Assessing the reactions of tourist markets to reinstated travel restrictions in the destination during the post-COVID-19 phase.

This study, leveraging search engine data, investigates the dynamics of China's domestic tourism markets in response to the August 2022 epidemic outbreak in Xinjiang. It focuses on understanding the reaction mechanisms of tourist-origin markets during destination crises in the post-pandemic phase. Notably, the research identifies a continuous rise in the potential tourism demand from tourist origin cities, despite the challenges posed by the epidemic. Further analysis uncovers a regional disparity in the growth of tourism demand, primarily influenced by the economic stratification of origin markets. Additionally, the study examines key tourism attractions such as Duku Road, highlighting its resilient competitive system, which consists of distinctive tourism experiences, economically robust tourist origins, diverse tourist markets, and spatial pattern stability driven by economic factors in source cities, illustrating an adaptive response to external challenges such as crises. The findings provide new insights into the dynamics of tourism demand, offering a foundation for developing strategies to bolster destination resilience and competitiveness in times of health crises.

Cyclopeptide moroidin inhibits vasculogenic mimicry formed by glioblastoma cells via regulating ß-catenin activation and EMT pathways.

Glioblastoma (GBM) is a highly vascularized malignant brain tumor with poor clinical outcomes. Vasculogenic mimicry (VM) formed by aggressive GBM cells is an alternative approach for tumor blood supply and contributes to the failure of anti-angiogenic therapy (AAT). However, there are still a lack of the effective drugs that target VM formation in GBM. In the present study, we evaluate the effects of a plant cyclopeptide moroidin on VM formed by GBM cells and explore its underlying molecular mechanisms. Moroidin evidently suppressed migration, tube formation and expression of α-SMA and metalloproteinase-9 in human GBM cell lines at sub-lethal concentrations. RNA sequencing data suggested the involvement of EMT pathway in the mechanism of moroidin. Exposing GBM cells to moroidin, the expression of EMT marker N-Cadherin and Vimentin decreased in a concentration-dependent manner. Moreover, moroidin significantly reduced the level of phosphorylated ERK and inhibited the activation ß-catenin. The plant cyclopeptide moroidin inhibited the VM formed by GBM cells by inhibiting ERK/ß-catenin-mediated EMT. Our study indicates a promising application of moroidin as an anti-VM agent to the treatment of GBM.

Clinical benefit and risk of elemene in cancer patients undergoing chemotherapy: a systematic review and meta-analysis.

Introduction: Elemene injection and oral emulsion, known as elemene, have been utilized have been used in adjuvant therapy for cancer patients in China for more than 20 years. In order to evaluate the efficacy and potential risks of the treatments in cancer patients undergoing chemotherapy, a system review and meta-analysis were conducted. Additionally, the factors that may influence the outcomes were also explored. Methods: A comprehensive search was conducted across various databases including PubMed, Cochrane Library, Web of Science, EMBASE, CKNI, Wan Fang, and VIP databases. Meta-regression, subgroup, and sensitivity analyses were conducted to explore the heterogeneity. GRADE system and TSA were used to assess the strength of evidence and robustness of the results. Results: The pooled data showed that combination with elemene could improve the response rate (RR:1.48, 95%CI:1.38-1.60, p < 0.00001), disease control rate (RR:1.20, 95%CI:1.15-1.25, p < 0.00001), the rate of quality-of-life improvement and stability (WMD:1.31, 95% CI:1.12-1.53, p = 0.0006), immune function (CD4+/CD8+: WMD:0.33, 95% CI:0.24-0.42, p < 0.00001), survival rate (1-year, RR:1.34, 95% CI:1.15-1.56, p = 0.0002; 2-year, RR:1.57, 95% CI:1.14-2.16, p = 0.006), and decrease the prevalence of most chemotherapy-induced side effects, especially leukopenia (Ⅲ-Ⅳ) (RR:0.46, 95% CI:0.35-0.61, p < 0.00001), thrombocytopenia (RR:0.86, 95% CI:0.78-0.95, p = 0.003), and hemoglobin reduction (RR:0.83, 95% CI:0.73-0.95, p = 0.007). However, the administration of elemene has been found to significantly increase the incidence of phlebitis in patients undergoing chemotherapy (RR:3.41, 95% CI:1.47-7.93, p = 0.004). Meta-regression and subgroup analyses discovered that the outcomes were rarely influenced by CR, CT, and dosage of elemene (DE) but the cycle number of elemene (CNE) and TT were the main sources of heterogeneity. Discussion: As the treatment time and the number of cycles increased, the efficacy of the elemene combination decreased across various aspects. Thus, shorter duration and fewer cycles are recommended.

