In this communication, we report a substrate‐controlled product diversity in the 1,5,7‐triazabicyclo4.4.0dec‐5‐ene (TBD)‐catalyzed cascade cyclization of 2‐alkynyl‐3,3‐difluoro‐3H‐indoles with N,N‐ ...or N,S‐bis‐nucleophiles. The products represent two important heterocyclic compounds, C2‐spiro indoline, and pyrimido1,2‐abenzimidazole, featuring a versatile gem‐difluoromethylene group on the framework. In these cascade processes, two new C−N bonds, or one C−S and one C−N bond, are consecutively formed in a single step. The present protocol is characterized with high regioselectivity, high yield, broad substrate scope, good functional group tolerance, facile scalability and mild reaction conditions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The XRF, XRD, polarizing microscopy and SEM-EDS were used to study the alteration mechanism of copper-bearing biotite and the leachable property of copper-bearing minerals in Mulyashy Copper Mine, ...Zambia. It was found that biotite can be divided into copper-bearing biotite and copper-free biotite. Some copper-bearing biotite existed in the form of monomer, and others aggregated with copper-bearing chlorite, malachite or copper-bearing limonite. The main reason for the occurrence of biotite aggregations was that copper-bearing biotite underwent two kinds of alteration mechanisms as follows: altering into copper-bearing chlorite and malachite, and altering into copper-bearing chlorite and copper-bearing limonite. The order of factors effecting the copper leaching rate of the ores in acid leaching experiments was temperature > sample size > H
SO
concentration > leaching time > stirring speed. In addition, the copper leaching rate of copper-bearing minerals at different temperatures was in the following order: malachite, chrysocolla and pseudomalachite > copper-bearing chlorite > copper-bearing muscovite > copper-bearing biotite > copper-bearing limonite. The leachable property of biotite is closely related to its special structure.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The Geographical Detector Model (GDM) is a popular statistical toolkit for geographical attribution analysis. Despite the striking resemblance of the q-statistic in GDM to the R-squared in linear ...regression models, their explicit connection has not yet been established. This study proves that the q-statistic reduces into the R-squared under a linear regression framework. Under linear regression and moderate-to-strong spatial autocorrelation, Monte Carlo simulation results show that the GDM tends to underestimate the importance of variables. In addition, an almost perfect power law relationship is present between the percentage bias and the degree of the spatial autocorrelations, indicating the presence of fast uplifting bias in response to increasing levels of spatial autocorrelations. We propose an integrated approach for variable importance quantification by bringing together the spatial econometrics model and the game theory based-Shapley value method. By applying our proposed methodology to a case study of land desertification in African, it is found human activity tends to affect land desertification both directly and indirectly. However, such effects appear to be underestimated or undistinguished in the classic GDM.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
This study aimed to explore the potential link between coffee and tea consumption and the risk of deep vein thrombosis (DVT) through Mendelian randomization (MR) analysis. Employing the MR, we ...identified 33 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for coffee intake and 38 SNPs for tea intake. The investigation employed the inverse-variance weighted (IVW) method to evaluate the causal impact of beverage consumption on DVT risk. Additionally, MR-Egger and MR-PRESSO tests were conducted to assess pleiotropy, while Cochran's Q test gauged heterogeneity. Robustness analysis was performed through a leave-one-out approach. The MR analysis uncovered a significant association between coffee intake and an increased risk of DVT (odds ratio OR 1.008, 95% confidence interval CI = 1.001-1.015, P = 0.025). Conversely, no substantial causal effect of tea consumption on DVT was observed (OR 1.001, 95% CI = 0.995-1.007, P = 0.735). Importantly, no significant levels of heterogeneity, pleiotropy, or bias were detected in the instrumental variables used. In summary, our findings suggest a modestly heightened risk of DVT associated with coffee intake, while tea consumption did not exhibit a significant impact on DVT risk.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Transcription factors (TFs) coordinate the on-and-off states of gene expression typically in a combinatorial fashion. Studies from embryonic stem cells and other cell types have revealed that a ...clique of self-regulated core TFs control cell identity and cell state. These core TFs form interconnected feed-forward transcriptional loops to establish and reinforce the cell-type-specific gene-expression program; the ensemble of core TFs and their regulatory loops constitutes core transcriptional regulatory circuitry (CRC). Here, we summarize recent progress in computational reconstitution and biologic exploration of CRCs across various human malignancies, and consolidate the strategy and methodology for CRC discovery. We also discuss the genetic basis and therapeutic vulnerability of CRC, and highlight new frontiers and future efforts for the study of CRC in cancer. Knowledge of CRC in cancer is fundamental to understanding cancer-specific transcriptional addiction, and should provide important insight to both pathobiology and therapeutics.