[Determination of 11 nutrients in liquid milk by ultra-performance liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 11 nutritional components(thiamine, riboflavin, nicotinamide, nicotinic acid, pantothenic acid, pyridoxine, pyridoxal, pyridoxamine, biotin, choline, L-carnitine) in liquid milk. METHODS: Milk samples were shaken with 20 mmol/L ammonium formate solution and heated in a water bath at 100 ℃ for 30 min, then incubated with papain and acid phosphatase at 45 ℃ for 16 h, the lower liquid was collected after centrifugation for analysis. UPLC separation was performed on an ACQUITY~(TM) HSS T3(3.0 mm×150 mm, 1.8 µm) column, 2 mmol/L ammonium formate(containing 0.1% formic acid) solution and acetonitrile(containing 0.1% formic acid) were used as mobile phase. Quantitative detection was performed by internal standard method. RESULTS: 11 nutritional components can be effectively separated and detected in 12 min, and the linear correlation coefficients(R~2) were all above 0.995. The limits of detection(LODs) were between 0.05 and 0.50 µg/L, and the limits of quantification(LOQs) were between 0.20 and 1.25 µg/L. The recovery rates of three-level addition were 85.6%-119.3%, and the precision RSDs were between 3.68% and 7.82%(n=6). Based on the detection of 60 liquid milk samples from 5 different animals, it was found that the contents of 11 nutrients in liquid milk from different milk sources were significantly different, but pyridoxine could not be detected. CONCLUSION: The method can quantitatively detect 11 water-soluble nutrients, including free and bound forms, by effective enzymolysis. It is sensitive, reproducible and can meet the needs of quantitative detection.

[Advances of the Regulation of microRNAs in Follicular Development].

In recent years,microRNAs(miRNAs)have been detected at different stages of follicular development and in different cells of follicles.Extracellular vesicle(EV)-derived miRNAs have also been detected in the follicular fluid of mature follicles.miRNAs participate in the regulation of normal follicular development,and the regulation disorder may lead to the occurrence of some ovarian diseases.In order to further systematically elucidate the regulatory mechanism of miRNAs on follicular development and find suitable EV-derived miRNAs that can predict oocyte development,we reviewed the functions of miRNAs in follicular development from the perspectives of granulosa cell development,oocyte development,and hormone synthesis.

[Association between sleep duration and mild cognitive impairment in people aged 55 and above in 4 provinces of China].

OBJECTIVE: To explore the association between sleep duration and mild cognitive impairment(MCI) in people aged 55 and above in 4 provinces of China. METHODS: A stratified multi-stage cluster random sampling method was adopted. From May to August 2018 in 32 survey districts and counties in 4 provinces of Hebei, Zhejiang, Shaanxi, and Hunan, 5334 55-year-old and older persons who met the inclusion criteria were randomly selected. Among them, there were 2362 males and 2972 females, with an average age of(67. 43±7. 48) years. A questionnaire survey was conducted to collect their basic information, lifestyle, disease history, sleep duration, etc. MCI were screened based on the Montreal cognitive assessment(MoCA). Multivariate Logistic regression was used to analyze the association between sleep duration and MCI. RESULTS: 16. 76% of them slept for less than 7. 0 hours, 19. 10% of the middle-aged and elderly people slept for 9 hours or more, and 36. 24% of them were found to be MCI. After adjusted the area, age, gender, education level, work status, family monthly income per capita, smoking, drinking, physical activity, meditation time, depression, hypertension, diabetes, myocardial infarction and stroke, the result of multivariate Logistic regression analysis shown that, compared with 7. 0-7. 9 hours of sleep, the risk of MCI among middle-aged and elderly people over 55 years old with <6. 0 hours and 8. 0-8. 9 hours of sleep were 1. 417 times(95%CI 1. 012-1. 984)and 1. 191 times(95%CI 1. 001-1. 418)of the former, respectively, and the differences were statistically significant(P<0. 05). The risk of men suffering from MCI for sleep duration <6. 0 hours was 2. 083 times(95%CI 1. 145-3. 789)that of the former, and the risk of women suffering from MCI for sleep duration ≥ 9. 0 hours was 1. 741 times(95%CI 1. 301-2. 331)that of MCI. The differences are statistically significant(P<0. 05). CONCLUSION: Shorter or longer sleep time is an important factor independently related to MCI. Insufficient sleep in men and longer sleep time in women can increase the risk of MCI.

