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Litsea cubeba (Lour.) Pers. is an important spice plant in southern China. The whole plant of Litsea cubeba contains essential oils, among which the fruit has the highest essential oil content. And there is a significant market demand and widespread use of essential oil of Litsea cubeba fruit. However, there are few systematic studies on the growth and development of the Litsea cubeba fruit. This study aims to determine the regularity of annual changes in fruit morphology, essential oil content, and components of Litsea cubeba essential oil to determine the optimal harvest period and improve the utilization efficiency of Litsea cubeba resource. The results show that the annual change of fruit morphology of Litsea cubeba was consistent with the double "S" curve, which shows a general trend of rapid growth first, then slow growth, and finally rapid growth again. While the annual change of the essential oil of Litsea cubeba fruits was consistent with a single "S" curve, which shows a general trend of slow growth first, then rapid growth, and finally decreasing rapidly. Correlation analysis showed a significant negative correlation between morphological changes and essential oil accumulation in Litsea cubeba fruit. Combining the growing periods of fruit morphology and essential oil accumulation, the growth and development of Litsea cubeba fruit can be divided into four general periods: the first rapid growth period (rapid growth in fruit diameter and fruit weight with slow accumulation of essential oil), the essential oil accumulation period (rapid accumulation of essential oil with slow growth in fruit diameter and fruit weight), the second rapid growth period (fruit diameter and fruit weight increased rapidly for the second time while the essential oil content started to decrease), and the shriveling period (fruit diameter and weight and essential oil content all decreased rapidly). This study further confirmed that citral was the highest component in the essential oil of Litsea cubeba. When citral extraction is needed, the fruit can be harvested 139–149 days after anthesis.

This study compared the effects on bone metabolism and morphology of pathological obesity induced by excessive fat intake in a non-hibernator (mice) versus healthy obesity due to pre-hibernation fattening in a hibernator (ground squirrels). Kunming mice were fed a high-fat diet to provide a model of pathological obesity (OB group). Daurian ground squirrels fattened naturally in their pre-hibernation season (PRE group) were used as a healthy obesity model. Micro-computed tomography (micro-CT) and three-point bending tests were used to determine the microstructure and mechanical properties of bone. Western blots were used to analyze protein expression levels related to bone metabolism (Runt-related transcription factor 2 (RunX2), osteocalcin (OCN), alkaline phosphatase (ALP), osteoprotegerin (OPG), receptor activator of nuclear factor-‍κB ligand (RANKL), cathepsin K, matrix metallopeptidase 9 (MMP9), patched protein homolog 1 (Ptch1), phosphorylated β‍-‍catenin (P‍-‍β‍-‍catenin), and glycogen synthase kinase-3β (GSK-3β)). Compared with controls, there was no obvious bone loss in the OB mice, and the stiffness of the femur was increased significantly. Compared with summer active squirrels, bone formation was enhanced but the mechanical properties did not change in the PRE group squirrels. In OB mice, western blots showed significantly increased expression levels of all proteins except RunX2, OPG, and Ptch1. PRE ground squirrels showed significantly increased expression of most proteins except OCN and Ptch1, which decreased significantly, and P‍-‍β‍-‍catenin and OPG, which did not change. In conclusion, for non-hibernating mice, moderate obesity had a certain protective effect on bones, demonstrating two-way regulation, increasing both bone loss and bone formation. For pre-hibernating ground squirrels, the healthy obesity acquired before hibernation had a positive effect on the microstructure of bones, and also enhanced the expression levels of proteins related to bone formation, bone resorption, and Wnt signaling.

