Dual cation-modified hierarchical nickel hydroxide nanosheet arrays as efficient and robust electrocatalysts for the urea oxidation reaction.

The rational modification of electronic structures to create catalytically active sites has been proved to be a promising strategy to efficiently facilitate the urea oxidation reaction (UOR). Herein, a well-defined nanosheet arrays catalyst of Ni(OH)2 doped with dual cations of Co and Mn on Ni foam (NF) (Co/Mn-Ni(OH)2) is synthesized through a simple hydrothermal process. Benefiting from the advantages of unique structures and modified binding strengths, it is found experimentally that the obtained Co/Mn-Ni(OH)2 catalyst only requires a potential of 1.38 V to deliver a current density of 100 mA cm-2 and exhibits a small Tafel slope of 35 mV dec-1, outperforming single-component-incorporated Ni(OH)2. Moreover, the catalyst has shown excellent stability for 25 h at a current density of 50 mA cm-2. Additionally, first-principles calculations demonstrate that the co-incorporation of Co and Mn remarkably lowers the adsorption barrier of CO(NH2)2* on the catalyst surface, and accelerates the dissociation of the CO(NH2)2* intermediate into CO* and NH* intermediates, which synergistically improve the UOR reaction kinetics. This work provides a generic paradigm for designing advanced and effective catalysts toward the UOR.

Clinical study of melodic intonation therapy combined with transcranial direct current stimulation for post-stroke aphasia: a single-blind, randomized controlled trial.

Background: Globally, more than 10 million new stroke cases occur annually, of which aphasia accounts for about one-third. Aphasia has become an independent predictor of functional dependence and death for the stroke population. The closed-loop rehabilitation of combining behavioral therapy with central nerve stimulation seems to be the research trend of post-stroke aphasia (PSA) due to its advantages in improving linguistic deficits. Objective: To verify the clinical efficacy of a closed-loop rehabilitation program combining melodic intonation therapy (MIT) with transcranial direct current stimulation (tDCS) for PSA. Methods: This was a single-center, assessor-blinded, randomized controlled clinical trial, which screened 179 patients and included 39 PSA subjects, with the registration number ChiCTR2200056393 in China. Demographic and clinical data were documented. The primary outcome was the Western Aphasia Battery (WAB) used to assess language function, and the secondary outcomes included Montreal Cognitive Assessment (MoCA), Fugl-Meyer Assessment (FMA), and Barthel Index (BI) for evaluating cognition, motor, and activities of daily living, respectively. With the computer-generated randomization sequence, subjects were randomly divided into the conventional group (CG), MIT combined with sham stimulation group (SG), and MIT combined with tDCS group (TG). After the three-week intervention, the functional changes in each group were analyzed by the paired sample T-test, and the functional difference between the three groups was analyzed by ANOVA. Results: There was no statistical difference on the baseline. After the intervention, the WAB's aphasia quotient (WAB-AQ), MoCA, FMA, and BI were statistically different in SG and TG, including all the sub-items in WAB and FMA, while only listening comprehension, FMA, and BI were statistically different in CG. The differences of WAB-AQ, MoCA, and FMA were statistically different among the three groups, but BI was not. The post hoc test results revealed that the changes of WAB-AQ and MoCA in TG were more significant than the others. Conclusion: MIT combined with tDCS can augment the positive effect on language and cognitive recovery in PSA.

Minimizing heat generation in quantum dot light-emitting diodes by increasing quasi-Fermi-level splitting.

Minimizing heat accumulation is essential to prolonging the operational lifetime of quantum dot light-emitting diodes (QD-LEDs). Reducing heat generation at the source is the ideal solution, which requires high brightness and quantum efficiency at low driving voltages. Here we propose to enhance the brightness of QD-LEDs at low driving voltages by using a monolayer of large QDs to reduce the packing number in the emitting layer. This strategy allows us to achieve a higher charge population per QD for a given number of charges without charge leakage, enabling enhanced quasi-Fermi-level splitting and brightness at low driving voltage. Due to the minimized heat generation, these LEDs show a high power conversion efficiency of 23% and a T95 operation lifetime (the time for the luminance to decrease to 95% of the initial value) of more than 48,000 h at 1,000 cd m-2.

