MicroRNA-877-5p promotes osteoblast differentiation by targeting EIF4G2 expression.

Stimulating bone formation potentially suggests therapeutics for orthopedic diseases including osteoporosis and osteoarthritis. Osteoblasts are key to bone remodeling because they act as the only bone-forming cells. miR-877-5p has a chondrocyte-improving function in osteoarthritis, but its effect on osteoblast differentiation is unknown. Here, miR-877-5p-mediated osteoblast differentiation was studied. Real-time reverse transcriptase-polymerase chain reaction was performed to measure miR-877-5p expression during the osteogenic differentiation of MC3T3-E1 cells. Osteoblast markers, including alkaline phosphatase (ALP), collagen type I a1 chain, and osteopontin, were measured and detected by alizarin red staining and ALP staining. Potential targets of miR-877-5p were predicted from three different algorithms: starBase ( http://starbase.sysu.edu.cn/ ), PITA ( http://genie.weizmann.ac.il/pubs/mir07/mir07_data.html ), and miRanda ( http://www.microrna.org/microrna/home.do ). It was further verified by dual luciferase reporter gene assay. The experimental results found that miR-877-5p was upregulated during the osteogenic differentiation of MC3T3-E1 cells. Overexpression of miR-877-5p promoted osteogenic differentiation, which was characterized by increased cell mineralization, ALP activity, and osteogenesis-related gene expression. Knockdown of miR-877-5p produced the opposite result. Dual luciferase reporter gene assay showed that miR-877-5p directly targeted eukaryotic translation initiation factor 4γ2 (EIF4G2). Overexpression of EIF4G2 inhibited osteogenic differentiation and reversed the promoting effect of overexpression of miR-135-5p on osteogenic differentiation. These results indicate that miR-877-5p might have a therapeutic application related to its promotion of bone formation through targeting EIF4G2.

Beclin 1 Haploinsufficiency Ameliorates High-Fat Diet-Induced Myocardial Injury via Inhibiting Alternative Mitophagy.

Aims: Mitochondrial homeostasis is essential for maintaining redox balance. Besides canonical autophagy, Rab9-dependent alternative autophagy is a crucial mechanism in metabolic cardiomyopathy. Here, we aim to investigate the role of alternative mitophagy and Beclin 1 haploinsufficiency (Beclin 1+/-) in high-fat diet (HFD)-induced metabolic cardiomyopathy. Results: Twenty-four-week HFD impaired glucose tolerance and cardiomyocyte contraction in wild-type mice, both of which were rescued in Beclin 1+/- mice. Beclin 1 haploinsufficiency had little effect on the conventional autophagy mediators (ATG5, LC3 II/LC3 I) but further upregulated Rab9 expression, a marker of alternative autophagy, in response to HFD challenge. Furthermore, either the inhibition of alternative autophagy or Beclin 1 haploinsufficiency abolished palmitic acid (PA)-induced cardiomyocyte contractile anomalies. In vitro, PA overactivated mitophagy, resulting in decreased mitochondrial content in H9C2 cells. These aberrations were alleviated in cells deficient in alternative autophagy but not in cells deficient in conventional autophagy. Mechanistically, HFD promoted reactive oxygen species (ROS) production, activated Rab9-dependent alternative mitophagy, and inhibited mitochondrial biosynthesis. Beclin 1+/- rescued HFD-induced ROS overflow, mitochondrial biogenesis impairment, and prevented Rab9 translocation from the cytoplasm to the mitochondria, thereby inhibiting Rab9-mediated mitophagy overactivation. Innovation: For the first time, this study suggests that prolonged alternative mitophagy exacerbates chronic HFD-induced cardiac dysfunction and supports the protective role of Beclin 1 haploinsufficiency in metabolic cardiomyopathy. This provides additional evidence for a target-based pharmacological intervention. Conclusion: Beclin 1 haploinsufficiency protects against HFD-induced cardiac dysfunction by inhibiting Rab9-dependent alternative mitophagy and ROS production, while promoting mitochondrial biogenesis. Modulating Beclin 1 expression holds promise in preventing chronic HFD-related cardiomyopathy.