Hibernators are a natural model of vascular ischemia–reperfusion injury; however, the protective mechanisms involved in dealing with such an injury over the torpor–arousal cycle are unclear. The present study aimed to clarify the changes in the thoracic aorta and serum in summer-active (SA), late-torpor (LT) and interbout-arousal (IBA) Daurian ground squirrels (Spermophilus dauricus). The results show that total antioxidant capacity (TAC) was unchanged, but malondialdehyde (MDA), hydrogen peroxide (H2O2), interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) were significantly increased for the LT group, whereas the levels of superoxide dismutase (SOD) and interleukin-10 (IL-10) were significantly reduced in the LT group as compared with the SA group. Moreover, the levels of MDA and IL-1β were significantly reduced, whereas SOD and IL-10 were significantly increased in the IBA group as compared with the SA group. In addition, the lumen area of the thoracic aorta and the expression of the smooth muscle cells (SMCs) contractile marker protein 22α (SM22α) were significantly reduced, whereas the protein expression of the synthetic marker proteins osteopontin (OPN), vimentin (VIM) and proliferating cell nuclear antigen (PCNA) were significantly increased in the LT group as compared with the SA group. Furthermore, the smooth muscle layer of the thoracic aorta was significantly thickened, and PCNA protein expression was significantly reduced in the IBA group as compared with the SA group. The contractile marker proteins SM22α and synthetic marker protein VIM underwent significant localization changes in both LT and IBA groups, with localization of the contractile marker protein α-smooth muscle actin (αSMA) changing only in the IBA group as compared with the SA group. In tunica intima, the serum levels of heparin sulfate (HS) and syndecan-1 (Sy-1) in the LT group were significantly reduced, but the serum level of HS in the IBA group increased significantly as compared with the SA group. Protein expression and localization of endothelial nitric oxide synthase (eNOS) was unchanged in the three groups. In summary, the decrease in reactive oxygen species (ROS) and pro-inflammatory factors and increase in SOD and anti-inflammatory factors during the IBA period induced controlled phenotypic switching of thoracic aortic SMCs and restoration of endothelial permeability to resist ischemic and hypoxic injury during torpor of Daurian ground squirrels.

Background: Both pathological conditions and hibernation can affect the barrier function of small intestine mucosa. However, the effect of hibernation on the barrier function of colonic mucosa remains unclear. Methods: We investigated morphological changes in colonic mucosa, the concentrations of specific proteins and molecules, and the enzymatic activity of diamine oxidase (DAO), in serum and colonic tissue; the expression of tight junction proteins and mucin, and the changes in inflammatory, farnesoid X receptor (FXR)–small heterodimer partner (SHP), and apoptosis-related molecules that could play a role in gut permeability changes in Daurian ground squirrels in summer active (SA), late torpor (LT), and interbout arousal (IBA) periods. Results: The results show that hibernation reduced the thickness of the colonic mucosa and the depth of the crypt, decreased the number of goblet cells (GCs), and damaged the structure of some microvilli. The concentrations of proteins and molecules, and the enzymatic activity of DAO, were all increased in the serum and colon, and the localization of tight junction proteins and mucin in the colonic mucosa were altered (compensatory response). Although the ground squirrels ate during the interbout arousal period, the changes remained similar to the response to torpor. Inflammation, apoptosis–anti-apoptosis, and FXR–SHP signaling may be involved in the possible changes in intestinal gut permeability during the torpor–arousal cycle in Daurian ground squirrels. In addition, periodic interbout arousal may play an inflammation-correcting role during the long hibernation season of Daurian ground squirrels.

FOXD2-AS1 is known to promote the development of several cancers. However, its role in pancreatic adenocarcinoma (PAAD) is unclear.Expression of FOXD2-AS1 and miR-30a-3p in PAAD patients was analyzed with RT-qPCR. A follow-up study was performed to analyze the prognostic value of FOXD2-AS1 for PAAD. Overexpression assays were performed to analyze the crosstalk between FOXD2-AS1 and miR-30a-3p. Cell invasion and migration were analyzed by transwell assays.Analysis of the TCGA dataset revealed that FOXD2-AS1 was upregulated in PAAD tissues compared to the non-cancer tissues (1.89 vs. 0.2 TPM), indicating potential involvement of FOXD2-AS1 in PAAD. Our own data also showed FOXD2-AS1 was overexpressed in PAAD. Moreover, high FOXD2-AS1 levels predicted poor survival. It is predicted that miR-30a-3p can bind FOXD2-AS1, while their overexpression did not affect each other's expression. Correlation analysis revealed a significant correlation between FOXD2-AS1 and COX-2. In addition, FOXD2-AS1 overexpression increased COX-2 level, while miR-30a-3p played an opposite role. FOXD2-AS1 and COX-2 overexpression increased PAAD cell invasion and migration. MiR-30a-3p played an opposite role and inhibited the effects of FOXD2-AS1 and COX-2 overexpression.FOXD2-AS1 may promote PAAD cell invasion and migration by sponging miR-30a-3p to upregulate COX-2.

