Protective effect of brain-derived neurotrophic factor on retinal neurovascular unit / 国际眼科杂志(Guoji Yanke Zazhi)

Based on the neurovascular unit(NVU), neurovascular coupling functions as a barrier to maintain the homeostasis of the microenvironment by regulating the signaling and metabolic activity of nerve cells and capillaries. Widely dispersed across the retina, the NVU is essential to preserving its normal physiological function. A disturbance in retinal neurovascular homeostasis produced by a range of factors can result in a variety of retinal disorders, such as diabetic retinopathy(DR), glaucoma, retinitis pigmentosa(RP)and age-related macular degeneration(ARMD). The retina also has a widespread distribution of brain-derived neurotrophic factor(BDNF), which functions to promote neuron growth and repair damage by binding to its receptor TrkB. In recent years, BDNF was found to play a protective role against damage in the early stage of retinal neurovascular homeostasis imbalance, often known as the neurodegenerative stage. It also helps to reduce the production of pro-angiogenic substances of neurological origin and offers a fresh approach for the early detection and treatment of associated eye disorders.

Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interfere with 5-HT Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms.@*METHODS@#Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05).@*CONCLUSION@#EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.

Neurovascular coupling and central nervous system diseases / 中国药理学通报

Neurovascular coupling is the function of regulating blood flow of the central nervous system at the level of neurovascular units. The central nervous system diseases related to neurovascular coupling mainly include cerebrovascular diseases such as chronic cerebral ischemia and neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease and Lewy body dementia. The main mechanism of neurovascular coupling dysfunction leading to the above diseases is cerebrovascular dysfunction or loss,which leads to serious damage to neuronal ischemia and affects its function. Therefore,this paper reviews the research status of neurovascular coupling and its related central nervous system diseases,in order to guide the follow-up research. The purpose of this paper is to provide a basis for the prevention,relief and treatment of central nervous system diseases related to neurovascular coupling through the mechanism of neurovascular coupling.

Study on effects of 40 Hz light flicker stimulation on spatial working memory in rats and its neural mechanism / 生物医学工程学杂志

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment, with the predominant clinical diagnosis of spatial working memory (SWM) deficiency, which seriously affects the physical and mental health of patients. However, the current pharmacological therapies have unsatisfactory cure rates and other problems, so non-pharmacological physical therapies have gradually received widespread attention. Recently, a novel treatment using 40 Hz light flicker stimulation (40 Hz-LFS) to rescue the cognitive function of model animals with AD has made initial progress, but the neurophysiological mechanism remains unclear. Therefore, this paper will explore the potential neural mechanisms underlying the modulation of SWM by 40 Hz-LFS based on cross-frequency coupling (CFC). Ten adult Wistar rats were first subjected to acute LFS at frequencies of 20, 40, and 60 Hz. The entrainment effect of LFS with different frequency on neural oscillations in the hippocampus (HPC) and medial prefrontal cortex (mPFC) was analyzed. The results showed that acute 40 Hz-LFS was able to develop strong entrainment and significantly modulate the oscillation power of the low-frequency gamma (lγ) rhythms. The rats were then randomly divided into experimental and control groups of 5 rats each for a long-term 40 Hz-LFS (7 d). Their SWM function was assessed by a T-maze task, and the CFC changes in the HPC-mPFC circuit were analyzed by phase-amplitude coupling (PAC). The results showed that the behavioral performance of the experimental group was improved and the PAC of θ-lγ rhythm was enhanced, and the difference was statistically significant. The results of this paper suggested that the long-term 40 Hz-LFS effectively improved SWM function in rats, which may be attributed to its enhanced communication of different rhythmic oscillations in the relevant neural circuits. It is expected that the study in this paper will build a foundation for further research on the mechanism of 40 Hz-LFS to improve cognitive function and promote its clinical application in the future.