Identifying misdiagnosed bipolar disorder using support vector machine: feature selection based on fMRI of follow-up confirmed affective disorders.

Nearly a quarter of bipolar disorder (BD) patients were misdiagnosed as major depressive disorder (MDD) patients, which cannot be corrected until mania/hypomania develops. It is important to recognize these obstacles so that the appropriate treatment can be initiated. Thus, we sought to distinguish patients with BD from MDD, especially to identify misdiagnosed BD before mania/hypomania, and further explore potential trait features that allow accurate differential diagnosis independent of state matters. Functional magnetic resonance imaging scans were performed at baseline on 92 MDD patients and 48 BD patients. The MDD patients were then followed up for more than two years. After follow-up, 23 patients transformed into BD (tBD), and 69 patients whose diagnoses remained unchanged were eligible for unipolar depression (UD). A support vector machine classifier was trained on the amygdala-based functional connectivity (FC) of 48 BD and 50 UD patients using a novel region-based feature selection. Then, the classifier was tested on the dataset, encompassing tBD and the remaining UD. It performed well for known BD and UD and can also distinguish tBD from UD with an accuracy of 81%, sensitivity of 82.6%, specificity of 79%, and AUC of 74.6%, respectively. Feature selection results revealed that ten regions within the cortico-limbic neural circuit contributed most to classification. Furthermore, in the FC comparisons among diseases, BD and tBD shared almost overlapped FC patterns in the cortico-limbic neural circuit, and both of them presented pronounced differences in most regions within the circuit compared with UD. The FC values of the most discriminating brain regions had no prominent correlations with the severity of depression, anxiety, and mania/hypomania (FDR correction). It suggests that BD possesses some trait features in the cortico-limbic neural circuit, rendering it dichotomized by the classifier based on known-diagnosis data.

Evaluation of physical education teaching effect using Random Forest model under artificial intelligence.

This work aims to optimize the physical education (PE) teaching effect based on deep learning (DL) to cultivate high-level college students better. Firstly, the present situation of college teachers' teaching ability is surveyed to realize the deficiencies in teaching. Secondly, an optimization algorithm is proposed to improve the node splitting mode. This algorithm can solve the problem of single and similar node splitting modes in the Random Forest (RF) algorithm. The independent node splitting method Iterative Dichotomiser 3 and Classification and Regression Tree in the algorithm are recombined, and new splitting rules are obtained through adaptive parameter selection. Finally, the scheme designed is tested. The results suggest: The results suggest: (1) During the training of the proposed algorithm, although the loss curve at 4550 and 6800 points has a small crest, the error of the network loss function shows a downward trend and tends to be flat; (2) Compared with unoptimized Genetic Algorithm (GA) and Genetic Algorithm-Back Propagation (GA-BP), the proposed algorithm shows better performance both in terms of time consumption and accuracy (time consumption is less than 5.4 ms, and accuracy is more than 95 %). In a word, using the GA-BP-RF algorithm proposed to improve the PE teaching effect is feasible. The proposed model provides ideas for applying DL technology to improve teachers' teaching abilities.

Enhancement of multilayer lithium storage in a ß12-borophene/graphene heterostructure with built-in dipoles.

