Experimental X-ray crystallography, NMR (Nuclear Magnetic Resonance) spectroscopy, dual polarization interferometry, etc. are indeed very powerful tools to determine the 3-Dimensional structure of a protein (including...Experimental X-ray crystallography, NMR (Nuclear Magnetic Resonance) spectroscopy, dual polarization interferometry, etc. are indeed very powerful tools to determine the 3-Dimensional structure of a protein (including the membrane protein);theoretical mathematical and physical computational approaches can also allow us to obtain a description of the protein 3D structure at a submicroscopic level for some unstable, noncrystalline and insoluble proteins. X-ray crystallography finds the X-ray final structure of a protein, which usually need refinements using theoretical protocols in order to produce a better structure. This means theoretical methods are also important in determinations of protein structures. Optimization is always needed in the computer-aided drug design, structure-based drug design, molecular dynamics, and quantum and molecular mechanics. This paper introduces some optimization algorithms used in these research fields and presents a new theoretical computational method—an improved LBFGS Quasi-Newtonian mathematical optimization method—to produce 3D structures of prion AGAAAAGA amyloid fibrils (which are unstable, noncrystalline and insoluble), from the potential energy minimization point of view. Because the NMR or X-ray structure of the hydrophobic region AGAAAAGA of prion proteins has not yet been determined, the model constructed by this paper can be used as a reference for experimental studies on this region, and may be useful in furthering the goals of medicinal chemistry in this field.展开更多
The assessment of nanomechanical properties of a single amyloid fibril in a confined space provides important information for understanding the role of fibrils in a cell microenvironment. In this study, the structure ...The assessment of nanomechanical properties of a single amyloid fibril in a confined space provides important information for understanding the role of fibrils in a cell microenvironment. In this study, the structure and nanomechanical properties of different fibrils formed in water nanofilms on mica surface are carefully investigated by using the new atomic force microscopy imaging mode-peak force quantitative nanomechanics (PF-QNM). We find that two types of fibrils with different morphologies are formed in water nanofilm on mica. The compression elasticities of these two types of fibrils are 3.9±0.9 and 2.5±0.6 GPa, respectively. The remarkable difference is possibly due to the structural discrepancy in two types of fibrils.展开更多
Amyloid fibrils are widely recognized as a cause of serious amyloidosis such as Alzheimer’s disease. Although dissociation of amyloid fibril aggregates is expected to lead to a decrease in the toxicity of the fibrils...Amyloid fibrils are widely recognized as a cause of serious amyloidosis such as Alzheimer’s disease. Although dissociation of amyloid fibril aggregates is expected to lead to a decrease in the toxicity of the fibrils in cells, the fibril structure is robust under physiological conditions. We have irradiated amyloid fibrils with a free-electron laser (FEL) tuned to mid-infrared frequencies to induce dissociation of the aggregates into monomer forms. We have previously succeeded in dissociating fibril structures of a short peptide of the thyroid hormone by tuning the oscillation frequency to the amide I band, but the detailed structural changes of the peptide have not yet been determined at a high spatial resolution. Synchrotron-radiation infrared microscopy (SR-IRM) is a powerful tool for in situ analysis of minute structural changes of various materials, and in this study, the feasibility of SR-IRM for analyzing the microscopic conformational changes of amyloid fibrils after FEL irradiation was investigated. Reflection spectra of the amyloid fibril surface showed that the amide I peaks shifted to higher wave numbers after the FEL irradiation, indicating that the initial β-sheet-rich structure transformed into a mixture of non-ordered and turn-like peptide conformations. This result demonstrates that conformational changes of the fibril structure after the FEL irradiation can be observed at a high spatial resolution using SR-IRM analysis and the FEL irradiation system can be useful for dissociation of amyloid aggregates.展开更多
According to current knowledge on collagen fibril-logenesis, collagen fibrils are formed by a cooperative process involving lateral fusion of small protofibrils. Almost all the experimental research, however, was carr...According to current knowledge on collagen fibril-logenesis, collagen fibrils are formed by a cooperative process involving lateral fusion of small protofibrils. Almost all the experimental research, however, was carried out on tendon collagen, whose fibrils are characterized by approximately straight subfibrils. By contrast, in most tissues the collagen fibril sub-units follow a helical course in which geometrical constraints prevent lateral fusions, thereby implying a different mechanism where collagen fibrils grow by addition of individual microfibrils rather than by lateral fusion of pre-assembled subfibrils. The proc-ess at the origin of these fibrils may provide a simple, automatic explanation for the remarkable uniformity in fibrils size observed in most tissues without re-quiring the intervention of unknown mechanisms of diameter control. Other mechanisms of growth con-trol remain indispensable to terminate the fibril-logenesis process in tendons and ligaments.展开更多
The cornea is a soft tissue located at the front of the eye with the principal function of transmitting and refracting light rays to precisely sense visual information. Corneal shape, refraction, and stromal stiffness...The cornea is a soft tissue located at the front of the eye with the principal function of transmitting and refracting light rays to precisely sense visual information. Corneal shape, refraction, and stromal stiffness are to a large part determined by corneal fibrils, the arrangements of which define the corneal cells and their functional behaviour. However, the modality and alignment of native corneal collagen lamellae are altered in various corneal pathological states such as infection, injury, keratoconus, corneal scar formation, and keratoprosthesis. Furthermore, corneal recuperation after corneal pathological change is dependent on the balance of corneal collagen degradation and contraction. A thorough understanding of the characteristics of corneal collagen is thus necessary to develop viable therapies using the outcome of strategies using engineered corneas. In this review, we discuss the composition and distribution of corneal collagens as well as their degradation and contraction, and address the current status of corneal tissue engineering and the progress of corneal cross-linking.展开更多
