Brain Metastasis from EGFR-Mutated Non-Small Cell Lung Cancer: Secretion of IL11 from Astrocytes Up-Regulates PDL1 and Promotes Immune Escape.

Patients who have non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations are more prone to brain metastasis (BM) and poor prognosis. Previous studies showed that the tumor microenvironment of BM in these patients is immunosuppressed, as indicated by reduced T-cell abundance and activity, although the mechanism of this immunosuppression requires further study. This study shows that reactive astrocytes play a critical role in promoting the immune escape of BM from EGFR-mutated NSCLC by increasing the apoptosis of CD8+ T lymphocytes. The increased secretion of interleukin 11(IL11) by astrocytes promotes the expression of PDL1 in BM, and this is responsible for the increased apoptosis of T lymphocytes. IL11 functions as a ligand of EGFR, and this binding activates EGFR and downstream signaling to increase the expression of PDL1, culminating in the immune escape of tumor cells. IL11 also promotes immune escape by binding to its intrinsic receptor (IL11Rα/glycoprotein 130 [gp130]). Additional in vivo studies show that the targeted inhibition of gp130 and EGFR suppresses the growth of BM and prolongs the survival time of mice. These results suggest a novel therapeutic strategy for treatment of NSCLC patients with EGFR mutations.

Structural equation modeling of dispositional mindfulness, internal environmental factors, external environmental factors, and self-care behaviors in people with type 2 diabetes.

BACKGROUND: To achieve suitable diabetes care, understanding the factors that affect self-care behaviors is necessary. OBJECTIVE: To construct a model of dispositional mindfulness, internal environmental factors, external environmental factors, and self-care behaviors in people with diabetes. DESIGN AND METHODS: This cross-sectional study analyzed a convenience sample of 311 people with type 2 diabetes in Taiwan. Data were collected through questionnaires, including the Diabetes Symptoms Checklist, Emotional Distress Scale, Empowerment Process Scale, Interpersonal Communication Scale and Self-Care Behavior scale. RESULTS: Structural equation modeling indicated that a model of dispositional mindfulness, internal environmental factors, external environmental factors, and self-care behaviors in the patients with diabetes best fit the data. Dispositional mindfulness (ß = 0.39), internal environmental factors (ß = 0.52), and external environmental factors (ß = 0.71) directly influenced self-care behaviors in the patients with diabetes. Dispositional mindfulness significantly indirectly affected self-care behaviors via internal and external environmental factors. CONCLUSIONS: To improve self-care behaviors, interventions should consider mindfulness training, and also include internal environmental factors and external environmental factors in the mindfulness training.

The Effect of Vocational Training on Visually Impaired People's Quality of Life.

BACKGROUND: Quality of life (QOL) is frequently utilized in clinical medicine and research to assess a patient's health status and treatment effectiveness. OBJECTIVES: This study investigates the impact of vocational training on the QOL of visually impaired individuals. METHODS: We employed the brief Taiwan version of the World Health Organization QOL Questionnaire (WHOQOL-BREFTW) to assess four domains: physical, psychological, social, and environmental, using a nonequivalent pretest-posttest control group design. The experimental group participated in 6 months of vocational training, including life and career reconstruction. After completing the vocational training, the average QOL score for the experimental group was 3.34 ± 0.18, while the control group had a score of 3.10 ± 0.85. The generalized estimating equation (GEE) results revealed a notable improvement of 10.81 (1.10) in the posttest overall QOL scores compared to the pretest scores in the control group. CONCLUSION: Vocational training significantly improves the overall QOL for visually impaired individuals. It is noteworthy that the psychological, social relationship, and physical health domains of WHOQOL-BREF TW exhibited the most significant improvements. This emphasizes the following: 1. professional knowledge and technical learning can enhance the abilities of the visually impaired. 2. The improvement in QOL occurs primarily at physical, psychological, and social levels. These levels involve maintaining physical health, reducing dependence on medical care, and enhancing self-care abilities for life reconstruction. 3. Integrating electronics with directional action can help to mitigate the risks associated with outdoor activities.

Identifying multi-target drugs for prostate cancer using machine learning-assisted transcriptomic analysis.

