The human HtrA family of serine proteases (HtrA1, HtrA2, HtrA3, and HtrA4) are the key enzymes associated with pregnancy and closely related to the development and progression of many pathological ...events. Previously, it was found that halogen substitution at the indole moiety of peptide Trp‐1 residue can form a geometrically satisfactory halogen bond with the Drosophila discs large, zona occludens‐1 (PDZ) domain of HtrA proteases. Here, we attempt to systematically investigate the effect of substitution with 4 halogen types and 2 indole positions on the binding affinity and specificity of peptide ligands to the 4 HtrA PDZ domains. The complex structures, interaction energies, halogen‐bonding strength, and binding affinity of domain‐peptide systems were modeled, analyzed, and measured via computational modeling and fluorescence‐based assay. It is revealed that there is a compromise between the local rearrangement of halogen bond involving different halogen atoms and the global optimization of domain‐peptide interaction; the substitution position is fundamentally important for peptide‐binding affinity, while the halogen type can effectively shift peptide selectivity between the 4 domains. The HtrA1‐PDZ and HtrA4‐PDZ as well as HtrA2‐PDZ and HtrA3‐PDZ respond similarly to different halogen substitutions of peptide; –Br substitution at R2‐position and –I substitution at R4‐position are most effective in improving peptide selectivity for HtrA1‐PDZ/HtrA4‐PDZ and HtrA2‐PDZ/HtrA3‐PDZ, respectively; –F substitution would not address substantial effect on peptide selectivity for all the 4 domains. Consequently, the binding affinities of a native peptide ligand DSRIWWV–COOH as well as its 4 R2‐halogenated counterparts were determined as 1.9, 1.4, 0.5, 0.27, and 0.92 μM, which are basically consistent with computational analysis. This study would help to rationally design selective peptide inhibitors of HtrA family members by using different halogen substitutions.
The effect of substitution with 4 halogen types and 2 indole positions on the binding affinity and specificity of peptide ligands to the 4 HtrA PDZ domains is investigated systematically. It is revealed that the substitution position is fundamentally important for ligand affinity, while the halogen type can effectively shift ligand selectivity between the four domains.
In conjunction with the classical functions of regulating intestinal, bone, and kidney calcium and phosphorus absorption, as well as bone mineralization of vitamin D, the population-based association ...between low vitamin D status and increased cancer risk is now generally accepted. Inflammation is causally related to oncogenesis. It is widely thought that vitamin D plays an important role in the modulation of the inflammation system by regulating the production of inflammatory cytokines and immune cells, which are crucial for the pathogenesis of many immune-related diseases. Mechanistic studies have shown that vitamin D influences inflammatory processes involved in cancer progression, including cytokines, prostaglandins, MAP kinase phosphatase 5 (MKP5), the nuclear factor kappa B (NF-κB) pathway, and immune cells. Multiple studies have shown that vitamin D has the potential to inhibit tumor development by interfering with the inflammation system. The present review summarizes recent studies of the mechanisms of vitamin D on regulating the inflammation system, which contributes to its potential for cancer prevention and therapy. This review helps answer whether inflammation mediates a causal relationship between vitamin D and tumorigenesis.
Summary
Sugars increase with drought stress in plants and accumulate in the vacuole. However, the exact molecular mechanism underlying this process is not clear yet. In this study, protein ...interaction and phosphorylation experiments were conducted for sucrose transporter and CIPK kinase in apple. The specific phosphorylation site of sucrose transporter was identified with mass spectrometry. Transgenic analyses were performed to characterize their biological function. It was found that overexpression of sucrose transporter gene MdSUT2.2 in apple plants promoted sugar accumulation and drought tolerance. MdSUT2.2 protein was phosphorylated at Ser381 site in response to drought. A DUALmembrane system using MdSUT2.2 as bait through an apple cDNA library got a protein kinase MdCIPK22. Bimolecular fluorescence complementary (BiFC), pull‐down and co‐immunoprecipitation (Co‐IP) assays further demonstrated that MdCIPK22 interacted with MdSUT2.2. A series of transgenic analysis showed that MdCIPK22 was required for the drought‐induced phosphylation at Ser381 site of MdSUT2.2 protein, and that it enhanced the stability and transport activity of MdSUT2.2 protein. Finally, it was found that MdCIPK22 overexpression promoted sugar accumulation and improved drought tolerance in an MdSUT2.2‐dependent manner in transgenic apple plants. MdCIPK22‐MdSUT2.2 regulatory module shed light on the molecular mechanism by which plant accumulates sugars and enhances tolerance in response to drought stress.
