Analysis of spatial-temporal pattern, dynamic evolution and influencing factors of health tourism development in China.

The evaluation index system is constructed based on the connotation and characteristics of health tourism. Using the entropy method, Thiel index, exploratory spatial data analysis method, spatial Markov chain and spatial econometric model, research is carried out around the development index, difference status, spatial-temporal pattern, dynamic evolution and influencing factors of health tourism. The following results were drawn: (1) The development index of health tourism in China is low, but the development speed is fast. The inter-regional development index shows an eastern China > central China > western China pattern, and the development speed exhibits a western China > central China > eastern China situation. (2) In the overall difference in China's health tourism development, the intra-regional difference is consistently higher than the inter-regional difference. Among the three major regions, the overall difference between eastern China and western China is always higher than that of central China. (3) The development of health tourism in China is positively correlated in the global space, with some local spatial clustering. (4) The dynamic evolution of health tourism development in China shows part of the "Matthew effect" characteristics, with an obvious spatial spillover effect. (5) Various influencing factors produced widely varying direct, indirect and total effects on health tourism development in China, eastern China, central China and western China. Finally, based on the results of the above empirical analysis, policy recommendations to promote the development of health tourism in China are proposed.

Integrated Analysis Identifies DPP7 as a Prognostic Biomarker in Colorectal Cancer.

Colorectal cancer has a poor prognosis and is prone to recurrence and metastasis. DPP7, a prolyl peptidase, is reported to regulate lymphocyte quiescence. However, the correlation of DPP7 with prognosis in CRC remains unclear. With publicly available cohorts, the Wilcoxon rank-sum test and logistic regression were employed to analyze the relationship between DPP7 expression and the clinicopathological features of CRC patients. Specific pathways of differentially expressed genes were determined through biofunctional analysis and gene set enrichment analysis (GSEA). qPCR and immunohistochemical staining were used to determine DPP7 expression levels in surgical specimens. The public dataset and analysis of the biospecimens of CRC patients revealed that DPP7, in the CRC samples, was expressed significantly higher than in non-tumor tissues. Moreover, increased DPP7 was significantly associated with a higher N stage, lymphatic invasion, and shorter overall survival. Functionally, DPP7 is involved in neuroactive ligand-receptor interaction and olfactory transduction signaling. We identified a series of targeted drugs and small-molecule drugs with responses to DPP7. To conclude, DPP7 is a valuable diagnostic and prognostic biomarker for CRC and considered as a new therapeutic target.

College students' learning stress, psychological resilience and learning burnout: status quo and coping strategies.

BACKGROUND: The relationships of college students' learning stress, psychological resilience and learning burnout remain unclear. We aimed to investigate the status quo and relationship of college students' learning stress, psychological resilience and learning burnout, to provide insights to the management and nursing care of college students. METHODS: From September 1 to October 31, 2022, students in our college were selected by stratified cluster sampling and underwent survey with the learning stress scale, college students' learning burnout scale and the psychological resilience scale of college students. RESULTS: A total of 1680 college students were surveyed in this study. The score of learning burnout was positively correlated with the score of learning stress (r = 0.69), and negatively correlated with the score of psychological resilience (r = 0.59), and the score of learning stress was negatively correlated with the score of psychological resilience (r = 0.61). Learning pressure was correlated with the age(r=-0.60) and monthly family income(r=-0.56), the burnout was correlated with the monthly family income(r=-0.61), and psychological resilience was correlated with the age(r = 0.66) (all P < 0.05). Psychological resilience played an intermediary role in the prediction of learning burnout by learning stress, with an total intermediary role of-0.48, accounting for 75.94% of the total effect. CONCLUSIONS: Psychological resilience is the mediating variable of the influence of learning stress on learning burnout. College managers should take various effective measures to improve college students' psychological resilience to reduce college students' learning burnout.

The genome of single-petal jasmine (Jasminum sambac) provides insights into heat stress tolerance and aroma compound biosynthesis.