The Feasibility of An Automatical Facial Evaluation System Providing Objective and Reliable Results for Facial Palsy.

Facial palsy would lead to a series of physical and mental problems, as facial function plays an important role in various aspects of daily life. However, the current strategies for evaluating facial function relied heavily on raters and the results varied from the experience of raters. Thus, an objective and accurate facial evaluation system is always claimed. In this study, a customized automatical facial evaluation system (AFES) was proposed, which might have the potential to be employed as an adjunctive and efficient assessing method in clinic. In order to investigate the feasibility of AFES, ninety-two participants with facial palsy were recruited and received scale-based subjective manual evaluation (including mHBGS and mSFGS) and objective automatical evaluation of AFES (including aHBGS, aSFGS and indicators of facial regional features) at enrollment and after two weeks. The correlations between the results of the two methods were analyzed and the participants were stratified according to the severity of facial function for further analyses. Strong positive correlations between manual and automatical HBGS and SFGS were observed and higher correlations were reported in the participants with normal-mild and moderate facial palsy. Significant improvements in clinical scales and indicator of eye synkinesis were found in forty-two participants in two weeks. Furthermore, some of the indicators were correlated with scale scores (I4, I7) and one of them presented a significant change between the baseline evaluation and follow-up evaluation (I7). According to the results, AFES could be considered as a viable method to perform objective and reliable evaluation for patients with facial palsy and provide clarified results for prognosis.

Effects of the Left M1 iTBS on Brain Semantic Network Plasticity in Patients with Post-Stroke Aphasia: A Preliminary Study.

BACKGROUND: The left primary motor area (M1) stimulation has recently been revealed to promote post-stroke aphasia (PSA) recovery, of which a plausible mechanism might be the semantic and/or the mirror neuron system reorganization, but the direct evidence is still scarce. The aim of this study was to explore the functional connectivity (FC) alterations induced by the left M1 intermittent theta burst stimulation (iTBS), a new transcranial magnetic stimulation paradigm, in the semantic and mirror neuron systems of PSA patients. METHODS: Sixteen PSA patients accepted the left M1 iTBS and underwent a resting-state functional magnetic resonance image (fMRI) scanning before and immediately after the first session of iTBS, of which six underwent another fMRI scanning after twenty sessions of iTBS. Three brain networks covering the semantic and the mirror neuron systems were constructed using the fMRI data, and the FC alterations following one-session iTBS were investigated in the networks. Additional seed-based FC analyses were conducted to explore the longitudinal FC patterns changes during the course of multi-session iTBS. The Aphasia quotient of the Chinese version of the western aphasia battery (WAB-AQ) was used to assess the severity of the language impairments of the participants. The relationship between the longitudinal WAB-AQ and network FC changes was analyzed by Spearman's correlation coefficients in the multi-session iTBS sub-group. RESULTS: Decreased FCs were noted in the bilateral semantic rather than in the mirror neuron networks following one-session of iTBS (p < 0.05, network based statistical corrected). Longitudinal seed-based FC analyses revealed changing FC ranges along the multi-session iTBS course, extending beyond the semantic networks. No significant relationship was found between the longitudinal WAB-AQ and network FC changes in the multi-session iTBS sub-group. CONCLUSIONS: The left M1 iTBS might induce FC changes in the semantic system of PSA patients. CLINICAL TRIAL REGISTRATION: This research was registered on the Chinese Clinical Trial Registry website (http://www.chictr.org.cn/index.aspx), and the registration number is ChiCTR2100041936.

Comparison of three cognitive assessment methods in post-stroke aphasia patients.

