Search Results (11)

Due to the limitations of planar mode wharfs, this paper proposes a new type of wharf—the three-dimensional cantilevered wharf. The proposed wharf is defined as an improvement of the traditional wharf, extending the traditional wharf upward and cantilevering out to the sea. The three-dimensional cantilevered wharf is a composite truss structure that meets structural and functional requirements. The composite truss structure is formed by connecting the beams of frame structures as a whole. The material consumption of the three-dimensional cantilevered wharf is decreased by controlling stresses and optimizing components. A finite element model of the proposed wharf, with a length of 200 m, width of 105 m, and cantilever length of 80 m, was established to analyze the basic mechanical performance. In this paper, the force distribution of the pile foundation, the vertical force transfer efficiency of web members, the structural stiffness, and the natural frequencies of the proposed wharf are analyzed. Tests regarding the stress and stiffness of different plane cantilever trusses are carried out, and finite element analysis is used for comparison. The test results show that the high-rise cantilever truss has a great in-plane stiffness and a reasonable component stress distribution. Additionally, the three-dimensional cantilevered wharf significantly improves the utilization efficiency of the wharf. Full article

Despite the notable achievements of programmed death 1 (PD-1) antibodies in treating various cancers, the overall efficacy remains limited in the majority of colorectal cancer (CRC) cases. Metabolism reprogramming of tumors inhibits the tricarboxylic acid (TCA) cycle, leading to down-regulation of fumarate hydratase (FH), which is related to poor prognosis in CRC patients. By establishing a tumor-bearing mouse model of CRC with Fh1 expression deficiency, we confirmed that the therapeutic effect of PD-1 antibodies alone was suboptimal in mice with low Fh1 expression, which was improved by combination with a protein invertase subtilisin/kexin 9 (PCSK9) inhibitor. Mechanistically, FH binds to Ras-related nucleoprotein (RAN), which inhibits the nuclear import of the PCSK9 transcription factor SREBF1/2, thus reducing the expression of PCSK9. This leads to increased clonal expansion of CD8+ T cells while the number of Tregs remains unchanged, and the expression of PD-L1 does not change significantly, thus enhancing the immunotherapy response. On the contrary, the expression of PCSK9 increased in CRC cells with low FH expression, which antagonized the effects of immunotherapy. Overall, CRC patients with low FH expression may benefit from combinatorial therapy with PD-1 antibodies and PCSK9 inhibitors to enhance the curative effect. Full article

The latest progress in the field of renal fibrosis mainly focuses on the new concept of “partial epithelial-mesenchymal transition (pEMT)” to explain the contribution of renal tubular epithelial (RTE) cells to renal fibrosis and the crucial role of fatty acid oxidation (FAO) dysfunction in RTE cells for the development of renal fibrosis. FAO depression is considered to be secondary or occur simultaneously with pEMT. We explored the relationship between pEMT and FAO and the effect of rhein on them. Intragastric administration of rhein significantly improved the levels of BUN, Scr, α-SMA, collagen 1A and histopathological changes in UUO-rats. Transcriptomic and metabolomic analyses revealed that abnormal signaling pathways were involved in EMT and FAO disorders. RTE cell experiments showed that TGF-β could inhibit the activity of Cpt1a, resulting in ATP depletion and lipid deposition. Cpt1a inhibitor induced EMT, while Cpt1 substrate or rhein inhibited EMT, indicating that Cpt1a-mediated FAO dysfunction is essential for RTE cells EMT. Further studies showed that Cpt1a activity were regulated by SirT1/STAT3/Twist1 pathway. Rhein inhibits RTE cell EMT by promoting Cpt1a-mediated FAO through the SirT1/STAT3/Twist1 pathway. Surprisingly and importantly, our experiments showed that FAO depression occurs before EMT, and EMT is one of the results of FAO depression. Full article

Upland cotton is the most economically important fibre crop. The human-mediated selection has resulted in modern upland cultivars with higher yield and better fibre quality. However, changes in genome structure resulted from human-mediated selection are poorly understood. Comparative population genomics offers us tools to dissect the genetic history of domestication and helps to understand the genome-wide effects of human-mediated selection. Hereby, we report a comprehensive assessment of Gossypium hirsutum landraces, obsolete cultivars and modern cultivars based on high throughput genome-wide sequencing of the core set of genotypes. As a result of the genome-wide scan, we identified 93 differential regions and 311 selection sweeps associated with domestication and improvement. Furthermore, we performed genome-wide association studies to identify traits associated with the differential regions and selection sweeps. Our study provides a genetic basis to understand the domestication process in Chinese cotton cultivars. It also provides a comprehensive insight into changes in genome structure due to selection and improvement during the last century. We also identified multiple genome-wide associations (GWAS associations) for fibre yield, quality and other morphological characteristics. Full article

Cotton possesses certain physical features, including leaf and stem trichomes that help plants deter damage caused by insect pests, and to some extent, from abiotic factors as well. Among those features, trichomes (pubescence) hold a special place as a first line of defense and a managemental tool against sucking insect pests of cotton. Different insect pests of cotton (whiteflies, aphids, jassids, and boll weevil) severely damage the yield and quality of the crop. Likewise, whiteflies, aphids, jassids, and other insect pests are considered as potential carriers for cotton leaf curl viruses and other diseases. Genotyping by sequencing (GBS) study was conducted to understand and explore the genomic regions governing hairy (Pubescence) leaves and stem phenotypes. A total of 224 individuals developed from an intraspecific cross (densely haired cotton (Liaoyang duomao mian) × hairless cotton (Zong 128)) and characterized phenotypically for leaf and stem pubescence in different environments. Here we identify and report significant QTLs (quantitative trait loci) associated with leaf and stem pubescence, and the response of plant under pest (aphid) infestation. Further, we identified putative genes colocalized on chromosome A06 governing mechanism for trichome development and host–pest interaction. Our study provides a comprehensive insight into genetic architecture that can be employed to improve molecular marker-assisted breeding programs aimed at developing biotic (insect pests) resilient cotton cultivars. Full article