Predictive Significance of High-Sensitivity C-Reactive Protein Combined with Homocysteine for Coronary Heart Disease in Patients with Anxiety Disorders.

Background: Currently, there are few studies on biomarkers for predicting coronary heart disease (CHD) with anxiety disorders. Objective: To explore risk factors and investigate the predictive value of common clinical peripheral blood indicators, such as high-sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy) for CHD patients with anxiety disorders. Methods: One hundred fifty-three hospitalized patients with chest pain as the main symptom and a Hamilton Anxiety Scale score > 14 were recruited from October 2020 to September 2021 in the hospital. Then, they were divided into an anxiety disorder with CHD group (observation group, n = 64) and a simple anxiety disorder group (control group, n = 89), according to coronary angiography (CAG) findings. Patients' demographic and clinical messages were collected and compared. Diabetes mellitus and hypertension, body mass index (BMI), and peripheral blood interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), homocysteine (Hcy), fibrinogen, D-dimer, cortisol, and norepinephrine expression levels were compared. Binary logistic regression analysis screened independent risk factors of CHD patients with anxiety disorders. The effectiveness of independent risk factors in predicting CHD with anxiety disorders was analyzed using receiver operating characteristic (ROC) curves. Results: IL-6, hs-CRP, and Hcy levels of anxiety disorder in the CHD group were significantly higher than those in the simple anxiety disorder group. Binary multiple logistic regression analysis indicated that IL-6, hs-CRP, and Hcy were independent risk factors for CHD in patients with anxiety disorders. hs-CRP and Hcy levels were positively correlated with the Gensini score. ROC curve analysis indicated that the detection of hs-CRP or Hcy alone or the combined detection of the 2 had clinical predictive value for CHD in patients with anxiety disorders, and the area under the curve (AUC) of the combined detection of the 2 was significantly larger than that of any single factor alone (vs. hs-CRP, P = 0.045; vs. Hcy, P = 0.045). Conclusion: IL-6, hs-CRP, and Hcy are related to CHD with anxiety disorders. Serum levels of the combined detection of hs-CRP and Hcy have a high clinical predictive value for CHD in patients with anxiety disorders.

Endothelium-derived Cdk5 deficit aggravates air pollution-induced peripheral vasoconstriction through AT1R upregulation.

PM2.5 infiltrates into circulation and increases the risk of systemic vascular dysfunction. As the first-line barrier against external stimuli, the molecular mechanism of the biological response of vascular endothelial cells to PM2.5 exposure remains unclear. In this study, 4-week-old mice were exposed to Hangzhou 'real' airborne PM2.5 for 2 months and were found to display bronchial and alveolar damage. Importantly, in the present study, we have demonstrated that Cdk5 deficit induced peripheral vasoconstriction through angiotensin II type 1 receptor under angiotensin II stimulation in Cdh5-cre;Cdk5f/n mice. In the brain, Cdk5 deficit increased the myogenic activity in the medullary arterioles under external pressure. On the other hand, no changes in cerebral blood flow and behavior patterns were observed in the Cdh5-cre;Cdk5f/n mice exposed to PM2.5. Therefore, our current findings indicate that CDK5 plays an important role in endothelium cell growth, migration, and molecular transduction, which is also a sensor for the response of vascular endothelial cells to PM2.5.

Targeted Regulation of Blood-Brain Barrier for Enhanced Therapeutic Efficiency of Hypoxia-Modifier Nanoparticles and Immune Checkpoint Blockade Antibodies for Glioblastoma.