in situ Fibril formation of polyamide-6 (PA6) in isotropic polypropylene (iPP) was first fabricated using a slit die extrusion and hot stretching process. Then the prepared materials were subjected to injection mo...in situ Fibril formation of polyamide-6 (PA6) in isotropic polypropylene (iPP) was first fabricated using a slit die extrusion and hot stretching process. Then the prepared materials were subjected to injection molding in the temperature range higher than the melting temperature of iPP but lower than that of PA6. The obtained injection-molded samples were characterized via scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and two-dimensional wide- angle X-ray scattering (2D-WAXS). Mechanical properties were also investigated. The SEM result shows that the optimum fibril formation could be only achieved in the range of 20 wt% to 30 wt% of PA6 content for the studied system. The fibril morphology changes along the sample thickness in the injection-molded bars. The fibril morphology in the skin layer was better than that in the core layer. 2D-WAXS results showed that the orientation of PP decreased with the increase of PA6 content, which indicated that the orientation of PP was confined by PA6 fibrils. Combined consideration of mechanical properties and morphology indicates that only PP/PA6 composites with 20 wt% of PA6 content show better properties because of the better fibril morphology and PP chain orientation.展开更多
In artificial photosynthesis systems,synthetic diiron complexes are popular[FeFe]-hydrogenase mimics,which are attractive for the fabrication of photocatalyst-protein hybrid structures to amplify hydrogen(H2)generatio...In artificial photosynthesis systems,synthetic diiron complexes are popular[FeFe]-hydrogenase mimics,which are attractive for the fabrication of photocatalyst-protein hybrid structures to amplify hydrogen(H2)generation capability.However,constructing a highly bionic and efficient catalytic hybrid system is a major challenge.Notably,we designed an ideal hybrid nanofibrils system that incorporates the crucial components:(1)a[FeFe]-H2ase mimic,which has a three-arm architecture(named triFeFe)for more interaction sites and higher catalytic activity and(2)uniform hybrid nanofibrils as the biological environment in which cysteine-catalyst coordination and the hydrogen-bonding network play a vital role in both catalyst binding and hydrogen evolution reaction activity.The assembled hybrid nanofibrils achieve efficient H2 generation with a turnover number of 2.3×103,outperforming previously reported diiron catalyst-protein hybrid systems.Additionally,the hybrid nanofibrils work with photosynthetic thylakoids to produce H2,without extra photosensitizers or electron shuttle proteins,which advances the bioengineering of living systems for solar-driven biofuel production.展开更多
α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and...α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and highly phospho rylated a-synuclein constitutes the main component of Lewy bodies in the brain,the pathological hallmark of Parkinson s disease.For decades,much attention has been focused on the accumulation of α-synuclein in the brain parenchyma rather than considering Parkinson s disease as a systemic disease.Recent evidence demonstrates that,at least in some patients,the initial α-synuclein pathology originates in the peripheral organs and spreads to the brain.Injection of α-synuclein preformed fibrils into the gastrointestinal tra ct trigge rs the gutto-brain propagation of α-synuclein pathology.However,whether α-synuclein pathology can occur spontaneously in peripheral organs independent of exogenous α-synuclein preformed fibrils or pathological α-synuclein leakage from the central nervous system remains under investigation.In this review,we aimed to summarize the role of peripheral α-synuclein pathology in the pathogenesis of Parkinson’s disease.We also discuss the pathways by which α-synuclein pathology spreads from the body to the brain.展开更多
Polyacrylonitrile (PAN) fiber is an important precursor fiber for high performance carbon fiber.The properties of the final carbon fiber depend strongly on the nature of the PAN fibers.The PAN fibrils were separated s...Polyacrylonitrile (PAN) fiber is an important precursor fiber for high performance carbon fiber.The properties of the final carbon fiber depend strongly on the nature of the PAN fibers.The PAN fibrils were separated successfully from fibers by ultrasonic etching and were systematically investigated by field emission scanning electron microscopy (FESEM) and high resolution transmission electron microscopy (HRTEM).It is found that in certain ultrasonic etching conditions (at 75±2oC for 6 h with a frequency of 40 kHz) the PAN fibers are dissolved in the 95 wt.% aqueous dimethylsulphoxide (DMSO) solution;the fibrils consisting of numerous periodic lamellae with thickness of 30-45 nm and perpendicular to the fiber axis are separated in the 90 wt.% aqueous DMSO solution;and the fibrils with smooth surface exfoliated from the PAN fibers are obtained in the 70-90 wt.% aqueous DMSO solutions.Inner periodical structure of fibrils was observed in HRTEM,which indicates that there are different densities and two phases in fibrils.The PAN fibers are dissolved layer by layer with increasing ultrasonic etching time.The fiber surface experiences ultrasonic cleaning,selective etching,excessive etching and dissolution,and then the sublayer experiences the same process.There are numerous periodic lamellae in fibrils of nascent fibers.This means that the fibrils with lamellae are formed by orientation and crystallization in shearing field of spinning pipe and drawing stress field of coagulation bath.展开更多
Collagen,one of the major components in the mammalian connective tissues,plays an essential role in many vital physiological processes.Many common diseases,such as fibrosis,overuse injuries,and bone fracture,are assoc...Collagen,one of the major components in the mammalian connective tissues,plays an essential role in many vital physiological processes.Many common diseases,such as fibrosis,overuse injuries,and bone fracture,are associated with collagen arrangement defects.However,the underlying mechanism of collagen arrangement defects remains elusive.In this study,we applied infrared scattering-type scanning near-field optical microscopy to study collagen fibrils’structural properties.Experimentally,we observed two types of collagen fibrils’arrangement with different periodic characteristics.A crystal sliding model was employed to explain this observation qualitatively.Our results suggest that the collagen dislocation propagates in collagen fibrils,which may shed light on many collagen diseases’pathogenesis.These findings help to understand the regulation mechanism of hierarchical biological structure.展开更多
The modification of amyloid fibrils cytotoxicity through exogenous nanomaterials is crucial to understand the processes controlling the role of protein aggregation in the related diseases.The influence of nanoparticle...The modification of amyloid fibrils cytotoxicity through exogenous nanomaterials is crucial to understand the processes controlling the role of protein aggregation in the related diseases.The influence of nanoparticles on amyloid stability yields great interest due to the small size and high surface area-to-volume ratio of nanoparticles.Various physico-chemical parameters play a role in the interaction of proteins and nanoparticles in solution,thus influencing the disaggregation of preformed fibrils.We have examined the influence of two kinds of metallic nanoparticles on lysozyme amyloid fibrils using a multi-technique approach and focalized their impact on cytotoxicity on human neuroblastoma cells(SH-SY5Y).In particular,fluorescence,infrared and circular dichroism spectroscopies,optical and atomic force microscopy experiments have been carried out;the results are analyzed to rationalize the effects of these complexes on neural cell viability.It is remarkable,that the fibrils in the presence of AuNPs,unlike fibrils alone or with AgNPs,do not generate a significant cytotoxic effect even at high concentration and an amyloid degradation effect is visible.展开更多
