Aiming at the problem that the optical link may be too expensive or even impossible to achieve in a large number of locations in the central part of the backhaul line, the proof-of-concept (PoC) ...verification of a millimeter-wave integrated heterogeneous network (HetNet) is proposed. HetNet includes a traditional macrocell network and a new small unit that uses a millimeter wave for backhaul line and link access. The concept of a segmentation control plane and user plane was introduced. In the HetNet integrated millimeter wave, the control plane and the user plane were segmented to support the uninterrupted connection and enhance the capacity of the millimeter wave small base station. Millimeter wave communication could be used not only for access links, but also for wireless backhaul links, which will facilitate the installation of small millimeter wave cells. Through conceptual verification (PoC), the feasibility of millimeter-wave integrated HetNet prototype with millimeter wave technology used for return lines and link access is proved.
Schizophrenia (SCZ) is a severe mental disorder, but its pathogenesis is still unknown, and its clinical treatment effect is very limited. Transient receptor potential vanilloid 1 (TRPV1) channel and ...the Endocannabinoid System (ECS)have been confirmed to be involved in the pathogenesis of SCZ, although their actions have not been fully clarified yet. The objective is to examine TRPV1 and ECS expression in the blood of schizophrenia patients and investigate their correlation with disease severity.
This is a cross-sectional investigation. Peripheral blood samples were gathered from normal controls (NC, n=37), as well as individuals with schizophrenia, including first episode (n=30) and recurrent (n=30) cases. We employed western blot and ELISA techniques to quantify TRPV1, cannabinoid receptors 1(CB1), anandamide (AEA), and 2-arachidonoylglycerol (2-AG), and assess the severity of the patient's symptoms by means of the PANSS scale.
Compared to NC, TRPV1 levels showed a noticeable decrease in both first episode schizophrenia (f-SCZ group) and recurrent schizophrenia (r-SCZ group) subjects. Additionally, CB1 levels appeared increased in f-SCZ group. Furthermore, 2-AG levels were found to be elevated in both f-SCZ group and r-SCZ group compared to NC, whereas AEA levels were decreased in f-SCZ group but increased in r-SCZ group. Moreover, among schizophrenia patients, TRPV1 demonstrated a negative correlation with negative symptoms. Within r-SCZ subjects, CB1 displayed a negative correlation with relapse number, while 2-AG showed a correlation in the opposite direction.
This study provides initial clinical evidence of changed TRPV1 expression in schizophrenia, potentially linked to negative symptoms. These results suggest a possible dysfunction of TRPV1 and the endocannabinoid system (ECS), which might offer new avenues for medical interventions.
•TRPV1 and the ECS may be involved in the development of schizophrenia and its clinical course.•TRPV1 might negatively correlated with negative symptom severity.•CB1 and 2-AG was negatively and positively correlated with the number of relapses in r-SCZ group.•TRPV1 and the ECS could be considered as potential biomarker and therapeutic target.
In this work, we proposed a novel modification technique to immobilize nanoparticles by the nanopores on a boron-doped diamond surface, preventing the aggregation of nanoparticles physically and ...improving the stability of nanoparticles layer by the anchoring effect. All the exposed surfaces of a bare boron-doped diamond were etched into nanoporous form and larger electrochemically active surface area was obtained on the porous boron-doped diamond electrode. The carbon black nanoparticles modified porous boron-doped diamond electrode showed good selectivity to separate the oxidation potential of three molecules, but led to an extra increase in the peak current of dopamine (DA). The carbon black/Nafion modified porous diamond electrode effectively suppress the oxidation current of ascorbic acid (AA), enhancing the sensitivity of DA. The dual layer treatment enables a wide linear range, 0.1–100 μM and a low limit of detection, 54 nM for DA detection, which is almost unaffected by the excess AA and uric acid (UA). At last, real sample tests of the carbon black/Nafion modified porous diamond electrode was validated by applying to the detection of DA in human serum and dopamine hydrochloride injection, which were found to be promising at our preliminary experiments. Additionally, the fabricated carbon black/Nafion modified porous diamond electrode also demonstrated good stability and long-term functionality.
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•A novel modification on porous boron-doped diamond electrode for determination of dopamine was developed.•The elimination of the interference was realized and a low detection limit of 54 nM for DA was obtained.•Reproducibility of the CB-Nafion/p-BDD electrode in real sample and excess interferents was validated.•Excellent stability and long-term functionality of the CB-Nafion/p-BDD electrode were confirmed.