Cycloartenol exerts anti-proliferative effects on Glioma U87 cells via induction of cell cycle arrest and p38 MAPK-mediated apoptosis.

PURPOSE: Gliomas are destructive malignancies affecting mainly the central nervous system. Gliomas constitute around 50% of all the central nervous system tumors. The purpose of this study was to examine the anticancer activity of cycloartenol against the glioma U87 cells and to investigate the underlying mechanisms. METHODS: MTT and colony formation assay were used to determine the proliferation rate. Acridine orange/ethidium bromide (AO/EB) and annexin V/propidium iodide (PI) were used to determine apoptosis and cell cycle analysis was carried out by western blotting. Cell migration was checked by cell migration assay and immunoblotting was used for checking protein expressions. RESULTS: The results revealed that cycloartenol inhibited the proliferation and the colony formation potential of the glioma U87 cells in a concentration-dependent manner. The antiproliferative effects were found to be due to induction of Sub-G1 cell cycle arrest and triggering of apoptosis. These effects were found to be dose-dependent. Cycloartenol also caused significant alteration in the expression of Bax and Bcl-2. Furthermore, cycloartenol inhibited the migration of glioma cells and suppressed the phosphorylation of the p38 MAP kinase. CONCLUSION: These findings indicate that cycloartenol may prove beneficial in the treatment of glioma and warrants further investigation.

[Regulatory Role of Nitric Oxide in Development and Hatching of Mouse Blastocysts].

OBJECTIVE: To determine the regulatory role and mechanism of nitric oxide (NO) in the development and hatching of mouse blastocysts. METHODS: The Kunming female mice were superovulated and then mated with mature male mice. On the day 2.5 of their pregnancy, morulae were flushed from their uterine horns with culture media. Morulae were cultured in different concentrations of N-nitro-L arginine methyl ester (L-NAME), sodium nitroprusside (SNP), or the combination of L-NAME and SNP in culture media for 48 hours. The development and hatching of blastocysts were examined on day 4 and day 5 and the total numbers of blastocyst cells and cysteinyl aspartate specific proteinase 3 (caspase 3) were observed under confocal laser scanning microscope. RESULTS: With the increase of the concentration of L-NAME or SNP, the hatching rate of blastocysts and the total number of blastocyst cells were significantly reduced. The addition of 10 nmol/L SNP in culture media with 5 mmol/L L-NAME significantly increased the development of blastocysts and promoted hatching of blastocysts. However, with increase of SNP concentration in culture media with 5 mmol/L L-NAME, the development and hatching rates of blastocysts were significantly decreased. L-NAME had no obvious effect on the expression of active caspase 3 in blastocyst cells. However,when being above 500 nmol/L,SNP significantly increased the expression of caspase 3 in blastocyst cells. CONCLUSIONS: NO plays an important role in development and hatching of mouse blastocysts. Excessively high or low NO can damage the division of blastomeres, resulting in the failure of the blastocyst development and hatching. Also, excessively high NO can lead to the apoptosis of the blastocyst cells.

Effect of BMP-6 on development and maturation of mouse preantral follicles in vitro.

The aim of this study was to investigate the effect and mechanism of bone morphogenetic protein-6 (BMP-6) on the growth and maturation of mouse follicles in vitro. Preantral follicles isolated from mice were incubated with recombinant human BMP-6 (rhBMP-6) before analysis. BMP-6 expression was detected by immunofluorescence and western blot. Maturation of oocytes was observed microscopically. Estradiol (E2) and progesterone (P4) levels were measured by enzyme-linked immunosorbent assay. Expression of steroidogenesis-related genes was detected by reverse transcription quantitative polymerase chain reaction. There was a marked increase in the preantral follicles maturation in cells incubated with 50 ng/mL of rhBMP-6 for eight days, compared with the control. The levels of E2, P4 and steroidogenesis-related genes were also significantly increased in granulosa cells and theca cells cultured for 6, 10 and 11 days, respectively. Conversely, the preantral follicle maturing rate was remarkably decreased in cells incubated with 50 ng/mL of rhBMP-6 for day 11, accompanied with reduction in E2, P4 levels and steroidogenesis-related genes levels. Meanwhile, compared with the control, the maturing rate was not significantly different in cells incubated with 100 ng/mL of rhBMP-6 for day 8 or day 11. However, the E2 levels and its relevant regulation gene expression all increased significantly, while the P4 content and its relevant regulation gene expression decreased. The results indicate that BMP-6 can promote the maturation of preantral follicles in vitro in a concentration and time-dependent manner and may play a role in the regulation of steroid hormone synthesis and/or secretion.

