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.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective To compare the pain relief and long-term clinical success rate of vital pulp therapy and root canal treatment in mature permanent teeth with carious irreversible pulpitis.Methods A total of 90 patients diagnosed with carious irreversible pulpitis in mature permanent teeth were collected at Shanghai Stomatological Hospital from Jan 2021 to Jun 2022.They were randomly divided into two groups:test group(n=45)undergoing vital pulp therapy(VPT)and control group(n=45)undergoing root canal treatment(RCT).Pain scores were recorded before treatment,24 hours after operation and 7 days after operation.We conducted clinical evaluation and imaging analysis at 1,6,and 12 months after the surgery,then compared the pain scores and treatment success rates between the two groups.Results Eighty-one patients,including 39 patients in group VPT aged(31.00±1.43)years old and 42 patients in group RCT aged(30.60±1.54)years old,received follow-up for more than 1 year,and the success rate of the test group and control was 97.44%and 95.24%.The pain degree of the two groups was reduced at 24 hours and 7 days after operation(P<0.05),and the pain score of the test group was reduced compared with that in the control group 7 days after operation(P<0.01).Conclusion Compared with root canal treatment,vital pulp therapy for mature permanent teeth with carious irreversible pulpitis can achieve good results in short-term pain evolution and long-term clinical success.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective To compare the pain relief and long-term clinical success rate of vital pulp therapy and root canal treatment in mature permanent teeth with carious irreversible pulpitis.Methods A total of 90 patients diagnosed with carious irreversible pulpitis in mature permanent teeth were collected at Shanghai Stomatological Hospital from Jan 2021 to Jun 2022.They were randomly divided into two groups:test group(n=45)undergoing vital pulp therapy(VPT)and control group(n=45)undergoing root canal treatment(RCT).Pain scores were recorded before treatment,24 hours after operation and 7 days after operation.We conducted clinical evaluation and imaging analysis at 1,6,and 12 months after the surgery,then compared the pain scores and treatment success rates between the two groups.Results Eighty-one patients,including 39 patients in group VPT aged(31.00±1.43)years old and 42 patients in group RCT aged(30.60±1.54)years old,received follow-up for more than 1 year,and the success rate of the test group and control was 97.44%and 95.24%.The pain degree of the two groups was reduced at 24 hours and 7 days after operation(P<0.05),and the pain score of the test group was reduced compared with that in the control group 7 days after operation(P<0.01).Conclusion Compared with root canal treatment,vital pulp therapy for mature permanent teeth with carious irreversible pulpitis can achieve good results in short-term pain evolution and long-term clinical success.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

Objective To investigate the effect of Eriodictyol(ERI)on the development of metabolic dysfunction-associated steatotic liver disease by regulating the expression of ubiquitin A 52(UBA52)at both in vivo and in vitro levels.Methods A mouse metabolic dysfunction-associated steatotic liver disease model was established using a high-fat diet induction.The mice were randomly separated into the normal control group(normal group),the model group,the low-dose ERI group(ERI-L group,50 mg/kg ERI)and the high-dose ERI group(ERI-H group,100 mg/kg ERI),with 12 mice in each group.Oil red O staining was applied to observe lipid deposition in mouse liver tissue.HE staining was applied to observe pathological changes in mouse liver tissue.ELISA method was applied to detect serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC)and triglycerides(TG)in mice.The expression of UBA52 protein in liver was detected by Western blot assay.HepG2 cells were treated with 0.5 mmol/L oleic acid to induce an in vitro metabolic dysfunction-associated steatotic liver disease model.HepG2 cells were randomly divide into the control group,the oleic acid induced group,the low concentration ERI group(ERI low group,50 μmol/L ERI),the high concentration ERI group(ERI high group,100 μmol/L ERI),the high concentration ERI+si-NC group(ERI high+si-NC group,100 μmol/L ERI+transfected with si-NC)and the high concentration ERI+si-UBA52 group(ERI high+si-UBA52 group,100 μmol/L ERI+transfected with si-UBA52).Oil red O staining was applied to detect lipid deposition in HepG2 cells of each group.ELISA method was applied to detect the levels of TG,TC,SOD and MDA in HepG2 cells in each group.Immunoblotting was used to detect the expression levels of UBA52,p62 and autophagy related proteins in HepG2 cells.Results Compared with the normal group,serum levels of ALT,AST,LDL-C,TC,TG and the expression of UBA52 protein in liver tissue were increased in the model group(P＜0.05),and the lipid deposition in liver increased,pathological damage was severe,and the proportion of lipid deposition area and non-alcoholic fatty liver disease(NAFLD)activity score were also increased(P＜0.05).Changes in the corresponding indicators in the ERI-L group and the ERI-H group were opposite to those of the model group(P＜0.05),and the ERI-H group was even lower(P＜0.05).The lipid deposition in liver decreased and the pathological damage was alleviated.Compared with the control group,the levels of TG,TC,MDA,the proportion of lipid droplet area and the expression of UBA52 protein were increased in HepG2 cells of the oleic acid-induced group,while the levels of SOD,p62 and LC3Ⅱ/LC3Ⅰ decreased(P＜0.05).Changes in the corresponding indicators of the low-concentration ERI group and the high-concentration ERI group were opposite to those of the oleic acid-induced group(P＜0.05),and the therapeutic effect of ERI on metabolic dysfuntion-associated steatotic liver disease was enhanced after knocking down the expression of UBA52.Conclusion ERI may slow down the progression of metabolic dysfuntion-associated steatotic liver disease by down-regulating the expression of UBA52 at both in vivo and in vitro levels.

