Background The postmitotic state of adult cardiomyocytes, maintained by the cell cycle repressor Rbl2 (retinoblastoma‐like 2), is associated with considerable resistance to apoptosis. However, ...whether Rbl2 regulates cardiomyocyte apoptosis remains unknown. Methods and Results Here, we show that ablation of Rbl2 increased cardiomyocyte apoptosis following acute myocardial ischemia/reperfusion injury, leading to diminished cardiac function and exaggerated ventricular remodeling in the long term. Mechanistically, ischemia/reperfusion induced expression of the proapoptotic protein BCL2 interacting protein 3 (Bnip3), which was augmented by deletion of Rbl2. Because the Bnip3 promoter contains an adenoviral early region 2 binding factor (E2F)‐binding site, we further showed that loss of Rbl2 upregulated the transcriptional activator E2F1 but downregulated the transcriptional repressor E2F4. In cultured cardiomyocytes, treatment with H 2 O 2 markedly increased the levels of E2F1 and Bnip3, resulting in mitochondrial depolarization and apoptosis. Depletion of Rbl2 significantly augmented H 2 O 2 ‐induced mitochondrial damage and apoptosis in vitro. Conclusions Rbl2 deficiency enhanced E2F1‐mediated Bnip3 expression, resulting in aggravated cardiomyocyte apoptosis and ischemia/reperfusion injury. Our results uncover a novel antiapoptotic role for Rbl2 in cardiomyocytes, suggesting that the cell cycle machinery may directly regulate apoptosis in postmitotic cardiomyocytes. These findings may be exploited to develop new strategies to limit ischemia/reperfusion injury in the treatment of acute myocardial infarction.
Anti-inflammatory drugs have become the second-largest class of common drugs after anti-infective drugs in animal clinical care worldwide and are often combined with other drugs to treat fever and ...viral diseases caused by various factors. In our previous study, a novel serine protease inhibitor-encoding gene (
) with improved anti-inflammatory activity was selected from a constructed suppressive subducted hybridization library of housefly larvae. This protein could easily induce an immune response in animals and had a short half-life, which limited its wide application in the clinic. Thus, in this study, mPEG-succinimidyl propionate (mPEG-SPA, Mw = 5 kDa) was used to molecularly modify the MDSPI16 protein, and the modified product mPEG-SPA-MDSPI16, which strongly inhibited elastase production, was purified. It had good stability and safety, low immunogenicity, and a long half-life, and the IC
for elastase was 86 nM. mPEG-SPA-MDSPI16 effectively inhibited the expression of neutrophil elastase and decreased ROS levels. Moreover, mPEG-SPA-MDSPI16 exerted anti-inflammatory effects by inhibiting activation of the NF-κB signaling pathway and the MAPK signaling pathway in neutrophils. It also exerted therapeutic effects on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. In summary, mPEG-SPA-MDSPI16 is a novel anti-inflammatory protein modified with PEG that has the advantages of safety, nontoxicity, improved stability, and strong anti-inflammatory activity in vivo and in vitro and is expected to become an effective anti-inflammatory drug.
Using 34 products from China’s commodity futures market, this study examines the impact of social network attention and sentiment on its futures market returns. A machine learning text analysis ...algorithm was used to construct social network investor sentiment in consultation with three search volume indices. We find that: social network sentiment is a good predictor of commodity futures returns, investor attention has a significant positive impact on returns and absolute returns, and the Baidu index is better at forecasting returns than the Sogou and 360 indices. In addition, we examine how social network sentiment affects returns at different levels. We find that extremely high, market social network sentiments of investors changed the predicted results significantly; thus, the bases of the specified trading strategies of investors were altered. Regulators should therefore incorporate investor sentiment into regulatory targets and enhance retail investor education.
