Stable-Isotope N-Me Aziridination Enables Accurate Quantitative C═C Isomeric Lipidomics.

Accurate lipid quantification is essential to revealing their roles in physiological and pathological processes. However, difficulties in the structural resolution of lipid isomers hinder their further accurate quantification. To address this challenge, we developed a novel stable-isotope N-Me aziridination strategy that enables simultaneous qualification and quantification of unsaturated lipid isomers. The one-step introduction of the 1-methylaziridine structure not only serves as an activating group for the C═C bond to facilitate positional identification but also as an isotopic inserter to achieve accurate relative quantification. The high performance of this reaction for the identification of unsaturated lipids was verified by large-scale resolution of the C═C positions of 468 lipids in serum. More importantly, by using this bifunctional duplex labeling method, various unsaturated lipids such as fatty acids, phospholipids, glycerides, and cholesterol ester were accurately and individually quantified at the C═C bond isomeric level during the mouse brain ischemia. This study provides a new approach to quantitative structural lipidomics.

Effect of cesarean section on the risk of autism spectrum disorders/attention deficit hyperactivity disorder in offspring: a meta-analysis.

PURPOSE: This study was conducted to investigate the relationship between cesarean section (CS) offspring and autism spectrum disorders (ASD)/attention deficit hyperactivity disorder (ADHD). METHODS: Searching of the databases (PubMed, Web of Science, Embase, and Cochrane Library) for studies on the relationship between mode of delivery and ASD/ADHD until August 2022. The primary outcome was the incidence of ASD/ADHD in the offspring. RESULTS: This meta-analysis included 35 studies (12 cohort studies and 23 case-control studies). Statistical results showed a higher risk of ASD (odds ratio (OR) = 1.25, P < 0.001) and ADHD (OR = 1.11, P < 0.001) in CS offspring compared to the VD group. Partial subgroup analysis showed no difference in ASD risk between CS and VD offspring in sibling-matched groups (OR = 0.98, P = 0.625). The risk of ASD was higher in females (OR = 1.66, P = 0.003) than in males (OR = 1.17, P = 0.004) in the CS offspring compared with the VD group. There was no difference in the risk of ASD between CS under regional anesthesia group and VD group (OR = 1.07, P = 0.173). However, the risk of ASD was higher in the CS offspring under general anesthesia than in the VD offspring (OR = 1.62, P < 0.001). CS offspring developed autism (OR = 1.38, P = 0.011) and pervasive developmental disorder-not otherwise specified (OR = 1.46, P = 0.004) had a higher risk than VD offspring, but there was no difference in Asperger syndrome (OR = 1.19, P = 0.115). Offspring born via CS had a higher incidence of ADHD in different subgroup analyses (sibling-matched, type of CS, and study design). CONCLUSIONS: In this meta-analysis, CS was a risk factor for ASD/ADHD in offspring compared with VD.

Efficient treatment of colon cancer with codelivery of TRAIL and imatinib by liposomes.

To solve the problem of resistance of tumor cells to TRAIL and the inevitable side effects of imatinib during treatment, we successfully prepared a kind of multifunctional liposome that encapsulated imatinib in its internal water phase and inserted TRAIL on its membrane in this study, which named ITLPs. The liposomes appeared uniform spherical and the particle size was approximately 150 nm. ITLPs showed high accumulation in TRAIL-resistance cells and HT-29 tumor-bearing mice model. In vitro cytotoxicity assay results showed that the killing activity of HT-29 cells treated with ITLPs increased by 50% and confirmed that this killing activity was mediated by the apoptosis pathway. Through mechanism studies, it was found that ITLPs arrested up to 32.3% of cells in phase M to exert anti-tumor effects. In vivo anti-tumor study showed that ITLPs achieved 61.8% tumor suppression and little toxicity in the HT-29 tumor-bearing mice model. Overall results demonstrated that codelivery of imatinib and TRAIL via liposomes may be a prospective method in the treatment of the TRAIL-resistance tumor.

Association of cesarean section with risk of childhood leukemia: A meta-analysis from an observational study.

