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.

ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

OBJECTIVE To systematically review the key regulatory requirements for pharmacy compounding drug products in the United States， and to provide references for improving the management framework of pharmacy compounding drug products in China， thereby ensuring the safety and accessibility of medication use. METHODS A literature revi ew was conducted to summarize the regulatory requirements and practical characteristics of pharmacy compounding drug products under Section 503A of the United States Federal Food， Drug， and Cosmetic Act . Based on regulatory experience of the United States， current status and existing deficiencies in pharmacy compounding drug products in China were analyzed， and targeted recommendations were proposed. RESULTS &CONCLUSIONS The United States has established a systematic regulatory framework for pharmacy compounding drug products under Section 503A， covering prescription management， active pharmaceutical ingredient management， list management of withdrawn or removed drugs and drugs that present demonstrable difficulties for compounding， recordkeeping management， interstate distribution and so on. Through standardized regulation of the entire compounding process and collaborative governance with expert advisory committees， this framework effectively balances individualized medication needs with drug quality and safety. In contrast， pharmacy compounding drug products in China remain largely confined to traditional Chinese medicine and face several challenges， including the lack of legal and regulatory support， inadequate quality control， lagging development of industry standards， and shortages of specialized personnel. It is recommended that China should establish a tiered regulatory system， develop comprehensive technical standards， build a localized regulatory framework， promote technological innovation， and strengthen professional talent cultivation to better balance the legitimate rights and interests of public medication use with drug safety and efficacy， thereby enhancing public health.

Objective To investigate the correlation between serum levels of microRNA(miR)-489-3p and miR-214-3p in patients with Psoriasis and the severity of disease.Methods From March 2022 to January 2024,138 Psoriasis patients who visited Zhangjiakou First Hospital were regarded as the study subjects(disease group).According to the psoriasis area and severity index(PASI)score,the 138 Psoriasis patients were separated into mild group(n=46),moderate group(n=54)and severe group(n=38).112 healthy individuals who underwent physical examinations in Zhangjiakou First Hospital during the same period were included in the control group.Real-time fluorescence quantitative PCR(RT-qPCR)method was applied to determine the serum levels of miR-489-3p and miR-214-3p in the subjects.The serum levels of miR-489-3p and miR-214-3p were compared between the disease group and the control group,and among patients with different degrees of disease.Spearman correlation analysis was applied to explore the relationship between serum miR-489-3p,miR-214-3p levels and disease severity in Psoriasis patients.Logistic regression analysis was performed to analyze the related factors affecting the severity of Psoriasis.Receiver operating characteristic(ROC)curve was applied to investigate the diagnostic value of serum miR-489-3p and miR-214-3p levels for severe Psoriasis.Results The serum levels of miR-489-3p(0.81±0.23)and miR-214-3p(0.79±0.22)in the disease group were lower than those in the control group(1.05±0.28,1.02±0.25),and the differences were statistically significant(t=7.441,7.732,all P<0.05).Serum miR-489-3p in mild,moderate and severe Psoriasis groups(0.93±0.24,0.80±0.23,0.69±0.22),miR-214-3p levels(0.91±0.24,0.77±0.22,0.66±0.21)decreased gradually,and the differences were statistically significant(F=12.423,13.168,all P<0.05).Spearman's results showed that serum levels of miR-489-3p and miR-214-3p were negatively correlated with the severity of Psoriasis in patients(r=-0.490,-0.463,all P<0.05).Serum miR-489-3p and miR-214-3p were independent protective factors for the severity of Psoriasis patients(Wald χ2=5.751,8.753,all P<0.05).ROC curve results showed that the area under the curve(AUC)of serum miR-489-3p and miR-214-3p for diagnosing severe Psoriasis alone was 0.785 and 0.792,with sensitivity of 78.9%and 73.7%,specificity of 49.9%and 54.7%,respectively.The AUC of the combined diagnosis for severe Psoriasis was 0.931,the sensitivity and specificity were 71.7%,71.1%,respectively,and the combined diagnostic efficacy of the two was better than that of miR-489-3p and miR-214-3p alone,and the differences were statistically significant(Z=3.018,2.773,all P<0.05).Conclusion The serum levels of miR-489-3p and miR-214-3p in patients with Psoriasis are both reduced,and both are negatively correlated with the severity of the disease in Psoriasis patients.The combined determination of the two has high efficacy in the diagnosis of severe Psoriasis.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

