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Abstract Numerous studies have reported that long-term sports training can affect inhibitory control and induce brain functional alterations. However, the influence of environmental dynamics in sports training on inter-cortical connectivity has not been well studied. In the current study, we used twin-coil transcranial magnetic stimulation to investigate the functional connectivity between dorsolateral prefrontal cortex (DLPFC) and ipsilateral primary motor cortex (M1) during proactive and reactive inhibition in participants with sports skills in dynamic environment (open-skill experts), stable environment (closed-skill experts), and no sports skills (controls). Using a modified stop signal task, proactive inhibition was measured by the response delay effect (RDE), and reactive inhibition was measured by the stop-signal reaction time (SSRT). Intra-hemispheric DLPFC-M1 interactions and single pulse motor-evoked potentials (MEPs) were measured during the task. A stronger inhibitory effect of the DLPFC over M1 was observed during early reactive control stages compared to baseline levels. In addition, this inhibitory effect was pronounced when comparing open-skill experts to non-athlete controls, a relationship that was significantly correlated with superior reactive control performance. Furthermore, DLPFC to M1 influencing direction shifted from late proactive control to reactive control. Behavioral results also demonstrated enhanced proactive control abilities in open-skill experts relative to controls. Such enhancement may be due to the combination of environmental complexity and physical fitness in long-term skill training.

Abstract With the rapid development of white LEDs, the research of new and efficient white light emitting materials has attracted increasing attention. Zero dimensional (0D) organic–inorganic hybrid metal halide perovskites with superior luminescent property are promising candidates for LED application, due to their abundant and tailorable structure. Herein, [(CH3)3S]2SnCl6·H2O is synthesized as a host for dopant ions Bi3+ and Sb3+. The Sb3+ doped, or Bi3+/Sb3+ co-doped, [(CH3)3S]2SnCl6·H2O has a tunable optical emission spectrum by means of varying dopant ratio and excitation wavelength. As a result, we can achieve single-phase materials suitable for emission ranging from cold white light to warm white light. The intrinsic mechanism is examined in this work, to clarify the dopant effect on the optical properties. The high stability of title crystalline material, against water, oxygen and heat, makes it promising for further application. Graphical Abstract

Type 2 diabetes mellitus (T2DM) as a chronic metabolic disease has become a global public health problem. Insulin resistance (IR) is the main pathogenesis of T2DM. Oxidative stress refers to an imbalance between free radical production and the antioxidant system, causing insulin resistance and contributing to the development of T2DM via several molecular mechanisms. Besides, the reduction in hepatic glycogen synthesis also leads to a decrease in peripheral insulin sensitivity. Thus, reducing oxidative stress and promoting glycogen synthesis are both targets for improving insulin resistance and treating T2DM. The current study aims to investigate the pharmacological effects of single-atom Ce-N-C nanozyme (SACe-N-C) on the improvement of insulin resistance and to elucidate its underlying mechanisms using HFD/STZ-induced C57BL/6J mice and insulin-resistant HepG2 cells. The results indicate that SACe-N-C significantly improves hepatic glycogen synthesis and reduces oxidative stress, as well as pancreatic and liver injury. Specifically, compared to the T2DM model group, fasting blood glucose decreased by 29%, hepatic glycogen synthesis increased by 17.13%, and insulin secretion increased by 18.87%. The sod and GPx in the liver increased by 17.80% and 25.28%, respectively. In terms of mechanism, SACe-N-C modulated glycogen synthesis through the PI3K/AKT/GSK3β signaling pathway and activated the Keap1/Nrf2 pathway to alleviate oxidative stress. Collectively, this study suggests that SACe-N-C has the potential to treat T2DM.

Information about estuarine mixing and its control of sediment transport is crucial to elucidating the dynamics and evolution of estuaries. Here, the microtidal and funnel-shaped Zhenhai Estuary, located in the southwestern Pearl River Delta of China, is used to investigate the characteristics and mechanisms of water mixing and sediment transport based on observations from three spring tides. The results reveal that the studied estuary remains well mixed during spring tides from 2013–2022 despite its microtidal regime. Tidal stirring, which is enhanced by tidal energy convergence and benefits from the funnel-shaped geometry and shallow bathymetry, favors vertical mixing, contributing to the formation of strong mixing in the estuary. Due to the well-mixed regime, sediment transport in the estuary is dominated by the advective term, followed by a moderate tidal pumping term and minor estuarine circulation term. Accordingly, sediments within the estuary tend to be transported landward owing to the regulation of the funnel-shaped geometry, and a gradual but slow infilling trend is predictable. This paper deepens our understanding of hydrodynamics and sediment transport in microtidal estuaries.