Effects of 50 Hz electromagnetic field on rat working memory and investigation of neural mechanisms / 生物医学工程学杂志

With the widespread use of electrical equipment, cognitive functions such as working memory (WM) could be severely affected when people are exposed to 50 Hz electromagnetic fields (EMF) for long term. However, the effects of EMF exposure on WM and its neural mechanism remain unclear. In the present paper, 15 rats were randomly assigned to three groups, and exposed to an EMF environment at 50 Hz and 2 mT for a different duration: 0 days (control group), 24 days (experimental group I), and 48 days (experimental group II). Then, their WM function was assessed by the T-maze task. Besides, their local field potential (LFP) in the media prefrontal cortex (mPFC) was recorded by the in vivo multichannel electrophysiological recording system to study the power spectral density (PSD) of θ and γ oscillations and the phase-amplitude coupling (PAC) intensity of θ-γ oscillations during the T-maze task. The results showed that the PSD of θ and γ oscillations decreased in experimental groups I and II, and the PAC intensity between θ and high-frequency γ (hγ) decreased significantly compared to the control group. The number of days needed to meet the task criterion was more in experimental groups I and II than that of control group. The results indicate that long-term exposure to EMF could impair WM function. The possible reason may be the impaired communication between different rhythmic oscillations caused by a decrease in θ-hγ PAC intensity. This paper demonstrates the negative effects of EMF on WM and reveals the potential neural mechanisms from the changes of PAC intensity, which provides important support for further investigation of the biological effects of EMF and its mechanisms.

A study on the application of cross-frequency coupling characteristics of neural oscillation in the diagnosis of mild cognitive impairment / 生物医学工程学杂志

In order to fully explore the neural oscillatory coupling characteristics of patients with mild cognitive impairment (MCI), this paper analyzed and compared the strength of the coupling characteristics for 28 MCI patients and 21 normal subjects under six different-frequency combinations. The results showed that the difference in the global phase synchronization index of cross-frequency coupling under δ-θ rhythm combination was statistically significant in the MCI group compared with the normal control group ( P = 0.025, d = 0.398). To further validate this coupling feature, this paper proposed an optimized convolutional neural network model that incorporated a time-frequency data enhancement module and batch normalization layers to prevent overfitting while enhancing the robustness of the model. Based on this optimized model, with the phase locking value matrix of δ-θ rhythm combination as the single input feature, the diagnostic accuracy of MCI patients was (95.49 ± 4.15)%, sensitivity and specificity were (93.71 ± 7.21)% and (97.50 ± 5.34)%, respectively. The results showed that the characteristics of the phase locking value matrix under the combination of δ-θ rhythms can adequately reflect the cognitive status of MCI patients, which is helpful to assist the diagnosis of MCI.

Alterations of β-γ coupling of scalp electroencephalography during epilepsy / 生物医学工程学杂志

Uncovering the alterations of neural interactions within the brain during epilepsy is important for the clinical diagnosis and treatment. Previous studies have shown that the phase-amplitude coupling (PAC) can be used as a potential biomarker for locating epileptic zones and characterizing the transition of epileptic phases. However, in contrast to the θ-γ coupling widely investigated in epilepsy, few studies have paid attention to the β-γ coupling, as well as its potential applications. In the current study, we use the modulation index (MI) to calculate the scalp electroencephalography (EEG)-based β-γ coupling and investigate the corresponding changes during different epileptic phases. The results show that the β-γ coupling of each brain region changes with the evolution of epilepsy, and in several brain regions, the β-γ coupling decreases during the ictal period but increases in the post-ictal period, where the differences are statistically significant. Moreover, the alterations of β-γ coupling between different brain regions can also be observed, and the strength of β-γ coupling increases in the post-ictal period, where the differences are also significant. Taken together, these findings not only contribute to understanding neural interactions within the brain during the evolution of epilepsy, but also provide a new insight into the clinical treatment.

The Structure and Function of Glial Networks: Beyond the Neuronal Connections / 神经科学通报·英文版

Glial cells, consisting of astrocytes, oligodendrocyte lineage cells, and microglia, account for >50% of the total number of cells in the mammalian brain. They play key roles in the modulation of various brain activities under physiological and pathological conditions. Although the typical morphological features and characteristic functions of these cells are well described, the organization of interconnections of the different glial cell populations and their impact on the healthy and diseased brain is not completely understood. Understanding these processes remains a profound challenge. Accumulating evidence suggests that glial cells can form highly complex interconnections with each other. The astroglial network has been well described. Oligodendrocytes and microglia may also contribute to the formation of glial networks under various circumstances. In this review, we discuss the structure and function of glial networks and their pathological relevance to central nervous system diseases. We also highlight opportunities for future research on the glial connectome.