Jasmine [Jasminum sambac (L.) Aiton] is a commercially important cultivated plant species known for its fragrant flowers used in the perfume industry, medicine and cosmetics. In the present study, we obtained a draft genome for the J. sambac cultivar 'Danbanmoli' (JSDB, a single-petal phenotype). We showed that the final genome of J. sambac was 520.80 Mb in size (contig N50 = 145.43 kb; scaffold N50 = 145.53 kb) and comprised 35,363 genes. Our analyses revealed that the J. sambac genome has undergone only an ancient whole-genome duplication (WGD) event. We estimated that the lineage that has given rise to J. sambac diverged from the lineage leading to Osmanthus fragrans and Olea europaea approximately 31.1 million years ago (Mya). On the basis of a combination of genomic and transcriptomic analyses, we identified 92 transcription factors (TFs) and 206 genes related to heat stress response. Base on a combination of genomic, transcriptomic and metabolomic analyses, a range of aroma compounds and genes involved in the benzenoid/phenylpropanoid and terpenoid biosynthesis pathways were identified. In the newly assembled J. sambac genome, we identified a total of 122 MYB, 122 bHLH and 69 WRKY genes. Our assembled J. sambac JSDB genome provides fundamental knowledge to study the molecular mechanism of heat stress tolerance, and improve jasmine flowers and dissect its fragrance.

Comparative physiology and transcriptome analysis reveals that chloroplast development influences silver-white leaf color formation in Hydrangea macrophylla var. maculata.

BACKGROUND: Hydrangea macrophylla var. Maculata 'Yinbianxiuqiu' (YB) is an excellent plant species with beautiful flowers and leaves with silvery white edges. However, there are few reports on its leaf color characteristics and color formation mechanism. RESULTS: The present study compared the phenotypic, physiological and transcriptomic differences between YB and a full-green leaf mutant (YM) obtained from YB. The results showed that YB and YM had similar genetic backgrounds, but photosynthesis was reduced in YB. The contents of pigments were significantly decreased at the edges of YB leaves compared to YM leaves. The ultrastructure of chloroplasts in the YB leaves was irregular. Transcriptome profiling identified 7,023 differentially expressed genes between YB and YM. The expression levels of genes involved in photosynthesis, chloroplast development and division were different between YB and YM. Quantitative real-time PCR showed that the expression trends were generally consistent with the transcriptome data. CONCLUSIONS: Taken together, the formation of the silvery white leaf color of H. macrophylla var. maculata was primarily due to the abnormal development of chloroplasts. This study facilitates the molecular function analysis of key genes involved in chloroplast development and provides new insights into the molecular mechanisms involved in leaf coloration in H. macrophylla.

Identification of aluminum-activated malate transporters (ALMT) family genes in hydrangea and functional characterization of HmALMT5/9/11 under aluminum stress.

Hydrangea (Hydrangea macrophylla (Thunb.) Ser.) is a famous ornamental plant species with high resistance to aluminum (Al). The aluminum-activated malate transporter (ALMT) family encodes anion channels, which participate in many physiological processes, such as Al tolerance, pH regulation, stomatal movement, and mineral nutrition. However, systematic studies on the gene family have not been reported in hydrangea. In this study, 11 candidate ALMT family members were identified from the transcriptome data for hydrangea, which could be divided into three clusters according to the phylogenetic tree. The protein physicochemical properties, phylogeny, conserved motifs and protein structure were analyzed. The distribution of base conservative motifs of HmALMTs was consistent with that of other species, with a highly conserved WEP motif. Furthermore, tissue-specific analysis showed that most of the HmALMTs were highly expressed in the stem under Al treatment. In addition, overexpression of HmALMT5, HmALMT9 and HmALMT11 in yeasts enhanced their tolerance to Al stress. Therefore, the above results reveal the functional role of HmALMTs underlying the Al tolerance of hydrangea. The present study provides a reference for further research to elucidate the functional mechanism and expression regulation of the ALMT gene family in hydrangea.

Biochemistry and transcriptome analyses reveal key genes and pathways involved in high-aluminum stress response and tolerance in hydrangea sepals.

