Preeclampsia, defined as a hypertensive disorder during pregnancy, is a major cause of maternal and fetal mortality. Observational studies have shown that the exposure of per- and polyfluoroalkyl ...substances, such as perfluorooctane sulfonate (PFOS), is emerging as a significant environmental factor associated with preeclampsia risk. However, epidemiologic evidence is of correlative in nature, and unable to establish a causal relationship. Here, we established an animal model of PFOS-induced preeclampsia to explore the molecular mechanism of PFOS in placental trophoblast. In the mouse model, PFOS exposure by gavage at a dose of 10 mg/kg/d from embryonic day 7.5–16.5 was sufficient to induce preeclampsia-like symptoms such as hypertension, proteinuria, and renal glomerular endotheliosis, accompanied with placental abnormal stromal collagen deposition. In-vitro experiments of JEG-3 cells, PFOS exposure impaired trophoblast motility including the compromised abilities of migration, invasion and vascularization. Mechanistically, these pathological effects on cells resulted from SLC25A5-mediated mitochondrial damages, characterized by excessive ROS generation, decreased ATP production and mitochondrial membrane potential loss, and accompanied by the activation of p38 MAPK and JNK signaling pathways. This pioneering study provided biological plausibility to the causality verified by the animal model and the in vitro experiments, which indicates that PFOS exposure may cause preeclampsia during pregnancy via impairing trophoblast mitochondria.
•Animal models and in vitro experiments shed light on the causality between PFAS and preeclampsia.•PFOS exposure by gavage was sufficient to induce preeclampsia-like phenotypes in pregnant mice.•PFOS exposure induced mitochondrial damages accompanied by the activation of p38 and JNK MAPK signaling pathway.
A
bstract
We have studied color-octet contributions for
J/ψ
inclusive production at B factories, i.e.,
e
+
e
−
→
J/ψ
(
3
P
J
8
,
1
S
0
8
) +
X
non
−
c
c
¯
, using the soft gluon factorization (SGF) ...approach, in which the
J/ψ
energy spectrum is expressed in a form of perturbatively calculable short-distance hard parts convoluted with one-dimensional soft gluon distributions (SGDs). The series of velocity corrections originated from kinematic effect can be naturally resummed in this approach. Short-distance hard parts have been calculated analytically to next-to-leading order in
α
s
. Renormalization group equations for SGDs have been derived and solved, which resums Sudakov logarithms originated from soft gluon emissions. Our final result gives a upper bound for color-octet matrix elements consistent with that extracted from hadron colliders. This may relieve the well-known universality problem in the NRQCD factorization.
As a comparison, we also analytically calculated short-distance hard parts in the NRQCD factorization, with Sudakov logarithms resummed by using soft collinear effective theory. The comparison shows that velocity corrections from kinematic effect, which have been resummed in SGF, are significant for phenomenological study. Furthermore, it is found that Sudakov logarithms originated from soft gluon emissions are very important, while it is not the case for Sudakov logarithms originated from jet function. Therefore, the partial Sudakov resummation in SGF has already captured the main physics.
Assessing the response of flood risk caused by climate change and social development is very important in terms of determining high risk areas in different periods as well as making disaster ...mitigating plans. We establish a flood risk assessment model based on geographic information system and natural disaster risk assessment theory. In order to compare the index value in different periods and spaces, we utilize the spatial and temporal standardization method to standardized index. To avoid one-sidedness caused by using one weight calibration method only, we employ the least square method to synthesize weights determine by the Analytic Hierarchy Process (AHP) method and the Entropy weight method. We adopt the observed data of the Huaihe River basin from 1960 to 2010 to assess the changing of flood risk between period I (1960–1980) and period II (1980–2010). After pre-processing the atmosphere–ocean coupled global circulation models (AOGCM) data, including bias correction and downscaling, we use the corrected data to predict the flood risk during future period III (2010–2040). The results show that high risk areas and moderate to high risk areas during period I take up 17.68 and 33.88 % of the total area of the Huaihe River basin, respectively. During period II, the high risk areas show an increasing percent change of 1.93 % and a decreasing trend in moderate to high risk areas of 3.8 %. Compared with period II, the high risk areas and the moderate to high risk areas during period III show an increasing trend of 8.02 and 0.77 %, which is the result of the combined effects of climate change and social development. The results presented here can provide useful information for decision-makers.
