Association of IL­6 and MMP­3 gene polymorphisms with adolescent idiopathic scoliosis: A systematic review and meta­analysis.

The pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear. It has been found that interleukin-6 (IL-6) rs1800795 locus and matrix metalloproteinase-3 (MMP-3) rs3025058 locus gene polymorphisms may be associated with AIS susceptibility, which has been controversial and needs to be further confirmed by updated meta-analysis. The aim of the present study was to investigate the association of MMP-3 rs3025058 and IL-6 rs1800795 single nucleotide polymorphisms (SNPs) with susceptibility to AIS. All relevant articles that met the criteria were retrieved and included, and the publication dates were limited from January 2005 to December 2023. The allele frequencies and different genotype frequencies of IL-6 rs1800795 and MMP-3 rs3025058 loci in each study were extracted and statistically analyzed by ReviewManager 5.4 software, and the odds ratio (OR) and 95% confidence interval (95% CI) of different genetic models were calculated. The results of the meta-analysis showed that there was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS. The allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility (5A vs. 6A, OR=1.18; 95% CI, 1.04-1.33; 5A5A vs. 6A6A, OR=1.65; 95% CI, 1.23-2.21; and 5A5A vs. 5A6A + 6A6A, OR=1.54; 95% CI, 1.19-1.99). Results of subgroup analysis revealed that the allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility in the Caucasian population, and the susceptibility of AIS was associated with the genotype 5A5A of MMP-3 rs3025058 SNP in an Asian population. There was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS, while the allele 5A of MMP-3 rs3025058 locus was associated with the susceptibility to AIS, especially in the Caucasian population.

Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.

Endoscopic Submucosal Dissection Criteria for Differentiated-type Early Gastric Cancer Are Applicable to Mixed-type Differentiated Predominant.

BACKGROUND: There is a lack of sufficient evidence on whether mixed-type differentiated predominant early gastric cancer (MD-EGC) can be treated endoscopically by referring to the criteria for differentiated-type early gastric cancer (EGC). This study aims to evaluate the efficacy of endoscopic submucosal dissection (ESD) in MD-EGC. METHODS: Patients with differentiated-type EGC treated with ESD first from January 2015 to June 2021 were reviewed, including MD-EGC and pure differentiated-type EGC (PD-EGC). Clinical data, including the clinicopathological characteristics, resection outcomes of ESD, and recurrence and survival time, were collected, and the difference between MD-EGC and PD-EGC was tested. RESULTS: A total of 48 patients (48 lesions) with MD-EGC and 850 patients (890 lesions) with PD-EGC were included. Compared with PD-EGC, MD-EGC had a higher submucosal invasion rate (37.5% vs. 13.7%, P<0.001) and lymphatic invasion rate (10.4% vs. 0.4%, P<0.001). The rates of complete resection (70.8% vs. 92.5%, P<0.001) and curative resection (54.2% vs. 87.4%, P<0.001) in MD-EGC were lower than those of PD-EGC. Multivariate analysis revealed that MD-EGC (OR 4.26, 95% CI, 2.22-8.17, P<0.001) was an independent risk factor for noncurative resection. However, when curative resection was achieved, there was no significant difference in the rates of recurrence (P=0.424) between the 2 groups, whether local or metachronous recurrence. Similarly, the rates of survival(P=0.168) were no significant difference. CONCLUSIONS: Despite the greater malignancy and lower endoscopic curative resection rate of MD-EGC, patients who met curative resection had a favorable long-term prognosis.

Inhibition of ferroptosis by POLE2 in gastric cancer cells involves the activation of NRF2/GPX4 pathway.

