Associations between multiple metals exposure and cognitive function in the middle-aged and older adults from China: A cross-sectional study.

The rapidly rising risk of cognitive decline is a serious challenge for the elderly. As the wide-distributed environmental chemicals, the effects of metals exposure on cognitive function have attracted much attention, but the results remain inclusive. This study aimed to investigate the roles of multiple metals co-exposure on cognition. We included a total of 6112 middle-aged and older participants, detected their plasma levels of 23 metals by using inductively coupled plasma mass spectrometry, and assessed their cognitive function by using the Mini-Mental State Examination (MMSE). The results showed that increased plasma levels of iron (Fe) and zinc (Zn) were positively associated with MMSE score, but the increased levels of nickel (Ni) and lead (Pb) were associated with decreased MMSE score (all FDR < 0.05). Subjects exposed to both high levels of Ni and Pb showed the lowest MMSE score [ß (95% CI) = -0.310 (-0.519, -0.100)], suggesting that Ni and Pb had a synergistic toxic effect on cognitive function. In addition, the hazardous roles of Ni and Pb were mainly found among subjects with low plasma level of Zn, but were not significant among those with high-Zn level [Ni: ß (95% CI) = -0.281 (-0.546, -0.015) vs. -0.146 (-0.351, 0.058); Pb: ß (95% CI) = -0.410 (-0.651, -0.169) vs. -0.060 (-0.275, 0.155)], which suggested that Zn could attenuate the adverse effects of Pb and Ni on cognitive function. The cognitive function was gradually decreased among subjects with increased number of adverse exposures to the above four metals (Ptrend < 0.001). In conclusion, our findings revealed the individual, interactive, and combined effects of Fe, Ni, Pb, and Zn on cognitive function, which may provide new perspectives on cognitive protection, but further prospective cohort studies and biological researches are needed to validate these findings.

Exploring the effects of an online learning platform in stage III cardiac rehabilitation for individuals with coronary heart disease: Randomized controlled study.

The objective of this study is to assess the influence of blended education methodologies, utilizing an online education platform, among stage III cardiac rehabilitation (CR) patients diagnosed with coronary heart disease (CHD). Between June and August 2021, a cohort of 90 patients diagnosed with CHD, previously discharged from a second-class hospital 1 year earlier, were randomly allocated into 2 groups: the experimental and control groups, with each comprising 45 patients. Patients in the control group received out-of-hospital CR education via WeChat, while those in the experimental group received blended CR education utilizing an online education platform. Following a 24-week period, the self-management behavior and negative emotions of both groups were compared before and after the intervention. The final count of patients in the control and experimental groups was 39 and 37, respectively. Post the intervention, in terms of self-management behavior, the control group achieved an average score of 90.69 ±â€…7.13, while the experimental group scored 96.11 ±â€…5.42 (P < .05). Concerning negative emotions, the anxiety scores for the control and experimental groups were 3.03 ±â€…2.63 and 1.86 ±â€…1.80, respectively, and the depression scores were 3.00 (3.00) and 2.00 (3.00), respectively (P < .05). The differences in the outcomes mentioned above were statistically significant. The implementation of a blended educational approach utilizing an online platform has resulted in notable improvements in self-management skills and the reduction of negative emotions among patients with CHD. As a result, this educational strategy has demonstrated effectiveness in providing post-discharge CR education for patients with CHD.

Effects of educational attainment on comorbidity of pain and depression in Chinese older adults.

Pain and depression comorbidity (PD) among older adults in China is common and significantly affects their physical and mental health. The psychosocial factors may affect people's feelings, understanding and expression of pain and depression, leading to inaccurate assessment of this condition. Educational attainment is thought to be associated with either pain or depression. However, we do not yet know the relationship between educational attainment and PD. Using data from the 2018 China Health and Retirement Longitudinal Study in 2018, we analyzed various variables in 7742 individuals aged 60 years and older. Our results indicate significant differences between the PD and non-PD populations in terms of social, lifestyle, and behavioral factors. We observed a significant decrease in the incidence of PD among older adults with higher levels of education (p < 0.001). This association appears to be partially mediated by cognitive ability, suggesting that educational attainment may mitigate the risk of PD through cognitive enhancement. In addition, our analysis shows that the effect of educational attainment on PD is moderated by additional psychosocial factors, including living environment and alcohol consumption patterns. Older adults with higher levels of education tend to live in urban areas and have better control over alcohol consumption, which may contribute to a lower incidence of PD. Therefore, interventions aimed at enhancing cognitive abilities, improving living environments, and promoting healthier lifestyles and habits among older adults could potentially reduce their burden of PD.