[Histone modifications during spermatogenesis and male infertility].

Many pathological phenomena of male infertility are related to epigenetic changes in male germ cells. Epigenetic regulation during spermatogenesis plays an important role in mitotic/meiotic divisions and spermiogenesis. The histones have various post-translational modifications on different amino acid residues during spermatogenesis. These modifications are crucial to the precise regulation of spermatogenesis. Moreover, the histone-to-protamine transition will occur during spermiogenesis. Many studies have also found that abnormal changes of histone modifications during spermatogenesis may damage the sperm development, leading to male sterility. This article reviews the changes of histone modifications during spermatogenesis, the regulation of the development of male germ cells, and the relationship between histone abnormalities and male sterility.

[Effects of bisphenol-A on blastocyst development and implantation].

OBJECTIVE: To determine the effects of bisphenol-A (BPA) on blastocyst development and implantation. METHODS: According to completely randomized grouping method, 90 pregnant mice were divided into 100, 300, and 600 mg/(kg·d)BPA groups and control group. BPA-treated pregnant mice were orally administered with BPA at concentrations of 100, 300 and 600 mg/(kg·d) from day 0.5 to day 3.5 of their pregnancy. Blastocyst implantation and development were studied. RESULTS: In the 300 mg/(kg·d) BPA group, the number of implantation sites and implantation rate were significantly decreased. In the 600 mg/(kg·d) group, no implantation sites were observed among pregnant mice and BPA inhibited embryo implantation. Blastocyst development on day 4 was examined, and findings showed that the development rate and total numbers of blastocysts in BPA treatment groups had no significant difference from the control group. However, BPA at 300 and 600 mg/(kg·d) significantly reduced blastocyst hatching rate and dramatically increased the number of blastocyst apoptotic cells when compared with those in the control group. CONCLUSION: BPA at a high concentration damages the blastocyst development before implantation and inhibits embryo implantation.

A layer discrete particle based soft contact model in corroded rebar monitoring using linear and nonlinear ultrasonic guided waves.

In offshore reinforced concrete (RC) structures, the phenomenon of rebar corrosion is widespread, seriously threatening the durability of the structures. However, the issue of rebar corrosion detection especially for the early corrosion situation is also challengeable. It is of great significance to use ultrasonic guided waves (UGWs) for monitoring the situation of the rebar corrosion entire process. In this paper, a mechanical model was used to establish the relationship between different rebar corrosion expansion states and layer-surface contact pressures in the layered RC components with radial cracks. Based on this model, a soft pressure-dependent contact 2D model in Abaqus was used to simulate the local corrosion layer. A linear and nonlinear signal joint analysis (LNSJA) method using PZT-based UGWs was proposed to monitor rebar corrosions, and an LNSJA-based rebar corrosion damage index (RCDI) for corroded RC components was proposed. The proposed method which can effectively detect both the micro- and macro-thickness as well as local area of rebar corrosion layer was validated by the relevant experiment and finite element analysis (FEA).

ALKBH5-mediated m6A demethylation of Runx2 mRNA promotes extracellular matrix degradation and intervertebral disc degeneration.

