Bio-inspired Cu2O cathode for O2 capturing and oxidation boosting in electro-Fenton for sulfathiazole decay.

A hydrophobic Cu2O cathode (CuxO-L) was designed to solve the challenge of low oxidation ability in electro-Fenton (EF) for treating emerging pollutants. This fabrication process involved forming Cu(OH)2 nanorods by oxidizing copper foam (Cu-F) with (NH4)2S2O8, followed by coating them with glucose via hydrothermal treatment. Finally, a self-assembled monolayer of 1-octadecanethiol was introduced to create a low-surface-energy, functionalized CuxO-L cathode. Results exhibited an approximately 7.9-fold increase in hydroxyl radical (·OH) generation compared to the initial Cu-F. This enhancement was attributed to two key factors: (Ⅰ) the superior O2-capturing ability of CuxO-L cathode, which led to high H2O2 production due to a 2 nm thick hydrophobic gas layer facilitated O2-capturing; (Ⅱ) a relative high concentration of Cu+ at the CuxO-L cathode promoted the activation of H2O2 into·OH. In addition, the performance of EF with the CuxO-L cathode using sulfathiazole (STZ) as a model pollutant was evaluated. This study offers valuable insights into the design of O2-capturing cathodes in EF processes, particularly for treating emerging organic pollutants.

Differential distribution of fibrovascular proliferative membranes in 25-gauge vitrectomy for proliferative diabetic retinopathy.

AIM: To analyze the distribution of fibrovascular proliferative membranes (FVPMs) in proliferative diabetic retinopathy (PDR) patients that treated with pars plana vitrectomy (PPV), and to evaluate the outcomes separately. METHODS: This was a retrospective and cross-sectional study. Consecutive 25-gauge (25-G) PPV cases operated for PDR from May 2018 to April 2020. According to the FVPMs images outlined after operations, subjects were assigned into three groups: arcade type group, juxtapapillary type group, and central type group. All patients were followed up for over one year. General characteristics, operation-related variables, postoperative parameters and complications were recorded. RESULTS: Among 103 eyes recruited, the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different (both P<0.01), with 95 (92.23%) FVPMs located in the nasal quadrants, and 74 (71.84%) in the inferior. The eyes with a central FVPM required the longest operation time, with silicon oil used in most patients, generally combined with tractional retinal detachment (RD) and rhegmatogenous RD, the worst postoperative best-corrected visual acuity (BCVA) and the highest rates of recurrent RD (all P<0.05). FVPM type, age of onset diabetes mellitus, preoperative BCVA, and combined with tractional RD and rhegmatogenous RD were significantly associated with BCVA improvement (all P<0.05). Compared with the central type group, the arcade type group had higher rates of BCVA improvement. CONCLUSION: FVPMs are more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade vessels. Performing 25-G PPV for treating PDR eyes with central FVPM have relatively worse prognosis.

Characterization of chemical constituents and metabolites in rat plasma after oral administration of Ainsliaea fragrans Champ by using UHPLC-QTOF-MS/MS.

Ainsliaea fragrans Champ, a strong heat-clearing and detoxifying traditional Chinese medicine, has been effectively used for treating chronic cervicitis, endometritis, pelvic inflammatory diseases, and other conditions caused by damp heat. It shows a good effect in the treatment of cervicitis and has broad clinical application prospects. Nevertheless, there is no comprehensive study on its in vivo and in vitro chemical analysis. UHPLC-QTOF-MS/MS combined with the non-targeted characteristic filter analysis were used to conjecture and characterize the chemical components and in vivo metabolites of rats following oral administration of Ainsliaea fragrans Champ. In this study, A total of 85 compounds were identified in Ainsliaea fragrans Champ, including 29 flavonoids, 14 sesquiterpenoids, 25 chlorogenic acids, and 17 other compounds. In the plasma of rats after administration of Ainsliaea fragrans Champ, 160 compounds were deduced (19 prototype compounds and 141 metabolites). The 141 metabolites consist of 50 flavonoids, 80 phenolic acids and 11 Chlorogenic acids. The related metabolic pathways mainly involved demethylation, reduction, sulfonation, decarboxylation, hydroxylation, methylation, and glucuronide conjunction. In summary, the chemical components and metabolites of Ainsliaea fragrans Champ were comprehensively identified by using a rapid and accurate analysis method, which laid a foundation for dissecting its bioactive substances. In addition, it provides a scientific basis for the in-depth study of the material basis of Ainsliaea fragrans Champ efficacy and theoretical support for illustrating the mechanism of medical action and its clinical application.