The formation of amyloid plaques usually occurs in the early-stage of Alzheimer’s disease(AD).Stimulated emission depletion(STED)imaging provided a powerful tool for visualizing amyloid structures on the nanometer sc...The formation of amyloid plaques usually occurs in the early-stage of Alzheimer’s disease(AD).Stimulated emission depletion(STED)imaging provided a powerful tool for visualizing amyloid structures on the nanometer scale.However,many commercial probes adopted in detecting amyloid fibrils are inapplicable to STED imaging,owing to their unmatched absorption and emission wavelengths,small Stokes'shift,easy photo-bleaching,etc.Herein,we demonstrated a polarity-activated STED probe based on an intramolecular charge transfer donor(D)-7c-acceptor(A)compound.The electron-rich carbazole group and the electron-poor pyridinium bromide group,linked by 7i-conjugated thiophen-bridge,ensure strong near infrared(NIR)emission with a Stokes'shift larger than 200 nm.The tiny change in polarity before and after binding with amyloid plaques leads to a transition from weakly emission charge-transfer(CT)state(Φ<0.04)to highly emissive locally-excited(LE)state(Φ=0.57),giving rise to a fluorescence Turn-On probe.Together with large Stokes'shift,good photostability and high depletion efficiency,the super-resolution imaging of the formation and morphology of amyloid fibrils in vitro based on this probe was realized with a lateral spatial resolution better than 33 nm at an extremely low depletion power.Moreover,the ex-vivo super-resolution imaging of(E)-1-butyl-4(2-(5-(9-ethyl-9Hcarbazol-3-yl)thiophen-2-yl)vinyl)pyridinium bromide(CTPB)probe in Aβ plaques in the brain slices of a Tg mouse was demonstrated.This research provides a demonstration of the super resolution imaging probe of amyloid fibrils based on polarity-response mechanism,providing a new approach to the development of future amyloid probes.展开更多
BACKGROUND Triglyceride-glucose(TyG)index values are a new surrogate marker for insulin resistance.This study aimed to explore the relationship between cumulative TyG index values and atrial fibrillation(AF)recurrence...BACKGROUND Triglyceride-glucose(TyG)index values are a new surrogate marker for insulin resistance.This study aimed to explore the relationship between cumulative TyG index values and atrial fibrillation(AF)recurrence after radiofrequency catheter ablation(RFCA).METHODS A total of 576 patients with AF who underwent RFCA at the Second Affiliated Hospital of Xi'an Jiaotong University were included in this study.The participants were grouped based on cumulative TyG index values tertiles within 3 months after ablation.Cox regression and restricted cubic spline analyses were used to determine the relationship between cumulative TyG index values and AF recurrence.The predictive value of all risk factors was assessed by receiver operating curve analysis.RESULTS There were 375 patients completed the study(age:63.23±10.73 years,64.27%male).The risk of AF recurrence increased with increasing cumulative TyG index values tertiles.After adjusting for potential confounders,patients in the medium cumulative TyG index group[hazard ratio(HR)=4.949,95%CI:1.778–13.778,P=0.002]and the high cumulative TyG index group(HR=8.716,95%CI:3.371–22.536,P<0.001)had a higher risk of AF recurrence than those in the low cumulative TyG index group.The restricted cubic spline regression model also showed an increased risk of AF recurrence with increasing cumulative TyG index values.When considering cumulative TyG index values,left atrial diameter,and lactate dehydrogenase levels as a comprehensive factor,the model could effectively predict AF recurrence after RFCA[area under the curve(AUC)=0.847,95%CI:0.797–0.897,P<0.001].CONCLUSIONS Cumulative TyG index values were a risk factor for AF recurrence after RFCA.Monitoring longitudinal TyG index values may assist with optimized for risk stratification and outcome prediction for AF recurrence.展开更多
The application of deep learning techniques in the medical field,specifically for Atrial Fibrillation(AFib)detection through Electrocardiogram(ECG)signals,has witnessed significant interest.Accurate and timely diagnos...The application of deep learning techniques in the medical field,specifically for Atrial Fibrillation(AFib)detection through Electrocardiogram(ECG)signals,has witnessed significant interest.Accurate and timely diagnosis increases the patient’s chances of recovery.However,issues like overfitting and inconsistent accuracy across datasets remain challenges.In a quest to address these challenges,a study presents two prominent deep learning architectures,ResNet-50 and DenseNet-121,to evaluate their effectiveness in AFib detection.The aim was to create a robust detection mechanism that consistently performs well.Metrics such as loss,accuracy,precision,sensitivity,and Area Under the Curve(AUC)were utilized for evaluation.The findings revealed that ResNet-50 surpassed DenseNet-121 in all evaluated categories.It demonstrated lower loss rate 0.0315 and 0.0305 superior accuracy of 98.77%and 98.88%,precision of 98.78%and 98.89%and sensitivity of 98.76%and 98.86%for training and validation,hinting at its advanced capability for AFib detection.These insights offer a substantial contribution to the existing literature on deep learning applications for AFib detection from ECG signals.The comparative performance data assists future researchers in selecting suitable deep-learning architectures for AFib detection.Moreover,the outcomes of this study are anticipated to stimulate the development of more advanced and efficient ECG-based AFib detection methodologies,for more accurate and early detection of AFib,thereby fostering improved patient care and outcomes.展开更多
Atrial fibrillation(AF)is the most common cardiac arrhythmia.Many medical conditions,including hypertension,diabetes,obesity,sleep apnea,and heart failure(HF),increase the risk for AF.Cardiomyocytes have unique metabo...Atrial fibrillation(AF)is the most common cardiac arrhythmia.Many medical conditions,including hypertension,diabetes,obesity,sleep apnea,and heart failure(HF),increase the risk for AF.Cardiomyocytes have unique metabolic characteristics to maintain adenosine triphosphate production.Significant changes occur in myocardial metabolism in AF.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)have been used to control blood glucose fluctuations and weight in the treatment of type 2 diabetes mellitus(T2DM)and obesity.GLP-1RAs have also been shown to reduce oxidative stress,inflammation,autonomic nervous system modulation,and mitochondrial function.This article reviews the changes in metabolic characteristics in cardiomyocytes in AF.Although the clinical trial outcomes are unsatisfactory,the findings demonstrate that GLP-1 RAs can improve myocardial metabolism in the presence of various risk factors,lowering the incidence of AF.展开更多
