence and prognosis of AD, which provides a new insight for studying the potential pathogenesis of AD and exploring new targets.

The presence of pesticide residues has become one of the main risk factors affecting the safety and quality of agro-food. In this study, a multi-residue method for the analysis of 284 pesticides in five local fruit cultivars in Shanghai was developed based on ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The limits of determination and the limits of quantitation of pesticides were 0.6–10 and 2–30 μg/kg, respectively. A total of 44, 10, 10, 18, and 7 pesticides were detected in strawberries, watermelons, melons, peaches, and grapes, respectively. The pesticide levels in 95.0% of the samples were below the maximum residual limits (MRLs) prescribed by China, and in 66.2% of the samples below the EU MRLs. The dietary risk assessment study showed big differences in the chronic and acute exposure risk values among different Chinese consumer groups. Through fruit consumption, children/females showed higher exposure risks than adults/males. But both the risk values were less than 100%, indicating that potential dietary risk induced by the pesticides was not significant for Chinese consumers. Nevertheless, certain measures are needed for both growers and the government in order to decrease the MRL-exceeding rate of pesticide residues and ensure the quality and safety of fruits for consumers.

Studies have indicated that the dorsal attention network (DAN) and the ventral attention network (VAN) functionally interact via several fronto-parietal connector hubs. However, the anatomical connectivity profiles of these connector hubs, and the coupling between the anatomical and functional connectivities of them, are still unknown. In the present study, we found that functional connector hubs anatomically bridged the DAN and VAN based on multimodal magnetic resonance imaging data from the Human Connectome Project (HCP) Consortium and an independent Chinese cohort. The three hubs had unique anatomical connectivity patterns with the attention sub-networks. For each connector hub, the pattern of anatomical connectivity resembled the functional one. Finally, the strength of the anatomical connectivity of these connector hubs was positively associated with the functional connectivity at the group- and individual-levels. Our findings help to better understand the anatomical mechanisms underlying the functional interactions between the DAN and the VAN.

The hemoglobin to red cell distribution width ratio (HRR) has been experimentally associated with the prognosis of acute ischemic stroke (AIS). However, its relationship with mechanical thrombectomy (MT) for AIS remains unclear. Therefore, this study aimed to investigate the relationship between HRR at admission, follow-up HRR, and clinical outcomes in patients undergoing MT. Acute ischemic stroke patients undergoing MT were consecutively enrolled from January 2017 to December 2022. Demographic, clinical, and laboratory information were collected. HRR was measured by dividing hemoglobin (Hb) by red cell distribution width (RDW) at admission and after 24 h of MT. Clinical outcomes after 3 months were evaluated using the modified Rankin Scale (mRS). The primary outcome was poor prognosis (mRS > 2) at 3 months, while the secondary outcome was death within 3 months. A total of 310 patients were analyzed, of whom 216 patients (69.7%) had poor prognosis, and 92 patients (29.6%) died. Patients with a poor prognosis and death had significantly lower HRR levels at admission and after 24 h. HRR at admission was not associated with clinical outcomes according to multivariable logistic regression analysis. However, HRR after 24 h was significantly associated with poor prognosis (adjusted odds ratio [OR]: 0.646, 95% confidence interval [CI]: 0.520-0.803, < 0.001) and death (adjusted OR: 0.615, 95% CI: 0.508-0.744, < 0.001). Receiver-operating characteristic curve analysis demonstrated the predictive ability of HRR after 24 h, with areas under the curves of 0.790 for poor prognosis and 0.771 for death. Rapidly measurable HRR levels are an independent marker of outcome after MT in AIS patients. This may provide a reliable auxiliary outcome measure for clinical routine and interventional therapy.

