Preeclampsia is a significant contributor for maternal or fetal morbidity and mortality, which is characterized by reduced invasion capacity of trophoblasts and is regulated by extracellular matrix ...(ECM). It is still under investigation whether chorionic villus‐derived mesenchymal stem cells (CVMSC) could affect the functionality of trophoblasts. In this study, CVMSC‐derived exosomes were isolated; their effect on trophoblasts was investigated based on the CCK8 assay, migration assay, and apoptosis detection. And the underlying mechanism of this effect was investigated using mRNA sequencing, western blot, co‐immunoprecipitation, luciferase report assay, and ubiquitination assay. The results show that CVMSC‐derived exosomes promote migration and proliferation of trophoblasts, and also reduce cell apoptosis. mRNA sequencing confirmed that after treatment of CVMSC‐derived exosomes, Tripartite Motif Containing 72 (TRIM72) expression was upregulated and Tumor Protein P53 (P53) expression was downregulated, both significantly in trophoblasts. Subsequent study confirms that TRM72 can directly interact with P53 and promote P53 ubiquitination and proteasomal degradation, reducing apoptosis rate and elevating proliferation and migration in trophoblasts. Our study confirms that CVMSC‐derived exosomes promote trophoblast migration and proliferation by upregulating TRIM72 expression, and subsequently advance P53 ubiquitination and proteasomal degradation.
Abstract
The aim of this study was to clarify pathological and anatomical relationships between adamantinomatous craniopharyngiomas (ACP) and their surrounding structures. We previously established a ...QST classification scheme based on the apparent anatomic origin of the tumors. According to this classification, 13 type Q tumors, 6 type S tumors, and 42 type T ACPs were analyzed. Type Q tumors, which are most likely to involve the pituitary gland, did not invade the area of contact with the adenohypophysis. Instead, tumor invasion was observed in areas where the tumor contacted the neurohypophysis. Type S tumors primarily involved the pituitary stalk; the arachnoid remained present between these tumors and normal structures. Type T tumors were located beneath the basal arachnoid membrane and outside the pia mater. The pia mater was disrupted and finger-like invasions were found in the neural layer of the third ventricle floor along the invasive front. Tumors were never observed to break through the ependymal layer of the third ventricle. The QST classification has important implications for understanding the growth pattern of tumors and can be used to guide surgical procedures.
With the increasing pressure on reducing CO2 emissions, China promised to reduce carbon intensity by 60–65% by 2030 from 2005 levels. This study aims at identifying the driving forces of national and ...regional carbon intensity changes in China at multiple levels by a newly extended multiplicative structural decomposition analysis. Attribution analysis is further adopted to identify sectors with large intensity-reduction potential. National and regional carbon intensity changes during 2007–2012 are decomposed into three determinants: intensity (or efficiency) effect, input structure effect and final demand effect. Temporal decomposition results suggest that 29.0% decline of national carbon intensity is mainly due to intensity effect, while input structure and final demand effect drive the increment of national carbon intensity. Eight regions are divided into two groups: carbon intensity in Northwest, South Coast and Northeast increased due to input structure and final demand effect; carbon intensity in other regions decreased due to intensity effect and final demand effect. Investment and export are the dominant final demand categories to carbon intensity decline in most regions. Spatial decomposition results reveal the huge contribution discrepancy of driving forces among 30 provinces, and 30 provinces are accordingly classified into four groups. For most regions, simultaneously optimizing input structure and final demand are preferred in sectors with large intensity-reduction potential like Mining, Manufacture, Metals and metal productions and Production and supply of electricity, gas and water. Targeted intensity-reduction strategies at multiple levels are suggested.
•A newly extended multiplicative structural decomposition framework is developed.•Driving forces of multiple-level carbon intensity changes in China are discussed.•Investment and export are dominant for carbon intensity decline in most regions.•30 provinces are grouped into 4 types with differentiated intensity-reducing focus.•Most regions should improve input structure and final demand simultaneously.
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•First theoretical study on earthworm bioluminescence.•Calculations involve all reactions in bioluminescence of earthworm F. heliota.•Helpful for understanding F. heliota ...bioluminescence as well as oligochaete bioluminescence.
