NUMERICAL AND EXPERIMENTAL STUDY ON RESISTANCE OF ASYMMETRIC CATAMARAN WITH DIFFERENT LAYOUTS

It is meaningful to study the wave-resistance reduction of an asymmetric catamaran because of interference effects between the two sets of ship-generated waves. The influence of lateral separation and longitudinal stagger on the resistance and the wave interference are analyzed within this paper. Numerical calculations of resistance, sinkage and trim of the asymmetric catamaran are carried out for several Froude number ranging from 0.24 to 0.48, for six different lateral separations and four longitudinal staggers. Verification of numerical results is provided. The model tests are then carried out for three stagger distances to validate the numerical results. Results of this study indicate that the wave-resistance can be effectively reduced by certain hull layouts at different Froude numbers

Programmable base editing of zebrafish genome using a modified CRISPR-Cas9 system.

Precise genetic modifications in model animals are essential for biomedical research. Here, we report a programmable "base editing" system to induce precise base conversion with high efficiency in zebrafish. Using cytidine deaminase fused to Cas9 nickase, up to 28% of site-specific single-base mutations are achieved in multiple gene loci. In addition, an engineered Cas9-VQR variant with 5'-NGA PAM specificities is used to induce base conversion in zebrafish. This shows that Cas9 variants can be used to expand the utility of this technology. Collectively, the targeted base editing system represents a strategy for precise and effective genome editing in zebrafish.The use of base editing enables precise genetic modifications in model animals. Here the authors show high efficient single-base editing in zebrafish using modified Cas9 and its VQR variant with an altered PAM specificity

Geochemical evidence for in situ accumulation of tight gas in the Xujiahe Formation coal measures in the central Sichuan Basin, China

The study of accumulation mechanisms of tight gas has attracted much attention in recent years. One of the focuses is whether natural gas can migrate on a large scale in tight reservoirs. In this work, geochemical parameters (such as C1/C1+, C1/(C2+ C3), C1+, δ13C1, δ13C2, iC4/nC4, iC5/nC5) of the tight gas reservoirs in the central Sichuan Basin, China have been studied to characterize the accumulation mechanisms in these fields. Results show that the tight gas accumulation in the Xujiahe Formation in the central Sichuan is in situ, and natural gas has not experienced large-scale migration. In gases from the central Sichuan Basin, δ13C1 ranges from −44.1‰ to −37.1‰ with an average of −40.1‰, and C1/C1+ ranges from 0.80 to 0.97 with an average of 0.91. While in the gases from the western Sichuan Basin, δ13C1 is between −35.5‰ and − 30‰ with an average of −32.2‰, and C1/C1+ ranges from 0.95to 0.99with an average of 0.98. Based on geochemical indicators of natural gas, the gases of Xujiahe Formation in the Central Sichuan Basin originated from the local coal measures of the Xujiahe Formation in horizontal direction with little contribution from the western Sichuan. In central Sichuan Basin, there is also no horizontal migration of natural gas in the same formation between adjacent gas fields. Vertically, the Xujiahe Formation is an independent gas generating system and has no relationship with the underlying Mid-Lower Triassic formations and the Jurassic natural gas formation above it. The δ13C2of Xujiahe Formation in central Sichuan ranges from −28.3‰ to −25.9‰, with an average of −27.5‰. However, the δ13C2 of Lower Jurassic above Xujiahe Formation ranges from −36.8‰ to −30.5‰, with an average of −33.0‰. Under the Xujiahe Formation, the δ13C2 in Leikoupo Formation ranges from −35.5‰ to −32.1‰, with an average of −33.1‰, and in Jialingjiang Formation ranges from −34.6‰ to −33.2‰, with an average of −33.8‰. There is also a clear distinction in the geochemical characteristics of natural gas between the upper and lower gas reservoirs in the Xujiahe Formation, indicating that there is no obvious vertical migration of natural gas. Geochemical evidence shows that there is no large-scale gas migration in the Xujiahe Formation. The tight gas is generated in situ and accumulated in the formation in the central Sichuan Basin

miR-221/222 promotes S-phase entry and cellular migration in control of basal-like breast cancer.

