Changes in metabolic hormones and trace elements in CSF in active smokers indicate oxidative damage to brain cells.

Objective: This study aimed to reveal associations between metabolic hormones in cerebral spinal fluid (CSF) and cigarette smoking-induced weight gain and to explore the underlying mechanism. Methods: A total of 156 adult men were included, comprising active smokers and nonsmokers. In addition to demographic information and body mass index (BMI), plasma levels of ApoA1 and ApoB, high-density lipoprotein, low-density lipoprotein, cholesterol, triglyceride, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase in the participants were measured. Moreover, the metabolic hormones adiponectin, fibroblast growth factor 21 (FGF21), ghrelin, leptin, and orexin A, as well as the trace elements iron and zinc in CSF, were assessed. Results: Compared to nonsmokers, active smokers showed higher BMI, and elevated CSF levels of FGF21, Zn, and Fe, but decreased levels of metabolic hormones adiponectin, ghrelin, leptin, and orexin A. Negative correlations existed between CSF FGF21 and ghrelin, between CSF Zn and ghrelin, as well as between CSF Fe and orexin A in active smokers. Furthermore, elevated CSF FGF21 and Zn predicted ghrelin level decrease in the smokers. Conclusion: These data relate smoking-induced weight gain to its neurotoxic effect on the neurons that synthesize metabolic hormones such as adiponectin, ghrelin, leptin, or orexin A in the brain, by disrupting mitochondrial function and causing oxidative stress in the neurons.

SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer's Disease.

Neuroinflammation plays a crucial role in the pathogenesis and progression of Alzheimer's disease (AD). The Sterile Alpha and Toll Interleukin Receptor Motif-containing protein 1 (SARM1) has been shown to promote axonal degeneration and is involved in neuroinflammation. However, the role of SARM1 in AD remains unclear. In this study, we found that SARM1 was reduced in hippocampal neurons of AD model mice. Interestingly, conditional knockout (CKO) of SARM1 in the central nervous system (CNS, SARM1Nestin-CKO mice) delayed the cognitive decline in APP/PS1 AD model mice. Furthermore, SARM1 deletion reduced the Aß deposition and inflammatory infiltration in the hippocampus and inhibited neurodegeneration in APP/PS1 AD model mice. Further investigation into the underlying mechanisms revealed that the signaling of tumor necrosis factor-α (TNF-α) was downregulated in the hippocampus tissues of APP/PS1;SARM1Nestin-CKO mice, thereby alleviating the cognitive decline, Aß deposition and inflammatory infiltration. These findings identify unrecognized functions of SARM1 in promoting AD and reveal the SARM1-TNF-α pathway in AD model mice.

A Sparse-Array Design Method Using Q Uniform Linear Arrays for Direction-of-Arrival Estimation.

Nowadays, sparse arrays have been a hotspot for research in the direction of arrival (DOA). In order to achieve a big value for degrees of freedom (DOFs) using spatial smoothing methods, researchers try to use multiple uniform linear arrays (ULAs) to construct sparse arrays. But, with the number of subarrays increasing, the complexity also increases. Hence, in this paper, a design method, named as the cross-coarray consecutive-connected (4C) criterion, and the sparse array using Q ULAs (SA-UQ) are proposed. We first analyze the virtual sensor distribution of SA-U2 and extend the conclusions to SA-UQ, which is the 4C criterion. Then, we give an algorithm to solve the displacement between subarrays under the given Q ULAs. At last, we consider a special case, SA-U3. Through the analysis of DOFs, SA-UQ can find underdetermined signals. Moreover, SA-U3 can obtain DOFs close to other sparse arrays using three ULAs. The simulation experiments prove the performance of SA-UQ.

Hypercoagulable state in patients with schizophrenia: different effects of acute and chronic antipsychotic medications.

