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This study presents an interactive visualization-based Model-Based Systems Engineering (MBSE) technique that is especially designed to handle requirements analysis and design issues in joint test settings. Standardized operational requirement description, test requirement analysis, test design, and first test system plan generation are the four primary phases that make up the technique. This method provides a more thorough and approachable depiction of both operational and test requirements by utilizing interactive visualization techniques. This makes it possible for test staff to more accurately and efficiently develop, visualize, and improve test plans. The methodology's efficacy in augmenting the capabilities of joint testing platforms is demonstrated through a thorough case study of a joint test. Higher levels of accuracy and dependability in test results are eventually a result of this approach's strong support for requirements analysis, test design, and the general execution and assessment of joint tests inside complex systems. more...

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. more...

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. more...

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 more...

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. more...

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. more...

Aimed at the problem that the existing K-means clustering (KMC) algorithm is greatly affected by initialization, and the randomly generated clustering center can easily make the clustering result fall into local optimum and stop iterating, resulting in low clustering accuracy and poor robustness, a K-means hybrid iterative clustering algorithm based on memory transfer sailfish optimization (MTSFO-HIKMC) is proposed. First, learning from the existing improvement ideas, the maximum and minimum distance product is introduced to initialize the KMC cluster center, to avoid the uncertainty caused by random initialization. At the same time, in the iterative process, the current optimal solution is made to locally perform adaptive memory transfer correction to solve the problem of poor global optimization ability and insufficient search accuracy caused by the single search path of the sailfish algorithm. Using the Iris, Seeds, CMC and Wine international standard data sets, the MTSFO-HIKMC, the sailfish optimized K-means hybrid iterative clustering (SFO-KMC) algorithm, the introduction of the improved Moth-to-fire K-means cross iterative clustering (IMFO-KMC) algorithm, the KMC algorithm, and the fuzzy C-means (FCM) algorithm are compared and tested. From the obtained convergence curves and performance indicators, it can be seen that the MTSFO-HIKMC algorithm proposed in this paper has a faster convergence speed than IMFO-KMC. Compared with the IMFO-KMC algorithm, the dimensional space has a higher search accuracy. Compared with the KMC algorithm and FCM, it has a higher search accuracy. Compared with the SFO-KMC algorithm, its convergence speed and search accuracy are significantly improved, especially in high-dimensional data sets. more...

Mechanism of action of SNORD89

We constructed the high-quality perovskite films with bottom-up n–p homojunctions via a modified sequential two-step deposition technique, which optimized the energy level alignment between the perovskite layer and the adjacent contacts for promoting charge separation and extraction, as well as suppressing non-radiative recombination. The resultant n–p homojunction-based electron transport layer-free perovskite solar cells achieved improved efficiency, which was ∼13% higher than that of the control counterpart. [ABSTRACT FROM AUTHOR] more...

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. more...

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. more...

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. more...

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. more...

C36H32ClN3O7, orthorhombic, P212121 (no. 19), a = 11.4608(5) Å, b = 12.1489(5) Å, c = 23.1684(7) Å, V = 3225.9(2) Å3, Z = 4, Rgt(F) = 0.0588, wRref(F2) = 0.1546, T = 293 K.

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. more...

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. more...