Glioblastoma is the most destructive type of brain cancer. The blood-brain barrier (BBB) is a tremendous obstacle that hinders therapeutic agents, such as chemical drugs and antibodies, from reaching glioblastoma tissues. Meanwhile, the abnormal microenvironment of glioblastoma extremely restricts the expected therapeutic effects of accumulated drugs. Therefore, in the present study, BBB-regulating nanovesicles (BRN) are developed to achieve targeted and controlled BBB regulation, carrying adenosine 2A receptor (A2AR) agonists and perfluorocarbon (PF). The red-blood-cell membrane (RBCM) is included on the outside to avoid the premature release of therapeutic agents. In the presence of ultrasonication (US), A2AR agonists are released and induce effects on both F-actin and tight junctions of endothelial cells. Subsequently, BBB permeability is temporarily increased and enables small molecules and nanoparticles to enter brain parenchymal tissues. The high affinity between manganese dioxide and temozolomide (TMZ) is utilized to form multifunctional nanoparticles to ameliorate the hypoxic microenvironment, which yields improved glioblastoma inhibition combined with radiotherapy. Moreover, with the aid of targeted BBB regulation, programmed death ligand-1 (PD-L1) antibody induces a tumor-specific immune response. Taken together, the findings suggest that synergistic combination may have the potential in amplifying the therapeutic efficacies of clinical drugs and immune checkpoint blockade antibodies to overcome the therapeutic resistance of glioblastoma.

Suitability evaluation for mountain-based adventure tourism: A case study of Xinjiang Tianshan, China.

In recent years, there has been considerable growth in the provision of and demand for adventure tourism; however, research that examines the resources regarding adventure tourism is limited. A spatial suitability evaluation system for mountain-based adventure tourism (MBAT) was developed via the integration of the AHP-Delphi technique. The evaluation system parameters included resource conditions, difficulty levels, safety conditions, and ecological sensitivity. Furthermore, each parameter contained several indicators that can be quantified and visualised in ArcGIS. The results showed that suitable areas for professional adventure tourism in Xinjiang Tianshan include the Kurdening and Tomur regions, and the those for adventure tourism include the Tianshan Tianchi lake. Furthermore, suitable areas for experiential adventure tourism include the Tianshan Tianchi lake, Tianshan Grand Canyon, Jiangbulak, East Tianshan, Tuohurasu scenic area, and the Gongliu wild fruit forest, while those for mass adventure tourism include large areas in the middle and low altitude range of Tianshan. The methods and results proposed in this paper are expected to be significant for planning adventure tourism and can be helpful for mountain communities when choosing regions to develop for adventure tourism, formulating tourism development strategies, increasing tourism opportunities, and thus improving regional competitiveness.

GRPr-mediated photothermal and thermodynamic dual-therapy for prostate cancer with synergistic anti-apoptosis mechanism.

Conventional prostate cancer treatment strategies, including chemotherapy and radiotherapy, cannot effectively eradicate prostate cancer, especially castration resistance prostate cancer. Herein, we developed a novel nanotherapy platform that consists of synergic photothermal and photodynamic therapy via the unique properties of photothermal conversion by gold nanorods and free radicals generation by encapsulated initiators (AIPH). Mesoporous silica was employed as a coating material, and the bombesin peptide was conjugated onto the mesoporous silica coating layer as the targeting moiety to prostate cancer via its overexpressed gastrin-releasing peptide receptors. An in vitro study with the castration resistance prostate cancer cell exhibited a significant photothermal therapeutic effect as well as enhanced thermodynamic therapy via generating free radicals. P-p38 and p-JNK proteins, as key proteins involved in the cells' stress responses, were found to be upregulated by the synergetic treatment. The in vivo study demonstrated that a significant eradication of prostate tumour could be achieved by the nanoparticle therapeutic platform with a good biocompatibility profile. This work pioneers a novel approach for high-efficient castration resistance prostate cancer treatment by combining photothermal, thermodynamic, and site-specific drug delivery directed by an integrated nanoparticle system.