BACKGROUND Bradycardia-induced cardiomyopathy(BIC),which is a disease resulting from bradycardia,is characterized by cardiac chamber enlargement and diminished cardiac function.The correction of bradycardia can allow ...BACKGROUND Bradycardia-induced cardiomyopathy(BIC),which is a disease resulting from bradycardia,is characterized by cardiac chamber enlargement and diminished cardiac function.The correction of bradycardia can allow for significant improvements in both cardiac function and structure;however,this disease has been infrequently documented.In this case,we conducted a longitudinal followup of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention.CASE SUMMARY A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7.Since she had no obvious symptoms,she did not receive any treatment to improve her bradycardia during the 42-year follow-up,except for the implantation of a temporary pacemaker during labor induction surgery.As time progressed,the patient's heart gradually expanded due to her low ventricular rate,and she was diagnosed with BIC.In 2014,the patient developed atrial fibrillation,her ventricular rate gradually increased,and her heart shape gradually returned to normal.This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years,introduces another possible outcome of BIC,and emphasizes the importance of early intervention in treating BIC.CONCLUSION BIC can induce atrial fibrillation,causing an increased ventricular rate and leading to positive cardiac remodeling.展开更多
BACKGROUND Patients with tetralogy of Fallot(TOF)often have arrhythmias,commonly being atrial fibrillation(AF).Radiofrequency ablation is an effective treatment for AF and does not usually cause severe postoperative h...BACKGROUND Patients with tetralogy of Fallot(TOF)often have arrhythmias,commonly being atrial fibrillation(AF).Radiofrequency ablation is an effective treatment for AF and does not usually cause severe postoperative hypoxemia,but the risk of complications may increase in patients with conditions such as TOF.CASE SUMMARY We report a young male patient with a history of TOF repair who developed severe hypoxemia after radiofrequency ablation for AF and was ultimately confirmed to have a new right-to-left shunt.The patient subsequently underwent atrial septal occlusion and eventually recovered.CONCLUSION Radiofrequency ablation may cause iatrogenic atrial septal injury;thus possible complications should be predicted in order to ensure successful treatment and patient safety.展开更多
In 2023,Baishideng Publishing Group(Baishideng)routinely published 47 openaccess journals,including 46 English-language journals and 1 Chinese-language journal.Our successes were accomplished through the collective de...In 2023,Baishideng Publishing Group(Baishideng)routinely published 47 openaccess journals,including 46 English-language journals and 1 Chinese-language journal.Our successes were accomplished through the collective dedicated efforts of Baishideng staffs,Editorial Board Members,and Peer Reviewers.Among these 47 Baishideng journals,7 are included in the Science Citation Index Expanded(SCIE)and 6 in the Emerging Sources Citation Index(ESCI).With the support of Baishideng authors,company staffs,Editorial Board Members,and Peer Reviewers,the publication work of 2023 is about to be successfully completed.This editorial summarizes the 2023 activities and accomplishments of the 13 SCIEand ESCI-indexed Baishideng journals,outlines the Baishideng publishing policy changes and additions made this year,and highlights the unique advantages of Baishideng journals.展开更多
The use of anticoagulation therapy could prove to be controversial when trying to balance ischemic stroke and intracranial bleeding risks in patients with concurrent cerebral amyloid angiopathy(CAA)and atrial fibrilla...The use of anticoagulation therapy could prove to be controversial when trying to balance ischemic stroke and intracranial bleeding risks in patients with concurrent cerebral amyloid angiopathy(CAA)and atrial fibrillation(AF).In fact,CAA is an age-related cerebral vasculopathy that predisposes patients to intracerebral hemorrhage.Nevertheless,many AF patients require oral systemic dose-adjusted warfarin,direct oral anticoagulants(such as factor Xa inhibitors)or direct thrombin inhibitors to control often associated with cardioembolic stroke risk.The prevalence of both CAA and AF is expected to rise,due to the aging of the population.This clinical dilemma is becoming increasingly common.In patients with coexisting AF and CAA,the risks/benefits profile of anticoagulant therapy must be assessed for each patient individually due to the lack of a clear-cut consensus with regard to its risks in scientific literature.This review aims to provide an overview of the management of patients with concomitant AF and CAA and proposes the implementation of a risk-based decision-making algorithm.展开更多
Ibrutinib,a targeted therapy for B-cell malignancies,has shown remarkable efficacy in treating various hematologic cancers.However,its clinical use has raised concerns regarding cardiovascular complications,notably at...Ibrutinib,a targeted therapy for B-cell malignancies,has shown remarkable efficacy in treating various hematologic cancers.However,its clinical use has raised concerns regarding cardiovascular complications,notably atrial fibrillation(AF).This comprehensive review critically evaluates the association between ibrutinib and AF by examining incidence,risk factors,mechanistic links,and management strategies.Through an extensive analysis of original research articles,this review elucidates the complex interplay between ibrutinib’s therapeutic benefits and cardiovascular risks.Moreover,it highlights the need for personalized treatment approaches,vigilant monitoring,and interdisciplinary collaboration to optimize patient outcomes and safety in the context of ibrutinib therapy.The review provides a valuable resource for healthcare professionals aiming to navigate the intricacies of ibrutinib’s therapeutic landscape while prioritizing patient well-being.展开更多
文摘Experimental X-ray crystallography, NMR (Nuclear Magnetic Resonance) spectroscopy, dual polarization interferometry, etc. are indeed very powerful tools to determine the 3-Dimensional structure of a protein (including the membrane protein);theoretical mathematical and physical computational approaches can also allow us to obtain a description of the protein 3D structure at a submicroscopic level for some unstable, noncrystalline and insoluble proteins. X-ray crystallography finds the X-ray final structure of a protein, which usually need refinements using theoretical protocols in order to produce a better structure. This means theoretical methods are also important in determinations of protein structures. Optimization is always needed in the computer-aided drug design, structure-based drug design, molecular dynamics, and quantum and molecular mechanics. This paper introduces some optimization algorithms used in these research fields and presents a new theoretical computational method—an improved LBFGS Quasi-Newtonian mathematical optimization method—to produce 3D structures of prion AGAAAAGA amyloid fibrils (which are unstable, noncrystalline and insoluble), from the potential energy minimization point of view. Because the NMR or X-ray structure of the hydrophobic region AGAAAAGA of prion proteins has not yet been determined, the model constructed by this paper can be used as a reference for experimental studies on this region, and may be useful in furthering the goals of medicinal chemistry in this field.