Background: The cognitive level of post-stroke aphasia (PSA) patients is generally lower than non-aphasia patients, and cognitive impairment (CI) affects the outcome of stroke. However, for different types of PSA, what kind of cognitive assessment methods to choose is not completely clear. We investigated the Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), and the Non-language-based Cognitive Assessment (NLCA) to observe the evaluation effect of CI in patients with fluent aphasia (FA) and non-fluent aphasia (NFA). Methods: 92 stroke patients were included in this study. Demographic and clinical data of the stroke group were documented. The language and cognition were evaluated by Western Aphasia Battery (WAB), MoCA, MMSE, and NLCA. PSA were divided into FA and NFA according to the Chinese aphasia fluency characteristic scale. Pearson's product-moment correlation coefficient test and multiple linear regression analysis were performed to explore the relationship between the sub-items of WAB and cognitive scores. The classification rate of CI was tested by Pearson's Chi-square test or Fisher's exact test. Results: The scores of aphasia quotient (AQ), MoCA, MMSE, and NLCA in NFA were lower than FA. AQ was positively correlated with MoCA, MMSE, and NLCA scores. Stepwise multiple linear regression analysis suggested that naming explained 70.7% of variance of MoCA and 79.9% of variance of MMSE; comprehension explained 46.7% of variance of NLCA. In the same type of PSA, there was no significant difference in the classification rate. The classification rate of CI in NFA by MoCA and MMSE was higher than that in FA. There was no significant difference in the classification rate of CI between FA and NFA by NLCA. Conclusion: MoCA, MMSE, and NLCA can be applied in FA. NLCA is recommended for NFA.

The Facial Skin Blood Flow Change of Stroke Patients with Facial Paralysis after Peripheral Magnetic Stimulation: A Pilot Study.

BACKGROUND: Facial paralysis (FP) is a common symptom after stroke, which influences the quality of life and prognosis of patients. Recently, peripheral magnetic stimulation (PMS) shows potential effects on peripheral and central nervous system damage. However, the effect of PMS on FP after stroke is still unclear. METHODS: In this study, we applied PMS on the facial nerve of nine stroke patients with FP. At the same time, laser speckle contrast imaging (LSCI) was used to explore the facial skin blood flow (SkBF) in 19 healthy subjects and nine stroke patients with FP before and after the PMS intervention. The whole face was divided into 14 regions to compare the SkBF in different sub-areas. RESULTS: In baseline SkBF, we found that there were no significant differences in the SkBF between the left and right faces in the healthy subjects. However, there was a significant difference in the SkBF between the affected and unaffected faces in Region 7 (Chin area, p = 0.046). In the following five minutes after the PMS intervention (Pre_0-5 min), the SkBF increased in Region 5 (p = 0.014) and Region 7 (p = 0.046) and there was an increasing trend in Region 3 (p = 0.088) and Region 6 (p = 0.069). In the five to ten minutes after the intervention (Post_6-10 min), the SkBF increased in Region 5 (p = 0.009), Region 6 (p = 0.021) and Region 7 (p = 0.023) and there was an increasing trend in Region 3 (p = 0.080) and left and right whole face (p = 0.051). CONCLUSIONS: These pilot results indicate that PMS intervention could increase facial skin blood flow in stroke patients with FP. A further randomized controlled trial can be performed to explore its possible clinical efficacy.

Determining levels of linguistic deficit by applying cluster analysis to the aphasia quotient of Western Aphasia Battery in post-stroke aphasia.

The aphasia quotient of Western Aphasia Battery (WAB-AQ) has been used as an inclusion criterion and as an outcome measure in clinical, research, or community settings. The WAB-AQ is also commonly used to measure recovery. This study aimed to quantitatively determine levels of the linguistic deficit by using a cluster analysis of the WAB-AQ in post-stroke aphasia (PSA). 308 patients were extracted from the database. Cutoff scores are defined by mean overlap WAB-AQ scores of clusters by systematic cluster analysis, the method of which is the farthest neighbor element, and the metrics are square Euclidean distance and Pearson correlation, performed on the full sample of WAB-AQ individual subitem scores. A 1-way analysis of variance, with post hoc comparisons conducted, was used to determine whether clusters had significant differences. Three clusters were identified. The scores for severe, moderate, and mild linguistic deficit levels ranged from 0 to 30, 30.1 to 50.3, and 50.4 to 93.7, respectively. For PSA, the cluster analysis of WAB-AQ supports a 3-impairment level classification scheme.

Effects of oxygen on the adsorption/oxidation of aqueous Sb(III) by Fe-loaded biochar: An X-ray absorption spectroscopy study.