Mechano-Chemical Coupling in Living Organisms and Possible Road Map of Mechanomedicine / 医用生物力学

In view of fundamental challenges to the current life and medical researches, this paper analyzes the mechano-chemical coupling behaviors of living organisms at molecular, sub-cellular, cellular and tissue levels, attempting to explain the quantitative relationships in those mechano-chemical coupling behaviors at different scales. These quantitative relationships show that the structures of living organisms at various scales are closely related to their tensional homeostasis, i. e. , the structural changes will inevitably lead to the changes of tensional homeostasis; Conversely, the changes of the tensional homeostasis will inevitably lead to structural changes. The tensional homeostasis in living organisms stems from contractile force in actin cytoskeleton generated by the action of myosin II at molecular level, and the tensional homeostasis at higher structural levels is realized with the help of hierarchical structures of the living organisms. Therefore, the mechano-chemical coupling mechanisms and their corresponding quantitative relationships inspire scientists to develop a new way of understanding and dealing with diseases, called as mechanomedicine. Finally, the paper discusses possible ways / road maps of mechanomedicine to understand and treat diseases, in order to provide diagnostic and therapeutic ideas for this new medical paradigm.

Biomechanical Characteristics Analysis of Human-Machine Coupling on Ankle / 医用生物力学

Objective A 2-PSU/ RR parallel ankle rehabilitation robot was designed, and the biomechanical properties of human muscles were also analyzed, so as to study rehabilitation strategy of the ankle rehabilitation robot. Methods The actual workspace of the robot was obtained by numerical discrete search method, and the effect of structural parameter changes on the height of robot moving platform was explored. Then the human biomechanical responses such as muscle force and muscle mobility were obtained by human biomechanical simulation software AnyBody, so as to investigate the effect of moving platform height changes on muscle behavior. Results The robot could meet the demand of ankle plantarflexion/ dorsiflexion and inversion/ eversion motion. Appropriately increasing the initial inclination angle and decreasing the length of the fixed-length bar enabled the ankle rehabilitation robot to have a lower overall height. The height of the moving platform was decreased by 10 mm in turn, and the muscle force and muscle activity of the human body involved in the movement were decreased to a certain extent. Conclusions This study provides a new design solution for ankle rehabilitation, offers theoretical guidance for motion analysis of the ankle rehabilitation robot, and accelerates rehabilitation of the patients’ ankles by modifying the mechanism parameters.

The role of neutrophil CD 11b, soluble CD 14 subtype and mitochondrial coupling factor-6 in the risk stratification of disease outcome in neonatal sepsis and its clinical significance / 中国医师进修杂志

Objective:To investigate the role of neutrophil CD 11b (nCD 11b), soluble CD 14 subtype (sCD 14-St) and mitochondrial coupling factor-6 (CF-6) in the risk stratification of disease outcome in neonatal sepsis and its clinical significance. Methods:The clinical data of 121 septic neonates from July 2019 to March 2020 in Shanxi Children′s Hospital were retrospectively analyzed. According to the neonatal critical illness score (NCIS), the neonates were divided into non-critical group (NCIS>90 scores) with 35 cases, critical group (NCIS 70 to 90 scores) with 49 cases, very critical group (NCIS<70 scores) with 37 cases. There were 25 cases with poor prognosis (death), and 96 cases with good prognosis (survival). The C-reactive protein (CRP), procalcitonin (PCT), nCD 11b, sCD 14-St and CF-6 before treatment were detected. The correlation between nCD 11b, sCD 14-St, CF-6 and disease severity was analyzed by Spearman method; the value of nCD 11b, sCD 14-St and CF-6 in predicting poor disease outcome in sepsis neonates was analyzed by the receiver operating characteristic (ROC) curve. Results:The nCD 11b, sCD 14-St, CF-6, PCT and CRP in critical group and very critical group were significantly higher than those in non-critical group: (414.68 ± 93.29) and (532.74 ± 101.85) MFI vs. (325.45 ± 71.90) MFI, (892.40 ± 113.72) and (1 249.53 ± 95.41) ng/L vs. (784.66 ± 103.72) ng/L, (84.79 ± 28.35) and (121.66 ± 34.27) ng/L vs. (42.59 ± 13.51) ng/L, (19.24 ± 6.30) and (34.96 ± 11.95) μg/L vs. (8.89 ± 2.24) μg/L, (109.49 ± 36.77) and (247.13 ± 82.06) mg/L vs. (56.84 ± 17.25) mg/L; the indexes in very critical group were significantly higher than those in critical group, and there were statistical differences ( P<0.05). Spearman correlation analysis result showed that nCD 11b, sCD 14-St and CF-6 were positively correlated with disease severity in sepsis neonates ( r = 0.719, 0.813 and 0.823; P<0.01). The nCD 11b, sCD 14-St, CF-6, PCT and CRP in poor prognosis neonates were significantly higher than those in good prognosis neonates: (618.58 ± 146.92) MFI vs. (374.55 ± 120.03) MFI, (1 516.91 ± 194.38) ng/L vs. (828.13 ± 175.67) ng/L, (165.84 ± 25.63) ng/L vs. (62.51 ± 16.75) ng/L, (43.46 ± 10.14) μg/L vs. (20.19 ± 6.30) μg/L and (321.09 ± 94.56) mg/L vs. (88.24 ± 29.19) mg/L, and there were statistical differences ( P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of nCD 11b, sCD 14-St and CF-6 for predicting poor disease outcome in sepsis neonates were 0.763, 0.796 and 0.838 (95% CI 0.678 to 0.836, 0.713 to 0.864 and 0.760 to 0.899), and the AUC of combination the 2 indexes was 0.921 (95% CI 0.858 to 0.962). Conclusions:The nCD 11b, sCD 14-St and CF-6 are associated with the disease severity and prognosis in sepsis neonates, and can be used as markers for risk stratification of disease outcome and assessment prognosis.

