ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Although global brain science research has progressed rapidly in recent decades, several fundamental questions in neuroscience remain unresolved. In particular, the physical mechanism underlying neural signal transmission remains controversial, and the carriers responsible for neural information storage and retrieval have not yet been fully clarified. These unresolved issues motivate us to re-examine the processes of neural information generation, transmission, integration, storage, and retrieval from multiple perspectives. A key observation is that neural electromagnetic activities are closely associated with time. Their duration, temporal structure, and dynamic evolution play crucial roles in neural information processing. In this work, we analyze neural electromagnetic activities from the perspective of temporal scales (referred to here as the “time course”). By reviewing and integrating findings from previous studies, we examine the characteristic time requirements and dynamic features of neural processes occurring at different stages of information processing. These stages include neural signal generation, signal transmission along axons, synaptic integration, synaptic plasticity, and memory formation and retrieval. Based on this temporal analysis, we outline a framework describing neural electromagnetic activities across a wide range of time scales, spanning from microseconds to minutes, hours, or even longer periods associated with long-term memory, which suggests that neural information processing involves multiple physical processes operating at different time levels. Rapid electromagnetic events may occur on microsecond scales, whereas electrophysiological phenomena such as action potentials typically last on the order of milliseconds. Longer time scales are associated with synaptic plasticity and memory-related processes. From this perspective, we propose that the physical carrier of neural information may be transient electromagnetic pulses with durations on the microsecond scale. In this framework, action potentials can be interpreted as the macroscopic electrophysiological manifestation of underlying electromagnetic processes triggered by ionic currents across neuronal membranes. Rather than being the fundamental neural signal itself, the action potential may represent a measurable membrane-level response associated with the successful activation of these electromagnetic events. Moreover, we discuss a possible mechanism for long-term memory storage. Considering the apparent temporal contradiction between the millisecond-scale excitation of neurons and the long-term persistence of memories, we believe that long-term memory information may be stored within neural network topologies formed by electrical synapse coupling. Such structures, referred to as electrically coupled memory networks (ECMNs), may enable neurons within the same network to respond rapidly and synchronously to stimuli, thereby facilitating efficient memory retrieval. Overall, this study emphasizes the importance of considering the temporal organization of neural electromagnetic activities when interpreting neural signaling mechanisms. It may provide new insights into the physical nature of neural information carriers and the mechanisms of memory storage and retrieval. Furthermore, highlighting the potential role of electromagnetic interactions in neural activity may contribute to the development of new theoretical frameworks and experimental approaches in neuroscience. Such perspectives may also offer valuable references for future research on neural coding, brain function mechanisms, and neuromodulation technologies.