Background: Previous studies reported higher incidences of venous thromboembolism and cardiovascular disease in schizophrenia patients and higher indicators of thrombosis, thrombocyte activation, and platelet dysfunction. Objectives: To check if first-episode schizophrenia (FES) patients have a hypercoagulable state and determine whether acute and chronic antipsychotics have the same effect on blood coagulation or fibrinolysis-related biomarkers. Design: Case-control study. Methods: A total of 81 participants were grouped in FES, chronic schizophrenia (CS), and healthy controls (HCs). In addition to demographic data and clinical characteristics, immunological analyses were performed to measure plasma levels of D-dimer, plasminogen activator inhibitor-1 (PAI-1), soluble P selectin (sP-sel), tissue plasminogen activator (tPA), thrombotic precursor protein (TpP), and von Willebrand's disease factor (vWF). Results: Compared to HC group, FES patients showed higher PAI-1 (28.61 ng/ml versus 15.69 ng/ml), sP-sel (2.78 ng/ml versus 1.18 ng/ml), and TpP (15.61 µg/ml versus 5.59 µg/ml) along with a higher PAI-1/tPA (3.12 versus 2.00). Acute antipsychotic medication reduced higher PAI-1 (28.61 → 21.99), sP-sel (2.78 → 1.87), tPA (9.59 → 5.83), TpP (15.61 → 10.54), and vWF (383.18 → 291.08) in FES patients. However, plasma sP-sel and vWF in CS patients returned to the pre-treatment levels in FES patients, and PAI-1/tPA significantly decreased compared to FES patients. Conclusion: These results suggest a hypercoagulable state in FES patients and demonstrate contrast effects of acute and chronic antipsychotics on coagulation or fibrinolysis in schizophrenia patients.

Application of a Digital Mental Health Clinic in Secondary Schools: Functionality and Effectiveness Evaluation.

BACKGROUND: Adolescents experience relatively more stress than other populations as they are facing rapid physical changes and adapting to complex social environments. However, access for this population to professional service providers is limited. Therefore, there is an increasing need for access to mental health services and new mental health care resources tailored to adolescents. OBJECTIVE: The aim of this study was to evaluate the functionality and effectiveness of a school digital mental health clinic (DMHC) created by a Chinese psychiatric hospital and provided to secondary school students for a trial. METHODS: The trial period of the DMHC was from January to July 2021 at three secondary schools in Taizhou City, China. Under a collaborative agreement between the local educational bureau and provider, use of the DMHC was free to all students, teachers, and staff of the schools. The functionality of the DMHC was compared with existing digital health interventions introduced in the literature and its effectiveness was quantitatively analyzed in terms of the volume of received counseling calls, number of calls per 100 students, length and time of calls, and reasons for the calls. The mini course video views were analyzed by topics and viewing time. RESULTS: The design functions of the DMHC are well aligned with required factors defined in the literature. The first advantage of this DMHC is its high accessibility to students in the three schools. All functions of the DMHC are free to use by students, thereby eliminating the economic barriers to seeking and receiving care. Students can receive virtual counseling during or after regular working hours. Acceptability of the DHMC was further ensured by the full support from a national top-tier mental health facility. Any audio or video call from a student user would connect them to a live, qualified professional (ie, a psychiatrist or psychologist). Options are provided to view and listen to resources for stress relief or tips to help address mental health needs. The major reasons for the counseling calls included difficulties in learning, interpersonal relationships, and emotional distress. The three topics with the highest level of interest for the mini course videos were emotional assistance, personal growth, and family member relationships. The DMHC served as an effective tool for crisis prevention and intervention during nonworking hours as most of the live calls and mini video viewing occurred after school or over the weekend. Furthermore, the DMHC helped three students at high risk for suicide and self-injury through live-call intervention. CONCLUSIONS: The DMHC is an effective complementary solution to improve access to professional mental health care facilities, especially during nonworking hours, thereby helping adolescents meet their mental health needs. Extension of the DMHC into more schools and other settings is recommended.

Health effects of future dioxins emission mitigation from Chinese municipal solid waste incinerators.

