Microbiological interpretation of weak ultrasound enhanced biological wastewater treatment - using Escherichia coli degrading glucose as model system.

The Escherichia coli (E.coli) degrading glucose irradiated by ultrasound irradiation (20 W, 14 min) was investigated as the model system, the glucose degradation increased by 13 % while the E.coli proliferation decreased by 10 % after culture for 18 h. It indicated a tradeoff effect between substrate degradation and cell proliferation, which drove the enhanced contaminants removal and excess sludge reduction in a weak ultrasound enhanced biological wastewater treatment. The enzymatic activities (catalase, superoxide dismutase, adenosine triphosphatases, lactic dehydrogenase, membrane permeability, intracellular reactive oxygen species and calcium ion of E. coli increased immediately by 12 %, 63 %, 124 %, 19 %, 15 %, 4-fold and 38-fold, respectively by ultrasound irradiation power of 20 W for 14 min. Furthermore, the membrane permeability of irradiated E. coli increased by 26 % even though the ultrasound stopped for 10 h. Additionally, pathways associated with glucose degradation and cell proliferation were continuously up-regulated and down-regulated, respectively.

Acacetin alleviates autoimmune myocarditis by regulating CD4+ T cell mitochondrial respiration.

BACKGROUND: Myocarditis refers to an autoimmune inflammatory response of the myocardium with characterization of self-reactive CD4+ T cell activation, which lacks effective treatment and has a poor prognosis. Acacetin is a natural flavonoid product that has been reported to have anti-inflammatory effects. However, acacetin has not been investigated in myocarditis. METHODS: Oral acacetin treatment was administered in an experimental autoimmune myocarditis model established with myosin heavy chain-alpha peptide. Echocardiography, pathological staining, and RT-qPCR were used to detect cardiac function, myocardial injury, and inflammation levels. Flow cytometry was utilized to detect the effect of acacetin on CD4+ T cell function. RNA-seq, molecular docking, and microscale thermophoresis (MST) were employed to investigate potential mechanisms. Seahorse analysis, mitoSOX, JC-1, and mitotracker were utilized to detect the effect of acacetin on mitochondrial function. RESULTS: Acacetin attenuated cardiac injury and fibrosis as well as heart dysfunction, and reduced cardiac inflammatory cytokines and ratio of effector CD4+ T and Th17 cells. Acacetin inhibited CD4+ T cell activation, proliferation, and Th17 cell differentiation. Mechanistically, the effects of acacetin were related to reducing mitochondrial complex II activity thereby inhibiting mitochondrial respiration and mitochondrial reactive oxygen species in CD4+ T cells. CONCLUSION: Acacetin may be a valuable therapeutic drug in treating CD4+ T cell-mediated myocarditis.

Study on the relationship between the changes in polyamine content and seedless grapes embryo rescue breeding.

This study was envisaged to investigate the physiological reasons affecting the embryo development and abortion of seedless grapes on the basis of the previous embryo rescue breeding techniques of seedless grapes. Specifically, the relationship between the embryo rescue breeding of seedless grapes and the change of polyamine content was evaluated, in order to provide hybrid germplasm in the breeding of new seedless grape cultivars. Four ovules of 4 naturally pollinated Eurasian seedless grape cultivars, including 'Thompson Seedless' grape (hereinafter referred to as 'Seedless White' grape), 'Flame Seedless' grape, 'Heshi Seedless' grape and 'Ruby Seedless' grape were employed for the study. Changes in the endogenous polyamine content, exogenous polyamine content, and the suitable combination of exogenous polyamines in the seedless grape berries and isolated ovules were determined during the best embryo rescue period. Furthermore, the effect of different exogenous polyamine contents on the germination and seedling rate of different seedless grape embryos was analyzed. In the best embryo rescue period, the number of ovules had different effects on the content of polyamines. For seedless grape cultivars with 4 ovules, a high content of polyamines was found to be more beneficial in the embryonic development. The existence of embryos had different effects on the development of embryos. In the ovules with embryo, an increase in the content of polyamine was beneficial to the growth and development of the ovule. Different ratios of exogenous polyamines had varying effects on the embryonic development. Putrescine (Put) exhibited the greatest effect on the embryonic development. Further, correlation analysis showed that different combinations of exogenous polyamines had varying effects on the embryonic development. A maximal ovule development was observed in the combination of exogenous polyamines of putrescine2+spermidine2+spermine1. For maximal embryo germination and seeding formation, the optimal combination was putrescine2+spermidine2+spermine2. Irrespective to the number of ovules or the existence of embryos, the results indicated that a high content of endogenous polyamines promoted the growth and development of embryos. The embryo rescue efficiency of different exogenous polyamines was different, and the appropriate combination of exogenous polyamines was beneficial to the growth and development of ovules, with a high development rate of the ovule and seedling.

