Autotaxin upregulated by STAT3 activation contributes to invasion in pancreatic neuroendocrine neoplasms

Although the upregulation of autotaxin (ATX) is associated with many solid tumours, its role in pancreatic neuroendocrine neoplasms (pNEN) has not been well elucidated. The expression of ATX in pNEN tissues and pNEN cell line BON1 was analysed by Western blot, PCR and immunocytochemistry upon exposure to interleukin-6 (IL-6). Additionally, pNEN cell line BON1 was transfected with siRNAs against ATX or signal transducer and activator of transcription 3 (STAT3) and assessed by in vitro invasion assays. The following results were obtained. The expression of ATX in pNEN tissues was significantly increased compared with that in normal pancreatic tissues. High ATX expression was strongly correlated with tumour grade, lymph node metastasis and tumour-node-metastasis stage. Furthermore, ATX downregulation notably inhibited the metastatic capacity of pNEN cells, whereas STAT3 knockdown was found to downregulate the expression of ATX. ATX expression was upregulated in BON1 cells upon stimulation with IL-6, and this was accompanied by activation/phosphorylation of STAT3. Western blot analysis of human pNEN tissue extracts confirmed increased ATX expression and STAT3 phosphorylation with elevated expression levels of IL-6. In conclusion, ATX is upregulated in pNEN and is correlated with the metastatic capacity of pNEN cells, potentially via interaction with STAT3 activation

The effect of vector control strategy against Dengue transmission between mosquitoes and humans

With the consideration of mechanism of prevention and control for the spread of dengue fever, a mathematical model of dengue fever dynamical transmission between mosquitoes and humans, incorporating a vector control strategy of impulsive culling of mosquitoes, is proposed in this paper. By using the comparison principle, Floquet theorem and some of analytical methods, we obtain the basic reproductive number $\mathcal{R}_0$ for this infectious disease, which illustrates the stability of the disease-free periodic solution and the uniform persistence of the disease. Further, the explicit conditions determining the backward or forward bifurcation are obtained and the culling rate $\phi$ is a major effect on the occurrence of backward bifurcation. Finally, numerical simulations are given to verify the correctness of theoretical results and the most efficiency of vector control strategy

Influences of graphene oxide support on the electrochemical performances of graphene oxide-MnO2 nanocomposites

MnO2 supported on graphene oxide (GO) made from different graphite materials has been synthesized and further investigated as electrode materials for supercapacitors. The structure and morphology of MnO2-GO nanocomposites are characterized by X-ray diffraction, X-ray photoemission spectroscopy, scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, and Nitrogen adsorption-desorption. As demonstrated, the GO fabricated from commercial expanded graphite (denoted as GO(1)) possesses more functional groups and larger interplane gap compared to the GO from commercial graphite powder (denoted as GO(2)). The surface area and functionalities of GO have significant effects on the morphology and electrochemical activity of MnO2, which lead to the fact that the loading amount of MnO2 on GO(1) is much higher than that on GO(2). Elemental analysis performed via inductively coupled plasma optical emission spectroscopy confirmed higher amounts of MnO2 loading on GO(1). As the electrode of supercapacitor, MnO2-GO(1) nanocomposites show larger capacitance (307.7 F g-1) and better electrochemical activity than MnO2-GO(2) possibly due to the high loading, good uniformity, and homogeneous distribution of MnO2 on GO(1) support

Ubiquitin ligase RNF125 targets PD-L1 for ubiquitination and degradation

As a critical immune checkpoint molecule, PD-L1 is expressed at significantly higher levels in multiple neoplastic tissues compared to normal ones. PD-L1/PD-1 axis is a critical target for tumor immunotherapy, blocking the PD-L1/PD-1 axis is recognized and has achieved unprecedented success in clinical applications. However, the clinical efficacy of therapies targeting the PD-1/PD-L1 pathway remains limited, emphasizing the need for the mechanistic elucidation of PD-1/PD-L1 expression. In this study, we found that RNF125 interacted with PD-L1 and regulated PD-L1 protein expression. Mechanistically, RNF125 promoted K48-linked polyubiquitination of PD-L1 and mediated its degradation. Notably, MC-38 and H22 cell lines with RNF125 knockout, transplanted in C57BL/6 mice, exhibited a higher PD-L1 level and faster tumor growth than their parental cell lines. In contrast, overexpression of RNF125 in MC-38 and H22 cells had the opposite effect, resulting in lower PD-L1 levels and delayed tumor growth compared with parental cell lines. In addition, immunohistochemical analysis of MC-38 tumors with RNF125 overexpression showed significantly increased infiltration of CD4+, CD8+ T cells and macrophages. Consistent with these findings, analyses using The Cancer Genome Atlas (TCGA) public database revealed a positive correlation of RNF125 expression with CD4+, CD8+ T cell and macrophage tumor infiltration. Moreover, RNF125 expression was significantly downregulated in several human cancer tissues, and was negatively correlated with the clinical stage of these tumors, and patients with higher RNF125 expression had better clinical outcomes. Our findings identify a novel mechanism for regulating PD-L1 expression and may provide a new strategy to increase the efficacy of immunotherapy

