Intelligent ankle-foot prosthesis based on human structure and motion bionics.

The ankle-foot prosthesis aims to compensate for the missing motor functions by fitting the motion characteristics of the human ankle, which contributes to enabling the lower-limb amputees to take care of themselves and improve mobility in daily life. To address the problems of poor bionic motion of the ankle-foot prosthesis and the lack of natural interaction among the patient, prosthesis, and the environment, we developed a complex reverse-rolling conjugate joint based on the human ankle-foot structure and motion characteristics, the rolling joint was used to simulate the rolling-sliding characteristics of the knee joint. Meanwhile, we established a segmental dynamics model of the prosthesis in the stance phase, and the prosthetic structure parameters were obtained with the optimal prosthetic structure dimensions and driving force. In addition, a carbon fiber energy-storage foot was designed based on the human foot profile, and the dynamic response of its elastic strain energy at different thicknesses was simulated and analyzed. Finally, we integrated a bionic ankle-foot prosthesis and experiments were conducted to verify the bionic nature of the prosthetic joint motion and the energy-storage characteristics of the carbon fiber prosthetic foot. The proposed ankle-foot prosthesis provides ambulation support to assist amputees in returning to social life normally and has the potential to help improve clinical viability to reduce medical rehabilitation costs.

Co-Regulating Solvation Structure and Hydrogen Bond Network via Bio-Inspired Additive for Highly Reversible Zinc Anode.

The feasibility of aqueous zinc-ion batteries for large-scale energy storage is hindered by the inherent challenges of Zn anode. Drawing inspiration from cellular mechanisms governing metal ion and nutrient transport, erythritol is introduced, a zincophilic additive, into the ZnSO4 electrolyte. This innovation stabilizes the Zn anode via chelation interactions between polysaccharides and Zn2+. Experimental tests in conjunction with theoretical calculation results verified that the erythritol additive can simultaneously regulate the solvation structure of hydrated Zn2+ and reconstruct the hydrogen bond network within the solution environment. Additionally, erythritol molecules preferentially adsorb onto the Zn anode, forming a dynamic protective layer. These modifications significantly mitigate undesirable side reactions, thus enhancing the Zn2+ transport and deposition behavior. Consequently, there is a notable increase in cumulative capacity, reaching 6000 mA h cm⁻2 at a current density of 5 mA cm-2. Specifically, a high average coulombic efficiency of 99.72% and long cycling stability of >500 cycles are obtained at 2 mA cm-2 and 1 mA h cm-2. Furthermore, full batteries comprised of MnO2 cathode and Zn anode in an erythritol-containing electrolyte deliver superior capacity retention. This work provides a strategy to promote the performance of Zn anodes toward practical applications.

An Effective and Promising Strategy for Plant Protection: Synthesis of L-Carvone-Based Thiazolinone-Hydrazone/Nanochitosan Complexes with Antifungal Activity and Sustained Releasing Performance.

The development of novel natural product-derived nano-pesticide systems with loading capacity and sustained releasing performance of bioactive compounds is considered an effective and promising plant protection strategy. In this work, 25 L-carvone-based thiazolinone-hydrazone compounds 4a~4y were synthesized by the multi-step modification of L-carvone and structurally confirmed. Compound 4h was found to show favorable and broad-spectrum antifungal activity through the in vitro antifungal activity evaluation of compounds 4a~4y against eight phytopathogenic fungi. Thus, it could serve as a leading compound for new antifungal agents in agriculture. Moreover, the L-carvone-based nanochitosan carrier 7 bearing the 1,3,4-thiadiazole-amide group was rationally designed for the loading and sustained releasing applications of compound 4h, synthesized, and characterized. It was proven that carrier 7 had good thermal stability below 200 °C, dispersed well in the aqueous phase to form numerous nanoparticles with a size of~20 nm, and exhibited an unconsolidated and multi-aperture micro-structure. Finally, L-carvone-based thiazolinone-hydrazone/nanochitosan complexes were fabricated and investigated for their sustained releasing behaviors. Among them, complex 7/4h-2 with a well-distributed, compact, and columnar micro-structure displayed the highest encapsulation efficiency and desirable sustained releasing property for compound 4h and thus showed great potential as an antifungal nano-pesticide for further studies.

Towards humanlike grasp in robotic hands: mechanical implementation of force synergies.

