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The accurate analysis of landscape pattern and ecological process characteristics in rapidly urbanized areas is crucial for formulating policies related to differentiated urban development and landscape management measures. However, there are no convincing set of overall indices suitable and the optimal scale in karst mountainous regions. This study determined optimal landscape indices and scales and analysed the temporal and spatial variation characteristics of landscape patterns in the karst mountainous city of central Guizhou Province by taking Guiyang City as a case study area using Principal component analysis and inflection point analysis. The results show that: (1) the nine landscape indices (i.e., edge density (ED), mean radius of gyration (GYRATE_MN), mean contiguity index (CONTIG_MN), mean shape index (SHAPE_MN), contagion index (CONTAG), interspersion and juxtaposition index (IJI), Shannon's diversity index (SHDI), proportion of urban area (UI), Gibbs-Martin diversity index(GM)) were optimal indices of landscape pattern analysis in karst mountainous cities, with optimal landscape grain and extent of 90 m and 1000 m, respectively; (2) from 1995 to 2019, the landscape pattern in karst mountainous region has changed dramatically under the impact of rapid urbanization, and urbanization and ecologization were main trends of landscape pattern changes; and (3) the landscape fragmentation was intensified with the regularity tendency of patch shape, which is still facing severe challenges to the protection of regional ecological environment. This study makes important contributions to exploring the response between landscape pattern changes and ecological processes and promoting ecological sustainable development in karst mountain cities.

Mechanism of action of SNORD89

Background and AimsAbnormal expression of E3 ubiquitin ligase plays an important role in the development and progression of hepatocellular carcinoma (HCC), although the mechanism has remained elusive. This study aimed to investigate the biological function and potential mechanism of FBXO43 in HCC.MethodsFBXO43 expression in tissues and cells were detected by quantitative real-time PCR (qRT−PCR), Western blot, and immunohistochemistry (IHC). The Kaplan-Meier method and Cox regression analysis were used to explore the correlation between the expression level of FBXO43 and the clinical survival. MTT assay, EdU incorporation, colony formation, Transwell, and wound healing assays were performed to evaluate the function of FBXO43 in cell proliferation and migration in vitro. The interaction between FBXO43 and cyclin D1 (CCND1) was assessed by co-immunoprecipitation (Co-IP) assay and in vivo ubiquitination assay.ResultsWe found that FBXO43 was upregulated in HCC patient tissues and positively associated with poor clinicopathological features. Meanwhile, HCC patients with high expression of FBXO43 had shorter overall survival (OS) and disease-free survival (DFS). Furthermore, knockdown of FBXO43 inhibited HCC cell proliferation, migration and epithelial-mesenchymal transition (EMT) in HCC cells. Mechanistically, FBXO43 interacted with CCND1 and promoted its stability by polyubiquitination, leading to HCC cell proliferation, migration and EMT. Functional rescue experiments demonstrated that knockdown of CCND1 blocks FBXO43-mediated cell proliferation and metastasis.ConclusionsFBXO43, as an independent prognostic biomarker, promotes HCC cell proliferation, metastasis and EMT by stability of CCND1, which provides a new potential strategy for HCC treatment by targeting FBXO43-CCND1 axis.

IntroductionIn recent decades, single-cell sequencing technology has developed rapidly and used widely in various fields of life sciences, especially for the detection of immune cells. A bibliometric analysis of single-cell sequencing research work on immune cells published during the 2011-2021 period should provide new insight on the use of single-cell sequencing.MethodsWe screened 1,460 publications on single-cell sequencing on immune cells according to the publication date, article type, language, and country.ReultsThe United States published the first and largest number of articles, while China’s research started relatively late, but ranked second in the number of publications. T cells were the most commonly studied immune cells by single-cell sequencing, followed by mononuclear macrophages. Cancer biology was the most common field of immune cell research by single-cell sequencing. Single-cell sequencing studies using γδ T cells were mainly in the fields of cancer biology and cell development, and focused over time from cell surface receptor to cell function. Through in-depth analysis of the articles on single-cell sequencing of T cells in the oncology field, our analysis found that immunotherapy and tumor microenvironment were the most popular research directions in recent years.DiscussionThe combination of DNA damage repair and immunotherapy seems to provide a new strategy for cancer therapy.