Gastric cancer results in great cancer mortality worldwide, and inducing ferroptosis dramatically improves the malignant phenotypes of gastric cancer. DNA polymerase epsilon subunit 2 (POLE2) plays indispensable roles in tumorigenesis; however, its involvement and molecular basis in ferroptosis and gastric cancer are not clear. Human gastric cancer cells were infected with lentiviral vectors to knock down or overexpress POLE2, and cell ferroptosis was detected. To further validate the involvement of nuclear factor erythroid 2-related factor 2 (NRF2) and glutathione peroxidase 4 (GPX4), lentiviral vectors were used. POLE2 expression was elevated in human gastric cancer cells and tissues and closely correlated with clinicopathological features in gastric cancer patients. POLE2 knockdown was induced, while POLE2 overexpression inhibited ferroptosis of human gastric cancer cells, thereby modulating the malignant phenotypes of gastric cancer. Mechanistic studies revealed that POLE2 overexpression elevated NRF2 expression and activity and subsequently activated GPX4, which then prevented lipid peroxidation and ferroptosis in human gastric cancer cells. In contrast, either NRF2 or GPX4 silence significantly prevented POLE2 overexpression-mediated inductions of cell proliferation, migration, invasion and inhibition of ferroptosis. POLE2 overexpression inhibits ferroptosis in human gastric cancer cells through activating NRF2/GPX4 pathway, and inhibiting POLE2 may be a crucial strategy to treat gastric cancer.

The association of growth differentiation factor 5 rs143383 gene polymorphism with osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Osteoarthritis (OA) is caused by a complex set of pathophysiological factors. The genetic factors involved in the occurrence and progress of the disease have been widely discussed by scholars. It was found that growth differentiation factor 5 (GDF5) gene polymorphisms may be linked to OA susceptibility, which has been controversial and needs to be further confirmed by an updated meta-analysis. OBJECTIVES: We examined the association between GDF5 rs143383 single nucleotide polymorphism (SNP) and OA susceptibility. METHODS: All relevant articles that met the criteria are retrieved and included, and the search deadline is June 2022. The allele frequencies and different genotype frequencies of GDF5 rs143383 loci in each study were extracted and statistically analyzed by R4.1.3 software, and the different genetic models were analyzed based on their odds ratio (OR) and 95% confidence interval (CI). RESULTS: The meta-analysis explained that GDF5 rs143383 SNP was crucial correlated with OA in all patients with OA of knee, hip and hand. The codominant gene model in the whole crowd (OR = 1.17, 95% CI 1.07-1.27, P < 0.01) enlightened that OA was vitally associated with GDF5 gene polymorphism. At the same time, we did a subgroup analysis based on ethnicity. The codominant gene model (OR = 1.31, 95% CI 1.12-1.53, P < 0.01) in Asian population, the codominant homozygote model (OR = 1.28, 95% CI 1.14-1.43), codominant heterozygote gene model (OR = 1.12, 95% CI 1.01-1.23, P = 0.02), and dominant gene model (OR = 1.19, 95% CI 1.09-1.31, P < 0.01) in Caucasian are analyzed by subgroup analysis. It means that there is a momentous relationship between the GDF5rs143383 gene polymorphism and OA, especially among Caucasians. In addition, we also discussed different types of OA separately and discover that the GDF5rs143383 gene polymorphism was relevant for knee osteoarthritis (KOA) and hand osteoarthritis, and it was more significant in the Caucasian population. But due to the high heterogeneity in hip osteoarthritis, it could not be accurately concluded. Furthermore, we also analyzed the osteoarthritis of different genders and found that the GDF5 rs143383 SNP was associated with both men and women and was still significant in the Caucasian population. CONCLUSION: We found a close association between osteoarthritis and GDF5rs143383SNP in this study. From the analysis of each group, we got the same conclusion in KOA and hand OA, but which need further verification in hip OA. Considering gender, we found a close relationship between GDF5 rs143383 SNP and OA of the knee, hip and hand, both for men and women. This conclusion is more obvious in Caucasian people.

CNIH4 governs cervical cancer progression through reducing ferroptosis.

