Rice (
Oryza
) is a staple food in China, and rice yield is inherently sensitive to climate change. It is of great regional and global importance to understand how and to what degree climate change ...will impact rice yields and to determine the adaptation options effectiveness for mitigating possible adverse impacts or for taking advantage of beneficial changes. The objectives of this study are to assess the climate change impact, the carbon dioxide (CO
2
) fertilization effect, and the adaptation strategy effectiveness on rice yields during future periods (2011–2099) under the newly released Representative Concentration Pathway (RCP) 4.5 scenario in the Sichuan Basin, one of the most important rice production areas of China. For this purpose, the Crop Estimation through Resource and Environment Synthesis (CERES)-Rice model was applied to conduct simulation, based on high-quality meteorological, soil and agricultural experimental data. The modeling results indicated a continuing rice reduction in the future periods. Compared to that without incorporating of increased CO
2
concentration, a CO
2
fertilization effect could mitigate but still not totally offset the negative climate change impacts on rice yields. Three adaptive measures, including advancing planting dates, switching to current high temperature tolerant varieties, and breeding new varieties, could effectively offset the negative climate change impacts with various degrees. Our results will not only contribute to inform regional future agricultural adaptation decisions in the Sichuan Basin but also gain insight into the mechanism of regional rice yield response to global climate change and the effectiveness of widely practiced global thereby assisting with appropriate adaptive strategies.
Urban traffic pollution, which is strongly influenced by the complex urban morphology, has posed a great threat to human health. In this study, we performed a high-resolution simulation of traffic ...pollution in a typical city block in Baoding, China, based on the Parallelized Large-eddy simulation Model (PALM), to examine the distribution patterns of traffic-related pollutants and explore their relationship with urban morphology. Based on the model results, we conducted a multi-linear regression (MLR) analysis and found that the distribution of air pollutants inside the city block was dominated by both traffic emissions and urban morphology, which explained about 70% of the total variance in spatial distribution of air pollutants. Excluding the contribution of emissions, over 50% of the total variance can still be explained by the urban morphology. Among these urban morphological factors, the key factors determining the spatial distribution of air pollution are “Distance from the road” (DR), “Building Coverage Ratio” (BCR) and “Aspect Ratio” (H/W) of the street canyon. Specifically, urban areas with lower Aspect Ratio, lower BCR and larger DR are less affected by traffic pollution. Compiling these individual factors, we developed a complex Urban Morphology Pollution Index (UMPI). Each unit increase in UMPI is associated with a one percent increase of nearby traffic pollution contribution. This index can help urban planners to semi-quantitatively evaluate building groups which tend to trap or ventilate traffic pollution and thus help to reduce human exposure to street canyon level pollution through either traffic emission control or urban morphology amelioration.
INTRODUCTION
The prevalence of hyperuricenlia （HUA） has increased in China in the recent years in relation to socioeconomic developments and changing lifestyles and diets, with a trend toward onset ...at younger age. HUA has become the second most common metabolic disease after diabetes mellitus. Like gout, HUA is also associated with the occurrence and progression of disorders of the urinary, endocrine, metabolic, cardio-cerebrovascular, and other systems.
Using 4.7 fb^{-1} of e^{+}e^{-} collision data at center-of-mass energies from 4.661 to 4.951 GeV collected by the BESIII detector at the BEPCII collider, we observe the X(3872) production process ...e^{+}e^{-}→ωX(3872) for the first time. The significance is 7.8σ, including both the statistical and systematic uncertainties. The e^{+}e^{-}→ωX(3872) Born cross section and the corresponding upper limit at 90% confidence level at each energy point are reported. The line shape of the cross section indicates that the ωX(3872) signals may be from the decays of some nontrivial structures.
Fangchinoline (Fan) inhibits cell proliferation and induces apoptosis in several cancer cell lines. The effects of Fan on cell growth and proliferation in breast cancer cells remain to be elucidated. ...Here, we show that Fan inhibited cell proliferation in the MDA-MB-231 breast cancer cell line through suppression of the AKT/Gsk- 3beta/cyclin D1 signaling pathway. Furthermore, Fan induced apoptosis by increasing the expression of Bax (relative to Bcl-2), active caspase 3 and cytochrome-c. Fan significantly inhibited cell proliferation of MDA- MB-231 cells in a concentration and time dependent manner as determined by MTT assay. Flow cytometry analysis demonstrated that Fan treatment of MDA-MB-231 cells resulted in cell cycle arrest at the G1 phase, which correlated with apparent downregulation of both mRNA and protein levels of both PCNA and cyclin D1. Further analysis demonstrated that Fan decreased the phosphorylation of AKT and GSK-3beta. In addition, Fan up-regulated active caspase3, cytochrome-c protein levels and the ratio of Bax/Bcl-2, accompanied by apoptosis. Taken together, these results suggest that Fan is a potential natural product for the treatment of breast cancer.