Intermittent hypoxia is the best predictor of developing cognitive decline and Alzheimer’s disease progression in patients with obstructive sleep apnea. The nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome has been poorly studied as a regulator of neuroinflammation in cognitive impairment caused by intermittent hypoxia. As critical inflammatory cells, exosomes secreted by microglia have been found to affect the spread of pathologic proteins and neuropathology in neurodegenerative diseases. However, the effects of microglial exosomes on neuroinflammation and cognitive outcomes after intermittent hypoxia remain unclear. In this study, the role of miRNAs in microglial exosomes in improving cognitive deficits in mice exposed to intermittent hypoxia was investigated. We demonstrated that miR-146a-5p fluctuated over time in microglial exosomes of mice exposed to intermittent hypoxia for different periods of time, which could regulate neuronal NLRP3 inflammasome and neuroinflammation. In primary neurons, we found that miR-146a-5p regulated mitochondrial reactive oxygen species by targeting HIF1α, thus affecting the NLRP3 inflammasome and secretion of inflammatory factors. Similarly, further studies showed that inhibition of NLRP3 by administering overexpressed miR-146a-5p in microglial exosomes and MCC950 has improved neuroinflammation and cognitive dysfunction in mice after intermittent hypoxia. In conclusion, NLRP3 inflammasome may be a regulatory target for ameliorating cognitive impairment caused by intermittent hypoxia, and microglial exosomal miR-146a-5p may be a promising therapeutic strategy.

The steel surface defect detection is crucial for steel quality and usage safety. The high computational cost and low detection accuracy are still the main issues in current steel detection models. To efficiently address the issues above, this paper proposes a new steel surface defect detection model named DIDW-YOLOv11. In the proposed DIDW-YOLOv11, the YOLOv11 C3k2 module is first innovatively improved by C3K2-DIMB, which integrates C3K2 and DIMB by introducing DynamicInceptionDWConv2d (DIDW) to sufficiently strengthen the detailed feature extraction for tiny defects and weak-texture defects, improving the matching degree of multi-scale receptive fields. Then the YOLOv11 SPPF module is enhanced by integrating the IDWFSPPF module for optimizing the fusion of local and global information, which combines average pooling and max pooling to enhance the model’s multi-scale feature fusion capability. An auxiliary detection head (ADH) is finally proposed with an additional coarse loss function to process shallow feature information into the model, which uses extra supervision for shallow features to suppress background noise and reduce false detections. Experimental results on the NEU-DET and GC10-DET datasets show that DIDW-YOLOv11 achieves 4.9% and 3.8% improvements in mAP@0.5 compared to the baseline model YOLOv11s. Our research indicates that DIDW-YOLOv11 exhibits stronger recognition ability and robustness in complex and diverse defect detection, providing an effective solution for steel defect detection in industrial production. In addition, experimental results show that our model offers improved performance over the baseline methods.

IntroductionPostoperative sore throat and hoarseness are common complications following lung isolation with double-lumen tubes (DLTs) in video-assisted thoracoscopic surgery (VATS). Laryngeal mask airway (LMA) combined with a visual bronchial blocker (VBB) may reduce airway trauma while maintaining effective lung isolation.Methods and analysisThis is a prospective, randomised, controlled, single-blind, multicentre clinical trial conducted at three major thoracic surgery centres in Shanghai, China. A total of 270 patients aged ≥18 years scheduled for elective VATS anatomical lung resection will be randomly allocated 1:1 to either the VBB group (n=135) using LMA combined with VBB or the DLT group (n=135) using conventional DLT (see Consolidated Standards of Reporting Trials diagram). The primary outcome is the incidence of sore throat and hoarseness at 24 hours postoperatively. Secondary outcomes include sore throat and hoarseness at 1 and 48 hours, intraoperative device performance, lung collapse quality, intubation time, haemodynamic changes, emergence quality, device-related complications and hospital length of stay.Ethics and disseminationThe study protocol was approved by the Ethics Committee of Shanghai Chest Hospital (KS24042). Results will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberClinicalTrials.gov (NCT07117539).