The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both significantly suppressed cellular migration, invasion and G1/S transition of the cell cycle in BLBC cell types. Proteomic analysis demonstrated the down-regulation of two tumor suppressor genes, suppressor of cytokine signaling 1 (SOCS1) and cyclin-dependent kinase inhibit 1B (CDKN1B), by miR-221/222. This is the first report to reveal miR-221/222 regulation of G1/S transition of the cell cycle. These findings demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC

Analysis of temporal variation characteristics in water resources in typical ecosystems of the Genhe River Basin

The Genhe River Basin is an ecological barrier and water conservation area in northern China, but its hydrological process has undergone significant changes due to climate change and human activities, endangering ecosystem functions and water resource security. Systematic research on the influencing mechanisms and laws of hydrological processes in different ecosystems in this region remains lacking. Therefore, this study analyzed the effects of different anthropogenic factors on the hydrological processes of typical ecosystems in the Genhe River Basin. The Soil and Water Assessment Tool distributed hydrological model was used to simulate the surface runoff, evapotranspiration, and soil water content of the three ecosystems of forest, grassland, and farmland in four different periods of 1980, 1990, 2000, and 2010. The spatial and temporal changes in water resources in typical ecosystems under the influence of historical climate change were demonstrated. Results showed that under different land use scenarios, the surface runoff of the farmland ecosystem increased, the evapotranspiration remained unchanged, and the soil water content decreased. The surface runoff of forest and grassland ecosystems did not change significantly, the evapotranspiration increased, and the soil water content decreased. This study reveals the influence of different human factors on the hydrological processes of typical ecosystems in the Genhe River Basin and provides a scientific basis for water resources management and ecological protection in the region

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Synthesis and Biological Testing of Quinone-Based Natural Products

Natural products are organic molecules produced by living organisms in nature. Many of them exhibit interesting biological activities and have pharmaceutical potential. However, they exist in only very small amounts in nature which poses a limitation in the discovery of their medicinal properties; therefore, synthesizing natural products in the lab in sufficient amounts is meaningful to enable scientists to better study their properties. Quinones are a class of very versatile organic molecules, ubiquitously in living organisms. Many quinones are involved in biological functions, such as the electron transport chain. This paper is divided into two projects involving quinone natural product synthesis. The first project describes the synthesis of 3- methylbuteneoxide-1,4-anthraquinone (3.8), which is a mitochondrial complex I (MCI) inhibitor with an IC50 of 5 μM, utilizing substrate-based inhibitor design. Compound 3.8 also has high inhibitory selectivity for MCI when tested against other quinone-converting enzymes, including succinate dehydrogenase, and the Na (+)-translocating NADH:quinone oxidoreductase. Additionally, it also shows anti-cancer proliferation properties comparable to doxorubicin in cell-based proliferation assays. The second project describes the discovery of a cyclization reaction yielding the natural product and potent anti-cancer agent Chimaphilin, which was discovered during the optimization of the reaction in the first project. Reaction optimization, the proposed mechanism, and regioisomer identification are discussed

Comparison of different intervention methods to reduce the incidence of venous thromboembolism: study protocol for a cluster-randomized, crossover trial

Abstract Background Venous thromboembolism (VTE) remains a priority challenge among orthopedic trauma patients. It is crucial to further improve the prophylaxis against VTE in routine orthopedic treatment. This study aims to compare the efficacy of two low molecular weight heparin (LMWH) regimens and additional intermittent pneumatic compression in preventing VTE among orthopedic trauma patients. Methods and analysis This is a cluster-randomized crossover clinical study conducted in four hospitals in Shanghai from December 2019 to December 2023. The unit of randomization is orthopedic wards, and each ward will define a cluster. All clusters will implement four diverse intervention measures and one control measure in a given random sequence. Perioperative orthopedic trauma patients aged ≥ 18 years with stable vital signs, Caprini score > 2, and no contraindication of anticoagulation or intermittent pneumatic compression (IPC) devices will be eligible. The sample size will be determined to be 2590, considering cluster effect, period effect, and interactions. We will generally use the intention-to-treat (ITT) at the subject level for each outcome. For the primary outcome of the study, the incidence of VTE will be presented as risk ratio and 95% CIs. Generalized estimating equation (GEE) will be deployed to compare differences and adjust cluster effect, period effect, and interaction among interventions and periods if applicable. Discussion VTE is a complication that cannot be underestimated after major orthopedic surgery. Early identification, early assessment, and early prevention can significantly reduce the incidence of VTE. Most guidelines recommend both medical and physical prevention, and we hope to demonstrate how they would affect the incidence among perioperative orthopedic patients. We want to explore if there is a difference between the two types of LWMH with or without an IPC device to provide more evidence for future guidelines and prevent more patients from the threat of VTE. Ethics and dissemination The study received approval from the IRB of the coordinating center and all participating hospitals. Findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration ChiCTR1900027659. Registered on 17 November 201