Dioxins (including 2,3,7,8-tetrachlorodibenzo-p-dioxin, as Group 1 Carcinogen) in the atmosphere mainly originate from incomplete combustion during municipal solid waste (MSW) incineration. To significantly reduce dioxins emission from the MSW incineration industry, China has promulgated a set of ambitious plans regulating MSW-related pollution; however, the emission reduction potentials and concomitant environmental and health impacts associated with the implementation of these programs on a national scale remain unknown. Here, we use real measurements from official environmental impact assessment systems and continuous emissions monitoring systems (covering 96.6% of national MSW incinerators) to estimate unit-level dioxins emission and concomitant environmental and health impacts. We find that in 2018, 99.3% and 66.7% of Chinese incinerators met such concentration and temperature standards, respectively, controlling the total emissions to 19.6 g toxic equivalency quantity and maintaining carcinogenic and noncarcinogenic risks significantly below safety levels nationwide. Fully achieving both current standards and future regulations will reduce emissions and health risks by 67.7% and 62.6%, respectively, with waste sorting program contributing the majority. This study reveals substantial benefits from curbing MSW-related dioxins pollution and underscores the promise of ongoing management.

GDCNet: Graph Enrichment Learning via Graph Dropping Convolutional Networks.

Graph convolutional networks (GCNs) have been widely studied to address graph data representation and learning. In contrast to traditional convolutional neural networks (CNNs) that employ many various (spatial) convolution filters to obtain rich feature descriptors to encode complex patterns of image data, GCNs, however, are defined on the input observed graph G(X,A) and usually adopt the single fixed spatial convolution filter for graph data feature extraction. This limits the capacity of the existing GCNs to encode the complex patterns of graph data. To overcome this issue, inspired by depthwise separable convolution and DropEdge operation, we first propose to generate various graph convolution filters by randomly dropping out some edges from the input graph A . Then, we propose a novel graph-dropping convolution layer (GDCLayer) to produce rich feature descriptors for graph data. Using GDCLayer, we finally design a new end-to-end network architecture, that is, a graph-dropping convolutional network (GDCNet), for graph data learning. Experiments on several datasets demonstrate the effectiveness of the proposed GDCNet.

A Mixed-Field Circular and Non-Circular Source Localization Algorithm Based on Exact Spatial Propagation Geometry.

In passive localization techniques, as the scale of the array of the sensors used increases, the source distribution may be a coexistence of near-field (NF) and far-field (FF) sources. Most of the existing algorithms dedicated to the localization of mixed-field sources are based on a simplified model, which has model errors and cannot make good use of non-circular properties when non-circular signals are present in the sources. In this paper, we present a mixed-field circular and non-circular source localization algorithm based on exact spatial propagation geometry. First, we make an initial estimate of the source parameters using exact spatial geometry relations. The MUSIC algorithm is then used in combination with the non-circular properties of the signal to achieve an accurate estimate. The algorithm does not lose performance due to model mismatch and is able to make good use of the non-circular properties of the sources to improve the estimation accuracy. The simulation results show that the proposed algorithm can effectively distinguish between sources and that the algorithm performs satisfactorily.

An L-Shaped Three-Level and Single Common Element Sparse Sensor Array for 2-D DOA Estimation.

The degree of freedom (DOF) is an important performance metric for evaluating the design of a sparse array structure. Designing novel sparse arrays with higher degrees of freedom, while ensuring that the array structure can be mathematically represented, is a crucial research direction in the field of direction of arrival (DOA) estimation. In this paper, we propose a novel L-shaped sparse sensor array by adjusting the physical placement of the sensors in the sparse array. The proposed L-shaped sparse array consists of two sets of three-level and single-element sparse arrays (TSESAs), which estimate the azimuth and elevation angles, respectively, through one-dimensional (1-D) spatial spectrum search. Each TSESA is composed of a uniform linear subarray and two sparse subarrays, with one single common element in the two sparse subarrays. Compared to existing L-shaped sparse arrays, the proposed array achieves higher degrees of freedom, up to 4Q1Q2+8Q1-5, when estimating DOA using the received signal covariance. To facilitate the correct matching of azimuth and elevation angles, the cross-covariance between the two TSESA arrays is utilized for estimation. By comparing and analyzing performance parameters with commonly used L-shaped and other sparse arrays, it is found that the proposed L-shaped TSESA has higher degrees of freedom and array aperture, leading to improved two-dimensional (2-D) DOA estimation results. Finally, simulation experiments validate the excellent performance of the L-shaped TSESA in 2-D DOA estimation.