Ischemic stroke or transient ischemic attack due to cervical and intracranial large-vessel vasculitis secondary to primary Sjögren's syndrome: A case series and literature review.

Introduction: Primary Sjögren's syndrome (PSS) is a systemic autoimmune disease that mainly affects exocrine glands. Little is known about PSS associated cervical and intracranial cerebral large-vessel vasculitis outside of individual case reports. Methods: We present 5 cases of ischemic stroke or transient ischemic stroke (TIA) caused by PSS associated cervical and intracranial large-vessel vasculitis. Literature review was performed to summarize and identify the demographic, clinical features, treatment, and prognosis of this condition. Results: The review resulted in 8 included articles with 8 patients, plus our 5 new patients, leading to a total of 13 subjects included in the analysis. The median age was 43 (range, 17-69) years old, among which 69.2 % (9/13) were female, and 92.3 % (12/13) came from Asia. Among them, 84.6 % (11/13) presented with cerebral infarction and 70.0 % (7/10) with watershed infarction. Middle cerebral artery (MCA) (6/13, 46.2 %) and internal carotid artery (ICA) (6/13, 46.2 %) were the most frequently involved arteries. Remarkable vessel wall concentric thickening and enhancement was observed in 57.1 % (4/7) patients and intravascular thrombi was identified in 28.6 % (2/7) patients. Glucocorticoid combined with non-glucocorticoid immunosuppressants (8/12, 66.7 %) were the most often chosen medication therapy and 4 patients received surgical intervention. Conclusion: Asian females are the most vulnerable population to ischemic stroke or TIA due to PSS associated cervical and intracranial large-vessel vasculitis. Cerebral infarctions were characterized by recurrence and watershed pattern. Magnetic resonance vessel wall imaging (MR-VWI) helps to identify the inflammatory pathology of large vessel lesion in PSS.

CT perfusion for predicting intracranial atherosclerotic middle cerebral artery occlusion.

Backgrounds and purpose: Identifying the underlying cause of acute middle cerebral artery occlusion (MCAO) as intracranial atherosclerotic stenosis (ICAS) or embolism is essential for determining the optimal treatment strategy before endovascular thrombectomy. We aimed to evaluate whether baseline computed tomography perfusion (CTP) characteristics could differentiate ICAS-related MCAO from embolic MCAO. Methods: We conducted a retrospective analysis of the clinical and baseline CTP data from patients who underwent endovascular thrombectomy for acute MCAO between January 2018 and December 2022. Core volume growth rate was defined as core volume on CTP divided by onset to CTP time. Multivariate logistic analysis was utilized to identify independent predictors for ICAS-related acute MCAO, and the diagnostic performance of these predictors was evaluated using receiver operating characteristic curve analysis. Results: Among the 97 patients included (median age, 71 years; 60% male), 31 (32%) were diagnosed with ICAS-related MCAO, and 66 (68%) had embolism-related MCAO. The ICAS group was younger (p = 0.002), had a higher proportion of males (p = 0.04) and smokers (p = 0.001), a lower prevalence of atrial fibrillation (AF) (p < 0.001), lower NIHSS score at admission (p = 0.04), smaller core volume (p < 0.001), slower core volume growth rate (p < 0.001), and more frequent core located deep in the brain (p < 0.001) compared to the embolism group. Multivariate logistic analysis identified core volume growth rate (aOR 0.46, 95% CI 0.26-0.83, p = 0.01) as an independent predictor of ICAS-related MCAO. A cutoff value of 2.5 mL/h for core volume growth rate in predicting ICAS-related MCAO was determined from the receiver operating characteristic curve analysis, with a sensitivity of 81%, specificity of 80%, positive predictive value of 66%, and negative predictive value of 90%. Conclusion: Slow core volume growth rate identified on baseline CTP can predict ICAS-related MCAO. Further prospective studies are warranted to confirm and validate these findings.

