Following Zhou's framework, we consider the emergent geometry of the generalized Brézin-Gross-Witten models whose partition functions are known to be a family of tau-functions of the BKP hierarchy. More precisely, we construct a spectral curve together with its special deformation, and show that the Eynard-Orantin topological recursion on this spectral curve emerges naturally from the Virasoro constraints for the generalized BGW tau-functions. Moreover, we give the explicit expressions for the BKP-affine coordinates of these tau-functions and their generating series. The BKP-affine coordinates and the topological recursion provide two different approaches towards the concrete computations of the connected n-point functions. Finally, we show that the quantum spectral curve of type B in the sense of Gukov-Sułkowski emerges from the BKP-affine coordinates and Eynard-Orantin topological recursion.

We establish an explicit relationship between the partition function of certain special cubic Hodge integrals and the generalized Brezin--Gross--Witten (BGW) partition function, which we refer to as the Hodge-BGW correspondence. As an application, we obtain an ELSV-like formula for generalized BGW correlators.

Okuyama and Sakai [JT supergravity and Brézin–Gross–Witten tau-function, J. High Energy Phys. 2020 (2020) 160] gave a conjectural equality for the higher genus generalized Brézin–Gross–Witten (BGW) free energies. In a recent work [D. Yang and Q. Zhang, On the Hodge-BGW correspondence, preprint (2021), arXiv:2112.12736], we established the Hodge-BGW correspondence on the relationship between certain special cubic Hodge integrals and the generalized BGW correlators, and a proof of the Okuyama–Sakai conjecture was also given ibid. In this paper, we give a new proof of the Okuyama–Sakai conjecture by a further application of the Dubrovin–Zhang theory for the KdV hierarchy.

We propose a generalization of the Witten conjecture, which connects a descendent enumerative theory with a specific reduction of KP integrable hierarchy. Our conjecture is realized by two parts: Part I (Geometry) establishes a correspondence between the descendent potential function (apart from ancestors) and the topological recursion of specific spectral curve data $(\Sigma, x,y,B)$; Part II (Integrability) claims that the TR descendent potential, defined at the boundary points of the spectral curve (where $dx$ has poles), is a tau function of a certain reduction of the multi-component KP hierarchy. In this paper, we show the geometry part for any formal descendent theory by using a generalized Laplace transform, and show the integrability part for the one-boundary cases. As applications, we generalize and prove the $r$KdV integrability of negative $r$-spin theory conjectured by Chidambaram, Garcia-Falide and Giacchetto [6], and prove the KdV integrability for the theory associated with the Weierstrass curve introduced by Dubrovin.

We apply the renormalized coupling constants and Virasoro constraints to derive the Itzykson-Zuber Ansatz on the form of the free energy in 2D topological gravity. We also treat the 1D topological gravity and the Hermitian one-matrix models in the same fashion. Some uniform behaviors are discovered in this approach.

Deficits in neurite outgrowth and synaptogenesis have been recognized as an underlying developmental aetiology of psychosis. Electrical stimulation promotes neuronal induction including neurite outgrowth and branching. However, the effect of electrical stimulation using 3D electrodes on neurite outgrowth and synaptogenesis has not been explored. This study examined the effect of 3D electrical stimulation on 3D primary cortical neuronal cultures. 3D electrical stimulation improved neurite outgrowth in 3D neuronal cultures from both wild-type and NRG1-knockout (NRG1-KO) mice. The expression of synaptophysin and PSD95 were elevated under 3D electrical stimulation. Interestingly, 3D electrical stimulation also improved neural cell aggregation as well as the expression of PSA-NCAM. Our findings suggest that the 3D electrical stimulation system can rescue neurite outgrowth deficits in a 3D culturing environment, one that more closely resembles the in vivo biological system compared to more traditionally used 2D cell culture, including the observation of cell aggregates as well as the upregulated PSA-NCAM protein and transcript expression. This study provides a new concept for a possible diagnostic platform for neurite deficits in neurodevelopmental diseases, as well as a viable platform to test treatment options (such as drug delivery) in combination with electrical stimulation.