Recent studies suggest that children born via cesarean section (CS) are predisposed to immune-mediated diseases later in life. The association between CS and childhood leukemia was investigated in this meta-analysis of observational studies. Two researchers independently searched PubMed, Web of Science, Embase, and Cochrane Library for literature on the association between CS and childhood leukemia before February 2022. And pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated to determine the link between CS and childhood leukemia. The preliminary search resulted in 1321 articles and 16 articles were finally included after screening. The primary outcome was the risk of leukemia in children born via CS versus those born vaginally. The results revealed that having a CS was associated with an increased risk of childhood leukemia compared to having vaginal section (VS) (OR = 1.07, 95% CI: 1.02-1.13, p = 0.01), especially for acute lymphoblastic leukemia (ALL) (OR = 1.09, 95% CI: 1.03-1.16, p = 0.004). Children delivered via elective CS had a higher risk of ALL (OR = 1.18, 95% CI: 1.07-1.31, p = 0.001), but emergency CS did not. It is worth noting that neither emergency CS nor elective CS were found to be associated with acute myeloid leukemia. Compared to VS, CS increased the risk of leukemia in children, with elective CS significantly increasing ALL risk.

Codelivery of TRAIL and Mitomycin C via Liposomes Shows Improved Antitumor Effect on TRAIL-Resistant Tumors.

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) constitutes a promising antitumor drug, tumor resistance to TRAIL has become a major obstacle in its clinical application. Mitomycin C (MMC) is an effective TRAIL-resistant tumor sensitizer, which indicates a potential utility of combination therapy. However, the efficacy of this combination therapy is limited owing to its short half-life and the cumulative toxicity of MMC. To address these issues, we successfully developed a multifunctional liposome (MTLPs) with human TRAIL protein on the surface and MMC encapsulated in the internal aqueous phase to codeliver TRAIL and MMC. MTLPs are uniform spherical particles that exhibit efficient cellular uptake by HT-29 TRAIL-resistant tumor cells, thereby inducing a stronger killing effect compared with control groups. In vivo assays revealed that MTLPs efficiently accumulated in tumors and safely achieved 97.8% tumor suppression via the synergistic effect of TRAIL and MMC in an HT-29 tumor xenograft model while ensuring biosafety. These results suggest that the liposomal codelivery of TRAIL and MMC provides a novel approach to overcome TRAIL-resistant tumors.

Effects of Polyunsaturated Fatty Acids on Colorectal Cancer Patients: A Meta-Analysis of Randomized Controlled Trials.

This study aimed to investigate the effects of polyunsaturated fatty acids (PUFAs) on patients with colorectal cancer (CRC). Electronic databases such as PubMed and Web of Science were searched. Studies on the application of PUFAs in patients with CRC, published up to January 2022, were conducted. Twelve studies involving 702 CRC patients were included. For patients undergoing surgery, subgroup analyses indicated that preoperative supplementation with PUFAs improved total postoperative infectious complications (RR: 0.37, p = 0.02). Furthermore, the supplementation of PUFAs in preoperative (WMD: -2.27, p < 0.001) and postoperative (WMD: -2.66, p = 0.01) groups was effective in shortening the postoperative hospital stay for patients with CRC. Tumor necrosis factor-α (TNF-α) (SMD: -0.56, p = 0.007) and interleukin-6 (IL-6) (SMD: -0.54, p = 0.004) levels were lower in all CRC patients receiving PUFAs intervention than in the control group. Moreover, supplementation with PUFAs in chemotherapy patients significantly increased albumin (WMD: 0.48, p = 0.03) and decreased C-reactive protein (CRP) (WMD: -6.12, p = 0.02) compared to the control group. This study demonstrated that PUFAs intervention could diminish the total postoperative infection complications of CRC patients, shorten the postoperative hospital stay, and reduce inflammation.

Liposome-Based Co-Immunotherapy with TLR Agonist and CD47-SIRPα Checkpoint Blockade for Efficient Treatment of Colon Cancer.

