Advanced nerve regeneration enabled by neural conformal electronic stimulators enhancing mitochondrial transport.

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. Numerous recent studies report the potential of wireless electronic system for nerve defects repair. Unfortunately, few has met clinical needs for inadequate electrode precision, poor nerve entrapment and insufficient bioactivity of the matrix material. Herein, we present an advanced wireless electrical nerve stimulator, based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.

Strategies for measuring concentrations and forms of amyloid-ß peptides.

Alzheimer's disease (AD) is affecting more and more people worldwide without the effective treatment, while the existed pathological mechanism has been confirmed barely useful in the treatment. Amyloid-ß peptide (Aß), a main component of senile plaque, is regarded as the most promising target in AD treatment. Aß clearance from AD brain seems to be a reliably therapeutic strategy, as the two exited drugs, GV-971 and aducanumab, are both developed based on it. However, doubt still exists. To exhaustive expound on the pathological mechanism of Aß, rigorous analyses on the concentrations and aggregation forms are essential. Thus, it is attracting broad attention these years. However, most of the sensors have not been used in pathological studies, as the lack of the bridge between analytical chemist and pathologists. In this review, we made a brief introduce on Aß-related pathological mechanism included in ß-amyloid hypothesis to elucidate the detection conditions of sensor methods. Furthermore, a summary of the sensor methods was made, which were based on Aß concentrations and form detections that have been developed in the past 10 years. As the greatest number of the sensors were built on fluorescent spectroscopy, electrochemistry, and Roman spectroscopy, detailed elucidation on them was made. Notably, the aggregation process is another important factor in revealing the progress of AD and developing the treatment methods, so the sensors on monitoring Aß aggregation processes were also summarized.

Construction of a pH- and viscosity-switchable near-infrared fluorescent probe and its imaging application.

Viscosity is a parameter used to measure the fluidity of liquids and a key indicator in evaluating the states of body fluid in biological tissues and lesions. Most traditional detection methods have many drawbacks such as a short emission wavelength and interference by background fluorescence. Inspired by the multiple double bond structure of retinal, a novel pH and viscosity dual-response fluorescent probe (Rh-TR) was constructed in this study. Rh-TR exhibited two emission signals centered at 510 and 660 nm. As the pH of the phosphate-buffered saline increased, the fluorescence at 510 nm increased by about 124-fold, while the change in fluorescence at 660 nm was not obvious. When detecting the change in viscosity using the probe, the fluorescence at 510 nm decreased by about 85 %, while the fluorescence at 660 nm increased by over 20-fold. The probe also showed high selectivity and little toxicity. As demonstrated by the biological imaging experiment, the probe successfully imaged changes in the pH and viscosity of cells and in a live animal model of zebrafish. Considering the unique structure of Rh-TR with retinal and its pH- and viscosity-switchable spectral property, the probe may find further application in detecting viscosity-related diseases and industrial detection.

Water-Responsive Self-Contractive Silk-Based Skin Anti-Aging Tensioners with Customizable Biofunctions.

Skin anti-aging treatments have become increasingly popular. Currently, the prevalent treatment method involves implanting skin tension regulation threads (skin lifting threads) under the skin, and radiofrequency treatments. In this study, inspired by the natural supercontraction of spider silk, the molecular structure of silk fibroin fibers is modulated into an oriented configuration. This modification endows silk proteins with water-responsive self-contraction capabilities, leading to the development of innovative self-contracting silk-based skin tensioners (SSSTs). To align with clinical requirements, skin tension regulation materials are functionalized by testing for their self-contraction, near-infrared laser heating function, and bacteriostatic properties. The SSSTs exhibited remarkable self-contraction properties, drug-loading and sustained-release capabilities, notable antibacterial effects, controllable degradation, and good biocompatibility. Moreover, the near-infrared light heating function effectively increased subcutaneous temperature, demonstrating its potential for enhancing and prolonging skin lifting effects. Therefore, SSSTs can be applied for skin tension regulation to improve and delay skin aging. The results may pave the way for novel strategies in skin rejuvenation, with broad implications for the field of skin anti-aging.