BACKGROUND: N6-methyladenosine (m6A) methylation is a prevalent RNA modification implicated in various diseases. However, its role in intervertebral disc degeneration (IDD), a common cause of low back pain, remains unclear. RESULTS: In this investigation, we explored the involvement of m6A demethylation in the pathogenesis of IDD. Our findings revealed that ALKBH5 (alkylated DNA repair protein AlkB homolog 5), an m6A demethylase, exhibited upregulation in degenerative discs upon mild inflammatory stimulation. ALKBH5 facilitated m6A demethylation within the three prime untranslated region (3'-UTR) of Runx2 mRNA, consequently enhancing its mRNA stability in a YTHDF1 (YTH N6-methyladenosine RNA binding protein F1)-dependent manner. The subsequent elevation in Runx2 expression instigated the upregulation of ADAMTSs and MMPs, pivotal proteases implicated in extracellular matrix (ECM) degradation and IDD progression. In murine models, subcutaneous administration of recombinant Runx2 protein proximal to the lumbar disc in mice elicited complete degradation of intervertebral discs (IVDs). Injection of recombinant MMP1a and ADAMTS10 proteins individually induced mild to moderate degeneration of the IVDs, while co-administration of MMP1a and ADAMTS10 resulted in moderate to severe degeneration. Notably, concurrent injection of the Runx2 inhibitor CADD522 with recombinant Runx2 protein did not result in IVD degeneration in mice. Furthermore, genetic knockout of ALKBH5 and overexpression of YTHDF1 in mice, along with lipopolysaccharide (LPS) treatment to induce inflammation, did not alter the expression of Runx2, MMPs, and ADAMTSs, and no degeneration of the IVDs was observed. CONCLUSION: Our study elucidates the role of ALKBH5-mediated m6A demethylation of Runx2 mRNA in activating MMPs and ADAMTSs, thereby facilitating ECM degradation and promoting the occurrence of IDD. Our findings suggest that targeting the ALKBH5/Runx2/MMPs/ADAMTSs axis may represent a promising therapeutic strategy for preventing IDD.

[Effects of bisphenol A on the female reproductive organs and their mechanisms].

Bisphenol A (BPA) is a commonly used phenolic environmental estrogen. Long-term exposure of female mammalians to BPA can lead to endocrine disorders, followed by the morphological and functional changes in ovary, uterus, vagina, and oviducts. The interactions of BPA with various target molecules or tissues will cause different effects. To further elucidate the effects of BPA on female reproductive system, we review the changes in the structure and functions of female reproduction system after BPA exposure and their possible mechanisms.

EEG-Based Parkinson's Disease Recognition via Attention-Based Sparse Graph Convolutional Neural Network.

Parkinson's disease (PD) is a complicated neurological ailment that affects both the physical and mental wellness of elderly individuals which makes it problematic to diagnose in its initial stages. Electroencephalogram (EEG) promises to be an efficient and cost-effective method for promptly detecting cognitive impairment in PD. Nevertheless, prevailing diagnostic practices utilizing EEG features have failed to examine the functional connectivity among EEG channels and the response of associated brain areas causing an unsatisfactory level of precision. Here, we construct an attention-based sparse graph convolutional neural network (ASGCNN) for diagnosing PD. Our ASGCNN model uses a graph structure to represent channel relationships, the attention mechanism for selecting channels, and the L1 norm to capture channel sparsity. We conduct extensive experiments on the publicly available PD auditory oddball dataset, which consists of 24 PD patients (under ON/OFF drug status) and 24 matched controls, to validate the effectiveness of our method. Our results show that the proposed method provides better results compared to the publicly available baselines. The achieved scores for Recall, Precision, F1-score, Accuracy and Kappa measures are 90.36%, 88.43%, 88.41%, 87.67%, and 75.24%, respectively. Our study reveals that the frontal and temporal lobes show significant differences between PD patients and healthy individuals. In addition, EEG features extracted by ASGCNN demonstrate significant asymmetry in the frontal lobe among PD patients. These findings can offer a basis for the establishment of a clinical system for intelligent diagnosis of PD by using auditory cognitive impairment features.

USP24-dependent stabilization of Runx2 recruits a p300/NCOA3 complex to transactivate ADAMTS genes and promote degeneration of intervertebral disc in chronic inflammation mice.