Antitumor immunity is an essential component of cancer therapy and is primarily mediated by the innate immune response, which plays a critical role in initiating and shaping the adaptive immune response. Emerging evidence has identified innate immune checkpoints and pattern recognition receptors, such as CD47 and Toll-like receptor 7 (TLR7), as promising therapeutic targets for cancer treatment. Based on the fusion protein Fc-CV1, which comprises a high-affinity SIRPα variant (CV1), and the Fc fragment of the human IgG1 antibody, we exploited a preparation which coupled Fc-CV1 to imiquimod (TLR7 agonist)-loaded liposomes (CILPs) to actively target CT26. WT syngeneic colon tumor models. In vitro studies revealed that CILPs exhibited superior sustained release properties and cell uptake efficiency compared to free imiquimod. In vivo assays proved that CILPs exhibited more efficient accumulation in tumors, and a more significant tumor suppression effect than the control groups. This immunotherapy preparation possessed the advantages of low doses and low toxicity. These results demonstrated that a combination of immune checkpoint blockade (ICB) therapy and innate immunity agonists, such as the Fc-CV1 and imiquimod-loaded liposome preparation utilized in this study, could represent a highly effective strategy for tumor therapy.

Lipidomic Characterization of Oocytes at Single-Cell Level Using Nanoflow Chromatography-Trapped Ion Mobility Spectrometry-Mass Spectrometry.

Mass spectrometry (MS)-based lipidomic has become a powerful tool for studying lipids in biological systems. However, lipidome analysis at the single-cell level remains a challenge. Here, we report a highly sensitive lipidomic workflow based on nanoflow liquid chromatography and trapped ion mobility spectrometry (TIMS)-MS. This approach enables the high-coverage identification of lipidome landscape at the single-oocyte level. By using the proposed method, comprehensive lipid changes in porcine oocytes during their maturation were revealed. The results provide valuable insights into the structural changes of lipid molecules during porcine oocyte maturation, highlighting the significance of sphingolipids and glycerophospholipids. This study offers a new approach to the single-cell lipidomic.

Effect of Intraperitoneal Local Anesthetics in Laparoscopic Bariatric Surgery: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The effectiveness of intraperitoneal local anesthesia (IPLA) has been confirmed in other fields, but its use in bariatric surgery remains debatable. This study aimed to evaluate the analgesic effect of IPLA in bariatric surgery. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to February 2022. All randomized controlled trials (RCTs) assessing IPLA's analgesic effect in bariatric surgery were included in this study. Pain-related indicators were the outcome. RESULTS: Ten RCTs with 979 patients were included. Postoperative pain scores were significantly lower in IPLA group. Subgroup analysis demonstrated that IPLA was associated with lower pain scores in 6 h and at 24 h compared to the control group, without significant differences at 8, 12, and 48 h. Meanwhile, IPLA reduced the dose of opioids taken postoperatively. Additionally, there were no differences in adverse events between the two groups. As far as the number of postoperative analgesics used and hospital stays were concerned, our results did not show statistical differences between the two groups. CONCLUSION: IPLA can reduce postoperative pain safely and effectively, particularly during the early postoperative stage.

Early versus Delayed Minimally Invasive Intervention for Acute Necrotizing Pancreatitis: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Nowadays, minimally invasive intervention (MII) has largely replaced delayed open surgery in acute necrotizing pancreatitis (ANP). However, the timing of MII remains unclear. The present study investigated the effect of early versus delayed MII on complications in ANP. METHODS: Studies evaluating the impact of the timing of MII on complications in ANP patients were thoroughly searched on PubMed, Embase, Cochrane Library, and Web of Science from inception to June 2022. The primary outcome of interest was mortality. Secondary outcomes were the incidence of complications. RESULTS: Nine studies reporting 870 patients undergoing MII for ANP were included. No significant difference was found in mortality between the early and delayed intervention groups. In addition, the timing of MII was not associated with the incidence of new-onset respiratory failure, new-onset cardiovascular failure, new-onset renal failure, new-onset multiple organ failure, gastrointestinal fistula or perforation, pancreatic fistula, stent migration, bleeding, venous thrombosis, and new-onset pancreatic endocrine insufficiency. Notably, in the subgroup analysis of biliary and Asian ANP patients, early intervention was associated with a significantly higher risk of new-onset renal failure than delayed intervention. CONCLUSIONS: Early intervention is safe and recommended only for patients with indications for intervention, such as infection.