基金Supported by the National Natural Science Foundation of China under Grant No 11474173the Natural Science Foundation of Zhejiang Province under Grant Nos LY14A040006 and LQ14F040002+1 种基金the Ningbo Natural Science Foundation under Grant Nos2014A610202 and 2014A610149the K.C.Wong Magna Fund in Ningbo University
文摘The assessment of nanomechanical properties of a single amyloid fibril in a confined space provides important information for understanding the role of fibrils in a cell microenvironment. In this study, the structure and nanomechanical properties of different fibrils formed in water nanofilms on mica surface are carefully investigated by using the new atomic force microscopy imaging mode-peak force quantitative nanomechanics (PF-QNM). We find that two types of fibrils with different morphologies are formed in water nanofilm on mica. The compression elasticities of these two types of fibrils are 3.9±0.9 and 2.5±0.6 GPa, respectively. The remarkable difference is possibly due to the structural discrepancy in two types of fibrils.
文摘Amyloid fibrils are widely recognized as a cause of serious amyloidosis such as Alzheimer’s disease. Although dissociation of amyloid fibril aggregates is expected to lead to a decrease in the toxicity of the fibrils in cells, the fibril structure is robust under physiological conditions. We have irradiated amyloid fibrils with a free-electron laser (FEL) tuned to mid-infrared frequencies to induce dissociation of the aggregates into monomer forms. We have previously succeeded in dissociating fibril structures of a short peptide of the thyroid hormone by tuning the oscillation frequency to the amide I band, but the detailed structural changes of the peptide have not yet been determined at a high spatial resolution. Synchrotron-radiation infrared microscopy (SR-IRM) is a powerful tool for in situ analysis of minute structural changes of various materials, and in this study, the feasibility of SR-IRM for analyzing the microscopic conformational changes of amyloid fibrils after FEL irradiation was investigated. Reflection spectra of the amyloid fibril surface showed that the amide I peaks shifted to higher wave numbers after the FEL irradiation, indicating that the initial β-sheet-rich structure transformed into a mixture of non-ordered and turn-like peptide conformations. This result demonstrates that conformational changes of the fibril structure after the FEL irradiation can be observed at a high spatial resolution using SR-IRM analysis and the FEL irradiation system can be useful for dissociation of amyloid aggregates.
文摘According to current knowledge on collagen fibril-logenesis, collagen fibrils are formed by a cooperative process involving lateral fusion of small protofibrils. Almost all the experimental research, however, was carried out on tendon collagen, whose fibrils are characterized by approximately straight subfibrils. By contrast, in most tissues the collagen fibril sub-units follow a helical course in which geometrical constraints prevent lateral fusions, thereby implying a different mechanism where collagen fibrils grow by addition of individual microfibrils rather than by lateral fusion of pre-assembled subfibrils. The proc-ess at the origin of these fibrils may provide a simple, automatic explanation for the remarkable uniformity in fibrils size observed in most tissues without re-quiring the intervention of unknown mechanisms of diameter control. Other mechanisms of growth con-trol remain indispensable to terminate the fibril-logenesis process in tendons and ligaments.
基金Supported by Science and Technology Department of Jilin Province Research Fund(No.20160101011JC)Development and Reform Commission of Jilin Province(No.2016C044-1)
文摘The cornea is a soft tissue located at the front of the eye with the principal function of transmitting and refracting light rays to precisely sense visual information. Corneal shape, refraction, and stromal stiffness are to a large part determined by corneal fibrils, the arrangements of which define the corneal cells and their functional behaviour. However, the modality and alignment of native corneal collagen lamellae are altered in various corneal pathological states such as infection, injury, keratoconus, corneal scar formation, and keratoprosthesis. Furthermore, corneal recuperation after corneal pathological change is dependent on the balance of corneal collagen degradation and contraction. A thorough understanding of the characteristics of corneal collagen is thus necessary to develop viable therapies using the outcome of strategies using engineered corneas. In this review, we discuss the composition and distribution of corneal collagens as well as their degradation and contraction, and address the current status of corneal tissue engineering and the progress of corneal cross-linking.
基金This work was supported by the National Natural Science Foundation of China(Nos.50533050,20490220,20404008,and50373030)This work was subsidized by the Special Funds for Major State Basic Research Projects of China(No.2003CB615600)by the Ministry of Education of China(No.20050610030).