Magnetic shielding properties of an iron-based nanocrystalline alloy for induction heating systems.

A nanocrystalline alloy, with an iron-based composition (Fe58.5Si16.7B6.5Nb5.1Cu13.2) and a Curie temperature of 570 °C, was investigated for its effectiveness as magnetic shielding films in an induction heating system. The primary focus of the research was to evaluate the shielding performance of the 3-turned (9-layered) shielding films with dimensions of 135 mm × 17 mm × 0.15 mm. Upon winding, these films formed a cylindrical structure that enveloped the coil, with a diameter of 13.9 mm and a height of 17 mm. The results showed that increasing the degree of fragmentation within the nanocrystalline shielding films significantly reduced the magnetic permeability by decreasing the real component from 11,500 to 400 and the imaginary part from 2800 to 20. However, a lower degree of fragmentation led to a 10 % increase in the resistance (Rs) of the heating module, although this effect was less pronounced as the relative permeability continued to increase. Furthermore, observations on preheating time to a set temperature of 400 °C and total energy consumption over a duration of 250s revealed an initial downward trend, followed by a rapid increase that even exceeded the initial values as the magnetic permeability of the nanocrystalline shielding films augmented. Notably, the study emphasized that nanocrystalline shielding films with a relative permeability value of 1000 demonstrated exceptional magnetic shielding performance, resulting in a 12.5 % reduction in preheat time and 7 % less energy consumption during preheating. In addition to empirical findings, the study developed a theoretical model elucidating the shielding mechanism inherent in induction heating systems. This model serves as a robust framework for the application of nanocrystalline shielding materials in such systems, laying the groundwork for enhanced magnetic shielding capabilities in future applications.

Self-management interventions for chronic widespread pain including fibromyalgia: a systematic review and qualitative evidence synthesis.

ABSTRACT: Supporting behavioural self-management is increasingly important in the care for chronic widespread pain (CWP), including fibromyalgia. Understanding peoples' experiences of these interventions may elucidate processes and mechanisms that lead to or hinder their intended impact. We conducted a systematic review and thematic synthesis of qualitative studies exploring peoples' experiences of self-management interventions for CWP, including fibromyalgia. MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science were searched. Primary qualitative or mixed-methods studies were included if they explored people's self-management intervention experiences for their CWP, including fibromyalgia. Screening, data extraction, and critical appraisal were conducted by 2 reviewers. Data analysis was conducted through thematic synthesis. Twenty-three studies were included, mostly were rated as high or moderate quality. We developed 4 analytic themes: A multifaceted experience of the intervention, potential for transformative experience of group cohesion, a new outlook, and striving for change after the loss of support. Broadly, personalisation was perceived as beneficial and people experienced a range of emotional experiences. These appeared to support positive behavioural and cognitive changes. For most, group activities promoted acceptance and support, fostering new perspectives and improved self-management, although some found aspects of group contexts challenging. Lack of on-going support after interventions led to challenges in applying behavioural strategies, and some struggled without social support from the group. The experiences of self-management interventions for CWP reflect a complex, multifaceted process. Although many reported positive experiences, addressing issues with integration of physical activity, group dynamics and postintervention support may improve effectiveness for a broader range of people.

Effect of uric acid on lipid metabolism assessed via restricted cubic splines: A new insight.

