Considering the majority of previous assessment perspectives on tourism carrying capacity are limited by “the number of visitors”, this paper develops an innovative approach from the “visitors’ ...experience utility” perspective. Using the choice experiment method, tourism carrying capacity is assessed by exploring the marginal utility and sensitivity of visitors to changes in recreational attributes. Xian-Ren-Tai National Forest Park in China is employed as the case park to demonstrate the application of this assessment method. The conclusions are as follows: the carrying capacity threshold of the crowding level in this urban forest park ranges from 20–35 people/100 m2, the threshold of “vegetation coverage” ranges from 70% to 80%, and the “number of garbage” is 3–10 pieces/200 m. The acceptable traffic accessibility level for visitors is within 3 h. At present, Xian-Ren-Tai National Forest Park as a whole is in a state of “low carrying capacity”, there are potential risks of underutilization in this park. In addition, this paper provides the carrying capacity state of 27 potential recreational attribute sets.
•The total economic value of grasslands in China was 10,876 yuan/ha/yr.•Grassland soil fertility and erosion control were the most valuable services.•The grassland value was affected by the valuation ...methods.•Our findings are helpful for better accounting for grassland ecosystem services.
Grasslands provide a variety of ecosystem services (ESs) that contribute to human beings. However, most grassland ESs are public goods with no market value and consequently ignored in private land use decisions. Thus, it is important for grassland conservation to consider the potential economic value of grassland ESs in policymaking. We tried to provide a comprehensive evaluation of the economic value of grassland ESs and the influential factors via a meta-regression analysis with 745 observations from 69 studies. The results showed that the total economic value of grasslands in China was 10,876 yuan/ha in constant year 2015, and also revealed large variations in the reported economic values of grassland ESs. Soil fertility (1,899 yuan/ha/yr) and erosion control (1,492 yuan/ha/yr) were the two most valuable services. Further, factors such as valuation methods, research characteristics and study site characteristics all affected the estimates of grassland values. The market price method was most likely to provide higher grassland ES values among all the methods. Lastly, the economic value of grassland ESs showed geographical differences, with eastern China higher than western China. These findings contributed to the literature evaluating the economic value of grassland ESs regarding discrepancies in economic values, thus helping to inform grassland management. Further, these findings are helpful for better accounting for the services provided by grassland ecosystems, which can significantly facilitate land use decision making for sustainable ecosystem management.
Glioblastoma is highly enriched with macrophages, and osteopontin (OPN) expression levels correlate with glioma grade and the degree of macrophage infiltration; thus, we studied whether OPN plays a ...crucial role in immune modulation. Quantitative PCR, immunoblotting, and ELISA were used to determine OPN expression. Knockdown of OPN was achieved using complementary siRNA, shRNA, and CRISPR/Cas9 techniques, followed by a series of in vitro functional migration and immunological assays. OPN gene-deficient mice were used to examine the roles of non-tumor-derived OPN on survival of mice harboring intracranial gliomas. Patients with mesenchymal glioblastoma multiforme (GBM) show high OPN expression, a negative survival prognosticator. OPN is a potent chemokine for macrophages, and its blockade significantly impaired the ability of glioma cells to recruit macrophages. Integrin αvβ5 (ITGαvβ5) is highly expressed on glioblastoma-infiltrating macrophages and constitutes a major OPN receptor. OPN maintains the M2 macrophage gene signature and phenotype. Both tumor-derived and host-derived OPN were critical for glioma development. OPN deficiency in either innate immune or glioma cells resulted in a marked reduction in M2 macrophages and elevated T cell effector activity infiltrating the glioma. Furthermore, OPN deficiency in the glioma cells sensitized them to direct CD8+ T cell cytotoxicity. Systemic administration in mice of 4-1BB-OPN bispecific aptamers was efficacious, increasing median survival time by 68% (P < 0.05). OPN is thus an important chemokine for recruiting macrophages to glioblastoma, mediates crosstalk between tumor cells and the innate immune system, and has the potential to be exploited as a therapeutic target.