Status and influencing factors of work stress among nurse managers in western China: a cross-sectional survey study.

AIMS: Due to the nature of their work, nurses are more prone to experiencing psychological consequences than other healthcare workers. However, evidence on the emotional burden of nurse managers in China is limited. Furthermore, perceived organizational support has been approved that can affect mental health outcomes. Therefore, this study aimed to investigate the status quo and influencing factors of nurse managers' work stress, and their possible relationship with perceived organizational support, which could further provide more countermeasures to safeguard their health. METHODS: A cross-sectional online survey of 21 secondary and tertiary hospitals was conducted in a city in Sichuan province, Southwest China, using a convenience sampling method between October and November 2022. Data were collected using the general information questionnaire, the Chinese version of the Stress Overload Scale (SOS) and the perceived Organizational Support Scale (POSS). SPSS 23.0 was applied to analyze the data. RESULTS: In total, 380 participants completed the survey. The median scores (interquartile range [IQR]) for SOS and POSS were 60.50 (50.00, 70.75) and 51.00 (44.00, 55.00), respectively. The work stress of the nurse managers was negatively correlated with perceived organizational support (P < 0.01). Multiple linear regression analysis showed that age older than 40 years, from secondary hospitals, working in emergency or pediatric wards, and professional qualification of supervisor nurse or deputy supervisor nurse, and the scores of POSS less than 51 significantly influenced the work stress of the nurse managers. CONCLUSIONS: Our study shows that nurse managers are more prone to work stress, and organizational support can effectively reduce this stress. Governments and hospital administrators should pay more attention to providing comprehensive strategies based on various risk factors to protect and promote psychological health.

Parental readiness for hospital discharge and the relationship with growth and development of infant in China.

PURPOSE: This study aimed to evaluate the associations between parental readiness for discharge and neonatal growth. DESIGN AND METHODS: This cross-sectional study included 549 newborns whose parents filled out the Newborn-Parental Readiness for Discharge Scale (N-PRDS).Additionally, data on birth weight, length, and head circumference were collected.The total N-PRDS scores were divided into three levels in terms of readiness: low, intermediate, and high readiness. Parents and infants were followed up 42 days after the birth, and the weight, length, and head circumference of the newborns were measured at the hospital. RESULTS: A total of 306 data were obtained. The generalized linear mixed model (GLMM) showed that time and parental readiness had an interaction effect on the weight, length and head circumference of infants. The difference in weight between infants under the high and low readiness conditions at 42 days increased by 0.357 kg compared to the difference at birth. The difference in length between high readiness infants and low readiness infants at 42 days increased by 2.155 cm compared to the difference at birth. The difference between the infants' head circumference under the high and low readiness conditions at 42 days was 0.873 cm higher than that at birth. CONCLUSIONS: High readiness for discharge could promote an increase in infant weight, length,and head circumference at 42 days after birth. PRACTICE IMPLICATIONS: Nurses should assess parental readiness prior to the discharge of newborns by using the N-PRDS and provide discharge guidance and education to newborns' parents based on the outcomes of this scale.

Research progress of hexokinase 2 in inflammatory-related diseases and its inhibitors.