High-intensity anthropogenic activities have greatly altered the estuarine-shelf depositional processes of sediments, and the intensity and frequency of the impacts of human interventions have far exceeded the natural development of estuarine systems. Since the reform and opening up, human activities such as dams, sand mining, channel dredging, and reclamation have already caused anomalous changes in the dynamical–sedimentary–geomorphological processes of the Lingdingyang Estuary (LE). Analyzing the impact of high-intensity anthropogenic activities on sedimentary processes and the hydrodynamic environment through sedimentary records can provide a scientific basis for predicting the evolution of the estuary and the sustainable development of the Guangdong–Hongkong–Macao Greater Bay Area. The aims of this study are to reveal the impact of varying intensity human activities across different periods on depositional pattern and conduct a preliminary investigation into the spatial differences in sedimentary characteristic attributed to human activities. Two cores (LD11 and LD13) located in the LE were selected for continuous scanning of high-resolution XRF, grain size, and 210Pbex dating tests, and scrutinized with the previous studies of the historical process of human activities in the LE. The results show the following: (1) The abrupt alterations in 210Pbex, geochemical indices, and grain size in LD13 happened in close proximity to the 95 cm layer, suggesting a shift in the sedimentary environment during 1994. (2) In the context of the continuous reduction in water and sediment flux into the LE after 1994, the large-scale and high-intensity human activities like sand mining, channel dredging, and reclamation are responsible for the sedimentation rate increase rather than decrease, the coarsening of sediment fractions, the frequent fluctuations in Zr/Rb, Zr/Al, Sr/Fe, and Sr/Al ratios, and the increase in anomalous extremes. (3) Sedimentary records found in locations varying in anthropogenic intensities differ greatly. Compared with the nearshore siltation area, the grain size composition in the channel area is noticeably coarser and exhibits a wider range of grain size variations. The 210Pbex is strongly perturbed and the vertical distribution is disturbed; the phenomenon of multiple inversions from the surface downwards is shown, making it impossible to carry out sedimentation rate and dating analysis, and the geochemical indicators have changed drastically without any obvious pattern. The evidence of the human activities can be retrieved in the sedimentary record of the estuary and provide a different angle to examine the impacts of the human activities.

Diabetic cardiomyopathy (DCM) is a serious complication and death cause of diabetes mellitus (DM). Recent cardiology studies suggest that spermidine (SPD) has cardioprotective effects. Here, we verified the hypothesis of SPD’s protective effects on DCM. Therefore, db/db mice and primary neonatal mouse cardiomyocytes were used to observe the effects of SPD. Immunoblotting showed that ornithine decarboxylase (ODC) and SPD/spermine N1-acetyltransferase (SSAT) were downregulated and upregulated in the myocardium of db/db mice, respectively. We found that diabetic mice showed cardiac dysfunction in 12 weeks. Conversely, exogenous SPD could improve cardiac functions and reduce the deposition of collagens, myocardial damage, reactive oxygen species (ROS) levels, and endoplasmic reticulum stress (ERS) in diabetic mouse hearts. Our results also demonstrated that cardiomyocytes displayed ferroptosis and then activated Pannexin-1 expression, which resulted in the increase of the extracellular adenosine triphosphate (ATP). Subsequently, increased ATP as a paracrine molecule combined to purinergic receptor P2X7 to activate ERK1/2 signaling pathway in cardiomyocytes and activated NCOA4-mediated ferroptinophagy to promote lipid peroxidation and ferroptosis. Interestingly, SPD could reverse these molecular processes. Our findings indicate an important new mechanism for DCM and suggest that SPD has potential applicability to protect against deterioration of cardiac function with DCM.