Deficits in neurite outgrowth, possibly involving dysregulation of risk genes neuregulin-1 (NRG1) and disrupted in schizophrenia 1 (DISC1) have been implicated in psychiatric disorders including schizophrenia. Electrical stimulation using conductive polymers has been shown to stimulate neurite outgrowth of differentiating human neural stem cells. This study investigated the use of the electroactive conductive polymer polypyrrole (Ppy) to counter impaired neurite outgrowth of primary pre-frontal cortical (PFC) neurons from NRG1-knock out (NRG1-KO) and DISC1-locus impairment (DISC1-LI) mice. Whereas NRG1-KO and DISC1-LI exhibited reduced neurite length and number of neurite branches compared to wild-type controls, this was not apparent for cultures on electroactive Ppy. Additionally, the use of the Ppy substrate normalised the synaptophysin and PSD95 protein and mRNA expression whereas both are usually reduced by NRG1-KO or DISC1-LI. Our findings support the utility of Ppy mediated electrical stimulation to prevent the reduction of neurite outgrowth and related synaptic protein expression in the primary PFC neurons from NRG1-KO and DISC1-LI mice, providing proof-of-concept for treating neurodevelopmental diseases including schizophrenia.

Antipsychotic treatment, particularly olanzapine and clozapine, induces severe obesity. The Histamine H1 receptor is considered to be an important contributor to olanzapine-induced obesity, however how olanzapine modulates the histaminergic system is not sufficiently understood. This study examined the effect of olanzapine on key molecules of the histaminergic system, including histidine decarboxylase (HDC), H1 receptor (H1R) and H3 receptor (H3R), in the brain at different stages of olanzapine-induced obesity. During short-term treatment (8-day), olanzapine increased hypothalamic HDC mRNA expression and H1R binding in the arcuate nucleus (Arc) and ventromedial hypothalamus (VMH), without changing H3R binding density. HDC mRNA and Arc H1R binding were positively correlated with increased food intake, feeding efficiency and weight gain. When the treatment was extended to 16 and 36 days, H1R binding was increased not only in the hypothalamic Arc and VMH but also in the brainstem dorsal vagal complex (DVC). The H1R bindings in the Arc, VMH and DVC were positively correlated with weight gain induced by olanzapine treatment. However, the expression of HDC and H3R mRNA was not increased. These results suggest that olanzapine time-dependently modulates histamine neurotransmission, which suggested the different neuronal mechanisms underlying different stages of weight gain development. Treatment targeting the H1R may be effective for both short- and long-term olanzapine-induced weight gain.

A neuronal growth underlies the prefrontal cortical (PFC) pathology of many neurodegenerative disorders. Current treatments are inadequate and commonly cause severe side effects. Importantly, conventional pharmacotherapy strategies have limited efficacy in treating PFC dis-regulation in neurodegenerative disorders. Electrical stimulation is a modern treatment method which can include electroconvulsive therapy, Deep-Brain Stimulation (DBS) and epidural stimulation, etc. Previous studied showed that the application of electrical stimulations promotes neuritis outgrowth resulted to inter neuronal networking. Wide range of metallic microelectrodes composed of gold, steel, platinum etc. have been previously utilized to perform electrical stimulation however, rigidity, incompatible mechanical properties, high initial impedance and low chargetransfer capacity limit their application. Graphene and its derivatives are an exciting class of materials, which are utilized in microelectrodes due to having excellent mechanical stability, electrical conductivity, biocompatibility, flexibility and ability to fabricate and scale up. This work develops three-dimensional (3D) flexible electrode composed of 3D printed Reduced Liquid Crystalline Graphene Oxide (rLCGO) on a polyurethane (PU) substrate. The flexible conducting electrode is used as Host Template for Human Neural Stem Cells (hNSCs) development during proliferation and differentiation. The application of electrical stimulation on hNSC using graphene/PU electrodes revealed promising results to improve neurites guidance through 3D printed lines and enhanced cell-cell communication and networking.

