HIV-1gp120 Induces Neuronal Apoptosis through Enhancement of 4-Aminopyridine-Senstive Outward K+ Currents

Human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) usually occurs late in the course of HIV-1 infection and the mechanisms underlying HAD pathogenesis are not well understood. Accumulating evidence indicates that neuronal voltage-gated potassium (Kv) channels play an important role in memory processes and acquired neuronal channelopathies in HAD. To examine whether Kv channels are involved in HIV-1-associated neuronal injury, we studied the effects of HIV-1 glycoprotein 120 (gp120) on outward K+ currents in rat cortical neuronal cultures using whole-cell patch techniques. Exposure of cortical neurons to gp120 produced a dose-dependent enhancement of A-type transient outward K+ currents (IA). The gp120-induced increase of IA was attenuated by T140, a specific antagonist for chemokine receptor CXCR4, suggesting gp120 enhancement of neuronal IA via CXCR4. Pretreatment of neuronal cultures with a protein kinase C (PKC) inhibitor, GF109203X, inhibited the gp120-induced increase of IA. Biological significance of gp120 enhancement of IA was demonstrated by experimental results showing that gp120-induced neuronal apoptosis, as detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and caspase-3 staining, was attenuated by either an IA blocker 4-aminopyridine or a specific CXCR4 antagonist T140. Taken together, these results suggest that gp120 may induce caspase-3 dependent neuronal apoptosis by enhancing IA via CXCR4-PKC signaling

The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo

Decay-accelerating factor ([DAF] CD55) is a glycosylphosphatidylinositol-anchored membrane inhibitor of complement with broad clinical relevance. Here, we establish an additional and unexpected role for DAF in the suppression of adaptive immune responses in vivo. In both C57BL/6 and BALB/c mice, deficiency of the Daf1 gene, which encodes the murine homologue of human DAF, significantly enhanced T cell responses to active immunization. This phenotype was characterized by hypersecretion of interferon (IFN)-γ and interleukin (IL)-2, as well as down-regulation of the inhibitory cytokine IL-10 during antigen restimulation of lymphocytes in vitro. Compared with wild-type mice, Daf1−/− mice also displayed markedly exacerbated disease progression and pathology in a T cell–dependent experimental autoimmune encephalomyelitis (EAE) model. However, disabling the complement system in Daf1−/− mice normalized T cell secretion of IFN-γ and IL-2 and attenuated disease severity in the EAE model. These findings establish a critical link between complement and T cell immunity and have implications for the role of DAF and complement in organ transplantation, tumor evasion, and vaccine development

Proteomic Modeling for HIV-1 Infected Microglia-Astrocyte Crosstalk

Background: HIV-1-infected and immune competent brain mononuclear phagocytes (MP; macrophages and microglia) secrete cellular and viral toxins that affect neuronal damage during advanced disease. In contrast, astrocytes can affect disease by modulating the nervous system’s microenvironment. Interestingly, little is known how astrocytes communicate with MP to influence disease. Methods and Findings: MP-astrocyte crosstalk was investigated by a proteomic platform analysis using vesicular stomatitis virus pseudotyped HIV infected murine microglia. The microglial-astrocyte dialogue was significant and affected microglial cytoskeleton by modulation of cell death and migratory pathways. These were mediated, in part, through F-actin polymerization and filament formation. Astrocyte secretions attenuated HIV-1 infected microglia neurotoxicity and viral growth linked to the regulation of reactive oxygen species. Conclusions: These observations provide unique insights into glial crosstalk during disease by supporting astrocytemediated regulation of microglial function and its influence on the onset and progression of neuroAIDS. The results open new insights into previously undisclosed pathogenic mechanisms and open the potential for biomarker discovery an

Study on Core Values of Smart Tourism and Empirical Research Based on Tourist Perception

With the depth integration of the information technology industry and tourism industry, the intelligent tourism has become the inevitable choice of tourism transformation and upgrading. Represented by cloud computing and internet of things, the intelligent capability which was produced by the information technology industrial integration innovation application mode has become the main power to promote deep change of tourism industry. The article made an empirical analysis of smart tourism and extracted the five core values which are experience value, information value, innovation value, function value and cost value. Thus to put forward the four innovative development countermeasures so that make the smart tourism became the important grasp of promoting science technology value and strategic position of tourism industry

Oligodendrocyte Injury and Pathogenesis of HIV-1-Associated Neurocognitive Disorders

Oligodendrocytes wrap neuronal axons to form myelin, an insulating sheath which is essential for nervous impulse conduction along axons. Axonal myelination is highly regulated by neuronal and astrocytic signals and the maintenance of myelin sheaths is a very complex process. Oligodendrocyte damage can cause axonal demyelination and neuronal injury, leading to neurological disorders. Demyelination in the cerebrum may produce cognitive impairment in a variety of neurological disorders, including human immunodeficiency virus type one (HIV-1)-associated neurocognitive disorders (HAND). Although the combined antiretroviral therapy has markedly reduced the incidence of HIV-1-associated dementia, a severe form of HAND, milder forms of HAND remain prevalent even when the peripheral viral load is well controlled. HAND manifests as a subcortical dementia with damage in the brain white matter (e.g., corpus callosum), which consists of myelinated axonal fibers. How HIV-1 brain infection causes myelin injury and resultant white matter damage is an interesting area of current HIV research. In this review, we tentatively address recent progress on oligodendrocyte dysregulation and HAND pathogenesis

Ecological and Health Risk Assessment of Heavy Metals in Soils from Recycled Lead Smelting Sites

