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Objectives. Schizophrenia (SCZ) is associated with disrupted functional brain connectivity, and antipsychotic medications are the primary and most commonly used treatment for schizophrenia. However, not all patients respond to antipsychotic medications. Methods. The study is aimed at investigating whether the graph-theory-based degree centrality (DC), derived from resting-state functional MRI (rs-fMRI), can predict the treatment outcomes. rs-fMRI data from 38 SCZ patients were collected and compared with findings from 38 age- and gender-matched healthy controls (HCs). The patients were treated with antipsychotic medications for 16 weeks before undergoing a second rs-fMRI scan. DC data were processed using DPABI and SPM12 software. Results. SCZ patients at baseline showed increased DC in the frontal and temporal gyrus, anterior cingulate cortex, and precuneus and reduced DC in bilateral subcortical gray matter structures. However, those abnormalities showed a clear renormalization after antipsychotic medication treatments. Support vector machine analysis using leave-one-out cross-validation achieved a correct classification rate of 84.2% (sensitivity 78.9%, specificity 89.5%, and area under the receiver operating characteristic curve (AUC) 0.925) for differentiating effective subjects from ineffective subjects. Brain areas that contributed most to the classification model were mainly located within the bilateral putamen, left inferior frontal gyrus, left middle occipital cortex, bilateral middle frontal gyrus, left cerebellum, left medial frontal gyrus, left inferior temporal gyrus, and left angular. Furthermore, the DC change within the bilateral putamen is negatively correlated with the symptom improvements after treatment. Conclusions. Our study confirmed that graph-theory-based measures, combined with machine-learning algorithms, can provide crucial insights into pathophysiological mechanisms and the effectiveness of antipsychotic medications.

To explore the impact of pre-hospital ACEI and ARB exposure on the prognosis of ARF patients.A single-center retrospective cohort study.Medical Information Mart for Intensive Care-III (MIMIC-III) database.The patients meeting ICD-9 code of acute respiratory failure were enrolled.The primary exposure was the pre-hospital exposure of ACEI and ARB.The primary outcome was in-hospital mortality. Multiple logistic regression analysis was conducted to determine the independent effect of ACEI/ARB exposure on mortality. Propensity score matching (PSM) method was adopted to reduce bias of the confounders. Subgroup analysis and sensitivity analysis were used to test the stability of the conclusion. 5335 adult ARF patients were enrolled. Mortality was significantly decreased in patients with ACEI/ARB exposure before and after PSM, and the adjusted odds ratio (OR) of ACEI/ARB exposure was 0.56 (95% CI 0.43-0.72). In the subgroup analysis, ACEI/ARB lost its protective effect in young subgroup, but no significant interaction was found between ACEI/ARB exposure and age (p = 0.082). The point estimation and lower 95% limit of E-value was 2.97 and 2.12. In sensitivity analysis, ACEI/ARB exposure showed similar effect in ARDS cohort, but no significantly difference was found in the MIMIC-IV database, which may be explained by small sample size of the ACEI/ARB group.Among patients with acute respiratory failure, pre-hospital ACEI/ARB exposure was associated with better outcomes and acted as an independent factor. The relationship between ACEI/ARB and prognosis of ARF is worth investigating further.

Synergetic recovery of both somatosensory and motor functions is highly desired by limb amputees to fully regain their lost limb abilities. The commercially available prostheses can restore the lost motor function in amputees but lack intuitive sensory feedback. The previous studies showed that electrical stimulation on the arm stump would be a promising approach to induce sensory information into the nervous system, enabling the possibility of realizing sensory feedback in limb prostheses. However, there are currently limited studies on the effective evaluation of the sensations evoked by transcutaneous electrical nerve stimulation (TENS). In this paper, a multichannel TENS platform was developed and the different stimulus patterns were designed to evoke stable finger sensations for a transradial amputee. Electroencephalogram (EEG) was recorded simultaneously during TENS on the arm stump, which was utilized to evaluate the evoked sensations. The experimental results revealed that different types of sensations on three phantom fingers could be stably evoked for the amputee by properly selecting TENS patterns. The analysis of the event-related potential (ERP) of EEG recordings further confirmed the evoked sensations, and ERP latencies and curve characteristics for different phantom fingers showed significant differences. This work may provide insight for an in-depth understanding of how somatosensation could be restored in limb amputees and offer technical support for the applications of non-invasive sensory feedback systems.

Objective: Electrophysiological signals are recorded generally by metal electrodes placed on body surface. For long term use, the signal quality may decay with the change of interface impedance between electrodes and skin due to the conductive hydrogel dehydration. Besides, electrodes may shift during body movements, which causes unstable signal recordings. Methods: To improve the quality of electrophysiological signal recordings on human body surface, a type of microneedle electrode array (MEA) with microneedles around 550 μm in length was fabricated with a magnetization-induce self-assembly method. Results: Compared with the commonly used dry electrode array, the MEA has lower and more stable interface impedance, especially when the electrode-skin interface is under unstable pressures. For electrophysiological signal recording, the MEA can acquire electromyography (EMG) with significantly lower noise energy, higher signal-to-noise ratio, and higher motion-classification accuracy based on the EMG pattern-recognition method. Additionally, high quality electrocardiography (ECG) can be recorded by using the MEA, where more accurate R-peaks are extracted in different scenarios. Besides, there was no report about any discomfort like bleeding or inflammation by all the subjects. Conclusion: This research proved that the microneedles on the MEA can penetrate through the corneum and reach the epidermis of the subjects, which could avoid the influence of corneum and fix the electrode on the body surface for high-quality signal recording especially during body movements. Furthermore, the microneedles would not touch the dermis, enabling a painless signal acquisition. Significance: This work is beneficial to the applications of wearable human-machine interface technology.

Background: Amnestic mild cognitive impairment (aMCI) is the transitional stage between normal aging and Alzheimer’s disease (AD). Some aMCI patients will progress into AD eventually, whereas others will not. If the trajectory of aMCI can be predicted, it would enable early diagnosis and early therapy of AD. Objective: To explore the development trajectory of aMCI patients, we used diffusion tensor imaging to analyze the white matter microstructure changes of patients with different trajectories of aMCI. Methods: We included three groups of subjects:1) aMCI patients who convert to AD (MCI-P); 2) aMCI patients who remain in MCI status (MCI-S); 3) normal controls (NC). We analyzed the fractional anisotropy and mean diffusion rate of brain regions, and we adopted logistic binomial regression model to predicate the development trajectory of aMCI. Results: The fraction anisotropy value is significantly reduced, the mean diffusivity value is significantly increased in the two aMCI patient groups, and the MCI-P patients presented greater changes. Significant changes are mainly located in the cingulum, fornix, hippocampus, and uncinate fasciculus. These changed brain regions significantly correlated with the patient’s Mini-Mental State Examination scores. Conclusion: The study predicted the disease trajectory of different types of aMCI patients based on the characteristic values of the above-mentioned brain regions. The prediction accuracy rate can reach 90.2%, and the microstructure characteristics of the right cingulate band and the right hippocampus may have potential clinical application value to predict the disease trajectory.

Cortical tremor/myoclonus is the hallmark feature of benign adult familial myoclonic epilepsy (BAFME), the mechanism of which remains elusive. A hypothesis is that a defective control in the preexisting cerebellar-motor loop drives cortical tremor. Meanwhile, the basal ganglia system might also participate in BAFME. This study aimed to discover the structural basis of cortical tremor/myoclonus in BAFME.Nineteen patients with BAFME type 1 (BAFME1) and 30 matched healthy controls underwent T1-weighted and diffusion tensor imaging scans. FreeSurfer and spatially unbiased infratentorial template (SUIT) toolboxes were utilized to assess the motor cortex and the cerebellum. Probabilistic tractography was generated for two fibers to test the hypothesis: the dentato-thalamo-(M1) (primary motor cortex) and globus pallidus internus (GPi)-thalamic projections. Average fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) of each tract were extracted.Cerebellar atrophy and dentate nucleus alteration were observed in the patients. In addition, patients with BAFME1 exhibited reduced AD and FA in the left and right dentato-thalamo-M1 nondecussating fibers, respectively false discovery rate (FDR) correction q .05. Cerebellar projections showed negative correlations with somatosensory-evoked potential P25-N33 amplitude and were independent of disease duration and medication. BAFME1 patients also had increased FA and decreased MD in the left GPi-thalamic projection. Higher FA and lower RD in the right GPi-thalamic projection were also observed (FDR q .05).The present findings support the hypothesis that the cerebello-thalamo-M1 loop might be the structural basis of cortical tremor in BAFME1. The basal ganglia system also participates in BAFME1 and probably serves a regulatory role.

