ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

ObjectiveThe frequency difference limen (FDL) serves as a fundamental metric utilized for effectively quantifying the precise perceptual capabilities of the central auditory system. However, traditional measurement methods rely heavily on the active behavioral responses of subjects and are consequently highly susceptible to the negative influence of confounding subjective factors. Furthermore, existing research paradigms frequently employ uniform stimulus configurations that overlook critical individual perceptual differences. Based on brain-computer interface (BCI) technology, this comprehensive study aims to establish an objective and quantitative evaluation method for auditory frequency discrimination by systematically analyzing and decoding the specific neural responses elicited at the exact threshold state. MethodsWe designed a personalized rapid serial auditory presentation (RSAP) paradigm customized based on each individual’s precise FDL. A cohort of eleven healthy participants was recruited to evaluate the paradigm using pure-tone sequences at a baseline frequency of 4 000 Hz. This experimental paradigm simulates a realistic auditory perception environment through the continuous presentation of acoustic stimuli, thereby allowing for an in-depth investigation into the specific neural representations evoked by weak frequency deviations at the threshold state. Given that auditory stimulus-evoked response features exhibit complex and differentiated spatiotemporal distribution patterns across multiple frequency domains, this study further deeply integrates the cross-scale feature interaction module with the dynamic spatiotemporal attention allocation strategy, innovatively proposing the Multi-Scale Spatial-Temporal Dual Attention Network (MS-STAMNet). Specifically, the network constructs parallel processing branches with multiple receptive fields and introduces a dynamic adaptive weighting strategy to precisely localize core neural activity signals, further deeply integrating multi-scale information through cross-branch feature information interaction to achieve robust single-trial decoding of weak auditory evoked responses. ResultsThe comprehensive electrophysiological data analysis demonstrated that subtle auditory frequency deviation stimuli presented at the threshold level successfully elicited pronounced N2 and P3 event-related potential features, reflecting pre-attentive mismatch detection and subsequent cognitive evaluation, which were prominently distributed over the frontal, central, and temporal regions of the scalp. In the complex time-frequency domain, the extracted neural response characteristics exhibited distinct, statistically significant event-related synchronization within both the low-frequency δ and θ frequency bands, which was simultaneously accompanied by a widespread, prominent event-related desynchronization within the higher α band. A comparative analysis of model performance demonstrated that MS-STAMNet achieved an average unweighted average recall (UAR) of (69.67±6.12)% and area under the curve (AUC) of 0.761 8±0.07, significantly outperforming the established baseline models such as EEGNet and PLNet. Furthermore, a distinct dissociation phenomenon was verified between neural decoding and behavioral performance through regression analysis (R²=0.016, P=0.709), indicating that this model can effectively capture the implicit features of subtle frequency deviations, even when they fail to trigger explicit conscious responses. Additionally, attention weight visualization analysis further reveals the highly accurate focus of the network on key features concentrated over the bilateral temporal and fronto-parietal regions. ConclusionThis study systematically and comprehensively uncovers the multi-dimensional spatiotemporal evolutionary patterns of complex neural responses processing subtle acoustic variations under long-sequence threshold auditory stimulation. Concurrently, it verifies the efficacy and robustness of the proposed MS-STAMNet architecture in accurately deciphering weak, single-trial electroencephalogram signals amidst complex background noise. Ultimately, these neurophysiological and algorithmic findings lay a solid theoretical and methodological foundation for the objective and quantitative evaluation of individual auditory cognitive capabilities in clinical applications, transcending the fundamental limitations of traditional behavioral paradigms and providing robust technical support for future auditory research and related clinical assessments.

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Enzymatic cascade catalysis has emerged as an effective means to enhance the sensitivity of biosensors due to its remarkable amplification effect on electrochemical signals.However,the most used natural enzymes have high specificity and high catalytic activity,but are susceptible to environmental factors,easy denaturation and inactivation,and high cost,which limit their practical applications.Additionally,the majority of nanozymes with excellent catalytic activity cannot be directly used as redox probes.The redox signal can only be required under high potentials in strong acid/alkali solutions,or functionalized with electroactive substances.To tackle this problem,herein,AuNPs(glucose oxidase-like activity)and Mn,Zr dual-doped CeO2 nanozymes(Mn,Zr-CeO2,peroxidase-like activity)were used as model enzymes to construct a high-performance nanozymes cascade catalytic system.Owing to high Ce4+/Ce3+ratio and a considerable number of oxygen vacancies,Mn,Zr-CeO2 nanozymes exhibited excellent peroxidase-like activity and could generate amplified electrochemical signals in neutral medium at low potentials.Furthermore,the porous structure of Mn,Zr-CeO2 nanozymes could accelerate the mass transfer of intermediate H2O2,thereby enhancing the efficiency of enzymatic cascade catalysis.As a result,a label-free electrochemical biosensor was constructed for sensitive detection of the cancer marker miRNA-21 at physiological pH,with a detection limit as low as 32.5 fmol/L.This strategy offered a novel approach for the development of a new generation of high-performance nanozymes cascade platforms,which could be widely applied in the fields such as biotechnology,bioanalysis,and disease diagnosis.