Background: Hyperuricemia can promote both blood lipids and non-alcoholic fatty liver disease (NAFLD). However, the role of the entire uric acid (UA) span, especially low concentrations below hyperuricemia, on lipid metabolism remains unclear. Methods: A cross-sectional study was designed. Data on the age, sex, UA, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) of 1977 participants, who underwent physical examination, were collected. NAFLD and non-alcoholic fatty pancreas disease (NAFPD) were diagnosed using abdominal ultrasound. Restricted cubic splines (RCS) linear regression model was used to evaluate the effect of the UA span on TG, TC, HDL, and LDL, respectively. RCS logistic regression model was employed to evaluate the effect of the UA span on NAFLD and NAFPD. Results: RCS linear regression model showed that TG was negatively correlated with UA at first, then exhibiting a positive correlation. Meanwhile, HDL was positively correlated with UA at first, then negatively correlated. There was a positive linear correlation between TC and UA (P for nonlinear = 0.578) and a positive nonlinear correlation between LDL and UA (P for nonlinear = 0.021). RCS logistic regression model showed that NAFLD and NAFPD were negatively correlated with UA at first and then positively correlated with UA. Conclusion: our study showed that the entire UA span has a J-shaped effect on some lipids, NAFLD, and NAFPD. Besides, TG and HDL, compared with TC or LDL, may better reflect the status of NAFLD and NAFPD.

iP3T: an interpretable multimodal time-series model for enhanced gait phase prediction in wearable exoskeletons.

Introduction: Wearable exoskeletons assist individuals with mobility impairments, enhancing their gait and quality of life. This study presents the iP3T model, designed to optimize gait phase prediction through the fusion of multimodal time-series data. Methods: The iP3T model integrates data from stretch sensors, inertial measurement units (IMUs), and surface electromyography (sEMG) to capture comprehensive biomechanical and neuromuscular signals. The model's architecture leverages transformer-based attention mechanisms to prioritize crucial data points. A series of experiments were conducted on a treadmill with five participants to validate the model's performance. Results: The iP3T model consistently outperformed traditional single-modality approaches. In the post-stance phase, the model achieved an RMSE of 1.073 and an R2 of 0.985. The integration of multimodal data enhanced prediction accuracy and reduced metabolic cost during assisted treadmill walking. Discussion: The study highlights the critical role of each sensor type in providing a holistic understanding of the gait cycle. The attention mechanisms within the iP3T model contribute to its interpretability, allowing for effective optimization of sensor configurations and ultimately improving mobility and quality of life for individuals with gait impairments.

Development of Highly Sensitive and Thermostable Microelectromechanical System Pressure Sensor Based on Array-Type Aluminum-Silicon Hybrid Structures.

In order to meet the better performance requirements of pressure detection, a microelectromechanical system (MEMS) piezoresistive pressure sensor utilizing an array-type aluminum-silicon hybrid structure with high sensitivity and low temperature drift is designed, fabricated, and characterized. Each element of the 3 × 3 sensor array has one stress-sensitive aluminum-silicon hybrid structure on the strain membrane for measuring pressure and another temperature-dependent structure outside the strain membrane for measuring temperature and temperature drift compensation. Finite-element numerical simulation has been adopted to verify that the array-type pressure sensor has an enhanced piezoresistive effect and high sensitivity, and then this sensor is fabricated based on the standard MEMS process. In order to further reduce the temperature drift, a thermodynamic control system whose heating feedback temperature is measured by the temperature-dependent structure is adopted to keep the working temperature of the sensor constant by using the PID algorithm. The experiment test results show that the average sensitivity of the proposed sensor after temperature compensation reaches 0.25 mV/ (V kPa) in the range of 0-370 kPa, the average nonlinear error is about 1.7%, and the thermal sensitivity drift coefficient (TCS) is reduced to 0.0152%FS/°C when the ambient temperature ranges from -20 °C to 50 °C. The research results may provide a useful reference for the development of a high-performance MEMS array-type pressure sensor.

Y9, a Gboxin analog, displays anti-tumor effect in non-small cell lung cancer by inducing lysosomal dysfunction and apoptosis.