Near-infrared dual-response fluorescent probe for detection of N2H4 and intracellular viscosity changes in biological samples and various water samples.

N2H4 is a common raw material used in the production of pesticides and has good water solubility, so it may contaminate water sources and eventually enter living organisms, causing serious health problems. Viscosity is an important indicator of the cellular microenvironment and an early warning signal for many diseases. The high reactivity of hydrazine depletes glutathione (GSH) in hepatocytes, causing oxidative stress ultimately leading to significant changes in intracellular viscosity and even death. Therefore, it is particularly important to develop an effective method to detect N2H4 and viscosity in environmental and biological systems. On this basis, we developed two fluorescent probes, BDD and BHD, based on xanthene and 2-benzothiazole acetonitrile. The experimental results show that BHD and BDD have good imaging capabilities for N2H4 in cells, zebrafish and Arabidopsis. BHD and BDD also showed sensitive detection and fluorescence enhancement in the near-infrared region when the intracellular viscosity was changed. Notably, the probe BDD has also successfully imaged N2H4 in a variety of real water samples.

A fluorescent probe for detecting H2O2 and delivering H2S in lysosomes and its application in maintaining the redox environments.

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that can be used as a marker for the occurrence of oxidative stress in the organism. Lysosomes serve as intracellular digestive sites, and when the concentration of H2O2 in them is abnormal, lysosomal function is often impaired, leading to the development of diseases. Hydrogen sulfide (H2S) acts as a gaseous signaling molecule that scavenges H2O2 from cells and tissues, thereby maintaining the redox environment of the body. However, most of the reported hydrogen peroxide fluorescent probes so far can only detect H2O2, but cannot maintain the intracellular redox environment. In this paper, an H2O2 fluorescent probe LN-HOD with lysosomal targeting properties was designed and synthesized by combining the H2O2 recognition site with a naphthylamine fluorophore via a thiocarbamate moiety. The probe has the advantages of large Stokes shift (110 nm), high sensitivity and good H2S release capability. The probe LN-HOD can be used to detect H2O2 in cells, zebrafish and plant roots. In addition, LN-HOD detects changes in the concentration of H2O2 in plant roots when Arabidopsis is stressed by cadmium ion (Cd2+). And through its ability to release H2S, it can help to remove excess H2O2 and maintain the redox environment in cells, zebrafish and plant roots. The present work provides new ideas for the detection and assisted removal of H2O2, which contributes to the in-depth study of the cellular microenvironment in organisms.

A highly sensitive fluorescent probe RN-NA reveals peroxynitrite as a novel biomarker for primary open angle glaucoma.

AIM: To directly quantify peroxynitrite (ONOO-) using a highly sensitive fluorescence resonance energy transfer probe RN-NA, investigate the association between ONOO- and primary open angle glaucoma (POAG), and clarify whether RN-NA could be used as a potential tool for POAG diagnosis. METHODS: Plasma and aqueous humor (AH) samples were collected from POAG patients (n=100, age: 59.70±6.87y) and age-related cataract (ARC) patients (n=100, age: 61.15±4.60y) admitted to our hospital. Next, RN-NA was used to detect ONOO- in plasma and AH samples, and the relationship between ONOO- level and POAG was analyzed using binary logistic regression. Besides, Pearson correlation analysis was applied to characterize the correlation of the levels of ONOO- with the patients' age, intraocular pressure (IOP), and mean deviation of visual field testing. The ONOO- scavenger MnTMPyP was employed to treat the 3-morpholinosyndnomine (SIN-1)-induced ocular hypertension in mice (n=7, 6-8wk). Finally, the IOP and ONOO- in both eyes were measured 30min after the last drug treatment. RESULTS: ONOO- levels of AH and plasma were significantly higher in the POAG group than in the ARC group (P<0.01). Additionally, ONOO- levels were closely correlated with POAG in a binary logistic regression analysis [odds ratio (OR)=1.008, 95% confidence interval (CI): 1.002-1.013, P<0.01 for AH; OR=1.004, 95%CI: 1.002-1.006, P<0.001 for plasma]. Pearson correlation analysis showed that ONOO- levels in AH or plasma were positively associated with visual field defects (R=0.51, P<0.01 for AH; R=0.45, P<0.001 for plasma), and ONOO- levels in plasma and AH were correlated in the POAG group (R=0.69, P<0.001). However, administering MnTMPyP to mouse eyes reversed the elevated IOP caused by SIN-1 (P<0.05). CONCLUSION: ONOO- levels in AH and plasma, detected by RN-NA, are significantly related to POAG and positively correlated with visual field defects in POAG patients. Hence, ONOO- is a potential biomarker of POAG, especially advanced POAG. Besides, anti-nitration compounds may be novel ocular hypotensive agents based on the animal study.