Soil salinity hinders the growth of most higher plants and becomes a gradually increasing threat to the agricultural production of such crops as the woody plant apple. In this study, a calcineurin ...B-like protein (CBL)‐interacting protein kinase, MdCIPK24‐LIKE1 (named as MdSOS2L1), was identified. Quantitative real‐time polymerase chain reaction (qRT‐PCR) assay revealed that the expression of MdSOS2L1 was upregulated by CaCl₂. Yeast two‐hybrid (Y2H) assay and transiently transgenic analysis demonstrated that the MdSOS2L1 protein kinase physically interacted with MdCBL1, MdCBL4 and MdCBL10 proteins to increase salt tolerance in apple. Furthermore, iTRAQ proteome combined with liquid chromatography‐tandem mass spectrometry (LC/MS) analysis found that several proteins, which are involved in reactive oxygen species (ROS) scavenging, procyanidin biosynthesis and malate metabolism, were induced in MdSOS2L1‐overexpressing apple plants. Subsequent studies have shown that MdSOS2L1 increased antioxidant metabolites such as procyanidin and malate to improve salt tolerance in apple and tomato. In summary, our studies provide a mechanism in which SOS2L1 enhances the salt stress tolerance in apple and tomato.
A microstrip bandpass filter using stepped-impedance resonators is designed in low-temperature co-fired ceramic technology for dual-band applications at 2.4 and 5.2 GHz. New coupling schemes are ...proposed to replace the normal counterparts. It is found that the new coupling scheme for the interstages can enhance the layout compactness of the bandpass filter; while the new coupling scheme at the input and output can improve the performance of the bandpass filter. To validate the design and analysis, a prototype of the bandpass filter was fabricated and measured. It is shown that the measured and simulated performances are in good agreement. The prototype of the bandpass filter achieved insertion loss of 1.25 and 1.87 dB, S 11 of -29 and -40 dB, and bandwidth of 21% and 12.7% at 2.4 and 5.2 GHz, respectively. The bandpass filter is further studied for a single-package solution of dual-band radio transceivers. The bandpass filter is, therefore, integrated into a ceramic ball grid array package. The integration is analyzed with an emphasis on the connection of the bandpass filter to the antenna and to the transceiver die
In this study, the causal link amid economic growth, fossil fuel energy consumption, carbon emissions and oil price was empirically tested from 1990 to 2015 by using a panel of 22 African countries. ...The sample of African countries was divided into two subgroups namely; Oil exporters and Non-oil exporters. Using the PMG panel ARDL and panel econometric methods, heterogeneity and cross-sectional dependence were considered to examine the long and short-term dynamic relationships as well as validity of a proposed model. Findings from the Pesaran-Yamagata homogeneity test, Pesaran CD test, CIPS and CADF panel unit root tests and Westerlund-Edgerton bootstrap panel cointegration indicated, the panel time series data has heterogeneity and cross-sectional dependence, analysed variables are stationary and cointegrated respectively. With respect to the PMG panel ARDL estimation method it was evidenced that there exist, (i) a bilateral causal link flanked by fossil fuel energy consumption and economic growth as well as fossil fuel energy consumption and carbon emissions in long and shot-terms for all panels, (ii) a unilateral causality from carbon emissions to economic growth in long-term and short-term for non-oil exporters nonetheless a bilateral causal relationship only in long-term for oil exporting countries, and (iii) a unilateral cause-and-effect link from oil prices to economic growth, energy consumption (fossil fuel) and carbon emission across all country groups in long and short-terms. Policy recommendations are further discussed.
The identification of phosphorus (P) fractions is essential for understanding the transformation and availability of P in paddy soils. To investigate the soil P fractions associated with soil ...properties under long-term fertilization, we selected three fertilization treatments, including no fertilization (CK), chemical fertilizers (NPK) and chemical fertilizers combined with manure (NPKM), from three long-term experiments located in Nanchang (NC), Jinxian (JX) and Ningxiang (NX). The results showed that chemical fertilizers combined with manure (NPKM) significantly (P ≤ 0.05) increased the soil total phosphorus, Olsen P and soil organic matter (SOM) by 2, 3 and 1 times, respectively, compared with the NPK treatment, and by 4, 17 and 2 times, respectively, compared with the CK treatment. NPKM significantly increased the grain yield compared with CK and NPK at all sites. The apparent P balance with NPK was higher in NC and NX but lower in JX compared with NPKM. Hedley fractionation revealed the predominance of most of the organic and inorganic phosphorus (Po and Pi) fractions with long-term fertilization, especially with the NPKM treatment, at all sites. The nonlabile P pool decreased by 14% and 18% whereas the moderately labile P pool proportions increased by 3 and 6 times with the NPK and NPKM treatments, respectively, compared to the CK treatment. The labile P pool showed a significant positive relationship with the SOM, total P and Olsen P contents. The moderately labile P was positively correlated with the total P and Olsen P. A significant positive correlation was observed between soil pH and the nonlabile P pool. Redundancy analysis revealed that the moderately labile P fraction (HCl dil. Pi fraction) was remarkably increased by the NPKM treatment and significantly correlated with the soil pH and total P concentration. The labile P fraction (NaHCO3-Pi) showed a strong relationship with the Olsen P and total P. However, the residual P fraction was negatively correlated with the HCl. dil. Pi fraction. We concluded that NPKM application improved P availability by many folds compared to NPK, which could lead to environmental pollution; therefore, the rate of combined application of manure and chemical fertilizer should be reduced compared to chemical fertilizer inputs to minimize the wastage of resources and environmental P losses.