Prostate cancer is a leading cause of cancer death in men, and the development of effective treatments is of great importance. This study explored to identify the candidate drugs for prostate cancer by transcriptomic data and CMap database analysis. After integrating the results of omics analysis, bisoprolol is confirmed as a promising drug. Moreover, cell experiment reveals its potential inhibitory effect on the proliferation of prostate cancer cells. Importantly, machine learning methods are employed to predict the targets of bisoprolol, and the dual-target ADRB3 and hERG are explored by dynamic simulation. The findings of this study demonstrate the potential of bisoprolol as a multi-target drug for prostate cancer treatment and the feasibility of using beta-adrenergic receptor inhibitors in prostate cancer treatment. In addition, the proposed research approach is promising for discovering potential drugs for cancer treatment by leveraging the concept of drug side effects leading to anticancer effects. Further research is necessary to investigate the pharmacological action, potential toxicity, and underlying mechanisms of bisoprolol in treating prostate cancer with ADRB3.Communicated by Ramaswamy H. Sarma.

Voltage-gated sodium channels in cancer and their specific inhibitors.

Voltage-gated sodium channels (VGSCs) participate in generating and spreading action potentials in electrically excited cells such as neurons and muscle fibers. Abnormal expression of VGSCs has been observed in various types of tumors, while they are either not expressed or expressed at a low level in the matching normal tissue. Hence, this abnormal expression suggests that VGSCs confer some advantage or viability on tumor cells, making them a valuable indicator for identifying tumor cells. In addition, overexpression of VGSCs increased the ability of cancer cells to metastasize and invade, as well as correlated with the metastatic behavior of different cancers. Therefore, blocking VGSCs presents a new strategy for the treatment of cancers. A portion of this review summarizes the structure and function of VGSCs and also describes the correlation between VGSCs and cancers. Most importantly, we provide an overview of current research on various subtype-selective VGSC inhibitors and updates on ongoing clinical studies.

Structural insights into the mechanism of GTP initiation of microtubule assembly.

In eukaryotes, the dynamic assembly of microtubules (MT) plays an important role in numerous cellular processes. The underlying mechanism of GTP triggering MT assembly is still unknown. Here, we present cryo-EM structures of tubulin heterodimer at their GTP- and GDP-bound states, intermediate assembly states of GTP-tubulin, and final assembly stages of MT. Both GTP- and GDP-tubulin heterodimers adopt similar curved conformations with subtle flexibility differences. In head-to-tail oligomers of tubulin heterodimers, the inter-dimer interface of GDP-tubulin exhibits greater flexibility, particularly in tangential bending. Cryo-EM of the intermediate assembly states reveals two types of tubulin lateral contacts, "Tube-bond" and "MT-bond". Further, molecular dynamics (MD) simulations show that GTP triggers lateral contact formation in MT assembly in multiple sequential steps, gradually straightening the curved tubulin heterodimers. Therefore, we propose a flexible model of GTP-initiated MT assembly, including the formation of longitudinal and lateral contacts, to explain the nucleation and assembly of MT.

Polarizable atomic multipole-based force field for cholesterol.

Cholesterol is one of the essential component of lipid in membrane. We present a polarizable atomic multipole force field (FF) for the molecular dynamic simulation of cholesterol. The FF building process follows the computational framework as the atomic multipole optimized energetics for biomolecular applications (AMOEBA) model. In this framework, the electronics parameters, including atomic monopole moments, dipole moments, and quadrupole moments calculated from ab initio calculations in the gas phase, are applied to represent the charge distribution. Furthermore, the many-body polarization is modeled by following the same pattern of distributed atomic polarizabilities. Then, the bilayers composed of two typical phospholipid molecules, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), in a range of different cholesterol concentrations are built and implemented by molecular dynamics (MD) simulations based on the proposed polarizable FF. The simulation results are statistically analyzed to validate the feasibility of the proposed FF. The structural properties of the bilayers are calculated to compare with the related experimental values. The MD values show the same trend of experimental values changes.Communicated by Ramaswamy H. Sarma.

Self-Consistent Quantum Mechanics/Embedded Charge Study on Aggregation-Enhanced Delayed Fluorescence of Cu(I) Complexes: Luminescence Mechanism and Molecular Design Strategy.