In the field of robotic hands, finger force coordination is usually achieved by complex mechanical structures and control systems. This study presents the design of a novel transmission system inspired from the physiological concept of force synergies, aiming to simplify the control of multifingered robotic hands. To this end, we collected human finger force data during six isometric grasping tasks, and force synergies (i.e. the synergy weightings and the corresponding activation coefficients) were extracted from the concatenated force data to explore their potential for force modulation. We then implemented two force synergies with a cable-driven transmission mechanism consisting of two spring-loaded sliders and five V-shaped bars. Specifically, we used fixed synergy weightings to determine the stiffness of the compression springs, and the displacements of sliders were determined by time-varying activation coefficients. The derived transmission system was then used to drive a five-finger robotic hand named SYN hand. We also designed a motion encoder to selectively activate desired fingers, making it possible for two motors to empower a variety of hand postures. Experiments on the prototype demonstrate successful grasp of a wide range of objects in everyday life, and the finger force distribution of SYN hand can approximate that of human hand during six typical tasks. To our best knowledge, this study shows the first attempt to mechanically implement force synergies for finger force modulation in a robotic hand. In comparison to state-of-the-art robotic hands with similar functionality, the proposed hand can distribute humanlike force ratios on the fingers by simple position control, rather than resorting to additional force sensors or complex control strategies. The outcome of this study may provide alternatives for the design of novel anthropomorphic robotic hands, and thus show application prospects in the field of hand prostheses and exoskeletons.

Hydrogen Isotope Effect Endows a Breakthrough in Photoluminescent Covalent Organic Frameworks.

Luminescent covalent organic frameworks (LCOFs) have emerged as indispensable candidates in various applications due to their greater tunable emitting properties and structural robustness compared to small molecule emitters. An unsolved issue in this area is developing highly luminescent LCOFs of which the nonradiative quenching pathways were suppressed as much as possible. Here, a robust aminal-linked COF (DD-COF) possessing perdeuterated light-emitting monomers was designed and synthesized. The solid-state photoluminescence quantum yield of the DD-COF reaches 81%, significantly outcompeting all state-of-the-art LCOFs reported so far. The exceptional luminescent efficiency is attributed to the inhibition of different pathways of nonradiative decay, especially from bond vibrations where only substitution by a heavier isotope with a lower zero-point vibration frequency works. Furthermore, the prepared deuterated COF not only boosts higher photostability under UV irradiation but also enables superior fluorescence sensing performance for iodine detection compared to nondeuterated COF.

Bionic intelligent ankle-foot prosthesis based on the conjugate curved surface.

Given the poor biomimetic motion of traditional ankle-foot prostheses, it is of great significance to develop an intelligent prosthesis that can realize the biomimetic mechanism of human feet and ankles. To this end, we presented a bionic intelligent ankle-foot prosthesis based on the complex conjugate curved surface. The proposed prosthesis is mainly composed of the rolling conjugated joints with a bionic design and the carbon fiber energy-storage foot. We investigated the flexibility of the prosthetic ankle joint movement, and the ability of the prosthetic foot to absorb ground impact during the gait cycle. Experimental results showed the matching of the ankle/toe position relationship of the human foot during simulated walking, which is helpful to realize the biomimetic motion of the human foot and ankle. It can also help therapists and clinicians provide better rehabilitation for lower-limb amputees.

A novel untrained SSVEP-EEG feature enhancement method using canonical correlation analysis and underdamped second-order stochastic resonance.

Objective: Compared with the light-flashing paradigm, the ring-shaped motion checkerboard patterns avoid uncomfortable flicker or brightness modulation, improving the practical interactivity of brain-computer interface (BCI) applications. However, due to fewer harmonic responses and more concentrated frequency energy elicited by the ring-shaped checkerboard patterns, the mainstream untrained algorithms such as canonical correlation analysis (CCA) and filter bank canonical correlation analysis (FBCCA) methods have poor recognition performance and low information transmission rate (ITR). Methods: To address this issue, a novel untrained SSVEP-EEG feature enhancement method using CCA and underdamped second-order stochastic resonance (USSR) is proposed to extract electroencephalogram (EEG) features. Results: In contrast to typical unsupervised dimensionality reduction methods such as common average reference (CAR), principal component analysis (PCA), multidimensional scaling (MDS), and locally linear embedding (LLE), CCA exhibits higher adaptability for SSVEP rhythm components. Conclusion: This study recruits 42 subjects to evaluate the proposed method and experimental results show that the untrained method can achieve higher detection accuracy and robustness. Significance: This untrained method provides the possibility of applying a nonlinear model from one-dimensional signals to multi-dimensional signals.