Sustained inflammatory responses are closely related to various severe diseases,and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment.Natural products have garnered considerable concern for the treatment of inflammation.Huanglian-Wumei decoction(HLWMD)is a classic prescription used for treating inflammatory diseases,but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated.Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory,we successfully obtained berberine(BBR)-chlorogenic acid(CGA)supramolecular(BCS),which is an herbal pair from HLWMD.Using a series of characterization methods,we confirmed the self-assembly mechanism of BCS.BBR and CGA were self-assembled and stacked into amphiphilic spherical supra-molecules in a 2:1 molar ratio,driven by electrostatic interactions,hydrophobic interactions,and π-πstacking;the hydrophilic fragments of CGA were outside,and the hydrophobic fragments of BBR were inside.This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules.Compared with free molecules,BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide(LPS)-induced pyroptosis.Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB(NF-κB)p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Objective To explore the association between nocturnal blood pressure decline rate and chronic heart failure(CHF).Methods In this study,a total of 711 individuals who underwent 24-h ambulatory blood pressure monitoring were divided into control group(n=433)and CHF group(n=278).The characteristics of the study population and nocturnal blood pressure decline rate were compared between CHF group and control group.Restricted spline analysis was utilized to examine the linear or non-linear association between nocturnal blood pressure decline rate and the prevalence of CHF.The relationship between nocturnal blood pressure decline rate and CHF was further investigated based on multivariable Logistic regression model.Results Nocturnal systolic blood pressure decline rate was significantly different in CHF group and control group[(3.3±7.1)mmHg vs.(5.0+6.7)mmHg,P=0.001].No significant difference in nocturnal diastolic blood pressure was found between the two groups[(5.7±7.6)mmHg vs.(6.8±7.2)mmHg,P=0.061].Restricted spline analysis showed a significant linear association between nocturnal systolic blood pressure decline rate and CHF risk.After adjusting for age,sex,smoking,body mass index,24-hour systolic blood pressure,24-hour diastolic blood pressure,type 2 diabetes mellitus and hyperlipidemia,multivariate Logistic regression analysis revealed that nocturnal systolic blood pressure decline rate was negatively associated with the prevalence of CHF(OR=0.97,95％CI:0.95-0.99;P=0.010).However,no significant association was found between nocturnal diastolic blood pressure decline rate and CHF risk.Conclusion Nocturnal systolic blood pressure decline rate is associated with the prevalence of CHF.Individuals with decreased nocturnal systolic blood pressure decline have a significantly increased risk of CHF.

Objective To explore the association between nocturnal blood pressure decline rate and chronic heart failure(CHF).Methods In this study,a total of 711 individuals who underwent 24-h ambulatory blood pressure monitoring were divided into control group(n=433)and CHF group(n=278).The characteristics of the study population and nocturnal blood pressure decline rate were compared between CHF group and control group.Restricted spline analysis was utilized to examine the linear or non-linear association between nocturnal blood pressure decline rate and the prevalence of CHF.The relationship between nocturnal blood pressure decline rate and CHF was further investigated based on multivariable Logistic regression model.Results Nocturnal systolic blood pressure decline rate was significantly different in CHF group and control group[(3.3±7.1)mmHg vs.(5.0+6.7)mmHg,P=0.001].No significant difference in nocturnal diastolic blood pressure was found between the two groups[(5.7±7.6)mmHg vs.(6.8±7.2)mmHg,P=0.061].Restricted spline analysis showed a significant linear association between nocturnal systolic blood pressure decline rate and CHF risk.After adjusting for age,sex,smoking,body mass index,24-hour systolic blood pressure,24-hour diastolic blood pressure,type 2 diabetes mellitus and hyperlipidemia,multivariate Logistic regression analysis revealed that nocturnal systolic blood pressure decline rate was negatively associated with the prevalence of CHF(OR=0.97,95％CI:0.95-0.99;P=0.010).However,no significant association was found between nocturnal diastolic blood pressure decline rate and CHF risk.Conclusion Nocturnal systolic blood pressure decline rate is associated with the prevalence of CHF.Individuals with decreased nocturnal systolic blood pressure decline have a significantly increased risk of CHF.