Sediment dynamics under floods are critical for estuarine morphological evolution. A two-dimensional coupled hydrodynamic/sediment transport numerical modeling was adapted to investigate the flood-driven jet structure and the resultant sedimentary regime in a river-dominated estuary, Modaomen Estuary, Pearl River Delta, China. The results show that the flow velocity of flood jet exhibits a Gaussian distribution in the transverse direction and shows a linear decreasing trend in the longitudinal direction. Moreover, a distinct zonation, including a zone of flow establishment (ZOFE) and a zone of established flow (ZOEF), was detected. The ZOFE was the core area of high turbidity and strong erosion and provided sufficient sediments to the ZOEF, where sediment diffused and settled. Due to the settling lag, the sediment diffusion and deposition areas were larger than those of the jet. Estuarine geomorphology regulates the shape of flood jet, which shows an asymmetry configuration with the main body located at the west side of the bifurcated estuary. Tidal dynamics play a crucial role in altering the range of jet diffusion, especially in the longitudinal direction. Increased flood intensity has little effect on the jet structure and erosion/deposition pattern, but significantly increases the magnitude of seaward current velocities and bed level changes, as well as the transverse diffusion range of jet and sedimentation.

The enzyme-mimicking catalytic activity of single-atom nanozymes has been widely used in tumor treatment. However, research on alleviating metabolic diseases, such as hyperglycemia, has not been reported. Herein, we found that the single-atom Ce-N4-C-(OH)2 (SACe-N4-C-(OH)2) nanozyme promoted glucose absorption in lysosomes, resulting in increased reactive oxygen species production in HepG2 cells. Furthermore, the SACe-N4-C-(OH)2 nanozyme initiated a cascade reaction involving superoxide dismutase-, oxidase-, catalase-, and peroxidase-like activity to overcome the limitations associated with the substrate and produce •OH, thus improving glucose intolerance and insulin resistance by increasing the phosphorylation of protein kinase B and glycogen synthase kinase 3β, and the expression of glycogen synthase, promoting glycogen synthesis to improve glucose intolerance and insulin resistance in high-fat diet-induced hyperglycemic mice. Altogether, these results demonstrated that the novel nanozyme SACe-N4-C-(OH)2 alleviated the effects of hyperglycemia without evident toxicity, demonstrating its excellent clinical application potential.

Diabetic cardiomyopathy (DCM) is one of the most serious complications of diabetes. Recent cardiology studies suggest that spermine has a cardioprotective effect. Here, we used proteomic and metabolomic analyses to reveal the underlying research targets in a type II diabetic (T2D) mouse model treated with spermine. Left ventricular tissues from nine mice (Control group, three; T2D group, three; T2D+SP group, three) were excised and analyzed. Quantitative analysis of the global proteome and metabolome was performed using the 4D label-free technique and untargeted metabolomics, respectively, and differentially expressed proteins (DEPs) and metabolites were used to perform bioinformatic analyses. A total of 169 DEPs were identified in T2D/Control group, including 115 upregulated and 54 downregulated proteins. Furthermore, 16 DEPs were identified in T2D+SP/T2D group, where these DEPs were found highly enriched in the cellular, metabolic processes, biological regulation, response to stimulus, and immune system process. The results of association analysis between proteomics and metabolomics showed that SP could affect the production of 51 metabolites by regulating the expression of 16 DEPs in the T2D+SP/T2D group. We also found that PRKG1 was closely related to the expressions of 10 overlapping metabolites between db/db and SP-treated mice. Our findings provide insights into the underlying mechanisms for DCM and suggest the potential applicability of utilizing spermine on protecting against DCM-associated cardiac function deterioration.

To clarify the precipitation forecast skills of climate forecast operations in the flood season in Liaoning Province of China, this study examines the forecast accuracies of China’s national and provincial operational climate prediction products and the self-developed objective prediction methods and climate model products by Shenyang Regional Climate Center (SRCC) in the flood season in Liaoning. Furthermore, the forecast accuracies of the main influencing factors on the precipitation in the flood season of Liaoning are assessed. The results show that the SRCC objective methods have a relatively high accuracy. The European Centre for Medium-Range Weather Forecasts (ECMWF) sub-seasonal forecast initialized at the sub-nearest time has the best performance in June. The National Climate Center (NCC) Climate System Model sub-seasonal forecast initialized at the sub-nearest time, and the ECMWF seasonal and sub-seasonal forecasts initialized at the nearest time, perform the best in July. The NCC sub-seasonal forecast initialized at the sub-nearest time has the best performance in August. For the accuracy of the SRCC objective method, the more significant the equatorial Middle East Pacific sea surface temperature (SST) anomaly is, the higher the evaluation score of the dynamic–analogue correction method is. The more significant the North Atlantic SST tripole is, the higher the score of the hybrid downscaling method is. For the forecast accuracy of the main influencing factors of precipitation, the tropical Atlantic SST and the north–south anti-phase SST in the northwest Pacific can well predict the locations of the southern vortex and the northern vortex in early summer, respectively. The warm (clod) SST in China offshore has a good forecast performance on the weak (strong) southerly wind in midsummer in Northeast China. The accuracy of using the SST in the Nino 1+2 areas to predict the north–south location of the western Pacific subtropical high is better than that of using Kuroshio SST. The accuracy of predicting northward-moving typhoons from July to September by using the SST in the west-wind-drift area is better than using the SST in the Nino 3 area. The above conclusions are of great significance for improving the short-term climate prediction in Liaoning.