Electrochemical oxidative selective halogenation of pyrazolones for the synthesis of 4-halopyrazolones.

An efficient and environmentally friendly electrochemical oxidative selective halogenation of pyrazolones has been developed under conditions free of metals, external oxidants, and external supporting electrolytes. The reaction demonstrates good functional group tolerance and maintains high efficiency in large-scale synthesis, yielding moderate to excellent yields of the desired 4-halopyrazolones. This method provides a green and convenient route for the direct installation of a halogen moiety into bioactive pyrazolone derivatives, which can be utilized in a myriad of applications.

GWAS-based polygenic risk scoring for predicting cerebral artery dissection in the Chinese population.

OBJECTIVE: Cerebral artery dissection (CeAD) is a rare but serious disease. Genetic risk assessment for CeAD is lacking in Chinese population. We performed genome-wide association study (GWAS) and computed polygenic risk score (PRS) to explore genetic susceptibility factors and prediction model of CeAD based on patients in Huashan Hospital. METHODS: A total of 210 CeAD patients and 280 controls were enrolled from June 2017 to September 2022 in Department of Neurology, Huashan Hospital, Fudan University. We performed GWAS to identify genetic variants associated with CeAD in 140 CeAD patients and 210 control individuals according to a case and control 1:1.5 design rule in the training dataset, while the other 70 patients with CeAD and 70 controls were used as validation. Then Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were utilized to identify the significant pathways. We constructed a PRS by capturing all independent GWAS SNPs in the analysis and explored the predictivity of PRS, age, and sex for CeAD. RESULTS: Through GWAS analysis of the 140 cases and 210 controls in the training dataset, we identified 13 leading SNPs associated with CeAD at a genome-wide significance level of P < 5 × 10- 8. Among them, 10 SNPs were annotated in or near (in the upstream and downstream regions of ± 500Kb) 10 functional genes. rs34508376 (OR2L13) played a suggestive role in CeAD pathophysiology which was in line with previous observations in aortic aneurysms. The other nine genes were first-time associations in CeAD cases. GO enrichment analyses showed that these 10 genes have known roles in 20 important GO terms clustered into two groups: (1) cellular biological processes (BP); (2) molecular function (MF). We used genome-wide association data to compute PRS including 32 independent SNPs and constructed predictive model for CeAD by using age, sex and PRS as predictors both in training and validation test. The area under curve (AUC) of PRS predictive model for CeAD reached 99% and 95% in the training test and validation test respectively, which were significantly larger than the age and sex models of 83% and 86%. CONCLUSIONS: Our study showed that ten risk loci were associated with CeAD susceptibility, and annotated functional genes had roles in 20 important GO terms clustered into biological process and molecular function. The PRS derived from risk variants was associated with CeAD incidence after adjusting for age and sex both in training test and validation.

Anemoside B4 attenuates abdominal aortic aneurysm by limiting smooth muscle cell transdifferentiation and its mediated inflammation.

Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by local abnormal dilation of the aorta accompanied by vascular smooth muscle cell (VSMC) dysfunction and chronic inflammation. VSMC dedifferentiation, transdifferentiation, and increased expression of matrix metalloproteinases (MMPs) are essential causes of AAA formation. Previous studies from us and others have shown that Anemoside B4 (AB4), a saponin from Pulsatilla chinensis, has anti-inflammatory, anti-tumor, and regulatory effects on VSMC dedifferentiation. The current study aimed to investigate whether AB4 inhibits AAA development and its underlying mechanisms. By using an Ang II induced AAA model in vivo and cholesterol loading mediated VSMC to macrophage transdifferentiation model in vitro, our study demonstrated that AB4 could attenuate AAA pathogenesis, prevent VSMC dedifferentiation and transdifferentiation to macrophage-like cells, decrease vascular inflammation, and suppress MMP expression and activity. Furthermore, KLF4 overexpression attenuated the effects of AB4 on VSMC to macrophage-like cell transition and VSMC inflammation in vitro. In conclusion, AB4 protects against AAA formation in mice by inhibiting KLF4 mediated VSMC transdifferentiation and inflammation. Our study provides the first proof of concept of using AB4 for AAA management.