Harmonizing Thickness and Permeability in Bone Tissue Engineering: A Novel Silk Fibroin Membrane Inspired by Spider Silk Dynamics.

Guided bone regeneration gathers significant interest in the realm of bone tissue engineering; however, the interplay between membrane thickness and permeability continues to pose a challenge that can be addressed by the water-collecting mechanism of spider silk, where water droplets efficiently move from smooth filaments to rough conical nodules. Inspired by the natural design of spider silk, an innovative silk fibroin membrane is developed featuring directional fluid transportation via harmoniously integrating a smooth, dense layer with a rough, loose layer; conical microchannels are engineered in the smooth and compact layer. Consequently, double-layered membranes with cone-shaped microporous passageways (CSMP-DSF membrane) are designed for in situ bone repair. Through extensive in vitro testing, it is noted that the CSMP-DSF membrane guides liquid flow from the compact layer's surface to the loose layer, enabling rapid diffusion. Remarkably, the CSMP-DSF membrane demonstrates superior mechanical properties and resistance to bacterial adhesion. When applied in vivo, the CSMP-DSF membrane achieves results on par with the commercial Bio-Gide collagen membranes. This innovative integration of a cross-thickness wetting gradient structure offers a novel solution, harmonizing the often-conflicting requirements of material transport, mechanical strength, and barrier effectiveness, while also addressing issues related to tissue engineering scaffold perfusion.

Construction of a novel chitosan-based macromolecular nanoprobe for specific fluorescent detection of H2S in live animals.

H2S is one of the signal molecules in live organisms and a poisonous gas, which is closely related to our life. The traditional synthetic small molecular organic probes often have the disadvantages of low biocompatibility. In this paper, a fluorescent nanoprobe for detecting H2S in live organisms was constructed based on chitosan. The structure of CH-CN was characterized by infrared spectroscopy, nuclear magnetic resonance, x-ray photoelectron spectroscopy (XPS), XRD and scanning electron microscope (SEM). In the presence of Na2S, the fluorescence intensity at 560 nm was significantly enhanced, and showed high selectivity and sensitivity toward H2S. Based on the good fluorescence response of CH-CN, the probe was also successfully applied to H2S imaging in HepG2 cells and zebrafish. These experimental results indicate that the probe has lower cytotoxicity and excellent stability. The present research shows a typical example of construction of chitosan-based macromolecular fluorescent materials and their bio-imaging application.

Development of a novel chitosan-based two-photon fluorescent nanoprobe with enhanced stability for the specific detection of endogenous H2O2.

Hydrogen peroxide (H2O2) acts as an important reactive oxygen species (ROS) and maintains the redox equilibrium in organisms. Imbalance of H2O2 concentration is associated with the development of many diseases. Traditional small molecular based fluorescent probes often show drawbacks of cytotoxicity and easily metabolic clearance. Herein, a chitosan-based two-photon fluorescent nanoprobe (DC-BI) was constructed and applied for H2O2 detection in live organisms. DC-BI was composed by chitosan nanoparticles and a two-photon fluorophore of naphthalimide analogues (BI) with H2O2-responsive property. The structure of DC-BI was characterized by NMR, FTIR, XPS, XRD, DLS and MLS analyses. As study shown, the nanoprobe DC-BI exhibited improved distribution stability and smaller cytotoxicity. In the presence of H2O2, both the absorption and emission spectra show dramatic changes, the fluorescence intensity at 580 nm obviously enhanced. Furthermore, fluorescence imaging results indicate that DC-BI is capable of imaging endogenous H2O2 in cells and zebrafish. The design and development of chitosan-based nanoprobe DC-BI has provided a general example of nanoprobe construction with excellent distribution stability, two-photon property, and biocompatibility.