Despite the increasing number of visitors to Galapagos National Park, the tourism industry pays little attention to the distinct preferences of tourists toward park attributes, including both its ...natural resources and managerial emphasis. To “monetize” the benefits of these attributes requires utilizing nonmarket valuation techniques. Using a stated preference questionnaire, we estimated the economic value of the park’s recreational attributes. The following five attributes were selected: endangered species, prevalence of garbage, site infrastructure, air quality, and entrance fees. The results of this study demonstrate that tourists place the highest willingness to pay values on increased protection of animal species (US$26.9) and garbage reduction (US$111.2). These results highlight the economic contributions for park management, with a potential for value improvement of US$38.1 per tourist if the park’s combined attributes are upgraded from the present condition to the optimum condition.
Adenomyosis is a chronic gynecological disease characterized by invasion of the uterine endometrium into the muscle layer. In assisted reproductive technology (ART), gonadotropin-releasing hormone ...agonist (GnRHa) is often used to improve pregnancy rates in patients with adenomyosis, but the underlying mechanisms are poorly understood.
Eutopic endometrial specimens were collected from patients with adenomyosis before and after GnRHa treatment in the midsecretory phase. RNA sequencing (RNA-Seq) of these specimens was performed for transcriptome analysis. The differentially expressed genes (DEGs) of interest were confirmed by real-time PCR and immunohistochemistry.
A total of 132 DEGs were identified in the endometrium of patients with adenomyosis after GnRHa treatment compared with the control group. Bioinformatics analysis predicted that immune system-associated signal transduction changed significantly after GnRHa treatment. Chemokine (C-C motif) ligand 21 (CCL21) was found to be highly expressed in the eutopic endometrium after GnRHa treatment, which may be involved in the improvement of endometrial receptivity in adenomyosis.
This study suggests that molecular regulation related to immune system-associated signal transduction is an important mechanism of GnRHa treatment in adenomyosis. Immunoreactive CCL21 is thought to regulate inflammatory events and participate in endometrial receptivity in adenomyosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increasing researches have focused on cancer metastasis and development. The ectonucleotidase CD73 is one of the most common cell surface enzymes that are involved in immunosuppression. In this ...study, the recombinant plasmid pET28a-CD73 was constructed and the CD73 protein was overexpressed in
as an inclusion body that was then subjected to refolding. The anti-CD73 monoclonal antibody (3F7) was obtained by hybridoma technology. The antibody subtype was identified as IgG2a with an affinity constant of 5.75 nM. This antibody could be applied to immunofluorescence and flow cytometry. The results showed that the CD73 protein was not only located in the cytoplasm but also distributed on the surface of triple-negative breast cancer cells MDA-MB-231 and MDA-MB-468. Moreover, the level of CD73 protein was associated with the survival rate. Although the anti-CD73 antibody was not able to inhibit tumor cell growth, it could enhance the cytotoxic effect of Doxorubicin to triple-negative breast cancer cells. In vitro function assay results indicated that anti-CD73 mAb could inhibit cell migration and invasion in both human triple-negative breast cancer and mouse 4T1 cell lines. In this process, both the LC3I/LC3II ratio and p62 protein levels increased, which indicated that the blockage of CD73 could inhibit cell autophagy, and cell migration and invasion were restored by rapamycin. In vivo, anti-CD73 mAb could significantly inhibit lung metastasis of 4T1 cells in a mouse xenograft model. Taken together, this novel anti-CD73 antibody could be developed as an adjuvant drug for triple-negative breast cancer therapy and can be useful in tumor diagnosis.
Estimating the economic value of ecosystem services has become one of the most fertile areas in ecological economics. In this paper, we propose a novel method of using a tourist satisfaction model to ...evaluate the recreational services being embedded in forest ecosystems. We establish a functional relationship between tourist satisfaction and recreational attributes based on the survey data of China National Forest Parks. The results indicate that each recreational attribute considered enables the generation of a significant amount of tourism welfare for tourists, whereas tourist congestion was found to be a negative contributor to tourists’ satisfaction. Reducing congestion from the current level is the most valued recreational attribute for tourists, and the willingness to pay for it is as high as CNY 623.18 (USD 92.29) per visitor per trip. Additionally, local and nonlocal tourists display a divergent degree of preference for the recreational attributes and their levels of willingness to pay.