Fridericia heliota (F. heliota) is a kind of bioluminescent earthworm discovered in Siberia. As a novel ATP-dependent bioluminescent system, its luciferin and oxyluciferin structures have been elucidated by Yampolsky group recently. Based on reliable experimental evidences, this group outlined the bioluminescent mechanism of F. heliota, which represents a momentous breakthrough in the research of earthworm bioluminescence (BL). Understandably, the experimentally proposed mechanism does not embody the details of the related chemical reactions and light emission. For the first time, the theoretical investigation in the present paper concretely described the entire process of F. heliota BL from luciferin to light emission at the molecular and electronic-state level. The calculated results indicated that the F. heliota BL initiates from the oxygenation of luciferin induced by a single electron transfer (SET) and produces the light emitter through the thermolysis of a dioxtanone intermediate via a mechanism of gradually reversible charge-transfer initiated luminescence (GRCTIL). This study not only supports and improves experimentally proposed BL mechanism, but also enriches the details of the BL process. It will be helpful for understanding F. heliota BL as well as oligochaete BL in nature.
Adiponectin plays role in multiple metabolic pathways. Previous studies in cardiovascular disease evaluated the association between adiponectin and clinical outcomes, yielding conflicting results. ...The aim of this study was to investigate the association of adiponectin with major adverse cardiovascular and cerebrovascular events (MACCE) and mortality in Chinese patients with first-ever acute ischemic stroke (AIS).
This was a prospective, multicenter cohort study. From September 2009 through October 2015, all patients with AIS from 3 stroke centers in Shandong were included. Serum levels of adiponectin at admission were tested. The prognostic role of adiponectin to predict the MACCE and mortality within 3 years was evaluated by multivariable-adjusted Cox proportional hazards models.
This study included 4274 patients (median age 68 years interquartile ranges {IQR}: 61-76; 53.2% men). There were 794 deaths and 899 MACCE events. Higher serum levels of adiponectin on admission were found in patients with MACCE events and nonsurvivors (P < 0.001 and P < 0.001). In multivariable models adjusted for factors that confirmed in the univariate model, elevated serum levels of adiponectin were associated with a higher risk of MACCE (QuartileQ4 vs. Q1, Hazard ratioHR = 4.95 95% confidence interval {CI}: 3.03-7.06) and mortality (Q4 vs. Q1, HR = 5.63 95% CI 3.15-7.99). Adiponectin improved the prognostic value of the National Institutes of Health Stroke Scale (NIHSS) to predict MACCE (combined areas under the curve AUC, 0.76; 95% CI 0.68-0.88; P = 0.001) and mortality (0.780.69-0.91; P < 0.01). Subgroups analysis indicated that the prognostic role of adiponectin was more pronounced in women and patients with high levels of N-terminal-pro B-type natriuretic peptide(NT-pro BNP) (P < 0.001 and P < 0.001).
Elevated serum levels of adiponectin were associated with a higher risk of MACCE and mortality independent of traditional risk factors in ischemic stroke patients.