Non-small cell lung cancer (NSCLC) ranks among the most prevalent malignancies globally. Gboxin, a novel inhibitor of mitochondrial complex V that exerts unique anti-tumor effects via oxidative phosphorylation inhibition, but shows no efficacy against NSCLC in vivo. Through chemical structure optimization, we designed and synthesized Gboxin analog Y9, which demonstrates significantly enhanced potency over its predecessor. Specifically, Y9 inhibited NSCLC significantly more strongly than Gboxin and possessed the ability to inhibit cell cycle progression and induce oxidative stress similar to Gboxin. Further investigation revealed that unlike Gboxin, Y9 selectively acidifies lysosomes and induces lysosomal dysfunction. This leads to hyperactive autophagy with impaired substrate clearance, and ultimately resulting in apoptosis. Animal studies confirmed the efficacy of Y9 in suppressing tumor growth in a xenograft mouse model. Collectively, Y9 is a distinctive Gboxin analog that outperforms its prototype by inducing lysosomal dysfunction and apoptosis, and has the potential to be developed as a novel anti-NSCLC lead compound.

Dynamic transcriptomic and regulatory networks underpinning the transition from fetal primordial germ cells to spermatogonia in mice.

The transition from fetal primordial germ cells (PGCs) to spermatogonia (SPG) is critical for male germ cell development; however, the detailed transcriptomic dynamics and regulation underlying this transition remain poorly understood. Here by interrogating the comprehensive transcriptome atlas dataset of mouse male germ cells and gonadal cells development, we elucidated the regulatory networks underlying this transition. Our single-cell transcriptome analysis revealed that the transition from PGCs to SPG was characterized by global hypertranscription. A total of 315 highly active regulators were identified to be potentially involved in this transition, among which a non-transcription factor (TF) regulator TAGLN2 was validated to be essential for spermatogonial stem cells (SSCs) maintenance and differentiation. Metabolism profiling analysis also revealed dynamic changes in metabolism-related gene expression during PGC to SPG transition. Furthermore, we uncovered that intricate cell-cell communication exerted potential functions in the regulation of hypertranscription in germ cells by collaborating with stage-specific active regulators. Collectively, our work extends the understanding of molecular mechanisms underlying male germ cell development, offering insights into the recapitulation of germ cell generation in vitro.

A Multi-Functional Nanoadjuvant Coupling Manganese with Toll-Like 9 Agonist Stimulates Potent Innate and Adaptive Anti-Tumor Immunity.

The effectiveness of Toll-like 9 agonists (CpG) as an adjuvant for tumor immunotherapy is restricted due to their insufficient ability to activate anti-tumor immunity. To address that, the common nutrient metal ions are explored (Mn2+, Cu2+, Ca2+, Mg2+, Zn2+, Fe3+, and Al3+), identifying Mn2+ as a key enhancer of CpG to mediate immune activation by augmenting the STING-NF-κB pathway. Mn2+ and CpG are then self-assembled with epigallocatechin gallate (EGCG) into a nanoadjuvant MPN/CpG. Local delivery of MPN/CpG effectively inhibits tumor growth in a B16 melanoma-bearing mouse model, reshaping the tumor microenvironment (TME) by repolarizing M2-type tumor-associated macrophages (TAMs) to an M1-type and boosting intra-tumoral infiltration of CD8+/CD4+ T lymphocytes and DCs. Furthermore, compared to free CpG, MPN/CpG exhibits heightened accumulation in lymph nodes, enhancing CpG uptake and DC activation, consequently inducing significant antigen-specific cytotoxic CD8+ T cell immune response and humoral immunity. In a prophylactic tumor-bearing mouse model, MPN/CpG vaccination with OVA antigen significantly delays B16-OVA melanoma growth and extends mouse survival. These findings underscore the potential of MPN/CpG as a multifunctional adjuvant platform to drive powerful innate and adaptive immunity and regulate TME against tumors.

Gated Recurrent Neural Network for Predicting the Plasmonic Colloid Composition from Spectra.