(Chinese milk vetch) is a well-established resource of organic fertilizer widely used in paddy soil to partially replace chemical fertilizers. However, the influence of returning
to fields on the ...soil bacterial community remains poorly understood. Here, we used different amounts of
partially replacing chemical fertilizers and investigated the changes in soil physicochemical factors and the soil bacterial community structure responses. Returning
to the field significantly increased the soil total nitrogen and available phosphorus content (
< 0.05). Weighted gene correlation network analysis (WGCNA) was applied to detect significant associations between the soil microbiome data and physicochemical factors. Two key ecological bacterial clusters (MEturquoise and MEgreen), mainly containing Acidobacteria, Proteobacteria, and Chloroflexi, were significantly correlated with soil nitrogen (N) levels.
partially replacing chemical fertilizers reduced the normalized stochasticity ratio (NST) of rare amplicon sequence variants (ASVs), abundant ASVs, MEturquoise, and MEgreen (
< 0.05). Our results further indicated that a moderate amount of
returned to the soil effectively mitigated the trend of reduced relative abundance of N fixation function of key ecological clusters caused by chemical fertilizer. However, a large amount of
led to a significant increase in relative abundance of denitrification function and a significant decrease in relative abundance of N fixation function of key ecological clusters. This implies that the moderate substitution of
returning for chemical fertilizer improves the N cycling function of key ecological bacterial clusters in soil. From the perspective of the bacterial community in paddy soil, this study provides new insight and a reference on how to find a good balance between the amount of
returned to the soil and ecological safety.
The Heishan geothermal area is positioned above the sole Yunnan–Tibet high-temperature geothermal belt, where huge geothermal energy resources are available. Utilizing the characteristics of large ...exploration depth, extensive coverage, and high precision of the wide-field electromagnetic method, four survey lines were deployed, totaling 29.8 km, to enable a comprehensive analysis of the granite structure and fault distribution. The results indicate that the rocks within the area can be vertically divided into a granite basement and a fractured layer. Moreover, three different zones of resistivity were identified: the granite basement zone has a resistivity range of 2500–20000 Ω m, whereas the compressional shear zone and the secondary fault zone have a resistivity range of 750–2500 Ω m, and the extensional fault zone and the main fault zone have resistivity values below 750 Ω m. The Heishan-Hejian fault and the fault zone formed during its right-lateral strike-slip process, as well as the controlled area of the Qianmaihe fault, are all favorable targets. Of these, the Qianmahe fault possesses a larger-scale heat-conducting and water-controlling structure. In addition, in the secondary fault-controlled area extending to the west, the zone between F2’ and F4 exhibits renewed tectonic activity, suggesting a greater potential for geothermal resources.
Background
Preterm birth is one of the leading causes of perinatal morbidity and mortality. Gut microbiome dysbiosis is closely related to adverse pregnancy outcomes. However, the role of the gut ...microbiome in the pathogenesis of preterm birth remains poorly studied.
Method
We collected fecal samples from 41 women (cases presenting with threatened preterm labor =19, 11 of which delivered preterm; gestational age-matched no-labor controls, all of which delivered at term = 22) were recruited for the study. We performed 16S rRNA amplicon sequencing to compare the composition of the gut microbiome in threatened preterm labor cases and controls and among women who delivered preterm and at term. By annotating taxonomic biomarkers with the Human Oral Microbiome Database, we observed an increased abundance of potential oral-to-gut bacteria in preterm patients.
Results
Patients with preterm birth showed a distinct gut microbiome dysbiosis compared with those who delivered at term. Opportunistic pathogens, particularly
Porphyromonas
,
Streptococcus
,
Fusobacterium
, and
Veillonella
, were enriched, whereas
Coprococcus
and
Gemmiger
were markedly depleted in the preterm group. Most of the enriched bacteria were annotated oral bacteria using the Human Oral Microbiome Database. These potential oral-to-gut bacteria were correlated with clinical parameters that reflected maternal and fetal status.
Conclusions
This study suggests that patients who deliver preterm demonstrate altered gut microbiome that may contain higher common oral bacteria.