Hexokinase 2 (HK2) is a crucial enzyme involved in glycolysis, which converts glucose into glucose-6-phosphate and plays a significant role in glucose metabolism. HK2 can mediate glycolysis, which is linked to the release of inflammatory factors. The over-expression of HK2 increases the production of pro-inflammatory cytokines, exacerbating the inflammatory reaction. Consequently, HK2 is closely linked to various inflammatory-related diseases affecting multiple systems, including the digestive, nervous, circulatory, respiratory, reproductive systems, as well as rheumatoid arthritis. HK2 is regarded as a novel therapeutic target for inflammatory-related diseases, and this article provides a comprehensive review of its roles in these conditions. Furthermore, the development of potent HK2 inhibitors has garnered significant attention in recent years. Therefore, this review also presents a summary of potential HK2 inhibitors, offering promising prospects for the treatment of inflammatory-related diseases in the future.

Deficiency of HtrA3 Attenuates Bleomycin-Induced Pulmonary Fibrosis Via TGF-ß1/Smad Signaling Pathway.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by excessive extracellular matrix deposition. No effective treatments are currently available for IPF. High-temperature requirement A3 (HtrA3) suppresses tumor development by antagonizing transforming growth factor ß (TGF-ß) signaling; however, little is known about the role of HtrA3 in IPF. This study investigated the role of HtrA3 in IPF and underlying mechanisms. METHODS: Lung tissues were collected from patients with IPF and mice with bleomycin (BLM)-induced pulmonary fibrosis, and HtrA3 expression was measured in tissue samples. Then, HtrA3 gene knockout mice were treated with BLM to induce pulmonary fibrosis and explore the effects and underlying mechanism of HtrA3 on pulmonary fibrosis. RESULTS: HtrA3 was up-regulated in the lung tissues of patients with IPF and the pulmonary fibrotic mouse model compared to corresponding control groups. HtrA3 knockout decreased pulmonary fibrosis-related protein expression, alleviated the symptoms of pulmonary fibrosis, and inhibited epithelial-mesenchymal transition (EMT) in BLM-induced lung tissue compared with BLM-induced wild-type mice. The TGF-ß1/Smad signaling pathway was activated in fibrotic lung tissue, whereas HtrA3 knockout inhibited this pathway. CONCLUSION: The expression level of HtrA3 is increased in fibrotic lungs. HtrA3 knockout alleviates the symptoms of pulmonary fibrosis probably via the TGF-ß1/Smad signaling pathway. Therefore, HtrA3 inhibition is a potential therapeutic target for pulmonary fibrosis.

A survey of caregiver burden for stroke survivors in non-teaching hospitals in Western China.

The social factors that moderate stroke caregiver burden have been found to be culture- and gender-specific. We examined the factors that influence the social support and self-efficacy of caregivers of stroke survivors and the burden of caregiving in China. To determine the caregiver burden of stroke survivors, their social support, and their self-efficacy. A total of 328 stroke survivors and their caregivers were recruited from 4 tertiary medical centers to participate in this cross-sectional study. The sociodemographic and stroke-related characteristics of the participants were obtained. Perceived social support and self-efficacy were assessed using the Social Support Rating Scale and General Self-efficacy Scale, respectively. Caregiver burden was assessed using the Zarit Burden Interview Scale. Relationships between the variables were assessed using Pearson's correlation, the chi-square test, and a paired t test. A total of 27.4% of the caregivers reported receiving adequate social support, while 20.7% reported high levels of self-efficacy. A total of 67.1% of the caregivers experienced varying degrees of care burden, while the remaining 32.9% felt no burden. Participants' sociodemographic characteristics (age, daily care time, self-rated health, and financial situation) were significantly related to caregiver burden, social support, and self-efficacy (P < .001). The findings indicate an inverse relationship between caregiver burden, social support and self-efficacy. Adequate social support and self-efficacy can reduce stroke caregivers' burden. Hospital departments should provide assistance to stroke caregivers through educational programs and group training to increase their social support and self-efficacy, thereby alleviating their burden.

Heart-targeting exosomes from human cardiosphere-derived cells improve the therapeutic effect on cardiac hypertrophy.