Long non-coding RNAs (lncRNAs) have been comprehensively implicated in various cellular functions by mediating transcriptional or post-transcriptional activities. MALAT1 is involved in the differentiation, proliferation, and apoptosis of multiple cell lines, including BMSCs, osteoblasts, osteoclasts, and chondrocytes. Interestingly, MALAT1 may interact with RNAs or proteins, regulating cellular processes. Recently, MALAT1 has been reported to be associated with the development of bone and cartilage diseases by orchestrating the signaling network. The involvement of MALAT1 in the pathological development of bone and cartilage diseases makes it available to be a potential biomarker for clinical diagnosis or prognosis. Although the potential mechanisms of MALAT1 in mediating the cellular processes of bone and cartilage diseases are still needed for further elucidation, MALAT1 shows great promise for drug development.

Dentate nuclei (DN) are vital structures in the anatomical circuits that link the cerebellum to the cerebrum. However, the characteristics of DN functional connectivity (FC) in schizophrenia remain largely unknown. In this study, we investigated the FC of the DN in patients with schizophrenia and examined their possible clinical correlates using resting-state functional magnetic imaging data. We found that the patient group had greater DN FC with the parietal lobe (e.g., postcentral gyrus and superior parietal lobule) and less DN FC with the prefrontal cortex (e.g., superior frontal gyrus), posterior cingulate cortex, and regional cerebellum (e.g., vermis 4-5 and crus I) than did the control group. Furthermore, some abnormal connectivities of the DN with these regions significantly correlated with psychiatric symptoms. These results suggest that the DN circuits are disturbed and may participate in the pathophysiology of schizophrenia.

Acute myeloid leukemia (AML) is a hematological malignancy with high incidence and recurrence rates. Gene expression profiling has revealed that transcriptional overexpression of glioma‐associated oncogene 1 (GLI1), a vital gene in the Hedgehog (Hh) signaling pathway, occurs in poor-prognosis AML, and high levels of phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1) and AKT3 predict shorter overall survival in AML patients. In this study, we discovered that GLI1 overexpression promotes cell proliferation and reduces chemotherapy sensitivity in AML cells while knocking down GLI1 has the opposite effect. Moreover, GLI1 promoted cell cycle progression and led to elevated protein levels of cyclins and cyclin-dependent kinases (CDKs) in AML cells. By luciferase assays and co-immunoprecipitation, we demonstrated that the PI3K/AKT pathway is directly activated by GLI1. GLI1 overexpression significantly accelerates tumor growth and upregulated p-AKT, CDK4, and cyclinD3 in vivo. Notably, the GLI1 inhibitor GANT61 and the CDK4/6 inhibitor PD 0332991 had synergistic effects in promoting Ara-c sensitivity in AML cell lines and patient samples. Collectively, our data demonstrate that GLI1 reduces drug sensitivity by regulating cell cycle through the PI3K/AKT/GSK3/CDK pathway, providing a new perspective for involving GLI1 and CDK4/6 inhibitors in relapsed/refractory (RR) patient treatment.

Background Dengue virus (DENV) infection is increasingly common in southern China and can be transmitted through blood transfusion but is not currently part of donor screening throughout the region. We assessed DENV prevalence among donors at the Xishuangbanna Blood Center, Yunnan, to support development of DENV screening strategies. Methods Blood samples were collected randomly between June 2019 and August 2019. These were screened for anti-DENV IgG and IgM using enzyme-linked immunosorbent assay (ELISA). Then, all reactive samples and some randomly-chosen non-reactive samples were used to detect DENV RNAs using real-time polymerase-chain-reaction (RT-PCR) assays. After RT-PCR, samples were further tested for soluble nonstructural protein 1 (NS1) using the colloidal gold method. Donors demographics were also collected and assessed. Results Over the study period, 2254 donor samples were collected and tested for anti-DENV IgG and IgM by ELISA. This revealed 598 anti-DENV IgG and/or IgM reactive samples, a serological prevalence of 26.53%. Of these, 26 were RT-PCR positive and/or NS1 positive. Significant differences in DENV prevalence were noted by occupation (P = 0.001), education (P ), and ethnicity (P = 0.026). Conclusion The prevalence of DENV in Xishuangbanna Blood Center was higher than most other blood centers that have implemented DENV donor screening. Our study provides first-hand data about the prevalence of DENV and allows the development of a screening strategy for clinical use.

Background A novel coronavirus has caused an international outbreak. Currently, there are no specific therapeutic agents for coronavirus infections. Convalescent plasma (CP) therapy is a potentially effective treatment option. Methods Patients who had recovered from COVID‐19 and had been discharged from the hospital for more than two weeks were recruited. COVID‐19 convalescent plasma (CCP)‐specific donor screening and selection were performed based the following criteria: 1) aged 18‐55 years; 2) eligible for blood donation; 3) diagnosed with COVID‐19; 4) had two consecutive negative COVID‐19 nasopharyngeal swab tests based on PCR (at least 24 h apart) prior to hospital discharge; 5) had been discharged from the hospital for more than 2 weeks; and 6) had no COVID‐19 symptoms prior to convalescent plasma donation. In addition, preference was given to CCP donors who had a fever lasting more than 3 days or a body temperature exceeding 38.5 Celsius, and 4 weeks after the onset of symptoms. CCP collection was performed using routine plasma collection procedures via plasmapheresis. In addition to routine donor testing, the CCP donors’ plasma was also tested for SARS‐CoV‐2 nucleic acid and S‐RBD‐specific IgG antibody. Results Of the 81 potential CCP donors, 64 (79%) plasma products were collected. There were 18 female donors and 46 male donors. There were 34 first‐time blood donors and 30 repeat donors. The average time between CCP collection and initial symptom onset was 49.1 days, and the average time between CCP collection and hospital discharge was 38.7 days. The average volume of CCP collected was 327.7 ml. All Alanine transaminase ( ALT ) testing results met blood donation requirements. HIV Ag/Ab, anti‐HCV, anti‐syphilis and HBsAg were all negative; NAT for HIV, HBV, and HCV were also negative. In addition, all of the CCP donors’ plasma units were negative for SARS‐CoV‐2 RNA. Of the total 64 CCP donors tested, only one had an S‐RBD‐specific IgG titer of 1:160, all others had a titer of ≥1:320. Conclusion Based on a feasibility study of a pilot CCP program in Wuhan China, we demonstrated the success and feasibility of CCP collection. In addition, all of the CCP units collected had a titer of ≥ 1:160 for S‐RBD‐specific IgG antibody, which met the CCP quality control requirements based on the Chinese national guidelines for CCP. This article is protected by copyright. All rights reserved.

Background Transfusion-related acute lung injury (TRALI) is an important cause of death associated with transfusion, and no specific clinical treatments are available. Endothelial cells are believed to play an important role in the development of TRALI. This study investigated whether IL-35, an endothelial stabilizing cytokine could regulate the severity of antibody-mediated TRALI in vivo. Study design and methods Human microvascular endothelial cells (HMVECs) were cultured in vitro, rIL-35(2 μg/mL) was added before HMVECs activation, and HMVECs were fully activated by LPS (0.5 μg/mL). Then cells were collected for flow cytometry analysis. We used a previously established "two-event" mouse model of TRALI with naive and lipopolysaccharide (LPS)-injected mice as controls. rIL-35(100 μg/kg) was injected into the tail vein for 3 consecutive days before the induction of the TRALI model. Samples were collected 2 hours after TRALI induction and tested for lung tissue myeloperoxidase activity, total protein levels, lung tissue histology, endothelial cell activation assay, and cytokine assay. Results In vitro culture of HMVECs with rIL-35 verified that rIL-35 inhibited endothelial cells. In a mouse model, prophylactic administration of rIL-35 prevented pulmonary edema, increased lung protein levels, and reduced polymorphonuclear neutrophil accumulation in the lung. Conclusions This work suggests that antibody-mediated murine TRALI can be prevented by rIL-35, and that rIL-35 appears to work by inhibiting the activation of lung endothelial cells.