BACKGROUND: Intervertebral disc degeneration (IDD) naturally occurs during the aging process. Its occurrence is closely related to chronic inflammation; however, the causal relationship between them is controversial. This study aimed to investigate if inflammation would promote IDD incidence and explore the underlying mechanism. METHODS: A chronic inflammation mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS). Enzyme-linked immunosorbent assay was performed to determine proinflammatory cytokines in serum. Histological staining was used to evaluate the degeneration of IVDs. Immunoblots and RT-qPCR analyses were performed to measure protein and mRNA expression levels. Immunoprecipitation, mass spectrometry, and co-immunoprecipitation assays were used to determine the assembly of protein complex. RESULTS: We found that an inflammatory microenvironment activated p38 kinase, which phosphorylated the Runx2 transcription factor at the Ser28 site. The phosphorylated Runx2 (pRunx2) then recruited a deubiquitinase, ubiquitin-specific peptidase 24 (USP24), which stabilized pRunx2 and protected it from ubiquitin-dependent proteasomal degradation. The stabilized pRunx2 recruited histone acetyltransferase p300 and nuclear receptor coactivator 3 (NCOA3) to assemble a complex. This NCOA3-p300-pRunx2 complex then transactivated the expression of 13 ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) genes, thereby promoting the degradation of extracellular matrix (ECM) in intervertebral discs (IVDs) and causing IDD. Administration of either a p38 inhibitor (doramapimod), a NCOA3 inhibitor (bufalin), or a p300 inhibitor (EML425) significantly decreased the expression of the 13 ADAMTS genes and slowed the degeneration of IVDs. CONCLUSION: In summary, our results demonstrate that USP24 protects pRunx2 from proteasomal degradation under chronic inflammation conditions, enabling pRunx2 to transactivate ADAMTS genes and degrade ECM. Our findings provide direct evidence that chronic inflammation triggers IDD and offer a therapeutic strategy for retarding IDD in patients with chronic inflammation.

Accumulation of NCOA1 dependent on HERC3 deficiency transactivates matrix metallopeptidases and promotes extracellular matrix degradation in intervertebral disc degeneration.

BACKGROUND: Matrix metallopeptidases (MMPs) are critical matrix-degrading molecules and they are frequently overexpressed in degenerative discs. This study aimed to investigate the mechanism for MMP upregulation. METHODS: Immunoblot and RT-qPCR were used for detecting protein and gene expression levels. 4-month-old and 24-month-old C57BL/6 mice were used for evaluating intervertebral disc degeneration (IDD). An ubiquitination assay was used to determine protein modification. Immunoprecipitation and mass spectrometry were used for identifying protein complex members. RESULTS: We identified the elevation of 14 MMPs among 23 members in aged mice with IDD. Eleven of these 14 MMP gene promoters contained a Runx2 (runt-related transcription factor 2) binding site. Biochemical analyses revealed that Runx2 recruited a histone acetyltransferase p300 and a coactivator NCOA1 (nuclear receptor coactivator 1) to assemble a complex, transactivating MMP expression. The deficiency of an E3 ligase called HERC3 (HECT and RLD domain containing E3 ubiquitin-protein ligase 3) resulted in the accumulation of NCOA1 in the inflammatory microenvironment. High throughput screening of small molecules that specifically target the NCOA1-p300 interaction identified a compound SMTNP-191, which showed an inhibitory effect on suppressing MMP expression and attenuating the IDD process in aged mice. CONCLUSION: Our data support a model in which deficiency of HERC3 fails to ubiquitinate NCOA1, leading to the assembly of NCOA1-p300-Runx2 and causing the transactivation of MMPs. These findings offer new insight into inflammation-mediated MMP accumulation and also provide a new therapeutic strategy to retard the IDD process.

Trigonochinene E promotes lysosomal biogenesis and enhances autophagy via TFEB/TFE3 in human degenerative NP cells against oxidative stress.