The objectives of the study were to explore the mechanism of rotenone-induced cell damage and to examine the protective effects of water-soluble Coenzyme Q10 (CoQ10) on the toxic effects of rotenone. ...Murine hippocampal HT22 cells were cultured with mitochondrial complex I inhibitor rotenone. Water-soluble CoQ10 was added to the culture media 3 h prior to the rotenone incubation. Cell viability was determined by alamar blue, reactive oxygen species (ROS) production by dihydroethidine (DHE) and mitochondrial membrane potential by tetramethyl rhodamine methyl ester (TMRM). Cytochrome c, caspase-9 and apoptosis-inducing factor (AIF) were measured using Western blotting after 24 h rotenone incubation. Rotenone caused more than 50% of cell death, increased ROS production, AIF nuclear translocation and reduction in mitochondrial membrane potential, but failed to cause mitochondrial cytochrome c release and caspase-9 activation. Pretreatment with water-soluble CoQ10 enhanced cell viability, decreased ROS production, maintained mitochondrial membrane potential and prevented AIF nuclear translocation. The results suggest that rotenone activates a mitochondria-initiated, caspase-independent cell death pathway. Water-soluble CoQ10 reduces ROS accumulation, prevents the fall of mitochondrial membrane potential, and inhibits AIF translocation and subsequent cell death.
Double aortic arch (DAA) with subaortic left brachiocephalic vein (LBCV) and right‐side ductus arteriosus (RDA) was not reported before delivery, only in adults with anatomy course findings. We ...present a case of fetal DAA with subaortic LBCV and RDA using high‐definition (HD) flow render mode and spatiotemporal image correlation (STIC).
Cancer remains a serious social health problem, and immunotherapy has become the major treatments in tumor treatment. Additionally, improving the efficiency and safety of treatment is necessary. ...Further, more therapy targets are warranted for future tumor treatments. In this review, in addition to examining the currently recognized role of immune regulation, we focus on the proliferative role of 15 immune checkpoints in various tumors, including PD1, PD-L1, FGL1, CD155, CD47, SIRPα, CD276, IDO1, SIGLEC-15, TIM3, Galectin-9, CD70, CD27, 4-1BBL, and HVEM. We managed to conclude that various immune checkpoints such as PD1/PD-L1, FGL1, CD155, CD47/SIRPα, CD276, and SIGLEC-15 all regulate the cell cycle, and specifically through Cyclin D1 regulation. Furthermore, a variety of signal pathways engage in proliferation regulation, such as P13K, AKT, mTOR, and NK-κB, which are also the most common pathways involved in the regulation of immune checkpoint proliferation. Currently, only PD1/PD-L1, CD47/SIRPα, TIM3/Galectin-9, and CD70/CD27 checkpoints have been shown to interact with each other to regulate tumor proliferation in pairs. However, for other immune checkpoints, the role of their receptors or ligands in tumor proliferation regulation is still unknown, and we consider the enormous potential in this area. An increasing number of studies have validated the various role of immune checkpoints in tumors, and based on this literature review, we found that most of the immune checkpoints play a dual regulatory role in immunity and proliferation. Therefore, the related pathways in proliferation regulation can served the role of therapy targets in tumor therapy. Further, great potential is displayed by IDO1, SIGLEC-15, 4-1BBL, and HVEM in tumor proliferation regulation, which may become novel therapy targets in tumor treatment.