Construction of a water-soluble fluorescent probe for copper (II) ion detection in live cells and food products.

The quality of wine can be affected by excess Cu2+ due to the occurrence of oxidation reactions or precipitation. Therefore, it is essential to use simple and effective testing methods to ensure the Cu2+ content in wine. In this work, we designed and synthesized a rhodamine polymer fluorescent probe (PEG-R). The water solubility of PEG-R was improved by the introduction of polyethylene glycol, which improved the performance and broadened its application in the food field. The PEG-R was characterized by high sensitivity, selectivity and fast response to Cu2+ and was able to complete the response process within 30 s, with approximately 29-fold fluorescence enhancement of the probe after exposure to Cu2+, the limit of detection (LOD) was 1.295 × 10-6 M. The probe can be used for the determination of Cu2+ in living cells, zebrafish, white wine and food products, and it was made into practical gels and test strips.

Spatiotemporal Regulation of Injectable Heterogeneous Silk Gel Scaffolds for Accelerating Guided Vertebral Repair.

Osteoporotic vertebral fracture is jeopardizing the health of the aged population around the world, while the hypoxia microenvironment and oxidative damage of bone defect make it difficult to perform effective tissue regeneration. The balance of oxidative stress and the coupling of vessel and bone ingrowth are critical for bone regeneration. In this study, an injectable heterogeneous silk gel scaffold which can spatiotemporally and sustainedly release bone mesenchymal stem cell-derived small extracellular vesicles, HIF-1α pathway activator, and inhibitor is developed for bone repair and vertebral reinforcement. The initial enhancement of HIF-1α upregulates the expression of VEGF to promote angiogenesis, and the balance of reactive oxygen species level is regulated to effectively eliminate oxidative damage and abnormal microenvironment. The subsequent inhibition of HIF-1α avoids the overexpression of VEGF and vascular overgrowth. Meanwhile, complex macroporous structures and suitable mechanical support can be obtained within the silk gel scaffolds, which will promote in situ bone regeneration. These findings provide a new clinical translation strategy for osteoporotic vertebral augmentation on basis of hypoxia microenvironment improvement.

Online Learning Koopman Operator for Closed-Loop Electrical Neurostimulation in Epilepsy.

Electrical neuromodulation as a palliative treatment has been increasingly used in the control of epilepsy. However, current neuromodulations commonly implement predetermined actuation strategies and lack the capability of self-adaptively adjusting stimulation inputs. In this work, rooted in optimal control theory, we propose a Koopman-MPC framework for real-time closed-loop electrical neuromodulation in epilepsy, which integrates i) a deep Koopman operator based dynamical model to predict the temporal evolution of epileptic electroencephalogram (EEG) with an approximate finite-dimensional linear dynamics and ii) a model predictive control (MPC) module to design optimal seizure suppression strategies. The Koopman operator based linear dynamical model is embedded in the latent state space of the autoencoder neural network, in which we can approximate and update the Koopman operator online. The linear dynamical property of the Koopman operator ensures the convexity of the optimization problem for subsequent MPC control. The proposed deep Koopman operator model shows greater predictive capability than the baseline models (e.g., vector autoregressive model, kernel based method and recurrent neural network (RNN)) in both synthetic and real epileptic EEG data. Moreover, compared with the RNN-MPC framework, our Koopman-MPC framework can suppress seizure dynamics with better computational efficiency in both the Jansen-Rit model and the Epileptor model. Koopman-MPC framework opens a new window for model-based closed-loop neuromodulation and sheds light on nonlinear neurodynamics and feedback control policies.