In this study, 258 soil samples were collected to determine the total content and each speciation fraction of chromium (Cr), manganese (Mn), copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) in the soil by inductively coupled plasma mass spectrometry (ICP-MS), and their potential ecological and human health risks were assessed using the geo-accumulation index (Igeo), risk assessment code (RAC), and health risk assessment. The results showed that: (1) The mean concentrations of heavy metals (HMs) (mg/kg) in the surface soil of the site were in the order of Pb (1921.77) > Mn (598.21) > Zn (162.29) > Cr (84.65) > Cu (15.16) > Cd (1.8), with the mean values of Cd and Pb exceeding the local background values by 164 and 725 times. (2) In the vertical direction, Cr, Mn, and Pb have no tendency to migrate downward; Cd and Zn demonstrate a strong ability to migrate. (3) The bioavailability of Cd is the highest in the surface soil, followed by Mn and Pb; in the soil below a depth of 0.5 m, the prevalent form of HMs is its residual state (F4). (4) The degree of Igeo pollution of each HMs is: Pb > Cd > Zn > Cr = Mn = Cu, where Pb pollutes the environment to an extremely contaminated level and Cd causes heavy pollution thereof. According to the RAC results, Cd in the surface soil poses a high risk to the environment, and Pb and Mn pose a moderate risk; meanwhile, with the increase of depth, the risk posed by Cd and Mn to the ecosystem shows a tendency to increase. Health risk evaluation indicated that respiratory intake was the main pathway affecting the carcinogenic risk (CR) and hazard quotient (HQ) of HMs, where Pb and Cr were the main hazard factors for non-CR and Cr was the main carcinogenic factor. This study can provide scientific guidance and technical support for soil risk control or remediation of HM-contaminated sites

Ecological and Health Risk Assessment of Heavy Metals in Soils from Recycled Lead Smelting Sites

In this study, 258 soil samples were collected to determine the total content and each speciation fraction of chromium (Cr), manganese (Mn), copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) in the soil by inductively coupled plasma mass spectrometry (ICP-MS), and their potential ecological and human health risks were assessed using the geo-accumulation index (Igeo), risk assessment code (RAC), and health risk assessment. The results showed that: (1) The mean concentrations of heavy metals (HMs) (mg/kg) in the surface soil of the site were in the order of Pb (1921.77) > Mn (598.21) > Zn (162.29) > Cr (84.65) > Cu (15.16) > Cd (1.8), with the mean values of Cd and Pb exceeding the local background values by 164 and 725 times. (2) In the vertical direction, Cr, Mn, and Pb have no tendency to migrate downward; Cd and Zn demonstrate a strong ability to migrate. (3) The bioavailability of Cd is the highest in the surface soil, followed by Mn and Pb; in the soil below a depth of 0.5 m, the prevalent form of HMs is its residual state (F4). (4) The degree of Igeo pollution of each HMs is: Pb > Cd > Zn > Cr = Mn = Cu, where Pb pollutes the environment to an extremely contaminated level and Cd causes heavy pollution thereof. According to the RAC results, Cd in the surface soil poses a high risk to the environment, and Pb and Mn pose a moderate risk; meanwhile, with the increase of depth, the risk posed by Cd and Mn to the ecosystem shows a tendency to increase. Health risk evaluation indicated that respiratory intake was the main pathway affecting the carcinogenic risk (CR) and hazard quotient (HQ) of HMs, where Pb and Cr were the main hazard factors for non-CR and Cr was the main carcinogenic factor. This study can provide scientific guidance and technical support for soil risk control or remediation of HM-contaminated sites

Gelatin/Hyaluronic Acid Photocrosslinked Double Network Hydrogel with Nano-Hydroxyapatite Composite for Potential Application in Bone Repair

The application of hydrogels in bone repair is limited due to their low mechanical strength. Simulating bone extracellular matrix, methylacrylylated gelatin (GelMA)/methylacrylylated hyaluronic acid (HAMA)/nano-hydroxyapatite(nHap) composite hydrogels were prepared by combining the double network strategy and composite of nHap in this study. The precursor solutions of the composite hydrogels were injectable due to their shear thinning property. The compressive elastic modulus of the composite hydrogel was significantly enhanced, the fracture strength of the composite hydrogel nearly reached 1 MPa, and the composite hydrogel retained its high water content at above 88%. The composite hydrogels possess good compatibility with BMSCS and have the potential to be used as injectable hydrogels for bone defect treatment

Economic Scheduling Model of an Active Distribution Network Based on Chaotic Particle Swarm Optimization

With the continuous increase in global energy demand and growing environmental awareness, the utilization of renewable energy has become a worldwide consensus. In order to address the challenges posed by the intermittent and unpredictable nature of renewable energy in distributed power distribution networks, as well as to improve the economic and operational stability of distribution systems, this paper proposes the establishment of an active distribution network capable of accommodating renewable energy. The objective is to enhance the efficiency of new energy utilization. This study investigates optimal scheduling models for energy storage technologies and economic-operation dispatching techniques in distributed power distribution networks. Additionally, it develops a comprehensive demand response model, with real-time pricing and incentive policies aiming to minimize load peak–valley differentials. The control mechanism incorporates time-of-use pricing and integrates a chaos particle swarm algorithm for a holistic approach to solution finding. By coordinating and optimizing the control of distributed power sources, energy storage systems, and flexible loads, the active distribution network achieves minimal operational costs while meeting demand-side power requirements, striving to smooth out load curves as much as possible. Case studies demonstrate significant enhancements during off-peak periods, with an approximately 60% increase in the load power overall elevation of load factors during regular periods, as well as a reduction in grid loads during evening peak hours, with a maximum decrease of nearly 65 kW. This approach mitigates grid operational pressures and user expense, effectively enhancing the stability and economic efficiency in distribution network operations