In vivo tracking or in vitro real sample analysis by electrochemistry is one of the most straight and useful methods in biosensor field. However, surface biofouling of electrodes by non-specific ...protein adsorption is inevitable and usually leads to a decrease in sensitivity. Here, we developed a Nafion-coated porous boron-doped diamond (NAF/pBDD) electrode with hydrophobic nanostructures to minimize the biofouling effect and selectively detect dopamine (DA). Larger active area was obtained by this procedure compared to a bare diamond electrode. The as-prepared electrode shows excellent antifouling property and enrichment capacity toward selective detection of dopamine (DA). The low background current of the BDD electrode and the enhanced signals enables a lower detection limit, 42 nmol L
−1
, and a wider linear range, 0.1–110 μmol L
−1
, for determination of DA in human serum. Additionally, the facile modified electrode demonstrated renewable property and long-term stability due to the fact that the antifouling nanostructures belong to its own.
Neuroinflammation and mitochondrial impairment play important roles in the neuropathogenesis of Parkinson's disease (PD). The activation of NLRP3 inflammasome and the accumulation of α-synuclein ...(α-Syn) are strictly correlated to neuroinflammation. Therefore, the regulation of NLRP3 inflammasome activation and α-Syn aggregation might have therapeutic potential. It has been indicated that Dl-3-n-butylphthalide (NBP) produces neuroprotection against some neurological diseases such as ischemic stroke. We here intended to explore whether NBP suppressed NLRP3 inflammasome activation and reduced α-Syn aggregation, thus protecting dopaminergic neurons against neuroinflammation.
In our study, we established a MPTP-induced mouse model and 6-OHDA-induced SH-SY5Y cell model to examine the neuroprotective actions of NBP. We then performed behavioral tests to examine motor dysfunction in MPTP-exposed mice after NBP treatment. Western blotting, immunofluorescence staining, flow cytometry and RT-qPCR were conducted to investigate the expression of NLRP3 inflammasomes, neuroinflammatory cytokines, PARP1, p-α-Syn, and markers of microgliosis and astrogliosis.
The results showed that NBP exerts a neuroprotective effect on experimental PD models.
, NBP ameliorated behavioral impairments and reduced dopaminergic neuron loss in MPTP-induced mice.
, treatment of SH-SY5Y cells with 6-OHDA (100uM,24 h) significantly decreased cell viability, increased intracellular ROS production, and induced apoptosis, while pretreatment with 5uM NBP could alleviated 6-OHDA-induced cytotoxicity, ROS production and cell apoptosis to some extent. Importantly, both
and
, NBP suppressed the activation of the NLRP3 inflammasome and the aggregation of α-Syn, thus inhibited neuroinflammation ameliorated mitochondrial impairments.
In summary, NBP rescued dopaminergic neurons by reducing NLRP3 inflammasome activation and ameliorating mitochondrial impairments and increases in p-α-Syn levels. This current study may provide novel neuroprotective mechanisms of NBP as a potential therapeutic agent.
Fulminant hepatic failure (FHF) is a potentially fatal liver disease that is associated with intrahepatic infiltration of inflammatory cells. As the receptor of polyunsaturated long chain fatty ...acids, GPR120 can regulate cell differentiation, proliferation, metabolism, and immune response. However, whether GPR120 is involved in FHF remains unknown. Using Propionibacterium acnes (P. acnes)-primed, LPS-induced FHF in mice, we found that interference with GPR120 activity using pharmacological agonist attenuated the severity of the liver injury and mortality of FHF in mice, while a lack of GPR120 exacerbated the disease. GPR120 activation potently alleviated FHF and led to decreased T helper (Th) 1 cell response and expansion of regulatory T cells (Tregs). Interestingly, GPR120 agonist didn't directly target T cells, but dramatically induced a distinct population of CD11c
MHC II
CD80
CD86
regulatory DCs in the livers of FHF mice. GPR120 was found to restrict HIF-1α-dependent glycolysis. The augmented HIF-1α stabilization caused by GPR120 antagonism or deletion could be attenuated by the inhibition of ERK or by the activation of AMPK. Through the analysis of the clinical FHF, we further confirmed the activation of GPR120 was negatively associated with the severity in patients. Our findings indicated that GPR120 activation has therapeutic potential in FHF. Strategies to target GPR120 using agonists or free fatty acids (FFAs) may represent a novel approach to FHF treatment.
Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer's disease ...(AD), dementia with Lewy bodies (DLB) and Parkinson's disease. Using a transgenic mouse model of Parkinson's disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage. Interestingly, we found that overexpressed ASYN interacted with dynein and induced a significant increase in the activated levels of small Rab GTPases such as Rab5 and Rab7, both key regulators of endocytic processes. Furthermore, expression of ASYN resulted in neuronal atrophy in DIV7 cortical cultures of either from E18 transgenic mouse model or from rat E18 embryos that were transiently transfected with ASYN-GFP for 72 hrs. Our studies suggest that excessive ASYN likely alters endocytic pathways leading to axonal dysfunction in embryonic cortical neurons in PD mouse models.