In current research on the synthesis of colloidal nanostructures, the size and morphology of nanoparticles still exhibit certain dispersion and variation from batch to batch. Characterization of size distribution and morphology distribution of nanoparticles often requires techniques such as scanning electron microscopy or transmission electron microscopy, which involve high vacuum environments, are time-consuming, and costly. Experienced researchers can roughly estimate the size and distribution of nanostructure from spectra for a given synthetic route, but the accuracy is often limited. This paper reports the potential of using neural networks to accurately predict the composition of colloidal nanostructures from spectra. We address several fundamental issues in neural network prediction of colloidal composition. We first demonstrate the prediction of the composition of a colloidal binary mixture of gold nanoparticles using a gated recurrent neural network (GRU). The evolution of prediction errors for scattering, absorption, and extinction spectra of nanostructures with sizes ranging from 5 to 120 nm are analyzed. Furthermore, we demonstrate that the neural network model operates robustly under white noise in experimental testing scenarios. Compared to fully connected neural networks, the gated recurrent unit exhibits better testing accuracy in spectral prediction. When confronted with experimental data that deviates from simulation outputs, minor adjustments to the training set can allow the predictions to align closely with the experimental spectra, paving the way for the characterization of complex colloidal compositions with artificial intelligence.

LLM-Enhanced Multi-Teacher Knowledge Distillation for Modality-Incomplete Emotion Recognition in Daily Healthcare.

The critical importance of monitoring and recognizing human emotional states in healthcare has led to a surge in proposals for EEG-based multimodal emotion recognition in recent years. However, practical challenges arise in acquiring EEG signals in daily healthcare settings due to stringent data acquisition conditions, resulting in the issue of incomplete modalities. Existing studies have turned to knowledge distillation as a means to mitigate this problem by transferring knowledge from multimodal networks to unimodal ones. However, these methods are constrained by the use of a single teacher model to transfer integrated feature extraction knowledge, particularly concerning spatial and temporal features in EEG data. To address this limitation, we propose a multi-teacher knowledge distillation framework enhanced with a Large Language Model (LLM), aimed at facilitating effective feature learning in the student network by transferring knowledge of extracting integrated features. Specifically, we employ an LLM as the teacher for extracting temporal features and a graph convolutional neural network for extracting spatial features. To further enhance knowledge distillation, we introduce causal masking and a confidence indicator into the LLM to facilitate the transfer of the most discriminative features. Extensive testing on the DEAP and MAHNOB-HCI datasets demonstrates that our model outperforms existing methods in the modality-incomplete scenario. This study underscores the potential application of large models in this field. The code is publicly available at https://github.com/yuzhezhangEEG/LM-KD.

Exosomal AC068768.1 enhances the proliferation, migration, and invasion of laryngeal squamous cell carcinoma through miR-139-5p/NOTCH1 axis.

Objective: Long non-coding RNAs (lncRNAs) are closely associated with the pathogenesis of laryngeal squamous cell carcinoma (LSCC). This study aimed to investigate the roles of AC068768.1 in LSCC. Methods: Exosomes were extracted by ultracentrifugation and identified by transmission electron microscopy (TEM) assay. The expression levels of mRNA and miRNA were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cellular functions were assesses through immunofluorescence, flow cytometry, colony formation, wound healing and transwell assays. Chromatin immunoprecipitation (ChIP) and luciferase assays were conducted to verify the binding of AC068768.1 by signal transducer and activator of transcription 3 (STAT3). Xenograft assays were performed to confirm the roles of AC068768.1 in LSCC, and hematoxylin-eosin (HE) staining was applied for histological analysis. Results: LSCC cell-derived exosomes induced M2-like tumor-associated macrophages (TAM2) polarization, which promoted the proliferation, migration, and invasion of LSCCs. Knockdown of exosomal AC068768.1 inhibited M2 polarization and suppressed LSCC aggressiveness both in vitro and in vivo. Moreover, AC068768.1 sponged miR-139-5p, inducing the upregulation of neurogenic locus notch homolog protein 1 (NOTCH1). LSCCs adapted to TAM2 polarization in the tumor microenvironment via AC068768.1-mediated activation of the NOTCH1 pathway. Additionally, NOTCH1 activated STAT3. Conclusion: The AC068768.1/miR-139-5p/NOTCH1/STAT3 axis promotes the metastasis of LSCC. This finding may provide a novel target for LSCC therapy.