Effect of Astrocyte-neuron Coupling Imbalance in Development of Alzheimer's Disease and Intervention Mechanism of Kidney-tonifying and Marrow-filling TCM Prescriptions / 中国实验方剂学杂志

Astrocytes are important nerve cells in the central nervous system （CNS）， which mainly play a key role in nutrition and support. Astrocytes and neurons undergo close energy coupling and substance coupling， which are closely related and interact with each other. In recent years， many studies have shown that the astrocyte-neuron coupling imbalance plays a central role in the occurrence and progression of Alzheimer's disease （AD） and serves as an important therapeutic target receiving increasing attention. According to traditional Chinese medicine （TCM） theory， the main pathogenesis of AD is kidney deficiency and marrow inadequacy， and in clinical medication， kidney-tonifying and marrow-filling TCM prescriptions are often employed with satisfactory results achieved. As reported， many kidney-tonifying and marrow-filling prescriptions exhibit regulatory and protective effects on the imbalance of astrocyte-neuron coupling， suggesting that the effect of kidney-tonifying and marrow-filling prescriptions in treating AD may have some internal relationship with its regulation of the imbalance of astrocyte-neuron coupling. This article reviewed the underlying internal relationship between the imbalance of astrocyte-neuron coupling and the pathogenesis of kidney deficiency and marrow inadequacy in AD and the research progress in the intervention mechanism of TCM for tonifying the kidney and filling the marrow.

Neurovascular unit and diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

The concept of neurovascular unit(NVU), formalized in 2001 at a stroke conference, emphasizes the intimate relationship between the brain and its vessels, i.e., symbiotic relationship between brain cells and cerebral blood vessels in the developmental, structural and functional interdependence. The retina is a piece of brain. Several researchers have introduced the concept of NVU to the retina since 2007. The NVU in the retina includes neurons, glial cells, microvascular endothelial cells and pericytes. Dysfunctional NVU plays a critical role in diabetic retinopathy(DR). The current limited treatments for DR focus on the late-stage complications, i.e., diabetic macular edema and proliferative DR. While the further study on retinal NVU will develop efficacious therapeutic options for the early and all stages of DR.

Sweroside Effectively Protects Against Ischemia/Reperfusion Injury by Regulating Excitation-contraction Coupling / 中国实验方剂学杂志