For any bent function, it is very interesting to determine its dual function, because the dual function is also bent in certain cases. For $k$ odd and $\gcd (n, k)=1$ , it is known that the Coulter–Matthews bent function $f(x)=Tr\left({ax^{\frac {3^{k}+1}{2}}}\right)$ is weakly regular bent over $\mathbb {F}_{3^{n}}$ , where $a\in \mathbb {F}_{3^{n}}^{*}$ , and $Tr(\cdot ):\mathbb {F}_{3^{n}}\rightarrow \mathbb {F}_{3}$ is the trace function. In this paper, we investigate the dual function of $f(x)$ , aiming to determine a universal formula. In particular, for two cases, we determine the formula explicitly: for the case of $n=3t+1$ and $k=2t+1$ with $t\geq 2$ , the dual function is given by \begin{equation*}Tr\left ({-\frac {x^{3^{2t+1}+3^{t+1}+2}}{a^{3^{2t+1}+3^{t+1}+1}}-\frac {x^{3^{2t}+1}}{a^{-3^{2t}+3^{t}+1}}+\frac {x^{2}}{a^{-3^{2t+1}+3^{t+1}+1}}}\right );\end{equation*} and for the case of $n=3t+2$ and $k=2t+1$ with $t\geq 2$ , the dual function is given by \begin{equation*}Tr\left ({-\frac {x^{3^{2t+2}+1}}{a^{3^{2t+2}-3^{t+1}+3}}-\frac {x^{2\cdot 3^{2t+1}+3^{t+1}+1}}{a^{3^{2t+2}+3^{t+1}+1}}+\frac {x^{2}}{a^{-3^{2t+2}+3^{t+1}+3}}}\right ).\end{equation*} As a byproduct, we find two new classes of ternary bent functions with only three terms. Moreover, we also prove that in certain cases $f(x)$ is regular bent.

High-fat (HF) diet modulates gut microbiota and increases plasma concentration of lipopolysaccharide (LPS) which is associated with obesity and its related low-grade inflammation and cognitive decline. Rhein is the main ingredient of the rhubarb plant which has been used as an anti-inflammatory agent for several millennia. However, the potential effects of rhein against HF diet-induced obesity and its associated alteration of gut microbiota, inflammation and cognitive decline have not been studied. In this study, C57BL/6J male mice were fed an HF diet for 8 weeks to induce obesity, and then treated with oral rhein (120 mg/kg body weight/day in HF diet) for a further 6 weeks. Chronic rhein treatment prevented the HF diet-induced recognition memory impairment assessed by the novel object recognition test, neuroinflammation and brain-derived neurotrophic factor (BDNF) deficits in the perirhinal cortex. Furthermore, rhein inhibited the HF diet-induced increased plasma LPS level and the proinflammatory macrophage accumulation in the colon and alteration of microbiota, including decreasing Bacteroides-Prevotella spp. and Desulfovibrios spp. DNA and increasing Bifidobacterium spp. and Lactobacillus spp. DNA. Moreover, rhein also reduced body weight and improved glucose tolerance in HF diet-induced obese mice. In conclusion, rhein improved recognition memory and prevented obesity in mice on a chronic HF diet. These beneficial effects occur via the modulation of microbiota, hypoendotoxinemia, inhibition of macrophage accumulation, anti-neuroinflammation and the improvement of BDNF expression. Therefore, supplementation with rhein-enriched food or herbal medicine could be beneficial as a preventive strategy for chronic HF diet-induced cognitive decline, microbiota alteration and neuroinflammation.

Obesity induces chronic, low-grade inflammation, which increases the risk of colon cancer. We investigated the preventive effects of Bardoxolone methyl (BARD) on high-fat diet (HFD)-induced inflammation in a mouse colon. Male C57BL/6J mice (n=7) were fed a HFD (HFD group), HFD plus BARD (10 mg/kg) in drinking water (HFD/BARD group), or normal laboratory chow diet (LFD group) for 21 weeks. In HFD mice, BARD reduced colon thickness and decreased colon weight per length. This was associated with an increase in colon crypt depth and the number of goblet cells per crypt. BARD reduced the expression of F4/80 and CD11c but increased CD206 and IL-10, indicating an anti-inflammatory effect. BARD prevented an increase of the intracellular pro-inflammatory biomarkers (NF-қB, p NF-қB, IL-6, TNF-α) and cell proliferation markers (Cox2 and Ki67). BARD prevented fat deposition in the colon wall and prevented microbial population changes. Overall, we report the preventive effects of BARD on colon inflammation in HFD-fed mice through its regulation of macrophages, NF-қB, cytokines, Cox2 and Ki67, fat deposition and microflora.