Background LncRNA NEAT1 was associated with the tumorigenesis of multiple myeloma (MM). However, the mechanisms of M2 macrophage polarization involved with NEAT1 in MM are still unknown. Methods Bone marrow samples, multiple myeloma cells RPMI 8226 and monocyte cell line THP-1 were used in this study. The expression of NEAT1 and miR-214 was modified by transfection with the shNEAT1 or miR-214 inhibitor. The expression of NEAT1, miR-214 and B7-H3 in MM patient tissues and cells was analyzed by RT-qPCR. ELISA assay was used to determine the release of B7-H3 in the supernatant of cell culture. The patient survival curve was analyzed using Kaplan-Meier method. The macrophage polarization markers were examined by RT-qPCR and western blotting. The interaction between NEAT1, miR-214 and B7-H3 was analyzed by Dual-Luciferase reporter and RIP assays. AG490 was used to block the JAK2/STAT3 signaling. Co-culture of THP-1 and RPMI 8226 cells was used for macrophage polarization. Results NEAT1 and B7-H3 were up-regulated, but miR-214 was obviously down-regulated in MM patients. B7-H3, NEAT1 and miR-214 were associated with overall survival time of MM patients. NEAT1 silencing induced miR-214 and inhibited the expression and release of B7-H3 and then suppressed M2 macrophage polarization via inhibiting the JAK2/STAT3 signaling. NEAT1 directly targeted miR-214, and miR-214 directly bound to B7-H3. MiR-214 inhibitor reversed the down-regulation and release of B7-H3 and M2 macrophage polarization caused by shNEAT1. The specific JAK2/STAT3 signaling inhibitor AG490 abrogated M2 macrophage polarization. Conclusion NEAT1 promoted M2 macrophage polarization by sponging miR-214 and then regulating B7-H3, thus accelerating MM progression via the JAK2/STAT3 signaling pathway. Our study revealed novel mechanisms of M2 macrophage polarization and provided new potential clinical therapeutic targets for MM.

Background Remifentanil patient-controlled analgesia (rPCA) and epidural analgesia (EA) has been used for pain relief in labor. We aimed to evaluate the efficacy and safety of rPCA versus EA in labor, to provide evidence support for clinical analgesia and pain care. Methods We searched PubMed, EMBASE, ScienceDirect, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang and Weipu databases for RCTs comparing rPCA and EA in labor until February 15, 2022. Two researchers independently screened literature and extracted data. RevMan 5.3 software was used for data analysis. Results A total of 10 RCTs involving 3086 parturients were enrolled, 1549 parturients received rPCA and 1537 received EA. Meta-analysis indicated that the incidence of intrapartum maternal fever within 1 hour of labor analgesia (OR = 0.43, 95%CI: 0.30~0.62), after 1 hour of labor analgesia (OR = 0.42, 95%CI: 0.20~0.90) in the rPCA was significantly less than that of EA (all P0.05). Conclusion rPCA can be an optional alternative to EA with similar pain relief and less risk of intrapartum maternal fever. However, rPCA was associated with increased risk of respiratory depression. Future studies with rigorous design and larger sample size are needed to provide more reliable evidences for clinical rPCA and EA use.

Microglia are widely distributed in the central nervous system (CNS), where they aid in the maintenance of neuronal function and perform key auxiliary roles in phagocytosis, neural repair, immunological control, and nutrition delivery. Microglia in the undamaged spinal cord is in a stable state and serve as immune monitors. In the event of spinal cord injury (SCI), severe changes in the microenvironment and glial scar formation lead to axonal regeneration failure. Microglia participates in a series of pathophysiological processes and behave both positive and negative consequences during this period. A deep understanding of the characteristics and functions of microglia can better identify therapeutic targets for SCI. Technological innovations such as single-cell RNA sequencing (Sc-RNAseq) have led to new advances in the study of microglia heterogeneity throughout the lifespan. Here,We review the updated studies searching for heterogeneity of microglia from the developmental and pathological state, survey the activity and function of microglia in SCI and explore the recent therapeutic strategies targeting microglia in the CNS injury.

The cerebellum plays an important role in cognitive functions through connecting with the cerebral cortical areas. However, the relationship between the resting-state functional connectivity (FC) pattern of human cerebro-cerebellar circuits and cognition is not fully understood. The present study investigated the FC patterns of human cerebro-cerebellar circuits and their associations with verbal working memory performance (an n-back task with three subtasks: 0-back, 1-back, and 2-back) through resting-state functional magnetic resonance imaging (fMRI) data from 34 healthy subjects. The whole-brain connectivity analysis was used to identify the cortical hubs as regions of interest (ROI). Then ROI-based FC analysis was performed to investigate the connectivity characteristics within the key cortical hubs and their associations with n-back task performance. The results showed that the bilateral cerebellum lobule VI as central hubs had increased FC with the default mode network (DMN) node (e.g., right posterior cingulate cortex) and salient network (SN) node (e.g., right anterior cingulate cortex), while decreased FC with the executive control network (ECN) node (e.g., the bilateral superior frontal gyrus). Furthermore, FC values of the cerebellum lobule VI with DMN and ECN nodes correlated with verbal working memory performance (response time of 2-back task). The results suggest that the cerebro-cerebellar circuits involve the underlying neural basis of verbal working memory processing during the resting state.

Nitroglycerin (NTG), a nitric oxide-donating drug, may increase tumor blood flow and consequently increase cancer drug delivery to tumor cells. Thymidylate synthase (TS) is an essential enzyme for the de novo synthesis of deoxythymidine monophosphate; we had found that knocking down the expression of TS sensitizes lung cancer cells to cisplatin-induced cytotoxicity. However, whether NTG and cisplatin could induce synergistic cytotoxicity in nonsmall cell lung cancer (NSCLC) cells through modulating TS expression is unknown. In this study, NTG decreased TS expression in an AKT, also known as Protein kinase B (PKB) inactivation dependent manner in human lung adenocarcinoma A549 and squamous cell carcinoma H1703 cells. Enhancement of AKT activity by transfection with constitutive active AKT vectors increased the TS expression level as well as the cell survival pretreated by NTG. Moreover, NTG synergistically enhanced cytotoxicity and cell growth inhibition by cisplatin treatment in NSCLC cells, which were associated with downregulation of TS expression and inactivation of AKT in A549 and H1703 cells. Together, these results may provide a rationale to combine NTG with cisplatin-based chemotherapy to enhance the therapeutic effect for lung cancer in the future.

This study focuses on the relationships of career calling to job satisfaction in army officers. The direct and indirect (via meaning in life and meaning in work) effects of career calling on job satisfaction were investigated in 355 male army officers in China. For this purpose, structural equation modeling and bootstrap method were used. Results of confirmatory factor analysis verified the latent structures of meaning in work and job satisfaction. Structural equation modeling and χ2test indicated meaning in work and presence meaning in life partially mediated the association between career calling and job satisfaction. The bootstrap method also revealed a significant indirect path from career calling to job satisfaction through them. These findings extend previous studies and shed light on promoting job satisfaction from a positive and meaningful perspective through the effect of adaptive career calling.