Background Antibiotics are frequently detected in aquatic environments, posing potential threats to ecological systems and public health. Objective To characterize antibiotic contamination in source water in Wuhan, evaluate the removal efficiency of conventional drinking water treatment processes, identify potential pollution sources, and assess ecological risks, thereby providing evidence to support water safety management. Methods A total of 34 source water samples and paired finished water samples were collected. Twenty-seven target antibiotics were analyzed via solid-phase extraction coupled with high-performance liquid chromatography-tandem mass spectrometry. Total antibiotic concentrations and the relative contributions of individual antibiotics were calculated for each sampling site. Differences in removal performance across seasons and waterworks scales were further assessed. Antibiotic pairs with co-occurrence frequencies of ≥ 10 were included in Spearman’s rank correlation analysis to explore co-occurrence patterns. Potential sources were inferred according to their approved clinic and veterinary uses. For ecological risk assessment, predicted no-effect concentrations were derived from chronic toxicity values for fish, Daphnia, green algae, and mysid obtained from the ECOSAR database. Risk quotients (RQ) were calculated using both the median and the 95th percentile concentrations to characterize typical and high-end ecological toxicity. Results Seventeen antibiotics were detected in the source water. Lincosamides, macrolides, and sulfonamides were frequently detected, with detection frequencies exceeding 50%. Although quinolones were detected less frequently (2.94%-38.24%), they exhibited episodic high concentrations; the 95th percentile concentration of cinoxacin (CNX) reached 365.73 ng·L⁻¹. The mean total antibiotic concentration was 1.79 times higher in the wet season (105.97 ng·L⁻¹) than in the dry season (59.21 ng·L⁻¹). The contribution of quinolones increased markedly from 0.87% in the dry season to 43.10% in the wet season. Except for flumequine (FQ), ofloxacin (OFX), enoxacin (ENX), and clarithromycin (CLR), the median removal rates of the remaining antibiotics by conventional treatment processes all exceeded 80%. Ten antibiotics achieved complete removal (100%) in the wet season, compared with 4 antibiotics in the dry season. The median removal rate of CLR declined with decreasing waterworks scale, from 67.92% in large-scale plants to –1.96% in medium-scale plants and –71.25% in small-scale plants. Apparent negative removal was observed for sulfadiazine (SDZ), FQ, OFX, and CLR, with OFX exhibiting the highest frequency of negative removal events (n=14). Correlation analysis revealed significant positive correlations between sulfonamides and macrolides (ρ=0.52-0.83), indicating mixed influences from livestock farming and domestic wastewater. Lincomycin (LIN) was positively correlated with sulfamethoxazole (SMX), but negatively correlated with the aforementioned antibiotic network, suggesting a predominantly human medical source. Based on median concentrations, the ecological risk of individual antibiotics was negligible. However, the cumulative risk to Daphnia reached a low level (RQ > 0.01), with sulfonamides contributing more than 70% of this risk. Based on the 95th percentile concentrations, bost individual and cumulative risks of quinolones to fish and Daphnia increased to low levels, with quinolones contributing more than 55% of the total risk. Conclusion Antibiotics are commonly detected in source water in Wuhan, and conventional drinking water treatment dose not completely eliminate all target compounds. Quinolones, despite their relatively low detection frequencies, occur at episodically high concentrations and pose low risks to fish and Daphnia under high-end exposure scenarios, warranting priority control. The coexistence of human-use and veterinary-use antibiotics reflects diverse pollution sources and highlights the need for coordinated multi-source pollution control.

Adipose tissue macrophages (ATMs) are crucial immunomodulatory factors in the adipose tissue (AT) microenvironment, playing an irreplaceable role in maintaining the balance of the local immune system and regulating metabolic homeostasis. Under obese conditions, the excessive accumulation of lipids leads to abnormal expansion of adipose tissue, which further disrupts the homeostasis of the local microenvironment, including the imbalance of inflammatory factors, the occurrence of oxidative stress, and the damage of microcirculation. As an essential immune cell population in adipose tissue, ATMs are deeply involved in the occurrence and progression of metabolic disorders and multiple obesity-related diseases, and their functional abnormalities are closely related to the initiation and development of adipose tissue inflammation and systemic metabolic disorders. The interaction between ATMs and adipokines, including adiponectin, leptin, resistin and retinol-binding protein 4 (RBP4), acts as the core immunological and molecular mechanism linking adipose tissue inflammation to continuous disease deterioration, and this interaction is also a key research focus in the field of obesity-related diseases in recent years. This review discusses in detail the facilitating effect of the AT inflammatory microenvironment on the differentiation of peripheral monocytes into ATMs, elaborating on the specific molecular mechanisms by which various inflammatory mediators and abnormal metabolic products in the inflammatory microenvironment induce the differentiation of peripheral monocytes into functional ATMs. It also focuses on the regulatory mechanisms of chemokine-mediated ATM polarization and recruitment, including the specific roles of key chemokines like monocyte chemoattractant protein‑1 (MCP-1) and C‑X‑C motif chemokine ligand 10 (CXCL10) in mediating the recruitment of ATMs to adipose tissue, as well as the molecular pathways that regulate the switch between M1 pro-inflammatory phenotype and M2 anti-inflammatory phenotype of ATMs. In addition, this review explores the specific process by which ATMs trigger AT inflammation by secreting various pro-inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, which further amplify the local inflammatory response and disrupt the metabolic homeostasis of adipose tissue. Furthermore, it analyzes the specific binding patterns and molecular characteristics of adiponectin, leptin, resistin and RBP4 with ATM surface receptors, and clarifies how the activation of downstream immune signaling pathways, such as Janus kinase‑signal transducer and activator of transcription (JAK-STAT), nuclear factor‑κB (NF‑κB), and phosphatidylinositol 3‑kinase‑protein kinase B (PI3K-AKT), triggered by these binding processes, induces the occurrence and development of various obesity-related diseases, including insulin resistance, cancer, metabolic-associated steatohepatitis (MASH) and cardiovascular diseases. This paper highlights the unique and crucial role of the interaction between ATMs and adipokines in the occurrence and progression of obesity-related diseases, emphasizing that this interaction is a key link connecting local adipose tissue inflammation to systemic metabolic disorders. It further summarizes the potential therapeutic strategies targeting the ATM-adipokine axis, and comprehensively illustrates three major clinical application barriers, namely biological complexity, technical bottlenecks, and clinical translation obstacles, in the process of applying these therapeutic strategies. For each barrier, this review puts forward corresponding feasible solutions and clear research directions, which not only enrich the theoretical system of the ATM-adipokine axis in the field of obesity research, but also provide a solid theoretical basis and practical ideas for the clinical intervention, prevention and treatment of obesity and its related diseases.