Exosomes of human cardiosphere-derived cells (CDCs) are very promising for treating cardiovascular disorders. However, the current challenge is inconvenient delivery methods of exosomes for clinical application. The present study aims to explore the potential to enhance the therapeutic effect of exosome (EXO) from human CDCs to myocardial hypertrophy. A heart homing peptide (HHP) was displayed on the surface of exosomes derived from CDCs that were forced to express the HHP fused on the N-terminus of the lysosomal-associated membrane protein 2b (LAMP2b). The cardiomyocyte-targeting capability of exosomes were analyzed and their therapeutic effects were evaluated in a mouse model of myocardial hypertrophy induced by transverse aorta constriction (TAC). The molecular mechanisms of the therapeutic effects were dissected in angiotensin II-induced neonatal rat cardiomyocyte (NRCMs) hypertrophy model using a combination of biochemistry, immunohistochemistry and molecular biology techniques. We found that HHP-exosomes (HHP-EXO) accumulated more in mouse hearts after intravenous delivery and in cultured NRCMs than control exosomes (CON-EXO). Cardiac function of TAC mice was significantly improved with intravenous HHP-EXO administration. Left ventricular hypertrophy was reduced more by HHP-EXO than CON-EXO via inhibition of ß-MHC, BNP, GP130, p-STAT3, p-ERK1/2, and p-AKT. Similar results were obtained in angiotensin II-induced hypertrophy of NRCMs, in which the beneficial effects of HHP-EXO were abolished by miRNA-148a inhibition. Our results indicate that HHP-EXO preferentially target the heart and improve the therapeutic effect of CDCs-exosomes on cardiac hypertrophy. The beneficial therapeutic effect is most likely attributed to miRNA-148a-mediated suppression of GP130, which in turn inhibits STAT3/ERK1/2/AKT signaling pathway, leading to improved cardiac function and remodeling.

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OBJECTIVES: To study the association between neonatal discharge preparedness and adverse health events. METHODS: The neonates who were born in hospitals from different regions of Gansu Province in China and their parents were enrolled as subjects, and an investigation was performed for the discharge preparedness. According to the level of discharge preparedness, the subjects were divided into low-, middle-, and high-level groups. The neonates were followed up to observe the incidence rate of adverse health events within one month after discharge. The association between neonatal discharge preparedness and adverse health events was analyzed. RESULTS: The neonates with adverse health events had a significantly lower level of discharge preparedness than those without adverse events (P<0.05). The multivariate logistic regression analysis showed that the incidence rate of adverse health events was reduced by 34.8% in the middle-level group and 78.7% in the high-level group compared with the low-level group (P<0.05). The readmission rate of neonates was 8.1% (35/430), and the neonates readmitted had a significantly lower level of discharge preparedness than those not readmitted (P<0.05). The multivariate logistic regression analysis showed that the readmission rate of neonates was reduced by 67.4% in the middle-level group and 84.2% in the high-level group compared with the low-level group (P<0.05). CONCLUSIONS: Discharge preparedness may affect the incidence of adverse health events and the rate of readmission within one month after discharge. Medical staff should adopt effective intervention measures to improve discharge preparedness, so as to reduce the incidence of adverse health events and the rate of readmission.

An R2R3-MYB transcription factor VyMYB24, isolated from wild grape Vitis yanshanesis J. X. Chen., regulates the plant development and confers the tolerance to drought.