Metabonomics/metabolomics is a rapid technology for comprehensive profiling of small molecule metabolites in cells, tissues, or whole organisms, the application of which has led to understanding ...pathophysiologic mechanisms of cardiometabolic diseases, defining predictive biomarkers for those diseases, and also assessing the efficacious effects of incident drugs. In this study, proton nuclear magnetic resonance (NMR)-based metabonomics was employed to identify the metabolic changes in rat plasma caused by myocardial ischemia-reperfusion injury (MIRI), and to compare the metabolic regulatory differences between traditional Chinese medicine Wenxin Keli (WXKL) and Western medicine verapamil. The results revealed that energy-substrate metabolism were significantly disturbed by ischemia-reperfusion (I/R) in myocardium and bulk of the key metabolites could be further modulated by verapamil and/or WXKL. Lipid metabolism and amino acid transamination occurred mainly following the treatment of verapamil, whereas glucose oxidation and BCAA degradation were prominently ameliorated by WXKL to content the energy demands of heart. Moreover, both WXKL and verapamil improved the secretions of taurine and ketone bodies to overcome the oxidative stress and the shortage of energy sources induced by ischemia-reperfusion.
The growing atmospheric mercury (Hg) emissions in China have raised ongoing concerns regarding contamination in marine fish. To better understand the pollution patterns and associated risks, we ...examined methylmercury (MeHg) content in demersal and pelagic fish from four commonly found families in three geographically distinct bays along the Chinese coast. We identified significant spatial variations in MeHg levels within the same fish family across regions. Specifically, fish collected from the Beibu Gulf in the South China Sea consistently exhibited significantly higher MeHg levels compared to those from the Laizhou Bay in the Northeast and/or Haizhou Bay in the East of China. In contrast, MeHg levels in fish collected from Haizhou Bay consistently remained the lowest. Within each region, we observed significantly higher MeHg concentrations in demersal species compared to pelagic species. This trend was particularly evident in fish species including bartail flathead ( Platycephalus indicus ), small-scale tongue sole ( Cynoglossus microlepis ) and greater lizardfish ( Saurida tumbil ) from the Beibu Gulf (0.50, 0.21, and 0.18 mg/kg dw, respectively), as well as bartail flathead and slender lizardfish ( Saurida elongata ) from Laizhou Bay (0.09 and 0.12 mg/kg dw, respectively). By comparison, MeHg content in silver pomfret ( Pampus argenteus ) from all three regions consistently remained relatively lower than in other species. Using target hazardous quotient (THQ) calculations, we estimated potential health risks in local populations associated with the consumption of the studied fish species. Our results showed a lack of apparent health risks to local residents, as all THQ values obtained from the three regions fell within the safe limits (0.02–0.94). However, it remains important to conduct additional assessments and spatiotemporal monitoring that encompass a broader range of species and regions.
Doxorubicin (DOX) is one of the most effective chemotherapy agents used in the treatment of hematological and solid tumors, however, it causes dose-related cardiotoxicity that may lead to heart ...failure in patients. One of the major reasons was increased reactive oxygen species (ROS) production. Ginsenoside Rg3 (Rg3), was powerful free radical scavengers and possessed cardioprotective effects. Nevertheless, Rg3 has low aqueous solubility and oral bioavailability, limiting its effects. Herein, we encapsulated Rg3 through spontaneous self-assembly of Pluronic F127 to improve its solubility and oral bioavailability. Moreover, co-administering Rg3 in Pluronic F127 micelles with doxorubicin can mitigate the cardiotoxicity, with ameliorating mitochondrial and metabolic function, improving calcium handling, and decreasing ROS production. In addition, it can improve the anticancer efficacy of doxorubicin. Therefore, our study provides a rational strategy for further developing a potentially viable adjunct-supportive treatment for reducing toxicity and increasing efficiency on chemotherapy.
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