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Abstract Introduction Pregnant women may need to undergo non‐obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane‐induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO‐induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO. Methods Pregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00–18:00 h) during GD15–21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti‐inflammatory markers and synaptic function‐related proteins were assessed using molecular biology methods. Results The results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐alpha and a reduction in the hippocampal levels of IL‐10, synaptophysin, post‐synaptic density‐95, growth‐associated protein‐43, and brain‐derived neurotrophic factor. Conclusion Our findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.

Background: Colon adenocarcinoma (COAD) is one of the most common malignant tumors. The interplay involving ferroptosis between tumor and immune cells plays a crucial in cancer progression. However, the biological basis of this interplay in COAD development remains elusive. Methods: Transcriptome data of COAD samples were obtained from The Cancer Genome Atlas and National Center for Biotechnology Information databases. Using single-sample gene set enrichment analysis, we calculated the ferroptosis score (FS) and immune cell infiltration levels for each sample, leveraging the expression levels of genes related to ferroptosis and various immune cell types. Samples with FSs greater than the 75th percentile were classified into the high-FS subgroup, while those below the 25th percentile were categorized as the low-FS subgroup. Moreover, tumor tissue samples and adjacent normal tissue samples were collected from twenty colon patients. Using real-time quantitative polymerase chain reaction, we validated the expression of certain genes in these samples. Results: The COAD samples with high FSs experienced favorable survival probability and heightened sensitivity to anticancer drugs, with FSs negatively associated with the pathological stages. Moreover, the up-regulated genes in high-FS subgroup exhibited enrichment in immune-related pathways, suggesting a correlation between immunity and ferroptosis. Importantly, we discovered a key lncRNA-mRNA co-expression network linking tumor cell ferroptosis and immune infiltration (e.g., neutrophil) in the progression and classification of COAD. Further analysis identified several ferroptosis-related lncRNAs (e.g., RP11-399O19.9) within this network, indicating their potential roles in COAD progression and deserving in-depth study. Conclusions: Our findings provide novel insights into the underlying biological basis, particularly involving lncRNAs, at gene expression level associated with ferroptosis in COAD and cancer therapy. Nevertheless, further analysis and validation are required to expand the findings.

Drone-based transportation is emerging as a novel mode in city logistics, featuring first-mile pickup and last-mile instant delivery using drones and truck transshipment. A fundamental challenge involves coordinating merchants, drones, transshipment hubs, trucks, and consumer communities through the hub-and-spoke network (HSN). This study formulated the optimization problem for HSN to minimize logistics costs and loss of orders constrained by service time limits. The ε-constraint model, two evolutionary algorithms based on Non-dominated Sorting Genetic Algorithm II (NSGA-II) using permutation (EAp) and rand key-based (EAr) encoding/decoding schemes were devised to solve the bi-objective mathematical program. Three groups of twelve experiments were conducted using ideal datasets and datasets generated from Shenzhen city to validate the models and algorithms. Relaxing the logistics objective by 10% and subsequently minimizing the loss of orders can significantly reduce average unmet orders by 24.61%; when spokes were beyond 20, the ε-constraint model failed to achieve solutions within an acceptable time. While EAp and EAr demonstrated competence, EAr proved to be more competitive in computation time, hypervolume, spacing metric, and the number of non-dominated solutions on the Pareto fronts. Key parameters influencing the HSN solutions include drone and truck speeds, acceptable delivery times, and the processing and waiting time at hubs.

ImportancePostoperative ileus is common after abdominal surgery, and small clinical studies have reported that intraoperative administration of dexmedetomidine may be associated with improvements in postoperative gastrointestinal function. However, findings have been inconsistent and study samples have been small. Further examination of the effects of intraoperative dexmedetomidine on postoperative gastrointestinal function is needed.ObjectiveTo evaluate the effects of intraoperative intravenous dexmedetomidine vs placebo on postoperative gastrointestinal function among older patients undergoing abdominal surgery.Design, setting, and participantsThis multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at the First Affiliated Hospital of Anhui Medical University in Hefei, China (lead site), and 12 other tertiary hospitals in Anhui Province, China. A total of 808 participants aged 60 years or older who were scheduled to receive abdominal surgery with an expected surgical duration of 1 to 6 hours were enrolled. The study was conducted from August 21, 2018, to December 9, 2019.InterventionsDexmedetomidine infusion (a loading dose of 0.5 μg/kg over 15 minutes followed by a maintenance dose of 0.2 μg/kg per hour) or placebo infusion (normal saline) during surgery.Main outcomes and measuresThe primary outcome was time to first flatus. Secondary outcomes were postoperative gastrointestinal function measured by the I-FEED (intake, feeling nauseated, emesis, physical examination, and duration of symptoms) scoring system, time to first feces, time to first oral feeding, incidence of delirium, pain scores, sleep quality, postoperative nausea and vomiting, hospital costs, and hospital length of stay.ResultsAmong 808 patients enrolled, 404 were randomized to receive intraoperative dexmedetomidine, and 404 were randomized to receive placebo. In total, 133 patients (60 in the dexmedetomidine group and 73 in the placebo group) were excluded because of protocol deviations, and 675 patients (344 in the dexmedetomidine group and 331 in the placebo group; mean [SD] age, 70.2 [6.1] years; 445 men [65.9%]) were included in the per-protocol analysis. The dexmedetomidine group had a significantly shorter time to first flatus (median, 65 hours [IQR, 48-78 hours] vs 78 hours [62-93 hours], respectively; P