The relationship between dairy products intake and breast cancer incidence: a meta-analysis of observational studies.

BACKGROUND: The effect of dairy products intake on breast cancer (BC) is highly controversial. This study aims to investigate the relationship between dairy intake and BC incidence. METHODS: A search was carried out in PubMed, EBSCO, Web of Science, and Cochrane Library databases before January 2021. The primary objective was the risk of BC and intake of dairy products were exposure variables. RESULTS: The meta-analysis comprised 36 articles with 1,019,232 participants. Total dairy products have a protective effect on female population (hazard ratio (HR) =0.95, 95% confidence interval (CI) =0.91-0.99, p = 0.019), especially for estrogen receptor-positive (ER+) (HR = 0.79, p = 0.002) and progesterone receptor-positive (PR+) BC (HR = 0.75, p = 0.027). For ER+/PR+ BC, there is a trend of protection, but it has not reached statistical significance (HR = 0.92, p = 0.075). Fermented dairy products can reduce BC risk in postmenopausal population (HR = 0.96, 95%CI = 0.93-0.99, p = 0.021), but have no protective effect on premenopausal population (HR = 0.98, 95%CI = 0.94-1.03, p = 0.52). Non-fermented dairy products have no significant effect on BC occurrence (p > 0.05). High-fat dairy products are harmful to women, without statistical difference (HR = 1.06, 95%CI = 1.00-1.13, p = 0.066). On the contrary, low-fat dairy products can protect the premenopausal population (HR = 0.94, 95%CI = 0.89-1.00, p = 0.048). CONCLUSION: The intake of dairy products can overall reduce BC risk in the female population, but different dairy products have varying effects on different BC subtypes and menopausal status.

Research on Driving Fatigue Alleviation Using Interesting Auditory Stimulation Based on VMD-MMSE.

The accurate detection and alleviation of driving fatigue are of great significance to traffic safety. In this study, we tried to apply the modified multi-scale entropy (MMSE) approach, based on variational mode decomposition (VMD), to driving fatigue detection. Firstly, the VMD was used to decompose EEG into multiple intrinsic mode functions (IMFs), then the best IMFs and scale factors were selected using the least square method (LSM). Finally, the MMSE features were extracted. Compared with the traditional sample entropy (SampEn), the VMD-MMSE method can identify the characteristics of driving fatigue more effectively. The VMD-MMSE characteristics combined with a subjective questionnaire (SQ) were used to analyze the change trends of driving fatigue under two driving modes: normal driving mode and interesting auditory stimulation mode. The results show that the interesting auditory stimulation method adopted in this paper can effectively relieve driving fatigue. In addition, the interesting auditory stimulation method, which simply involves playing interesting auditory information on the vehicle-mounted player, can effectively relieve driving fatigue. Compared with traditional driving fatigue-relieving methods, such as sleeping and drinking coffee, this interesting auditory stimulation method can relieve fatigue in real-time when the driver is driving normally.

Intentions Recognition of EEG Signals with High Arousal Degree for Complex Task.

This paper presents a novel electroencephalography (EEG) evoked paradigm based on neurological rehabilitation. By implementing a conceptual model "cup-and-ball" system, EEG signals in manipulating the dynamic constrained objects are generated. Based on the operational EEG signals, a method is proposed to recognize different mental intentions. Under the manipulating task with a high arousal level, common spatial patterns (CSP) is used to extract and optimize features of the EEG signals from ten participants. Quadratic discriminant analysis (QDA) is implemented on EEG signals in different dimensions to identify different EEG patterns. The cross-validation is used to make classifier adaptive to a given data set. The receiver operating characteristic (ROC) curves are presented to illustrate recognition performance. The classification effect of QDA is verified by paired t-test (P < 0.001). Based on the proposed method, the average accuracy of mental intentions is 0.9857 ± 0.0191 and the area under the ROC curve (AUC) is 0.9665 ± 0.0291. The performance of QDA is also compared with the other three classifiers such as the support vector machine (SVM), the decision tree (DT) and the k-nearest neighborhood (k-NN) rule. The results suggest that the proposed method is very competitive with other methods.