In grapevines, the MYB transcription factors play an important regulatory role in the phenylpropanoid pathway including proanthocyanidin, anthocyanin, and flavonoid biosynthesis. However, the role of MYB in abiotic stresses is not clear. In this study, an R2R3-MYB transcription factor, VyMYB24, was isolated from a high drought-tolerant Chinese wild Vitis species V. yanshanesis. Our findings demonstrated that it was involved in plant development and drought tolerance. VyMYB24 is a nuclear protein and is significantly induced by drought stress. When over-expressed in tobacco, VyMYB24 caused plant dwarfing including plant height, leaf area, flower size, and seed weight. The GA1+3 content in transgenic plants was reduced significantly, and spraying exogenous gibberellin could recover the dwarf phenotype of VyMYB24 transgenic plants, suggesting that VyMYB24 might inhibit plant development by the regulation of gibberellin (GA) metabolism. Under drought stress, the VyMYB24 transgenic plants improved their tolerance to drought with a lower wilting rate, lower relative electrical conductivity, and stronger roots. Compared to wild-type tobacco plants, VyMYB24 transgenic plants accumulated less reactive oxygen, accompanied by increased antioxidant enzyme activity and upregulated gene expression levels of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) genes. In addition, transgenic plants accumulated more proline, and their related synthetic genes NtP5CR and NtP5CS genes were significantly upregulated when exposed to drought. Besides, abiotic stress-responsive genes, NtDREB, NtERD10C, NtERD10D, and NtLEA5, were upregulated significantly in VyMYB24 transgenic plants. These results indicate that VyMYB24 plays a positive regulatory role in response to drought stress and also regulates plant development, which provides new evidence to further explore the molecular mechanism of drought stress of the MYB gene family.

Visual Analysis of Nutrient Deficiency and Treatment Protocols in Bariatric Surgery Based on VOSviewer.

Objective: To analyze the global literature on nutritional deficiencies in bariatric surgery (BS) since January 1, 1985, and to discuss the current status of research, research hotspots, and new development trend and treatment of nutritional deficiency in bariatric surgery. It provides ideas and basis for promoting the development of bariatric surgery and new alternative therapy or treatment protocols. Methods: The Web of Science (WOS) database core collection was used as the data source, and VOSviewer 1.6.17 software was used to search the literature on the topic of "nutritional deficiencies in bariatric surgery." The number of published literature, the distribution of authors, institutions, and countries, keyword cooccurrences, and journal cocitations were visualized and analyzed. Results: A total of 1015 relevant publications was obtained after searching and screening, and the overall trend of literature published was on the rise. The most published countries, institutions, and authors were USA, University of Sao Paulo, Ramalho, Andrea; Obesity Surgery has been the most frequently cited journal (7943 citations), and the top 10 journals had high impact factors. Keyword cooccurrence analysis showed that "bariatric surgery" and "nutritional deficiencies" are the hot topics of research in this field. Conclusion: There is an urgent need for bariatric surgery issuing institutions and authors to strengthen cross-institutional, cross-team, and multicenter and multidisciplinary cooperation, to promote and facilitate the exchange and cooperation in the field of bariatric surgery between developed countries in Europe and America and developing countries in Asia, Africa, and Latin America, to draw the attention of developing countries to the health problems caused by obesity, and to encourage and support the development of developing countries in this field. Bariatric surgery, obesity, weight loss, Y-type gastric bypass, gastric bypass, and nutritional deficiency are the hot research topics in the field of nutritional deficiency in bariatric surgery, and metabolic surgery, single anastomosis gastric bypass, micronutrient supplementation, micronutrient deficiency, intestinal microbiology, and guidelines are the new trends in this field.

Sustainable production of 4-hydroxyisoleucine with minimised carbon loss by simultaneously utilising glucose and xylose in engineered Escherichia coli.

4-Hydroxyisoleucine is a promising drug for diabetes therapy; however, microbial production of 4-hydroxyisoleucine is not economically efficient because of the carbon loss in the form of CO2. This study aims to achieve de novo synthesis of 4-hydroxyisoleucine with minimised carbon loss in engineered Escherichia coli. Initially, an L-isoleucine-producing strain, ILE-5, was established, and the 4-hydroxyisoleucine synthesis pathway was introduced. The flux toward α-ketoglutarate was enhanced by reinforcing the anaplerotic pathway and disrupting competitive pathways. Subsequently, the metabolic flux for 4-hydroxyisoleucine synthesis was redistributed by dynamically modulating the α-ketoglutarate dehydrogenase complex activity, achieving a 4-hydroxyisoleucine production of 16.53 g/L. Finally, carbon loss was minimised by employing the Weimberg pathway, resulting in a 24.5% decrease in sugar consumption and a 31.6% yield increase. The 4-hydroxyisoleucine production by strain IEOH-11 reached 29.16 g/L in a 5-L fermenter. The 4-hydroxyisoleucine yield (0.29 mol/mol sugar) and productivity (0.91 g/(L⋅h)) were higher than those previously reported.