Objective:The purpose of this study was to analyze the epidemiological characteristics of hand, foot, and mouth disease (HFMD) among individuals aged 6 years and above in Guangzhou from 2010 to 2023, with the intention that a scientific basis be provided for effective prevention and control measures in older age groups.Methods:Data on HFMD incidence among individuals aged 6 years and above in Guangzhou from 2010 to 2023 were collected and analyzed. Descriptive epidemiological methods were used to analyze the distributions and pathogen components of HFMD cases in Guangzhou residents aged 6 years and above. Spatial autocorrelation analysis and Getis-Ord Gi* analysis were conducted to identify the spatial clustering patterns of HFMD at the street town level. Results:From 2010 to 2023, the gender ratio of HFMD cases in persons aged 6 and above was 1.49∶1 in Guangzhou. The average annual incidence rate of HFMD among individuals aged 6 years and above in Guangzhou was 25.75 per 100 000. Furthermore, the reported incidence rate indicated an increased tendency. The annual incidence showed a bimodal distribution, with the main peak occurring from May to July and the secondary peak from September to October. HFMD incidence rates vary by townships, with hotspots clustered in urban and urban-rural regions. The dominant pathogen shifts from year to year. Enterovirus 71 (EV71) was the prevalent strain in 2010, followed by other enteroviruses and Coxsackievirus (CV)-A16 from 2011 to 2016. Since 2017, CV-A6 has steadily become the major pathogen.Conclusions:The incidence of HFMD cases among individuals aged 6 years and above in Guangzhou increased generally from 2010 to 2023, with hotspots localized in urban and urban-rural areas. The pathogen composition altered dramatically, with the proportion of EV71 dropping overall, while CV-A6 eventually became the dominating strain. Therefore, it is imperative to focus on the prevention and control of HFMD in this age group, especially by strengthening measures in areas with high prevalence.

Objective To explore the mediating role of mindful attention and awareness in depressive symptoms and insomnia severity among patients with comorbid depression and insomnia.Methods A cross-sectional study was conducted,enrolling 267 patients with comorbid depression and insomnia who were treated in the outpatient Department of Medical Psychology of Second Affiliated Hospital of Army Medical University,from March to May 2024.Basic demographic and clinical data were collected using a general information questionnaire.Depressive symptom severity was measured via the Patient Health Questionnaire-9(PHQ-9),insomnia severity via the Insomnia Severity Index(ISI),perceived stress via the Perceived Stress Scale-10(PSS-10),and mindful attention and awareness via the Mindful Attention Awareness Scale(MAAS).Pearson correlation analysis was used to examine the correlations between depressive severity,insomnia severity,perceived stress,and mindful attention and awareness.Mediation analysis was performed using Process 4.1.Results The PHQ-9 score was(13.80±5.98)and the ISI score was(17.10±5.56)in the 267 patients.Pearson correlation analysis showed that depressive severity and insomnia severity were positively correlated with perceived stress(r=0.531,0.351,P<0.001)and negatively correlated with mindful attention and awareness(r=-0.373,-0.350,P<0.001).Mediation analysis using Process 4.1 indicated that the combined mediating effect of mindful attention and awareness and insomnia between perceived stress level and depressive level was 0.157,with a 95%confidence interval(CI)of 0.102～0.217,and the total mediating effect was significant(P<0.001).Conclusion Perceived stress directly positively affects depression and indirectly exacerbates depression through insomnia as a mediator,and mindful attention and awareness can weaken the promoting effect of perceived stress on insomnia.

