Households’ Perceptions Toward Tourism Development In Mount Jizu Tourism Scenic Area, Shazhi Village Commune, Yunnan Province Of China

Tourism development is a very important industry to improve the development of countries, households is a key participator and practitioner about tourism development in the rural area, the manager of tourism and governors can set up the reasonable and effective strategy to driving the local economic development depend on the households' perceptions. This research aimed 1)to study perceptions of households toward tourism development, and 2) to analyze the factors related to the perceptions of households toward tourism development in Mount JIZU scenic area, SHASHI Village Commune, Dali City, Yunnan Province of China. The research was conducted using quantitative methods through the survey questionnaires, A total of 227 valid samples were collected. The finding revealed that 1)The households' head had positive perceptions toward tourism development in terms of economic, social-cultural and environment. 2) Also a series of independent variables were associated with the perceptions of the household head toward tourism development, the independent variables including of gender, age, education, income, length of residence, employed in the tourism industry, the management of government, the future planning of tourism project, and contact frequency with outside tourists

Modulation of hippocampal gamma oscillations by dopamine in heterozygous Reeler mice In vitro

The reelin haploinsufficient heterozygous reeler mouse (HRM), an animal model of schizophrenia, has altered mesolimbic dopaminergic pathways, shares similar neurochemical, and behavioral properties with the patients with schizophrenia. Dysfunctional neural circuitry with impaired gamma (γ) oscillation (30–80 Hz) has been implicated in abnormal cognition in patients with schizophrenia. However, the function of neural circuitry in terms of γ oscillation and its modulation by dopamine has not been reported in HRM. In this study, first, we recorded γ oscillations in CA3 from wide type (WT) mice and HRM hippocampal slices, and studied the effects of dopamine (DA) on γ oscillations. We found that there was no difference in γ power between WT mice and HRM and that dopamine increased γ power of WT mice but not HRM, suggesting that dopamine modulations of network oscillations in HRM are impaired. Second, we found that N-methyl-D-aspartate receptor (NMDAR) antagonist itself increased γ power and occluded DA-mediated enhancement of γ power in WT mice but partially restored DA modulation of γ oscillations in HRM. Third, inhibition of phosphoinositide 3-kinase (PI3K), a downstream molecule of NMDAR, increased γ power and blocked the effects of DA on γ oscillation in WT mice and had no significant effect on γ power but largely restored DA modulation of γ oscillations in HRM. Our results reveal that impaired DA function in HRM is associated with dysregulated NMDAR-PI3K signaling, a mechanism that may be relevant in the pathology of schizophrenia

Macrolides Selectively Inhibit Mutant KCNJ5 Potassium Channels that Cause Aldosterone-Producing Adenoma

Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce the salt-retaining steroid hormone aldosterone and cause millions of cases of severe hypertension worldwide. Either of 2 somatic mutations in the potassium channel KCNJ5 (G151R and L168R, hereafter referred to as KCNJ5MUT) in adrenocortical cells account for half of APAs worldwide. These mutations alter channel selectivity to allow abnormal Na+ conductance, resulting in membrane depolarization, calcium influx, aldosterone production, and cell proliferation. Because APA diagnosis requires a difficult invasive procedure, patients often remain undiagnosed and inadequately treated. Inhibitors of KCNJ5MUT could allow noninvasive diagnosis and therapy of APAs carrying KCNJ5 mutations. Here, we developed a high-throughput screen for rescue of KCNJ5MUT-induced lethality and identified a series of macrolide antibiotics, including roxithromycin, that potently inhibit KCNJ5MUT, but not KCNJ5WT. Electrophysiology demonstrated direct KCNJ5MUT inhibition. In human aldosterone-producing adrenocortical cancer cell lines, roxithromycin inhibited KCNJ5MUT-induced induction of CYP11B2 (encoding aldosterone synthase) expression and aldosterone production. Further exploration of macrolides showed that KCNJ5MUT was similarly selectively inhibited by idremcinal, a macrolide motilin receptor agonist, and by synthesized macrolide derivatives lacking antibiotic or motilide activity. Macrolide-derived selective KCNJ5MUT inhibitors thus have the potential to advance the diagnosis and treatment of APAs harboring KCNJ5MUT