Accumulating evidence suggests that reducing neurite outgrowth and synaptic plasticity plays a critical role in the pathology of cognitive deficits in schizophrenia. The N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) can induce symptoms of schizophrenia as well as reduce dendritic spine density and neurite growth. The antipsychotic drug olanzapine may improve these deficits. This study aimed to investigate: (1) if olanzapine prevents PCP-induced suppression of neurite outgrowth and synaptic protein expression; (2) if olanzapine affects the Akt-GSK3 signaling pathway; and (3) the role of neuregulin 1 (NRG1) in this process. Immunofluorescence revealed that PCP treatment for 24 hours reduces both neurite length (28.5%) and the number of neurite branches (35.6%) in primary prefrontal cortical neuron cultures. PCP reduced protein and mRNA expressions of synaptophysin (24.9% and 23.2%, respectively) and PSD95 (31.5% and 21.4%, respectively) and the protein expression of p-Akt (26.7%) and p-GSK3β (35.2%). Olanzapine co-treatment prevented these PCP-induced effects in normal neurons but not in neurons from NRG1-knockout mice. These results indicate that NRG1 mediates the preventive effects of olanzapine on the PCP-induced impairment of neurite outgrowth and synaptic protein expression. This study provides potential targets for interventions on improving the efficacy of olanzapine on preventing cognitive deficits in schizophrenia.

0引言神经根鞘囊肿,称为Tarlov囊肿,临床发生率较低,见于脊神经间隙,绝大部分见于骶管。河北医科大学附属哈励逊国际和平医院骨二科于2015年收治1例发生部位为颈椎、胸椎椎间孔且同时伴有神经节细胞瘤,极为罕见,现报道如下。1病例资料及诊疗过程患者,女,62岁,主因间断性颈肩部、后背伴左季肋放射性疼痛半年余入我院心内科。

Obesity results in changes in brown adipose tissue (BAT) morphology, leading to fat deposition, inflammation, and alterations in sympathetic nerve activity. Bardoxolone methyl (BARD) has been extensively studied for the treatment of chronic diseases. We present for the first time the effects of oral BARD treatment on BAT morphology and associated changes in the brainstem. Three groups (n = 7) of C57BL/6J mice were fed either a high-fat diet (HFD), a high-fat diet supplemented with BARD (HFD/BARD), or a low-fat diet (LFD) for 21 weeks. BARD was administered daily in drinking water. Interscapular BAT, and ventrolateral medulla (VLM) and dorsal vagal complex (DVC) in the brainstem, were collected for analysis by histology, immunohistochemistry and Western blot. BARD prevented fat deposition in BAT, demonstrated by the decreased accumulation of lipid droplets. When administered BARD, HFD mice had lower numbers of F4/80 and CD11c macrophages in the BAT with an increased proportion of CD206 macrophages, suggesting an anti-inflammatory effect. BARD increased phosphorylation of tyrosine hydroxylase in BAT and VLM. In the VLM, BARD increased energy expenditure proteins, including beta 3-adrenergic receptor (β3-AR) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Overall, oral BARD prevented fat deposition and inflammation in BAT, and stimulated sympathetic nerve activity.

Epidemiological evidence suggests that the consumption of a diet high in n-6 polyunsaturated fatty acids (PUFA) is associated with the development of leptin resistance and obesity. We aim to examine the central effect of n-6 PUFA, arachidonic acid (ARA) on leptin sensitivity and leptin-regulated hepatic glucose and lipid metabolism. We found that intracerebroventricular injection of ARA (25 nmol/day) for 2.5 days reversed the effect of central leptin on hypothalamic JAK2, pSTAT3, pAkt, and pFOXO1 protein levels, which was concomitant with a pro-inflammatory response in the hypothalamus. ARA also attenuated the effect of central leptin on hepatic glucose and lipid metabolism by reversing the mRNA expression of the genes involved in gluconeogenesis (G6Pase, PEPCK), glucose transportation (GLUT2), lipogenesis (FAS, SCD1), and cholesterol synthesis (HMG-CoA reductase). These results indicate that an increased exposure to central n-6 PUFA induces central cellular leptin resistance with concomitant defective JAK2-STAT3 and PI3K-Akt signaling. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