To elucidate the luminescence mechanism of highly efficient blue Cu(N^N)(POP)+-type thermally activated delayed fluorescence (TADF) materials, we have selected Cu(pytfmpz)(POP)+ (1) and Cu(pympz)(POP)+ (2) as targets to investigate the photophysical properties in both solution and solid phases. The self-consistent electrostatic potential (ESP) embedded charge within the quantum mechanics/molecular mechanics (QM/MM) method demonstrates a greater advantage over the charge equilibrium (QEQ) in accurately calculating atomic charges and reasonably describing the polarization effect, ultimately resulting in a favorable consistency between simulation and experimental measurements. After systematic and quantitative simulation, it has been found that complex 2, with an electron-donating group of -CH3, exhibits a much more blue-shifted spectrum and a significantly enhanced efficiency in comparison to complex 1 with -CF3. This is due to the widened HOMO-LUMO gap as well as the narrowed energy gap between the lowest singlet and triplet excited states (ΔEST), respectively. Then, the designed complex 3 is introduced with a stronger electron donor and larger tert-butyl group, which plays a key role in simultaneously suppressing the structural distortion and reducing the ΔEST. This leads to a faster reverse intersystem crossing process than that of the two experimental complexes in solution, turning out to be a new deep-blue-emitting material with excellent TADF performance.

The molecular mechanism of Y473 phosphorylation of UGDH relieves the inhibition effect of UDP-glucose on HuR.

Uridine diphosphate glucose (UDP-Glc) is able to accelerate the decay of snail family transcriptional repressor 1 (SNAI1) mRNA by inhibiting Hu antigen R (HuR, an RNA-binding protein), thereby preventing cancer invasiveness and drug resistance. Nevertheless, the phosphorylation of tyrosine 473 (Y473) of UDP-glucose dehydrogenase (UGDH is capable of converting UDP-Glc to uridine diphosphate glucuronic acid (UDP-GlcUA)) weakens the inhibition of UDP-Glc to HuR, thus initiating the epithelial-mesenchymal transformation of tumor cells and promoting tumor cell migration and metastasis. To address the mechanism, we performed molecular dynamics simulations combined with molecular mechanics generalized Born surface area (MM/GBSA) analysis on wild-type and Y473 phosphorylated UGDH and HuR, UDP-Glc, UDP-GlcUA complexes. We demonstrated that Y473 phosphorylation was able to enhance the binding between UGDH and the HuR/UDP-Glc complex. Compared with HuR, UGDH has a stronger binding ability with UDP-Glc; therefore, UDP-Glc was inclined to bind to UGDH and then was catalyzed to UDP-GlcUA by UGDH, which relieved the inhibition of UDP-Glc to HuR. In addition, the binding ability of HuR for UDP-GlcUA was lower than its affinity for UDP-Glc, significantly reducing the inhibition of HuR. Hence, HuR bound to SNAI1 mRNA more easily to increase the stability of mRNA. Our results revealed the micromolecular mechanism of Y473 phosphorylation of UGDH regulating the interaction between UGDH and HuR as well as relieving the inhibition of UDP-Glc on HuR, which contributed to understanding the role of UGDH and HuR in tumor metastasis and developing small molecule drugs targeting the interaction between UGDH and HuR.

A Glycosidic-Bond-Based Mass-Spectrometry-Cleavable Cross-linker Enables In Vivo Cross-linking for Protein Complex Analysis.

Chemical cross-linking mass spectrometry (CXMS) has emerged as a powerful technology to analyze protein complexes. However, the progress of in vivo CXMS studies has been limited by cross-linking biocompatibility and data analysis. Herein, a glycosidic bond-based MS-cleavable cross-linker of trehalose disuccinimidyl ester (TDS) was designed and synthesized, which was fragmented in MS under CID/HCD to simplify the cross-linked peptides into conventional single peptides via selective cleavage between glycosidic and peptide bonds under individual MS collision energy. Consequently, the cross-linking identification accuracy and throughput were significantly enhanced, and the popular MS mode of stepped HCD was allowed. In addition, TDS showed proper cell-penetrating properties while being highly water-soluble, making it non-DMSO dependent during solubilization. Collectively, TDS provides a promising toolkit for CXMS characterization of living systems with high biocompatibility and accuracy.

Fructose-1,6-bisphosphatase 1 dephosphorylates IκBα and suppresses colorectal tumorigenesis.