Dual-Modal Biosensor for Staphylococcus aureus Detection Based on a Porphyrin-Based Porous Organic Polymer FePor-TPA with Excellent Peroxidase-like, Catalase-like, and Photoelectrochemical Properties.

Bacterial infections seriously harm human health and cause many severe diseases, which triggered urgent demands to exploit specific and sensitive biosensor strategies for Staphylococcus aureus detection. Here, a colorimetric and photoelectrochemical dual-mode biosensor for S. aureus assay based on FePor-TPA was constructed. 2D FePor-TPA thin film and its bulk powder (FePor-TPA) were synthesized by in situ growth on ITO and a solvothermal condition, respectively, both of which exhibited excellent peroxidase-like and catalase-like activity, originating from their metalloporphyrin linkers. Benefiting from the in situ growth on ITO electrodes, the 2D FePor-TPA thin film also possessed a more ordered stacking mode and in turn exhibited good electrical conductivity, stable initial photocurrent, and high sensitivity to O2. As for bulk FePor-TPA, its porous structure and high specific surface area make it a possible scaffold to load an amount of AuNPs, the rabbit anti-Staphylococcus aureus Rosenbach tropina antibody (Ab2), and GOx for constructing the signal probe (GOx/Ab2@Au@FePor-TPA) and realizing catalytic amplification. With these satisfactory features in mind, the 2D FePor-TPA thin film and its bulk powder (FePor-TPA) were utilized to construct a dual and signal-on bioplatform for sensitively and selectively detecting S. aureus, which, as far as we know, has not been reported.

PEDV promotes the differentiation of CD4+T cells towards Th1, Tfh, and Treg cells via CD103+DCs.

Porcine epidemic diarrhea virus (PEDV) can infect all ages of pigs, particularly newborn piglets with a mortality almost reaching to 80-100%, causing significant economic losses to the global pig industry. The mucosal immune response is crucial for PEDV prevention, in which specific dendritic cells (DCs) and differentiated T cells play vital roles. In this study, CD103+DCs were differentiated successfully with retinoic acid (RA) treatment in vitro. PEDV could not replicate efficiently in differentiated CD103+DCs but could promote maturation of CD103+DCs by up-regulating the expression of SLA-DR, CD1a, CD86, and cytokines of IL-1ß and IL-10. In addition, PEDV-infected CD103+DCs and CD4+T cells were co-cultured, and the results showed that the differentiation of CD4+T cells toward Th1, Tfh, and Treg, but not Th2. These results demonstrate that PEDV-infected CD103+DCs could promote the differentiation of CD4+T cells, which provided the basis for further study of mucosal response induced by PEDV via CD103+DCs.

[Retracted] Actin­binding protein anillin promotes the progression of hepatocellular carcinoma in vitro and in mice.

[This retracts the article DOI: 10.3892/etm.2021.9885.].

[Retracted] KIF2C promotes the proliferation of hepatocellular carcinoma cells in vitro and in vivo.

[This retracts the article DOI: 10.3892/etm.2021.10528.].

Association of Plasma Vitamins and Carotenoids, DNA Methylation of LCAT, and Risk of Age-Related Macular Degeneration.

Dysregulation of lipid metabolism has been implicated in age-related macular degeneration (AMD), the leading cause of blindness among the elderly. Lecithin cholesterol acyltransferase (LCAT) is an important enzyme responsible for lipid metabolism, which could be regulated by DNA methylation during the development of various age-related diseases. This study aimed to assess the association between LCAT DNA methylation and the risk of AMD, and to examine whether plasma vitamin and carotenoid concentrations modified this association. A total of 126 cases of AMD and 174 controls were included in the present analysis. LCAT DNA methylation was detected by quantitative real-time methylation-1specific PCR (qMSP). Circulating vitamins and carotenoids were measured using reversed-phase high-performance liquid chromatography (RP-HPLC). DNA methylation of LCAT was significantly higher in patients with AMD than those in the control subjects. After multivariable adjustment, participants in the highest tertile of LCAT DNA methylation had a 5.37-fold higher risk (95% CI: 2.56, 11.28) of AMD compared with those in the lowest tertile. Each standard deviation (SD) increment of LCAT DNA methylation was associated with a 2.23-fold (95% CI: 1.58, 3.13) increased risk of AMD. There was a J-shaped association between LCAT DNA methylation and AMD risk (Pnon-linearity = 0.03). Higher concentrations of plasma retinol and ß-cryptoxanthin were significantly associated with decreased levels of LCAT DNA methylation, with the multivariate-adjusted ß coefficient being -0.05 (95% CI: -0.08, -0.01) and -0.25 (95% CI: -0.42, -0.08), respectively. In joint analyses of LCAT DNA methylation and plasma vitamin and carotenoid concentrations, the inverse association between increased LCAT DNA methylation and AMD risk was more pronounced among participants who had a lower concentration of plasma retinol and ß-cryptoxanthin. These findings highlight the importance of comprehensively assessing LCAT DNA methylation and increasing vitamin and carotenoid status for the prevention of AMD.

