Chronic heart failure (CHF) is the final outcome of many cardiovascular diseases, and is a severe health issue faced by the elderly population. Mixed lineage kinase 3 (MLK3), a member of MAP3K ...family, is associated with aging, inflammation, oxidative stress, and related diseases, such as CHF. MLK3 has also been reported to play an important role in protecting against cardiomyocyte injury; however, its function in myocardial fibrosis is unknown. To investigate the role of MLK3 in myocardial fibrosis, we inhibited the expression of MLK3, and examined cardiac function and remodeling in TAC mice. In addition, we assessed the expression of MLK3 protein in ventricular cells and its downstream associated protein. We found that MLK3 mainly regulates NF-κB/NLRP3 signaling pathway-mediated inflammation and that pyroptosis causes myocardial fibrosis in the early stages of CHF. Similarly, MLK3 mainly regulates the JNK/p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of CHF. We also found that promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC. These results suggest the pyroptosis and ferroptosis induced by MLK3 signaling in cardiomyocytes are essential for adverse myocardial fibrosis, in response to pressure overload. Furthermore, miR-351, which has a protective effect on ventricular remodeling in heart failure caused by pressure overload, may be a key target for the regulation of MLK3.
The species belonging to Sclerodermus (Hymenoptera: Bethylidae) are currently the most important insect natural enemies of wood borer pests, mainly buprestid and cerambycid beetles, in China. ...However, some sibling species of this genus are very difficult to distinguish because of their similar morphological features. To address this issue, we conducted phylogenetic and genetic analyses of cytochrome oxidase subunit I (COI) and 28S RNA gene sequences from eight species of Sclerodermus reared from different wood borer pests. The eight sibling species were as follows: S. guani Xiao et Wu, S. sichuanensis Xiao, S. pupariae Yang et Yao, and Sclerodermus spp. (Nos. 1-5). A 594-bp fragment of COI and 750-bp fragment of 28S were subsequently sequenced. For COI, the G-C content was found to be low in all the species, averaging to about 30.0%. Sequence divergences (Kimura-2-parameter distances) between congeneric species averaged to 4.5%, and intraspecific divergences averaged to about 0.09%. Further, the maximum sequence divergences between congeneric species and Sclerodermus sp. (No. 5) averaged to about 16.5%. All 136 samples analyzed were included in six reciprocally monophyletic clades in the COI neighbor-joining (NJ) tree. The NJ tree inferred from the 28S rRNA sequence yielded almost identical results, but the samples from S. guani, S. sichuanensis, S. pupariae, and Sclerodermus spp. (Nos. 1-4) clustered together and only Sclerodermus sp. (No. 5) clustered separately. Our findings indicate that the standard barcode region of COI can be efficiently used to distinguish morphologically similar Sclerodermus species. Further, we speculate that Sclerodermus sp. (No. 5) might be a new species of Sclerodermus.
The relationship between body size and fitness in parasitoid wasps has several effects on parasitic ability, reproductive behavior in female wasps, and progeny fitness. Female wasps with various body ...sizes were obtained by mass-rearing a gregarious ectoparasitoid, Sclerodermus pupariae, which is one of the excellent parasites to control the larvae and pupae of Buprestidae and Cerambycidae. We investigated the effects of body size of adult females introduced on Thyestilla gebleri (Coleoptera: Cerambycidae) larvae on their paralysis time, pre-oviposition period, oviposition period and fecundity, and the related fitness of their offspring. Results showed that small female wasps needed more time to paralyze a host and had a higher mortality rate than large female wasps. More offspring were produced by large female wasps than by small female wasps, and the percentage and body size of female offspring was not affected by maternal body size. The duration of the egg stage was not affected by foundress size, nor was that of the pupal stage, but the duration of the larval stage and generation time of small female wasps was longer than that of large females. Our findings suggest that the parasitic fitness and offspring performance are affected by maternal size, and there is need to choose reasonable body size of female wasps, to optimally utilize mass rearing and to control target pests with the lowest mortality cost.
The pure-MBBR process was applied to remove ammonia in a full-scale micro-polluted-water treatment plant with a daily treatment capacity of 260 × 10
m
/d, Guangdong, China. The relationship between ...treatment efficiency, physical and chemical properties and microbial diversity in the process of biofilm growth was explored, and the oxygen transfer model of biofilm was established. The results show that the effluent of two-stage pure MBBR process is stable and up to standard after 10 days' incubation. The nitrification loads of two-stage biofilm was stable on the 14th day. The biomass and biofilm thickness lagged behind the nitrification load, and reached a relatively stable level on the 28th day. The species richness of biofilm basically reached a stable level on the 21st day, and the microbial diversity of primary biofilm was higher. In the primary and secondary stage at different periods, the relative abundance of dominant nitrifying bacteria Nitrospira reaches 8.48-13.60%, 6.48-9.27%, and Nitrosomonas reaches 2.89-5.64%, 0.00-3.48%. The pure MBBR system mainly adopts perforated aeration. Through the cutting and blocking of bubbles by suspended carriers, the oxygen transfer rate of the system was greatly improved.
Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to cardiac fibrosis and heart failure (HF). Recent studies have demonstrated that EndMT is regulated by autophagy, and we ...previously showed suppression of excessive autophagy and alleviation of cardiac fibrosis in HF mice with inactivated receptor for advanced glycation end products (RAGE). Thus, we investigated whether reduced cardiac fibrosis due to RAGE knockout occurred by inhibiting EndMT mediated by excessive autophagy. We found a decrease in endothelial cells (CD31
/VE-Cadherin
) and an increase in cells co-expressing CD31 and α-smooth muscle actin (α-SMA, myofibroblast marker) at 8 weeks in heart tissue of mice subjected to transverse aortic constriction (TAC), which implied EndMT. Knockout RAGE decreased EndMT accompanied by decreased expression of autophagy-related proteins (LC3BII/I and Beclin 1), and alleviated cardiac fibrosis and improved cardiac function in TAC mice. Moreover, 3-methyladenine (3-MA) and chloroquine (CQ), inhibitors of autophagy, attenuated EndMT, and cardiac fibrosis in TAC mice. Importantly, EndMT induced by AGEs could be blocked by autophagy inhibitor in vivo and in vitro. These results suggested that AGEs/RAGE-autophagy-EndMT axis involved in the development of cardiac fibrosis and knockout RAGE ameliorated cardiac fibrosis through decreasing EndMT regulated by autophagy, which could be a promising therapeutic strategy for HF.
Since its outbreak in December 2019, a series of clinical trials on coronavirus disease 2019 (COVID-19) have been registered or carried out. However, the significant heterogeneity and less critical ...outcomes of such trials may be leading to a waste of research resources. This study aimed to develop a core outcome set (COS) for clinical trials on COVID-19 in order to tackle the outcome issues. The study was conducted according to the Core Outcome Measures in Effectiveness Trials (COMET) Handbook: Version 1.0, a guideline for COS development. A research group was set up that included experts in respiratory and critical medicine, traditional Chinese medicine (TCM), evidence-based medicine, clinical pharmacology, and statistics, in addition to medical journal editors. Clinical trial registry websites (www.chictr.org.cn and clinicaltrials.gov) were searched to retrieve clinical trial protocols and outcomes in order to form an outcome pool. A total of 78 clinical trial protocols on COVID-19 were included and 259 outcomes were collected. After standardization, 132 outcomes were identified within seven different categories, of which 58 were selected to develop a preliminary outcome list for further consensus. After two rounds of Delphi survey and one consensus meeting, the most important outcomes for the different clinical classifications of COVID-19 were identified and determined to constitute the COS for clinical trials on COVID-19 (COS-COVID). The COS-COVID includes one outcome for the mild type (time to 2019 novel coronavirus (2019-nCoV) reverse transcription-polymerase chain reaction (RT-PCR) negativity), four outcomes for the ordinary type (length of hospital stay, composite events, score of clinical symptoms, and time to 2019-nCoV RT-PCR negativity), five outcomes for the severe type (composite events, length of hospital stay, arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2), duration of mechanical ventilation, and time to 2019-nCoV RT-PCR negativity), one outcome for critical type (all-cause mortality), and one outcome for rehabilitation period (pulmonary function). The COS-COVID is currently the most valuable and practical clinical outcome set for the evaluation of intervention effect, and is useful for evidence assessment and decision-making. With a deepening understanding of COVID-19 and application feedback, the COS-COVID should be continuously updated.
Both executive corruption and corporate innovation are important factors affecting corporate development. This paper explores the impact of executive corruption on corporate innovation and examines ...the mechanism of their effects from the perspective of financing constraints. It is found that executive corruption significantly inhibits corporate innovation in general. In addition, financing constraints act as a mediator between executive corruption and corporate innovation, i.e., executive corruption exacerbates the financing constraints faced by firms and affects the access to and allocation of corporate resources, thus leading to a decrease in corporate innovation inputs and outputs. Further, the inhibitory effect of executive corruption on firm innovation is more pronounced in firms with low quality internal controls, strong professional background of executives, low quality external audit, low shareholding of institutional investors, strong political affiliation, and state-owned enterprises.
The autonomic nervous system (ANS) plays a central role in dynamic adaptation during pregnancy in accordance with the pregnancy demands which otherwise can lead to various pregnancy complications. ...Despite the importance of understanding the ANS function during pregnancy, the literature lacks sufficiency in the ANS assessment. In this study, we aimed to identify the heart rate variability (HRV) function during the second and third trimesters of pregnancy and 1 week after childbirth and its relevant predictors in healthy pregnant Latina individuals in Orange County, CA.
= 16 participants were enrolled into the study from which
= 14 (
= 13 healthy and n = 1 complicated) participants proceeded to the analysis phase. For the analysis, we conducted supervised machine learning modeling including the hierarchical linear model to understand the association between time and HRV and random forest regression to investigate the factors that may affect HRV during pregnancy. A
-test was used for exploratory analysis to compare the complicated case with healthy pregnancies.