Fulminant hepatic failure (FHF) is a clinical syndrome characterized by a sudden and severe impairment in liver function. However, the precise mechanism of immune dysregulation that is significant to ...FHF pathogenesis remains unclear. Enhancer of zeste homolog 2 (EZH2) has been implicated in inflammation as a regulator of immune cell function. In this study, we investigated the role of EZH2 in an animal model of human FHF induced by Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS). We demonstrated that EZH2 depletion in dendritic cells (DCs) and pharmacological inhibition of EZH2 using GSK126 both significantly ameliorated liver injury and improved the survival rates of mice with P. acnes plus LPS-induced FHF, which could be attributed to the decreased infiltration and activation of CD4
T cells in the liver, inhibition of T helper 1 cells and induction of regulatory T cells. The expression of EZH2 in DCs was increased after P. acnes administration, and EZH2 deficiency in DCs suppressed DC maturation and prevented DCs from efficiently stimulating CD4
T-cell proliferation. Further mechanistic analyses indicated that EZH2 deficiency directly increased the expression of the transcription factor RUNX1 and thereby suppressed the immune functions of DCs. The functional dependence of EZH2 on RUNX1 was further illustrated in DC-specific Ezh2-deficient mice. Taken together, our findings establish that EZH2 exhibits anti-inflammatory effects through inhibition of RUNX1 to regulate DC functions and that inhibition of EZH2 alleviates P. acnes plus LPS-induced FHF, probably by inhibiting DC-induced adaptive immune responses. These results highlight the effect of EZH2 on DCs, serving as a guide for the development of a promising immunotherapeutic strategy for FHF.
: Oxidative stress and inflammation play critical roles in the neuropathogenesis of PD. We aimed to evaluate oxidative stress and inflammation status by measuring serum superoxide dismutase (SOD) ...with lipoprotein cholesterol and high-sensitivity C-reactive protein (hsCRP) respectively in PD patients, and explore their correlation with the disease severity.
: We performed a cross-sectional study that included 204 PD patients and 204 age-matched healthy controls (HCs). Plasma levels of SOD, hsCRP, total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured. A series of neuropsychological assessments were performed to rate the severity of PD.
: The plasma levels of SOD (135.7 ± 20.14 vs. 147.2 ± 24.34,
< 0.0001), total cholesterol, HDL-C and LDL-C in PD were significantly lower than those in HCs; the hsCRP level was remarkably increased in PD compared to HC (2.766 ± 3.242 vs. 1.637 ± 1.597,
< 0.0001). The plasma SOD was negatively correlated with the hsCRP, while positively correlated with total cholesterol, HDL-C, and LDL-C in PD patients. The plasma SOD were negatively correlated with H&Y, total UPDRS, UPDRS (I), UPDRS (II), and UPDRS (III) scores, but positively correlated with MoCA and MMSE scores. Besides, hsCRP was negatively correlated with MoCA; while total cholesterol, HDL-C and LDL-C were positively correlated with the MoCA, respectively.
: Our findings suggest that lower SOD along with cholesterol, HDL-C and LDL-C, and higher hsCRP levels might be important markers to assess the PD severity. A better understanding of SOD and hsCRP may yield insights into the pathogenesis of PD.
Macroautophagy has been implicated in modulating the therapeutic function of mesenchymal stromal cells (MSCs). However, the biological function of chaperone-mediated autophagy (CMA) in MSCs remains ...elusive. Here, we found that CMA was inhibited in MSCs in response to the proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). In addition, suppression of CMA by knocking down the CMA-related lysosomal receptor lysosomal-associated membrane protein 2 (LAMP-2A) in MSCs significantly enhanced the immunosuppressive effect of MSCs on T cell proliferation, and as expected, LAMP-2A overexpression in MSCs exerted the opposite effect on T cell proliferation. This effect of CMA on the immunosuppressive function of MSCs was attributed to its negative regulation of the expression of chemokine C-X-C motif ligand 10 (CXCL10), which recruits inflammatory cells, especially T cells, to MSCs, and inducible nitric oxide synthase (iNOS), which leads to the subsequent inhibition of T cell proliferation via nitric oxide (NO). Mechanistically, CMA inhibition dramatically promoted IFN-γ plus TNF-α-induced activation of NF-κB and STAT1, leading to the enhanced expression of CXCL10 and iNOS in MSCs. Furthermore, we found that IFN-γ plus TNF-α-induced AKT activation contributed to CMA inhibition in MSCs. More interestingly, CMA-deficient MSCs exhibited improved therapeutic efficacy in inflammatory liver injury. Taken together, our findings established CMA inhibition as a critical contributor to the immunosuppressive function of MSCs induced by inflammatory cytokines and highlighted a previously unknown function of CMA.
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