Automatic Detection of Epileptic Seizures in EEG Using Sparse CSP and Fisher Linear Discrimination Analysis Algorithm.

In order to realize the automatic epileptic seizure detection, feature extraction and classification of electroencephalogram (EEG) signals are performed on the interictal, the pre-ictal, and the ictal status of epilepsy patients. There is no effective strategy for selecting the number of channels and spatial filters in feature extraction of multichannel EEG data. Therefore, this paper combined sparse idea and greedy search algorithm to improve the feature extraction of common space pattern. The feature extraction can effectively overcome the repeating selection problem of feature pattern in the eigenvector space by the traditional method. Then we used the Fisher linear discriminant analysis to realize the classification. The results show that the proposed method can get high classification accuracy using fewer data. For 10 subjects, the averaged accuracy of epilepsy detection is more than 99%. So, the detection of an epileptic seizure based on sparse features using Fisher linear discriminant analysis classifiers is more suitable for a reliable, automatic epileptic seizure detection system to enhance the patient's care and the quality of life.

Study on the Effect of Man-Machine Response Mode to Relieve Driving Fatigue Based on EEG and EOG.

Rapid and accurate detection of driver fatigue is of great significance to improve traffic safety. In the present work, we propose the man-machine response mode (MRM) to relieve driver fatigue caused by long-term driving. In this paper, the characteristics of the complex brain network, which can effectively reflect brain activity information, were used to detect the change of driving fatigue over time. Combined with the traditional eye movement characteristics and a subjective questionnaire (SQ), the changes in driving fatigue characteristics were comprehensively analyzed. The results show that driving fatigue can be effectively delayed using the MRM. Additionally, the response equipment is low in cost and practical, so it will be practical to use in actual driving situations in the future.

Expanding the flexibility of dynamics simulation on different size particle-particle interactions by dielectrophoresis.

In this paper, we perform flexible and reliable dynamics simulations on different sizes of two or more particles' interactive motions, where they encounter positive or negative dielectrophoresis (DEP) forces. The particles with identical or non-identical size are in close proximity suspended freely in a solution under a homogeneous electric field. According to the description of classic dipole moment, DEP forces make the particles form a straight chain. Therefore, dynamics simulation based on Newton's laws is utilized to understand AC DEP phenomena among multiple particles. To solve the relevant governing equations, Stokes drag and repulsive forces (including wall and particles) are combined with DEP forces to obtain the trajectories of particles. Results show that particles with the same sign of the Clausius-Mossotti (CM) factor revolve clockwise or counterclockwise to attract each other parallel to the electric field direction. Conversely, the particle chain is perpendicular to the field. This programmable advantage is of great benefit to the study of three or four particle motions. Meanwhile, the pearl chain consisting of three or four particles is related not only to an individual CM factor but also to initial spatial configuration. Both the cluster and short chain are dependent on symmetry between the geometric distribution and electric field, while it implies different size particles easily cause the chain structure with less time.

Improvement Motor Imagery EEG Classification Based on Regularized Linear Discriminant Analysis.

Mental tasks classification such as motor imagery, based on EEG signals is an important problem in brain computer interface systems (BCI). One of the major concerns in BCI is to have a high classification accuracy. The other concerning one is with the favorable result is guaranteed how to improve the computational efficiency. In this paper, Mu/Beta rhythm was obtained by bandpass filter from EEG signal. And the classical linear discriminant analysis (LDA) was used for deciding which rhythm can give the better classification performance. During this, the common spatial pattern (CSP) was used to project data subject to the ratio of projected energy of one class to that of the other class was maximized. The optimal projection dimension was determined corresponding to the maximum of area under the curve (AUC) for each participant. Eventually, regularized linear discriminant analysis (RLDA) is possible to decode the imagined motor sensed using electroencephalogram (EEG). Results show that higher classification accuracy can be provided by RLDA. And optimal projection dimensions determined by LDA and RLDA are of consistent solution, this improves computational efficiency of CSP-RLDA method without computation of projection dimension.

[Recognition method of single trial motor imagery electroencephalogram signal based on sparse common spatial pattern and Fisher discriminant analysis].