The combination of borophene with a supporting metallic layer is beneficial in stabilizing its structure and promoting its application in energy storage. Here, through first-principles calculations, we screen a ß12-borophene/graphene (ß12-B/G) heterostructure with superior structural integrity, strong interlayer binding, and high thermodynamic stability among different B/G heterostructures. Besides, it is noteworthy that ß12-B/G has been recently synthesized, further opening the possibility of expanding its use in energy storage. Then the selected target is systematically investigated as an anode material for lithium-ion batteries (LIBs). Compared with each monolayer component, multiple lithium-ion adsorption is achieved in the ß12-B/G heterostructure, resulting in an ultra-high theoretical specific capacity of 2267 mA h g-1. In addition, a lower diffusion energy barrier indicates faster electron transport and lithium-ion diffusion in the ß12-B/G heterostructure. Notably, the multilayer lithium adsorption avoids the formation of dendritic deposits, as evidenced by complete ionization of the cationic layers. Moreover, the disparity in the work functions of the individual layers gives rise to a built-in dipole in ß12-B/G, further enhancing the multilayer lithium storage and ion migration. All these results suggest that the construction of borophene-based heterostructures with built-in dipoles is a feasible way to design high-performance LIB anode materials.

Functional and structural alterations in different durations of untreated illness in the frontal and parietal lobe in major depressive disorder.

Major depressive disorder (MDD) is one of the most disabling illnesses that profoundly restricts psychosocial functions and impairs quality of life. However, the treatment rate of MDD is surprisingly low because the availability and acceptability of appropriate treatments are limited. Therefore, identifying whether and how treatment delay affects the brain and the initial time point of the alterations is imperative, but these changes have not been thoroughly explored. We investigated the functional and structural alterations of MDD for different durations of untreated illness (DUI) using regional homogeneity (ReHo) and voxel-based morphometry (VBM) with a sample of 125 treatment-naïve MDD patients and 100 healthy controls (HCs). The MDD patients were subgrouped based on the DUI, namely, DUI ≤ 1 M, 1 < DUI ≤ 6 M, 6 < DUI ≤ 12 M, and 12 < DUI ≤ 48 M. Subgroup comparison (MDD with different DUIs) was applied to compare ReHo and grey matter volume (GMV) extracted from clusters of regions with significant differences (the pooled MDD patients relative to HCs). Correlations and mediation effects were analysed to estimate the relationships between the functional and structural neuroimaging changes and clinical characteristics. MDD patients exhibited decreased ReHo in the left postcentral gyrus and precentral gyrus and reduced GMV in the left middle frontal gyrus and superior frontal gyrus relative to HCs. The initial functional abnormalities were detected after being untreated for 1 month, whereas this duration was 3 months for GMV reduction. Nevertheless, a transient increase in ReHo was observed after being untreated for 3 months. No significant differences were discovered between HCs and MDD patients with a DUI less than 1 month or among MDD patients with different DUIs in either ReHo or GMV. Longer DUI was related to reduced ReHo with GMV as mediator in MDD patients. We identified disassociated functional and anatomical alterations in treatment-naïve MDD patients at different time points in distinct brain regions at the early stage of the disease. Additionally, we also discovered that GMV mediated the relationship between a longer DUI and diminished ReHo in MDD patients, disclosing the latent deleterious and neuro-progressive implications of DUI on both the structure and function of the brain and indicating the necessity of early treatment of MDD.

Distributed Control for Nonlinear Time-Delay Multiagent Systems: Hybrid Saturation-Constraint Impulsive Approach.

This article mainly studies the problem of impulse consensus of multiagent systems under communication constraints and time delay. Considering the limited communication bandwidth of the agent, global and partial saturation constraints are considered. In addition, so as to further improve communication efficiency by reducing communication frequency, the novel control protocol combining event-triggered strategy and general impulse control protocol is proposed. Under this kind of novel control protocol, the communication frequency of multiagent systems can be reduced while avoiding "Zeno behavior." Through theoretical analysis, sufficient conditions for the systems to achieve consensus are obtained for the above two saturation constraint cases. In the end, the effectiveness of the novel protocols is proved by providing two different simulation instances.

Identifying the source and fate of boron in geothermal water: Evidence from B/Na and B isotopes.