ObjectiveTo explore the effect of sweroside on the protection of cardiac systolic/diastolic function during ischemia/reperfusion （I/R） injury. MethodTwenty-four healthy male SD rats were randomly divided into control group， model group， 10 μmol·L-1 sweroside group and 1 μmol·L-1 digoxin group. The I/R injury was modeled by Langendorff and ligation of the left anterior descending coronary artery. The infarct size in each group was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining and hemodynamic parameters such as left ventricular diastolic pressure （LVDP）， left ventricular end-diastolic pressure （LVEDP）， left ventricular end-systolic pressure （LVESP）， maximum rate of rising of left ventricular pressure （+dp/dtmax） and maximum rate of decreasing of left ventricular pressure （-dp/dtmax） of rat isolated heart were detected by Powerlab. In addition， neonatal rat cardiomyocytes （NRCMs） were isolated and randomly divided into control group， model group， 1 μmol·L-1 sweroside group and 10 μmol·L-1 sweroside group. Hypoxia/reoxygenation （H/R） injury model was established. Cardiac systolic function and calcium transients were examined by multi-functional cell imaging analyzer and laser confocal microscope. Furthermore， real-time polymerase chain reaction（Real-time PCR） was used to verify the mRNA expression of excitation-contraction coupling genes such as L-type calcium channel （Cacnb2）， cytochrome c oxidase subunit 6A2 （Cox6a2）， troponin （Tnnc1， Tnni3， Tnnt2）， actin （Actc1）， and myosin （Myh6， Myl2， Myl4） according to the results of previous transcriptome sequencing and literature investigation. Differentially expressed genes were subjected to cluster analysis. ResultCompared with the conditions in the control group， increased cardiac infarction size （P<0.01） and LVEDP （P<0.01） and decreased LVDP （P<0.01） and LVESP （P<0.05） were observed in the model group， with +dp/dtmax of increasing trend while -dp/dtmax decreasing. Moreover， the cell viability， heart rate and contraction amplitude of NRCMs was reduced （P<0.01）， while the contraction duration， time to peak and relaxation time was elevated （P<0.01） in the model group. Interestingly， sweroside could reverse these indicators （P<0.05）. In addition， the expression of Cacnb2， Cox6a2， Tnnc1， Tnni3， Tnnt2， Actc1， and Myh6， Myl2， and Myl4 was down-regulated in the model group （P<0.05， P<0.01）， but sweroside could up-regulate the expression of the above genes （P<0.05）. ConclusionSweroside effectively regulated Ca2+ level in NRCMs， enhanced cardiac systolic function， and protected against H/R injury by regulating excitation-contraction coupling.

Hemodynamic abnormality in patients with primary trigeminal neuralgia / 中华神经科杂志

Objective:To investigate specificity of neurovascular compression in patients with primary trigeminal neuralgia (PTN) by three-dimension reconstruction and computational fluid dynamics.Methods:Clinical characteristics and preoperative magnetic resonance imaging (MRI) data of 20 patients with both PTN and single artery compression (PTN group) and 10 patients without PTN but having neurovascular contact in MRI images (control group) in the Second Affiliated Hospital of Zhengzhou University from January 2018 to December 2019 were collected and analyzed. After three-dimension reconstruction of the MRI images, curvature of the arterial loop, angle between the plane of arterial loop and the trigeminal nerve and location of the compression were observed. Then bidirectional structure-fluid coupling based on the optimized stereolithography models of arterial loop and nerve were processed by ANSYS 19.2 software. In the location of the compression of contact, equivalent stress (ES) of arterial loop on the nerve, shearing stress (SS) of the blood flow and local deformation of the nerve were iteratively computed. All parameters were analyzed and compared between the PTN group and the control group, and the correlation analysis was proceeded between the anatomical parameters and hemodynamical parameters.Results:The curvature of arterial loop [0.21(0.12) mm -1vs 0.13(0.07) mm -1, U=34.00, P<0.05], the angle between vascular loop and nerve [69.70(30.67)° vs 43.40(37.21)°, U=38.00, P<0.05] in the PTN group were significantly greater than those in the control group, and the location of compression was significantly closer to the root of nerve in the PTN group [PTN group: (4.23±1.29) mm vs control group: (5.54±1.85) mm, t=-2.26, P<0.05]. The average SS [15 952.48(5 365.56) Pa vs 12 501.97(6 355.26) Pa, U=53.00, P<0.05], ES [24 965.65(7 693.22) Pa vs 14 992.99(9 824.08) Pa, U=32.00, P<0.05] in the PTN group were significantly greater than those in the control group. The curvature of arterial loop was positively correlated with the SS ( r=0.931, P<0.05) and ES ( r=0.962, P<0.05), and the latter two ( r=0.787, P<0.05; r=0.853, P<0.05) were positively correlated with the local neural deformation. Conclusions:In patients with PTN, offending artery compresses the root of nerve by greater arterial curvature and angle between the arterial loop and nerve. These anatomical differences will cause significantly greater SS, ES and local neural deformation.