Cervical cancer is one of the most leading causes of cancer death worldwide, and ferroptosis is implicated in the progression of cervical cancer. Cornichon family AMPA receptor auxiliary protein 4 (CNIH4) is involved in the progression of various human cancers; however, its function in cervical cancer remains unclear. The present study aims to investigate the role and mechanism of CNIH4 in cervical cancer using gain- and loss-of-function studies in vitro. SiHa and CaSki cells were infected with lentiviral vectors to manipulate the expression of CNIH4 in vitro, and cell viability, migration, invasion as well as ferroptosis were evaluated. Transcriptome sequencing analysis was performed to further validate the mechanism through which CNIH4 regulated the progression of cervical cancer. The expression of CNIH4 was upregulated in human cervical cancer tissues and cells, and strongly correlated with the decreases in overall survival and disease free survival rates of cervical cancer patients. CNIH4 silence inhibited, while CNIH4 overexpression facilitated the survival of human cervical cancer cells. Mechanistically, CNIH4 elevated solute carrier family 7 member 11 (SLC7A11)-mediated cystine import, and subsequently increased intracellular glutathione synthesis and glutathione peroxidase 4 activity, thereby inhibiting ferroptosis of human cervical cancer cells. SLC7A11 silence significantly abolished CNIH4-mediated inhibition of ferroptosis in cervical cancer cells in vitro. Our study for the first time reveals that CNIH4 inhibits ferroptosis of human cervical cancer cells through upregulating SLC7A11, defining CNIH4 as an attractive therapeutic and prognostic target for cervical cancer.

ANGPTL2 aggravates LPS-induced septic cardiomyopathy via NLRP3-mediated inflammasome in a DUSP1-dependent pathway.

Angiopoietin-like protein 2 (ANGPTL2) was implicated in various cardiovascular diseases; however, its role in lipopolysaccharide (LPS)-related septic cardiomyopathy remains unclear. Herein, mice were exposed to LPS to generate septic cardiomyopathy, and adeno-associated viral vector was employed to overexpress ANGPTL2 in the myocardium. Besides, mice were treated with adenoviral vector to knock down ANGPTL2 in hearts. ANGPTL2 expressions in hearts and cardiomyocytes were upregulated by LPS challenge. ANGPTL2 overexpression aggravated, while ANGPTL2 silence ameliorated LPS-associated cardiac impairment and inflammation. Mechanically, we found that ANGPTL2 activated NLRP3 inflammasome via suppressing DUSP1 signaling, and NLRP3 knockdown abrogated the detrimental role of ANGPTL2 in aggravating LPS-induced cardiac inflammation. Furthermore, DUSP1 overexpression significantly inhibited ANGPTL2-mediated NLRP3 activation, and subsequently improved LPS-related cardiac dysfunction. In summary, ANGPTL2 exacerbated septic cardiomyopathy via activating NLRP3-mediated inflammation in a DUSP1-dependent manner, and our study uncovered a promising therapeutic target in preventing septic cardiomyopathy.

Duration of SARS-CoV-2 Serum-Neutralizing Antibodies Against SARS-CoV-2 Dependent on the Individual.

We investigated the persistence of SARS-CoV-2-specific neutralizing antibodies in serum (CoV-2-SNAb) against the "WH-Human 1" coronavirus in 57 convalescent persons from January 2020 to January 2021. The CoV-2-SNAb response against authentic "WH-Human 1" showed a significant (p < 0.01) neutralizing high effect (≥95%) in the following manner: by 94.7% neutralization for up to 6 months, by 73.1% for up to 8 months, and by 31.7% for up to 10 months in correlation with a significant decrease in the concentration of the virus determined by SARS-CoV-2 spike protein extracellular domain and spike-receptor-binding domain (S-RBD). There was neutralizing effect (<95%) when the S-RBD optical density (OD) value was more than 1.0, showing a suitable threshold of S-RBD = 1.0 (antibody-tittering, OD). However, in some convalescent persons, no neutralizing effect (<95%) was observed although the SARS-CoV-2-specific neutralizing antibodies were bound to the S-RBD (OD >1.0). The neutralization of the virus in these cases may not involve S-RBD, but rather B- and T cell memory responses in overall immunity, using the threshold value (OD = 1.0) of S-RBD as a simple and effective method to determine the neutralization effect of the antibody efficacy and use of vaccination in combination with a standard pseudovirus neutralizing assay. We suggest that convalescent persons should contact their physicians 6-month postinfection to test the function of their serum neutralizing antibodies and determine whether administering a SARS-CoV-2 vaccine is necessary to prevent the development of severe illness in the future.