Comprehensive identification strategy for rapid profiling of chemical constituents using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry with Rhubarb as an example.

In this study, the collision induced dissociation tandem mass spectrometry (CID-MS/MS) fragmentation pathway of chemical components in rhubarb was wholly explored using 34 standards by UHPLC-QTOF-MS/MS in negative ion mode. In consequently, the diagnostic product ions for speedy screening and categorization of chemical components in rhubarb were ascertained based on their MS/MS splitting decomposition patterns and intensity analysis. According to these findings, a fresh two-step data mining strategy had set up. The initial key step involves the use of characteristic product ions and neutral loss to screen for different types of substituents and basic skeletons of compounds. The subsequent key step is to screen and classify different types of compounds based on their characteristic product ions. This method can be utilized for rapid research, classification, and identification of compounds in rhubarb. A total of 356 compounds were rapidly identified or tentatively characterized in three rhubarb species extracts, including 150 acylglucoside, 125 anthraquinone, 65 flavanols and 15 other compounds. This study manifests that the analytical strategy is feasible for the analysis of complex natural products in rhubarb.

[Mechanism of Puerariae Thomsonii Radix in treatment of mild dyslipidemia: based on clinical metabolomics and proteomics].

This study aims to explore the potential metabolic pathways and targets of Puerariae Thomsonii Radix in the clinical treatment of mild dyslipidemia. UPLC-Q-TOF-MS and EASY-nLC-timsTOF-Pro2 were employed to perform metabolomic and proteomic analyses of the plasma samples collected from the patients with mild dyslipidemia at baseline and after 12 weeks of treatment with Puerariae Thomsonii Radix. The multivariate statistical analysis was carried out for comparison between groups, and the correlation analysis was performed for the metabolites and proteins closely related to mild dyslipidemia with the blood lipid indexes. The possible pathways and targets for mitigating mild dyslipidemia were screened out by the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. The results showed that 56 differential metabolites and 78 differential proteins in the plasma of patients were associated with Puerariae Thomsonii Radix treatment. In addition, changes were detected for the proteins or metabolites(ApoB-100, 9,10-DHOME, GAPDH, PGK1, PGAM1, ENO1, etc.) involved in lipoprotein, lipid, and glucose metabolism and the proteins or metabolites(oxidized phospholipid, PLA2G7, LTA4H, etc.) related to inflammation and oxidative stress. Puerariae Thomsonii Radix may down-regulate the overexpression of ApoB-100, activate the peroxisome proliferator-activated receptor α/γ(PPARα/γ), promote the catabolism of fat and glycerol, and alleviate the oxidative stress mediated by oxidized phospholipids and leukotriene B4(LTB4) in the treatment of mild dyslipidemia.

Oleuropein alleviates myocardial ischemia-reperfusion injury by suppressing oxidative stress and excessive autophagy via TLR4/MAPK signaling pathway.