Formation and resuscitation of viable but non-culturable (VBNC) yeast in the food industry: A review.

The viable but non-culturable (VBNC) state is a survival strategy adopted by microorganisms in response to unfavorable conditions in the environment. VBNC cells are unable to form colonies but still maintain a low level of activity, posing a potential threat to food safety and public health. Therefore, the development of effective strategies to prevent the formation and resuscitation of VBNC cells of microorganisms is a key challenge in food science and microbiology research. However, current research on VBNC cells has primarily focused on bacteria, with relatively limited reports on fungi. This paper provides a comprehensive and systematic review of yeast in the VBNC state, discussing various factors that induce and facilitate resuscitation, along with detection methods and formation and recovery mechanisms. A comprehensive understanding of the induction and resuscitation of yeast in the VBNC state and exploration of its molecular mechanism hold significant implications for food safety and public health. It is imperative to enhance our comprehension of the underlying mechanisms and contributory factors pertaining to VBNC yeast, thereby facilitating the efficient management of the food fermentation process and ensuring the integrity of food quality and safety.

Virome-wide analysis of histone modification mimicry motifs carried by viral proteins.

Histone mimicry (HM) refers to the presence of short linear motifs in viral proteins that mimic critical regions of host histone proteins. These motifs have the potential to interfere with host cell epigenome and counteract antiviral responses. Recent research shows that HM is critical for the pathogenesis and transmissibility of influenza virus and coronavirus. However, the distribution, characteristics, and functions of HM in eukaryotic viruses remain obscure. Herein, we developed a bioinformatic pipeline, Histone Motif Scan (HiScan), to identify HM motifs in viral proteins and predict their functions in silico. By analyzing 592,643 viral proteins using HiScan, we found that putative HM motifs were widely distributed in most viral proteins. Among animal viruses, the ratio of HM motifs between DNA viruses and RNA viruses was approximately 1.9:1, and viruses with smaller genomes had a higher density of HM motifs. Notably, coronaviruses exhibited an uneven distribution of HM motifs, with ß-coronaviruses (including most human pathogenic coronaviruses) harboring more HM motifs than other coronaviruses, primarily in the NSP3, S, and N proteins. In summary, our virome-wide screening of HM motifs using HiScan revealed extensive but uneven distribution of HM motifs in most viral proteins, with a preference for DNA viruses. Viral HM may play an important role in modulating viral pathogenicity and virus-host interactions, making it an attractive area of research in virology and antiviral medication.

Global research trends in labor analgesia: A bibliometric analysis from 2013 to 2023.

Objective: In the past decade, thousands of original articles focus on labor analgesia have published. However, little has been published in the literature that includes a bibliometric analysis of labor analgesia. Therefore, this study is designed to analyze the current status of research on labor analgesia over the past ten years and explore potential directions for the future. Methods: We retrieved the Web of Science Core Collection (WOSCC) for labor analgesia articles published from 2013 to 2023 and extracted the data from the literature. To perform the bibliometric analysis, we used CiteSpace (6.2. R5) and VOS viewer (1.6.19) as our primary analysis tools. Results: A total of 2406 articles were included, and the number of publications has increased steadily in the last ten years. The United States was the leading contributor to the area, and Harvard University was the most productive institution. The American Journal of Obstetrics and Gynecology was the most cited and influential journal. The most co-cited reference was "Epidural versus non-epidural or no analgesia for pain management in labour". The labels of the co-citation cluster have identified the characteristics of 5major clusters, such as "postpartum depression", "programmed intermittent epidural bolus", "childbirth experience" "intrapartum maternal fever" and "dural puncture", which play important roles in this field. Keywords co-occurrence and keywords burst detection showed that "vaginal birth", "postpartum depression", "maternal fever", "inflammation", "systematic review", "guidelines", "decreased risk" and "scale" were the most recent and most prominent topics of labor analgesia. Discussion: This study provided a global review of labor analgesia using bibliometric and visual techniques to provide an intuitive understanding of this topic and identify hotspots and research trends. Notably, intrapartum fever and postpartum depression have emerged as hotpots and trends in labor analgesia research, reflecting the current research landscape.