Functional Nanomaterials: From Structures to Biomedical Applications.

In recent decades, a number of functional nanomaterials have attracted a great amount of attention and exhibited excellent performance for biomedical and pharmaceutical applications [...].

A novel and fast-responsive two-photon fluorescent probe with modified group for monitoring endogenous HClO accompanied by a large turn-on signal and its application in zebrafish imaging.

Hypochlorous acid (HClO) plays a critical role in physiological activities of maintaining the stable oxidation balance of organisms, which was proved to relate to some serious diseases. In this work, 4-nitrobenzenesulfonylhydrazide based fast-responsive two-photon fluorescent probe CoPh-ClO was designed and synthesized reasonably, which possessed low cytotoxicity, good anti-interference characteristics, a large Stokes shift (85 nm), and good two-photon performance. In addition, probe CoPh-ClO was successfully applied to detect exogenous HClO in living HeLa cells and endogenous HClO in living RAW264.7 cells respectively. Moreover, we successfully achieved tissues imaging with a deep penetration depth of 65 µm and zebrafish imaging accompanied with a high contrast (about 45-fold). Interestingly, the introduce of benzene ring between fluorophore and reaction site made probe CoPh-ClO more sensitive (only 20 s) with a large turn-on signal. The probe CoPh-ClO was modified and possessed better stability (more than 10 mins) even in excessive HClO. All of mentioned above merits demonstrated that CoPh-ClO could be a promising imaging tool for monitoring HClO in various physiological processes, and the introduction of benzene ring would provide a new perspective for the development of multi-function probes.

Cardiac function of basketball players under stress training / Função cardíaca de jogadores de basquetebol no treinamento de estresse / Función cardíaca de jugadores de baloncesto en el entrenamiento de esfuerzo

ABSTRACT Introduction: Basketball can enhance the physical fitness of young people, promote the growth and development of their bodies, and improve health and athletic ability. Objective: To explore the characteristics of basketball players' cardiac response to increasing load training. Methods: By analyzing 12 juvenile male amateur basketball training athletes, when performing incremental load exercises on the treadmill, using a 12-lead electrocardiograph to record the electrocardiogram, HR, and blood pressure responses for each level of exercise. Results: The mean heart rate of the basketball players before movement was 82.45± 11.44 bpm, slightly higher than the heart rate at rest. Depending on the exercise load, the blood pressure should increase by 5 to 12 mmHg. Under different load training conditions, each level of blood pressure in the Bruce treadmill test procedure should increase 12.5 ~ 44mmHg. The basketball player's systolic pressure increased by 2.25 ~ 15.7mmHg, diastolic pressure increased by 0.43 to 11.37 mmHg. Conclusions: In basketball players, the psychological stress is less than that of the average person performing the same exercise. The strong ability to adapt to exercise under incremental load training, the contractility of the ventricular muscles and the development of the heart are good. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: O basquete pode melhorar a aptidão física dos jovens, promover o crescimento e o desenvolvimento corporal e melhorar a saúde e a capacidade atlética. Objetivo: Explorar as características da resposta cardíaca de jogadores de basquete ao aumento da carga de treinamento. Métodos: Analisar 12 atletas juvenis em treinamento de basquete amador masculino durante exercícios de carga incremental em esteira por meio de eletrocardiógrafo de 12 derivações para registrar as respostas elétricas do coração, a FC e a pressão arterial em cada nível de exercício. Resultados: A frequência cardíaca média dos jogadores de basquete antes do exercício foi de 82,45 ± 11,44 bpm, ligeiramente superior à frequência cardíaca em repouso. Dependendo da carga de exercício, a pressão arterial deve aumentar de 5 a 12 mmHg. Em diferentes condições de treinamento de carga, cada nível de pressão arterial no teste em esteira Bruce deve aumentar 12,5 ~ 44 mmHg. A pressão sistólica dos jogadores de basquete aumentou 2,25 ~ 15,7 mmHg, a pressão diastólica aumentou 0,43 para 11,37 mmHg. Conclusões: Nos jogadores de basquete, o estresse psicológico é menor do que a dos não atletas que realizam o mesmo exercício. A grande capacidade de adaptação ao exercício com treinamento de carga incremental, a contratilidade dos músculos ventriculares e o desenvolvimento do coração são bons. Nível de Evidência II; Estudos terapêuticos - Investigação dos resultados do tratamento.