Emerging evidence demonstrates that some metabolic enzymes that phosphorylate soluble metabolites can also phosphorylate a variety of protein substrates as protein kinases to regulate cell cycle, apoptosis and many other fundamental cellular processes. However, whether a metabolic enzyme dephosphorylates protein as a protein phosphatase remains unknown. Here we reveal the gluconeogenic enzyme fructose 1,6-biphosphatase 1 (FBP1) that catalyzes the hydrolysis of fructose 1,6-bisphosphate (F-1,6-BP) to fructose 6-phosphate (F-6-P) as a protein phosphatase by performing a high-throughput screening of metabolic phosphatases with molecular docking followed by molecular dynamics (MD) simulations. Moreover, we identify IκBα as the substrate of FBP1-mediated dephosphorylation by performing phosphoproteomic analysis. Mechanistically, FBP1 directly interacts with and dephosphorylates the serine (S) 32/36 of IκBα upon TNFα stimulation, thereby inhibiting NF-κB activation. MD simulations indicate that the catalytic mechanism of FBP1-mediated IκBα dephosphorylation is similar to F-1,6-BP dephosphorylation, except for higher energetic barriers for IκBα dephosphorylation. Functionally, FBP1-dependent NF-κB inactivation suppresses colorectal tumorigenesis by sensitizing tumor cells to inflammatory stresses and preventing the mobilization of myeloid-derived suppressor cells. Our finding reveals a previously unrecognized role of FBP1 as a protein phosphatase and establishes the critical role of FBP1-mediated IκBα dephosphorylation in colorectal tumorigenesis.

Synergistic effect of conformational changes in phosphoglycerate kinase 1 product release.

In the glycolysis pathway, phosphoglycerate kinase 1 (PGK1) transfers one phosphoryl-group from 1,3-diphosphoglycerate (1,3BPG) to ADP to product 3-phosphoglycerate (3PG) and ATP. The catalytic process is accompanied with the conversion between the open conformation and the closed conformation of PGK1. However, the dynamic collaboration mechanism between the PGK1 conformation transition and the products releasing process remains poorly understood. Here using molecular dynamics simulations combined with molecular mechanics generalized born surface area (MM/GBSA) analysis, we demonstrated that PGK1 in the closed conformation first releases the product ATP to reach a semi-open conformation, and releases the product 3PG to achieve the full open conformation, which could accept new substrates ADP and 1,3BPG for the next cycle. It is noteworthy that the phosphorylation of PGK1 at T243 causes the loop region (residues L248-E260) flip outside the protein, and the phosphorylation of Y324 leads PGK1 become looser. Both modifications cause the exposure of the ADP/ATP binding site, which was beneficial for the substrates/products binding/releasing of PGK1. In addition, the other post translational modifications (PTMs) were also able to regulate the ligands binding/releasing with different effects. Our results revealed the dynamic cooperative molecular mechanism of PGK1 conformational transition with products releasing, as well as the influence of PTMs, which would contribute to the understanding of PGK1 substrates/products conversion process and the development of small molecule drugs targeting PGK1.Communicated by Ramaswamy H. Sarma.

Loneliness and Social Support among the Middle-Aged and Elderly People with Visual Impairment.

Loneliness is associated with depression, sleep disturbance, and an increased risk of cardiovascular disease, and it is a global public health problem. Since physical and mental health have a great impact on loneliness, middle-aged and elderly people who are blind or visually impaired may be more affected by loneliness. Previous research has confirmed that effective social support can enhance physical and mental health and alleviate the negative effects of life stress. Therefore, in this study, we applied a cross-sectional design where data were collected using questionnaires completed in person, by phone, or online for a total of 456 middle-aged and elderly people with visual impairment. We found that the enrolled participants who were unemployed, lacked a stable source of income, lived alone, or were unable to move independently were prone to experiencing high levels of loneliness and low social support, which highlights the necessity of interventions such as counseling to alleviate the sense of loneliness in such groups. During the COVID-19 pandemic, social support measures to reduce the sense of loneliness should be highly encouraged to ensure that middle-aged and elderly people with visual impairment can continue to live independently, and social support seems to be an important factor.

Effect of horticultural activities on quality of life, perceived stress, and working memory of community-dwelling older adults.

