This study examines the impact on inbound tourism caused by the presence of world heritage sites. The statistics are derived from panel data for 66 countries for the period 2006–2009. The results ...indicate that there exists a positive relationship between having such heritage sites and tourist numbers, and the relationship is stronger for natural rather than for cultural heritage sites. The evidence also indicates the presence of a U-shaped relationship between numbers of world heritage sites in a country and tourist numbers. These relationships are found to be robust even though differences in patterns are found in different regions.
•Investigate in the positive influence of world heritage sites on international tourist arrivals.•Divide the sample into several groups according to the number of WHSs to study effects of WHSs across these groups.•Explore the pooled, fixed and random effect models with panel data (66 countries, 2000–2009).•Eliminate the problem of time-invariant variables in panel data model by increasing the number of countries.
Postoperative cognitive dysfunction (POCD) is a very common complication that might increase the morbidity and mortality of elderly patients after surgery. However, the mechanism of POCD remains ...largely unknown. The NAD-dependent deacetylase protein Sirtuin 3 (SIRT3) is located in the mitochondria and regulates mitochondrial function. SIRT3 is the only sirtuin that specifically plays a role in extending lifespan in humans and is associated with neurodegenerative diseases. Therefore, the aim of this study was to evaluate the effect of SIRT3 on anesthesia/surgery-induced cognitive impairment in aged mice.
SIRT3 expression levels were decreased after surgery. For the interventional study, an adeno-associated virus (AAV)-SIRT3 vector or an empty vector was microinjected into hippocampal CA1 region before anesthesia/surgery. Western blotting, immunofluorescence staining, and enzyme-linked immune-sorbent assay (ELISA) were used to measure the oxidative stress response and downstream microglial activation and proinflammatory cytokines, and Golgi staining and long-term potentiation (LTP) recording were applied to evaluate synaptic plasticity.
Overexpression of SIRT3 in the CA1 region attenuated anesthesia/surgery-induced learning and memory dysfunction as well as synaptic plasticity dysfunction and the oxidative stress response (superoxide dismutase SOD and malondialdehyde MDA) in aged mice with POCD. In addition, microglia activation (ionized calcium binding adapter molecule 1 Iba1) and neuroinflammatory cytokine levels (tumor necrosis factor-alpha TNF-α, interleukin IL-1β and IL-6) were regulated after anesthesia/surgery in a SIRT3-dependent manner.
The results of the current study demonstrate that SIRT3 has a critical effect in the mechanism of POCD in aged mice by suppressing hippocampal neuroinflammation and reveal that SIRT3 may be a promising therapeutic and diagnostic target for POCD.
This paper analyzes the determinants of international tourist arrivals in China, especially for World Heritage Sites and various kinds of travel spots. Utilizing annual provincial panel data over the ...2000–2005 period, the empirical results suggest that key determinants include the relative income, population in the original country, cost of travel, and tourism infrastructure. In addition, World Heritage Sites are also found to be significant in explaining the numbers of international tourists and have a greater tourist-enhancing effect. Other famous tourist sites rated 4A- and 3A-class are also attractive to foreign tourism. Moreover, cultural rather than natural sites attract more interest among foreign tourists, because China is internationally renowned for its long-standing historical and cultural assets. Finally, the importance of the determinants of the demand for tourism varies from country to country.
• Seed germination is a crucial transition point in plant life and is tightly regulated by environmental conditions through the coordination of two phytohormones, gibberellin and abscisic acid (ABA). ...To avoid unfavorable conditions, plants have evolved safeguard mechanisms for seed germination.
• The present contribution reports a novel function of the Arabidopsis MCM1/AGAMOUS/DEFICIENS/SRF(MADS)-box transcription factor ARABIDOPSIS NITRATE REGULATED 1 (ANR1) in seed germination.
• ANR1 knockout mutant is insensitive to ABA, salt and osmotic stress during the seed germination and early seedling development stages, whereas ANR1-overexpressing lines are hypersensitive. ANR1 is responsive to ABA and abiotic stresses and upregulates the expression of ABA Intolerant (ABI)3 to suppress seed germination. ANR1 and ABI3 have similar expression pattern during seed germination. Genetically, ABI3 acts downstream of ANR1. Chromatin immunoprecipitation and yeast-one-hybrid assays showed that ANR1 could bind to the ABI3 promoter to regulate its expression. In addition, ANR1 acts synergistically with AGL21 to suppress seed germination in response to ABA as evidenced by anr1 agl21 double mutant.