Background This study compared effects on bone metabolism and morphology of pathological obesity induced by excessive fat intake in a non-hibernator (mice) versus healthy obesity due to pre-hibernation fattening in a hibernator (ground squirrels). Methods Kunming mice were fed a high-fat diet for 3 months to provide a model of pathological obesity (OB group). Daurian ground squirrels fattened naturally in their pre-hibernation season (PRE group) were used as a healthy obesity model. Body weight and adipose tissue wet weight were measured. Micro-computed tomography and three-point bending tests were used to determine the microstructure and mechanical properties of bone. Western blots were used to analyze protein expression levels related to bone formation (RunX2, OCN, ALP), bone resorption (RANKL, Cathepsin K, MMP9) and Wnt signaling (P-β-catenin, GSK-3β). Results Micro-CT showed that there was no obvious bone loss in the OB group, compared with controls, whereas bone formation in the PRE group was enhanced, compared to summer-active squirrels. Results of three-point bending tests showed that stiffness of the femur in OB mice was significantly enhanced, whereas the mechanical properties of bone in the PRE group did not change. Analysis of bone protein expression showed significantly increased expression levels of ALP, OCN, RANKL, MMP9, Cathepsin K, GSK-3β and P-β-catenin in OB mice, but RunX2 expression did not change. By contrast, PRE ground squirrels, showed significantly increased expression of most proteins except for OCN that decreased significantly, and P-β-catenin that did not change. Conclusion For non-hibernating mice, moderate obesity had a certain protective effect on bones, demonstrating two-way regulation, enhancing both bone loss and bone formation, so that bone metabolism was at a higher level of metabolic balance. For pre-hibernating ground squirrels, the healthy obesity acquired before hibernation had a positive effect on the microstructure of bones and also enhanced the expression levels of proteins related to bone formation, bone resorption and Wnt signaling.

To investigate whether RBM6 can serve as a suppressor gene in hepatocellular carcinoma (HCC) and affect its progression.QPCR and Western blot were carried out to measure RBM6 expression in tissue samples collected from HCC patients with different tumor sizes or in different stages. The relationship between overall survival (OS) and RBM6 expression in patients with HCC was analyzed using Kaplan-Meier survival method. Meanwhile, the effects of different factors on HCC progression were evaluated through Cox regression analysis. After over-expression of RBM6 in HepG2 and HB611 cells, the cell viability, cell migration and invasion abilities and apoptosis rate were assessed by cell counting kit-8 (CCK-8), transwell assay, and flow cytometry analysis, respectively.RBM6 expression, markedly down-regulated in HCC tissues, showed a great relevance to tumor size, TNM stage, and histological grade, and the survival rate of patients in high RBM6 expression group was higher than those in low RBM6 expression group. Besides, Cox regression analysis revealed that RBM6 expression, tumor size, TNM stage and histological grade were four independent factors affecting the OS of HCC patients. Moreover, in vitro cell experiments demonstrated that overexpression of RBM6 significantly attenuated the cell viability as well as the invasive ability while enhanced cell apoptosis.The low expression of RBM6 contributes to the improvement of the survival of patients with HCC. Therefore, RBM6 can serve as a tumor-suppressing gene to repress cell proliferation, migration and invasion and promote cell apoptosis, thereby affecting the progression of HCC.

Aim: Several studies reported the association of platelet-to-lymphocyte ratio (PLR) and prognosis in nasopharyngeal carcinoma (NPC), but the results remain controversial. Therefore, we investigated the prognostic value of PLR in NPC through meta-analysis. Materials & methods: A comprehensive literature search of PubMed, Embase and Web of Science was performed. Results: A total of 9 studies comprising of 3459 patients with NPC were included. The data demonstrated that an increased PLR predicted poor overall survival, progression-free survival and distant metastasis-free survival. There was no significant association between PLR and sex, age, T stage, N stage, tumor node metastasis (TNM) stage or intensity-modulated radiotherapy. Conclusion: This meta-analysis revealed that PLR might be a potential predicative biomarker of poor prognosis in patients with NPC.

International audience; Right heart catheterisation is considered as the gold standard for the assessment of patients with suspected pulmonary hyper-tension. It provides clinicians with meaningful data, such as pulmonary capillary wedge pressure and pulmonary vascular resistance, however its usage is limited due to its invasive nature. Non-invasive alternatives, like Doppler echocardiography could present insightful measurements of right heart but lack detailed information related to pulmonary vascu-lature. In order to explore non-invasive means, we studied a dataset of 95 pulmonary hypertension patients, which includes measurements from echocardiography and from right-heart catheterisation. We used data extracted from echocardiography to conduct cardiac circulation model per-sonalisation and tested its prediction power of catheter data. Standard machine learning methods were also investigated for pulmonary artery pressure prediction. Our preliminary results demonstrated the potential prediction power of both data-driven and model-based approaches.