TiC 0.5

TiCN-based cermets with varied fractions of Si3N4 nanopowder (0–5 wt.%) were prepared by spark plasma sintering. The microstructural and mechanical properties of these cermets were investigated. In general, with increasing addition amount of Si3N4 nanopowder the relative density as well as mechanical properties of the as-prepared TiCN cermets increased first and then decreased. The samples containing 2 wt.% Si3N4 nanopowder presented the best performance with the relative density of about 98%, bending strength of 1000 MPa, and Vickers microhardness of about 1810 HV10

Characteristics of Evoked Potential Multiple EEG Recordings in Patients with Chronic Pain by Means of Parallel Factor Analysis

This paper presents an alternative method, called as parallel factor analysis (PARAFAC) with a continuous wavelet transform, to analyze of brain activity in patients with chronic pain in the time-frequency-channel domain and quantifies differences between chronic pain patients and controls in these domains. The event related multiple EEG recordings of the chronic pain patients and non-pain controls with somatosensory stimuli (pain, random pain, touch, random touch) are analyzed. Multiple linear regression (MLR) is applied to describe the effects of aging on the frequency response differences between patients and controls. The results show that the somatosensory cortical responses occurred around 250 ms in both groups. In the frequency domain, the neural response frequency in the pain group (around 4 Hz) was less than that in the control group (around 5.5 Hz) under the somatosensory stimuli. In the channel domain, cortical activation was predominant in the frontal region for the chronic pain group and in the central region for controls. The indices of active ratios were statistical significant between the two groups in the frontal and central regions. These findings demonstrate that the PARAFAC is an interesting method to understanding the pathophysiological characteristics of chronic pain

CYP-omega-hydroxylation-dependent metabolites of arachidonic acid inhibit the basolateral 10pS chloride channel in the rat thick ascending limb

Metabolites of arachidonic acid influence sodium chloride (NaCl) transport in the thick ascending limb. Because a 10pS Cl channel is the major type of chloride channel in the basolateral membrane of this nephron segment, we explored the effect of arachidonic acid on this channel in cell-attached patches. Addition of 5μmol arachidonic acid significantly decreased channel activity (a product of channel number and open probability) while linoleic acid had no effect. To determine if this was mediated by acachidonic acid per se or by its metabolites, we measured channel activity in the presence of the cyclooxygenase inhibitor indomethacin, the selective lipoxygenase inhibitor nordihydroguaiaretic acid, and the cytochrome P-450 (CYP)-ω-hydroxylation inhibitor 17-octadecynoic acid. Neither cyclooxygenase nor lipoxygenase inhibition had an effect on basal chloride channel activity; further they failed to abolish the inhibitory effect of arachidonate on the 10pS channel. However, inhibition of CYP-ω-hydroxylation completely abolished the effect of arachidonic acid. The similarity of the effects of 20-hydroxyeicosatetraenoic acid (20-HETE) and arachidonic acid suggests that the effect of arachidonic acid was mediated by CYP-ω-hydroxylation-dependent metabolites. We conclude that arachidonic acid inhibits the 10pS chloride channel in the basolateral membrane of the medullary thick ascending limb, an effect mediated by the CYP-ω-hydroxylation-dependent metabolite 20-HETE

Preparation of Cementitious Material Using Smelting Slag and Tailings and the Solidification and Leaching of Pb 2+

The composite cementitious materials were prepared with lead-zinc tailings, lead-zinc smelting slag, and cement clinker. The effect of material ratio on the mechanical properties, the phase analysis, and microstructures were investigated. The effect of the pH and stripping time on the leaching amount of lead ion was discussed. The results show that the additive amount of the tailings should be minimized for the cementitious materials meeting the strength requirements, controlled within 10%. The leaching amount of cementitious materials remains low in a larger range of pH, which can effectively reduce the leaching of heavy metal lead. The leaching kinetics of lead ions in the three kinds of samples could be better described by the pseudo-second-model

