The protein levels and activities of calpain-1 and calpain-2 are increased in cardiac mitochondria under pathological conditions including ischemia, diabetes, and sepsis, and transgenic ...overexpression of mitochondrial-targeted calpain-1 induces dilated heart failure, which underscores an important role of increased calpain in mitochondria in mediating myocardial injury. However, it remains to be determined whether selective inhibition of calpain in mitochondria protects the heart under pathological conditions. In this study, we generated transgenic mice overexpressing mitochondrial-targeted calpastatin in cardiomyocytes. Their hearts were isolated and subjected to global ischemia/reperfusion. Hyperglycemia was induced in the transgenic mice by injections of STZ. We showed that transgenic calpastatin was expressed exclusively in mitochondria isolated from their hearts but not from other organs including skeletal muscle and lung tissues. Transgenic overexpression of mitochondrial-targeted calpastatin significantly attenuated mitochondrial oxidative stress and cell death induced by global ischemia/reperfusion in isolated hearts, and ameliorated mitochondrial oxidative stress, cell death, myocardial remodeling and dysfunction in STZ-treated transgenic mice. The protective effects of mitochondrial-targeted calpastatin were correlated with increased ATP5A1 protein expression and ATP synthase activity in isolated hearts subjected to global ischemia/reperfusion and hearts of STZ-treated transgenic mice. In cultured rat myoblast H9c2 cells, overexpression of mitochondrial-targeted calpastatin maintained the protein levels of ATP5A1 and ATP synthase activity, prevented mitochondrial ROS production and decreased cell death following hypoxia/reoxygenation, whereas upregulation of ATP5A1 or scavenging of mitochondrial ROS by mito-TEMPO abrogated mitochondrial ROS production and decreased cell death. These results confirm the role of calpain in myocardial injury, suggesting that selective inhibition of calpain in myocardial mitochondria by mitochondrial-targeted calpastatin is an effective strategy for alleviating myocardial injury and dysfunction in cardiac pathologies.
•Semen quality parameters were collected at multiple time points across study period.•Within subject variability was high for total and progressive sperm motility.•Short and long sleep duration were ...associated with impaired semen quality parameters.•Poor sleep quality may adversely affect human semen quality parameters.
Short sleep duration and poor sleep quality are increasingly prevalent in modern society and may be associated with impaired semen quality, yet studies are inconclusive.
To investigate the reproducibility of semen quality parameters among 842 healthy men screened as potential sperm donors and explore the associations of sleep duration and quality with repeated measures of semen quality parameters.
We assessed sleep duration (night sleep and daytime napping) and sleep quality using the Pittsburgh Sleep Quality Index (PSQI) among 842 healthy men screen as potential sperm donors. We examined sleep characteristics in relation to repeated measurements (n = 5601) of semen parameters using linear mixed-effects models.
High degrees of within-individual variability were found for total and progressive sperm motility with intraclass correlation coefficient (ICC) of 0.20 and 0.22, respectively; while fair-to-good reproducibilities were observed for sperm volume, concentration, and total count (ICC = 0.54, 0.62, and 0.50, respectively). Compared to men with total sleep duration of 8.0–8.5 h/day (h/d), men who slept less than 6.0 h/d and higher than 9.0 h/d had lower sperm volume of 12% 95% confidence interval (CI): −22%, −0.68% and 3.9% (95% CI: −7.3%, −0.44%), respectively. Compared to men with night sleep duration of 7.5–8.0 h/d, men who slept less than 6.0 h/d had lower total and progressive sperm motility of 4.4% (95 CI:−8.4%, −0.24%) and 5.0% (95% CI: −9.2%, −0.48%), respectively. Compared to men who reported good sleep quality (total PSQI score ≤5.0), those reporting poor sleep quality (total PSQI score >5.0) had lower total sperm count, total motility, and progressive motility of 8.0% (95% CI: −15%, −0.046%), 3.9% (95% CI: −6.2%, −1.5%), and 4.0% (95% CI: −6.5%, −1.4%), respectively.
Both long and short sleep duration and poor sleep quality were associated with impaired semen quality parameters. The high within-individual variability of total and progressive sperm motility suggests that a single measurement may result in a moderate degree of classification error.