In this study, the northward-moving tropical cyclones (TCs) that influence Northeast China (NEC) in July–September are identified based on the distance between the TC center and the boundaries of NEC. Then, based on a machine learning algorithm named hierarchical agglomerative clustering, the tracks of northward-moving TCs that influence NEC are classified into the eastern-track type and the turning type. In NEC, the precipitation induced by eastern-track type TCs gradually decreases from east to west, and the precipitation induced by turning-type TCs gradually decreases from south to north. For eastern-track type TCs, negative Niño3 sea surface temperature (SST) anomalies in preceding January–March can induce cyclonic circulation anomalies and positive vorticity anomalies over the Philippine Sea during subsequent July–September, which favors the genesis of TCs. Moreover, the westerly anomaly in the subtropical western north Pacific and the strengthening of cyclonic steering flow over the Philippines jointly steer the TCs to move northward along the northerly airflow on the west of the western Pacific subtropical high, which favors the genesis of eastern-track type TCs. For turning-type TCs, the positive SST anomalies in the West Wind Drift area during preceding May–July cause positive vorticity anomalies from the northern Philippines to Taiwan from July to September. The cyclonic steering flow over the Philippines and the anticyclonic steering flow over the Sea of Japan lead the TCs to move northwestwards and then turn to northeast, which is conducive to the genesis of turning type northward-moving TCs. Finally, the results of numerical experiments have confirmed these findings.

The Chinese medicinal herb Scutellaria barbata D. Don has antitumour effects and is used to treat liver cancer in the clinic. S. barbata polysaccharide (SBP), one of the main active components extracted from S. barbata D. Don, exhibits antitumour activity. However, there is still a lack of research on the extraction optimization, structural characterization, and anti-hepatoma activity of acidic polysaccharides from S. barbata D. Don. In this study, the optimal extraction conditions for SBP were determined by response surface methodology (RSM): the material-liquid ratio was 1:25, the extraction time was 2 h, and the extraction temperature was 90°C. Under these conditions, the average extraction efficiency was 3.85 ± 0.13%. Two water-soluble polysaccharides were isolated from S. barbata D. Don, namely, SBP-1A and SBP-2A, these homogeneous acidic polysaccharide components with average molecular weights of 1.15 × 105 Da and 1.4 × 105 Da, respectively, were obtained at high purity. The results showed that the monosaccharide constituents of the two components were fucose, galactosamine hydrochloride, rhamnose, arabinose, glucosamine hydrochloride, galactose, glucose, xylose, and mannose; the molar ratio of these constituents in SBP-1A was 0.6:0.3:0.6:30.6:3.3:38.4:16.1:8:1.4, and that in SBP-2A was 0.6:0.5:0.8:36.3:4.4:42.7:9.2:3.6:0.7. In addition, SBP-1A and SBP-2A contained uronic acid and β-glucan, and the residue on the polysaccharide was mainly pyranose. The in vitro results showed that the anti-hepatoma activity of SBP-2A was better than that of SBP-1A and SBP. In addition, SBP-2A significantly enhanced HepG2 cell death, as cell viability was decreased, and SBP-2A induced HepG2 cell apoptosis and blocked the G1 phase. This phenomenon was coupled with the upregulated expression of P53 and Bax/Bcl-2 ratio, as well as the downregulated expression of the cell cycle-regulating protein cyclinD1, CDK4, and Bcl-2 in this study. Further analysis showed that 50 mg/kg SBP-2A inhibited the tumour growth in H22 tumour-bearing mice, with an average inhibition rate of 40.33%. Taken together, SBP-2A, isolated and purified from S. barbata showed good antitumour activity in vivo and in vitro, and SBP-2A may be a candidate drug for further evaluation in cancer prevention. This study provides insight for further research on the molecular mechanism of the anti-hepatoma activity of S. barbata polysaccharide.