Fe/Mn/Gd polymetallic nanooxide(FMGN)were prepared by one-step solvent thermal reaction by using Fe(acac)3,Mn(acac)2 and Gd(acac)3 as reaction precursors.Next,hyaluronic acid(HA)was used to modify FMGN to fabricate tumor-targeting T 1-T 2 dual-mode magnetic resonance imaging(MRI)contrast agent(HA-FMGN)for accurate diagnosis of prostate cancer.The structure and morphology of FMGN were observed by transmission electron microscope(TEM).It was found that FMGN exhibited a uniform nanocluster spherical structure when the feeding ratio of iron acetylacetonate,manganese acetylacetonate,and gadolinium acetylacetonate was 3:2:1.X-ray diffraction(XRD)analysis showed that FMGN had a typical inverse spinel structure of Mn doped Fe 3O 4,with Gd existing in the form of amorphous gadolinium oxide.The longitudinal relaxivity(r 1)and transverse relaxivity(r 2)of FMGN were 13.395 and 428.535 L/(mmol·s),respectively,measured by 0.5 T MRI analyzer,which proved that FMGN had excellent T 1-T 2 dual-mode MRI contrast capability.The cytotoxicity and hemolysis test found that HA-FMGN didn't damage red cells and induce toxicity for normal cells,indicating that HA-FMGN had excellent cell biocompatibility.The internalization efficacy of HA-FMGN was observed by CLSM,and the results showed that HA-FMGN possessed excellent prostate tumor-targeting ability.In vivo MRI experiment showed that HA-FMGN significantly enhanced T 1 and T 2 weighted MRI signal to noise ratio(SNR)of prostate tumor,which promoted the accurate diagnosis of orthotopic prostate cancer.

BACKGROUND:More and more animal experiments and clinical studies have confirmed that electrical stimulation can promote the repair of peripheral nerve injury,but the specific mechanism is not yet fully understood. OBJECTIVE:To investigate the effect of electrical stimulation-induced miR-741-3p regulating Radil on Schwann cell migration. METHODS:(1)Twelve male SD rats were randomly divided into electrical stimulation group and control group.The electrical stimulation group received continuous electrical stimulation for 7 days after sciatic nerve compression injury,while the control group was not treated after sciatic nerve compression.The injured nerves were taken on day 7 after operation.The expression difference of miR-741-3p between the two groups was verified by fluorescence in situ hybridization.(2)The target genes of miR-741-3p were predicted by miRDB,TargetScan,and miRWalk databases.(3)Schwann cells were transfected with miR-741-3p mimetic and its control,miR-741-3p inhibitor and its control,Radil siRNA and its control,miR-741-3p inhibitor+Radil siRNA and miR-741-3p inhibitor+siRNA control.The transfection efficiency was detected by RT-PCR.The migration ability of Schwann cells was detected by Transwell chamber. RESULTS AND CONCLUSION:(1)The fluorescence intensity of miR-741-3p in the electrical stimulation group was lower than that in the control group.(2)The results of database prediction showed that 69 genes might be the target genes of miR-741-3p.Radil was one of the predicted target genes,which was mainly involved in cell adhesion and migration.(3)Compared with the miR-741-3p inhibitor control group,the number of Schwann cell migration increased in the miR-741-3p inhibitor group(P<0.05).Compared with the miR-741-3p mimic control group,the number of Schwann cell migration in the miR-741-3p mimic group decreased(P<0.05).Compared with the siRNA control group,the number of Schwann cell migration was decreased in the Radil siRNA group(P<0.05).(4)Compared with miR-741-3p inhibitor control group,the expression level of Radil was increased in miR-741-3p inhibitor group.Compared with miR-741-3p mimic control group,the expression level of Radil was decreased in miR-741-3p mimic group.(5)Compared with miR-741-3p inhibitor+siRNA control group,the number of Schwann cell migration was reduced in miR-741-3p inhibitor+Radil siRNA group(P<0.05).The results showed that electrical stimulation promoted the migration of Schwann cells by down-regulating miR-741-3p and targeting Radil gene.

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. This article presents the evidence and interpretation of the blood transfusion provisions for children with hematological diseases in the "Guideline for pediatric transfusion", aiming to assist in the understanding and implementing the blood transfusion section of this guideline.
Humans ; Child ; Hematologic Diseases/therapy* ; Blood Transfusion/standards* ; Practice Guidelines as Topic