Fe-loaded biochar (FeBC) has been considered for Sb(III) adsorption, but the effects of oxygen (O2) on the adsorption need further investigation. Liquid-/solid-phase analyses were conducted to investigate the role of O2 in the Sb(III) adsorption by FeBC. The adsorption was best described by the pseudo-second-order (PSO) model for kinetic results and by the Langmuir model for thermodynamic results. More than 96.8 % of Sb(III) was adsorbed by FeBC, and available O2 increased the liquid-phase Sb(III) oxidation efficiency by 2.1-7.5 times. The peak changes at ~1640 and 3450 cm-1 in FTIR spectra indicated the occurrence of inner-sphere complexation between Sb(III)/Sb(V) and hydroxyl (-OH)/carboxyl (-COOH) groups in FeBC under aerobic and anaerobic conditions. Fe/Sb X-ray absorption spectroscopy (XAS) analysis results showed aqueous Sb(III) complexed to the edge-sharing Fe(III)-O-Fe(III) in FeBC. Regardless of whether O2 was available or not, solid-phase edge-sharing Fe(III)-O-Sb(V) complexes (~3.05 Å), which had lower toxicity and migration ability than aqueous Sb(III), formed through a ligand-to-metal charge-transfer (LMCT) process. More than 91 % of adsorbed Sb(III) was oxidized to edge-sharing Fe(III)-O-Sb(V) complexes in 3 h. Additionally, the Sb(V) from liquid-phase oxidation could also directly complex to the Fe(III)-O-Fe(III) and form edge-sharing Fe(III)-O-Sb(V) complexes. These results provide evidence to inform further FeBC application for the Sb-contaminated water treatment.

Exploring Alternative Measurements of Cardiorespiratory Fitness in Patients With Mild Ischemic Stroke at Acute Phase.

BACKGROUND: While emerging studies have suggested an association of cardiorespiratory fitness (CRF) with stroke risk and overall health outcomes, little is known regarding the optimum methods of CRF measurement in patients with mild acute ischemic stroke. OBJECTIVE: The aim of this study was to explore the association between the 6-min walk distance (6MWD) and other measurements related to CRF in patients with mild ischemic stroke at the acute stage. METHODS: A total of 30 patients with stroke and 71 healthy subjects matched for age and grip strength (GS) were prospectively recruited. All patients were within 14 days after stroke onset and presented mild motor impairment (with a full score of Fugl-Meyer Motor Assessment). Demographic data of both groups and clinical information of the stroke group were documented, and the CRF comparison between the two groups was conducted. Each participant underwent a one-time assessment of 6MWD and a series of measurements related to CRF, including GS, 10-m walk test (10mWT), five-times sit-to-stand time (FTSST), functional reaching test (FRT), Berg Balance Scale (BBS), and waistline. Pearson's product-moment correlation coefficient test and multiple linear regression were performed to explore the indicators of CRF. RESULTS: Significant moderate correlations (0.3 < r <0.6) were found between 6MWD and GS of left hand (GS-left) (r = 0.573, p = 0.001), GS of right hand (GS-right) (r = 0.524, p = 0.003), FTSST (r = -0.551, p = 0.002), 10mWT (r = 0.554, p = 0.001), and FRT (r = 0.449, p = 0.021) in the patient group. While 6MWD displayed significant moderate correlations with waistline (r = 0.364, p = 0.002), 10mWT (r = 0.512, p < 0.001), FTSST (r = -0.573, p < 0.001), and FRT (r = 0.550, p < 0.001) in the healthy group. All these dependent variables were entered into a stepwise multiple linear regression analysis to evaluate their values in estimating CRF as measured by 6MWD in each group. Analyses suggested that GS-left (p = 0.002) and FTSST (p = 0.003) were the indicators of CRF in the patient group with stroke and explained 51.4% of the variance of 6MWD (R 2 = 0.514); FTSST (p < 0.001), 10mWT (p < 0.001), and FRT (p = 0.021) were the indicators of CRF in the healthy group and explained 58.9% of variance of 6MWD (R 2 = 0.589). CONCLUSIONS: Our data confirmed that CRF is impaired in patients with mild ischemic stroke at the acute phase. Moreover, GS-left may be an optional indicator of CRF in patients with mild acute ischemic stroke, but not in healthy people. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier: ChiCTR2000031379.