Hydrangea [Hydrangea macrophylla (Thunb.) Ser.] is a high aluminum-tolerant ornamental plant species, which has a specific characteristic of color change, ie. some cultivars' floral color will change from red to blue or blue-violet planted in acidic soil containing aluminum. This study aims to understand the complex molecular mechanisms of floral color change under Al stress, through comparative biochemistry and transcriptome analyses between an Al3+-sensitive cultivar 'Bailer' and insensitive cultivar 'Ruby' under Al-stress. The results of biochemistry analysis showed that 'Bailer' displayed higher contents of Al3+ and delphinium-3-O-glucoside than that of 'Ruby' after Al2(SO4)3 treating. Meanwhile, the transcriptome analysis of different tissues identified 12,321 differentially expressed genes (DEGs) in 'Bailer' and 6,703 in 'Ruby'. Transcriptome analysis showed that changes in genes' expression pattern in several genes and pathways [such as including metal transporters, reactive oxygen species (ROS) scavenging enzyme, plant hormone signal transduction and favonoid biosynthesis pathway] were the key contributors to the Al3+-sensitive cultivar 'Bailer'. Besides, gene co-expression network analysis (WGCNA) demonstrated that five hub genes, including ABC transporters (TRINITY_DN1053_c0_g1, TRINITY_DN3377_c0_g2), cationic amino acid transporter (TRINITY_DN9684_c0_g2), oligopeptide transporter (TRINITY_DN1147_c0_g2) and flavonol synthase (TRINITY_DN15902_c0_g1), played vital roles in the networks regulating Al tolerance in hydrangea. Furthermore, HmABCI17's (TRINITY_DN1053_c0_g1) expression enhanced Al tolerance in yeast. The conclusions of this study are helpful to elucidate the differences and molecular mechanisms of different hydrangea cultivars on Al tolerance, and provide new insights into molecular assisted-screening for breeding blue flowers in hydrangea and other ornamental plants.

An integrated transcriptomic and proteomic approach to dynamically study the mechanism of pollen-pistil interactions during jasmine crossing.

Jasmine (Jasminum sambac Aiton, Oleaceae) flowers are widely consumed in many countries for their tea-making, medicinal and ornamental properties. To improve the quality and yield of flowers, it is very important to carry out cross-breeding between different petal types of jasmine. However, because of the difficulty of sexual reproduction, there is no report on the success of jasmine crosses. In this paper, single- and double-petal jasmine plants were crossed artificially. The stigmas of single-petal plants post pollination, including those at 0 h after pollination (CK), 1 h after pollination (T1) and 6 h after pollination (T2), were sequenced by transcriptomic combined with proteomic analyses. A total of 178,098 gene products were assembled. Simultaneously, a total of 2337 protein species were identified. Some regulatory gene products and functional protein species were identified that may be involved in the process of pollen-pistil interactions. These findings suggest that the identified differentially expressed gene products and differentially accumulated protein species may play vital roles in jasmine plants in response to pollen-pistil interactions, providing important genetic resources for further functional dissection of the molecular mechanisms of these interactions. SIGNIFICANCE: These results have important scientific significance to take effective measures to overcome pre-fertilization barriers and to guide the cross breeding of jasmine. Further, they can also be used for reference in other plant breeding with the same fertilization barriers.

Deep Sequencing of T-Cell Receptors for Monitoring Peripheral CD8+ T Cells in Chinese Advanced Non-Small-Cell Lung Cancer Patients Treated With the Anti-PD-L1 Antibody.

Background: Atezolizumab, a high-affinity engineered human anti-PD-L1 antibody, has produced a clinical benefit for patients with advanced non-small-cell lung cancer (NSCLC). However, associated with T-cell regulation, the immunomodulatory effect of PD-L1 blockade and its biomarker in peripheral immunity remains elusive. Methods: In a prospective cohort with 12 Chinese advanced NSCLC patients who received atezolizumab 1,200 mg every 3 weeks as a second-line treatment, blood samples were obtained before and 6 weeks after atezolizumab initiation, and when disease progression was confirmed. Patients were classified into a response or progression group according to response evaluation criteria in solid tumors (RECIST) 1.1. Fresh peripheral blood mononuclear cells (PBMCs) from patients were stained with antihuman CD3, CD8, and PD-1 antibodies for flow cytometry analysis. T-cell receptor (TCR)-ß chains of CD8+ T cells were analyzed by next-generation sequencing (NGS) at the deep level. Diversity, clonality, and similarity of TCR have been calculated before and after treatment in both groups. Results: Clonal expansion with high PD-1 expression was detected in all patients' peripheral CD8+ T cells before the treatment of atezolizumab. Unlike the progression group, the diversity of TCR repertoire and singletons in the TCRß pool increased over time with atezolizumab administration, and the TCR repertoire dynamically changes in the response group. The percentage of CD8+ PD-1high terminal exhausted T cells declined in the response group after the PD-L1 blockade. Two patterns of TCR changes among patients who received PD-L1-targeted immunotherapy were observed. Conclusions: Deep sequencing of the T-cell receptors confirmed the existence of CD8+ PD-1high T cells with an exhaustion phenotype in Chinese NSCLC patients. Our study demonstrated that efficient anti-PD-L1 therapy could reshape the TCR repertoire for antitumor patients. Furthermore, singleton frequency may help us select patients who are sensitive to anti-PD-L1 immunotherapy.