Background The mechanism of podocyte apoptosis is not fully understood. In addition, the role of the inositol 1,4,5-triphosphate receptor (IP.sub.3R)/glucose-regulated protein 75 ...(Grp75)/voltage-dependent anion channel 1 (VDAC1)/mitochondrial calcium uniporter (MCU) calcium regulation axis, which is located at sites of endoplasmic reticulum (ER) mitochondria coupling, in the mechanism of podocyte apoptosis is unclear. This study aimed to understand the roles of this axis in podocyte apoptosis and explore potential targets for podocyte protection. Methods The expression of IP.sub.3R, Grp75, VDAC1, and MCU and mitochondrial Ca.sup.2+ were analyzed during Adriamycin- or angiotensin II-induced apoptosis in cultured mouse podocytes. The interaction between IP.sub.3R, Grp75, and VDAC1 was investigated using co-immunoprecipitation experiments. The effects of IP.sub.3R, Grp75, and MCU agonists and antagonists on mitochondrial Ca.sup.2+ and apoptosis were investigated in cultured podocytes. The podocyte-protective effects of an MCU inhibitor were further investigated in rats with Adriamycin-induced nephropathy. Results Increased expression of IP.sub.3R, Grp75, VDAC1 and MCU, enhanced interaction among the IP.sub.3R-Grp75-VDAC1 complex, mitochondrial Ca.sup.2+ overload, and increased active caspase-3 levels were confirmed during Adriamycin- or angiotensin II-induced mouse podocyte apoptosis. Agonists of this axis facilitated mitochondrial Ca.sup.2+ overload and podocyte apoptosis, whereas specific antagonists against IP.sub.3R, Grp75, or MCU prevented mitochondrial Ca.sup.2+ overload and podocyte apoptosis. A specific MCU inhibitor prevented Adriamycin-induced proteinuria and podocyte foot process effacement in rats. Conclusions This study identified a novel pathway in which the IP.sub.3R-Grp75-VDAC1-MCU calcium regulation axis mediated podocyte apoptosis by facilitating mitochondrial Ca.sup.2+ overload. Antagonists that inhibit Ca.sup.2+ transfer from ER to mitochondria protected mouse podocytes from apoptosis. An MCU inhibitor protected podocytes and decreased proteinuria in rats with Adriamycin-induced nephropathy. Therefore, antagonists to this pathway have promise as novel podocyte-protective drugs. Keywords: Podocyte, Apoptosis, Endoplasmic reticulum mitochondria coupling, Mitochondria, Calcium
ERECTA (ER) is a leucine-rich repeat-receptor-like kinase gene (LRR-RLK) encoding a protein isolated from Arabidopsis. Although the regulatory functions of ER genes have been widely explored in plant ...development and disease resistance, their roles in drought stress responses remain to be clarified.
In this study, we cloned and characterized two ER genes, SbER1-1 and SbER2-1, from the drought-tolerant model plant sorghum (Sorghum bicolor L.). Under drought stress, the two genes were expressed in the leaves and stems but not in the roots, and SbER2-1 transcript accumulation in the stem was increased. SbER2-1 was localized both on the plasma membrane and in the chloroplast. Moreover, SbER2-1 expression in Arabidopsis and maize conferred increased drought tolerance, especially in regard to water-use efficiency, increasing the net photosynthetic rate in maize under drought stress. Based on RNA-Seq analysis together with the physiological data, we conclude that the transgenic maize plants have upregulated phenylpropanoid metabolism and increased lignin accumulation under drought stress.
Our results demonstrate that SbER2-1 plays an important role in response to drought stress. Furthermore, photosynthetic systems and phenylpropanoid metabolism are implicated in SbER2-1-mediated drought stress tolerance mechanisms. The use of genetic engineering to regulate SbER2-1 expression in plants and to breed new varieties tolerant to drought is a research field full of potential.
Cell death‐inducing DFFA‐like effector C (CIDEC) is responsible for metabolic disturbance and insulin resistance, which are considered to be important triggers in the development of diabetic ...cardiomyopathy (DCM). To investigate whether CIDEC plays a critical role in DCM, DCM rat model was induced by a high‐fat diet and a single injection of low‐dose streptozotocin (27.5 mg/kg). DCM rats showed severe metabolic disturbance, insulin resistance, myocardial hypertrophy, interstitial fibrosis, ectopic lipid deposition, inflammation and cardiac dysfunction, accompanied by CIDEC elevation. With CIDEC gene silencing, the above pathophysiological characteristics were significantly ameliorated accompanied by significant improvements in cardiac function in DCM rats. Enhanced AMP‐activated protein kinase (AMPK) α activation was involved in the underlying pathophysiological molecular mechanisms. To further explore the underlying mechanisms that CIDEC facilitated collagen syntheses in vitro, insulin‐resistant cardiac fibroblast (CF) model was induced by high glucose (15.5 mmol/L) and high insulin (104 μU/mL). We observed that insulin‐resistant stimulation dramatically raised CIDEC expression and promoted CIDEC nuclear translocation in CFs. Meanwhile, AMPKα2 was observed to distribute almost completely inside CF nucleus. The results further proved that CIDEC biochemically interacted and co‐localized with AMPKα2 rather than AMPKα1 in CF nucleus, which provided a novel mechanism of CIDEC in promoting collagen syntheses. This study suggested that CIDEC gene silencing alleviates DCM via AMPKα signaling both in vivo and in vitro, implicating CIDEC may be a promising target for treatment of human DCM.