Abstract Background HER2-positive breast cancer is usually associated to the more aggressive progression and the worse prognosis, but the mechanism underlying the innate resistance to HER2-targeted therapy remains elusive. The scaffold protein SH3-domain-binding glutamic acid-rich protein-like protein (SH3BGRL) is indicated as a tumor suppressor in some cancers, but it is highly expressed in breast cancers. Here we characterized the tumorigenic function of SH3BGRL in HER2-expressing breast cancer cells and the subsequent effect in HER2-targeted therapies. Methods The interaction of SH3BGRL to HER2 were characterized with various truncated SH3BGRL mutants by immunoprecipitation and molecule docking simulation. The physiological roles of SH3BGRL interacting with HER2 in tumor progression and therapy implication were characterized by gain and loss of function approaches in vitro and in vivo. Immunohistochemistry was used for detections of SH3BGRL and p-HER2 (Y1196) expressions in xenografted tumors and human breast cancer tissues. Clinical relevance of SH3BGRL expression with HER2 was validated with both breast patient sample and the public data analyses. Results Our results demonstrated that SH3BGRL directly binds with HER2 on cell membrane via its motifs α1, α2 helixes and β3 sheet, which postpones HER2 internalization upon EGF stimulation. Consequently, the association between SH3BGRL and HER2 contributed to the prolonged HER2 phosphorylation at specific tyrosine sites, especially at Y1196, and their downstream signaling activation. The relevance between SH3BGRL expression and p-HER2 (Y1196) phosphorylation was validated in both xenografted tumors and the breast cancer patient tissues. Mechanistically, SH3BGRL promoted breast tumor cell proliferation and survival, while reduced the cell sensitivity to anti-tumor drugs, especially to the HER2-targeted drugs. In contrast, Silencing SH3BGRL or inhibiting its downstream signals efficiently induced apoptosis of breast tumor cells with HER2 and SH3BGRL doubly positive expression. Database analysis also highlighted that SH3BGRL is a poor prognostic marker, especially for HER2-positive breast cancers. Conclusions Our results disclose SH3BGRL as a novel posttranslational modulator of HER2 hyperactivation, which can lead to the intrinsic resistance to HER2-targeted therapy. SH3BGRL would be a pivotal therapy target and a diagnostic marker to HER2-positve patients. Thus, targeting SH3BGRL or the downstream signaling could relieve the innate resistance to some HER2-tageted therapies for both HER2 and SH3BGRL-postive breast cancers.

The environmental conditions affect the external insulation performance of power equipment. In order to study the physical characteristics of air discharge, the microscopic process of electron–molecule collision in the air based on the Boltzmann equation has been studied in this paper. The influence of humidity on the air gap insulation performance was also analyzed. The calculation results show that with the temperature 300 K and the pressure 1.0 atm, the electron energy distribution function and electron transport parameters varied with the air relative humidity. As the air relative humidity is increased by each 30%, the average electron energy decreases by about 0.2 eV, the reduced electron mobility decreases by about 0.25 × 1023 [1/(V·m·s)], the reduced electron diffusion coefficient decreases by about 0.2 × 1024 [1/(m s)], and the effective ionization coefficient decreases by about 4 × 10−24 m2. As the air relative humidity increases from 0% to 60%, the critical breakdown electric field increases by 1.22 kV/cm.

In the early summer (June) of 2022, the spatial mean precipitation in northeast China (NEC) was 62% higher than normal and broke the historical record since 1951. Based on the precipitation data of 245 meteorological stations in NEC and the National Centers for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) reanalysis, this paper analyzes the role of large-scale circulation and sea-surface temperature (SST) associated with anomalous precipitation over NEC in June using singular value decomposition (SVD), correlation analysis, regression analysis, and composite analysis methods, and further investigates the possible cause of the abnormal precipitation in June 2022. Results show that the northeast China cold vortex (NCCV) accompanying the blocking high in the Okhotsk Sea (BHOS) has been the primary mid-to-high latitude atmospheric circulation pattern affecting NEC precipitation in June since 2001. This circulation pattern is closely related to the tripole SST pattern over the North Atlantic (NAT) in March. In June 2022, the NAT SST anomaly in March stimulates eastward-propagating wave energy, resulting in the downstream anomalous circulation pattern in which the NCCV cooperates with the BHOS in the mid-high latitudes of East Asia. Under this background atmospheric circulation favorable for precipitation, the Kuroshio region SST anomaly in June led to a more northward and stronger anomalous anticyclone in the northwestern Pacific through local air–sea interaction, which provides more sufficient water vapor for NEC, resulting in unprecedented precipitation in June 2022.