Heterogeneity of T cells in periapical lesions and in vitro validation of the proangiogenic effect of GZMA on HUVECs.

AIM: T cells are key immunomodulatory cells in periapical lesions. This study aimed to explore the roles of T cells in chronic apical periodontitis (CAP) using single-cell RNA sequencing and to further investigate Granzyme A (GZMA) in angiogenesis regulation. METHODOLOGY: A total of five CAP samples were collected for single-cell RNA sequencing. We performed subcluster and lineage-tracing analyses for T cells. According to differential gene expression, distinct biological functions enriched in T cells of CAP were presented by gene set enrichment analysis (GSEA) and compared with healthy gingiva (data obtained from the GEO database). CellChat was used to explore potential ligand-receptor interactions between T cells and endothelial cells in CAP. The coculture of primary human umbilical vein endothelial cells (HUVECs) and Jurkat T cells, as well as the addition of GZMA recombinant protein, was used to validate the predicted pair of GZMA and coagulation factor II thrombin receptor (F2R) by RT-PCR, angiogenesis and migration assays. RESULTS: A transcriptomic atlas of 44 746 individual cells was constructed from the periapical lesions of five patients with CAP by single-cell RNA-seq, and eight cell types were identified. We identified nine subsets of T cells and deciphered the cellular heterogeneity of T cells in CAP at the functional level by subclustering and GSEA. Lineage tracing revealed a distinct lineage of T cells in CAP and predicted the transition of the T cellular state upon CAP. GSEA revealed multiple biological processes and relevant angiogenesis genes upregulated in CAP T cells. GZMA-F2R pairs were predicted by cell-cell interactions in CAP. High expression of GZMA and F2R was observed in the coculture of HUVECs and Jurkat T cells, and the proangiogenic capacity of the GZMA recombinant protein was emphasized by in vitro experiments. CONCLUSIONS: Our study provides novel insights into the heterogeneity of T cells in periapical lesions and reveals the potential role of GZMA in T cells in regulating angiogenesis in HUVECs.

Synthesis, Antifungal Activity, and Molecular Simulation Study of L-Carvone-Derived 1,3,4-Oxadiazole-Thioether Compounds.

To discover potent antifungal molecules with new and distinctive structures, 20 novel L-carvone-derived 1,3,4-oxadiazole-thioether compounds 5 a-5 t were synthesized through multi-step reaction of L-carvone, and their structures were confirmed by FT-IR, 1 H-NMR, 13 C-NMR, and HR-MS. The antifungal activities of compounds 5 a-5 t were preliminarily tested by in vitro method, and the results indicated that all of the title compounds displayed certain antifungal activities against the eight tested plant fungi, especially for P. piricola. Among them, compound 5 i (R=p-F) with the most significant antifungal activity deserved further study for discovering and developing novel natural product-based antifungal agents. Moreover, two molecular simulation technologies were employed for the investigation of their structure-activity relationships (SARs). Firstly, a reasonable and effective 3D-QSAR model was established by the comparative molecular field (CoMFA) method, and the relationship of the substituents linked with the benzene rings and the inhibitory activities of the title compounds against P. piricola was elucidated. Then, the binding mode of compound 5 i (R=p-F) and its potential biological target (CYP51) was simulated by molecular docking, and it was found that compound 5 i could readily bind with CYP51 in the active site, and the ligand-receptor interactions involved three hydrogen bonds and several hydrophobic effects.

Consumption of sugar sweetened beverages, artificially sweetened beverages and fruit juices and risk of type 2 diabetes, hypertension, cardiovascular disease, and mortality: A meta-analysis.