• Taken together, the results herein demonstrate that the ANR1 plays an important role in regulating seed germination and early postgermination growth. ANR1 and AGL21 together constitutes a safeguard mechanism for seed germination to avoid unfavorable conditions.
We investigate the observed pentaquark candidates Pc(4312), Pc(4440), and Pc(4457) from the latest LHCb measurement, as well as four possible spin partners in the D¯(*)Σc* system predicted from the ...heavy quark spin symmetry with the hadronic molecule scenarios. Similar to the previous calculation on Pc(4380) and Pc(4450), the partial widths of all the allowed decay channels for these Pc states are estimated with the effective Lagrangian method. The cutoff dependence of our numerical results is also presented. Comparing with the experimental widths, our results show that Pc(4312), Pc(4440), and Pc(4457) can be described well with the spin-parity-1/2−−D¯Σc, 1/2−−D¯*Σc, and 3/2−−D¯*Σc molecule pictures, respectively.
Known predictors of neurosyphilis were mainly drawn from human immunodeficiency virus (HIV)-infected syphilis patients, which may not be applicable to HIV-negative populations as they have different ...characteristics, particularly those with neurological symptoms. This study aimed to identify novel predictors of HIV-negative symptomatic neurosyphilis (S-NS).
From June 2005 to June 2015, 370 HIV-negative syphilis patients with neurological symptoms were recruited, consisting of 191 S-NS patients (including 123 confirmed neurosyphilis and 68 probable neurosyphilis patients) and 179 syphilis/non-neurosyphilis (N-NS) patients. Clinical and laboratory characteristics of S-NS were compared with N-NS to identify factors predictive of S-NS. Serum rapid plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and their parallel testing format for screening S-NS were evaluated.
The likelihood of S-NS was positively associated with the serum RPR and TPPA titers. The serum TPPA titers performed better than the serum RPR titers in screening S-NS. The optimal cut-off points to recognize S-NS were serum RPR titer ≥1:4 and serum TPPA titer ≥1:2560 respectively. A parallel testing format of a serum RPR titer ≥1:2 and serum TPPA titer ≥1:1280 screened out 95.8% of S-NS and all confirmed cases of neurosyphilis. S-NS was independently associated with male sex, serum RPR titer ≥1:4, serum TPPA titer ≥1:2560, and elevated serum creatine kinase. Concurrence of these factors increased the likelihood of S-NS.
Quantitation of serum TPPA is worthwhile and performs better than serum RPR in screening S-NS. Serum RPR, serum TPPA, male sex, and serum creatine kinase can predict S-NS. Moreover, patients with both a serum RPR titer <1:2 and a serum TPPA titer <1:1280 have a low probability of S-NS, suggesting that it is reasonable to reduce lumbar punctures in such individuals.
This article deals with the stability of neural networks (NNs) with time-varying delay. First, a generalized reciprocally convex inequality (RCI) is presented, providing a tight bound for ...reciprocally convex combinations. This inequality includes some existing ones as special case. Second, in order to cater for the use of the generalized RCI, a novel Lyapunov-Krasovskii functional (LKF) is constructed, which includes a generalized delay-product term. Third, based on the generalized RCI and the novel LKF, several stability criteria for the delayed NNs under study are put forward. Finally, two numerical examples are given to illustrate the effectiveness and advantages of the proposed stability criteria.
The second near‐infrared (NIR‐II) fluorescent imaging shows great potential for deep tissue analysis at high resolution in living body owing to low background autofluorescence and photon scattering. ...However, reversible monitoring of redox homeostasis using NIR‐II fluorescent imaging remains a challenge due to the lack of appropriate probes. In this study, a series of stable and multifunctional NIR‐II dyes (NIR‐II Cy3s) were constructed based on trimethine skeleton. Significantly, introducing the 1,4‐diethyl‐decahydroquinoxaline group to the NIR‐II Cy3s not only effectively increased the wavelength, but also served as an effective response site for HClO, which can be restored by reactive sulfur species (RSS). Based on this, NIR‐II Cy3s were used for reversible monitoring of HClO/RSS‐mediated redox processes in the pathophysiology environment. Finally, NIR‐II Cy3‐988 was successfully utilized for assessment of the redox environments and drug treatment effects in acute inflammation model.
