Human cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that regulates tissue and cell homeostasis and has been shown to antagonize heart fibrosis, which indicates a ...potential protective effect of CREG against cardiomyocyte chronic damage. However, little is known about the role of CREG in myocardial tissue acute injury, in this study, we aimed to investigate the role of CREG in myocardial ischemia/reperfusion (MI/R) injury and clarify the mechanism of action.
Wild-type Creg (Creg+/+), heterozygous Creg (Creg+/−) mice and mice pretreated with infusion of recombinant 0.3mg/kg·d CREG protein (reCreg+/+) were subjected to 30min of left ascending coronary ischemia and 24h of reperfusion. Evan's Blue-triphenyl- tetrazolium chloride (TTC) solution and echocardiography analysis were used to evaluate the effects of CREG on MI/R mice. The underlying mechanisms were further determined by cultured myocardial cells in vitro. Our findings revealed that the level of CREG protein in mouse hearts was significantly decreased after mice were subjected to MI/R. Moreover, Creg+/− mice had larger infarction size 2h after reperfusion and worse cardiac function 28days after MI/R injury compared to that in Creg+/+ mice. However, reCreg+/+ mice could maintain CREG at a high level even after MI/R injury, and mitigated infarction size and improved cardiac function significantly. In Creg+/− mice, myocardial autophagy was dysfunctional characterized by accumulation of LC3A and p62, while apoptotic cell number increase was detected by cleaved caspase-3 blotting and TUNEL staining. Conversely, decreased apoptosis and activated autophagy were detected in reCreg+/+ mice. Furthermore, chloroquine, a kind of autophagy blocker, was used to demonstrate recombinant CREG protected cardiomyocytes against apoptosis mediated by activating autophagy both in vivo and in vitro. Finally, we found CREG was involved into lysosomal protein transfer and improve cellular autophagy.
CREG protects heart against MI/R injury-induced cardiomyocytes apoptosis by activating lysosomal autophagy.
This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren and Megan Yingmei Zhang.
•CREG mitigates infarction and improves cardiac function induced by MI/R injury.•CREG plays an important role in anti-apoptosis of cardiomyocytes.•CREG activates lysosomal autophagy to protect heart from MI/R injury.
Determining the land surface temperature (LST) variations in urban surfaces using high spatiotemporal resolution thermal infrared data is necessary for urban microthermal environmental modeling. An ...unmanned aerial vehicle (UAV) equipped with a thermal infrared imager was used to monitor the high-precision spatiotemporal variation of LSTs for six typical urban surfaces, including water, tree canopy, grass, brick pavement, asphalt pavement, and marble pavement, in the Jiangning district, Nanjing. An estimation of sensible heat release was further conducted to quantitatively describe the fine characteristics of the LSTs of these surfaces. The factors influencing LST were investigated by correlating LSTs with the meteorological factors. The results showed that there were significant differences in LSTs and sensible heat release for six typical urban surfaces in sunny and cloudy days, respectively. On sunny days, the diurnal variations in different surfaces fluctuated substantially, which was not evident on cloudy days. The artificial surfaces always represented as the main source of sensible heat release. Solar radiation and air temperature, among the meteorological factors, were positively correlated with the LSTs of the surfaces. The air humidity was negatively correlated with the LSTs and played a role in cooling the land surface.
The stability of gossypol was investigated by the spectroscopic method. Gossypol was dissolved in three different solvents (CHCl₃, DMSO, and CH₃OH) under different storage conditions (dark and with ...nitrogen protection, natural light and with nitrogen protection, ambient air conditions) for different time intervals (0 days, 3 days, 5 days, 7 days, 15 days, 30 days, and 45 days) at room temperature. Then, the stability of gossypol was investigated by ¹H NMR, UV-vis, and HPLC-QTOF-MS spectrometry. Results showed that gossypol existed in aldehyde-aldehyde form in chloroform within five days. Then, both aldehyde-aldehyde and lactol-lactol tautomeric forms existed and maintained a stable solution for 45 days. Gossypol dissolved in methanol mainly existed in aldehyde-aldehyde form. Only a tiny amount of lactol-lactol was found in freshly prepared methanol solution. Gossypol was found to only exist in lactol-lactol form between 30-45 days. Gossypol existed in aldehyde-aldehyde, lactol-lactol, and ketol-ketol forms in dimethyl sulfoxide, and there was a competitive relationship between aldehyde-aldehyde and lactol-lactol form during the 45 days. Among all the solvents and conditions studied, gossypol was found to be highly stable in chloroform. Under the tested conditions, the natural light and atmospheric oxygen had little effect on its stability. Although the spectroscopy data seemed to be changed over time in the three different solvents, it was actually due to the tautomeric transformation rather than molecular decomposition.