Altered neurovascular coupling in arteriosclerotic cerebral small vessel disease and the correlation with cognitive function / 中华神经科杂志

Objective:To investigate the global and local changes of neurovascular coupling in arteriosclerotic cerebral small vessel disease (aCSVD) and the correlation with cognitive function.Methods:Forty-three patients with confirmed aCSVD from the outpatient department or ward of the Department of Neurology, the First Affiliated Hospital of Anhui Medical University between June 2020 and June 2021 were enrolled in this study. Meanwhile, 48 healthy subjects were selected as controls. Cognitive evaluation, resting-state functional magnetic resonance imaging and 3D pseudo-continuous arterial spin labeling magnetic resonance imaging scanning were performed in all subjects. The global cerebral blood flow-regional homogeneity (ReHo) correlation coefficient and the cerebral blood flow/ReHo ratio were used to evaluate global and local neurovascular coupling. Meanwhile, correlations between the cerebral blood flow/ReHo ratio and neuropsychological assessments were explored in aCSVD patients.Results:Global cerebral blood flow-ReHo coupling was decreased in aCSVD patients compared to healthy controls [aCSVD patients: 0.942(0.933, 0.950), healthy controls: 0.947(0.939, 0.954), Z=-2.11, P=0.035]. aCSVD patients showed decreased cerebral blood flow/ReHo ratio in the right lingual gyrus ( t=-4.45, P<0.05) and increased cerebral blood flow/ReHo ratio in the left ( t=4.91, P<0.05) and right ( t=4.72, P<0.05) inferior parietal lobule. Cerebral blood flow/ReHo ratio of the right inferior parietal lobule was negatively correlated with total score ( r=-0.33, P=0.031) and praxis score ( r=-0.43, P=0.004) in Cambridge Cognitive Examination-Chinese Version subitems and positively correlated with scores of Stroop Color Word Test (SCWT)-color ( r=0.33, P=0.032), SCWT-word ( r=0.34, P=0.025) and Trail Making Test-B ( r=0.31, P=0.043) in aCSVD patients. While the cerebral blood flow/ReHo ratio of the right lingual gyrus was negatively correlated with Visual Replicate-Immediate Recall score ( r=-0.36, P=0.017). Conclusion:aCSVD patients showed abnormal global and local neurovascular coupling, which was associated with attention, executive function, and visual space function.

Progress of Cell Biomechanics in 2021 / 医用生物力学

Cells are in complicated mechanical and physical microenvironment in vivo. The former mainly includes flow shear, tension, compression or torsion, and the latter covers stiffness and topography of extracellular matrix, spatial location, volume constraint or osmotic pressure, featured with various types, patterns, and parameters of mechanical or physical loading. Cell biomechanics mainly focuses on the alteration of mechanical properties of cells and the mechanical remodeling of subcellular components, the cell development, growth, proliferation, differentiation, and apoptosis under distinct mechanical stimuli, and the cellular sensation, transmission, transduction, and responses to external forces. This review summarized the major progresses in cell biomechanics in 2021, including studies on cardiomyocytes, endothelial cells, osteoblasts, immune cells, cancer cells and stem cells, as well as the related new techniques.

Characteristic Analysis on Human-Machine Interaction Force of Lower Limb Exoskeleton / 医用生物力学

Objective To propose a human-machine coupling dynamics modeling method based on virtual muscles, so as to quantitatively analyze the characteristics of human-computer interaction force and muscle activation of the musculoskeletal system. Methods First, in the gait experiment of wearing exoskeleton, the human motion capture system and self-developed mechanical monitoring device were used to obtain the wearer’s walking dynamics, electromyography (EMG) signals, exoskeleton drive status and local human-computer interaction information. The human-machine coupling model was established in modeling environment of the bone system, and the gait experiment data and the exoskeleton joint torques were used as driving information of the coupling model to perform inverse mechanical calculations. Finally, by adjusting strength and stiffness parameters of the virtual muscles, the real data of the model was compared with the experimental test result, to quantitatively evaluate effectiveness of the human-machine coupling model of the lower extremity exoskeleton. Results The normal interaction force calculated by inverse dynamics of the coupled model and the activation of lower limb muscles had a good consistency in response curve trend compared with measurement results of the gait experiment, and the interaction force results had a high degree of correlation (r=0.931, P<0.01), the root mean square error was small, and the peak error of lower limb muscle activation was lower than 5%. Conclusions The human-machine coupling model proposed in this study can effectively calculate the interaction force between human and exoskeleton. The establishment of the coupling model provides a theoretical basis for verification and iteration of the exoskeleton structure optimization and control algorithm, as well as performance evaluation on mobility assistance effects of the exoskeleton.