We report a new class of trimethine skeleton NIR‐II fluorophores (NIR‐II Cy3s) with improved stability over traditional heptamethine NIR‐II fluorophores and emission above 1000 nm. The NIR‐II Cy3s can reversibly respond to HClO and reactive sulfur species (RSS) and can serve as an effective platform for the reversible monitoring of the HClO/RSS‐mediated redox process in a pathophysiology environment. Finally, we applied NIR‐II Cy3‐988 to the reversible assessment of the redox environment and dynamic effect of drug treatment in an acute inflammation model and of redox potential changes during liver injury and repair.
Key points
μ‐Opioid receptors (MORs) are expressed peripherally and centrally, but the loci of MORs responsible for clinically relevant opioid analgesia are uncertain.
Crossing Oprm1flox/flox and ...AdvillinCre/+ mice completely ablates MORs in dorsal root ganglion neurons and reduces the MOR expression level in the spinal cord.
Presynaptic MORs expressed at primary afferent central terminals are essential for synaptic inhibition and potentiation of sensory input by opioids.
MOR ablation in primary sensory neurons diminishes analgesic effects produced by systemic and intrathecal opioid agonists and abolishes chronic opioid treatment‐induced hyperalgesia.
These findings demonstrate a critical role of MORs expressed in primary sensory neurons in opioid analgesia and suggest new strategies to increase the efficacy and reduce adverse effects of opioids.
The pain and analgesic systems are complex, and the actions of systemically administered opioids may be mediated by simultaneous activation of μ‐opioid receptors (MORs, encoded by the Oprm1 gene) at multiple, interacting sites. The loci of MORs and circuits responsible for systemic opioid‐induced analgesia and hyperalgesia remain unclear. Previous studies using mice in which MORs are removed from Nav1.8‐ or TRPV1‐expressing neurons provided only an incomplete and erroneous view about the role of peripheral MORs in opioid actions in vivo. In the present study, we determined the specific role of MORs expressed in primary sensory neurons in the analgesic and hyperalgesic effects produced by systemic opioid administration. We generated Oprm1 conditional knockout (Oprm1‐cKO) mice in which MOR expression is completely deleted from dorsal root ganglion neurons and substantially reduced in the spinal cord, which was confirmed by immunoblotting and immunocytochemical labelling. Both opioid‐induced inhibition and potentiation of primary sensory input were abrogated in Oprm1‐cKO mice. Remarkably, systemically administered morphine potently inhibited acute thermal and mechanical nociception and persistent inflammatory pain in control mice but had little effect in Oprm1‐cKO mice. The analgesic effect of intrathecally administered morphine was also profoundly reduced in Oprm1‐cKO mice. Additionally, chronic morphine treatment‐induced hyperalgesia was absent in Oprm1‐cKO mice. Our findings directly challenge the notion that clinically relevant opioid analgesia is mediated mostly by centrally expressed MORs. MORs in primary sensory neurons, particularly those expressed presynaptically at the first sensory synapse in the spinal cord, are crucial for both opioid analgesia and opioid‐induced hyperalgesia.
Key points
μ‐Opioid receptors (MORs) are expressed peripherally and centrally, but the loci of MORs responsible for clinically relevant opioid analgesia are uncertain.
Crossing Oprm1flox/flox and AdvillinCre/+ mice completely ablates MORs in dorsal root ganglion neurons and reduces the MOR expression level in the spinal cord.
Presynaptic MORs expressed at primary afferent central terminals are essential for synaptic inhibition and potentiation of sensory input by opioids.
MOR ablation in primary sensory neurons diminishes analgesic effects produced by systemic and intrathecal opioid agonists and abolishes chronic opioid treatment‐induced hyperalgesia.
These findings demonstrate a critical role of MORs expressed in primary sensory neurons in opioid analgesia and suggest new strategies to increase the efficacy and reduce adverse effects of opioids.
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