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this study, juvenile cobia fish (Rachycentron canadum) (body weight: 50.44 ± 2.78 g) were used as a study object to investigate the effects of hypoxia stress (dissolved oxygen: 3.15 ± 0.21 mg/L) ...on the activities of their digestive enzymes, intestinal morphology and relative expression of tight junction proteins coding genes. Under the experimental conditions, the juvenile cobia were given 28 days of hypoxia stress. The results showed that the activities of digestive enzymes in the intestines of the hypoxia stress group decreased. In addition, the amylase and lipase activities decreased significantly (p < 0.05), and the trypsin activity in the hypoxia stress group compared to that in the control group. The morphology and structure of the intestine also showed significant changes. Under the microscopic observation, the mucosal fold height and muscle thickness of the intestine showed a significant decrease (p < 0.05); also, the villi's width showed a significant decrease (p < 0.05) in the hypoxia stress group as compared to that in the control group. The observation under a transmission electron microscope showed that the microvilli of juvenile cobia in the hypoxia stress group were irregularly arranged, atrophied and fallen off compared to the control group. Furthermore, there were gaps in the tight junction. In addition, the boundary between cells was unclear. The relative expression of intestinal tight junction proteins coding genes was down‐regulated to varying degrees. The mRNA expressions of ZO‐1 and claudin‐4 were significantly down‐regulated (p < 0.05) and ZO‐2 and occludin in the hypoxia stress group compared to those in the control group. These results indicated that hypoxia stress could inhibit the activities of intestinal digestive enzymes, damage intestinal morphology and decrease the expression of tight junction proteins coding genes in cobia. The present study provided a scientific foundation for evaluating the multifaceted impacts of hypoxia stress on fish species, such as cobia.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The construction of benzopyrone‐fused hydrobenzofuranones via DABCO‐catalyzed 3+2 cyclization/deformylation cascade of p‐quinols with 3‐formylchromones is described. The reaction works under mild ...reaction conditions to provide the desired products in 53–90% yields with complete diastereoselectivities. In addition, an enantioselective version with 81% ee is also realized in the presence of Takemoto's chiral thiourea catalyst.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Although “We-media” appeared earlier in foreign countries, its emergence in our country is relatively recent. It has the characteristics of commonality, low registration cost and fast information ...dissemination, which is favored by people of all ages, especially young people. The rise of “We-media” not only brings development opportunities to network security, but also can expand the scope of influence for publicizing network security credibility to a certain extent. However, at the same time, it also brings new challenges to network security. As a college educator, the author tries to analyze network security dialectically from the perspective of “We-media”, so as to further explain its influence on ideological and political education in colleges and universities. How to effectively manage the application and implementation of “We-media” and maintain a good network security environment is an important topic we will face in the current and future period.
Mitochondrial calcium (Ca
) uptake shapes cytosolic Ca
signals involved in countless cellular processes and more directly regulates numerous mitochondrial functions including ATP production, ...autophagy and apoptosis. Given the intimate link to both life and death processes, it is imperative that mitochondria tightly regulate intramitochondrial Ca
levels with a high degree of precision. Among the Ca
handling tools of mitochondria, the leucine zipper EF-hand containing transmembrane protein-1 (LETM1) is a transporter protein localized to the inner mitochondrial membrane shown to constitute a Ca
/H⁺ exchanger activity. The significance of LETM1 to mitochondrial Ca
regulation is evident from Wolf-Hirschhorn syndrome patients that harbor a haplodeficiency in LETM1 expression, leading to dysfunctional mitochondrial Ca
handling and from numerous types of cancer cells that show an upregulation of LETM1 expression. Despite the significance of LETM1 to cell physiology and pathophysiology, the molecular mechanisms of LETM1 function remain poorly defined. In this review, we aim to provide an overview of the current understanding of LETM1 structure and function and pinpoint the knowledge gaps that need to be filled in order to unravel the underlying mechanistic basis for LETM1 function.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A 600-km/h maglev train can effectively close the speed gap between civil aviation and rail-based trains, thereby alleviating the conflict between the existing demand and actual capacity. However, ...the hazards caused by the micro-pressure wave amplitude of the tunnel that occurs when the train is running at higher speeds are also unacceptable. At this stage, mitigation measures to control the amplitude of micro-pressure waves generated by maglev trains at 600 km/h within reasonable limits are urgent to develop new mitigation measures. In this study, a three-dimensional, compressible, unsteady SST K–ω equation turbulence model, and an overlapping grid technique were used to investigate the mechanism and mitigation effect of Helmholtz resonators with different arrangement schemes on the micro-pressure wave amplitude at a tunnel exit in conjunction with a 600-km/h maglev train dynamic model test. The results of the study showed that a pressure wave forms when the train enters the tunnel and passes through the Helmholtz resonator. This in turn leads to resonance of air column at its neck, which causes pressure wave energy dissipation as the incident wave frequency is in the resonator band. This suppresses the rise of the initial compressional wave gradient, resulting in an effective reduction in the micro-pressure wave amplitude at the tunnel exit. Compared to conventional tunnels, the Helmholtz resonator scheme with a 94-cavity new tunnel resulted in a 31.87% reduction in the micro-pressure wave amplitude at 20 m from the tunnel exit but a 16.69% increase in the maximum pressure at the tunnel wall. After the Helmholtz resonators were arranged according to the 72-cavity optimization scheme, the maximum pressure at the tunnel wall decreased by 10.57% when compared with that before optimization. However, the micro-pressure wave mitigation effect at 20 m from the tunnel exit did not significantly differ from that before the optimization.
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