Background The purpose/aim of this study was to 1) use magnetic resonance diffusion tensor imaging (DTI), fibre bundle/tract-based spatial statistics (TBSS) and machine learning methods to study changes in the white matter (WM) structure and whole brain WM network in different periods of the nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT), 2) identify the most discriminating WM regions and WM connections as biomarkers of radiation brain injury (RBI), and 3) supplement the understanding of the pathogenesis of RBI, which is useful for early diagnosis in the clinic. Methods A DTI scan was performed in 77 patients and 67 normal controls. A fractional anisotropy map was generated by DTIFit. TBSS was used to find the region where the FA differed between the case and control groups. Each resulting FA value image is registered with each other to create an average FA value skeleton. Each resultant FA skeleton image was connected to feature vectors, and features with significant differences were extracted and classified using a support vector machine (SVM). Next, brain segmentation was performed on each subject’s DTI image using automated anatomical labeling (AAL), and deterministic white matter fiber bundle tracking was performed to generate symmetrical brain matrix, select the upper triangular component as a classification feature. Two-sample t-test was used to extract the features with significant differences, then classified by SVM. Finally, we adopted a permutation test and ROC curves to evaluate the reliability of the classifier. Results For FA, the accuracy of classification between the 0–6, 6–12 and > 12 months post-RT groups and the control group was 84.5, 83.9 and 74.5%, respectively. In the case groups, the FA with discriminative ability was reduced, mainly in the bilateral cerebellum and bilateral temporal lobe, with prolonged time, the damage was aggravated. For WM connections, the SVM classifier classification recognition rates of the 0–6, 6–12 and > 12 months post-RT groups reached 82.5, 78.4 and 76.3%, respectively. The WM connections with discriminative ability were reduced. Conclusions RBI is a disease involving whole brain WM network anomalies. These brain discriminating WM regions and WM connection modes can supplement the understanding of RBI and be used as biomarkers for the early clinical diagnosis of RBI.

Background Since early 2020, convalescent plasma has been widely used for treating coronavirus disease 2019 (COVID‐19). There is limited information regarding donor tolerability of convalescent plasma donation. In this study, we evaluated the short‐term donor tolerability of convalescent plasma donation. Methods A prospective study of 309 convalescent plasma donation related adverse events were conducted at Wuhan Blood Center of China, from February 12 to April 1, 2020. Additionally, up to 28‐day post‐donation follow‐ups were performed on the donors. Results Sixteen (5.2%) adverse events were reported in 309 donations. All of these were mild vasovagal without loss of consciousness. The frequency of adverse reactions was higher in donors with a per donation volume of >8 mL/kg body weight or ≥ 600 mL

Cognitive impairments are the hallmark of schizophrenia and prominent in the early episode stage. However, the underlying pathological mechanisms of cognitive impairments are not fully understood. This study aimed to investigate the abnormal functional connectivity (FC) of the cerebellar dentate nucleus (DN) and its correlation with cognitive impairments in patients with drug-naive and first-episode schizophrenia. Resting-state functional magnetic resonance imaging data were acquired in 47 patients and 43 healthy controls. Cognitive functions were assessed by number sequence span, verbal category fluency, digit-symbol coding tests. The results showed that the patients had deficits in all three cognitive tests compared to the controls. Furthermore, the increased FC of DN with the bilateral postcentral gyrus and decreased FC of DN with the right inferior temporal gyrus and regional cerebellum (e.g., Vermis 4-5 and Crus I) were observed in the patient group compared to the control group. Importantly, these abnormal DN FC significantly correlated with cognitive tests (e.g., number sequence span and digit-symbol coding) and clinical symptoms (e.g., negative symptom) in the patient group. The results suggested that abnormal FC of DN with cortical and subcortical regions was associated with cognitive impairments and symptom severity and might be an underlying neural mechanism in schizophrenia.

Purpose. The purpose of the current study is to detect changes of topological organization of whole-brain functional networks and their relationship with the clinical treatment effects of antiepileptic drugs (AEDs) for patients with childhood absence epilepsy (CAE) using resting-state functional MRI (RS-fMRI). Patients and Methods. RS-fMRI data from 30 CAE patients were collected and compared with findings from 30 age- and gender-matched healthy controls (HCs). The patients were treated with first-line AEDs for 46.03 months before undergoing a second RS-fMRI scan. Results. CAE children at baseline showed a reduced clustering coefficient (Cp) and local efficiency (El) than the HC group, implying the reduction of functional segregation. CAE children at baseline also showed smaller characteristic path length (Lp) and higher global efficiency (Eg) compared with the HC group, implying the impairment of functional segregation. However, those metrics showed no significant differences between CAE children at follow-up and the HC group which indicated a clear renormalization of topological organization after AED treatments. CAE at follow-up also showed significantly decreased connectivity between several network regions, with which the thalamus is mainly involved. Furthermore, the reduced connectivity change between the left superior parietal gyrus and the left thalamus is positively correlated with the symptom improvements after AED treatment. Conclusion. We highlighted the convergence and divergence of brain functional network dysfunctions in CAE patients and provided crucial insights into pathophysiological mechanisms and the AED effects.

Hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a key enzyme in the mevalonate pathway of cholesterol synthesis. Dysregulation of HMGCS1 expression is a common occurrence in many solid tumors. It was also found to be overexpressed in newly diagnosed (ND) and relapsed/refractory (RR) acute myeloid leukemia (AML) patients. Previous study proved that HMGCS1 could induce drug-resistance in AML cells. However, the underlying mechanism how HMGCS1 contributed to chemoresistance remains elusive. Here, we confirmed that HMGCS1 inhibitor Hymeglusin enhanced cytarabine/Adriamycin (Ara-c/ADR) chemo-sensitivity in AML cells lines. Moreover, Ara-c-resistant HL-60 cells (HL-60/Ara-c) and ADR-resistant HL-60 cells (HL-60/ADR) were more sensitive to HMGCS1 inhibition than HL-60 cells. In addition, we demonstrated that the transcription factor GATA1 was the upstream regulator of HMGCS1 and could directly bind to the HMGCS1 promoter. After treatment of Tunicamycin (Tm), the number of mitochondria was increased and the damage of endoplasmic reticulum (ER) was reduced in bone marrow cells from AML-RR patients, compared to cells from AML-CR group. HMGCS1 protected mitochondria and ER under ER stress and up-regulated unfold protein response (UPR) downstream molecules in AML cells. In summary, we proved that HMGCS1 could upregulate UPR downstream components, protect mitochondria and ER from damage in AML cells under stress, therefore conferring drug resistance. Therefore, HMGCS1 could serve as a novel target for treatment of patients with intolerant chemotherapy and AML-RR patients.

Upper extremity motor function loss severely affects stroke survivors during daily life activities. Different rehabilitation robotic systems have been developed to allow stroke survivors regain their motor function. Meanwhile, most of the robots only operate in a passive mode and restrict the users to navigate predefined trajectories which may not align with their motion intent, thus limiting motor recovery. One way to resolve this issue would be to utilize a decoded movement intent to trigger intuitively active motor training for patients. In this direction, this study proposed and investigated the use of spatial-temporal neuromuscular descriptor (STD) for optimal decoding of multiple patterns of movement intents in patient to provide inputs for active motor training in the rehabilitation robotic systems. The STD performance was validated using High-Density surface electromyogram recordings from five stroke survivors who performed 21 limb movements. Experimental results show that the STD achieved a significant reduction in limb movement classification error (13.36%) even in the presence of the inevitable White Gaussian Noise compared to other methods (p

Background and objective Recognition of motor intention based on electroencephalogram (EEG) signals has attracted considerable research interest in the field of pattern recognition due to its notable application of non-muscular communication and control for those with severe motor disabilities. In analysis of EEG data, achieving a higher classification performance is dependent on the appropriate representation of EEG features which is mostly characterized by one unique frequency before applying a learning model. Neglecting other frequencies of EEG signals could deteriorate the recognition performance of the model because each frequency has its unique advantages. Motivated by this idea, we propose to obtain distinguishable features with different frequencies by introducing an integrated deep learning model to accurately classify multiple classes of upper limb movement intentions. Methods The proposed model is a combination of long short-term memory (LSTM) and stacked autoencoder (SAE). To validate the method, four high-level amputees were recruited to perform five motor intention tasks. The acquired EEG signals were first preprocessed before exploring the consequence of input representation on the performance of LSTM-SAE by feeding four frequency bands related to the tasks into the model. The learning model was further improved by t-distributed stochastic neighbor embedding (t-SNE) to eliminate feature redundancy, and to enhance the motor intention recognition. Results The experimental results of the classification performance showed that the proposed model achieves an average performance of 99.01% for accuracy, 99.10% for precision, 99.09% for recall, 99.09% for f1_score, 99.77% for specificity, and 99.0% for Cohen's kappa, across multi-subject and multi-class scenarios. Further evaluation with 2-dimensional t-SNE revealed that the signal decomposition has a distinct multi-class separability in the feature space. Conclusion This study demonstrated the predominance of the proposed model in its ability to accurately classify upper limb movements from multiple classes of EEG signals, and its potential application in the development of a more intuitive and naturalistic prosthetic control.