Exploring the effects of landscape pattern changes on ecosystem services (ESs) and its interactions could provide a new method to reduce the trade-offs between ESs from the perspective of landscape pattern optimization, thus contributing to the sustainable management of ESs. In this study, the Guiyang City which is a typical karst mountainous city in China was used as the study region, using InVEST model, Spearman’s correlation and Multiscale Geographically Weighted Regression (MGWR) model, the study assessed the changes and trade-offs of four key types of ESs (i.e., carbon storage (CS), habitat quality (HQ), soil conservation (SC), water yield (WY)) from 1995 to 2019, and analyzed the impacts of landscape pattern on the synergies of ESs. The results showed that ESs in Guiyang City steadily increased during 1995–2019, with CS, HQ, SC, WY, and total ecosystem services (TES) increased by 6.67%, 7.66%, 27.16%, 13.08%, and 11.81%, respectively. The relationship of CS-SC and SC-WY were mainly trade-offs, while the other ESs types were mainly synergies. Moreover, the interaction of static ESs was reversed with that of dynamic spatiotemporal ESs when the lower interaction relationship between static ESs. The effects of landscape pattern changes on ESs and ESs interactions have obvious spatial and scale heterogeneity. Landscape composition had a greater impact on ESs than landscape configuration. Proportion of woodland (Wood_per) and Shannon’s Diversity Index (SHDI) were the main factors influencing the synergies effect of TES. The results could provide practical references for ESs improvement-oriented landscape pattern planning and ecosystem service management in the Guiyang City and in similar fragile ecological regions, which is helpful for the improvement of ESs and high-quality sustainable development.

Abstract Gene fusions are thought to be driver mutations in multiple cancers and are an important factor for poor patient prognosis. Most of them appear in specific cancers, thus satisfactory strategies can be developed for the precise treatment of these types of cancer. Currently, there are few targeted drugs to treat gynecologic tumors, and patients with gynecologic cancer often have a poor prognosis because of tumor progression or recurrence. With the application of massively parallel sequencing, a large number of fusion genes have been discovered in gynecologic tumors, and some fusions have been confirmed to be involved in the biological process of tumor progression. To this end, the present article reviews the current research status of all confirmed fusion genes in gynecologic tumors, including their rearrangement mechanism and frequency in ovarian cancer, endometrial cancer, endometrial stromal sarcoma, and other types of uterine tumors. We also describe the mechanisms by which fusion genes are generated and their oncogenic mechanism. Finally, we discuss the prospect of fusion genes as therapeutic targets in gynecologic tumors.

In order to explore the molecular mechanism of acute rejection after liver transplantation (ARLT) in rats, we employed the GSE36798 data set in the Gene Expression Omnibust (GEO) database to construct a related ceRNA network. This dataset contained a total of 16 samples (8 graft samples and 8 plasma samples). Each kind of sample was divided into acute rejection (AR) groups and non-acute rejection (NR) groups, and each group had 4 replicates. First, we performed principal component analysis (PCA) with downloaded data to compare the difference between samples in a macroscopic way. Then, we used the “limma” R package to screen out differentially expressed miRNAs among different groups and used the “pheatmap” R package to perform bidirectional hierarchical clustering analysis for these differentially expressed miRNAs. The miRWalk database and the LncBase V.2 database were applied to predict downstream target genes and upstream-related lncRNAs, respectively. Meanwhile, the String database was used to predict the relationship between target genes, and the aforementioned results were processed for visualization by Cytoscape software. In addition, we exhibited the ultimate ceRNA network, including two lncRNAs, two miRNAs, and 77 mRNAs. Finally, we constructed a rat model of ARLT and applied graft specimens to relevant experimental verification. We found that the lncRNA Snhg1/rno-miR-139-5p axis might be involved in the regulation of ARLT in rats. In short, we demonstrated the differentially expressed miRNA profile, constructed a related ceRNA network, and screened out a possible regulatory axis. In view of the conservation of genes among species, this work was expected to provide a new strategy for the treatment and prevention of ARLT in the clinical setting.