Introduction: Sugar-sweetened beverage (SSB) intake is associated with an increased risk of cardiometabolic diseases. However, evidence regarding associations of artificially sweetened beverages (ASBs) and fruit juices with cardiometabolic diseases is mixed. In this study, we aimed to investigate the association between the SSB, ASB and fruit juice consumption with the incidence of cardiometabolic conditions and mortality. Methods: Relevant prospective studies were identified by searching PubMed, Web of Science, Embase, and Cochrane Library until December 2022 without language restrictions. The pooled relative risk (RR) and 95% confidence intervals (CIs) were estimated for the association of SSBs, ASBs, and fruit juices with the risk of type 2 diabetes (T2D), cardiovascular disease (CVD), and mortality by using random-effect models. Results: A total of 72 articles were included in this meta-analysis study. Significantly positive associations were observed between the consumption of individual beverages and T2D risk (RR: 1.27; 95% CI: 1.17, 1.38 for SSBs; RR: 1.32; 95% CI: 1.11, 1.56 for ASBs; and RR:0.98; 95% CI: 0.93, 1.03 for fruit juices). Moreover, our findings showed that intakes of SSBs and ASBs were significantly associated with risk of hypertension, stroke, and all-cause mortality (RR ranging from 1.08 to 1.54; all p < 0.05). A dose-response meta-analysis showed monotonic associations between SSB intake and hypertension, T2D, coronary heart disease (CHD), stroke and mortality, and the linear association was only significant between ASB consumption and hypertension risk. Higher SSB and ASB consumptions were associated with a greater risk of developing cardiometabolic diseases and mortality. Fruit juice intake was associated with a higher risk of T2D. Conclusion: Therefore, our findings suggest that neither ASBs nor fruit juices could be considered as healthier beverages alternative to SSBs for achieving improved health.Systematic Review Registration: [PROSPERO], identifier [No. CRD42022307003].

Hypoxia preconditioned DPSC-derived exosomes regulate angiogenesis via transferring LOXL2.

Hypoxia was proved to enhance the angiogenesis of stem cells. However, the mechanism of the angiogenic potential in hypoxia-pretreated dental pulp stem cells (DPSCs) is poorly understood. We previously confirmed that hypoxia enhances the angiogenic potential of DPSC-derived exosomes with upregulation of lysyl oxidase-like 2 (LOXL2). Therefore, our study aimed to illuminate whether these exosomes promote angiogenesis via transfer of LOXL2. Exosomes were generated from hypoxia-pretreated DPSCs (Hypo-Exos) stably silencing LOXL2 after lentiviral transfection and characterized with transmission electron microscopy, nanosight and Western blot. The efficiency of silencing was verified using quantitative real-time PCR (qRT-PCR) and Western blot. CCK-8, scratch and transwell assays were conducted to explore the effects of LOXL2 silencing on DPSCs proliferation and migration. Human umbilical vein endothelial cells (HUVECs) were co-incubated with exosomes to assess the migration and angiogenic capacity through transwell and matrigel tube formation assays. The relative expression of angiogenesis-associated genes was characterized by qRT-PCR and Western blot. LOXL2 was successfully silenced in DPSCs and inhibited DPSC proliferation and migration. LOXL2 silencing in Hypo-Exos partially reduced promotion of HUVEC migration and tube formation and inhibited the expression of angiogenesis-associated genes. Thus, LOXL2 is one of various factors mediating the angiogenic effects of Hypo-Exos.

Synthesis, Antifungal Activity, 3D-QSAR and Controlled Release on Hydrotalcite Study of Longifolene-Derived Diphenyl Ether Carboxylic Acid Compounds.

Twenty-two novel longifolene-derived diphenyl ether-carboxylic acid compounds 7a-7v were synthesized from renewable biomass resources longifolene, and their structures were confirmed by FT-IR, 1H NMR, 13C NMR, and HRMS. The preliminary evaluation of in vitro antifungal activity displayed that compound 7b presented inhibition rates of 85.9%, 82.7%, 82.7%, and 81.4% against Alternaria solani, Cercospora arachidicola, Rhizoctonia solani, and Physalospora piricola, respectively, and compound 7l possessed inhibition rates of 80.7%, 80.4%, and 80.3% against R. solani, C. arachidicola, P. piricola, respectively, exhibiting excellent and broad-spectrum antifungal activities. Besides, compounds 7f and 7a showed significant antifungal activities with inhibition rates of 81.2% and 80.7% against A.solani, respectively. Meanwhile, a reasonable and effective 3D-QSAR mode (r2 = 0.996, q2 = 0.572) has been established by the CoMFA method. Furthermore, the drug-loading complexes 7b/MgAl-LDH were prepared and characterized. Their pH-responsive controlled-release behavior was investigated as well. As a result, complex 7b/MgAl-LDH-2 exhibited excellent controlled-releasing performance in the water/ethanol (10:1, v:v) and under a pH of 5.7.