Phthalates are widely used synthetic chemicals that determine endocrine disruption effects on female reproductivity and oviposition. Our study demonstrated that the mitochondrial quality in ovarian ...granulosa cells (GCs) is associated with a poor prognosis in female reproduction. However, the molecular mechanism of di-(2-ethylhexyl) phthalate (DEHP) exposure on the quail ovarian GC layer is still unknown. To validate the effects of DEHP on the GC layer, 8 days’ old 150 female Japanese quail were treated orally with DEHP (250, 500, and 750 mg/kg BW/day) for 45 days to explore the toxic effects of DEHP on the ovarian GC layer. Histopathological assessment and ultrastructure observation found that DEHP decreased the thickness of the GC layer, resulted in mitochondrial damage, and activated mitocytosis. Additionally, the results further suggested that DEHP impacted the secretion of steroid hormones (reduced FSH, E2, and T levels and boosted Prog, PRL, and LH levels) by triggering mitocytosis (enhanced transcription of MYO19 and protein of KIF5B levels), mitochondrial dynamics (increasing mRNA and protein levels of OPA1, DRP1, MFN1, and MFN2), mitophagy (increasing mRNA and protein levels of Parkin, LC3B, and P62), and inducing GC function disorder. In conclusion, our research provided a new idea to explain the mechanism of DEHP toxicity of the ovarian GC layer in quail and presented insights into the role of mitocytosis in DEHP-induced ovarian GC layer injury.
Plant volatile organic compounds (VOCs) with antimicrobial activity could potentially be extremely useful fumigants to prevent and control the fungal decay of agricultural products postharvest. In ...this study, antifungal effects of volatile compounds in essential oils extracted from Origanum vulgare L. against Aspergillus flavus growth were investigated using transcriptomic and biochemical analyses. Carvacrol was identified as the major volatile constituent of the Origanum vulgare L. essential oil, accounting for 66.01 % of the total content. The minimum inhibitory concentrations of carvacrol were 0.071 and 0.18 μL/mL in gas-phase fumigation and liquid contact, respectively. Fumigation with 0.60 μL/mL of carvacrol could completely inhibit A. flavus proliferation in wheat grains with 20 % moisture, showing its potential as a biofumigant. Scanning electron microscopy revealed that carvacrol treatment caused morphological deformation of A. flavus mycelia, and the resulting increased electrolyte leakage indicates damage to the plasma membrane. Confocal laser scanning microscopy confirmed that the carvacrol treatment caused a decrease in mitochondrial membrane potential, reactive oxygen species accumulation, and DNA damage. Transcriptome analysis revealed that differentially expressed genes were mainly associated with fatty acid degradation, autophagy, peroxisomes, the tricarboxylic acid cycle, oxidative phosphorylation, and DNA replication in A. flavus mycelia exposed to carvacrol. Biochemical analyses of hydrogen peroxide and superoxide anion content, and catalase, superoxide dismutase, and glutathione S-transferase activities showed that carvacrol induced oxidative stress in A. flavus, which agreed with the transcriptome results. In summary, this study provides an experimental basis for the use of carvacrol as a promising biofumigant for the prevention of A. flavus contamination during postharvest grain storage.
Dynamic control of flood-limited water level (FLWL) is an effective method to realize floodwater utilization, which can alleviate the contradiction between flood control and conservation during flood ...seasons. In this study, a method of identifying upper bound of FLWL is presented simultaneously considering pre-release for water supply in rainless period and pre-release for flood control in the early period of flood. A risk analysis framework considering continuous rainless-day forecast error and flood forecast error is established. An improved truncated Gaussian distribution to describe rainless-day forecast error is proposed, combined with normal distribution describing flood forecast error to derive the distribution of excess storage determined by the method of pre-release based on forecasts. Then risk assessment and decision making are conducted. The Xianghongdian Reservoir is selected for a case study. The results indicate that the allowable excess storage can be determined under a given acceptable risk by using this analytical method. Moreover, the excess storage decreases with the safety margin reserved for the downstream increasing under the same acceptable risk.
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