This paper aims to realize the decoding of single trial motor imagery electroencephalogram (EEG) signal by extracting and classifying the optimized features of EEG signal. In the classification and recognition of multi-channel EEG signals, there is often a lack of effective feature selection strategies in the selection of the data of each channel and the dimension of spatial filters. In view of this problem, a method combining sparse idea and greedy search (GS) was proposed to improve the feature extraction of common spatial pattern (CSP). The improved common spatial pattern could effectively overcome the problem of repeated selection of feature patterns in the feature vector space extracted by the traditional method, and make the extracted features have more obvious characteristic differences. Then the extracted features were classified by Fisher linear discriminant analysis (FLDA). The experimental results showed that the classification accuracy obtained by proposed method was 19% higher on average than that of traditional common spatial pattern. And high classification accuracy could be obtained by selecting feature set with small size. The research results obtained in the feature extraction of EEG signals lay the foundation for the realization of motor imagery EEG decoding.

Study of the Home-Auxiliary Robot Based on BCI.

A home-auxiliary robot platform is developed in the current study which could assist patients with physical disabilities and older persons with mobility impairments. The robot, mainly controlled by brain computer interface (BCI) technology, can not only perform actions in a person's field of vision, but also work outside the field of vision. The wavelet decomposition (WD) is used in this study to extract the δ (0~4 Hz) and θ (4~8 Hz) sub-bands of subjects' electroencephalogram (EEG) signals. The correlation between pairs of 14 EEG channels is determined with synchronization likelihood (SL), and the brain network structure is generated. Then, the motion characteristics are analyzed using the brain network parameters clustering coefficient (C) and global efficiency (G). Meanwhile, the eye movement characteristics in the F3 and F4 channels are identified. Finally, the motion characteristics identified by brain networks and eye movement characteristics can be used to control the home-auxiliary robot platform. The experimental result shows that the accuracy rate of left and right motion recognition using this method is more than 93%. Additionally, the similarity between that autonomous return path and the real path of the home-auxiliary robot reaches up to 0.89.

Resveratrol mitigates the oxidative stress mediated by hypoxic-ischemic brain injury in neonatal rats via Nrf2/HO-1 pathway.

CONTEXT: Hypoxic-ischemic encephalopathy (HIE) has a high morbidity and mortality rate. Resveratrol possesses numerous biological properties including antioxidant, anti-inflammatory and neuroprotective activities. OBJECTIVE: The current experiment investigates the neuroprotective efficacy of resveratrol (RESV) against HIE by modulating Nrf2/HO-1 pathway in neonatal rats. MATERIALS AND METHODS: Seven-day-old pups (n = 48) were divided into four groups. Group-I rats receiving 2% DMSO saline (sham), group-II rats underwent unilateral carotid artery ligation and hypoxia (92% N2 and 8% O2) for 2.5 h (hypoxia-ischemia; HI), group-III and IV rats received 20 (RESV 20 + HI) or 40 mg/kg (RESV 40 + HI; group-IV) of RESV via intraperitoneal injection (ip), respectively, for 7 days prior to HI induction. RESULTS: Pre-treatment with RESV (20 or 40) markedly reduced (p < 0.01) the cerebral oedema (86.23-71.26 or 65.24%), infarct area (33.85-19.81 or 14.30%), lipid peroxidation products, inflammatory markers [IL-1ß 186-110 or 82; IL-6 255-146 or 103; TNF-α 310-204 or 137; NF-κB 205-115 or 91) p65 subunit] and significantly restored (p < 0.01) the antioxidative status by enhancing the activities of glutathione peroxidase (GPx) 5.22-6.49 or 7.78; catalase (CAT) 51-55 or 59, superoxide dismutase (SOD) 2.5-3.05 or 3.25; through marked upregulation (p < 0.01) of heme oxygenase 1 (HO-1) 0.65-0.69 or 0.73; and nuclear factor erythroid 2 related factor 2 (Nrf2) 0.73-0.86 or 0.91. DISCUSSION AND CONCLUSIONS: RESV displays its neurotherapeutic potential via upregulating the protein expression of Nrf2 and HO-1 signalling pathway and thereby attenuates oxidative stress and inflammatory response in HI-induced neonatal rats.