The metabolic side-effects of olanzapine have undermined drug compliance and increased concern for this otherwise-effective treatment for schizophrenia. As obesity and type 2 diabetes are associated with low-grade inflammation, and olanzapine-induced weight gain has three typical stages, the current study investigated the inflammatory effects of olanzapine in three treatment stages. Female Sprague-Dawley rats were treated orally with olanzapine (1 mg/kg three times daily) or vehicle for one week, two weeks, and five weeks. Olanzapine significantly increased body weight and white visceral fat deposition in all three treatment stages compared to control. Olanzapine enhanced average adipocyte size and level of macrophage infiltration in white adipose tissue (WAT) compared to control, with levels of macrophage infiltration increased over time. There was a high correlation between adipocyte size and macrophage infiltration rate. Olanzapine also caused increased macrophage infiltration in brown adipose tissue (BAT), but not liver. Additionally, pro-inflammatory cytokines tumor necrosis factor α (TNFα), interleukin (IL)-1β, and IL-6 were upregulated by olanzapine in the hypothalamus, WAT, and BAT compared to control, but not the liver. Finally, plasma triglycerides were elevated by olanzapine compared to control, but not total cholesterol, high density lipoprotein (HDL) or low density lipoprotein (LDL). These findings indicate that olanzapine-induced inflammation and adiposity are closely related, and that peripheral low-grade inflammation develops during olanzapine treatment.

Weight gain and its related metabolic disorders are major side effects associated with second generation antipsychotic drug treatment. The dorsal vagal complex (DVC) and AMP-activated protein kinase (AMPK) are implicated in the regulation of food intake and body weight. Blocking the histamine H1 receptor contributes to antipsychotic-induced weight gain. The present study investigated the time-dependent effect of olanzapine treatment (8, 16, and 36 d) on DVC AMPK signaling in olanzapine-induced weight gain and whether these changes are associated with olanzapine-induced H1 receptor antagonism. During the 8-day olanzapine treatment, the rats were hyperphagic and rapidly gained weight. The phosphorylation of AMPK (pAMPK) (activated AMPK) as well as its directly downstream phospho-acetyl-coenzyme A carboxylase was significantly increased. The pAMPK/AMPK ratio, an indicator of AMPK activity, was significantly positively correlated with feeding efficiency and weight gain. As treatment was prolonged (16 and 36 d of olanzapine treatment), the rats were no longer hyperphagic, and there were no longer any changes in DVC AMPK signaling. Although the DVC H1 receptor protein expression was not significantly altered by olanzapine, the pAMPK expression was significantly positively correlated with the H1 receptor level after the 8-, 16-, and 36-day olanzapine treatments. Moreover, we showed that an H1 receptor agonist, 2-(3-trifluoromethylphenyl) histamine, significantly inhibited the olanzapine-induced hyperphagia and DVC AMPK activation in a dose-dependent manner. These results suggest a time-dependent role of DVC AMPK in olanzapine-induced obesity. Thus, olanzapine-induced DVC AMPK activation may be at least partially related to olanzapine's antagonistic effect on the H1 receptor.

Excessive weight gain is a major metabolic side effect of second-generation antipsychotics (SGAs) in the treatment of schizophrenia. Ghrelin is an orexigenic hormone secreted mainly from the stomach, which can induce weight gain and hyperphagia through regulating neuropeptides at the hypothalamus. Accumulating evidence implicates a relationship between ghrelin signalling and SGA-induced hyperphagia and weight gain. We report that olanzapine (a SGA with high weight gain liability) potently and time-dependently up-regulate ghrelin and ghrelin signalling, leading to hyperphagia and weight gain in female Sprague-Dawley rats, an action reversed by i.c.v. injection of a ghrelin receptor (GHS-R1a) antagonist. These findings indicate a crucial role of ghrelin signalling in hyperphagia induced by olanzapine, supporting the notion that GHS-R1a antagonist may be useful for pharmacological treatment of SGA-induced weight gain resulted from hyperphagia.