MicroRNA-27 is a critical non-coding metabolic gene that is often aberrantly overexpressed in non-alcoholic fatty livers (NAFLD). However, the pathogenic role of miR-27 in NAFLD remains unknown. In this study, we attempted to identify the mechanism by which miR-27 was regulated in the context of insulin resistance, a predisposed metabolic disorder in NAFLD. Our data from cell culture and animal studies showed that insulin, CREB, and Hippo signalings coordinately regulated miR-27. First, miR-27 was upregulated in palmitate-treated cells and high fat diet-fed mouse livers, which exhibited insulin resistance and CREB overexpression. Second, miR-27 peaked in the mouse liver at the post-absorptive phase when CREB activity was increased. Also, miR-27 was increased rapidly in cell lines when CREB was deactivated by insulin treatment. Third, miR-27 was decreased in cultured cells when CREB was downregulated by siRNA or metformin treatment. In contrast, Forskolin-mediated activation of CREB promoted miR-27 expression. Fourth, Hippo signaling repressed miR-27 in a CREB-independent manner: miR-27 was reduced in cells at full confluence but was inhibited in cells transfected with siRNA against Lats2 and Nf2, which were two positive regulators of Hippo signaling. Lastly, bioinformatics and luciferase assay showed that miR-27 inhibited Akt phosphorylation by targeting Pdpk1 and Pik3r1. Overexpression of miR-27 impaired Akt phosphorylation in cell lines and primary mouse hepatocytes upon insulin stimulation. In conclusion, our data suggest that insulin, CREB, and Hippo signalings contribute to aberrant miR-27 overexpression and eventually lead to insulin resistance in NAFLD.

Recently, there is an increasing recognition that sensory feedback is critical for proper motor control. With the help of BCI, people with motor disabilities can communicate with their environments or control things around them by using signals extracted directly from the brain. The widely used non-invasive EEG based BCI system require that the brain signals are first preprocessed, and then translated into significant features that could be converted into commands for external control. To determine the appropriate information from the acquired brain signals is a major challenge for a reliable classification accuracy due to high data dimensions. The feature selection approach is a feasible technique to solving this problem, however, an effective selection method for determining the best set of features that would yield a significant classification performance has not yet been established for motor imagery (MI) based BCI. This paper explored the effectiveness of bio-inspired algorithms (BIA) such as Ant Colony Optimization (ACO), Genetic Algorithm (GA), Cuckoo Search Algorithm (CSA), and Modified Particle Swarm Optimization (M-PSO) on EEG and ECoG data. The performance of SVM classifier showed that M-PSO is highly efficacious with the least selected feature (SF), and converges at an acceptable speed in low iterations.

Introduction: The miniaturization of blood pumps has become a trend due to the advantage of easier transplantation, especially for pediatric patients. In small-scale pumps, it is much easier and more cost-efficient to manufacture the impeller with straight blades compared to spiral-profile blades. Methods: Straight-blade impeller designs with different blade angles, blade numbers, and impeller flow passage positions are evaluated using the computational fluid dynamics method. Blade angles (θ = 0°, 20°, 30°, and 40°), blade numbers ( N = 5, 6, 7, and 8), and three positions of impeller flow passage (referred to as top, middle, and bottom) are selected as the studied parametric values. Results: The numerical results reveal that with increasing blade angle, the pressure head and the hydraulic efficiency increase, and the average scalar shear stress and the normalized index of hemolysis decrease. The minimum radial force and axial thrust are obtained when θ equals 20°. In addition, the minimum average scalar shear stress and normalized index of hemolysis values are obtained when N = 6, and the maximum values are obtained when N = 5. Regarding the impeller flow passage position, the axial thrust and the stagnation area forming in the impeller eye are reduced as the flow passage height declines. Conclusion: The consideration of a blade angle can greatly improve the performance of blood pumps, although the influence of the blade number is not very easily determined. The bottom position of the impeller flow passage is the best design.

To study the effect of a new human sperm freezing method on the sperm recovery rate and search for an optimal method for cryopreservation of human epididymal sperm.We collected semen samples from 76 men with obstructive azoospermia by percutaneous epididymal sperm aspiration and divided each sample into two parts to be cryopreserved with a self-made metal freezing plate (the experimental group) or by slow freezing (the control group), respectively. We measured the percentage of progressively motile sperm (PMS) with the computer-assisted semen analysis system and compared the membrane function, DNA fragmentation index (DFI), acrosin activity and morphological abnormality of the sperm between the two groups before and after cryopreservation.After thawing, both the percentages of PMS and hypotonically swollen sperm were significantly higher in the experimental than in the control group (［12.0 ± 7.5］% vs ［8.0 ± 5.1］%, P0.05; ［22.0 ± 17.5］% vs ［18.0 ± 20.5］%, P0.05), though both decreased in comparison with the pre-freezing parameters (［20.7 ± 8.8］% and ［30.0 ± 13.5］%) (P0.05). The sperm acrosin activity was remarkably higher in the experimental than in the control group after thawing (［75.2 ± 9.5］ vs ［55.7 ± 8.3］ μIU/106sperm, P0.05), though decreased as compared with the baseline (［120.0 ± 10.5］ μIU/106 sperm, P0.05). No statistically significant differences were observed between the experimental and the control groups after thawing in the percentage of morphologically abnormal sperm (［98.7 ± 8.8］% vs ［98.5±9.2］%, P0.05) or sperm DFI ［38.2 ± 8.5］% vs ［39.5 ± 10.2］%, P0.05), though both markedly elevated in comparison with the pre-freezing parameters (［97.2 ± 9.5］% and ［30.8 ± 9.7］%) (P0.05). The post-thaw recovery rate of sperm was significantly higher in the experimental than in the control group (［65.2 ± 12.0］% vs ［52.3 ± 18.0］%, P0.05).The self-made metal freezing plate, with its advantages of low cost, high efficiency, and easy operation, can be used as an effective method for cryopreservation of human sperm to achieve a high post-thaw sperm recovery rate, progressive sperm motility, and sperm acrosin activity.

Prostate cancer (PCa) is one of the most frequent cancers in men, and its biomolecular targets have been extensively studied. This study aimed to analyze the expression of toll-like receptor 9 (TLR9) and vascular endothelial growth factor C (VEGF-C) and the clinical value of the coexpression of TLR9 and VEGF-C in PCa. We retrospectively evaluated 55 patients with clinically localized, intermediate-risk, or high-risk PCa who underwent laparoscopic radical prostatectomy (LRP) and extended pelvic lymph node dissection (ePLND) without neoadjuvant hormonal therapy at a single institution from June 2013 to December 2016. In all 55 patients, the median number of lymph nodes (LNs) resected was 23 (range: 18-31), and a total of 1269 LNs were removed, of which 78 LNs were positive. Seventeen patients had positive LNs, with a positive rate of 30.9%. In addition, the immunohistochemical results in the above patients revealed that high TLR9 expression was correlated with higher Gleason score (GS) (P = 0.049), increased LN metastasis (P = 0.004), and more perineural invasion (PNI) (P = 0.033). Moreover, VEGF-C expression was associated with GS (P = 0.040), pathological stage (pT stage) (P = 0.022), LN metastasis (P = 0.003), and PNI (P = 0.001). Furthermore, a significant positive correlation between TLR9 and VEGF-C was found (P < 0.001), and the TLR9/VEGF-C phenotype was associated with LN metastasis (P = 0.047). Collectively, we propose that TLR9 stimulation may promote LN metastasis in PCa cells through the upregulation of VEGF-C expression, thereby affecting the prognosis of PCa patients. Therefore, these markers may serve as valuable targets for the treatment of PCa.