Age-related decline in hippocampal tyrosine phosphatase PTPRO is a mechanistic factor in chemotherapy-related cognitive impairment.

Chemotherapy-related cognitive impairment (CRCI) or "chemo brain" is a devastating neurotoxic sequela of cancer-related treatments, especially for the elderly individuals. Here we show that PTPRO, a tyrosine phosphatase, is highly enriched in the hippocampus, and its level is tightly associated with neurocognitive function but declined significantly during aging. To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro-/- female mice with doxorubicin (DOX) because Ptpro-/- female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration. By analyzing PTPRO substrates that are neurocognition-associated tyrosine kinases, we found that SRC and EPHA4 are highly phosphorylated/activated in the hippocampi of Ptpro-/- female mice, with increased sensitivity to DOX-induced CRCI. On the other hand, restoration of PTPRO in the hippocampal CA3 region significantly ameliorate CRCI in Ptpro-/- female mice. In addition, we found that the plant alkaloid berberine (BBR) is capable of ameliorating CRCI in aged female mice by upregulating hippocampal PTPRO. Mechanistically, BBR upregulates PTPRO by downregulating miR-25-3p, which directly targeted PTPRO. These findings collectively demonstrate the protective role of hippocampal PTPRO against CRCI.

Regulatory T cells mediate insomnia-related psychotic symptoms and cognitive impairment in chronic schizophrenia patients.

Insomnia occurs frequently in schizophrenia patients and is often accompanied with severe psychotic symptoms and cognition impairment. Moreover, chronic insomnia is associated with immune alterations. This study explored the correlations between insomnia and clinical manifestations of schizophrenia and analyzed mediation effects of regulatory T cells (Tregs) on these correlations. In a total of 655 chronic schizophrenia patients, 70 persons (10.69%) had an ISI (Insomnia Severity Index) score >7 and were referred to as Insomnia group. Compared to non-Insomnia group, Insomnia group presented more severe psychotic symptoms (assessed by PANSS) and cognitive impairment (assessed by RBANS). The total effect of ISI on PANSS/RBANS total score was not significant due to the mediation effects by Tregs, in which Tregs strongly mediated the effect of ISI on PANSS total score in negative direction but mediated the effect of ISI on RBANS total score in positive direction. Pearson Correlation Coefficient revealed negative correlations between Tregs and PANSS total score or disorganization subscale of PANSS. Positive correlations existed between Tregs and RBANS total score, between Tregs and the subscales of attention, delayed memory, or language of RBANS. These mediation effects of Tregs on insomnia-related psychotic symptoms and cognitive impairment in chronic schizophrenia patients point to a potential therapeutic strategy of modulating Tregs for the patients.

DropAGG: Robust Graph Neural Networks via Drop Aggregation.

Robust learning on graph data is an active research problem in data mining field. Graph Neural Networks (GNNs) have gained great attention in graph data representation and learning tasks. The core of GNNs is the message propagation mechanism across node's neighbors in GNNs' layer-wise propagation. Existing GNNs generally adopt the deterministic message propagation mechanism which may (1) perform non-robustly w.r.t structural noises and adversarial attacks and (2) lead to over-smoothing issue. To alleviate these issues, this work rethinks dropout techniques in GNNs and proposes a novel random message propagation mechanism, named Drop Aggregation (DropAGG), for GNNs learning. The core of DropAGG is to randomly select a certain rate of nodes to participate in information aggregation. The proposed DropAGG is a general scheme which can incorporate any specific GNN model to enhance its robustness and mitigate the over-smoothing issue. Using DropAGG, we then design a novel Graph Random Aggregation Network (GRANet) for graph data robust learning. Extensive experiments on several benchmark datasets demonstrate the robustness of GRANet and effectiveness of DropAGG to mitigate the issue of over-smoothing.

Impacting factors and sources of perceived stress by home-quarantined residents in Shanghai during COVID-19 epidemic.