O-glycosylation(including mucin-type O-glycosylation and O-GlcNAcylation),as a critical post-translational modification(PTM),regulates protein function,stability,and subcellular localization through the addition of glycan chains to serine or threonine residues,which participates in cellular signa-ling,metabolic regulation,and stress responses.DNA damage refers to the disruption of genomic integri-ty caused by endogenous factors(e.g.,metabolic byproducts,replication errors)or exogenous agents(e.g.,radiation,chemical substances),leading to carcinogenesis,aging,and genetic disorders.To counteract DNA lesions,organisms have evolved the DNA damage response(DDR)system,which or-chestrates complex protein networks to detect DNA damage and facilitate repair processes.Emerging evi-dence indicates that O-glycosylation can modulate DDR by influencing the activity,localization,and in-teractions of DNA repair-associated proteins.However,the precise mechanisms underlying O-glycosyla-tion-mediated DDR remain to be clarified.This review systematically summarizes:(1)the biosynthetic pathways of mucin-type O-glycosylation and O-GlcNAcylation,the cascade reactions in DDR;and(2)current research advances regarding O-glycosylation in tumor-associated DDR.Furthermore,we propose novel mechanistic perspectives and therapeutic strategies targeting O-glycosylation-mediated DDR dysreg-ulation in malignancies,aiming to provide a theoretical basis for tumor treatment.

Broncholithiasis complicated with actinomycosis is a rare clinical disease.This paper reports a patient presenting cough and shortness of breath as the major symptoms.The diagnosis of broncholithiasis complicated with pulmonary actinomycosis was confirmed by chest CT,fiberoptic bronchoscopy,and biopsy of the lesion.The bron-choliths in the anterior segment of the right upper lobe were removed by repeated lavage,cryotherapy as well as the use of electrocautery snare and forceps under general anesthesia intubation bronchoscopy.After combined with anti-infection treatment,the patient's cough and shortness of breath improved significantly.Combined with reviewing the literature,this paper explores the pathophysiological mechanism,clinical manifestations,diagnosis and treat-ment of broncholithiasis complicated with actinomycosis,aiming to enhance the understanding and treatment of this disease.

Objective:To analyze the epidemiological, etiological characteristics and transmission of an imported D8 genotype measles case in a child in Shandong Province, August 2023.Methods:A study was conducted on a measles case and 16 contacts in Shandong Province in August 2023. Field epidemiological surveys, including recent exposure and immunization history, were conducted. Serum and throat swab samples were collected from all 16 subjects. Measles IgM and IgG antibody levels and avidity were measured by ELISA, while virus detection and genotyping were performed using fluorescence quantitative PCR and RT-PCR. Genetic evolutionary analysis of the obtained sequences was conducted using MEGA and Beast software.Results:The case was an 11-year-old boy, a fifth-grade student, who developed symptoms on August 28, 2023. A total of five close contacts were investigated, including three family members (grandfather, father and sister) and two playmates. Additionally, 11 classmates who had close contact with the case′s sister during the infectious period (within five days after the rash onset) were also investigated. Among the 16 serum samples tested, only one case was positive for IgM, while the other 15 samples were negative for IgM. The results of the serum antibody avidity test showed that among the 16 serum samples, 14 were positive for IgG. Of these, eight had a relative avidity index >55%, indicating high-avidity antibodies; one had a relative avidity index <45%, indicating low-avidity antibodies; and five had an avidity index between 45% and 55%. The IgG detection OD values for the case′s sister and grandfather were higher than those of the other contacts. Based on the vaccination history of the subjects and the results of IgM and IgG tests, it was preliminarily determined that the case had a recent wild-type measles virus infection. The case′s sister and grandfather had a history of measles wild-type virus infection, while the high-avidity antibodies in the other contacts were likely induced by the measles vaccine. The results of the pharyngeal swab tests showed that only the case was positive for measles virus nucleic acid, while the remaining 15 samples were negative for measles virus. The genetic evolutionary analysis revealed that the viral sequence of this case (Mvs/Shandong.CHN/38.23) had a 100% homology with the Hong Kong strain sequence from August 2023. It belonged to a different transmission chain from the D8 genotype strains that appeared in Shandong Province between 2018 and 2019, with sequence homology ranging from 98.0% to 98.8%. The sequence homology within the transmission chain of this case was between 99.1% and 100%. The evolutionary rate of this transmission chain was approximately 8.38×10 -3 sub/site/year, and the most recent common ancestor was estimated to have emerged around the year 2011. Conclusion:This case is the first imported D8 genotype measles case in Shandong Province. There is no spatio-temporal correlation between this case and adult cases of D8 genotype imported from Shandong Province in 2018-2019, indicating a new D8 genotype imported epidemic.

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.