RESUMEN Introducción: El baloncesto puede mejorar el acondicionamiento físico de los jóvenes, promover el crecimiento y el desarrollo corporal y mejorar la salud y la capacidad atlética. Objetivo: Explorar las características de la respuesta cardíaca de los jugadores de baloncesto al aumento de la carga de entrenamiento. Métodos: Analizar a 12 atletas juveniles de baloncesto amateur en entrenamiento durante ejercicios de carga incremental en caminadora utilizando un electrocardiógrafo de 12 derivaciones para registrar las respuestas eléctricas del corazón, la FC y la presión arterial en cada nivel de ejercicio. Resultados: La frecuencia cardíaca media de los jugadores de baloncesto antes del ejercicio fue de 82,45 ± 11,44 lpm, ligeramente superior a la frecuencia cardíaca en reposo. Dependiendo de la carga de ejercicio, la presión arterial debe aumentar entre 5 y 12 mmHg. Bajo diferentes condiciones de entrenamiento de carga, cada nivel de presión arterial en la prueba de Bruce debe aumentar en 12,5 ~ 44 mmHg. La presión sistólica de los jugadores de baloncesto aumentó de 2,25 a 15,7 mmHg, la presión diastólica aumentó de 0,43 a 11,37 mmHg. Conclusiones: En los jugadores de baloncesto, el estrés psicológico es menor que el de los no deportistas que realizan el mismo ejercicio. La gran capacidad de adaptación al ejercicio con entrenamiento de carga incremental, la contractilidad de los músculos ventriculares y el desarrollo del corazón son buenos. Nivel de Evidencia II; Estudios terapéuticos - Investigación de los resultados del tratamiento.

Construction of a unique two-photon fluorescent probe and the application for endogenous CO detection in live organisms.

Carbon monoxide (CO) is one of the most significant signal molecules and plays an important role in regulating human physiological and pathological processes. In this study, a novel Pd-based complex (Pd-BNP-OH) was developed for endogenous CO detection. The structure and morphology of Pd-BNP-OH was characterized by SEM, XPS, and NMR analyses. When Pd-BNP-OH was reacted with CO, a strong fluorescence enhancement at 510 nm was observed. In addition, Pd-BNP-OH exhibited high stability and selectivity toward CO in PBS buffer. In biological experiments, Pd-BNP-OH exhibited little cytotoxicity in cellular environment, and a bright fluorescence turn on was observed in the presence of exogenous CO and endogenous generated CO. The probe was then applied for CO detection in live zebrafish by both one-photon and two-photon excitation. Significantly, Pd-BNP-OH has excellent two-photon property, controllable structure and high biocompatibility. These features enable the probe to detect endogenously generated carbon monoxide in live organisms successfully.

A bifunctional sensitive fluorescence probe based on pyrene for the detection of pH and viscosity in lysosome.

Lysosome is one of the important organelles in intracellular transport. It plays a significant role in the physiological process. The lysosomal microenvironment affects the functions of lysosome. When the original acidic environment of lysozyme is destroyed or the fluid viscosity increases gradually, various diseases are easily induced. However, most fluorescent probes can only locate in cells. The fewer probes of subcellular organelles were found and their functions are often single. So, it is of great importance to design multifunctional fluorescent probes with the capable of localizing in lysosome. In this study, a novel lysosome probe, 4-(4-Pyren-1-yl-but-3-enyl)-morpholine (PIM), was synthesized using pyrene as a fluorescent group and morpholine as a target group. The introduction of morpholine group made PIM localize in lysosome with high selectivity. The fluorescence will be enhanced with the increased viscosity because of restricting the rotation of CC bond and CN in PIM, and the detecting linear range is from 4.05 cP to 393.48 cP, which qualified the requirement of the viscosity monitoring in body. Meanwhile, the fluorescence intensity of PIM declines with the decrease of pH because the Schiff base of PIM is hydrolyzed, which was affirmed by 1H NMR, LC-MS and fluorescence spectra. Moreover, cell imaging and MTT experiments confirmed that PIM as a novel bifunctional probe can be used to detect pH and endogenous viscosity in lysosome.