Research Hotspots and Frontiers of Transcranial Direct Current Stimulation in Stroke: A Bibliometric Analysis.

Background: Over the past decade, many studies in the field of transcranial direct current stimulation (tDCS) in stroke have been published in scholarly journals. However, a scientometric analysis focusing on tDCS after stroke is still missing. The purpose of this study is to deliver a bibliometric analysis to investigate the global hotspots and frontiers in the domain of tDCS in stroke from 2012 to 2021. Methods: Articles and reviews related to tDCS in stroke were retrieved and obtained from the Web of Science core collection database from 2012 to 2021. Data visualization and analysis were conducted by using CiteSpace, VOSviewer, and Microsoft Excel 2019. Results: Finally, 371 publications were included in the scientometric analysis, including 288 articles and 83 reviews. The results showed that the number of publications per year increased from 15 to 68 in the last 10 years. Neurosciences was the main research hotspot category (n = 201). Frontiers in Human Neuroscience was the most published journal with 14 papers. The most productive author, institution, and country were Fregni F (n = 13), the League of European Research Universities (n = 37), and the United States of America (n = 98), respectively. A burstness analysis of keywords and the literature indicated that current studies in the field of tDCS in stroke focused on poststroke aphasia, tDCS combined with robotic therapy, and anatomical parameters. Conclusion: The research of tDCS in stroke is predicted to remain a research hotspot in the future. We recommend investigating the curative effect of other different tDCS closed-loop rehabilitation methods for different stroke dysfunctions. In conclusion, this bibliometric study presented the hotspots and trends of tDCS in stroke over the last decade, which may help researchers manage their further studies.

Capturing Neuroplastic Changes after iTBS in Patients with Post-Stroke Aphasia: A Pilot fMRI Study.

Intermittent theta-burst stimulation (iTBS) is a high-efficiency transcranial magnetic stimulation (TMS) paradigm that has been applied to post-stroke aphasia (PSA). However, its efficacy mechanisms have not been clarified. This study aimed to explore the immediate effects of iTBS of the primary motor cortex (M1) of the affected hemisphere, on the functional activities and connectivity of the brains of PSA patients. A total of 16 patients with aphasia after stroke received iTBS with 800 pulses for 300 s. All patients underwent motor, language, and cognitive assessments and resting-state functional MRI scans immediately before and after the iTBS intervention. Regional, seed-based connectivity, and graph-based measures were used to test the immediate functional effects of the iTBS intervention, including the fractional amplitude of low-frequency fluctuation (fALFF), degree centrality (DC), and functional connectivity (FC) of the left M1 area throughout the whole brain. The results showed that after one session of iTBS intervention, the fALFF, DC, and FC values changed significantly in the patients' brains. Specifically, the DC values were significantly higher in the right middle frontal gyrus and parts of the left parietal lobe (p < 0.05), while fALFF values were significantly lower in the right medial frontal lobe and parts of the left intracalcarine cortex (p < 0.05), and the strength of the functional connectivity between the left M1 area and the left superior frontal gyrus was reduced (p < 0.05). Our findings provided preliminary evidences that the iTBS on the ipsilesional M1 could induce neural activity and functional connectivity changes in the motor, language, and other brain regions in patients with PSA, which may promote neuroplasticity and functional recovery.

Associations between Upper Extremity Motor Function and Aphasia after Stroke: A Multicenter Cross-Sectional Study.

METHODS: Patients with stroke were compared and correlated from overall and three periods (1-3 months, 4-6 months, and >6 months). Fugl-Meyer assessment for the upper extremity (FMA-UE) and action research and arm test (ARAT) were used to compare the UE motor status between patients with PSA and without PSA through a cross-sectional study among 435 patients. Then, the correlations between the evaluation scale scores of UE motor status and language function of patients with PSA were analyzed in various dimensions, and the language subfunction most closely related to UE motor function was analyzed by multiple linear regression analysis. RESULTS: We found that the scores of FMA-UE and ARAT in patients with PSA were 14 points ((CI) 10 to 18, p < 0.001) and 11 points lower ((CI) 8 to 13, p < 0.001), respectively, than those without PSA. Their FMA-UE (r = 0.70, p < 0.001) and ARAT (r = 0.62, p < 0.001) scores were positively correlated with language function. Regression analysis demonstrated that spontaneous speech ability may account for UE motor function (R 2 = 0.51, p < 0.001; R 2 = 0.42, p < 0.001). Consistent results were also obtained from the analyses within the three time subgroups. CONCLUSION: Stroke patients with PSA have worse UE motor performance. UE motor status and language function showed positive correlations, in which spontaneous speech ability significantly accounts for the associations.