This study sampled 86 community-dwelling older adults to investigate the effect of horticultural activities on their quality of life, perceived stress, and working memory. The results demonstrated that after 8 weeks of horticultural activities, the effect sizes (Cohen's d) of their quality of life, perceived stress, and working memory were 0.92, -1.32, and 0.62, respectively. Among the four domains of quality of life, the social relationships domain improved the most. For perceived stress, the score of the experimental group decreased from 1.70 (0.48) to 1.29 (0.58). For working memory, the score increased from 3.43 (1.13) to 4.14 (1.27), whereas the score of the control group did not change substantially. Statistical analysis conducted using a generalized estimating equation revealed a significant interaction effect between group and time (P < 0.001). This study provides a reference for improving the quality of life, perceived stress, and working memory in older people.

Combination of Serum Test and Questionnaire in Early Gastric Cancer Screening.

Background: We aimed to analyze the predictive role of serum test and questionnaire in Early Gastric Cancer in The First Affiliated Hospital of Xingtai Medical College, Hebei Province from 2019 to 2020. Methods: In this prospective study, 280 medical examiners underwent questionnaire, serum test and gastroscopy. They were divided into Gastric cancer (GC) and Non-Gastric cancer (NGC) group. NGC group was divided into Low-grade intraepithelial neoplasia (LGIN), Chronic atrophic gastritis (CAG) and Non-chronic atrophic gastritis (NCAG) group. Results: Age, drinking, sex and Gastrin-17(G-17) was respectively independent risk factors for GC. Age, drinking and G-17 was independent risk factors for GC in men. G-17 of GC group was higher than that of LGIN and NCAG group (P<0.05). Pepsinogen I/II ratio (PGR) of GC was lower than that of NCAG group (P<0.05). There was no significant difference between Pepsinogen I (PGI) and Pepsinogen II (PGII) in the four groups. Helicobacter pylori-immunoglobulin G antibodies (H. pylori-IgG) of LGIN group was significantly higher than that of CAG and NCAG group in gastritis group (P<0.008). G-17≥42.95 pmol/L, age≥69years, male and drinking can predict GC. Conclusion: Older, drinking, men and high G-17 could respectively predict GC. Especially in men, older, drinking and high G-17 could affect the occurrence of GC. G-17, age, drinking and sex used respectively to screen high-risk populations for GC were more efficient than combined screening. GC had a higher serum G-17 and a lower PG than other gastric diseases.

ZDHHC18 negatively regulates cGAS-mediated innate immunity through palmitoylation.

Double-stranded DNA is recognized as a danger signal by cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), triggering innate immune responses. Palmitoylation is an important post-translational modification (PTM) catalyzed by DHHC-palmitoyl transferases, which participate in the regulation of diverse biological processes. However, whether palmitoylation regulates cGAS function has not yet been explored. Here, we found that palmitoylation of cGAS at C474 restricted its enzymatic activity in the presence of double-stranded DNA. cGAS palmitoylation was catalyzed mainly by the palmitoyltransferase ZDHHC18 and double-stranded DNA promoted this modification. Mechanistically, palmitoylation of cGAS reduced the interaction between cGAS and double-stranded DNA, further inhibiting cGAS dimerization. Consistently, ZDHHC18 negatively regulated cGAS activation in human and mouse cell lines. In a more biologically relevant model system, Zdhhc18-deficient mice were found to be resistant to infection by DNA viruses, in agreement with the observation that ZDHHC18 negatively regulated cGAS mediated innate immune responses in human and mouse primary cells. In summary, the negative role of ZDHHC18-mediated cGAS palmitoylation may be a novel regulatory mechanism in the fine-tuning of innate immunity.

Mechanisms of distinctive mismatch tolerance between Rad51 and Dmc1 in homologous recombination.

Homologous recombination (HR) is a primary DNA double-strand breaks (DSBs) repair mechanism. The recombinases Rad51 and Dmc1 are highly conserved in the RecA family; Rad51 is mainly responsible for DNA repair in somatic cells during mitosis while Dmc1 only works during meiosis in germ cells. This spatiotemporal difference is probably due to their distinctive mismatch tolerance during HR: Rad51 does not permit HR in the presence of mismatches, whereas Dmc1 can tolerate certain mismatches. Here, the cryo-EM structures of Rad51-DNA and Dmc1-DNA complexes revealed that the major conformational differences between these two proteins are located in their Loop2 regions, which contain invading single-stranded DNA (ssDNA) binding residues and double-stranded DNA (dsDNA) complementary strand binding residues, stabilizing ssDNA and dsDNA in presynaptic and postsynaptic complexes, respectively. By combining molecular dynamic simulation and single-molecule FRET assays, we identified that V273 and D274 in the Loop2 region of human RAD51 (hRAD51), corresponding to P274 and G275 of human DMC1 (hDMC1), are the key residues regulating mismatch tolerance during strand exchange in HR. This HR accuracy control mechanism provides mechanistic insights into the specific roles of Rad51 and Dmc1 in DNA double-strand break repair and may shed light on the regulatory mechanism of genetic recombination in mitosis and meiosis.