Abstract Circular RNAs (circRNAs) play important roles in cancer tumorigenesis and progression, representing prognostic biomarkers and therapeutic targets. In this case, we demonstrated the role of circ-NOLC1 in epithelial ovarian cancer (EOC). Our results have shown that Circ-NOLC1 expression was higher in EOC tissues than in normal tissues, and was positively associated with FIGO stage, differentiation. Among ovarian cancer cell lines, circ-NOLC1 expression was the highest in A2780, and lowest in CAOV3. Overexpression of circ-NOLC1 in CAOV3 cells increased cell proliferation, migration, and invasion ability, whereas silencing of circ-NOLC1 in A2780 cells had the opposite effect: however, neither circ-NOLC1 downregulation nor overexpression influenced NOLC1 mRNA expression. In nude mice with subcutaneous tumors, circ-NOLC1 downregulation decreased tumor growth. Bioinformatic analysis and RNA-binding protein immunoprecipitation showed that circ-NOLC1 could bind to ESRP1. In addition, the overexpression of circ-NOLC1 significantly increased ESRP1, RhoA, and CDK1 protein and mRNA expression level; circ-NOLC1 downregulation had the opposite effects. The tumor-promoting effect of circ-NOLC1 was inhibited by knockdown of ESRP1, CDK1, or RhoA expression in circ-NOLC1-overexpressing cells, which might act by modulating RhoA and CDK1 expression. In conclusion, our study demonstrated that Circ-NOLC1 might promote EOC tumorigenesis and development by binding ESRP1 and modulating CDK1 and RhoA expression.

The sodium pump α3 subunit is associated with colorectal liver metastasis. However, the underlying mechanism involved in this effect is not yet known. In this study, we found that the expression levels of the sodium pump α3 subunit were positively associated with metastasis in colorectal cancer (CRC). Knockdown of the α3 subunit or inhibition of the sodium pump could significantly inhibit the migration of colorectal cancer cells, whereas overexpression of the α3 subunit promoted colorectal cancer cell migration. Mechanistically, the α3 subunit decreased p53 expression, which subsequently downregulated PTEN/IGFBP3 and activated mTOR, leading to the promotion of colorectal cancer cell metastasis. Reciprocally, knockdown of the α3 subunit or inhibition of the sodium pump dramatically blocked this effect in vitro and in vivo via the downregulation of mTOR activity. Furthermore, a positive correlation between α3 subunit expression and mTOR activity was observed in an aggressive CRC subtype. Conclusions: Elevated expression of the sodium pump α3 subunit promotes CRC liver metastasis via the PTEN/IGFBP3-mediated mTOR pathway, suggesting that sodium pump α3 could represent a critical prognostic marker and/or therapeutic target for this disease.

OBJECTIVE:To design and evaluate the accuracy of a novel navigation template suitable for posterior cervical screw placement surgery by using 3D printing technology to improve the existing guiding template design. METHODS:The researchers (including spine surgeons and technicians) used CT to perform thin-slice scanning on 12 cases of normal upper cervical vertebral specimens and defined the screw channels that were completely located in the pedicle without penetrating the cortex as ideal screw channels, then designed the ideal channel of the upper cervical vertebral (atlantoaxial) pedicle screw by computer software which was regarded as the preset values, and recorded the screw entrance point, transverse angle and sagittal angle of the ideal channel. Then, researchers designed the novel navigation templates for placement pedicle screw according to the ideal screw channel preset values and manufactured them with one for every single vertebra by 3D printer. A senior spine surgeon performed the posterior surgery to implant pedicle screw on the specimens by the novel navigation templates, then performed CT thin-slice scanning on the specimens again after removing the screws, and reconstructed the actual screws channel by computer software, recorded the screw entrance point, transverse angle and sagittal angle of the actual channels which were defined as the actual values and evaluated them according to Kawaguchi's pedicle screw evaluation standard finally. The differences between the preoperative preset values of ideal screw channel and the postoperative actual values of actual screw channel were compared by a nonparametric paired rank test. RESULTS:48 screws were placed on 12 cases of upper cervical vertebral specimens in total. It showed that the grade 0, I, II, III channels in this study were 47, 1, 0, 0, respectively. The grade 0 channels accounted for 97.92% of the total number of channels. There was no significant difference with regard to the screw entrance point, the transverse angle, and the sagittal angle between the preoperative preset values of ideal screw channels and the postoperative actual values of actual screw channels. CONCLUSION:To implant pedicle screw assisted with the novel individually navigation template designed by 3D printed in the posterior cervical surgery can improve accuracy of pedicle screw placement and safety of the surgery.