A Prediction Model Based on the Risk Factors Associated with Pathological Upgrading in Patients with Early-Stage Gastric Neoplasms Diagnosed by Endoscopic Forceps Biopsy.

Background/Aims: The discrepancies between the diagnosis of preoperative endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) in patients with early gastric neoplasm (EGN) exist objectively. Among them, pathological upgrading directly influences the accuracy and appropriateness of clinical decisions. The aims of this study were to investigate the risk factors for the discrepancies, with a particular focus on pathological upgrading and to establish a prediction model for estimating the risk of pathological upgrading after EFB. Methods: We retrospectively collected the records of 978 patients who underwent ESD from December 1, 2017 to July 31, 2021 and who had a final histopathology determination of EGN. A nomogram to predict the risk of pathological upgrading was constructed after analyzing subgroup differences among the 901 lesions enrolled. Results: The ratio of pathological upgrading was 510 of 953 (53.5%). Clinical, laboratorial and endoscopic characteristics were analyzed using univariable and binary multivariable logistic regression analyses. A nomogram was constructed by including age, history of chronic atrophic gastritis, symptoms of digestive system, blood high density lipoprotein concentration, macroscopic type, pathological diagnosis of EFB, uneven surface, remarkable redness, and lesion size. The C-statistics were 0.804 (95% confidence interval, 0.774 to 0.834) and 0.748 (95% confidence interval, 0.664 to 0.832) in the training and validation set, respectively. We also built an online webserver based on the proposed nomogram for convenient clinical use. Conclusions: The clinical value of identifying the preoperative diagnosis of EGN lesions is limited when using EFB separately. We have developed a nomogram that can predict the probability of pathological upgrading with good calibration and discrimination value.

Copper-Catalyzed, N-Directed Distal C(sp3)-H Functionalization toward Azepanes.

We herein report a copper-catalyzed formal [5 + 2] aza-annulation of N-fluorosulfonamides and 1,3-dienes/1,3-enynes for synthesis of structurally diverse alkene/alkyne-containing azepanes. The reaction features selective functionalization of distal unactivated C(sp3)-H bonds and a broad substrate scope, thus allowing the late-stage modification of pharmaceuticals and natural products. A radical mechanism involving 1,5-hydrogen atom transfer of N-radicals, facile coupling of alkyl radicals with 1,3-dienes/1,3-enynes, and the construction of azepane motifs via C-N bond formation is proposed.

Clinical Features Analysis and Survival Nomogram of Primary Small Intestinal Diffuse Large B-Cell Lymphoma.

Purpose: This study aimed to analyze the clinical features and survival of primary small intestinal diffuse large B-cell lymphoma (PsI-DLBCL), and establish and independently validate a prognostic nomogram for individual risk prediction. Patients and methods: Data for 24 patients from the Renmin Hospital of Wuhan University were used as an independent validation cohort, data for 1144 patients with PsI-DLBCL from the SEER database were randomly assigned to training (N=817) and internal validation (N=327) sets. The survival nomogram was constructed with the most significant factors associated with OS using Univariate and multivariate analyses on the training set. Decision curve analysis (DCA) was conducted. Internal validation was SEER validation set. Our cancer center cohort was used as an external validation set to further verify the survival nomogram. Results: Five clinicopathological feature factors associated with OS of the training set yielded (age, marital status, Ann Arbor stage, surgery for primary site and chemotherapy), which were used to create a survival nomogram. Additionally, the calibration curves of the prognostic nomogram revealed good agreement between the predicted survival probabilities and the ground truth values. The stability of our survival nomogram was explained by internal and external validation data. Conclusion: Our nomogram proposes the clinical and therapeutic factors affecting OS for patients with PsI-DLBCL. It shows that chemotherapy and surgery are beneficial to patients in the choice of treatment options. These results suggest that a survival nomogram may be better at predicting OS for PsI-DLBCL patients.