Efficacy and safety of combined immunotherapy and antiangiogenic therapy for advanced non-small cell lung cancer: A two-center retrospective study.

BACKGROUND: The synergistic effects of immunotherapy and antiangiogenic therapy in advanced non-small cell lung cancer (NSCLC) have been reported in both preclinical and clinical trials. Herein, we evaluated the preliminary efficacy and safety of combined immunotherapy and antiangiogenic therapy in patients with previously treated advanced NSCLC in a real-world setting. METHODS: We conducted a 2-center, retrospective study of previously treated advanced NSCLC patients who received any anti-programmed death-1 antibody combined with antiangiogenic agent between May 2018 and March 2020. RESULTS: In total, 57 patients were included in this study, and the objective response rate and disease control rate were 19.3% and 63.2%, respectively. The median progression-free survival (PFS) was 4.2 months (95% confidence interval [CI]: 3.2-5.2 months). Bone metastases (odds ratio [OR] not available; P < .01) and ≥ 3 treatment lines (OR 6.8; 95% CI: 1.6-29.6; P < .05) were independent negative predictors of objective response. Additionally, liver metastases (hazard ratio [HR] 3.7; 95% CI: 1.6-8.5; P < 0.01), poor performance status score (PS) (HR 3.4; 95% CI: 1.6-7.5; P < 0.01) and ≥ 3 treatment lines (HR 3.5; 95% CI: 1.7-7.4; P < 0.01) were found to be negative predictors of PFS. Eighty-nine percent of the patients experienced an adverse event. CONCLUSIONS: Metastatic sites (bone and liver), ≥3 treatment lines and poor PS were potential negative predictors of the efficacy of immunotherapy combined with antiangiogenic therapy for treating NSCLC. Further investigations and randomized controlled trials are needed.

Fabrication of Hydrogel Tubes with Vascular Mimicked Stiffness for Construction of in Vitro Vascular Models.

Stiffness of blood vessels is one of the most important parameters involving in vascular diseases. However, no vascular model well mimics the stiffness of native blood vessels, and thus, the effects of vascular stiffness on endothelial cells cannot be studied in vitro. For this purpose, we fabricated the gelatin/carboxybetaine (CBMA) interpenetrating network (IPN) hydrogel tubes to exactly present the stiffness of soft (i.e., physical) and stiff (i.e., pathological) arteries in human. The vascular models are then constructed via endothelial cell culture inside the gel tubes under a cardiac-like pulsatile perfusion. As found, the velocity magnitude and wall shear stress in the stiff gel tube are much higher than those in the soft one. Correspondingly, the endothelial cells in the soft gel tube (i.e., physical model) express higher vascular functions than those in the stiff one (i.e., pathological model). Moreover, a pathological model was more sensitive to ethanol-induced vascular injury than the physical model. Thus, the new vascular models with a tunable stiffness provide a useful tool to investigate the stiffness involved mechanism in vascular diseases under in vivo mimicked microenvironments.

Quantitation of cell-free DNA in blood is a potential screening and diagnostic maker of breast cancer: a meta-analysis.

INTRODUCTION: Increased cell-free DNA (cfDNA) levels in circulating blood have been associated with higher possibility of breast cancer, however, researchers have not reached an agreement on its analysis. MATERIALS AND METHODS: We conducted a meta-analysis of 12 retrospective studies to clarify the value of cfDNA quantification in screening and diagnosis of breast cancer. PubMed, EMBASE, Web of Science and Cochrane library were searched from January, 2000 to October, 2016. Pooled analyses were estimated using a random effects model. RESULTS: In total, 1003 primary breast cancer patients, 283 cases with benign breast disease and 575 healthy individuals were included. Pooled diagnostic odds ratio (DOR) was 27.63 (95% confidence interval [CI]: 10.96~69.61, I2 = 86.2%, P < 0.001) in discriminating between breast cancer and healthy controls; the area under the summary receiver operating characteristic (SROC) curve measured 0.91 (95% CI: 0.17~1.00). Analysis of available data in distinguishing breast cancer and benign breast disease showed a pooled DOR of 35.30 (95% CI: 7.58~164.39, I2 = 79.9%, P = 0.002) with an area under SROC of 0.91 (95% CI: 0.89~0.93). Ethnic group distribution based geographical factors suggested by meta-regression and subgroup analyses explained most of the heterogeneity. CONCLUSIONS: Quantification of cfDNA is a promising test in screening and diagnostic of breast cancer, but population-based standardization of test methods require completion prior to clinical use.