With the microelectronics technology going toward its physical limits and the emergence of three-dimensional chip stack architectures, now more than ever there are both needs and opportunities for ...novel materials to help address some of these pressing thermal management challenges. In this paper, a high-thermal-conductivity insulative SiO
2
-coated nano-Cu particle is prepared for new-type underfill materials of high-performance microelectronics packaging. It was found that nano-Cu can be successfully coated with SiO
2
by using the surface modification between cetyltrimethyl ammonium bromide and silane coupling agent although nano-Cu particles have silicon-disordered property during the coating process of tetraethyl orthosilicate hydrolysis. Moreover, the thermal conductivity of epoxy mixed with nano-Cu@SiO
2
as the packaging underfill is dramatically increased from 0.15 W/m K of the pure-EP and 0.60 W/m K of the EP/SiO
2
to 2.9 W/m K due to electronic heat transfer, heat network and fast heat transfer center. It effectively releases the heat generated by the IC device, and the service life of the device is significantly improved from 63 min of pure-EP and 350 min of the EP/nano-SiO
2
to 1039 min. The new material creates a challenging environment for keeping modern electronic devices cool, a critical factor in determining their speed, efficiency and reliability.
In flowering plants, diploid sporophytic tissues in ovules and anthers support meiosis and subsequent haploid gametophyte development. These analogous reproductive functions suggest that common ...mechanisms may regulate ovule and anther development. Two Arabidopsis Auxin Response Factors, ARF6 and ARF8, regulate gynoecium and stamen development in immature flowers. Wild-type pollen grew poorly in arf6 arf8 gynoecia, correlating with ARF6 and ARF8 expression in style and transmitting tract. ARF6 and ARF8 transcripts are cleavage targets of the microRNA miR167 , and overexpressing miR167 mimicked arf6 arf8 phenotypes. Mutations in the miR167 target sites of ARF6 or ARF8 caused ectopic expression of these genes in domains of both ovules and anthers where miR167 was normally present. As a result, ovule integuments had arrested growth, and anthers grew abnormally and failed to release pollen. Thus, miR167 is essential for correct patterning of gene expression, and for fertility of both ovules and anthers. The essential patterning function of miR167 contrasts with cases from animals in which miRNAs reinforce or maintain transcriptionally established gene expression patterns.
Polydopamine (PD) coating and PD-graft-poly(ethylene glycol) (PD-g-PEG) surface modification can be used to improve the anti-fouling properties of membrane surface. This work studies the features of ...polyethersulfone (PES) membranes with different molecular weight cut-off (MWCO) modified by PD coating and PD-g-PEG modification on their morphology, stability, and adsorbability. The stability of modified membranes was evaluated by immersion tests. Bovine serum albumin (BSA) was used as a model foulant to investigate the anti-biofouling performance of modified membranes. The results of stability tests showed that both modified membranes had a fine mechanical stability, and the PD-g-PEG modified membrane had a better chemical stability. The images of FESEM and AFM indicate the modifications of PD coating and PD-g-PEG changes the morphology of the PES ultrafiltration (UF) membrane apparently. The modified membranes had less flux reduction in filtration and lower adsorptive amount of BSA in isothermal adsorption tests. The PD-g-PEG modification improves the stability of the PES membrane and the adsorbability for BSA more significantly.
•Roughness of the membrane surface increases after the modifications.•The layer stability of coated PD and grafting PD-g-PEG was evaluated.•The modifications of coating and grafting reduce the adsorptive fouling of BSA.
Deep vein thrombosis (DVT) significantly influences the prognosis of patients. It's necessary to analyze the risk factors for postoperative DVT in patients undergone gynecological laparoscopic ...surgery.
Patients who underwent gynecological laparoscopic surgery from January 1, 2018 to May 31, 2020 were included. The characteristics and clinical data of DVT and non DVT patients were collected and analyzed. Logistic regression analysis was performed to identify the risk factors of DVT in patients undergone gynecological laparoscopic surgery.
A total of 355 patients undergone gynecological laparoscopic surgery were included, the incidence of postoperative DVT was 11.55%. There were significant differences in the age, hypertension, D-dimer, duration of surgery, intraoperative pneumoperitoneum pressure, duration of days in bed between DVT and non-DVT groups (all p < 0.05), and there were no significant difference in the BMI, diabetes, hyperlipidemia, ASA classification and intraoperative blood transfusion between DVT and non-DVT groups (all p > 0.05). Age > 50 years (OR 4.246, 95% CI 1.234-7.114), hypertension (OR 2.219, 95% CI 1.153-4.591), D-dimer > 0.5 mg/L (OR 3.914, 95% CI 1.083-5.229), duration of surgery ≥ 60 min (OR 2.542, 95% CI 1.101-4.723), intraoperative pneumoperitoneum pressure ≥ 15 mmHg (OR 3.845, 95% CI 1.119-5.218), duration of days in bed > 3 days (OR 1.566, 95% CI 1.182-1.994) was the independent risk factors for DVT in patients undergone gynecological laparoscopic surgery (all p < 0.05).