High level dissolved B, which poses risks to human health, has been widely observed in geothermal water. In the Guide Basin, NW China, a series of geothermal water samples along a fault show a wide range of B contents ranging from 3.14 to 8.33 mg/L, which are higher than the WHO Guideline value equaling 2.4 mg/L in drinking water. To identify the sources and fate of B, we conduct a comprehensive analysis of hydrochemistry and stable isotopes (D, 18O and 11B) of three thermal fields representing three stages of hydrogeochemical evolution (stages I, II and III). From stage I to III, there are trends of increasing mineral dissolution, which is supported by increasing mean reservoir temperature and concentrations of conservative elements (Cl, Na, K, Li and Si). Geothermal water in stage I with meteoric origin and the lowest reservoir temperature has the highest B/Na resulting from silicate dissolution and falls on the mixing line between granitoids and cold water on the plot of δ11B versus 1/B, showing the control of silicate dissolution. However, geothermal water in stage III has lower Ca, B Sr and B/Na than that in stage II. Because of the occurrence of other processes, geothermal water in stages II and III deviates from the LMWL. Compared with geothermal water in stage I, the increased Sr/Ca and decreased B/Ca show that B are removed by both coprecipitation and vapor separation. With the aid of B isotopes, we find vapor separation dominates in stage II, whereas carbonate precipitation dominates in stage III. Overall, a combined use of three isotopes (H, O and B) and three element ratios (B/Na, B/Ca and Sr/Ca) leads to a complete understanding of B cycle and hydrogeochemical evolution in hydrothermal systems.

Acute or Chronic Exposure to Corticosterone Promotes Wakefulness in Mice.

Elevated glucocorticoid levels triggered by stress potentially contribute to sleep disturbances in stress-induced depression. However, sleep changes in response to elevated corticosterone (CORT), the major glucocorticoid in rodents, remain unclear. Here, we investigated the effects of acute or chronic CORT administration on sleep using electroencephalogram (EEG) and electromyography (EMG) recordings in freely moving mice. Acute CORT exposure rapidly promoted wakefulness, marked by increased episodes and enhanced EEG delta power, while simultaneously suppressing rapid eye movement (REM) and non-rapid eye movement (NREM) sleep, with the latter marked by decreased mean duration and reduced delta power. Prolonged 28-day CORT exposure led to excessive wakefulness and REM sleep, characterized by higher episodes, and decreased NREM sleep, characterized by higher episodes and reduced mean duration. EEG theta activity during REM sleep and delta activity during NREM sleep were attenuated following 28-day CORT exposure. These effects persisted, except for REM sleep amounts, even 7 days after the drug withdrawal. Elevated plasma CORT levels and depressive phenotypes were identified and correlated with observed sleep changes during and after administration. Fos expression significantly increased in the lateral habenula, lateral hypothalamus, and ventral tegmental area following acute or chronic CORT treatment. Our findings demonstrate that CORT exposure enhanced wakefulness, suppressed and fragmented NREM sleep, and altered EEG activity across all stages. This study illuminates sleep alterations during short or extended periods of heightened CORT levels in mice, providing a neural link connecting insomnia and depression.

Circular RNA-FK501 binding protein 51 boosts bone marrow mesenchymal stem cell proliferation and osteogenic differentiation via modulating microRNA-205-5p/Runt-associated transcription factor 2 axis.