Background: The dorsolateral prefrontal cortex (DLPFC) in both hemispheres have a central integrative function for motor control and behavior. Understanding the hemispheric difference between DLPFC and ipsilateral motor cortex connection in the resting-state will provide fundamental knowledge to explain the different roles DLPFC plays in motor behavior.Purpose: The current study tested the interactions between the ipsilateral DLPFC and the primary motor cortex (M1) in each hemisphere at rest. We hypothesized that left DLPFC has a greater inhibitory effect on the ipsilateral M1 compared to the right DLPFC.Methods: Fourteen right-handed subjects were tested in a dual-coil paired-pulse paradigm using transcranial magnetic stimulation. The conditioning stimulus (CS) was applied to the DLPFC and the test stimulus (TS) was applied to M1. Interstimulus intervals (ISIs) between CS and TS were 2, 4, 6, 8, 10, 15, 20, 25, and 30 ms. The result was expressed as a percentage of the mean peak-to-peak amplitude of the unconditioned test pulse.Results: There was stronger inhibitory effect for the left compared to the right hemisphere at ISIs of 2 (p = 0.045), 10 (p = 0.006), 15 (p = 0.029) and 20 (p = 0.024) ms. There was no significant inhibition or facilitation at any ISI in the right hemisphere.Conclusions: The two hemispheres have distinct DLPFC and M1 cortico-cortical connectivity at rest. Left hemisphere DLPFC is dominant in inhibiting ipsilateral M1.

Abstract The role of alcohol consumption as a mediator in the risk between sarcopenia and dementia remains inadequately studied. There is currently limited research on whether the association between sarcopenia and the risk of Alzheimer’s disease (AD) is influenced by genetic susceptibility. Our study incorporated a total of 483,637 baseline non-dementia participants, who were classified into groups of individuals with no sarcopenia and those with probable sarcopenia based on the definition. We employed Cox proportional hazards models to evaluate the association between probable sarcopenia and the risk of all cause dementia (ACD), AD, and vascular dementia (VD). We conducted mediation analysis to explore the role of alcohol consumption in the association between probable sarcopenia and the risk of ACD, AD, and VD. During the median follow-up period of 13.6 years, we documented 9000 new cases of ACD (including 4061 AD and 2025 VD). Fully adjusted multivariate model revealed a significant correlation between probable sarcopenia and elevated risk for ACD (HR = 1.54, 95% CI: 1.46–1.62, p

Abstract Background Core biomarkers for Alzheimer’s disease (AD), such as Aβ42 and tau, have demonstrated high prognostic accuracy but do not fully capture the complex pathophysiology of AD. In this study, our objective was to identify novel cerebrospinal fluid (CSF) biomarkers using proteomics across the entire AD continuum to predict conversion to AD and explore their involvement in AD pathogenesis. Methods A cohort of 186 cognitively normal (CN), 127 subjective memory complaint (SMC), 79 early mild cognitive impairment (EMCI), 249 late MCI (LMCI), and 132 AD individuals was analyzed, with a follow-up period of over 3 years for non-AD participants. CSF 65 peptides, as well as hippocampal and entorhinal volumes were analyzed, and cognitive function was evaluated using the 13-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog 13). Cox proportional hazards models and mediation analysis were performed to investigate associations and causal relationships. Results During the follow-up, approximately one-fourth (146/580) of the non-AD participants progressed to AD. After adjusting for baseline diagnosis (CN to LMCI) and other variables, multivariable Cox regression analysis identified three peptides (VAELEDEK, VSFELFADK, and VVSSIEQK) as significant predictors of conversion to AD. Incorporating these three peptides into the initial model significantly improved the C-statistic from 0.82 to 0.85 for predicting AD conversion, surpassing the predictive ability of Aβ42 and P-tau. Moreover, hippocampal and entorhinal volumes mediated 30.3–53.8% of the association between the three peptides and ADAS-Cog 13 scores. Conclusions These findings underscore the potential of these three peptides as robust prognostic biomarker candidates for AD conversion across the entire AD continuum, with a mechanism involving the mediation of hippocampal and entorhinal volumes.