Biomass-based functional rubber adsorbents were designed and prepared via inverse vulcanization and post-modification. The plant rubber was synthesized with sulfur and renewable cottonseed oil as ...well as various micromolecular modifiers with nitrogen-containing functional groups. Results showed that types of nitrogen-containing functional groups and dosages of modifiers had a significant impact on the adsorption capacities of the resulting polymers for Hg
. Notably, when the mass ratio of 2-aminoethyl methacrylate (AEMA) to sulfur was 0.05, the resulting polymer polysulfide-co-cottonseed oil modified by AEMA (SCOA2) showed the highest adsorption capacity (343.3 mg g
) among all the prepared samples. Furthermore, the Hg
removal efficiency of SCOA2 remained over 80% of its original value after five adsorption-desorption cycles. It demonstrated a promising case for utilizing cheap industrial by-products (sulfur) and renewable materials (cottonseed oil). The prepared functional rubber provides alternative approach for mercury removal in waste utilization and sustainable chemistry.
The Patient-Reported Outcomes Measurement Information System 29-item Profile version 2.1 (PROMIS-29 V2.1) is a widely utilized self-reported instrument for assessing health outcomes from the ...patients' perspectives. This study aimed to evaluate the psychometric properties of the PROMIS-29 V2.1 Chinese version among patients with hematological malignancy. Conducted as a cross-sectional, this research was approved by the Medical Ethical Committee of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (registration number QTJC2022002-EC-1). We employed convenience sampling to enroll eligible patients with hematological malignancy from four tertiary hospitals in Tianjin, Shandong, Jiangsu, and Anhui province in China between June and August 2023. Participants were asked to complete a socio-demographic information questionnaire, the PROMIS-29 V2.1, and the Functional Assessment of Cancer Therapy-General (FACT-G). We assessed the reliability, ceiling and floor effects, structural, convergent discriminant and criterion validity of the PROMIS-29 V2.1. A total of 354 patients with a mean age of 46.93 years was included in the final analysis. The reliability of the PROMIS-29 V2.1 was affirmed, with Cronbach's α for the domains ranging from 0.787 to 0.968. Except sleep disturbance, the other six domains had ceiling effects, which were seen on physical function (26.0%), anxiety (37.0%), depression (40.4%), fatigue (18.4%), social roles (18.9%) and pain interference (43.2%), respectively. Criterion validity was supported by significant correlations between the PROMIS-29 V2.1 and FACT-G scores, as determined by the Spearman correlation test (P < 0.001). Confirmatory factor analysis (CFA) indicated a good model fit, with indices of χ
/df (2.602), IFI (0.960), and RMSEA (0.067). The Average Variance Extracted (AVE) values for the seven dimensions of PROMIS-29 V2.1, ranging from 0.500 to 0.910, demonstrated satisfactory convergent validity. Discriminant validity was confirmed by ideal √AVE values. The Chinese version of the PROMIS-29 V2.1 profile has been validated as an effective instrument for assessing symptoms and functions in patients with hematological malignancy, underscoring its reliability and applicability in this specific patient group.
Aphidius gifuensis is the dominant parasitic natural enemy of aphids. Elucidating the molecular mechanism of host recognition of A. gifuensis would improve its biological control effect. Chemosensory ...proteins (CSPs) play a crucial role in insect olfactory systems and are mainly involved in host localization. In this study, a total of nine CSPs of A. gifuensis with complete open reading frames were identified based on antennal transcriptome data. Phylogenetic analysis revealed that AgifCSPs were mainly clustered into three subgroups (AgifCSP1/2/7/8, AgifCSP3/9, and AgifCSP4/5/6). AgifCSP2/5 showed high expression in the antennae of both sexes. Moreover, AgifCSP5 was found to be specifically expressed in the antennae. In addition, fluorescent binding assays revealed that AifCSP5 had greater affinities for 7 of 32 volatile odor molecules from various sources. Molecular docking and site-directed mutagenesis results revealed that the residue at which AgifCSP5 binds to these seven plant volatiles is Tyr75. Behavior tests further confirmed that trans-2-nonenal, one of the seven active volatiles in the ligand binding test, significantly attracted female adults at a relatively low concentration of 10 mg/mL. In conclusion, AgifCSP5 may be involved in locating aphid-infested crops from long distances by detecting and binding trans-2-nonenal. These findings provide a theoretical foundation for further understanding the olfactory recognition mechanisms and indirect aphid localization behavior of A. gifuensis from long distances by first identifying the host plant of aphids.
Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved intracellular mechanism for lysosomal degradation of damaged cellular components. The specific degradation of ...nuclear components by the autophagy pathway is called nucleophagy. Most studies have focused on autophagic turnover of cytoplasmic materials, and little is known about the role of autophagy in the degradation of nuclear components.