Decreased circulating omega-3 fatty acids increase the risk of myocardial infarction: a two-sample Mendelian randomization study

BackgroundMany studies have shown that omega-3 fatty acids may play critical roles in cardiovascular diseases. Myocardial infarction (MI) typically results from a thrombotic occlusion of a coronary artery leading to myocardial ischemia. Thus, this study aims to examine the association between omega-3 fatty acids and MI.MethodsA two-sample Mendelian randomization study was used to explore the causal relationship between circulating omega-3 fatty acids and the risk of MI performed by MR-Egger regression, inverse-variance weighted (IVW), weighted median, and weighted mode.ResultsFive single-nucleotide polymorphisms strongly related to circulating omega-3 fatty acids were selected as instrumental variables from a published genome-wide association study (GWAS) meta-analysis including 13,544 subjects. We extracted summary data for the risk of MI from another GWAS meta-analysis including 171,875 individuals (43,676 cases and 128,199 controls). The genetically predicted lower circulating omega-3 increased the risk of myocardial infarction showed by the results of IVW [odds ratio (OR) = 1.224, 95% CI = 1.045–1.433, P = 0.012], weighted median method (OR = 1.171, 95% CI = 1.042–1.315, P = 0.008), and weighted mode (OR = 1.149, 95% CI = 1.002–1.317, P = 0.117), although the result of MR-Egger was not significant (OR = 0.950, 95% CI = 0.513–1.760, P = 0.880) with a wider confidence interval.ConclusionThe findings from our Mendelian randomization analysis suggest that the association between omega-3 fatty acid levels and MI is likely causal

Using High-Density Rain Gauges to Validate the Accuracy of Satellite Precipitation Products over Complex Terrains

Topography and precipitation intensity are important factors that affect the quality of satellite precipitation products (SPPs). A clear understanding of the accuracy performance of SPPs over complex terrains and its relationship with topography is valuable for further improvement of product algorithms. The objective of this study is to evaluate three SPPs—the Climate Prediction Center morphing method bias corrected product (CMORPH CRT), Global Precipitation Measurement Integrated MultisatellitE Retrievals (IMERG), and Tropical Rainfall Measuring Mission 3B42V7 (TRMM 3B42V7) against a high-density network of 104 rain gauges over the Taihang Mountains from 1 January 2016 to 31 December 2017, with special focus on the reliability of products’ performance at different elevation and precipitation intensity. The results show that three SPPs slightly overestimate daily precipitation, compared to rain gauge observations, with bias ratios (β) from 1.02 to 1.06 over the entire regions. In terms of accuracy, 3B42 slightly outperforms CRT and IMERG over the Taihang Mountains. As for different elevation ranges, three SPPs show better performance in terms of accuracy in low and moderate elevation (0–500 m) regions. Similar performances of precipitation detection capability can be found for three products over the whole areas, with detection scores ranging from 0.53 to 0.58. Better precipitation detecting performance of three SPPs was discovered in high-elevation (>1000 m) regions. We adopted a linear regression (LR) model and Locally Weighted Regression (LWR) model in an attempt to discover the linear/non-linear relationships between SPPs’ performances and topographic variations. In the accuracy statistical metrics, the errors of 3B42 and CRT showed significantly positive correlations (p < 0.01) with elevation variations. The critical success index for three products gradually increased with elevation variation based on the LR model. The correlation coefficient and probability of detection for three products showed significant non-linear trends in the LWR model. The probability distribution function for the three products in different elevation regions is similar to that over the entire regions. Three SPPs slightly overestimated the frequency of heavy rain events (6.9 < precipitation intensity (PI) ≤ 19.6 mm/d); CRT and 3B42 tended to underestimate the frequency of no rain events (PI < 0.1 mm/d), while IMERG generally overestimated the frequency of no rain events. Our results not only give a detailed assessment of mainly current SPPs over the Taihang Mountains, but also recommend that further improvement on retrieval algorithm is needed by considering topographical impacts for SPPs in the future

A 2.5-W 40-MHz-bandwidth hybrid supply modulator with 91% peak efficiency, 3-V output swing, and 4-mV output ripple at 3.6-V supply

We describe a supply modulator comprising a proposed delay-based hysteresis controller, proposed wideband class-AB amplifier, and class-D amplifier for an envelope tracking (ET) power amplifier (PA). We investigate the power dissipation and optimization method of the supply modulator for wideband applications taking into consideration the propagation delay, and show that a controller with zero threshold current not only improves the bandwidth of the supply modulator but also reduces its power dissipation. Based on our investigations, we propose a delay-based hysteresis controller embodying a novel high-speed current comparator whose reference current (threshold current) is zero, thereby achieving higher power-efficiency and simpler hardware. We further propose a class-AB amplifier, which features a high bandwidth and accurately controlled quiescent current. The proposed supply modulator features simultaneously the wide bandwidth (40 MHz), high output power (2.5 W), high peak efficiency (91%), high output voltage swing (3 V), and low output ripple noise (4 mVrms) at 3.6-V supply. The ET PA embodying our proposed supply modulator achieves a high power-efficiency of 41.4% at 28.5-dBm peak output power and 34.4% at 3-dB backoff- A significant >1.6× improvement over the radio frequency PA without the supply modulator