Long-term Effectiveness and Adoption of a Cellphone Augmented Reality System on Patients with Stroke: Randomized Controlled Trial.

BACKGROUND: A serious game-based cellphone augmented reality system (CARS) was developed for rehabilitation of stroke survivors, which is portable, convenient, and suitable for self-training. OBJECTIVE: This study aims to examine the effectiveness of CARS in improving upper limb motor function and cognitive function of stroke survivors via conducting a long-term randomized controlled trial and analyze the patient's acceptance of the proposed system. METHODS: A double-blind randomized controlled trial was performed with 30 poststroke, subacute phase patients. All patients in both the experimental group (n=15) and the control group (n=15) performed a 1-hour session of therapy each day, 5 days per week for 2 weeks. Patients in the experimental group received 30 minutes of rehabilitation training with CARS and 30 minutes of conventional occupational therapy (OT) each session, while patients in the control group received conventional OT for the full 1 hour each session. The Fugl-Meyer Assessment of Upper Extremity (FMA-UE) subscale, Action Research Arm Test (ARAT), manual muscle test and Brunnstrom stage were used to assess motor function; the Mini-Mental State Examination, Add VS Sub, and Stroop Game were used to assess cognitive function; and the Barthel index was used to assess activities of daily living before and after the 2-week treatment period. In addition, the User Satisfaction Evaluation Questionnaire was used to reflect the patients' adoption of the system in the experimental group after the final intervention. RESULTS: All the assessment scores of the experimental group and control group were significantly improved after intervention. After the intervention. The experimental group's FMA-UE and ARAT scores increased by 11.47 and 5.86, respectively, and were both significantly higher than the increase of the control group. Similarly, the score of the Add VS Sub and Stroop Game in the experimental group increased by 7.53 and 6.83, respectively, after the intervention, which also represented a higher increase than that in the control group. The evaluation of the adoption of this system had 3 sub-dimensions. In terms of accessibility, the patients reported a mean score of 4.27 (SD 0.704) for the enjoyment of their experience with the system, a mean 4.33 (SD 0.816) for success in using the system, and a mean 4.67 (SD 0.617) for the ability to control the system. In terms of comfort, the patients reported a mean 4.40 (SD 0.737) for the clarity of information provided by the system and a mean 4.40 (SD 0.632) for comfort. In terms of acceptability, the patients reported a mean 4.27 (SD 0.884) for usefulness in their rehabilitation and a mean 4.67 (0.617) in agreeing that CARS is a suitable tool for home-based rehabilitation. CONCLUSIONS: The rehabilitation based on combined CARS and conventional OT was more effective in improving both upper limb motor function and cognitive function than was conventional OT. Due to the low cost and ease of use, CARS is also potentially suitable for home-based rehabilitation. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800017568; https://tinyurl.com/xbkkyfyz.

Two cosine wave elastic-plastic contact model.

Based on Hertz elastic contact theory, the contact mechanics model of two cosine wave is established. The mechanical characteristics of the model in the elastic, elastic-plastic, and plastic stages were studied. The influence of load on contact deformation and other characteristics is considered. The finite element method is used to analyze the deformation process of the model, and the results are compared with those of the mechanical model. The effects of amplitude and wavelength of cosine wave on its mechanical characteristics are discussed. The results show that the model reflects the relationship between the load and the mechanical characteristics of the model, and the difference of amplitude and wavelength will affect this characteristic.

Ubiquitin C-terminal hydrolase L1 (UCHL1) regulates post-myocardial infarction cardiac fibrosis through glucose-regulated protein of 78 kDa (GRP78).