BACKGROUND: Macroautophagy (henceforth autophagy) is the major form of autophagy, which delivers intracellular cargo to lysosomes for degradation. Considerable research has revealed that the impairment of lysosomal biogenesis and autophagic flux exacerbates the development of autophagy-related diseases. Therefore, reparative medicines restoring lysosomal biogenesis and autophagic flux in cells may have therapeutic potential against the increasing prevalence of these diseases. PURPOSE: The aim of the present study was thus to explore the effect of trigonochinene E (TE), an aromatic tetranorditerpene isolated from Trigonostemon flavidus, on lysosomal biogenesis and autophagy and to elucidate the potential underlying mechanism. METHODS: Four human cell lines, HepG2, nucleus pulposus (NP), HeLa and HEK293 cells were applied in this study. The cytotoxicity of TE was evaluated by MTT assay. Lysosomal biogenesis and autophagic flux induced by 40 µM TE were analyzed using gene transfer techniques, western blotting, real-time PCR and confocal microscopy. Immunofluorescence, immunoblotting and pharmacological inhibitors/activators were applied to determine the changes in the protein expression levels in mTOR, PKC, PERK, and IRE1α signaling pathways. RESULTS: Our results showed that TE promotes lysosomal biogenesis and autophagic flux by activating the transcription factors of lysosomes, transcription factor EB (TFEB) and transcription factor E3 (TFE3). Mechanistically, TE induces TFEB and TFE3 nuclear translocation through an mTOR/PKC/ROS-independent and endoplasmic reticulum (ER) stress-mediated pathway. The PERK and IRE1α branches of ER stress are crucial for TE-induced autophagy and lysosomal biogenesis. Whereas TE activated PERK, which mediated calcineurin dephosphorylation of TFEB/TFE3, IRE1α was activated and led to inactivation of STAT3, which further enhanced autophagy and lysosomal biogenesis. Functionally, knockdown of TFEB or TFE3 impairs TE-induced lysosomal biogenesis and autophagic flux. Furthermore, TE-induced autophagy protects NP cells from oxidative stress to ameliorate intervertebral disc degeneration (IVDD). CONCLUSIONS: Here, our study showed that TE can induce TFEB/TFE3-dependent lysosomal biogenesis and autophagy via the PERK-calcineurin axis and IRE1α-STAT3 axis. Unlike other agents regulating lysosomal biogenesis and autophagy, TE showed limited cytotoxicity, thereby providing a new direction for therapeutic opportunities to use TE to treat diseases with impaired autophagy-lysosomal pathways, including IVDD.

EEG-based major depressive disorder recognition by selecting discriminative features via stochastic search.

Objective. Major depressive disorder (MDD) is a prevalent psychiatric disorder whose diagnosis relies on experienced psychiatrists, resulting in a low diagnosis rate. As a typical physiological signal, electroencephalography (EEG) has indicated a strong association with human beings' mental activities and can be served as an objective biomarker for diagnosing MDD.Approach. The basic idea of the proposed method fully considers all the channel information in EEG-based MDD recognition and designs a stochastic search algorithm to select the best discriminative features for describing the individual channels.Main results. To evaluate the proposed method, we conducted extensive experiments on the MODMA dataset (including dot-probe tasks and resting state), a 128-electrode public EEG-based MDD dataset including 24 patients with depressive disorder and 29 healthy controls. Under the leave-one-subject-out cross-validation protocol, the proposed method achieved an average accuracy of 99.53% in the fear-neutral face pairs cued experiment and 99.32% in the resting state, outperforming state-of-the-art MDD recognition methods. Moreover, our experimental results also indicated that negative emotional stimuli could induce depressive states, and high-frequency EEG features contributed significantly to distinguishing between normal and depressive patients, which can be served as a marker for MDD recognition.Significance. The proposed method provided a possible solution to an intelligent diagnosis of MDD and can be used to develop a computer-aided diagnostic tool to aid clinicians in early diagnosis for clinical purposes.

Neural pathway connectivity and discharge changes between M1 and STN in hemiparkinsonian rats.