OBJECTIVE: Osteogenesis is the key process of bone homeostasis differentiation. Numerous studies have manifested that circular RNA (circRNA) is a critical regulator of osteogenesis. The research was to explore circRNA-mediated mechanisms in osteogenesis. METHODS: Bone marrow mesenchymal stem cells (BMSCs) were cultured and induced to osteogenic differentiation (OD). Then, oe-circ-FKBP5, oe-NC, si-circ-FKBP5, si-NC, miR-205-5p mimic, mimic NC, miR-205-5p inhibitor, inhibitor NC, sh-RUNX2, or sh-NC were transfected into BMSCs. Alkaline phosphatase (ALP) activity was detected by ALP staining, cell mineralization was detected by alizarin red staining, cell proliferation was detected by CCK-8, and cell apoptosis was detected by flow cytometry. Then, the expression of circ-FKBP5, miR-205-5p, RUNX2 and osteogenic marker genes was detected by RT-qPCR, and the expression of RUNX2 protein was detected by Western blot. Finally, the targeting relationship between miR-205-5p and circ-FKBP5 or RUNX2 was verified by bioinformation website analysis and dual luciferase reporter gene detection. RESULTS: Circ-FK501 binding protein 51 (FKBP5) was distinctly elevated during OD of BMSCs. Elevated circ-FKBP5 boosted the proliferation and OD, as well as expression of osteogenic marker genes while reduced apoptosis of BMSCs. Down-regulation of circ-FKBP5 inhibited BMSCs proliferation, OD and osteogenic marker gene expression, and promoted apoptosis of BMSCs. Subsequently, circ-FKBP5 combined with miR-205-5p and constrained miR-205-5p expression. Silenced miR-205-5p boosted proliferation, OD, and expression of osteogenic marker genes and suppressed apoptosis of BMSCs. However, up-regulation of miR-205-5p inhibited BMSC proliferation, OD and osteogenic marker gene expression, and promoted apoptosis. Additionally, miR-205-5p targeted Runt-associated transcription factor 2 (RUNX2). Repression of RUNX2 turned around the effect of circ-FKBP5 overexpression on BMSCs. CONCLUSION: In brief, circ-FKBP5 boosted BMSC proliferation and OD by mediating the miR-205-5p/RUNX2 axis.

Sex effects on differentiating patients with major depressive disorder from bipolar disorder in depressive state: A fMRI study with follow-up.

BACKGROUND: Bipolar disorder (BD) is difficult to discriminate from major depressive disorder (MDD) before the appearance of mania or hypomania. This study was designed to identify whether patients with MDD and those who converted to BD are distinguishable using dynamic amplitude low-frequency fluctuations (dALFF) and describe the sex effects on the identification of the two disorders. METHODS: We compared the dALFF values of 35 BD patients who converted from MDD during the 2-year follow-up, 99 MDD patients, and 130 healthy controls (HCs) using two-way ANOVA. Pearson's correlation was used to compare dALFF in dysfunctional brain regions and clinical characteristics. RESULTS: A main effect of diagnosis was discovered in the frontal and occipital gyrus. For the main effect of sex, both the left middle occipital gyrus and the medial part of the superior frontal gyrus had higher dALFF values in males compared to females. An interaction of sex and diagnosis effect was observed in the right precentral gyrus. Male MDD patients exhibited a higher dALFF value than male BD patients. Additionally, we discovered a higher dALFF value in females than in males in BD patients. WCST scores were positively associated with dALFF values in the frontal and occipital gyrus in MDD patients. Meanwhile, dALFF values in the occipital gyrus positively correlated with WCST in female MDD patients only. LIMITATION: Most of the participants were on medication and the sample size was small. CONCLUSIONS: Our study is the first to find the non-neglectable role of sex effects in differentiating BD and MDD at an early stage.

Theoretical Enhancement of the Goos-Hänchen Shift with a Metasurface Based on Bound States in the Continuum.

The enhancement of the Goos-Hänchen (GH) shift has become a research hotspot due to its promoted application of the GH effect in various fields. However, currently, the maximum GH shift is located at the reflectance dip, making it difficult to detect GH shift signals in practical applications. This paper proposes a new metasurface to achieve reflection-type bound states in the continuum (BIC). The GH shift can be significantly enhanced by the quasi-BIC with a high quality factor. The maximum GH shift can reach more than 400 times the resonant wavelength, and the maximum GH shift is located exactly at the reflection peak with unity reflectance, which can be applied to detect the GH shift signal. Finally, the metasurface is used to detect the variation in the refractive index, and the sensitivity can reach 3.58 × 106 µm/RIU (refractive index unit) according to the simulation's calculations. The findings provide a theoretical basis to prepare a metasurface with high refractive index sensitivity, a large GH shift, and high reflection.

The RAGE signaling in osteoporosis.