Abnormal cardiac fibrosis indicates cardiac dysfunction and poor prognosis in myocardial infarction (MI) patients. Many studies have demonstrated that the ubiquitin proteasome system (UPS) plays a significant role in the pathogenesis of fibrosis. Ubiquitin C-terminal hydrolase L1 (UCHL1), a member of the UPS, is related to fibrosis in several heart diseases. However, whether UCHL1 regulates cardiac fibrosis following MI has yet to be determined. In the present study, we found that UCHL1 was dramatically increased in infarct hearts and TGF-ß1-stimulated cardiac fibroblasts (CFs). Inhibition of UCHL1 with LDN57444 (LDN) reversed the myocardial fibrosis in post-MI heart and improved cardiac function. Treatment of LDN or UCHL1 siRNA abolished the TGF-ß1-induced fibrotic response of CFs. We further identified GRP78 as an interactor of UCHL1 through screening using immunoprecipitation-mass spectrometer. We determined that UCHL1 interacted with glucose-regulated protein of 78 kDa (GRP78) and prompted GRP78 degradation via ubiquitination. Furthermore, we found that GRP78 was upregulated after UCHL1 knockdown and that the GRP78 inhibitor HA15 diminished the antifibrotic function exerted by UCHL1 knockdown in CFs stimulated with TGF-ß1. This suggests that UCHL1 regulates cardiac fibrosis post MI through interactions with GRP78. This work identifies that the UCHL1-GRP78 axis is involved in cardiac fibrosis after MI.

Research on the elastic-plastic external contact mechanical properties of cylinder.

Based on Hertz contact theory, an elastic-plastic contact mechanics model of outer cylinder under different contact angles of axis is proposed. The relationship among contact angle, load and contact deformation, contact stiffness and contact area is established. The finite element method is used to simulate the elastic-plastic contact process of the cylinder. The influence of the load and radius of the cylinder model on the contact deformation and the contact stiffness is compared and analyzed under different contact angles. The error of the analysis results of the finite element and the mechanical model is within 9%. On this basis, the influence of contact deformation, contact area and contact angle on the contact stiffness of the outer cylinder in elastic and plastic stage is explored. The results show that in the stage of elastic and plastic deformation, the amount of contact deformation and contact area increase with the increase of load. The contact stiffness decreases with the increase of contact angle and increases with the increase of cylinder radius. The amount of contact deformation decreases with the increase of cylinder radius, and tends to constant gradually. In the elastic stage, the contact stiffness increases with the increase of load. The contact area decreases with the increase of contact angle and increases with the increase of cylinder radius. In the plastic stage, the contact stiffness is constant with the increase of load, and the contact area is independent of contact angle and cylinder radius.

A Water-soluble Near-infrared Fluorescent Probe for Cysteine/Homocysteine and Its Application in Live Cells and Mice.

A near-infrared (NIR) and water-soluble probe was synthesized and studied for the detection of Cys/Hcy in aqueous solution, living cells and mice. The probe was composed of cyanine derivative as the NIR fluorescent reporting unit and pyrimidiny-thioether moiety as the Cys/Hcy responsive unit. Treatment with Cys/Hcy induced the formation of sulfur-substituted products, then intramolecular rearrangement reaction would occur to produce amino-substituted products and resulting in enhanced red fluorescence emissions. It could be applied to sense Cys/Hcy both in solution with the detection limit of 0.17 µM (or 0.32 µM) and in living cells. Cell imaging experiments proved that such a probe exhibited good cell penetration. In addition, the probe could detect Cys/Hcy in live mice with strong turn-on fluorescent response.

Synthesis and biological evaluation of quinoxaline derivatives as tubulin polymerization inhibitors that elevate intracellular ROS and triggers apoptosis via mitochondrial pathway.

A series of novel quinoxaline derivatives were synthesized and evaluated for their antiproliferative activity in three human cancer cell lines. Compound 12 exhibited the most potent antiproliferative activity with IC50 in the range of 0.19-0.51 µM. The compound inhibited tubulin polymerization and disrupted the microtubule network, leading to G2/M phase arrest. Furthermore, compound 12 induced ROS production and malfunction of mitochondrial membrane potential. Compound 12 led to cancer cells apoptosis in a dose-dependent manner. Western blot analysis showed that compound 12 induced up-regulation of p21 and affected the expression of cell cycle-related proteins. The binding mode was also probed by molecular docking.