文摘in situ Fibril formation of polyamide-6 (PA6) in isotropic polypropylene (iPP) was first fabricated using a slit die extrusion and hot stretching process. Then the prepared materials were subjected to injection molding in the temperature range higher than the melting temperature of iPP but lower than that of PA6. The obtained injection-molded samples were characterized via scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and two-dimensional wide- angle X-ray scattering (2D-WAXS). Mechanical properties were also investigated. The SEM result shows that the optimum fibril formation could be only achieved in the range of 20 wt% to 30 wt% of PA6 content for the studied system. The fibril morphology changes along the sample thickness in the injection-molded bars. The fibril morphology in the skin layer was better than that in the core layer. 2D-WAXS results showed that the orientation of PP decreased with the increase of PA6 content, which indicated that the orientation of PP was confined by PA6 fibrils. Combined consideration of mechanical properties and morphology indicates that only PP/PA6 composites with 20 wt% of PA6 content show better properties because of the better fibril morphology and PP chain orientation.
基金the National Natural Science Foundation of China(grant nos.22077065,22021002,and 22277054)the National Key R&D Program of China(grant no.2018YFE0200700)+1 种基金the China Postdoctoral Science Foundation(grant no.2021M703264)the Beijing National Laboratory for Molecular Sciences for financial support.
文摘In artificial photosynthesis systems,synthetic diiron complexes are popular[FeFe]-hydrogenase mimics,which are attractive for the fabrication of photocatalyst-protein hybrid structures to amplify hydrogen(H2)generation capability.However,constructing a highly bionic and efficient catalytic hybrid system is a major challenge.Notably,we designed an ideal hybrid nanofibrils system that incorporates the crucial components:(1)a[FeFe]-H2ase mimic,which has a three-arm architecture(named triFeFe)for more interaction sites and higher catalytic activity and(2)uniform hybrid nanofibrils as the biological environment in which cysteine-catalyst coordination and the hydrogen-bonding network play a vital role in both catalyst binding and hydrogen evolution reaction activity.The assembled hybrid nanofibrils achieve efficient H2 generation with a turnover number of 2.3×103,outperforming previously reported diiron catalyst-protein hybrid systems.Additionally,the hybrid nanofibrils work with photosynthetic thylakoids to produce H2,without extra photosensitizers or electron shuttle proteins,which advances the bioengineering of living systems for solar-driven biofuel production.
基金supported by the National Natural Science Foundation of China,Nos.82271447,81771382the National Key Research and Development Program of China,No.2019 YFE0115900the"New 20 Terms of Universities in Jinan,No.202228022 (all to ZZ)。
文摘α-Synuclein is a protein that mainly exists in the presynaptic terminals.Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases,including Parkinson’s disease.Aggregated and highly phospho rylated a-synuclein constitutes the main component of Lewy bodies in the brain,the pathological hallmark of Parkinson s disease.For decades,much attention has been focused on the accumulation of α-synuclein in the brain parenchyma rather than considering Parkinson s disease as a systemic disease.Recent evidence demonstrates that,at least in some patients,the initial α-synuclein pathology originates in the peripheral organs and spreads to the brain.Injection of α-synuclein preformed fibrils into the gastrointestinal tra ct trigge rs the gutto-brain propagation of α-synuclein pathology.However,whether α-synuclein pathology can occur spontaneously in peripheral organs independent of exogenous α-synuclein preformed fibrils or pathological α-synuclein leakage from the central nervous system remains under investigation.In this review,we aimed to summarize the role of peripheral α-synuclein pathology in the pathogenesis of Parkinson’s disease.We also discuss the pathways by which α-synuclein pathology spreads from the body to the brain.
基金supported by the National Natural Science Foundation of China (Grant No.50673052)the Major State Basic Research Development Program of China (973 Program) (Grant No.2006CB605314)the Provincial Natural Science Foundation of Shandong Province (Grant No.Z2008F02)
文摘Polyacrylonitrile (PAN) fiber is an important precursor fiber for high performance carbon fiber.The properties of the final carbon fiber depend strongly on the nature of the PAN fibers.The PAN fibrils were separated successfully from fibers by ultrasonic etching and were systematically investigated by field emission scanning electron microscopy (FESEM) and high resolution transmission electron microscopy (HRTEM).It is found that in certain ultrasonic etching conditions (at 75±2oC for 6 h with a frequency of 40 kHz) the PAN fibers are dissolved in the 95 wt.% aqueous dimethylsulphoxide (DMSO) solution;the fibrils consisting of numerous periodic lamellae with thickness of 30-45 nm and perpendicular to the fiber axis are separated in the 90 wt.% aqueous DMSO solution;and the fibrils with smooth surface exfoliated from the PAN fibers are obtained in the 70-90 wt.% aqueous DMSO solutions.Inner periodical structure of fibrils was observed in HRTEM,which indicates that there are different densities and two phases in fibrils.The PAN fibers are dissolved layer by layer with increasing ultrasonic etching time.The fiber surface experiences ultrasonic cleaning,selective etching,excessive etching and dissolution,and then the sublayer experiences the same process.There are numerous periodic lamellae in fibrils of nascent fibers.This means that the fibrils with lamellae are formed by orientation and crystallization in shearing field of spinning pipe and drawing stress field of coagulation bath.
基金the National Key Research and Development Program of China(No.2016YFA0203500)the National Natural Science Foundation of China(No.11874407)Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB 30000000)。
文摘Collagen,one of the major components in the mammalian connective tissues,plays an essential role in many vital physiological processes.Many common diseases,such as fibrosis,overuse injuries,and bone fracture,are associated with collagen arrangement defects.However,the underlying mechanism of collagen arrangement defects remains elusive.In this study,we applied infrared scattering-type scanning near-field optical microscopy to study collagen fibrils’structural properties.Experimentally,we observed two types of collagen fibrils’arrangement with different periodic characteristics.A crystal sliding model was employed to explain this observation qualitatively.Our results suggest that the collagen dislocation propagates in collagen fibrils,which may shed light on many collagen diseases’pathogenesis.These findings help to understand the regulation mechanism of hierarchical biological structure.
基金This work was partially supported by Slovak grand agency VEGA 2/0145/17,APW-18-0284,Italian flagship NANOMAX,N-CHEM,Ministery o f Education,University and Research(PRIN grant 20173L7W8K).Microscopy was carried out at the SPM@ISMN facility.