BACKGROUND: Myocardial ischemia/reperfusion injury (MIRI) is an important complication of reperfusion therapy, and has a lack of effective prevention and treatment methods. Oleuropein (OP) is a natural strong antioxidant with many protective effects on cardiovascular diseases, but its protective effect on MIRI has not yet been studied in depth. METHODS: Tert-Butyl hydroperoxide (tBHP) was used to establish an in vitro oxidative stress model. Cell viability was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH). Flow cytometry and fluorescence assays were performed for evaluating the ROS levels and mitochondrial membrane potential (MMP). Immunofluorescence analysis detected the NRF2 nuclear translocation and autophagy indicators. Further, Western blotting and quantitative real-time PCR were performed to evaluate the expression levels of proteins and mRNAs. Molecular docking, CETSA, and molecular interaction analysis explored the binding between OP and TLR4. The protective effects of OP in vivo were determined using a preclinical MIRI rat model. RESULTS: OP protected against tBHP-treated injury, reduced ROS levels and reversed the damaged MMP. Mechanistically, OP activated NRF2-related antioxidant pathways, inhibited autophagy and attenuated the TLR4/MAPK signaling pathway in tBHP-treated H9C2 cells with a high binding affinity to TLR4 (KD = 37.5 µM). The TLR4 inhibitor TAK242 showed a similar effect as OP. In vivo, OP could alleviate cardiac ischemia/reperfusion injury and it ameliorated adverse cardiac remodeling. Consistent with in vitro studies, OP inhibited TLR4/MAPK and autophagy pathway and activated NRF2-dependent antioxidant pathways in vivo. CONCLUSION: This study shows that OP binds to TLR4 to regulate oxidative stress and autophagy for protecting damaged cardiomyocytes, supporting that OP can be a potential therapeutic agent for MIRI.

Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites.

Pulchinenoside B4, a natural saponin monomer from the Pulsatilla plant, plays an important role as an immunomodulator in the treatment of acute inflammation. Oral ulcer (OU) is a common ulcerative injury disease that occurs in the oral mucosa, including mucosal ulceration and abnormalities of lips and tongue. A close correlation exists between gut microbiota and circulating metabolites in patients with OU. However, the correlation between gut microbiota and serum metabolomics is not clear. Therefore, this study aimed to explore the changes in gut microbiota and metabolites in OU. The 16S ribosomal RNA (16S rRNA) gene sequencing was used to detect the changes in the composition of gut microbiota in OU rat model. Moreover, the endogenous small metabolites were explored by collecting the non-targeted serum metabolomics data. A total of 34 OU-related biomarkers were identified, mainly related to fatty acid metabolism and inflammatory pathways. The administration of B4 effectively reduced the occurrence of OU and restored the levels of multiple endogenous biomarkers and key gut microbial species to the normal level. This study demonstrated that the gut microbiota and metabolites were altered in the OU rat model, which were significantly restored to the normal level by B4, thereby showing good application prospects in the treatment of OU. KEY POINTS: • The first investigating the correlation between OU and gut microbiota. • A close correlation between metabolites and gut microbiota in OU disease was successfully identified. • Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites.

Discovery of a New Anti-Inflammatory Agent from Anemoside B4 Derivatives and Its Therapeutic Effect on Colitis by Targeting Pyruvate Carboxylase.

Anemoside B4 (AB4), a triterpenoidal saponin from Pulsatilla chinensis, shows significant anti-inflammatory activity, and may be used for treating inflammatory bowel disease (IBD). Nevertheless, its application is limited due to its high molecular weight and pronounced water solubility. To discover new effective agents for treating IBD, we synthesized 28 AB4 derivatives and evaluated their cytotoxic and anti-inflammatory activities in vitro. Among them, A3-6 exhibited significantly superior anti-inflammatory activity compared to AB4. It showed a significant improvement in the symptoms of DSS-induced colitis in mice, with a notably lower oral effective dose compared to AB4. Furthermore, we discovered that A3-6 bound with pyruvate carboxylase (PC), then inhibited PC activity, reprogramming macrophage function, and alleviated colitis. These findings indicate that A3-6 is a promising therapeutic candidate for colitis, and PC may be a potential new target for treating colitis.

Abnormal thermally-stimulated dynamic organic phosphorescence.