Human MDA-MB-231 and MCF-7 breast cancer cell lines were used as model systems in vitro. Induction of nucleophagy by nuclear DNA leakage was determined by western blot and immunofluorescence analyses. The interaction and colocalization of LC3 and lamin A/C was determined by immunoprecipitation and immunofluorescence. The role of the SUMO E2 ligase, UBC9, on the regulation of SUMOylation of lamin A/C and nucleophagy was determined by siRNA silencing of UBC9, and analyzed by immunoprecipitation and immunofluorescence.
DNA damage induced nuclear accumulation of UBC9 ligase which resulted in SUMOylation of lamin A/C and that SUMOylation of this protein was required for the interaction between the autophagy protein LC3 and lamin A/C, which was required for nucleophagy. Knockdown of UBC9 prevented SUMOylation of lamin A/C and LC3-lamin A/C interaction. This attenuated nucleophagy which degraded nuclear components lamin A/C and leaked nuclear DNA mediated by DNA damage.
Our findings suggest that nuclear DNA leakage activates nucleophagy through UBC9-mediated SUMOylation of lamin A/C, leading to degradation of nuclear components including lamin A/C and leaked nuclear DNA.
The differentiation capacity of human embryonic stem cells (hESCs) holds great promise for therapeutic applications. We report a novel three‐stage method to efficiently direct the differentiation of ...human embryonic stem cells into hepatic cells in serum‐free medium. Human ESCs were first differentiated into definitive endoderm cells by 3 days of Activin A treatment. Next, the presence of fibroblast growth factor‐4 and bone morphogenetic protein‐2 in the culture medium for 5 days induced efficient hepatic differentiation from definitive endoderm cells. Approximately 70% of the cells expressed the hepatic marker albumin. After 10 days of further in vitro maturation, these cells expressed the adult liver cell markers tyrosine aminotransferase, tryptophan oxygenase 2, phosphoenolpyruvate carboxykinase (PEPCK), Cyp7A1, Cyp3A4 and Cyp2B6. Furthermore, these cells exhibited functions associated with mature hepatocytes including albumin secretion, glycogen storage, indocyanine green, and low‐density lipoprotein uptake, and inducible cytochrome P450 activity. When transplanted into CCl4 injured severe combined immunodeficiency mice, these cells integrated into the mouse liver and expressed human alpha‐1 antitrypsin for at least 2 months. In addition, we found that the hESC‐derived hepatic cells were readily infected by human immunodeficiency virus‐hepatitis C virus pseudotype viruses. Conclusion: We have developed an efficient way to direct the differentiation of human embryonic stem cells into cells that exhibit characteristics of mature hepatocytes. Our studies should facilitate searching the molecular mechanisms underlying human liver development, and form the basis for hepatocyte transplantation and drug tests. (HEPATOLOGY 2007;45:1229–1239.)
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•Sulfur-doped graphene (SG) was synthesized by a rapid and efficient MAS method.•MAS process involved simultaneous S-doping and GO reduction.•SG showed a high S-doping level and a ...sole thiophene-S bonding configuration.•SG outperformed undoped graphene in electrocatalytic reduction of H2O2.•SG may be a promising electrode material for electrochemical sensor applications.
Heteroatom doping is an effective way to modulate the electronic structure and properties of graphene. Despite a growing interest in sulfur (S)-doped graphene (SG), synthesis of high-quality SG at low cost remains a great challenge. In this study, we developed a rapid, efficient and cost-effective microwave-assisted solvothermal (MAS) method for the preparation of SG. It was found that a short MAS time of 6min could generate few-layer SG (0.5μm in lateral size) having effective oxygen reduction, high level of S-doping, sole thiophene-S bonding configuration, and high electrical conductivity. Furthermore, the resulting SG could serve as an effective electrocatalyst for H2O2 reduction, showing improved electrocatalytic activity over its undoped counterpart and good sensing performances for highly sensitive and selective detection of H2O2, indicating that SG may be a promising candidate for electrochemical sensor applications.
Non-dissociative chemisorption solid-state storage of hydrogen molecules in host materials is promising to achieve both high hydrogen capacity and uptake rate, but there is the lack of ...non-dissociative hydrogen storage theories that can guide the rational design of the materials. Herein, we establish generalized design principle to design such materials via the first-principles calculations, theoretical analysis and focused experimental verifications of a series of heteroatom-doped-graphene-supported Ca single-atom carbon nanomaterials as efficient non-dissociative solid-state hydrogen storage materials. An intrinsic descriptor has been proposed to correlate the inherent properties of dopants with the hydrogen storage capability of the carbon-based host materials. The generalized design principle and the intrinsic descriptor have the predictive ability to screen out the best dual-doped-graphene-supported Ca single-atom hydrogen storage materials. The dual-doped materials have much higher hydrogen storage capability than the sole-doped ones, and exceed the current best carbon-based hydrogen storage materials.