This study aimed to identify the neuroanatomical substrates and white matter connectivity in children with autism spectrum disorder (ASD) and the association between gray matter and structural connectivity. A total of 36 children including patients with ASD and healthy controls between 6 and 15 years of age were enrolled in this study. High-resolution structural MRI and functional MRI were performed and analyzed using voxel-based morphometry and tract-based spatial statistics. The relationship between gray matter volume and structural connectivity was generated using Pearson correlation analysis. Voxel-based morphometry analysis showed significantly reduced areas of gray matter in the left cerebellum. Tract-based spatial statistics analysis showed white matter abnormalities in several distinct clusters within the right inferior frontal gyrus (opercular part), the left inferior parietal lobule, and the right mentary motor area. Neither ASD nor healthy controls showed a significant correlation between gray matter volume and white matter integrity. Our study confirmed the presence of several structural and regional abnormalities in ASD children. These findings suggest that there are significant differences in some brain regions in children with autism relative to healthy children, but no association between them.

Etoposide (VP16) is a topoisomerase II inhibitor and has been used for the treatment of non-small cell lung cancer (NSCLC). Xeroderma pigmentosum complementation group C (XPC) protein is a DNA damage recognition factor in nucleotide excision repair and involved in regulating NSCLC cell proliferation and viability. Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. In this study, we report whether Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) enhanced etoposide-induced cytotoxicity in NSCLC cells through modulating the XPC expression. We found that etoposide increased XPC expression in an AKT activation manner in 2 squamous cell carcinoma H1703 and H520 cells. Knockdown of XPC using siRNA or inactivation of AKT by pharmacological inhibitor PI3K inhibitor (LY294002) enhanced the cytotoxic effects of etoposide. In contrast, enforced expression of XPC cDNA or AKT-CA (a constitutively active form of AKT) reduced the cytotoxicity and cell growth inhibition of etoposide. Hsp90 inhibitor 17-AAG enhanced cytotoxicity and cell growth inhibition of etoposide in NSCLC cells, which were associated with the downregulation of XPC expression and inactivation of AKT. Our findings suggested that the Hsp90 inhibition induced XPC downregulation involved in enhancing the etoposide-induced cytotoxicity in H1703 and H520 cells.

Multisensory processing is a prevalent research issue. However, multisensory working memory research has received inadequate attention. The present study aimed to investigate the behavioral performance of an audiovisual working memory task and its association with resting-state functional magnetic resonance imaging (fMRI) regional homogeneity (ReHo). A total of 128 healthy participants were enrolled in this study. The participants completed a modified Sternberg working memory task using complex auditory and visual objects as materials involved in different encoding conditions, including semantically congruent audiovisual, semantically incongruent audiovisual, and single modality of auditory or visual object encoding. Two subgroups received resting-state fMRI scans according to their behavioral performances. The results showed that the semantically congruent audiovisual object encoding sped up the later unisensory memory recognition in this task. Moreover, the high behavioral performance (response time, RT) group showed increased ReHo in the executive control network (ECN) and decreased ReHo in the default mode network (DMN) and saline network (SN). In addition, resting-state ReHo values in the ECN nodes (e.g., middle frontal gyrus and superior frontal gyrus) was correlated with RT. These findings suggested that semantically congruent audiovisual processing in working memory was superior to unisensory memory recognition and may be involved in the different functional networks such as ECN.

Electromyogram pattern recognition (EMG-PR) based control for upper-limb prostheses conventionally focuses on the classification of signals acquired in a controlled laboratory setting. In such a setting, relatively stable and high performances are often reported because subjects could consistently perform muscle contractions corresponding to a targeted limb motion. Meanwhile the clinical implementation of EMG-PR method is characterized by degradations in stability and classification performances due to the disparities between the constrained laboratory setting and clinical use. One of such disparities is the mobility of subject that would cause changes in the EMG signal patterns when eliciting identical limb motions in mobile scenarios. In this study, the effect of mobility on the performance of EMG-PR motion classifier was firstly investigated based on myoelectric and accelerometer signals acquired from six upper-limb amputees across four scenarios. Secondly, three methods were proposed to mitigate such effect on the EMG-PR motion classifier. From the obtained results, an average classification error (CE) of 9.50% (intra-scenario) was achieved when data from the same scenarios were used to train and test the EMG-PR classifier, while the CE increased to 18.48% (inter-scenario) when trained and tested with dataset from different scenarios. This implies that mobility would significantly lead to about 8.98% increase of classification error (p 0.05). By applying the proposed methods, the degradation in classification performance was significantly reduced from 8.98% to 1.86% (Dual-stage sequential method), 3.17% (Hybrid strategy), and 4.64% (Multi-scenario strategy). Hence, the proposed methods may potentially improve the clinical robustness of the currently available multifunctional prostheses.The study was approved by the ethics committee of Institutional Review Board of Shenzhen Institutes of Advanced Technology, and the reference number is SIAT-IRB-150515-H0077.

Left and right mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS) exhibits similar functional and clinical dysfunctions, such as depressive mood and emotional dysregulation, implying that the left and right mTLE may share a common network substrate. However, the convergent anatomical network disruption between the left and right HS remains largely uncharacterized. This study aimed to investigate whether the left and right mTLE share a similar anatomical network. We examined 43 (22 left, 21 right) mTLE patients with HS and 39 healthy controls using diffusion tensor imaging. Machine learning approaches were applied to extract the abnormal anatomical connectivity patterns in both the left and right mTLE. The left and right mTLE showed that 28 discriminating connections were exactly the same when compared to the controls. The same 28 connections showed high discriminating power in comparisons of the left mTLE versus controls (91.7%) and the right mTLE versus controls (90.0%); however, these connections failed to discriminate the left from the right mTLE. These discriminating connections, which were diminished both in the left and right mTLE, were primarily located in the limbic-frontal network, partially agreeing with the limbic-frontal dysregulation model of depression. These findings suggest that left and right mTLE share a convergent circuit, which may account for the mood and emotional deficits in mTLE and may suggest the neuropathological mechanisms underlying the comorbidity of depression and mTLE.

As an integral part of the body, the limb poses dexterous and fine motor grasping and sensing capabilities that enable humans to effectively communicate with their environment during activities of daily living (ADL). Hence, limb loss severely limits individuals' ability especially when they need to perform tasks requiring their limb functions during ADL, thus leading to decreased quality of life. To effectively restore limb functions in amputees, the advanced prostheses that are controlled by electromyography (EMG) signal have been widely investigated and used. Since EMG signals reflect neural activity, they would contain information on the muscle activation related to limb motions. Pattern recognition-based myoelectric control is an important branch of the EMG-based prosthetic control. And the EMG-based prosthetic control theoretically supports multiple degrees of freedom movements that allows amputees to intuitively manipulate the device. This chapter focuses on EMG-based prosthetic control strategy that involves utilizing intelligent computational technique to decode upper limb movement intentions from which control commands are derived. Additionally, different techniques/methods for improving the overall performance of EMG-based prostheses control strategy were introduced and discussed in this chapter.