BACKGROUND: Home-quarantine is one of the most common measures implemented to prevent or minimize the transmission of COVID-19 among communities. This study assessed stress levels of the home-quarantined residents in Shanghai during a massive wave of COVID-19 epidemic this year, explored the stress sources perceived by the respondents, and analyzed the association between each of the sociodemographic factors and the stress level. METHODS: This online survey was launched during April 23 - 30, 2022, the early stage of a massive wave of COVID-19 in Shanghai, China. Participants were quarantined-residents negative for COVID-19. They were asked to list some situations that were their major concerns and perceived stressful, in addition to sociodemographic and COVID-19 related information. Moreover, they were asked to complete the Perceived Stress Scale-14 (PSS-14) for the assessment of stress level. RESULTS: A total of 488 valid questionnaires were collected from 192 male and 296 female respondents. Overall, 207 persons (42.42%) presented high stress level (PSS-14 score ≥43). The top three concerns perceived stressful by respondents are "not allowed to go outdoors", "uncertain duration of the epidemic", and "lack of food supply". Fewer than 50% of the respondents perceived the other situations stressful. Higher proportions of young adults (≤ 29 years old), males, unemployed, singles, and those with low income (≤ 1999 yuan/month) perceived high stress compared to their counterparts, none of COVID-19 related factors is associated with the stress level, including location of residence, result of nucleic acid test, knowledge about COVID-19, whether vaccinated, and quarantine duration. CONCLUSION: Home-quarantine applied to people negative for COVID-19 led to a lot of major concerns that may be perceived stressful, whereas the virus-related factors did not show significant impact on mental health of the respondents.

Imaging findings and clinical function after combined surgery for recurrent patella dislocation: a comparative study.

Background: Limited research has evaluated imaging results following a combination of operations for recurrent patella dislocation (RPD) based on medial patellofemoral ligament (MPFL) reconstruction. Therefore, this study aimed to retrospectively compare the imaging and clinical results of RPD following 2 types of combined surgical techniques. Methods: Patients who underwent combined surgery for RPD from January 2008 to December 2019 were enrolled in the study and allocated into 2 groups. MPFL reconstruction combined with lateral retinacular release (LRR) was performed in groups A and B, and an additional tibial tuberosity transfer (TTT) was performed in group B only. Patients in group A with a tibial tuberosity trochlear groove (TT-TG) distance greater than 15 mm were included in subgroup A*. Congruence angle (CA), patellar tilt angle (PTA), lateral patellofemoral angle (LPA), lateral patellar displacement (LPD), TT-TG, Insall-Salvati Index (ISI), the Dejour type of trochlear dysplasia, and knee function were assessed. All groups were followed up in the short-term (1-2 years), and group B was also followed up in the mid-term (over 5 years). Results: A total of 40 knees (36 patients) were included in group A, 26 knees (24 patients) in subgroup A*, and 27 knees (26 patients) in group B. In group A, CA, PTA, and LPD had increased at the short-term follow-up, yet LPA had decreased compared to the results 3 days after surgery. In group B, at the mid-term follow-up, PTA (12.54±6.88 vs. 15.23±6.10; P=0.002) increased while LPD (7.08±6.48 vs. 4.69±6.28; P=0.049) decreased compared with the short-term outcomes. The more severe the femoral trochlear dysplasia, the lower the mid-term Kujala scores in group B (P=0.007). The short-term TT-TG (17.32±4.288 vs. 12.84±3.758; P<0.001) and ISI [1.25 (1.1075, 1.300) vs. 1.06 (1.00, 1.16); P<0.001] in group B were lower than those in group A, who had a higher Kujala score (P<0.001). The CA, LPD, ISI, TT-TG, and Kujala score in subgroup A* were higher than those in group B at the short-term follow-up (P<0.05). Conclusions: Both types of combination treatments were successful in altering the patellofemoral joint in a satisfactory manner, and the knee function improved in both groups. A TTT might not be necessary for patients with a TT-TG distance greater than 15 mm.

The interplay of dopamine metabolism abnormalities and mitochondrial defects in the pathogenesis of schizophrenia.