Background Neoadjuvant chemotherapy (NAC) response in terms of tumor necrosis for osteosarcoma is of clinical significance for subsequent treatment, CT-acquired parameters indicating sarcopenia were reported to be the risk factors of low NAC efficacy in a variety of malignant tumors, yet the association between chest CT-derived pectoralis major muscle measurements and tumor necrosis of osteosarcoma have not been revealed. Methods The pectoralis major muscle area, normalized pectoralis major muscle index (PMI) and CT attenuation acquired from preoperative chest CT as well as clinical data of 131 osteosarcoma patients were retrospectively analyzed and compared between favorable NAC response (tumor necrosis ≥ 90%) and poor NAC response group (tumor necrosis < 90%). For the evaluation of interobserver reproducibility, interclass correlation coefficient (ICC) with 95% confidence interval (CI) was used. The receiver operating characteristic (ROC) analysis was performed to determine the efficiency of each measurement and to calculate the optimal cut-off values of significant parameters. Multivariable binary logistic regression analysis was performed to determine the risk factors of low NAC efficacy. Results A total of 79 lesions from 78 patients were eligible for this study (mean age, 17.6 ± 0.9 years; 45 male), 34 lesions constituted the favorable response (FR) group and 45 lesions constituted the poor response (PR) group. Pectoralis major muscle measurements were significantly higher in FR group than in PR group (muscle area, 11.56 ± 4.48 VS 9.42 ± 3.57, P  = 0.021; PMI, 7.32 ± 2.23 VS 5.64 ± 1.54, P  < 0.001; CT attenuation, 38.78 ± 8.44 VS 31.96 ± 11.37, P  = 0.004). Excellent interobserver agreement was found in these parameters with ICC values ranging 0.925–0.944. In ROC analysis, PMI showed an area under curve (AUC) of 0.727, 95% CI: 0.612, 0.842, the threshold value for differentiating FR from PR was 7.147. PMI were risk factors of low NAC efficacy with the P value of 0.007. Conclusions Chest CT-accessed pectoralis major muscle area, PMI and CT attenuation were significantly correlated with tumor necrosis in osteosarcoma, these can be potentially helpful imaging auxiliary biomarkers for predicting NAC response of osteosarcoma.

Therapeutic gastrointestinal endoscopy, including endoscopic retrograde cholangiopancreatography and endoscopic submucosal dissection, requires effective sedation strategies to ensure procedural success and patient safety. However, optimal pharmacological regimens remain unclear, particularly for prolonged procedures. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomised controlled trials comparing pharmacological sedation strategies in patients undergoing therapeutic gastrointestinal endoscopy. Outcomes included procedural interference events, hypoxia, hypotension, bradycardia, recovery time, induction time, satisfaction, and postoperative nausea and vomiting. Risk of bias was assessed using the Cochrane RoB 2.0 tool, and certainty of evidence was rated using GRADE framework. A frequentist random-effects network meta-analysis was conducted, along with cluster ranking of co-primary outcomes to evaluate benefit-risk trade-offs. Sixty randomised controlled trials involving 7,071 patients and 32 pharmacological regimens were included. Compared with propofol-opioid, which remained the reference standard, no regimen significantly reduced procedural interference events. Ketamine-propofol demonstrated consistent advantages across hypoxia (relative risk [RR] 0.12, 95% confidence interval [CI] 0.03 to 0.59, P = 0.009; moderate certainty), hypotension (RR 0.28, 95% CI 0.09 to 0.83, P = 0.021; low certainty), and bradycardia (RR 0.11, 95% CI 0.01 to 0.86, P = 0.035; moderate certainty). Cluster rank analyses identified ketamine-propofol and lidocaine-midazolam-propofol as the highest-ranking regimens in both efficacy and safety domains. Meta-regression revealed no significant effect modifiers. While propofol-opioid remains the standard reference, alternative sedation strategies such as ketamine-propofol and lidocaine-midazolam-propofol offer favourable profiles for therapeutic gastrointestinal endoscopy. These findings support individualised regimen selection based on patient and procedural needs. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251018215.