Extracellular histone H3 facilitates ferroptosis in sepsis through ROS/JNK pathway

Abstract Introduction Previous evidence realized the critical role of histone in disease control. The anti‐inflammatory function of estradiol (E2) in sepsis has been documented. We here intended to unveil the role of extracellular histone H3 in sepsis regarding cell ferroptosis and the role of E2 in a such mechanism. Methods Clinical sample, cecal ligation and puncture (CLP)‐induced animal models and lipopolysaccharides (LPS)‐induced cell models were prepared for testing relative expression of extracellular histone H3 and E2 as well as analyzing the role of extracellular histone H3 and E2 in sepsis concerning cell viability, reactive oxygen species (ROS), and ferroptosis. Results Under sepsis, we found increased ferroptosis and extracellular histone H3 content, but reduced E2 concentration. Extracellular histone H3 facilitated ferroptosis of human umbilical vein endothelial cells (HUVECs) induced by LPS through activating the ROS/c‐Jun N‐terminal kinase (JNK) pathway. Moreover, E2 antagonized the effect of extracellular histone H3 on LPS‐induced HUVEC ferroptosis and sepsis injury in CLP‐induced animal models. Conclusion We highlighted that extracellular histone H3 facilitated lipopolysaccharides‐induced HUVEC ferroptosis via activating ROS/JNK pathway, and such an effect could be antagonized by E2

Sodium butyrate reduces ammonia production in the cecum of laying hens by regulating ammonia-producing bacteria

ABSTRACT: Sodium butyrate is a commonly used feed additive and can reduce ammonia (NH3) emissions from laying hens, but the mechanism of this effect is unknown. In this study, the sodium butyrate and cecal content of Lohmann pink laying hens were measured, and in vitro fermentation experiments and NH3-producing bacteria coculture experiments were carried out to explore the relationship between NH3 emissions and its associated microbiota metabolism. Sodium butyrate was found to significantly reduce NH3 emission from the cecal microbial fermentation of Lohmann pink laying hens (P < 0.05). The concentration of NO3−-N in the fermentation broth of the sodium butyrate-supplemented group increased significantly, and the concentration of NH4+-N decreased significantly (P < 0.05). Moreover, sodium butyrate significantly reduced the abundance of harmful bacteria and increased the abundance of beneficial bacteria in the cecum. The culturable NH3-producing bacteria consisted mainly of Escherichia and Shigella, such as Escherichia fergusonii, Escherichia marmotae and Shigella flexnerii. Among them, E. fergusonii had the highest potential for NH3 production. The coculture experiment showed that sodium butyrate can significantly downregulate the expression of the lpdA, sdaA, gcvP, gcvH and gcvT genes of E. fergusonii (P < 0.05), thus reducing the NH3 emission produced by the bacteria during metabolism. In general, sodium butyrate regulated NH3-producing bacteria to reduce NH3 production in the cecum of laying hens. These results are of great significance for NH3 emission reduction in the layer breeding industry and for future research

Assessment of Economic Efficiency of Water Use through a Household Farmer Survey in North China

Water use efficiency (WUE) is one of the most widely used indicators in agricultural water management. Although this indicator has obvious advantages, it is limited to measuring the relationship between crop yield and corresponding water use. In recent years, many researchers have noted that understanding the economic efficiency of water use (EEWU) could have great water-saving potential, while it has been poorly investigated with respect to China&rsquo;s agricultural water management. This paper assesses EEWU through a household farmer-level survey in the piedmont region of North China. First, EEWU of crops are estimated based on agricultural water consumption (including irrigation water and effective precipitation) and profit (including gross profit and net profit); Second, the impact of monthly price changes in 2019 and annual price changes in 2014&ndash;2019 on EEWU is analysed. Main conclusions are as follows: (1) EEWU values of cash crops such as apple and cauliflower are much higher than those of grain crops such as wheat and maize; (2) For different crops, the median economic efficiency of irrigation water (EEWiU) and total water (EEWtU) range from 31.71 to 99.54 &yen;/m3 and 11.31 to 44.05 &yen;/m3, respectively; (3) The multi-year average EEWiU and EEWtU ranged from 4.75 to 63.99 &yen;/m3 and from 2.67 to 31.71 &yen;/m3, respectively. Economic efficiency of water use shows a slightly downward trend in the period of study, which would contradict the trend towards the use of more water-efficient technologies and shows an even larger margin of improvement in the domain of agricultural water efficiency. The results provide a powerful reference for the management of agricultural water use through economic leverage