Mammalian reproduction depends on the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone, which are secreted by pituitary gonadotrope cells. The zinc-finger transcription ...factor GATA2 was previously implicated in FSH production in male mice; however, its mechanisms of action and role in females were not determined. To directly address GATA2 function in gonadotropes, we generated and analyzed gonadotrope-specific Gata2 KO mice using the Cre-lox system. We found that while conditional KO (cKO) males exhibited ∼50% reductions in serum FSH levels and pituitary FSHβ subunit (Fshb) expression relative to controls, FSH production was apparently normal in cKO females. In addition, RNA-seq analysis of purified gonadotropes from control and cKO males revealed a profound decrease in expression of gremlin (Grem1), a bone morphogenetic protein (BMP) antagonist. We show Grem1 was expressed in gonadotropes, but not other cell lineages, in the adult male mouse pituitary. Furthermore, Gata2, Grem1, and Fshb mRNA levels were significantly higher in the pituitaries of WT males relative to females but decreased in males treated with estradiol and increased following ovariectomy in control but not cKO females. Finally, we found that recombinant gremlin stimulated Fshb expression in pituitary cultures from WT mice. Collectively, the data suggest that GATA2 promotes Grem1 expression in gonadotropes and that the gremlin protein potentiates FSH production. The mechanisms of gremlin action have not yet been established but may involve attenuation of BMP binding to activin type II receptors in gonadotropes, facilitating induction of Fshb transcription by activins or related ligands.
The orphan G protein-coupled receptor 35 (GPR35) is a potential target for the treatment of pain, inflammation, and metabolic diseases. Although many GPR35 agonists have been discovered, research on ...functional GPR35 ligands, such as fluorescent probes, is still limited. Herein, we developed a series of GPR35 fluorescent probes by conjugating a BODIPY fluorophore to DQDA, a known GPR35 agonist. All probes exhibited excellent GPR35 agonistic activity and desired spectroscopic properties, as determined by the DMR assay, bioluminescence resonance energy transfer (BRET)-based saturation, and kinetic binding experiments. Notably, compound 15 showed the highest binding potency and the weakest nonspecific BRET binding signal (K d = 3.9 nM). A BRET-based competition binding assay with 15 was also established and used to determine the binding constants and kinetics of unlabeled GPR35 ligands.
The metanephric mesenchyme (MM) cells are a subset of kidney progenitor cells and play an essential role in mesenchymal-epithelial transition (MET), the key step of nephron generation. Six2, a ...biological marker related to Wnt signaling pathway, promotes the proliferation, inhibits the apoptosis and maintains the un-differentiation of MM cells. Besides, LiCl is an activator of Wnt signaling pathway. However, the role of LiCl in cellular regulation of MM cells remains unclear, and the relationship between LiCl and Six2 in this process is also little known. Here, we performed EdU assay and flow cytometry assay to, respectively, detect the proliferation and apoptosis of MM cells treated with LiCl of increasing dosages. In addition, reverse transcription-PCR (RT-PCR) and Western-blot were conducted to measure the expression of Six2 and some maker genes of Wnt and bone-morphogenetic-protein (BMP) signaling pathway. Furthermore, luciferase assay was also carried out to detect the transcriptional regulation of Six2. Then we found LiCl promoted MM cell proliferation at low-concentration (10, 20, 30, and 40 mM). The expression of Six2 was dose-dependently increased in low-concentration (10, 20, 30, and 40 mM) at both mRNA and protein level. In addition, both of cell proliferation and Six2 expression in MM cells declined when dosage reached high-concentration (50 mM). However, Six2 knock-down converted the proliferation reduction at 50 mM. Furthermore, Six2 deficiency increased the apoptosis of MM cells, compared with negative control cells at relative LiCl concentration. However, the abnormal rise of apoptosis at 30 mM of LiCl concentration implies that it might be the reduction of GSK3β that increased cell apoptosis. Together, these demonstrate that LiCl can induce the proliferation and apoptosis of MM cells coordinating with Six2.