The main purpose is to compare the characteristics and performance of a centrifugal blood pump with and without center post. Furthermore, to propose a center post design guide for the development of centrifugal blood pumps: finding the appropriate height and diameter of the center post. A centrifugal blood pump with different center post configurations is investigated using Computational Fluid Dynamics (CFD) in an extensive parametric approach. Height and diameter of the center post are varied on 4 levels each. Pressure head and hydraulic efficiency curves, pressure and velocity contours and volumetric histograms of scalar shear stress (SSS) distribution are discussed in detail. The simulation results show uniform pressure distribution around the casing in the baseline design. Although obtaining the minimum Normalized Index of Hemolysis (NIH), average scalar shear stress (ASSS), and volumetric percentage ratios (SSS > 9, 50 and 150 Pa), a stagnation and recirculation zone in the impeller eye above the casing bottom is detected in center post free (H = 0 mm) pump. With the establishment and further increase of the center post height, the stagnation zone disappears gradually. The results also indicate that flow recirculation and stagnation around the circumference of the center post occurs when the center post has a small diameter. As the diameter increases, a reversed flow is formed between the impeller and the center post. The center post can greatly reduce the stagnation zone occurring in the center post free pump. The diameter of center post makes a difference to the flow field in the gap between the impeller and the center post.

This paper presents an unobtrusive method for automatic detection of atrial fibrillation (AF) from single-channel ballistocardiogram (BCG) recordings during sleep. We developed a remote data acquisition system that measures BCG signals through an electromechanical-film sensor embedded into a bed's mattress and transmits the BCG data to a remote database on the cloud server. In the feasibility study, 12 AF patients' data were recorded during entire night of sleep. Each BCG recording was split into nonoverlapping 30s epochs labeled either AF or normal. Using the features extracted from stationary wavelet transform of these epochs, three popular machine learning classifiers (support vector machine, K-nearest neighbor, and ensembles) have been trained and evaluated on the set of 7816 epochs employing 30% hold-out validation. The results showed that all the trained classifiers could achieve an accuracy rate above 91.5%. The optimized ensembles model (Bagged Trees) could achieve accuracy, sensitivity, and specificity of 0.944, 0.970 and 0.891, respectively. These results suggest that the proposed BCG-based AF detection can be a potential initial screening and detection tool of AF in home-monitoring applications.

Purpose: To evaluate the usefulness of preoperative computed tomography (CT)-guided coil localization in patients with lung nodules who underwent video-assisted thoracoscopic surgery (VATS)...

Acute monocytic leukemia remains a big challenge, and there are a series of non-specific esterases which can be inhibited by sodium fluoride (NaF) in mononuclear cells, providing insights into the leukemia targeted therapy. In this study, the apoptotic effect of NaF with human mononuclear leukemia THP-1 cells and the inhibition of α-naphthol acetate esterase (α-NAE) activity, and also the potentially underlying mechanisms were investigated.THP-1 cells were cultured with different concentrations of NaF (0, 0.5, 1, 2, 4, 8 mM) for 24, 48 and 72 hrs. The α-NAE staining and chromogenic method were used to detect the activation of α-NAE. The 3-(4, 5-dimethylthiazol-2-yl)-2), 5-diphenyltetrazolium bromide (MTT) assay was used to detect the antitumor effect of NaF on THP-1 cells in vitro. Flow cytometry was used to observe the apoptotic ratio following treatment with NaF in THP-1 cells. The mRNA levels of mammalian target of Bcl-2 and Bax were detected pre and post-NaF treatment using reverse transcription polymerase chain reaction (RT-PCR).The generation of depression effects of THP-1 cells cultured in vitro were detected using MTT technology, which revealed a dose- and time-dependent association. After 24hrs of exposure to NaF at greater than 1mmol/L, typical apoptotic changes were observed, accompanied by the α-NAE positive reaction and decreased intensity. The IC50 was 4 mmol/L at 24hrs. Flow cytometric analysis indicated that treatment with NaF at concentrations of 2, 4 and 8 mmol/L increased the apoptotic rate of THP-1 cells. RT-PCR indicated that NaF upregulated the gene expression of Bax and downregulated the expression of Bcl-2.NaF inhibited the proliferation of THP-1 cells and the activation of α-NAE by adversely regulating the expression of Bax and Bcl-2.

Patients with type 2 diabetes mellitus (T2DM) have usually been found cognitive impairment associated with brain white matter (WM) abnormalities. However, findings have varied across studies, and any potential relationship with Alzheimer's disease (AD) remains unclear. The aim of this study was to assess the whole-brain WM integrity of T2DM patients and to compare our findings with those of published AD cases.In this study, we used diffusion tensor imaging (DTI) combined with tract-based spatial statistics (TBSS) to investigate whole-brain WM abnormalities in 48 T2DM patients and 48 healthy controls. The effects of age and gender were also evaluated.In our study, significantly decreasing FA and increasing MD and DA values (P0.05) were found in some WM regions closely related to the default mode network (DMN), including cingulum, the right frontal lobe involving the right uncinate fasciculus (UF), bilateral parietal lobes involving the superior longitudinal fasciculus (SLF) and the inferior longitudinal fasciculus (ILF), and the right middle temporal gyrus (MTG) involving the UF and the ILF. We also found abnormalities in the thalamus involving the fornix (FX), anterior thalamic radiation (ATR), and posterior thalamic radiation (PTR). The damaged regions above are similar to those found in patients with AD, as reported in previous studies.The present study not only provides useful information about the WM regions and tracts affected by T2DM but also offers insight into the underlying neuropathological process in T2DM patients and the relationship between T2DM and AD.

INTRODUCTION: Several mitochondrial DNA mutations have been reported to be associated with nonsyndromic hearing loss in several families. However, little is known about the prevalence of these mutations in sporadic patients with nonsyndromic sensorineural hearing loss. OBJECTIVE: The purpose of our study was to investigate the incidence of these mitochondrial DNA mutations in such population. METHODS: A total of 178 sporadic patients with nonsyndromic sensorineural hearing loss were enrolled in this study. Genomic DNA was extracted from the peripheral blood sample. We employed the SNaPshot(r) sequencing method to detect five mitochondrial DNA mutations, including A1555G and A827G in 12S rRNA gene and A7445G, 7472insC, and T7511C in tRNASerUCN gene. Meanwhile, we used polymerase chain reaction and sequenced the products to screen GJB2 gene mutations in patients carrying mitochondrial DNA mutations. RESULTS: We failed to detect the presence of A1555G mutation in 12S rRNA gene, and of A7445G, 7472insC, T7511C mutations in tRNASerUCN gene in our population. However, we found that 6 patients (3.37%) were carriers of a homozygous A827G mutation and one of them also carried homozygous GJB2 235delC mutation. CONCLUSION: Our findings in the present study indicate that even in sporadic patients with nonsyndromic sensorineural hearing loss, mitochondrial DNA mutations might also contribute to the clinical phenotype. Resumo Introdução: Diversas mutações do DNA mitocondrial tem sido descritas, em diferentes famílias, associadas à deficiência auditiva não sindrômica. No entanto, pouco se sabe sobrea prevalência dessas mutações em pacientes esporádicos com deficiência auditiva sensorioneural não sindrômica. Objetivo: A finalidade do nosso estudo foi investigar a incidência dessas mutações no DNA mitocondrial nessa população. Método: No total, 178 pacientes esporádicos com deficiência auditiva sensorioneural não sindrômica foram recrutados para participação no estudo. O DNA genômico foi extraído de amostra, de sangue periférico. Utilizamos o método de sequenciamento SNaPshot(r) para detecção de cinco mutações do DNA mitocondrial: A1555G e A827G no gene 12S rRNA e A7445G, 7472insCe T7511C no gene tRNASerUCN. Paralelamente, utilizamos a reação de polimerase em cadeia e sequenciamos os produtos para triagem das mutações no gene GJB2 nos pacientes portadores de mutações no DNA mitocondrial. Resultados: Em nossa população, não conseguimos detectar a presença da mutação A1555G no gene 12S rRNA e nem as mutações A7445G, 7472insC e T7511C no gene tRNASerUCN. Entretanto, constatamos que seis pacientes (3,37%) eram portadores da mutação homozigota A827G; e um deles também portava a mutação homozigota GJB2 235delC. Conclusão: Nossos achados no presente estudo indicam que, mesmo em pacientes esporádicos com deficiência auditiva sensorioneural não sindrômica, as mutações do DNA mitocondrial também podem contribuir para o fenótipo clínico.