The incidence of postoperative DVT in patients undergone gynecological laparoscopic surgery is high, and those high-risk factors should be targeted to intervene in order to reduce the postoperative DVT.
The growth factor progranulin (PGRN) has been implicated in embryonic development, tissue repair, tumorigenesis, and inflammation, but its receptors remain unidentified. We report that PGRN bound ...directly to tumor necrosis factor receptors (TNFRs) and disturbed the TNFα-TNFR interaction. PGRN-deficient mice were susceptible to collagen-induced arthritis, and administration of PGRN reversed inflammatory arthritis. Atsttrin, an engineered protein composed of three PGRN fragments, exhibited selective TNFR binding. PGRN and Atsttrin prevented inflammation in multiple arthritis mouse models and inhibited TNFα-activated intracellular signaling. Collectively, these findings demonstrate that PGRN is a ligand of TNFR, an antagonist of TNFα signaling, and plays a critical role in the pathogenesis of inflammatory arthritis in mice. They also suggest new potential therapeutic interventions for various TNFα-mediated pathologies and conditions, including rheumatoid arthritis.
Pigeon-inspired optimization (PIO) is a new type of intelligent algorithm. It is proposed that the algorithm simulates the movement of pigeons going home. In this paper, a new pigeon herding ...algorithm called compact pigeon-inspired optimization (CPIO) is proposed. The challenging task for multiple algorithms is not only combining operations, but also constraining existing devices. The proposed algorithm aims to solve complex scientific and industrial problems with many data packets, including the use of classical optimization problems and the ability to find optimal solutions in many solution spaces with limited hardware resources. A real-valued prototype vector performs probability and statistical calculations, and then generates optimal candidate solutions for CPIO optimization algorithms. The CPIO algorithm was used to evaluate a variety of continuous multi-model functions and the largest model of hydropower short-term generation. The experimental results show that the proposed algorithm is a more effective way to produce competitive results in the case of limited memory devices.
Cytosine methylation is an important mechanism for dynamical regulation of gene expression and trans- posable element （TE） mobility during plant developmental processes. Here, we identified the ...transcription start sites of genes using high-throughput sequencing and then analyzed the DNA methylation status in soybean roots, stems, leaves, and cotyledons of developing seeds at single-base resolution. Profiling of DNA methylation in different organs revealed 2162 differentially methylated regions among organs, and a portion of hypomethylated regions were correlated with high expression of neighboring genes. Because of the different distribution of class I TEs （retrotransposons） and class II TEs （DNA transposons）, the promoters of the lowest-expressed genes showed higher levels of CG and CHG methyla- tion but a lower level of CHH methylation. We further found that the CHH methylation level of class II TEs was higher than class I TEs, possibly due to the presence of more smRNAs in class II TEs. In cotyledons of developing seeds, smRNA abundance was roughly positively correlated with hypermethylated regions but negatively related to hypomethylated regions. These studies provide significant insights into the complicated interplays among DNA methylation, smRNA abundance, TE distribution, and gene expression in soybean.
This study aimed to assess the safety of SGLT2 inhibitors in type 2 diabetes, chronic kidney disease, and chronic heart failure considering the number needed to treat (NNT).Methods: Data were ...obtained from 10 morbidity-mortality trials and were pooled to calculate the NNTs. The number needed to treat to benefit (NNTB) is used to express beneficial outcomes, whereas the number needed to treat to be harmed (NNTH) is used for harmful outcomes. The eight safety outcomes of interest were fracture, diabetic ketoacidosis, amputation, urinary tract infection, genital infection, acute kidney injury, severe hypoglycemia, and volume depletion.A total of 10 trials involving 76319 patients were included in this meta-analysis. The mean follow-up was 2.35 years. SGLT2 inhibitors play a positive role in acute kidney injury and severe hypoglycemia, with the corresponding mean NNTBs being 157 and 561, respectively. SGLT2 inhibitors significantly increased the risk of diabetic ketoacidosis, genital infection, and volume depletion, with the corresponding mean NNTHs being 1014, 41, and 139. It was found that the safety of SGLT2 inhibitors was the same in three diseases and five SGLT2 inhibitors.SGLT2 inhibitors have a positive impact on acute kidney injury and severe hypoglycemia, but they increase the incidence of diabetic ketoacidosis, genital infection, and volume depletion.
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