Osteoporosis (OP), characterized by an imbalance of bone remodeling between formation and resorption, has become a health issue worldwide. The receptor for advanced glycation end product (RAGE), a transmembrane protein in the immunoglobin family, has multiple ligands and has been involved in many chronic diseases, such as diabetes and OP. Increasing evidence shows that activation of the RAGE signaling negatively affects bone remodeling. Ligands, such as advanced glycation end products (AGEs), S100, ß-amyloid (Aß), and high mobility group box 1 (HMGB1), have been well documented that they may negatively regulate the proliferation and differentiation of osteoblasts and positively stimulate osteoclastogenesis by activating the expression of RAGE. In this review, we comprehensively discuss the structure of RAGE and its biological functions in the pathogenesis of OP. The research findings suggest that RAGE signaling has become a potential target for the therapeutic management of OP.

Analysis of the regulatory role of miR-34a-5p/PLCD3 in the progression of osteoarthritis.

Osteoarthritis is a heterogeneous disease with a complex etiology. However, there is no effective treatment strategy at present. The purpose of this study was to explore the miRNA‒mRNA regulatory network and molecular mechanism that regulate the progression of osteoarthritis. In this article, we downloaded datasets (GSE55457, GSE82107, GSE143514 and GSE55235) from Gene Expression Omnibus (GEO) to screen differentially expressed mRNAs in osteoarthritis. Then, through weighted gene coexpression network (WGCNA), functional enrichment, protein‒protein interaction (PPI) network, miRNA‒mRNA coexpression network, ROC curve, and immune infiltration analyses and qPCR, the mRNA PLCD3, which was highly expressed in osteoarthritis and had clinical predictive value, was screened. We found that PLCD3 directly targets miR-34a-5p through DIANA and dual-luciferase experiments. The expression levels of PLCD3 and miR-34a-5p were negatively correlated. In addition, CCK-8 and wound healing assays showed that the miR-34a-5p mimic inhibited hFLS-OA cell proliferation and promoted hFLS-OA cell migration. PLCD3 overexpression showed the opposite trend. Western blotting further found that overexpression of miR-34a-5p reduced the protein expression levels of p-PI3K and p-AKT, while overexpression of PLCD3 showed the opposite trend. In addition, combined with the effect of the PI3K/AKT pathway inhibitor BIO (IC50 = 5.95 µM), the results showed that overexpression of miR-34a-5p increased the inhibitory effects of BIO on p-PI3K and p-AKT protein expression, while overexpression of PLCD3 significantly reversed these inhibitory effects. Overall, the miR-34a-5p/PLCD3 axis may mediate the PI3K/AKT pathway in regulating cartilage homeostasis in synovial osteoarthritis. These data indicate that miR-34a-5p/PLCD3 may be a new prognostic factor in the pathology of synovial osteoarthritis.

Altered gray matter volumes and plasma IL-6 level in major depressive disorder patients with suicidal ideation.

BACKGROUNDS: Suicidal ideation (SI) is one of the most serious consequences of major depressive disorder (MDD). Understanding the unique mechanism of MDD with SI (MDD + S) is crucial for treatment development. While abundant research has studied MDD, past studies have not reached a consensus on the mechanism of MDD + S. The study aimed to investigate the abnormalities of the gray matter volumes (GMVs) and plasma IL-6 level in MDD + S to further reveal the mechanism of MDD + S. METHODS: We tested the plasma IL-6 level using Luminex multifactor assays and collected the Structural Magnetic Resonance Imaging (SMRI) data from 34 healthy controls (HCs), 36 MDD patients without SI (MDD - S) and 34 MDD + S patients. We performed a partial correlation between the GMVs of the brain regions with significant differences and plasma IL-6 level with age, sex, medication, scores of HAMD-17 and HAMA as the covariates. RESULTS: Compared with HCs and MDD - S, MDD + S had significantly decreased GMVs in the left cerebellum Crus I/II and significantly increased plasma IL-6 level; compared with HCs, both the MDD + S and MDD - S had significantly decreased GMVs in right precentral and postcentral gyri. No significant correlation was found between the GMVs and the plasma IL-6 level in the MDD + S and MDD - S, respectively. While the GMVs of the right precentral and postcentral gyri negatively correlated with the level of IL-6 in the whole MDD (r = -0.28, P = 0.03). The GMVs of the left cerebellum Crus I/II (r = -0.47, P = 0.02), and the right precentral and postcentral gyri (r = -0.42, P = 0.04) negatively correlated with the level of IL-6 in HCs. CONCLUSION: The altered GMVs and the plasma IL-6 level may provide a scientific basis to understand the pathophysiological mechanisms of MDD + S.