文摘The modification of amyloid fibrils cytotoxicity through exogenous nanomaterials is crucial to understand the processes controlling the role of protein aggregation in the related diseases.The influence of nanoparticles on amyloid stability yields great interest due to the small size and high surface area-to-volume ratio of nanoparticles.Various physico-chemical parameters play a role in the interaction of proteins and nanoparticles in solution,thus influencing the disaggregation of preformed fibrils.We have examined the influence of two kinds of metallic nanoparticles on lysozyme amyloid fibrils using a multi-technique approach and focalized their impact on cytotoxicity on human neuroblastoma cells(SH-SY5Y).In particular,fluorescence,infrared and circular dichroism spectroscopies,optical and atomic force microscopy experiments have been carried out;the results are analyzed to rationalize the effects of these complexes on neural cell viability.It is remarkable,that the fibrils in the presence of AuNPs,unlike fibrils alone or with AgNPs,do not generate a significant cytotoxic effect even at high concentration and an amyloid degradation effect is visible.
基金This work was supported by the Ministry of Science and Technology of China(Nos.2017YFA0204503 and 2018YFA0704805)the National Natural Science Foundation of China(Nos.21503139,21573251,21673144,21873065,21833005,81970425 and 21790364)+5 种基金the Beijing Natural Science Foundation of China(No.2192011)the High-level Teachers in Bejing Municipal Universities in the Period of 13^th Five-year Plan(Nos.IDHT20180517 and CIT&TCD20180331)the Open Fund of the State Key Laboratory of Integrated Optoelectronics(No.IOSKL2019KF01)Capacity Building for Sci-Tech Innovation-Fundamental Scientific Research Funds(Nos.025185305000/210,009/19530050162 and 19530012018)Youth Innovative Research Team of Capital Normal University(No,009/19530050148)Beijing Advanced Innovation Center for Imaging Theory and Technology(No.009/19530011009).
文摘The formation of amyloid plaques usually occurs in the early-stage of Alzheimer’s disease(AD).Stimulated emission depletion(STED)imaging provided a powerful tool for visualizing amyloid structures on the nanometer scale.However,many commercial probes adopted in detecting amyloid fibrils are inapplicable to STED imaging,owing to their unmatched absorption and emission wavelengths,small Stokes'shift,easy photo-bleaching,etc.Herein,we demonstrated a polarity-activated STED probe based on an intramolecular charge transfer donor(D)-7c-acceptor(A)compound.The electron-rich carbazole group and the electron-poor pyridinium bromide group,linked by 7i-conjugated thiophen-bridge,ensure strong near infrared(NIR)emission with a Stokes'shift larger than 200 nm.The tiny change in polarity before and after binding with amyloid plaques leads to a transition from weakly emission charge-transfer(CT)state(Φ<0.04)to highly emissive locally-excited(LE)state(Φ=0.57),giving rise to a fluorescence Turn-On probe.Together with large Stokes'shift,good photostability and high depletion efficiency,the super-resolution imaging of the formation and morphology of amyloid fibrils in vitro based on this probe was realized with a lateral spatial resolution better than 33 nm at an extremely low depletion power.Moreover,the ex-vivo super-resolution imaging of(E)-1-butyl-4(2-(5-(9-ethyl-9Hcarbazol-3-yl)thiophen-2-yl)vinyl)pyridinium bromide(CTPB)probe in Aβ plaques in the brain slices of a Tg mouse was demonstrated.This research provides a demonstration of the super resolution imaging probe of amyloid fibrils based on polarity-response mechanism,providing a new approach to the development of future amyloid probes.
基金supported by the National Natural Science Foundation of China(No.82360608)the Free Exploration Project of the Second Affiliated Hospital of Xi’an Jiaotong University(2020YJ153)。
文摘BACKGROUND Triglyceride-glucose(TyG)index values are a new surrogate marker for insulin resistance.This study aimed to explore the relationship between cumulative TyG index values and atrial fibrillation(AF)recurrence after radiofrequency catheter ablation(RFCA).METHODS A total of 576 patients with AF who underwent RFCA at the Second Affiliated Hospital of Xi'an Jiaotong University were included in this study.The participants were grouped based on cumulative TyG index values tertiles within 3 months after ablation.Cox regression and restricted cubic spline analyses were used to determine the relationship between cumulative TyG index values and AF recurrence.The predictive value of all risk factors was assessed by receiver operating curve analysis.RESULTS There were 375 patients completed the study(age:63.23±10.73 years,64.27%male).The risk of AF recurrence increased with increasing cumulative TyG index values tertiles.After adjusting for potential confounders,patients in the medium cumulative TyG index group[hazard ratio(HR)=4.949,95%CI:1.778–13.778,P=0.002]and the high cumulative TyG index group(HR=8.716,95%CI:3.371–22.536,P<0.001)had a higher risk of AF recurrence than those in the low cumulative TyG index group.The restricted cubic spline regression model also showed an increased risk of AF recurrence with increasing cumulative TyG index values.When considering cumulative TyG index values,left atrial diameter,and lactate dehydrogenase levels as a comprehensive factor,the model could effectively predict AF recurrence after RFCA[area under the curve(AUC)=0.847,95%CI:0.797–0.897,P<0.001].CONCLUSIONS Cumulative TyG index values were a risk factor for AF recurrence after RFCA.Monitoring longitudinal TyG index values may assist with optimized for risk stratification and outcome prediction for AF recurrence.