The development of drug resistance in malignant tumors leads to disease progression, creating a bottleneck in treatment. Bevacizumab is widely used clinically, and acts by inhibiting angiogenesis to ..."starve" tumors. Continuous treatment can readily induce rebound proliferation of tumor blood vessels, leading to drug resistance. Previously, we found that the fragment crystallizable (Fc) region of bevacizumab cooperates with the Toll-like receptor-4 (TLR4) ligand to induce M2b polarization in macrophages and secrete tumor necrosis factor-α (TNFα), which promotes immunosuppression, tumor metastasis, and angiogenesis. However, the downstream mechanism underlying TNFα-mediated bevacizumab resistance requires further investigation. Our RNA-Seq analysis results revealed that the expression of endothelial cell specific molecule-1 (ESM1) increased significantly in drug-resistant tumors and promoted metastasis and angiogenesis in vitro and in vivo. Furthermore, TNFα induced the upregulation of ESM1, which promotes metastasis and angiogenesis and regulates matrix metalloprotease-9 (MMP9), vascular endothelial growth factor (VEGF), and delta-like ligand-4 molecules (DLL4). Accordingly, the curative effect of bevacizumab improved by neutralizing ESM1 with high-affinity anti-ESM1 monoclonal antibody 1-2B7 in bevacizumab-resistant mice. This study provides important insights regarding the molecular mechanism by which TNFα-induced ESM1 expression promotes angiogenesis, which is significant for elucidating the mechanism of bevacizumab drug resistance and possibly identifying appropriate biosimilar molecules.
Abstract
Background
With advanced maternal age, abnormalities during oocyte meiosis increase significantly. Aneuploidy is an important reason for the reduction in the quality of aged oocytes. ...However, the molecular mechanism of aneuploidy in aged oocytes is far from understood. Histone acetyltransferase 1 (HAT1) has been reported to be essential for mammalian development and genome stability, and involved in multiple organ aging. Whether HAT1 is involved in ovarian aging and the detailed mechanisms remain to be elucidated.
Methods
The level of HAT1 in aged mice ovaries was detected by immunohistochemical and immunoblotting. To explore the function of HAT1 in the process of mouse oocyte maturation, we used Anacardic Acid (AA) and small interfering RNAs (siRNA) to culture cumulus-oocyte complexes (COCs) from ICR female mice in vitro and gathered statistics of germinal vesicle breakdown (GVBD), the first polar body extrusion (PBE), meiotic defects, aneuploidy, 2-cell embryos formation, and blastocyst formation rate. Moreover, the human granulosa cell (GC)-like line KGN cells were used to investigate the mechanisms of HAT1 in this progress.
Results
HAT1 was highly expressed in ovarian granulosa cells (GCs) from young mice and the expression of HAT1 was significantly decreased in aged GCs. AA and siRNAs mediated inhibition of HAT1 in GCs decreased the PBE rate, and increased meiotic defects and aneuploidy in oocytes. Further studies showed that HAT1 could acetylate Forkhead box transcription factor O1 (FoxO1), leading to the translocation of FoxO1 into the nucleus. Resultantly, the translocation of acetylated FoxO1 increased the expression of amphiregulin (AREG) in GCs, which plays a significant role in oocyte meiosis.
Conclusion
The present study suggests that decreased expression of HAT1 in GCs is a potential reason corresponding to oocyte age-related meiotic defects and provides a potential therapeutic target for clinical intervention to reduce aneuploid oocytes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Breast cancer is a commonly diagnosed cancer worldwide. Human MutT homolog 1 (MTH1) is found to be elevated in breast tumors and cancer cells need MTH1 for survival. Pharmacological inhibition of ...MTH1 may be potentially beneficial in the treatment of breast cancer.
MA-24 was screened by malachite green colorimetric assay for MTH1 inhibitors and the kinetic characteristics of MA-24 were assessed. The features of MA-24's binding with MTH1 were ascertained through molecular docking, and the cytotoxic activity of MA-24 was validated in vitro and in vivo. Target engagement assays, comet assay, and Western blot confirmed the intracellular target and mechanism of MA-24.
MA-24 shows potent antitumor bioactivity both in vitro and in vivo. MA-24 competitively inhibited the MTH1 and further induced DNA strand breaks, leading to increased apoptosis of cancer cells depending on the upregulation of the cleaved-caspase 3-cleaved-PARP axis. In particular, MA-24 exhibited a powerful efficacy and safety in vivo (tumor growth inhibition rate: 61.8%).
MA-24 possesses a broad spectrum of breast cancer cytotoxicity and offered valuable insights for overcoming the challenges of chemotherapy-related toxicity, which holds great potential for the further development MA-24 as an anti-cancer drug.
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