Abstract Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48–0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

Mutations in the well-known Myostatin (MSTN) produce a ‘double-muscle’ phenotype, which makes it commercially invaluable for improving livestock meat production and providing high-quality protein for humans. However, mutations at different loci of the MSTN often produce a variety of different phenotypes. In the current study, we increased the delivery ratio of Cas9 mRNA to sgRNA from the traditional 1:2 to 1:10, which improves the efficiency of the homozygous mutation of biallelic gene. Here, a MSTNDel73C mutation with FGF5 knockout sheep, in which the MSTN and FGF5 dual-gene biallelic homozygous mutations were produced via the deletion of 3-base pairs of AGC in the third exon of MSTN, resulting in cysteine-depleted at amino acid position 73, and the FGF5 double allele mutation led to inactivation of FGF5 gene. The MSTNDel73C mutation with FGF5 knockout sheep highlights a dominant ‘double-muscle’ phenotype, which can be stably inherited. Both F0 and F1 generation mutants highlight the excellent trait of high-yield meat with a smaller cross-sectional area and higher number of muscle fibers per unit area. Mechanistically, the MSTNDel73C mutation with FGF5 knockout mediated the activation of FOSL1 via the MEK-ERK-FOSL1 axis. The activated FOSL1 promotes skeletal muscle satellite cell proliferation and inhibits myogenic differentiation by inhibiting the expression of MyoD1, and resulting in smaller myotubes. In addition, activated ERK1/2 may inhibit the secondary fusion of myotubes by Ca2+-dependent CaMKII activation pathway, leading to myoblasts fusion to form smaller myotubes.

Abstract Background The morphological information of the pulmonary vein (PV) and left atrium (LA) is of immense clinical importance for effective atrial fibrillation ablation. The aim of this study is to examine the consistency in different LA diameter measurement techniques. Methods Retrospective imaging data from 87 patients diagnosed with PV computed tomography angiography were included. The patients consisted of 50 males and 37 females, with an average age of (60.74 ± 8.70) years. Two physicians independently measured the anteroposterior diameter, long diameter, and transverse diameter of the LA using six different methods. Additionally, we recorded the post-processing time of the images. Physician 1 conducted measurements twice with a one-month interval between the measurements to assess intra-rater reliability. Using the intraclass correlation coefficient (ICC), the consistency of each LA diameter measurement by the two physicians was evaluated. We compared the differences in the LA diameter and the time consumed for measurements using different methods. This was done by employing the rank sum test of a randomized block design (Friedman M test) and the q test for pairwise comparisons among multiple relevant samples. Results (1) The consistency of the measured LA diameter by the two physicians was strong or very strong. (2) There were statistical differences in the anteroposterior diameter, long diameter, and transverse diameter of LA assessed using different methods (χ 2 = 222.28, 32.74, 293.83, P

Abstract Background A mathematical model to understand, predict, control, or even design a real biological system is a central theme in systems biology. A dynamic biological system is always modeled as a nonlinear ordinary differential equation (ODE) system. How to simulate the dynamic behavior and dynamic parameter sensitivities of systems described by ODEs efficiently and accurately is a critical job. In many practical applications, e.g., the fed-batch fermentation systems, the system admissible input (corresponding to independent variables of the system) can be time-dependent. The main difficulty for investigating the dynamic log gains of these systems is the infinite dimension due to the time-dependent input. The classical dynamic sensitivity analysis does not take into account this case for the dynamic log gains. Results We present an algorithm with an adaptive step size control that can be used for computing the solution and dynamic sensitivities of an autonomous ODE system simultaneously. Although our algorithm is one of the decouple direct methods in computing dynamic sensitivities of an ODE system, the step size determined by model equations can be used on the computations of the time profile and dynamic sensitivities with moderate accuracy even when sensitivity equations are more stiff than model equations. To show this algorithm can perform the dynamic sensitivity analysis on very stiff ODE systems with moderate accuracy, it is implemented and applied to two sets of chemical reactions: pyrolysis of ethane and oxidation of formaldehyde. The accuracy of this algorithm is demonstrated by comparing the dynamic parameter sensitivities obtained from this new algorithm and from the direct method with Rosenbrock stiff integrator based on the indirect method. The same dynamic sensitivity analysis was performed on an ethanol fed-batch fermentation system with a time-varying feed rate to evaluate the applicability of the algorithm to realistic models with time-dependent admissible input. Conclusion By combining the accuracy we show with the efficiency of being a decouple direct method, our algorithm is an excellent method for computing dynamic parameter sensitivities in stiff problems. We extend the scope of classical dynamic sensitivity analysis to the investigation of dynamic log gains of models with time-dependent admissible input.