Adenosine stimulates the basolateral 50 pS K+ channel in renal proximal tubule via adenosine-A1 receptor

Background: The basolateral potassium channels play an important role in maintaining the membrane transport in the renal proximal tubules (PT) and adenosine receptors have been shown to regulate the trans-epithelial Na+ absorption in the PT. The aim of the present study is to explore whether adenosine also regulates the basolateral K+ channel of the PT and to determine the adenosine receptor type and the signaling pathway which mediates the effect of adenosine on the K+ channel.Methods: We have used the single channel recording to examine the basolateral K+ channel activity in the proximal tubules of the mouse kidney. All experiments were performed in cell-attached patches.Results: Single channel recording has detected a 50 pS inwardly-rectifying K+ channel with high channel open probability and this 50 pS K+ channel is a predominant type K+ channel in the basolateral membrane of the mouse PT. Adding adenosine increased 50 pS K+ channel activity in cell-attached patches, defined by NPo (a product of channel Numbers and Open Probability). The adenosine-induced stimulation of the 50 pS K+ channel was absent in the PT pretreated with DPCPX, a selective inhibitor of adenosine A1 receptor. In contrast, adenosine was still able to stimulate the 50 pS K+ channel in the PT pretreated with CP-66713, a selective adenosine A2 receptor antagonist. This suggests that the stimulatory effect of adenosine on the 50 pS K+ channel of the PT was mediated by adenosine-A1 receptor. Moreover, the effect of adenosine on the 50 pS K+ channel was blocked in the PT pretreated with U-73122 or Calphostin C, suggesting that adenosine-induced stimulation of the 50 pS K+ channels of the PT was due to the activation of phospholipase C (PLC) and protein kinase C (PKC) pathway. In contrast, the inhibition of phospholipase A2 (PLA2) with AACOCF3 or inhibition of protein kinase A (PKA) with H8 failed to block the adenosine-induced stimulation of the 50 pS K+ channel of the PT.Conclusion: We conclude that adenosine activates the 50 pS K+ channels in the basolateral membrane of PT via adenosine-A1 receptor. Furthermore, the effect of adenosine on the 50 pS K+ channel is mediated by PLC-PKC signaling pathway

A neutralizing bispecific single-chain antibody against SARS-CoV-2 Omicron variant produced based on CR3022

IntroductionThe constantly mutating SARS-CoV-2 has been infected an increasing number of people, hence the safe and efficacious treatment are urgently needed to combat the COVID-19 pandemic. Currently, neutralizing antibodies (Nabs), targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein are potentially effective therapeutics against COVID-19. As a new form of antibody, bispecific single chain antibodies (BscAbs) can be easily expressed in E. coli and exhibits broad-spectrum antiviral activity.MethodsIn this study, we constructed two BscAbs 16-29, 16-3022 and three single chain variable fragments (scFv) S1-16, S2-29 and S3022 as a comparison to explore their antiviral activity against SARS-CoV-2. The affinity of the five antibodies was characterized by ELISA and SPR and the neutralizing activity of them was analyzed using pseudovirus or authentic virus neutralization assay. Bioinformatics and competitive ELISA methods were used to identify different epitopes on RBD.ResultsOur results revealed the potent neutralizing activity of two BscAbs 16-29 and 16-3022 against SARS-CoV-2 original strain and Omicron variant infection. In addition, we also found that SARS-CoV RBD-targeted scFv S3022 could play a synergistic role with other SARS-CoV-2 RBD-targeted antibodies to enhance neutralizing activity in the form of a BscAb or in cocktail therapies.DiscussionThis innovative approach offers a promising avenue for the development of subsequent antibody therapies against SARSCoV-2. Combining the advantages of cocktails and single-molecule strategies, BscAb therapy has the potential to be developed as an effective immunotherapeutic for clinical use to mitigate the ongoing pandemic