Gray matter volume reduction in orbitofrontal cortex correlated with plasma glial cell line-derived neurotrophic factor (GDNF) levels within major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a severe mental disorder characterized by reduced gray matter volume (GMV). To date, the pathogenesis of MDD remains unclear, but neurotrophic factors play an essential role in the pathophysiological alterations of MDD during disease development. In particular, plasma glial cell line-derived neurotrophic factor (GDNF) has been suggested as a potential biomarker that may be associated with disease activity and neurological progression in MDD. Our study investigated whether plasma GDNF levels in MDD patients and healthy controls (HCs) are correlated with GMV alterations. METHODS: We studied 54 MDD patients and 48 HCs. The effect of different diagnoses on whole-brain GMV was investigated using ANOVA (Analysis of Variance). The threshold of significance was p < 0.05, and Gaussian random-field (GRF) correction for error was used. All analyses were controlled for covariates such as ethnicity, handedness, age, and gender that could affect GMV. RESULT: Compared with the HC group, the GMV in the MDD group was significantly reduced in the right inferior orbitofrontal cortex (OFC), and plasma GDNF levels were significantly higher in the MDD group than in the HC group. In the right inferior OFC, the GDNF levels were positively correlated with GMV reduction in the MDD group, whereas in the HC group, a negative correlation was observed between GDNF levels and GMV reduction. CONCLUSION: Although increased production of GDNF in MDD may help repair neural damage in brain regions associated with brain disease, its repairing effects may be interfered with and hindered by underlying neuroinflammatory processes.

Abnormal white matter integrity in Papez circuit in first-episode medication-naive adults with anxious depression: A combined voxel-based analysis and region of interest study.

BACKGROUND: Anxious depression is one of the subtypes of major depressive disorder (MDD), usually defined as "patients with MDD and high levels of anxiety symptoms". Compared to non-anxious MDD (naMDD), patients with anxious MDD (aMDD) have more severe depressive symptoms and suicidal ideation, worse treatment outcomes and remission rates, and poorer prognosis. Current research suggests that the Papez circuit is an important brain structure closely related to emotion, memory, and cognition. This study applied DTI to explore the altered white matter integrity in Papez circuit of patients with aMDD. METHODS: DTI data were acquired from 30 medication-naive outpatients with naMDD and 55 with aMDD and 88 demographically similar healthy control (HC) subjects. Voxel-based analysis (VBM) and region of interest (ROI) analysis were conducted to explore the significant difference of fractional anisotropy (FA) values among 3 groups. Pearson's correlations were performed to analyze the correlation between FA values and the score of HAMA-14 and HAMD-17. RESULTS: We found that aMDD patients had significantly higher FA values in left fornix (belong to Papez circuit) and left posterior thalamic radiation and right anterior corona radiata (belong to limbic-thalamo-cortical circuitry) compared with HC. And there was variability in the white matter integrity in right posterior thalamic radiation (belong to limbic-thalamo-cortical circuitry) and left fornix (belong to Papez circuit) between aMDD and naMDD patients. LIMITATIONS: The cross-sectional study and the population vary between aMDD group and naMDD group are limitations. CONCLUSIONS: Abnormal white matter integrity in Papez circuit and Limbic-Thalamo-Cortical circuitry may play an important role in the neuropathology of aMDD and might help to identify aMDD.