Objective To evaluate the efficacy,safety,and economy of 4 intravenous iron formulations in the treatment of iron deficiency anemia(IDA)by rapid health technology assessment,and to provide evidence for clinical decision-making.Methods PubMed,Embase,the Cochrane Library,CNKI,WanFang,SinoMed,and official websites of international health technology assessment agencies were electronically searched to collect health technology assessment reports,systematic reviews/Meta-analysis,and pharmacoeconomic studies concerning the treatment of IDA with iron sucrose(IS),iron dextran(ID),ferric carboxymaltose(FCM),and iron isomaltoside(IIM)from the inception to August 15,2024.Two researchers independently screened the studies,extracted data and assessed the quality of included studies.The results were then qualitatively described and analyzed.Results A total of 32 studies were included,including one health technology assessment report,16 systematic reviews/Meta-analysis,and 15 pharmacoeconomic evaluations.In terms of effectiveness,FCM had a higher response rate than that of IS(P＜0.05),FCM and IIM had no statistical difference(P＞0.05).Regarding hemoglobin level change,patients treated with FCM had higher hemoglobin levels than those treated with IS(P＜0.05);the improvement in hemoglobin levels between IIM and FCM was inconclusive.In terms of ferritin level change,FCM might be superior to the other three intravenous iron formulations.In terms of safety,the adverse event rates for FCM,IS,ID and IIM were 12.0％,15.3％,12.0％and 17.0％,respectively;IIM was significantly associated with a lower rate of cardiovascular adverse events compared to FCM and IS(P＜0.05);FCM had the highest rate of hypophosphatemia among the four formulations(P＜0.05),and there was no significant difference among IIM,IS and ID(P＞0.05);IIM had a lower risk of severe or serious hypersensitivity reactions compared to FCM and IS.In terms of economy,FCM and IIM had an economic advantage compared to IS.The economic efficiency ranking among IS,ID,and FCM was in the order of FCM,ID,and IS,the economic comparison between FCM and IIM remains inconclusive and needs to be further demonstrated.Conclusion FCM and IIM have good efficacy,safety and economy in the treatment of IDA,but most of the included economy studies based on foreign populations,and domestic economic studies need to be further demonstrated.

AIM To investigate the clinical effects of Compound Shengdi Mixture on patients with mild to moderate systemic lupus erythematosus.METHODS One hundred and twenty patients were randomly assigned into control group (60 cases) for 12-week intervention of basic treatment,and observation group (60 cases) for 12-week intervention of both Compound Shengdi Mixture and basic treatment.The changes in clinical effects,SLEDAI score,TCM syndrome score,prednisone dose,laboratory indices (WBC,HGB,PLT,anti-ds-DNA,ANA titer,ESR,IL-6,TNF-α,C3,C4,IgG),24 h PRO and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group (P<0.05).After the treatment,the two groups displayed decreased SLEDAI score,TCM syndrome score,prednisone dose,IL-6,TNF-α(P<0.05,P<0.01),especially for the observation group (P<0.05,P<0.01);the observation group displayed decreased anti-ds-DNA,ANA titer,24 h PRO (P<0.05,P<0.01),along with increased HGB (P<0.01).No significant differences in WBC,PLT,ESR,C4,C3,IgG and incidence of adverse reactions were found between the two groups (P>0.05).CONCLUSION For the patients with mild to moderate systemic lupus erythematosus,Compound Shengdi Mixture can safely and effectively inhibit immunological inflammatory responses,improve clinical symptoms and alleviate disease activity.

ObjectiveTePixD (Tll0078) is a blue light-using flavin (BLUF) photoreceptor protein from Thermosynechococcus elongatus BP-1. TePixD protein has a conserved Tyr8-Gln50-Met93 triad around the FAD pocket to mediate the proton-coupled electron transfer (PCET) process. But the detailed light response mechanism needs further study. We aimed to elucidate the structure and biochemical properties of TePixD mutants at key light response sites to analyze the light response process of TePixD. MethodsWe employed X-ray crystallography to resolve the crystal structure of the TePixD Y8F mutant. The side chain of Tyr8 is involved in PCET while Phe8 in mutation loses the function due to the loss of its hydroxyl group. We compared the structure of TePixD Y8F mutation to TePixD wild type (WT) and its homology protein SyPixD Y8F. Using multi-angle light scattering (MALS), we analyzed the oligomerization of multiple TePixD mutations (Y8F, Q50L, W91F, Y8F/W91F, and Q50L/W91F), focusing specifically on mutational sites that are critical residues for the protein’s photo response to dark and light conditions. ResultsWe resolved the crystal structure of TePixD Y8F mutant at a resolution of 2.54 Å and found that it shares a similar overall structure with the TePixD WT but exhibits significant differences from the SyPixD Y8F structure. Biochemical analysis revealed differences in molecular mass and elution profiles between the TePixD mutants and the WT under dark and light conditions, indicating the perturbation on the light-induced conformational change by the mutants. ConclusionOur structure determination and biochemical analyses will add information to reveal the light response mechanism of BLUF proteins.