Oxycodone vs. sufentanil combined with quadratus lumborum block vs. transverse abdominis plane block in laparoscopic major gastrointestinal surgery: A randomized factorial trial protocol.

Background: Multimodal analgesia plays a key role in enhanced recovery after surgery. Herein, we describe a trial protocol investigating the effects of oxycodone-vs. sufentanil-based patient-controlled analgesia in combination with quadratus lumborum block (QLB) vs. transverse abdominis plane block (TAPB) on quality of recovery following major laparoscopic gastrointestinal surgery. Methods: and analysis: This is a prospective, randomized, controlled clinical trial with a 2 × 2 factorial design. A total of 120 adult patients undergoing laparoscopic major gastrointestinal surgery will be randomized, in a 1:1:1:1 ratio, to receive one of two patient-controlled analgesia regimens (based on oxycodone or sufentanil) and one of two regional blocks (QLB or TAPB). The primary outcome measure of this trial is the quality of recovery at 24 h after surgery, assessed using the 15-item quality of recovery (QoR-15) scale. The secondary outcomes include QoR-15 scores at 48 and 72 h after surgery; visceral and incisional pain at rest and while coughing at 1, 6, 24 and 48 h postoperatively; analgesic consumption within 0-24 h and 24-48 h postoperatively; need for rescue analgesia; postoperative flatus time; postoperative adverse events (sedation, nausea and vomiting, use of antiemetics, respiratory depression, and dizziness); and length of postoperative hospital stay. Discussion: The results of this trial will provide evidence for the optimal multimodal analgesic strategy to improve the quality of recovery for patients undergoing laparoscopic major gastrointestinal surgery. Trial registration: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR2400080766).

Spatiotemporal metabolomic approaches to the cancer-immunity panorama: a methodological perspective.

Metabolic reprogramming drives the development of an immunosuppressive tumor microenvironment (TME) through various pathways, contributing to cancer progression and reducing the effectiveness of anticancer immunotherapy. However, our understanding of the metabolic landscape within the tumor-immune context has been limited by conventional metabolic measurements, which have not provided comprehensive insights into the spatiotemporal heterogeneity of metabolism within TME. The emergence of single-cell, spatial, and in vivo metabolomic technologies has now enabled detailed and unbiased analysis, revealing unprecedented spatiotemporal heterogeneity that is particularly valuable in the field of cancer immunology. This review summarizes the methodologies of metabolomics and metabolic regulomics that can be applied to the study of cancer-immunity across single-cell, spatial, and in vivo dimensions, and systematically assesses their benefits and limitations.

Mitophagy Promotes Hair Regeneration by Activating Glutathione Metabolism.

Mitophagy maintains tissue homeostasis by self-eliminating defective mitochondria through autophagy. How mitophagy regulates stem cell activity during hair regeneration remains unclear. Here, we found that mitophagy promotes the proliferation of hair germ (HG) cells by regulating glutathione (GSH) metabolism. First, single-cell RNA sequencing, mitochondrial probe, transmission electron microscopy, and immunofluorescence staining showed stronger mitochondrial activity and increased mitophagy-related gene especially Prohibitin 2 (Phb2) expression at early-anagen HG compared to the telogen HG. Mitochondrial inner membrane receptor protein PHB2 binds to LC3 to initiate mitophagy. Second, molecular docking and functional studies revealed that PHB2-LC3 activates mitophagy to eliminate the damaged mitochondria in HG. RNA-seq, single-cell metabolism, immunofluorescence staining, and functional validation discovered that LC3 promotes GSH metabolism to supply energy for promoting HG proliferation. Third, transcriptomics analysis and immunofluorescence staining indicated that mitophagy was down-regulated in the aged compared to young-mouse HG. Activating mitophagy and GSH pathways through small-molecule administration can reactivate HG cell proliferation followed by hair regeneration in aged hair follicles. Our findings open up a new avenue for exploring autophagy that promotes hair regeneration and emphasizes the role of the self-elimination effect of mitophagy in controlling the proliferation of HG cells by regulating GSH metabolism.