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders in the world. Previous studies have focused on the basal ganglia and cerebral cortices. To date, the cerebellum has not been systematically investigated in patients with PD. In the current study, 45 probable PD patients and 40 age- and gender-matched healthy controls underwent structural magnetic resonance imaging, and we used support vector machines combining with voxel-based morphometry to explore the cerebellar structural changes in the probable PD patients relative to healthy controls. The results revealed that the gray matter alterations were primarily located within the cerebellar Crus I, implying a possible important role of this region in PD. Furthermore, the gray matter alterations in the cerebellum could differentiate the probable PD patients from healthy controls with accuracies of more than 95 % (p

Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by spasticity of the lower limbs due to pyramidal tract dysfunction. Here, we report that a missense homozygous mutation c.424G>T (p.D142Y) in the FARS2 gene, which encodes a mitochondrial phenylalanyl tRNA synthetase (mtPheRS), causes HSP in a Chinese consanguineous family by using combination of homozygous mapping and whole-exome sequencing. Immunohistochemical experiments were performed showing that the FARS2 protein was highly expressed in the Purkinje cells of rat cerebellum. The aminoacylation activity of mtPheRS was severely disrupted by the p.D142Y substitution in vitro not only in the first aminoacylation step but also in the last transfer step. Taken together, our results indicate that a missense mutation in FARS2 contributes to HSP, which has the clinical significance of the regulation of tRNA synthetases in human neurodegenerative diseases.

The current study aims to explore how coach&ndash, athlete attachment affects the subjective well-being (SWB) of athletes and is primarily focused on the confirmation of the mediating roles of athletes&rsquo, perceived coach support and self-esteem in the relationship between them. A total of 179 Chinese athletes participated in this study, in which they responded to questions comprising a coach&ndash, athlete attachment scale, a perceived coach support measurement, the Rosenberg self-esteem scale, and SWB measures. The results suggest that both attachment anxiety and attachment avoidance significantly predict SWB in athletes. The effects of attachment anxiety on SWB are partially mediated by perceived coach support and self-esteem, and the effects of attachment avoidance on SWB are completely mediated by perceived coach support and self-esteem. Moreover, a chain mediating effect was found: coach&ndash, athlete attachment &rarr, perceived coach support &rarr, self-esteem &rarr, SWB. These findings extend the conclusions of prior reports and shed light on how coach&ndash, athlete attachment influences the athlete&rsquo, s well-being.

Salinomycin is a polyether ionophore antibiotic having anti-tumorigenic property in various types of cancer. Elevated thymidine phosphorylase (TP) levels, a key enzyme in the pyrimidine nucleoside salvage pathway, are associated with an aggressive disease phenotype and poor prognoses. Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. In this study, we report whether Hsp90 inhibitor 17-AAG could enhance salinomycin-induced cytotoxicity in NSCLC cells through modulating TP expression in two non-small-cell lung cancer (NSCLC) cell lines, A549 and H1975. We found that salinomycin increased TP expression in a MKK3/6-p38 MAPK activation manner. Knockdown of TP using siRNA or inactivation of p38 MAPK by pharmacological inhibitor SB203580 enhanced the cytotoxic and growth inhibition effects of salinomycin. In contrast, enforced expression of MKK6E (a constitutively active form of MKK6) reduced the cytotoxicity and cell growth inhibition of salinomycin. Moreover, Hsp90 inhibitor 17-AAG enhanced cytotoxicity and cell growth inhibition of salinomycin in NSCLC cells, which were associated with down-regulation of TP expression and inactivation of p38 MAPK. Together, the Hsp90 inhibition induced TP down-regulation involved in enhancing the salinomycin-induced cytotoxicity in A549 and H1975 cells.

Human limb movement intent recognition fundamentally provides the control mechanism for assistive devices such as exoskeleton and limb prosthesis. While different biopotential signals have been utilized for limb movement intent decoding, they seldom could account for spatial information associated with changes in muscle shape that could also be used to characterize the limb motor intent. Therefore, this study developed a novel nano gold stretchable-flexible sensor that captures spatial information associated with the muscle shape change signal (MSCS) during different muscle activation patterns. The novel sensor consists of 2-channels to acquire MSCS at a sampling rate of 125 Hz, corresponding to multiple classes of upper limb movements acquired across six able-bodied subjects. By utilizing the linear discriminant analysis algorithm on the acquired data with a single extracted feature, an overall average motion decoding accuracy of 90.9% was achieved. In addition, the waveform analysis results show that the novel sensor's recordings were less affected by external interferences, thus yielding high quality signals. This study is the first to utilize nano gold stretchable-flexible material for sensor fabrication in pattern recognition of upper limb movement intent, which may facilitate the development of effective assistive devices.

Current valid treatments for acute myeloid leukemia (AML) include chemotherapy and hematopoietic stem cell transplantation, which are defective and limited respectively. The insulin-like growth factor 1 receptor (IGF-1R) is up-regulated in many solid tumors; therefore, it may be a target for tumor therapy. Interestingly, IGF-1R is modified by SUMOylation, a type of reversible post-translational modification. In this study, we found that IGF-1R was increased in both cell lines and clinical samples of AML and was modified by SUMO-1. Furthermore, IGF-1, ligand of IGF-1R, induced the up-regulation of IGF-1R and increased the proliferation of leukemia cell line. After mutation of Lys(1025) and Lys(1100) in IGF-1R, the evolutionarily conserved lysine residues were identified as the SUMOylation sites of IGF-1R, because the SUMOylation of IGF-1R in these mutants was significantly inhibited. Furthermore, the cell proliferation mediated by IGF-1 was also reduced. After inhibition of UBC9, the activating enzyme of SUMOylation, co-expression of IGF-1R and SUMO-1 was down-regulated, and cell proliferation was also inhibited. However, cell apoptosis was not significantly affected. These results suggest that IGF-1R and its SUMOylation may be a new therapeutic target for strategy of AML.

Behavioral evidence suggests functional remission or recovery in nonrefractory depressive disorder after successful antidepressant therapy, but the effect of treatment on brain structures remains unclear. It is possible that some specific structural changes are trait-related, in addition to some state-dependent anatomical regions that could be normalized by medications. In the current study, 32 treatment-naive nonrefractory depressive disorder patients and 34 matched healthy controls underwent structural MRI scans and a subgroup including 16 patients underwent the second scans after clinical recovery with antidepressant treatment. The statistical analysis of gray matter images showed that the state-dependent regions mainly comprised the key regions within the lateral default, dorsal attention, and frontoparietal networks, whereas the trait-related regions included the medial prefrontal cortex, right anterior insula, thalamus, right parahippocampal gyrus, and right middle occipital gyrus. Moreover, the gray matter changes in the left orbitofrontal cortex, right middle frontal gyrus, left inferior parietal lobule, thalamus, left precentral gyrus, left precuneus, and right middle occipital gyrus were significantly positively correlated with the durations of the current depressive episode. The current findings may not only shed new light on the neuronal effect of antidepressant on depression but also provide potential evidence of the relapse risks for the clinically recovered patients after antidepressant treatment.

Aminoacyl-tRNA synthetases (aaRSs) are a group of ancient enzymes catalyzing aminoacylation and editing reactions for protein biosynthesis. Increasing evidence suggests that these critical enzymes are often associated with mammalian disorders. Therefore, complete determination of the enzymes functions is essential for informed diagnosis and treatment. Here, we show that a yeast knock-out strain for the threonyl-tRNA synthetase (ThrRS) gene is an excellent platform for such an investigation. Saccharomyces cerevisiae ThrRS has a unique modular structure containing four structural domains and a eukaryote-specific N-terminal extension. Using randomly mutated libraries of the ThrRS gene (thrS) and a genetic screen, a set of loss-of-function mutants were identified. The mutations affected the synthetic and editing activities and influenced the dimer interface. The results also highlighted the role of the N-terminal extension for enzymatic activity and protein stability. To gain insights into the pathological mechanisms induced by mutated aaRSs, we systematically introduced the loss-of-function mutations into the human cytoplasmic ThrRS gene. All mutations induced similar detrimental effects, showing that the yeast model could be used to study pathology-associated point mutations in mammalian aaRSs.