Machine learning applications on neuroimaging for diagnosis and prognosis of epilepsy: A review.

Machine learning is playing an increasingly important role in medical image analysis, spawning new advances in the clinical application of neuroimaging. There have been some reviews on machine learning and epilepsy before, and they mainly focused on electrophysiological signals such as electroencephalography (EEG) and stereo electroencephalography (SEEG), while neglecting the potential of neuroimaging in epilepsy research. Neuroimaging has its important advantages in confirming the range of the epileptic region, which is essential in presurgical evaluation and assessment after surgery. However, it is difficult for EEG to locate the accurate epilepsy lesion region in the brain. In this review, we emphasize the interaction between neuroimaging and machine learning in the context of epilepsy diagnosis and prognosis. We start with an overview of epilepsy and typical neuroimaging modalities used in epilepsy clinics, MRI, DWI, fMRI, and PET. Then, we elaborate two approaches in applying machine learning methods to neuroimaging data: (i) the conventional machine learning approach combining manual feature engineering and classifiers, (ii) the deep learning approach, such as the convolutional neural networks and autoencoders. Subsequently, the application of machine learning on epilepsy neuroimaging, such as segmentation, localization, and lateralization tasks, as well as tasks directly related to diagnosis and prognosis are looked into in detail. Finally, we discuss the current achievements, challenges, and potential future directions in this field, hoping to pave the way for computer-aided diagnosis and prognosis of epilepsy.

Continuous Infusion of Angiotensin IV Protects against Acute Myocardial Infarction via the Inhibition of Inflammation and Autophagy.

Acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. Angiotensin (Ang) IV possesses many biological properties that are not yet completely understood. Therefore, we investigated the function and mechanism of Ang IV in AMI in in vivo and in vitro conditions. AMI was performed by ligation of the left anterior descending coronary artery (LAD) in male C57 mice. Ang IV was continuously infused by a minipump 3 d before AMI for 33 d. The neonatal rat ventricular myocytes (NRVCs) were stimulated with Ang IV and cultured under hypoxic conditions. In vivo, Ang IV infusion significantly reduced the mortality after AMI. By the 7th day after AMI, compared with the AMI group, Ang IV reduced the inflammatory cytokine expression. Moreover, terminal deoxyribonucleotidyl transferase- (TDT-) mediated dUTP nick-end labeling (TUNEL) assay showed that Ang IV infusion reduced AMI-induced cardiomyocyte apoptosis. Compared with AMI, Ang IV reduced autophagosomes in cardiomyocytes and improved mitochondrial swelling and disarrangement, as assessed by transmission electron microscopy. By 30th day after AMI, Ang IV significantly reduced the ratio of heart weight to body weight. Echocardiography showed that Ang IV improved impaired cardiac function. Hematoxylin and eosin (H&E) and Masson staining showed that Ang IV infusion reduced the infarction size and myocardial fibrosis. In vitro, dihydroethidium (DHE) staining and comet assay showed that, compared with the hypoxia group, Ang IV reduced oxidative stress and DNA damage. Enzyme-linked immunosorbent assay (ELISA) showed that Ang IV reduced hypoxia-induced secretion of the tumor necrosis factor- (TNF-) ɑ and interleukin- (IL-) 1ß. In addition, compared with the hypoxia group, Ang IV reduced the transformation of light chain 3- (LC3-) I to LC3-II but increased p62 expression and decreased cardiomyocyte apoptosis. Overall, the present study showed that Ang IV reduced the inflammatory response, autophagy, and fibrosis after AMI, leading to reduced infarction size and improved cardiac function. Therefore, administration of Ang IV may be a feasible strategy for the treatment of AMI.