Photodynamic therapy (PDT) is considered to be effective treatment for many cancers including lung cancer, head and neck cancers, and prostate cancer. It uses the combination of nontoxic ...photosensitizers and harmless visible light to generate reactive oxygen species and kill cells. However, DNA repair and reactive oxygen species‐induced signaling pathway activation play crucial roles in cellular response to PDT and may also result in therapeutic limitation of PDT. To improve the cancer therapeutic efficacy of PDT, we targeted apurinic/apyrimidinic endonuclease (APE1), which is essential for both DNA repair and redox regulation of gene transcription, as a potential candidate for PDT combined gene therapy. In our study, an adenovirus‐mediated APE1 silencing strategy was introduced to test its therapeutic enhancement for the non‐small cell lung cancer cell line A549 both in vitro and in vivo after hematoporphrphyrin derivative (HpD)‐mediated PDT. The adenovirus vector Ad5/F35‐shAPE1 was validated to significantly suppress the protein expression of APE1 in cultured A549 cell and in its xenograft of nude mice. Ad5/F35‐shAPE1 effectively inhibited APE1 protein upregulation induced by PDT and resulted in an increase in A549 cell killing by photoirradiation compared with the hematoporphrphyrin derivative‐PDT alone group. Ad5/F35‐shAPE1 suppressed the DNA repair capacity for single‐strand breaks and abolished the activation of some stress‐related transcription factors such as hypoxia‐induced factor (HIF)‐1 that consequently lead to increased cell apoptosis after PDT. Additionally, knock down of APE1 enhanced the tumor suppression efficacy of PDT on the A549 xenograft. Our study indicated that APE1‐targeted gene therapy combined with PDT is a promising strategy for enhancement of the efficacy of PDT in treatment of non‐small cell lung cancer. (Cancer Sci 2009)
Acute hepatopancreatic necrosis disease (AHPND), caused by certain strains of Vibrio, has resulted in substantial economic losses in global shrimp industries. Hence, developing effective and ...sustainable alternatives to antibiotics to control this disease is of profound importance. In this study, we isolated a strain of antagonistic bacterium, JSHY-K3, from shrimp pond sediment, evaluated its efficacy in preventing AHPND in shrimp and tentatively investigated its mechanism of defence and control against AHPND. The isolated strain exhibited strong antagonistic activity against Vibrio parahaemolyticus, the etiological agent of AHPND (VpAHPND) harboring toxin genes pirA and pirB. JSHY-K3 was identified as B. subtilis based on its morphological, physiological, biochemical characteristics and 16 S rDNA sequence analysis. In vivo challenge assays demonstrated that JSHY-K3 could significantly mitigate cumulative mortality of shrimps infected with VpAHPND, suppress the expression of VpAHPND virulence genes and modulate shrimp immune responses. To elucidate the mechanistic basis of JSHY-K3 in preventing and controlling AHPND, whole-genome sequencing and untargeted metabolomics-LCMS-EMDB analyses were conducted. Whole-genome analysis revealed 12 gene clusters involved in synthesizing of secondary metabolites including the bacteriostatic agents surfactin, aurantinin B/C/D, fengycin, sublancin 168, bacillibactin, subtilosin A and bacilysin. Untargeted metabolomics uncovered 3691 known metabolites, with caffeic acid, fosfomycin, minocycline and surfactin A documented as V. parahaemolyticus growth inhibitors. We hypothesize that the production of these bacteriostatic metabolites by JSHY-K3 underlies its antagonistic effects against VpAHPND. Collectively, these findings suggest B. subtilis JSHY-K3 could be applied as a probiotic to prevent AHPND in shrimp aquaculture.
•JSHY-K3, exhibited strong antagonistic activity, was identified as B. subtilis.•JSHY-K3 could significantly mitigate cumulative mortality of shrimps infected with VpAHPND.•Whole-genome analysis revealed 12 clusters of secondary metabolite synthesis genes with possible bacteriostatic potential.•Untargeted metabolomics found 4 possible inhibitors of V. parahaemolyticus: caffeic acid, fosfomycin, minocycline, surfactin.
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