Licochalcone A inhibits cell growth through the downregulation of the Hippo pathway via PES1 in cholangiocarcinoma cells.

Overexpression or activation of Yes-associated protein (YAP) is common in cancer cells. Thus, targeting YAP may be a strategy for cancer therapy. Licochalcone A (LicA) is a primary active compound of licorice root and is known to have medicinal effects, such as antioxidant, antibacterial, antiviral, and anticancer effects. However, the anticancer pharmacological mechanism of LicA has not been investigated in cholangiocarcinoma. In this study, we investigated the antiproliferative effect of LicA and the underlying molecular mechanism in HCCC-9810 and RBE human cholangiocarcinoma cells. Our experiments indicated that LicA suppressed the growth of cholangiocarcinoma cells through inactivation of the Hippo pathway. Pescadillo ribosomal biogenesis factor 1 (PES1) was notably upregulated and related to carcinogenesis. We also found that LicA suppressed the expression and nuclear localization of PES1, which was associated with the inhibition of YAP expression and transcriptional activity.

How to Choose a Survival Period? The Impact of Antibiotic Use on OS or PFS in NSCLC Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

BACKGROUND: The development of immunotherapy has dramatically changed the treatment of non-small-cell lung cancer. The negative association of antibiotics on the clinical activity of immune checkpoint inhibitors in patients with NSCLC is well known. METHODS: PubMed, Embase, and Medline databases were searched until January 11, 2020. We included retrospective studies of ICIs (e.g., PD-1, PD-L1, and CTLA-4). The clinical outcomes were progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and subgroup and sensitivity analyses were performed. RESULTS: Our results indicated that the use of antibiotics reduced the survival of NSCLC patients treated with ICIs. The pooled HRs of PFS and OS were HR = 1.41 (95% CI = 1.23-1.61; P < 0.001) and HR = 2.16 (95% CI = 1.79-2.60; P < 0.001). We divided the studies into 5 subgroups according to antibiotic exposure time. Subgroup analysis showed that the patients that were administered antibiotics [-60 days; 0 days] or [-30 days; 0 days] before the initiation of ICIs treatment had a poorer OS rate, whereas those patients that were administered antibiotics [0 days; 30 days] after the initiation of ICIs treatment had a poorer PFS rate. In summary, ATB treatment in patients [-60 days; +30 days] near the initiation of ICIs treatment significantly reduced the survival in NSCLC patients. CONCLUSION: Our results indicated that ATB use is negatively associated with survival in NSCLC patients treated with ICIs immunotherapy. Similar studies involving a larger sample of cases are still being published. This meta-analysis identified that the timing of ATB treatment in NSCLC patients receiving ICIs immunotherapy has different effects on the OS and PFS of these patients. ATB treatment prior to the initiation of ICIs treatment affects OS, whereas ATB treatment after the initiation of ICIs treatment affects PFS.

Bioenergy from dairy manure: technologies, challenges and opportunities.