Dopamine (DA) is a major monoamine neurotransmitter in the brain and has essential roles in higher functions of the brain. Malfunctions of dopaminergic signaling have been implicated in various mental disorders such as addiction, attention deficit/hyperactivity disorder, Huntington's disease, Parkinson's disease (PD), and schizophrenia. The pathogenesis of PD and schizophrenia involves the interplay of mitochondrial defect and DA metabolism abnormalities. This article focuses on this issue in schizophrenia. It started with the introduction of metabolism, behavioral action, and physiology of DA, followed by reviewing evidence for malfunctions of dopaminergic signaling in patients with schizophrenia. Then it provided an overview of multiple facets of mitochondrial physiology before summarizing mitochondrial defects reported in clinical studies with schizophrenia patients. Finally, it discussed the interplay between DA metabolism abnormalities and mitochondrial defects and outlined some clinical studies showing effects of combination therapy of antipsychotics and antioxidants in treating patients with schizophrenia. The update and integration of these lines of information may advance our understanding of the etiology, pathogenesis, phenomenology, and treatment of schizophrenia.

Plasma complement C3 and C3a are increased in major depressive disorder independent of childhood trauma.

BACKGROUND: Dysregulated complement system is linked to pathophysiology of major depressive disorder (MDD). Childhood trauma has been associated with an increased incidence of adult depression via a putative mechanism of immune activation. This study aimed to measure and compare peripheral levels of complement C3, C3a, C1q and C-reactive protein (CRP) in MDD patients and healthy controls and explore the relationship between these molecule levels and childhood trauma history in the participants. METHODS: The participants were 49 medication-free MDD patients and 45 healthy controls. All participants were asked to finish the Childhood Trauma Questionnaire, followed by blood sampling for measurement of plasma complement C3, C3a, C1q and CRP by means of enzyme-linked immunosorbent assay. RESULTS: Peripheral plasma concentration of C3 and C3a in medication-free MDD group was significantly higher than that in the healthy controls; whereas the concentration of plasma C1q and CRP in depressed patients was comparable to that in healthy controls. All these inflammatory factors were not associated to childhood trauma experience in patients with MDD. CONCLUSION: Our data suggest that complement C3 and C3a may be implicated in the pathophysiology of MDD, although traumatic childhood experiences were not associated with the circulating levels of complement C3, C3a, C1q and CRP.

Analysis of Efficacy, Complications, and Inflammatory Reactions of Bridge Combined Internal Fixation System for Periarticular Fractures of the Shoulder.

Objective: The aim of the present research is to analyze the impact of the bridge combined internal fixation system (BCFS) on efficacy, complications, and inflammatory reactions of periarticular fractures of the shoulder. Methods: A retrospective analysis was performed on 100 patients with periarticular fractures of the shoulder admitted between January 2016 and January 2020. Patients were assigned to the observation group (OG) and control group (CG) according to different treatment schemes, with 50 cases in each group. Patients in OG were intervened by BCFS, while those in CG were routinely given plate fixation. The treatment outcome, complications, and inflammatory reaction of the two groups were compared. Results: The results showed better treatment outcome, shoulder joint function recovery, and inflammatory reaction alleviation of OG compared with CG. Besides, statistically shorter fracture healing and hospitalization time as well as fewer complications were determined in OG. Conclusion: These results demonstrate that compared with the plate fixation system, BCFS can significantly improve the surgical efficacy and healing efficiency and alleviate the inflammatory response of patients, with a low complication rate, all of which contribute to faster recovery of periarticular fractures of the shoulder. Hence, BCFS is an ideal choice for periarticular fractures of the shoulder that deserves clinical promotion.

What Is the Effect of Cultural Greenway Projects in High-Density Urban Municipalities? Assessing the Public Living Desire near the Cultural Greenway in Central Beijing.