A new species of xenodermid snake, Achalinus nanshanensis H. Li, L.-Q. Zhu, Z.-Q. Zhang & X.-Y. Mo, sp. nov., is described based on three specimens collected from Nanshan National Park and Tongdao County of southwest Hunan Province. This new species is genetically distinct amongst its congeners with the mitochondrial COI uncorrected p-distance ranging from 4.4% (in A. yangdatongi) to 17.7% (in A. meiguensis). In addition, this new species can be distinguished from its congeners by a combination of the following morphological characters: (1) dorsal scales with 23 or 25 rows throughout and strongly keeled; (2) tail relatively longer so that TaL/ToL = 0.215–0.248; (3) length of suture between internasals significantly longer than that between prefrontals, LSBI/LSBP = 1.66–1.84; (4) single loreal scale present; (5) SPL 6 in number, with the fourth and fifth contacting eye; (6) IFL 6 in number, with the first three touching the first pair of chin shields; (7) TMP is 2-2-4/2-2(3)-4, with the anterior pair elongated and in contact with the eye; (8) ventrals 2 + 147–158; (9) subcaudals 64–77, unpaired; (10) dorsal body brownish black, with a bright yellow neck collar extending to the head and abdomen in the occipital region. The recognition of the new species increases the number of described Achalinus species to 28, of which 21 are found in China.

In order to fully grasp the current situation and development trend of mine emergency rescue research in China, based on China National Knowledge Infrastructure database, VOSviewer and CiteSpace were used to conduct bibliometric visualization analysis from multiple perspectives such as the number of publications, research institutions, researchers, journal sources and keywords, and the evolution process of emergency rescue research hotspots was analyzed from three aspects: management, technology and equipment. The results show that the research on mine emergency rescue in China has mainly experienced three stages of development: initial germination, rapid development and high fluctuation, and the number of published papers is on the rise. Research institutions are dominated by universities. The research team is distinctive, but the cooperation needs to be strengthened. At present, the research hotspots focus on emergency plan, emergency command, emergency communication, emergency drill, rescue equipment and IoT monitoring. Information technology plays an increasingly important role in mine disaster perception, transmission, evaluation, decision-making and command. Intelligence, informatization and integration have become the main development trend of mine emergency rescue in the future.

Specimens of Clavulinopsis (Clavariaceae, Agaricales) collected in China were studied using morphological and molecular methods. Six species—C. aspersa, C. bicolor, C. bispora, C. erubescens, C. incarnata, and C. tropicalis—are described as new to science, and C. trigonospora is a newly recorded species in China. Phylogenetic analysis was conducted based on a combined dataset of internal transcribed spacer and nuclear ribosomal RNA large subunit sequences. The phylogenetic reconstruction revealed that the six new species each formed an independent lineage, and the samples of C. trigonospora from China were nested with accessions of C. trigonospora collected from Italy. The morphology of the seven Chinese species is described in detail, and is illustrated with line drawings and photographs. A key to the known Clavulinopsis species in China is provided.

Photoactive black‐phase formamidinium lead triiodide (α‐FAPbI3) perovskite has dominated the prevailing high‐performance perovskite solar cells (PSCs), normally for those spin‐coated, conventional n‐i‐p structured devices. Unfortunately, α‐FAPbI3 has not been made full use of its advantages in inverted p‐i‐n structured PSCs fabricated via blade‐coating techniques owing to uncontrollable crystallization kinetics and complicated phase evolution of FAPbI3 perovskites during film formation. Herein, a customized crystal surface energy regulation strategy has been innovatively developed by incorporating 0.5 mol % of N‐aminoethylpiperazine hydroiodide (NAPI) additive into α‐FAPbI3 crystal‐derived perovskite ink, which enabled the formation of highly‐oriented α‐FAPbI3 films. We deciphered the phase transformation mechanisms and crystallization kinetics of blade‐coated α‐FAPbI3 perovskite films via combining a series of in‐situ characterizations and theoretical calculations. Interestingly, the strong chemical interactions between the NAPI and inorganic Pb−I framework help to reduce the surface energy of (100) crystal plane by 42 %, retard the crystallization rate and lower the formation energy of α‐FAPbI3. Benefited from multifaceted advantages of promoted charge extraction and suppressed non‐radiative recombination, the resultant blade‐coated inverted PSCs based on (100)‐oriented α‐FAPbI3 perovskite films realized promising efficiencies up to 24.16 % (~26.5 % higher than that of the randomly‐oriented counterparts), accompanied by improved operational stability. This result represented one of the best performances reported to date for FAPbI3‐based inverted PSCs fabricated via scalable deposition methods. [ABSTRACT FROM AUTHOR]