Vimentin (VIM), an indispensable protein, is responsible for the formation of intermediate filament structures within cells and plays a crucial role in viral infections. However, the precise role of ...VIM in classical swine fever virus (CSFV) infection remains unclear. Herein, we systematically investigated the function of VIM in CSFV replication. We demonstrated that both knockdown and overexpression of VIM affected CSFV replication. Furthermore, we observed by confocal microscopy the rearrangement of cellular VIM into a cage-like structure during CSFV infection. Three-dimensional (3D) imaging indicated that the cage-like structures were localized in the endoplasmic reticulum (ER) and ringed around the double-stranded RNA (dsRNA), thereby suggesting that VIM was associated with the formation of the viral replication complex (VRC). Mechanistically, phosphorylation of VIM at serine 72 (Ser72), regulated by the RhoA/ROCK signaling pathway, induced VIM rearrangement upon CSFV infection. Confocal microscopy and coimmunoprecipitation assays revealed that VIM colocalized and interacted with CSFV NS5A. Structurally, it was determined that amino acids 96 to 407 of VIM and amino acids 251 to 416 of NS5A were the respective important domains for this interaction. Importantly, both VIM knockdown and disruption of VIM rearrangement inhibited the localization of NS5A in the ER, implying that VIM rearrangement recruited NS5A to the ER for VRC formation. Collectively, our results suggest that VIM recruits NS5A to form a stable VRC that is protected by the cage-like structure formed by VIM rearrangement, ultimately leading to enhanced virus replication. These findings highlight the critical role of VIM in the formation and stabilization of VRC, which provides alternative strategies for the development of antiviral drugs.
Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is a highly infectious disease that poses a significant threat to the global pig industry. Therefore, gaining insights into the virus and its interaction with host cells is crucial for developing effective antiviral measures and controlling the spread of CSF. Previous studies have shown that CSFV infection induces rearrangement of the endoplasmic reticulum, leading to the formation of small vesicular organelles containing nonstructural protein and double-stranded RNA of CSFV, as well as some host factors. These organelles then assemble into viral replication complexes (VRCs). In this study, we have discovered that VIM recruited CSFV NS5A to form a stable VRC that was protected by a cage-like structure formed by rearranged VIM. This enhanced viral replication. Our findings not only shed light on the molecular mechanism of CSFV replication but also offer new insights into the development of antiviral strategies for controlling CSFV.
•Robust sparse coding for one-class classification based on correntropy and logarithmic penalty function is proposed.•The optimization problem of the proposed robust sparse coding is iteratively ...solved by the half-quadratic optimization technique.•The generalization performance of robust sparse coding is analyzed from the theoretical analysis.•The effectiveness of the proposed method is validated on twenty UCI benchmark data sets and one handwritten digit data set.
Similar to binary and multi-class classifiers, one-class classifiers have to face the difficulty of ’curse of dimensionality’ when they are applied to deal with high-dimensional samples. As an efficient dimensionality reduction method, sparse coding tries to learn a set of over-complete bases to represent the given samples. It can effectively overcome the ’curse of dimensionality’ problem. However, the traditional sparse coding only fit for tackling Gaussian noise. When the noise within the given set of samples obey non-Gaussian distribution, the conventional sparse coding cannot obtain accurate coefficient vectors. To make sparse coding more fit for dealing with non-Gaussian noise and enhance the sparseness of the obtained coefficient vectors, correntropy is utilized to substitute its reconstruction error term and logarithmic penalty function is introduced as its regularization term. Furthermore, the obtained sparse coefficient vectors are used as the input vectors for one-class support vector machine (OCSVM). Experimental results on twenty UCI benchmark data sets and one handwritten digit data set demonstrate that the proposed method achieves better anti-noise and generalization abilities in comparison with its related approaches.
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