Cultural greenway projects (CGPs) are widely regarded as an urban planning approach which connects open green spaces and sites of sociocultural value to provide access to living, working and recreational spaces and enhance local social well-being. This paper examines the impact of such CGPs on public living desire before and after a given project is completed through analyzing housing prices in the surrounding area. We deployed a hedonic pricing model (HPM) and differences in differences (DID) model to analyze and record any changes in housing market trends that may have been caused by such a cultural greenway project. Via analysis of single-family home sale transactions in central Beijing from 2013 to 2017, we found substantial evidence that proximity to a cultural greenway project is positively linked with rising property prices. Once complete, CGPs were similarly associated with positive increases per HPM and DID modeling. Our results revealed that the distance to greenway contributed significantly positive impact on the housing market after the cultural greenway project completed. Moreover, our result indicated that once a CGP was open to the public, it increased the price of properties within 1 km by 13.3%. Seller and buyer expectations of the development of local, green public infrastructure also began to factor into housing prices prior to the greenway opening to the public. Post-completion, the positive trend in property pricing due to local CGPs indicates that the public still have an increasing desire to live near the greenway. These results will help policymakers better understand how cultural greenways affect neighborhoods in high-density urban contexts, and will support the development of urban greenway policies for cities in China that reap the maximum economic benefit.

MiR-18a-3p improves cartilage matrix remodeling and inhibits inflammation in osteoarthritis by suppressing PDP1.

Osteoarthritis (OA) is a degenerative disease characterized by synovial inflammation. MiR-18a-3p was reported to be downregulated in knee anterior cruciate ligament of OA patients. In the present study, the specific functions and mechanism of miR-18a-3p in OA were explored. An in vitro model of OA was established using 10 ng/ml IL-1ß to treat ATDC5 cells, and medial meniscus instability surgery was performed on Wistar rats to establish in vivo rat model of OA. RT-qPCR revealed that miR-18a-3p was downregulated in IL-1ß-stimulated ATDC5 cells. MiR-18a-3p overexpression inhibited secretion of inflammatory cytokines and concentration of matrix metalloproteinases, as shown by ELISA and western blotting. The binding relation between miR-18a-3p and pyruvate dehydrogenase phosphatase catalytic subunit 1 (PDP1) was detected by luciferase reporter assays. MiR-18a-3p targeted PDP1 and negatively regulated PDP1 expression. Results of rescue assays revealed that PDP1 upregulation reserved the suppressive effect of miR-18a-3p overexpression on levels of inflammatory cytokines and matrix metalloproteinases in IL-1ß-stimulated ATDC5 cells. H&E staining was used to observe pathological changes of synovial tissues in the knee joint of Wistar rats. Safranin O-fast green/hematoxylin was used to stain cartilage samples of knee joints. MiR-18a-3p overexpression suppressed OA progression in vivo. Overall, miR-18a-3p improves cartilage matrix remodeling and suppresses inflammation in OA by targeting PDP1.

Cuprizone-induced dopaminergic hyperactivity and locomotor deficit in zebrafish larvae.

Cuprizone (CPZ) is a copper-chelator and toxic to mitochondria. Recent studies have shown oligodendrocyte (OL) loss and demyelination along with dopamine (DA) increase and behavioral abnormalities in CPZ-exposed mice, demonstrating its application in schizophrenia research. This study examined effects of CPZ exposure on autonomous behavior and dopaminergic neurotransmission in larval zebra fish. CPZ exposure was found to reduce the swimming velocity of zebra fish thus decreased swimming distance during day and night time. Moreover, the treatment induced a movement response of zebra fish larvae reacting to light-on/off switch featured by swimming velocity increase and decrease during the first and second half of the light-on/off phase, respectively. But, it abolished responses of zebra fish to sound-on/off seen in Control group. HPLC analysis showed elevated DA levels in the zebra fish, no change in NE and 5-HT levels. Transcriptome analysis reported changes in gene expression related to dopaminergic synapse and oxidative phosphorylation in CPZ-exposed larvae relative to Control group. Of the gene expression changes, up-regulation of drd2a, drd2b, drd4a and drd4rs was confirmed by RT-PCR, although no difference existed between Control and CPZ groups in dopaminergic neuron numbers. These results demonstrated dopaminergic hyperactivity and locomotor deficit in CPZ-exposed zebra fish larvae, encouraging further application of this model in exploring neurotoxic effects of CPZ on mitochondria and dopaminergic neurotransmission in zebra fish.