The results of hierarchical linear model analysis showed a significant positive relationship between time (day) and average HRV (estimated effect = 0.06;
< 0.0001), regardless of being healthy or complicated, indicating that HRV increases during pregnancy significantly. Random forest regression results identified some lifestyle and sociodemographic factors such as activity, sleep, diet, and mental stress as important predictors for HRV changes in addition to time. The findings of the
-test indicated that the average weekly HRV of healthy and non-healthy subjects differed significantly (
< 0.05) during the 17 weeks of the study.
It is imperative to focus our attention on potential autonomic changes, particularly the possibility of increased parasympathetic activity as pregnancy advances. This observation may challenge the existing literature that often suggests a decline in parasympathetic activity toward the end of pregnancy. Moreover, our findings indicated the complexity of HRV prediction, involving various factors beyond the mere passage of time. To gain a more comprehensive understanding of this dynamic state, future investigations should delve into the intricate relationship between autonomic activity, considering diverse parasympathetic and sympathetic metrics, and the progression of pregnancy.
Objective Xinyang Tablet (XYT) has emerged as a potential intervention to counter sepsis-induced myocardial dysfunction (SMID) by influencing macrophage autophagy and M2 polarization. This study ...aimed to unravel the underlying mechanism of XYT in sepsis-induced myocardial dysfunction (SIMD). Methods A microarray analysis was employed to explore sepsis-related changes, and bioinformatics analysis was used to predict lncRNAs binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). This studio utilized SIMD mouse models induced by lipopolysaccharide (LPS) injection, followed by treatments involving varied doses of XYT, digoxin (positive control), or si-LncSICRNT1. After seven days, evaluations encompassing mouse hair/mental state/diet/weight were measured, and cardiac function via echocardiography were conducted. Myocardial tissue changes were observed using hematoxylin-eosin staining. Additionally, bone marrow-derived macrophages (BMDMs) subjected to LPS for M1 polarization were treated with oe-LncSICRNT1, si-TRAF6 and their negative control, XYT, or autophagy inhibitor 3-Methyladenine (3-MA) (positive control). RT-qPCR and Western blot analyses were employed to assess LncSICRNT1, TRAF6, Beclin-1, LC3II/LC3I, and p62 levels. Immunohistochemistry and flow cytometry were used for M1/M2 polarization markers, while enzyme-linked immunosorbent assay (ELISA) gauged inflammatory factor levels. Interaction between TRAF6 and LncSICRNT1 was probed using RNA pull-down and RNA immunoprecipitation (RIP) assays. Results Chip analysis obtained 1463 differentially expressed lncRNAs, including LINC01550 (LncSICRNT1). Further prediction indicated that LncSICRNT1 was highly likely to directly bind to TRAF6. XYT treatment in LPS-induced SIMD mice led to notable enhancements in sleep/hair/diet/activity, increased weight/left ventricular end-diastolic diameter (LVEDd)/LV ejection fraction (LVEF)/LV fraction shortening (LVFS). These improvements were associated with elevated LncSICRNT1 expression and decreased TRAF6 protein levels, culminating in reduced myocardial inflammatory responses and improved cardiac function. Notably, XYT was found to suppress macrophage M1 polarization, while enhancing M2 polarization, ultimately benefitting cardiac function via LncSICRNT1 modulation. Furthermore, the study revealed LncSICRNT1 modulated Beclin-1 ubiquitination and restrained macrophage autophagy by targeting TRAF6 expression. Conclusion The study highlights XYT's potential to ameliorate LPS-induced SIMD by elevating LncSICRNT1 expression, influencing TRAF6 expression, and regulating Beclin-1 ubiquitination. These actions collectively inhibit macrophage autophagy and foster M1/M2 polarization, contributing to cardiac function improvement. Keywords: Xinyang tablet, Sepsis-induced myocardial dysfunction, LncSICRNT1, TRAF6, Macrophages, M1/M2 polarization, Beclin-1, Ubiquitination
The receptor for advanced glycation end products (RAGE) is involved in heart failure (HF) by mediating diverse pathologic processes, including the promotion of inflammation and autophagy. However, ...the role of RAGE in pressure overload-induced HF is not well understood. We found that stimulation of RAGE triggered the death of neonatal rat ventricular myocytes (NRVMs), while cell death was alleviated by ATG5 knockdown. Using transverse aortic constriction (TAC) in mice as a model of pressure overload-induced HF, we demonstrated that RAGE knockout or RAGE blockade attenuated cardiac hypertrophy and fibrosis as well as cardiac dysfunction at 8 weeks after TAC. Importantly, RAGE knockout reversed upregulation of autophagy related proteins (LC3BII/I and Beclin 1) and reduced cardiomyocyte death, indicating that excessive autophagy after TAC was inhibited. Moreover, RAGE knockout or blockade reduced the upregulation of pp65-NFκB and BNIP3, which mediate autophagy. Taken together, these results suggest that RAGE plays an important role in the progression of HF by regulating autophagy. Therefore, inhibition of the RAGE-autophagy axis could be a promising new strategy for treatment of heart failure.
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