Tracking performance for NCSs with multi-communication constraints.

In this paper, the tracking performance of multiple input multiple output (MIMO) networked control systems (NCSs) with multiple communication constraints is studied. The effects of network induced factors (packet loss and network delay) and basic communication constraints (bandwidth, encoding-decoding and different noise) are considered. By inner-outer factorization and Youla parameterization, the mathematical expressions of the performance of the one-degree of freedom (1DOF) controller and two-degree of freedom (2DOF) controller are obtained, respectively. It shows that internal characteristics and network constraints have different effects on the tracking performance of the plant, and the performance of the 2DOF controller is better than that of the 1DOF controller. Finally, several simulation examples are provided to verify the influence of each constraint.

Applying dimensional psychopathology: transdiagnostic prediction of executive cognition using brain connectivity and inflammatory biomarkers.

BACKGROUND: The association between executive dysfunction, brain dysconnectivity, and inflammation is a prominent feature across major psychiatric disorders (MPDs), schizophrenia, bipolar disorder, and major depressive disorder. A dimensional approach is warranted to delineate their mechanistic interplay across MPDs. METHODS: This single site study included a total of 1543 participants (1058 patients and 485 controls). In total, 1169 participants underwent diffusion tensor and resting-state functional magnetic resonance imaging (745 patients and 379 controls completed the Wisconsin Card Sorting Test). Fractional anisotropy (FA) and regional homogeneity (ReHo) assessed structural and functional connectivity, respectively. Pro-inflammatory cytokine levels [interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α] were obtained in 325 participants using blood samples collected with 24 h of scanning. Group differences were determined for main measures, and correlation and mediation analyses and machine learning prediction modeling were performed. RESULTS: Executive deficits were associated with decreased FA, increased ReHo, and elevated IL-1ß and IL-6 levels across MPDs, compared to controls. FA and ReHo alterations in fronto-limbic-striatal regions contributed to executive deficits. IL-1ß mediated the association between FA and cognition, and IL-6 mediated the relationship between ReHo and cognition. Executive cognition was better predicted by both brain connectivity and cytokine measures than either one alone for FA-IL-1ß and ReHo-IL-6. CONCLUSIONS: Transdiagnostic associations among brain connectivity, inflammation, and executive cognition exist across MPDs, implicating common neurobiological substrates and mechanisms for executive deficits in MPDs. Further, inflammation-related brain dysconnectivity within fronto-limbic-striatal regions may represent a transdiagnostic dimension underlying executive dysfunction that could be leveraged to advance treatment.

Gender differences in plasma glial cell line-derived neurotrophic factor levels of patients with bipolar disorder.

BACKGROUND: The glial cell line-derived neurotrophic factor (GDNF) has an important role in neurons and is closely associated with psychiatric disorders. The development of bipolar disorder (BD) may differ between genders. Existing studies have shown that plasma GDNF levels are altered in patients with BD. In this study, we investigate whether the GDNF levels in patients with BD differ in terms of gender. METHODS: Participants were divided into the BD group (n = 76, with 26 males and 50 females) and healthy control (HC) group (n = 89, with 35 males and 54 females). Plasma GDNF levels were detected via multifactor assay. Clinical symptoms of patients with BD were collected and assessed using the Hamilton Depression-17 Inventory, Hamilton Anxiety-17 Inventory, Young's Mania Rating Scale, and Brief Psychiatric Rating Scale. RESULTS: The GDNF levels were significantly higher in all participants in the HC group (F = 4.262, p < 0.05) compared with those in the BD group. In the HC group, the males (t = 4.814, p < 0.001) presented significantly higher levels than the females. The plasma GDNF levels in males in the BD group (t = 3.022, p < 0.05) were significantly lower than those in males in the HC group. CONCLUSION: Differences in plasma GDNF levels are associated with the gender of patients with BD.