文摘The application of deep learning techniques in the medical field,specifically for Atrial Fibrillation(AFib)detection through Electrocardiogram(ECG)signals,has witnessed significant interest.Accurate and timely diagnosis increases the patient’s chances of recovery.However,issues like overfitting and inconsistent accuracy across datasets remain challenges.In a quest to address these challenges,a study presents two prominent deep learning architectures,ResNet-50 and DenseNet-121,to evaluate their effectiveness in AFib detection.The aim was to create a robust detection mechanism that consistently performs well.Metrics such as loss,accuracy,precision,sensitivity,and Area Under the Curve(AUC)were utilized for evaluation.The findings revealed that ResNet-50 surpassed DenseNet-121 in all evaluated categories.It demonstrated lower loss rate 0.0315 and 0.0305 superior accuracy of 98.77%and 98.88%,precision of 98.78%and 98.89%and sensitivity of 98.76%and 98.86%for training and validation,hinting at its advanced capability for AFib detection.These insights offer a substantial contribution to the existing literature on deep learning applications for AFib detection from ECG signals.The comparative performance data assists future researchers in selecting suitable deep-learning architectures for AFib detection.Moreover,the outcomes of this study are anticipated to stimulate the development of more advanced and efficient ECG-based AFib detection methodologies,for more accurate and early detection of AFib,thereby fostering improved patient care and outcomes.
基金supported by the Clinical Medical Technology Innovation Project of Hunan Science and Technology Agency,China(Project No.:2021SK53519).
文摘Atrial fibrillation(AF)is the most common cardiac arrhythmia.Many medical conditions,including hypertension,diabetes,obesity,sleep apnea,and heart failure(HF),increase the risk for AF.Cardiomyocytes have unique metabolic characteristics to maintain adenosine triphosphate production.Significant changes occur in myocardial metabolism in AF.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)have been used to control blood glucose fluctuations and weight in the treatment of type 2 diabetes mellitus(T2DM)and obesity.GLP-1RAs have also been shown to reduce oxidative stress,inflammation,autonomic nervous system modulation,and mitochondrial function.This article reviews the changes in metabolic characteristics in cardiomyocytes in AF.Although the clinical trial outcomes are unsatisfactory,the findings demonstrate that GLP-1 RAs can improve myocardial metabolism in the presence of various risk factors,lowering the incidence of AF.
基金Supported by National Natural Science Foundation of China,No.81970241Tianfu Qingcheng Project-Tianfu Science and Technology Elite,No.1358.
文摘BACKGROUND Bradycardia-induced cardiomyopathy(BIC),which is a disease resulting from bradycardia,is characterized by cardiac chamber enlargement and diminished cardiac function.The correction of bradycardia can allow for significant improvements in both cardiac function and structure;however,this disease has been infrequently documented.In this case,we conducted a longitudinal followup of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention.CASE SUMMARY A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7.Since she had no obvious symptoms,she did not receive any treatment to improve her bradycardia during the 42-year follow-up,except for the implantation of a temporary pacemaker during labor induction surgery.As time progressed,the patient's heart gradually expanded due to her low ventricular rate,and she was diagnosed with BIC.In 2014,the patient developed atrial fibrillation,her ventricular rate gradually increased,and her heart shape gradually returned to normal.This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years,introduces another possible outcome of BIC,and emphasizes the importance of early intervention in treating BIC.CONCLUSION BIC can induce atrial fibrillation,causing an increased ventricular rate and leading to positive cardiac remodeling.
文摘BACKGROUND Patients with tetralogy of Fallot(TOF)often have arrhythmias,commonly being atrial fibrillation(AF).Radiofrequency ablation is an effective treatment for AF and does not usually cause severe postoperative hypoxemia,but the risk of complications may increase in patients with conditions such as TOF.CASE SUMMARY We report a young male patient with a history of TOF repair who developed severe hypoxemia after radiofrequency ablation for AF and was ultimately confirmed to have a new right-to-left shunt.The patient subsequently underwent atrial septal occlusion and eventually recovered.CONCLUSION Radiofrequency ablation may cause iatrogenic atrial septal injury;thus possible complications should be predicted in order to ensure successful treatment and patient safety.
文摘In 2023,Baishideng Publishing Group(Baishideng)routinely published 47 openaccess journals,including 46 English-language journals and 1 Chinese-language journal.Our successes were accomplished through the collective dedicated efforts of Baishideng staffs,Editorial Board Members,and Peer Reviewers.Among these 47 Baishideng journals,7 are included in the Science Citation Index Expanded(SCIE)and 6 in the Emerging Sources Citation Index(ESCI).With the support of Baishideng authors,company staffs,Editorial Board Members,and Peer Reviewers,the publication work of 2023 is about to be successfully completed.This editorial summarizes the 2023 activities and accomplishments of the 13 SCIEand ESCI-indexed Baishideng journals,outlines the Baishideng publishing policy changes and additions made this year,and highlights the unique advantages of Baishideng journals.
文摘The use of anticoagulation therapy could prove to be controversial when trying to balance ischemic stroke and intracranial bleeding risks in patients with concurrent cerebral amyloid angiopathy(CAA)and atrial fibrillation(AF).In fact,CAA is an age-related cerebral vasculopathy that predisposes patients to intracerebral hemorrhage.Nevertheless,many AF patients require oral systemic dose-adjusted warfarin,direct oral anticoagulants(such as factor Xa inhibitors)or direct thrombin inhibitors to control often associated with cardioembolic stroke risk.The prevalence of both CAA and AF is expected to rise,due to the aging of the population.This clinical dilemma is becoming increasingly common.In patients with coexisting AF and CAA,the risks/benefits profile of anticoagulant therapy must be assessed for each patient individually due to the lack of a clear-cut consensus with regard to its risks in scientific literature.This review aims to provide an overview of the management of patients with concomitant AF and CAA and proposes the implementation of a risk-based decision-making algorithm.
文摘Ibrutinib,a targeted therapy for B-cell malignancies,has shown remarkable efficacy in treating various hematologic cancers.However,its clinical use has raised concerns regarding cardiovascular complications,notably atrial fibrillation(AF).This comprehensive review critically evaluates the association between ibrutinib and AF by examining incidence,risk factors,mechanistic links,and management strategies.Through an extensive analysis of original research articles,this review elucidates the complex interplay between ibrutinib’s therapeutic benefits and cardiovascular risks.Moreover,it highlights the need for personalized treatment approaches,vigilant monitoring,and interdisciplinary collaboration to optimize patient outcomes and safety in the context of ibrutinib therapy.The review provides a valuable resource for healthcare professionals aiming to navigate the intricacies of ibrutinib’s therapeutic landscape while prioritizing patient well-being.