Expression of polyphosphate kinase from Sphingobacterium siyangensis and its application in ATP regeneration system / 生物工程学报

Polyphosphate kinase plays an important role in the catalytic synthesis of ATP in vitro. In order to find a polyphosphate kinase that can efficiently synthesize ATP using short-chain polyphosphate (polyP) as substrate, the polyphosphate kinase 2 (PPK2) from Sphingobacterium siyangensis was cloned and expressed in Escherichia coli BL21(DE3). As an enzyme for ATP regeneration, PPK2 was used in combination with l-amino acid ligase (YwfE) to produce l-alanyl-l-glutamine (Ala-Gln). The length of ppk2 of S. siyangensis is 810 bp, encoding 270 amino acids. The SDS-PAGE showed that PPK2 was expressed correctly and its molecular weight was 29.7 kDa as expected. The reaction conditions of PPK2 were optimized. PPK2 could maintain good activity in the range of 22-42 ℃ and pH 7-10. The highest enzyme activity was observed at 37 ℃, pH 7, 30 mmol/L magnesium ion (Mg2+), 5 mmol/L ADP and 10 mmol/L sodium hexametaphosphate, and the yield of ATP reached 60% of the theoretical value in 0.5 hours at this condition. When used in combination with YwfE to produce Ala-Gln, the PPK2 showed a good applicability as an ATP regeneration system, and the effect was similar to that of direct addition of ATP. The PPK2 from S. siyangensis shows good performance in a wide range of temperature and pH, synthesizes ATP with cheap and readily available short chain polyP as substrate. The PPK2 thus provides a new enzyme source for ATP dependent catalytic reaction system.

Molecular transduction in receptor-ligand systems by planar electromagnetic fields / Transdução molecular em sistemas receptor-ligante por campos electromagnéticos planares

The coupling of a ligand with a molecular receptor induces a signal that travels through the receptor, reaching the internal domain and triggering a response cascade. In previous work on T-cell receptors and their coupling with foreign antigens, we observed the presence of planar molecular patterns able to generate electromagnetic fields within the proteins. These planes showed a coherent (synchronized) behavior, replicating immediately in the intracellular domain that which occurred in the extracellular domain as the ligand was coupled. In the present study, we examined this molecular transduction - the capacity of the coupling signal to penetrate deep inside the receptor molecule and induce a response. We verified the presence of synchronized behavior in diverse receptorligand systems. To appreciate this diversity, we present four biochemically different systems - TCR-peptide, calcium pump-ADP, haemoglobin-oxygen, and gp120-CD4 viral coupling. The confirmation of synchronized molecular transduction in each of these systems suggests that the proposed mechanism would occur in all biochemical receptor-ligand systems.

A ligação de um ligante com um receptor molecular induz um sinal que viaja através do receptor, chegando ao domínio interno e disparando uma cascata de resposta. Em trabalhos anteriores em receptores de células T e sua ligação com antígenos estranhos, observamos a presença de padrões moleculares planares capazes de gerar campos eletromagnéticos dentro das proteínas. Esses planos mostraram um comportamento coerente (sincronizado), replicando, instantaneamente, no domínio intracelular o que ocorreu no domínio extracelular, enquanto o ligante era acoplado. No presente estudo, examinamos essa transdução ­ a capacidade de um sinal de acoplamento de penetrar profundamente a molécula receptora e induzir uma resposta. Verificamos a presença de um comportamento coerente em sistemas diversos de receptor-ligante. Para apreciar essa diversidade, apresentamos quatro sistemas bioquímicos diferentes: TCR-peptídeo, ADP-bomba de cálcio, hemoglobina-oxigênio e gp120-CD4 acoplamento viral. A confirmação de transdução molecular sincronizada em cada um desses sistemas sugere que o mecanismo proposto ocorreria em todos os sistemas bioquímicos receptor-ligante.