Alterations of electrophysiological activities, such as changed spike firing rates, reshaping the firing patterns, and aberrant frequency oscillations between the subthalamic nucleus (STN) and the primary motor cortex (M1), are thought to contribute to motor impairment in Parkinson's disease (PD). However, the alterations of electrophysiological characteristics of STN and M1 in PD are still unclear, especially under specific treadmill movement. To examine the relationship between electrophysiological activity in the STN-M1 pathway, extracellular spike trains and local field potential (LFPs) of STN and M1 were simultaneously recorded during resting and movement in unilateral 6-hydroxydopamine (6-OHDA) lesioned rats. The results showed that the identified STN neurons and M1 neurons exhibited abnormal neuronal activity after dopamine loss. The dopamine depletion altered the LFP power in STN and M1 whatever in rest or movement states. Furthermore, the enhanced synchronization of LFP oscillations after dopamine loss was found in 12-35 Hz (beta frequencies) between the STN and M1 during rest and movement. In addition, STN neurons were phase-locked firing to M1 oscillations at 12-35 Hz during rest epochs in 6-OHDA lesioned rats. The dopamine depletion also impaired the anatomical connectivity between the M1 and STN by injecting anterograde neuroanatomical tracing virus into M1 in control and PD rats. Collectively, impairment of' electrophysiological activity and anatomical connectivity in the M1-STN pathway may be the basis for dysfunction of the cortico-basal ganglia circuit, correlating with motor symptoms of PD.

An End-to-End Depression Recognition Method Based on EEGNet.

Major depressive disorder (MDD) is a common and highly debilitating condition that threatens the health of millions of people. However, current diagnosis of depression relies on questionnaires that are highly correlated with physician experience and hence not completely objective. Electroencephalography (EEG) signals combined with deep learning techniques may be an objective approach to effective diagnosis of MDD. This study proposes an end-to-end deep learning framework for MDD diagnosis based on EEG signals. We used EEG signals from 29 healthy subjects and 24 patients with severe depression to calculate Accuracy, Precision, Recall, F1-Score, and Kappa coefficient, which were 90.98%, 91.27%, 90.59%, and 81.68%, respectively. In addition, we found that these values were highest when happy-neutral face pairs were used as stimuli for detecting depression. Compared with exiting methods for EEG-based MDD classification, ours can maintain stable model performance without re-calibration. The present results suggest that the method is highly accurate for diagnosis of MDD and can be used to develop an automatic plug-and-play EEG-based system for diagnosing depression.

Beta band modulation by dopamine D2 receptors in the primary motor cortex and pedunculopontine nucleus in a rat model of Parkinson's disease.

Beta band (12-30 Hz) hypersynchrony within the basal ganglia-thalamocortical network has been suggested as a hallmark of Parkinson's disease (PD) pathophysiology. Abnormal beta band oscillations are found in the pedunculopontine nucleus (PPN) and primary motor cortex (M1) and are correlated with dopamine depletion. Dopamine acts locomotion and motor performance mainly through dopamine receptors (D1 and D2). However, the precise mechanism by which dopamine receptors regulate beta band electrophysiological activities between the PPN and M1 is still unknown. Here, we recorded the neuronal activity of the PPN and M1 simultaneously by the administration of the drug (SCH23390 and raclopride), selectively blocking the dopamine D1 receptor and D2 receptor. We discovered that the increased coherent activity of the beta band (12-30 Hz) between M1 and PPN in the lesioned group could be reduced and restored by injecting raclopride in the resting and wheel running states. Our studies revealed the unique role of D2 dopamine receptor signaling in regulating ß band oscillatory activity in M1 and PPN and their relationship after the loss of dopamine, which contributes to elucidating the underlying mechanism of the pathophysiology of PD.

Deep brain stimulation on the external segment of the globus pallidus improves the electrical activity of internal segment of globus pallidus in a rat model of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the progressive degeneration of neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) is an effective treatment for PD cardinal motor symptoms. DBS of GPe has been recognized as an effective treatment option for motor symptoms of PD, but the mechanism is still essentially unknown. To investigate the impact of DBS in the external segment of globus pallidus (GPe) on the pathway of the basal ganglia (BG), we recorded the electrical activities of single neurons and local field potential (LFP) of the internal segment of globus pallidus (GPi). The results showed that the firing rate of GPi neurons in the 6-OHDA lesioned rats returned to the normal level after GPe-DBS for two weeks. Moreover, the CV value of GPi neurons is significantly lower than that in the PD group. The different frequency bands of GPi LFP in PD rats have improved correspondingly. These findings indicate that the improvement of the electrical activity of GPi by GPe-DBS in PD rats may be an important electrophysiological mechanism for treating PD.