Dairy manure (DM) is a kind of cheap cellulosic biomass resource which includes lignocellulose and mineral nutrients. Random stacks not only leads damage to the environment, but also results in waste of natural resources. The traditional ways to use DM include returning it to the soil or acting as a fertilizer, which could reduce environmental pollution to some extent. However, the resource utilization rate is not high and socio-economic performance is not utilized. To expand the application of DM, more and more attention has been paid to explore its potential as bioenergy or bio-chemicals production. This article presented a comprehensive review of different types of bioenergy production from DM and provided a general overview for bioenergy production. Importantly, this paper discussed potentials of DM as candidate feedstocks not only for biogas, bioethanol, biohydrogen, microbial fuel cell, lactic acid, and fumaric acid production by microbial technology, but also for bio-oil and biochar production through apyrolysis process. Additionally, the use of manure for replacing freshwater or nutrients for algae cultivation and cellulase production were also discussed. Overall, DM could be a novel suitable material for future biorefinery. Importantly, considerable efforts and further extensive research on overcoming technical bottlenecks like pretreatment, the effective release of fermentable sugars, the absence of robust organisms for fermentation, energy balance, and life cycle assessment should be needed to develop a comprehensive biorefinery model.

[Study on improvement and mechanism of tableting properties of porous Fagopyri Dibotryis Rhizoma powders].

At present, there are many difficulties in the development and production of traditional Chinese medicine(TCM) tablets. This work aimed to explore the feasibility of improving dissolution difficulty and large dosage of TCM tablets by co-spray drying TCM extract with a small amount of pore-foaming agent ammonium bicarbonate. A series of porous Fagopyri Dibotryis Rhizoma powders were prepared by co-spray drying Fagopyri Dibotryis Rhizoma with different amounts of ammonium bicarbonate, and their powder pro-perties and tablet properties were comparatively investigated. At the same time, Fagopyri Dibotryis Rhizoma commercial tablets and raw material tablets were used as control drugs, the improvement degree of its compressibility and dissolution rate was investigated. The results showed that there were higher porosity, specific surface area and hollow spheroidal particles structure of powders via co-spray drying Fagopyri Dibotryis Rhizoma with NH_4HCO_3. Compared to parent and commercial Fagopyri Dibotryis Rhizoma tablets, the dissolution rates and compressibility of porous Fagopyri Dibotryis Rhizoma tablets were significantly increasing. High compressibility could increase drug loading by reducing excipients in manufacturing of tablets and lower the dose of Fagopyri Dibotryis Rhizoma tablets.

Hemodynamic Analysis of VenaTech Convertible Vena Cava Filter Using Computational Fluid Dynamics.

The VenaTech convertible filter (VTCF) has been widely used as an inferior vena cava (IVC) filter to prevent fatal pulmonary embolism in patients. However, its hemodynamics that greatly affect the filter efficacy and IVC patency are still unclear. This paper uses computational fluid dynamics with the Carreau model to simulate the non-Newtonian blood flows around the VTCF respectively deployed in the normal, reverse and three converted states in an IVC model. The results show that the prothrombotic stagnation zones are observed downstream from the normal, reverse and small open VTCFs, with the streamwise length is nearly eight times the IVC diameter. The no-slip boundary conditions of the thin-wire VTCF arms lead to the "viscous block" effect. The viscous block accelerates the blood flow by 5-15% inside the IVC and enhances the filter wall shear stress up to nearly 20 times that of the IVC only, which contributes to clot capture and thrombus lysis. The relative flow resistance is defined to evaluate the filter-induced resistance on the IVC blood flow that can be regarded as an index of IVC patency with the filter deployment. The flow resistance of the normal VTCF deployment increases dramatically by more than 60% compared with that of the IVC only and is a little higher (6%) than that of the reverse case. As the VTCF converts to a fully open configuration, the flow resistance gradually decreases to that of no filter. This work shows that even very thin VTCF arms can result in the viscous block effect and may cause significant hemodynamic impacts on clot capture, potential thrombosis and flow impedance inside the IVC. The present study also shows that CFD is a valuable and feasible in silico tool for analyzing the IVC filter hemodynamics to complement in vivo clinical and in vitro experimental studies.

The spatial effect of tourism economic development on regional ecological efficiency.