The prognosis of nasopharyngeal carcinoma (NPC) is poor with disease progression. Cadmium exposure is a risk factor for NPC. We aimed to investigate the effect of cadmium exposure, by measuring cadmium level, and clinicopathologic factors on NPC disease progression and prognosis. A total of 134 NPC cases were analyzed and venous blood samples were collected. Blood cadmium level was analyzed by graphite furnace atomic absorption spectrophotometry. Clinical data were collected at baseline for patients and tumor characteristics from medical records. Progression-free survival (PFS) was analyzed during follow-up. The effect of cadmium exposure and clinical factors on PFS was analyzed by the Kaplan–Meier method and Cox regression models. Blood cadmium level was associated with history of disease and smoking history and pack-years. On Kaplan–Meier analysis, a high blood cadmium level, male sex, smoking history and increasing pack-years, as well as advanced clinical stage were all associated with short PFS. On multivariate analysis, blood cadmium level was an independent risk factor and predictor of NPC prognosis and disease progression. Cadmium exposure and related clinical factors can affect the prognosis of NPC, which merits further study to clarify. Full article

Wind turbine anomaly or failure detection using machine learning techniques through supervisory control and data acquisition (SCADA) system is drawing wide attention from academic and industry While parameter selection is important for modelling a wind turbine’s condition, only a few papers have been published focusing on this issue and in those papers interconnections among sub-components in a wind turbine are used to address this problem. However, merely the interconnections for decision making sometimes is too general to provide a parameter list considering the differences of each SCADA dataset. In this paper, a method is proposed to provide more detailed suggestions on parameter selection based on mutual information. First, the copula is proven to be capable of simplifying the estimation of mutual information. Then an empirical copulabased mutual information estimation method (ECMI) is introduced for application. After that, a real SCADA dataset is adopted to test the method, and the results show the effectiveness of the ECMI in providing parameter selection suggestions when physical knowledge is not accurate enough. Full article

The rapid evolution of influenza virus makes antiviral drugs less effective, which is considered to be a major bottleneck in antiviral therapy. The key proteins in the host cells, which are related with the replication cycle of influenza virus, are regarded as potential drug targets due to their distinct advantage of lack of evolution and drug resistance. Cdc2-like kinase 1 (CLK1) in the host cells is responsible for alternative splicing of the M2 gene of influenza virus during influenza infection and replication. In this study, we carried out baculovirus-mediated expression and purification of CLK1 and established a reliable screening assay for CLK1 inhibitors. After a virtual screening of CLK1 inhibitors was performed, the activities of the selected compounds were evaluated. Finally, several compounds with strong inhibitory activity against CLK1 were discovered and their in vitro anti-influenza virus activities were validated using a cytopathic effect (CPE) reduction assay. The assay results showed that clypearin, corilagin, and pinosylvine were the most potential anti-influenza virus compounds as CLK1 inhibitors among the compounds tested. These findings will provide important information for new drug design and development in influenza treatment, and CLK1 may be a potent drug target for anti-influenza drug screening and discovery. Full article

A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide (9m) exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH. Full article

A series of novel aromatic carboxylic acid amides were synthesized and tested for their activities against six phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to good activity. Among them N-(2-(1H-indazol-1-yl)phenyl)-2-(trifluoromethyl)benzamide (3c) exhibited the highest antifungal activity against Pythium aphanidermatum (EC₅₀ = 16.75 µg/mL) and Rhizoctonia solani (EC₅₀ = 19.19 µg/mL), compared to the reference compound boscalid with EC₅₀ values of 10.68 and 14.47 µg/mL, respectively. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were employed to develop a three-dimensional quantitative structure-activity relationship model for the activity of the compounds. In the molecular docking, a fluorine atom and the carbonyl oxygen atom of 3c formed hydrogen bonds toward the hydroxyl hydrogens of TYR58 and TRP173. Full article

We examined the genetic variation and phylogeographic relationships among 10 populations of Lunella granulata from mainland China, Penghu Archipelago, Taiwan Island, and Japan using mitochondrial COI and 16S markers. A total of 45 haplotypes were obtained in 112 specimens, and relatively high levels of haplotype diversity (h = 0.903) and low levels of nucleotide diversity (π = 0.0046) were detected. Four major phylogenetic lineage clusters were revealed and were concordant with their geographic distribution, agreeing with the haplotype network. These results suggested that geographic barrier isolating effects were occurring among the populations. This hypothesis was also supported by a significant genetic differentiation index (F_ST = 0.709) and by a spatial analysis of molecular variance (SAMOVA) analysis. A mismatch distribution analysis, neutrality tests and Bayesian skyline plots found a single significant population expansion. This expansion occurred on the coast of mainland China before 20–17 ka. Consequently, although the dispersal ability of the planktonic stage and the circulation of ocean currents generally promote genetic exchanges among populations, L. granulata has tended to maintain distinct genetic groups that reflect the respective geographic origins of the constituent lineages. Although the circulation of ocean currents, in principle, may still play a role in determining the genetic composition of populations, long-distance migration between regions is difficult even at the planktonic stage. Full article