Three-dimensional hydroxylated covalent organic frameworks for solid phase extraction of glucocorticoids in environmental water samples.

It is challenging to achieve the highly sensitive detection of glucocorticoids at ultratrace levels because of the abundant hydrophilic groups in their molecules and the complexity of environmental water sample matrices. Here, a highly crystalline three-dimensional hydroxylated covalent organic frameworks (denoted by COF-301) with tetra(4-anilyl)methane (TAM) and 2,5-dihydroxyterephthalaldehyde (DHTA) as building units was constructed and proposed as adsorbent for solid phase extraction (SPE) of glucocorticoids. Theoretical studies were conducted to elucidate the potential adsorption mechanism of glucocorticoids on the COF-301. The COF-301 based SPE combined with liquid chromatography-tandem mass spectrometry provides a promising approach for the preconcentration and determination of glucocorticoids residue in water samples. Good linearity with a correlation coefficient exceeding 0.9988, low limits of detection ranging from 0.024 to 0.075 ng L-1 and relative standard deviations below 6.68% were achieved. The proposed method was successfully applied to analyze glucocorticoids residue in actual water samples, demonstrating the prospects of this method for the determination of trace glucocorticoids.

Dietary vitamins, carotenoids and their sources in relation to age-related macular degeneration risk in China: a population-based case-control study.

Mechanistic studies have suggested that antioxidants have beneficial effects on age-related macular degeneration (AMD). This study aimed to investigate the association between the types and sources of dietary vitamin and carotenoid intakes and AMD risk in China. A matched case-control study of 260 AMD cases and 260 matched controls was performed. The participants were interviewed for dietary information and potential confounders, and comprehensive ophthalmic examinations were performed. Conditional logistic models were used to estimate the odds ratio (OR) and 95 % confidence interval (CI) of specific vitamins and carotenoids and their main sources. When comparing the extreme quartiles, the ORs (95 % CI) were 0·30 (0·10, 0·88) for lutein and 0·28 (0·11, 0·74) for ß-cryptoxanthin. The associations for other dietary vitamin and carotenoid intakes were generally weaker and non-significant. Higher intakes of spinach and egg, which are important sources of lutein, were associated with a reduced odds of AMD. ORs (95% CIs) comparing extreme categories were 0·42 (0·20, 0·88) for spinach and 0·52 (95% CI: 0·27, 0·98) for egg. Participants who were in the highest category of both egg intake and spinach intake had a much greater reduced odds of having AMD (OR: 0·23; 95% CI: 0·08, 0·71) than those in the lowest category of egg intake and spinach intake. In conclusion, a higher intake of lutein and lutein-rich foods was associated with a significantly decreased odds of AMD. These findings provide further evidence of the benefits of lutein and lutein-rich foods in the prevention of AMD.

A wrinkled nanosurface causes accelerated protein unfolding revealing its critical role in nanotoxicity.

Wrinkles are often found to have a strong influence on the properties of nanomaterials and have attracted extensive research interest. However, the consequences of the use of wrinkled nanomaterials in biological systems remain largely unknown. Here, using molecular dynamics simulations, we studied the interactions of a wrinkled graphene with proteins, using the villin headpiece (HP35) as the representative model. Our results clearly revealed that the wrinkle, especially the wrinkle corner, showed stronger binding affinity to HP35 than the planar surface where HP35 experienced accelerated and more severe unfolding. This is because the transverse translocation of the aromatic residues of the protein is highly confined at the wrinkle corner. The movement of other parts of the protein causes unfolding of the protein secondary structure and releases hydrophobic residues to bind to graphene, causing complete denaturation. Further free energy analyses revealed that this is attributed to the stronger binding affinity of residues to the wrinkle corner than to the planar surface. The present findings provide a deeper understanding of the effect of graphene wrinkles on protein stability. This finding may be generalized to other types of biomolecules and may also guide the design of biomedical nanomaterials through surface structural engineering.