Effects of Horticultural Activities on Attitudes toward Aging, Sense of Hope and Hand-Eye Coordination in Older Adults in Residential Care Facilities.

This study investigated the effects of an 8-week horticultural activity intervention on attitudes toward aging, sense of hope, and hand-eye coordination in 88 older adults in residential care facilities. In the experimental group, the mean score for "attitudes toward aging" increased from 3.81 before the intervention to 4.74 points after the intervention (standard deviation SD = 0.24 and 0.27, respectively), and the control group dropped from 3.75 to 3.70 (standard deviations, respectively SD = 0.27 and 0.28). The mean score for "sense of hope" increased from 3.28 before the intervention to 3.81 points after the intervention (SD = 0.49 and 0.26, respectively). In contrast to the control group, the mean score gradually declined from 3.26 to 3.16 points (standard deviation SD = 0.54 and 0.48, respectively). In the test of hand-eye coordination, the time required to complete the cup stacking test significantly decreased from 33.56 to 25.38 s in the experimental group but did not significantly change in the control group. Generalized estimating equation analysis revealed a significant interaction between group and time (p < 0.001). The data trends revealed significant differences in outcomes between the experimental group and the control group. At 3 months after the end of the study, the effect size in the experimental group remained higher than that in the control group.

Modulation of the interfacial architecture enhancing the efficiency and energy density of ferroelectric nanocomposites via the irradiation method.

Flexible dielectric materials such as poly(vinylidene fluoride)-based nanocomposites with high energy density are employed for applications in modern electronic and electric systems. In this study, we improve traditional methods by optimizing the interfacial structure, achieving a 34% increase in energy density without reduced discharge efficiency. Herein, a simple solution-cast method is used to prepare poly(vinylidene fluoride-co-trifluoroethylene) nanocomposites filled by γ-methacryloyl-propyltrimethoxysilane (MPMS) grafting barium titanate nanoparticles, forming a class of cross-linking networks by irradiation. More additional interfaces arising from irradiation cross-linking give rise to high discharge energy density, and the small crystalline domain and cross-linking network enhance the charge-discharge efficiency. Furthermore, we find two types of cross-linking centers on the network. One is more beneficial to energy density, and the other is more beneficial to efficiency. Regulating two types of cross-linking centers can balance efficiency and energy density. In summary, this work provides a promising strategy for exploiting advanced flexible dielectric materials to meet application requirements.

Enhanced energy density of PVDF-based nanocomposites via a core-shell strategy.

In recent years, high energy density polymer capacitors have attracted a lot of scientific interest due to their potential applications in advanced power systems and electronic devices. Here, core-shell structured TiO2@SrTiO3@polydamine nanowires (TiO2@SrTiO3@PDA NWs) were synthesized via a combination of surface conversion reaction and in-situ polymerization method, and then incorporated into the poly(vinylidene fluoride) (PVDF) matrix. Our results showed that a small amount of TiO2@SrTiO3@PDA NWs can simultaneously enhance the breakdown strength and electric displacement of nanocomposite (NC) films, resulting in improved energy storage capability. The 5 wt% TiO2@SrTiO3@PDA NWs/PVDF NC demonstrates 1.72 times higher maximum discharge energy density compared to pristine PVDF (10.34 J/cm3 at 198 MV/m vs. 6.01 J/cm3 at 170 MV/m). In addition, the NC with 5 wt% TiO2@SrTiO3@PDA NWs also demonstrates an excellent charge-discharge efficiency (69% at 198 MV/m). Enhanced energy storage performance is due to hierarchical interfacial polarization among their multiple interfaces, the large aspect ratio as well as surface modification of the TiO2@SrTiO3 NWs. The results of this study provide guidelines and a foundation for the preparation of the polymer NCs with an outstanding discharge energy density.