Dynamic luminescence behavior by external stimuli, such as light, thermal field, electricity, mechanical force, etc., endows the materials with great promise in optoelectronic applications. Upon thermal stimulus, the emission is inevitably quenched due to intensive non-radiative transition, especially for phosphorescence at high temperature. Herein, we report an abnormal thermally-stimulated phosphorescence behavior in a series of organic phosphors. As temperature changes from 198 to 343 K, the phosphorescence at around 479 nm gradually enhances for the model phosphor, of which the phosphorescent colors are tuned from yellow to cyan-blue. Furthermore, we demonstrate the potential applications of such dynamic emission for smart dyes and colorful afterglow displays. Our results would initiate the exploration of dynamic high-temperature phosphorescence for applications in smart optoelectronics. This finding not only contributes to an in-depth understanding of the thermally-stimulated phosphorescence, but also paves the way toward the development of smart materials for applications in optoelectronics.

Post-stroke Chinese pure alexia: linguistic features and neuropsychological profiles.

PURPOSE: Very few cases of Chinese pure alexia have been reported to date. We aim to summarize the linguistic features and neuropsychological profiles of Chinese pure alexia through a case series study. METHODS: 11 consecutive patients with post-stroke Chinese pure alexia and 11 healthy controls were included. The Aphasia Battery of Chinese (ABC) and 68-Chinese character oral reading test (68-character test) were used to evaluate the reading and writing ability. Reading errors were classified based on the performance of 68-character test. Neuropsychological profiles were evaluated with corresponding scales. The possible correlation between the reading ability and the writing ability or neuropsychological performance was analyzed. RESULTS: The patients had a correct rate of 43.7 ± 23.2% in the 68-character test, significantly lower (P < 0.001) than that of controls. Shape-similar error was the most common type of reading error (101/209, 48.3%). The ABC total writing score rate of the patients ranged from 68.9% to 98.7% (median, 90.5%), significantly lower (P < 0.001) than that of the controls. The patients also showed worse performance in MMSE, auditory verbal learning test, Boston naming test, intersecting pentagons copying and clock-drawing test (all P < 0.05). In the patient group, the correct rate of 68-character test was significantly correlated with the ABC total writing score rate (P = 0.008), the score rate of Boston naming test (P = 0.017), and the clock-drawing test score (P = 0.010). CONCLUSION: Shape-similar errors may be a characteristic of Chinese pure alexia. The correlation between visuospatial dysfunction and pure alexia might explain the frequent occurrence of shape-similar errors in Chinese pure alexia.

Anemoside B4 inhibits SARS-CoV-2 replication in vitro and in vivo.

Objective: Anemoside B4 (AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in vitro. Methods: The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8 (CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore, label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type I IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical staining. Results: The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein (N), Spike protein (S), and 3C-like protease (3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon (IFN)-ß response via the activation of retinoic acid-inducible gene I (RIG-1) like receptor (RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA metabolism. Conclusion: Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.

Superior energy storage properties in SrTiO3-based dielectric ceramics through all-scale hierarchical architecture.

The restricted energy density in dielectric ceramic capacitors is challenging for their integration with advanced electronic systems. Numerous strategies have been proposed to boost the energy density at different scales or combine those multiscale effects. Herein, guided by all-scale synergistic design, we fabricated Sr0.7Bi0.2TiO3 ceramics doped with (Bi0.5Na0.5)(Zr0.5Ti0.5)O3 by sintering the nanopowders by solution combustion synthesis, which demonstrate exceptional energy storage performance (ESP). Notably, an ultrahigh recoverable energy density of 11.33 J cm-3, accompanied by an impressive energy efficiency of 89.30%, was achieved at an extremely high critical electric field of 961 kV cm-1. These primary energy storage parameters outperform those of previously reported ceramic capacitors based on SrTiO3. Additionally, an excellent comprehensive performance is also realized, including a substantial power density of 156.21 MW cm-3 (at 300 kV cm-1), an extraordinarily short discharge time of 97 ns, a high Vickers hardness rating of approximately 8.23 GPa, and outstanding thermal and frequency stability. This enhancement can be attributed to the synergistic effect at all scales from atomic substitution, polar nano regions, submicrometer grain, and sample thickness. Consequently, this panoscopic approach has effectively demonstrated the potential to enhance the ESP of dielectric ceramics.