China has become the largest producer and consumer of cement worldwide. In 2011, carbon emissions of China’s cement industries accounted for 60.6% of cement carbon emissions worldwide. In this ...context, this paper mainly investigates whether eco-efficiency of China’s cement manufacturers has converging tendency or not. First, we evaluated eco-efficiency under directional distance function (DDF) and the directional slack-based measure (DSBM) to compare their biases. Furthermore, we also implement unit root test of panel data to testify convergence analysis upon eco-efficiency in different regions of China in order to overcoming the demerit of conventional convergence approach, which might have invalid inferences. Our empirical analysis revealed that eco-efficiency under DDF has gaps with that under DSBM due to excess input or output shortages. Eco-efficiency in the east, middle and west converged. It is necessary to substitute raw material, increase additive and improve waste use for China’s cement manufacturers.
•We verify the convergence of eco-efficiency through unit root test.•Eco-efficiency in cement manufacturers converged in the east, middle and west.•China’s cement manufacturers should substitute raw material.
Extensive investigations into long noncoding RNAs (lncRNAs) in various diseases and cancers, including acute myocardial infarction (AMI) have been conducted. The current study aimed to investigate ...the role of lncRNA solute carrier family 8 member A1 antisense RNA 1 (SLC8A1‐AS1) in myocardial damage by targeting solute carrier family 8 member A1 (SLC8A1) via cyclic guanosine 3′,5′‐monophosphate‐protein kinase G (cGMP‐PKG) signaling pathway in AMI mouse models. Differentially expressed lncRNA in AMI were initially screened and target relationship between lncRNA SLC8A1‐AS1 and SLC8A1 was then verified. Infarct size, levels of inflammatory factors, biochemical indicators, and the positive expression of the SLC8A1 protein in AMI were subsequently determined. The expression of SLC8A1‐AS1, SLC8A1, PKG1, PKG2, atrial natriuretic peptide, and brain natriuretic peptide was detected to assess the effect of SLC8A1‐AS1 on SLC8A1 and cGMP‐PKG. The respective contents of superoxide dismutase, lactate dehydrogenase (LDH), and malondialdehyde (MDA) were detected accordingly. Microarray data GSE66360 provided evidence indicating that SLC8A1‐AS1 was poorly expressed in AMI. SLC8A1 was verified to be a target gene of lncRNA SLC8A1‐AS1. SLC8A1‐AS1 upregulation decreased levels of left ventricular end‐systolic diameter, −dp/
dt
max, interleukin 1β (IL‐1β), IL‐6, transforming growth factor α, nitric oxide, inducible nitric‐oxide synthase, endothelial nitric‐oxide synthase, infarct size, LDH activity and MDA content, and increased IL‐10, left ventricular end‐diastolic pressure and +
dp/
dt
max. Furthermore, the overexpression of SLC8A1‐AS1 was noted to elicit an inhibitory effect on the cGMP‐PKG signaling pathway via SLC8A1. In conclusion, lncRNA SLC8A1‐AS1, by downregulating SLC8A1 and activating the cGMP‐PKG signaling pathway, was observed to alleviate myocardial damage, inhibit the release of proinflammatory factors and reduce infarct size, ultimately protecting against myocardial damage.
In conclusion, long noncoding RNA (lncRNA) solute carrier family 8 member A1 antisense RNA 1 (SLC8A1‐AS1), by downregulating solute carrier family 8 member A1 (SLC8A1) and activating cyclic guanosine 3′,5′‐monophosphate‐protein kinase G (cGMP‐PKG) signaling pathway, was observed to alleviate myocardial damage, inhibit the release of proinflammatory factors and reduce infarct size, ultimately protecting against myocardial damage.
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