The process of tourism economic development is accompanied by the consumption of energy and environment. It is of a big significance to measure the level of tourism economic development and regional eco-efficiency correctly to clarify the relationship between them, as it contributes to realizing the high-quality development of the tourism economy and the construction of "beautiful China". On the basis of the panel data of China's 30 provinces and cities from 2002 to 2016, the paper intends to evaluate the regional eco-efficiency and tourism economic development level by using the super-efficiency DEA model and the grey entropy weight method, and then construct spatial panel econometric model which is based on the previous data to deeply discuss the influence of tourism economy development on regional ecological efficiency and its spatial effect. The research shows that (1) regional ecological efficiency has significant spatial dependence and spatial aggregation characteristics. With the passing of time, this kind of positive spatial autocorrelation is gradually strengthened. (2) In the long-term development, tourism economic development and regional ecological efficiency show a more obvious "Kuznets curve" effect. (3) The "U"-curve relationship between urbanization, environmental regulation, and regional eco-efficiency was confirmed. (4) In the process of tourism economic transformation and development, industrial pollution control, environmental regulation, technological level, urbanization, and investment openness are the main factors that affect the improvement of ecological efficiency in the local region. (5) Tourism economic development and urbanization levels have different spatial spillover effects in different periods, while investment openness has obvious positive spillover effects.

Long-Non Coding RNA SNHG16 Supports Colon Cancer Cell Growth by Modulating miR-302a-3p/AKT Axis.

Small nucleolar RNA host gene 16 (SNHG16) is reported to be involved in the tumorigenesis of various kinds of tumors. SNHG16 expression was reported to be upregulated in colon cancer, however, the underlying mechanism of how SNHG16 affects the colon cancer development remains poorly elucidated. In our study, with the aim to identify the role of SNHG16 on colon cell proliferation, SNHG16 was overexpressed or knocked down in vitro, respectively. SNHG16 overexpression accelerated colon cancer cell growth, while cell growth ability was impaired in SNHG16 silencing cells. Furthermore, the starBase database predicted that miR-302a-3p was the target gene of SNHG16, which was supported by dual luciferase assay. The effect of promoting cell proliferation ability induced by SNHG16 overexpression could be partly reversed by co-transfection of miR-302a-3p mimic. Application of the miRanda database indicated that AKT may be modulated by SNHG16, further evidenced by western blot and quantitative PCR assays. AKT overexpression could partly reverse the attenuated colon cancer cell growth caused by miR-302a-3p mimic transfection. Meanwhile, the combination of miR-302a-3p inhibitor and shAKT achieved the parallel result. In conclusion, our study revealed the SNHG16/miR-302a-3p/AKT axis might play a crucial role in colon cancer cell proliferation, thus participating in the process of colon cancer development.

NAA at a high concentration promotes efficient plant regeneration via direct somatic embryogenesis and SE-mediated transformation system in Ranunculus sceleratus.

The novel methods for efficient plant regeneration via direct somatic embryogenesis (SE) and SE-mediated transformation system under high concentration of NAA in Ranunculus sceleratus were established. On MS media containing a high concentration of NAA (10.0 mg/L) in the dark, all inoculated explants (root, stem and leaf) formed somatic embryos at high frequencies, respectively, 66.03, 126.47 and 213.63 embryoids per explant, and 100% of the embryoids developed into plantlets on 1/2 MS rooting media. Morphological and histological analyses revealed that SE in R. sceleratus followed a classical pattern. All inoculated explants can be used as receptors for genetic transformation in R. sceleratus, through direct SE-mediated method after Agrobacterium infection. RcLEC1-B, as a marker gene, changed the number and morphology of flower organs and the development of cuticle in R. sceleratus, which indicated that the efficient transgenic system of R. sceleratus was established. To our knowledge, this is the first observation that both direct SE and transgenic transformation system, via induction of a single plant growth regulator, have been successfully constructed in R. sceleratus.