Objective To investigate the effect of Eriodictyol(ERI)on the development of metabolic dysfunction-associated steatotic liver disease by regulating the expression of ubiquitin A 52(UBA52)at both in vivo and in vitro levels.Methods A mouse metabolic dysfunction-associated steatotic liver disease model was established using a high-fat diet induction.The mice were randomly separated into the normal control group(normal group),the model group,the low-dose ERI group(ERI-L group,50 mg/kg ERI)and the high-dose ERI group(ERI-H group,100 mg/kg ERI),with 12 mice in each group.Oil red O staining was applied to observe lipid deposition in mouse liver tissue.HE staining was applied to observe pathological changes in mouse liver tissue.ELISA method was applied to detect serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC)and triglycerides(TG)in mice.The expression of UBA52 protein in liver was detected by Western blot assay.HepG2 cells were treated with 0.5 mmol/L oleic acid to induce an in vitro metabolic dysfunction-associated steatotic liver disease model.HepG2 cells were randomly divide into the control group,the oleic acid induced group,the low concentration ERI group(ERI low group,50 μmol/L ERI),the high concentration ERI group(ERI high group,100 μmol/L ERI),the high concentration ERI+si-NC group(ERI high+si-NC group,100 μmol/L ERI+transfected with si-NC)and the high concentration ERI+si-UBA52 group(ERI high+si-UBA52 group,100 μmol/L ERI+transfected with si-UBA52).Oil red O staining was applied to detect lipid deposition in HepG2 cells of each group.ELISA method was applied to detect the levels of TG,TC,SOD and MDA in HepG2 cells in each group.Immunoblotting was used to detect the expression levels of UBA52,p62 and autophagy related proteins in HepG2 cells.Results Compared with the normal group,serum levels of ALT,AST,LDL-C,TC,TG and the expression of UBA52 protein in liver tissue were increased in the model group(P＜0.05),and the lipid deposition in liver increased,pathological damage was severe,and the proportion of lipid deposition area and non-alcoholic fatty liver disease(NAFLD)activity score were also increased(P＜0.05).Changes in the corresponding indicators in the ERI-L group and the ERI-H group were opposite to those of the model group(P＜0.05),and the ERI-H group was even lower(P＜0.05).The lipid deposition in liver decreased and the pathological damage was alleviated.Compared with the control group,the levels of TG,TC,MDA,the proportion of lipid droplet area and the expression of UBA52 protein were increased in HepG2 cells of the oleic acid-induced group,while the levels of SOD,p62 and LC3Ⅱ/LC3Ⅰ decreased(P＜0.05).Changes in the corresponding indicators of the low-concentration ERI group and the high-concentration ERI group were opposite to those of the oleic acid-induced group(P＜0.05),and the therapeutic effect of ERI on metabolic dysfuntion-associated steatotic liver disease was enhanced after knocking down the expression of UBA52.Conclusion ERI may slow down the progression of metabolic dysfuntion-associated steatotic liver disease by down-regulating the expression of UBA52 at both in vivo and in vitro levels.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.