Acacetin attenuates diabetes-induced cardiomyopathy by inhibiting oxidative stress and energy metabolism via PPAR-α/AMPK pathway.

Diabetic cardiomyopathy seriously affects the life quality of diabetic patients and can lead to heart failure and death in severe cases. Acacetin was reported to be an anti-oxidant and anti-inflammatory agent in several cardiovascular diseases. However, the effect of acacetin on diabetic cardiomyopathy was not understood. This study was designed to explore the therapeutic effect of acacetin on diabetic cardiomyopathy and the potential mechanism with in vitro and in vivo experimental techniques. In cultured neonatal rat cardiomyocytes and H9C2 cardiac cells, acacetin (0.3, 1, 3 µM) showed effective protection against high glucose-induced injury in a concentration-dependent manner. Acacetin countered high glucose-induced increase of Bax and decrease of Bcl-2, SOD1, and SOD2. In streptozotocin-induced rat diabetic cardiomyopathy model, treatment with acacetin prodrug (10 mg/kg, s.c., b.i.d.) significantly improved the cardiac function and reduced myocardial injury, and reversed the increase of serum MDA, Ang Ⅱ, and IL-6 levels and myocardial Bax and IL-6, and the decrease of serum SOD, indicating that acacetin plays a cardioprotective effect by inhibiting oxidative stress, inflammation, and apoptosis. In addition, both in vitro and in vivo experimental results showed that acacetin increased the expression of PPAR-α and pAMPK, indicating that PPAR-α and pAMPK are potential targets of acacetin for the protection against diabetic cardiomyopathy. This study demonstrates the new application of acacetin for treating diabetic cardiomyopathy.

Acacetin ameliorates cardiac hypertrophy by activating Sirt1/AMPK/PGC-1α pathway.

Cardiac hypertrophy is a major risk factor for developing heart failure. This study investigates the effects of the natural flavone acacetin on myocardial hypertrophy in cellular level and whole animals. In cardiomyocytes from neonatal rat with hypertrophy induced by angiotensin II (Ang II), acacetin at 0.3, 1, and 3 µM reduced the increased myocyte surface area, brain natriuretic peptide (BNP), and ROS production by upregulating anti-oxidative molecules (i.e. Nrf2, SOD1, SOD2, HO-1), anti-apoptotic protein Bcl-2, and downregulating the pro-apoptotic protein Bax and the inflammatory cytokine IL-6 in a concentration-dependent manner. In addition, acacetin rescued Ang II-induced impairment of PGC-1α, PPARα and pAMPK. These beneficial effects of acacetin were mediated by activation of Sirt1, which was confirmed in cardiac hypertrophy induced by abdominal aorta constriction (AAC) in SD rats. Acacetin prodrug (10 mg/kg, s.c., b.i.d.) treatment reduced the elevated artery blood pressure, improved the increased heart size and thickness of left ventricular wall and the ventricular fibrosis associated with inhibiting myocardial fibrosis and BNP, and reversed the impaired protective signal molecules including PGC-1α, Nrf2, PPARα, pAMPK and Sirt1 of left ventricular tissue. Our results demonstrate the novel pharmacological effect that acacetin ameliorates cardiac hypertrophy via Sirt1-mediated activation of AMPK/PGC-1α signal molecules followed by reducing oxidation, inflammation and apoptosis.

Early childhood development and parental training interventions in rural China: a systematic review and meta-analysis.

INTRODUCTION: Inadequate care during early childhood can lead to long-term deficits in skills. Parenting programmes that encourage investment in young children are a promising tool for improving early development outcomes and long-term opportunities in low-income and middle-income regions, such as rural China. METHODS: We conducted a systematic review and a meta-analysis to investigate the prevalence of early developmental delays and stimulating parenting practices as well as the effect of parental training programmes on child development outcomes in rural China. We obtained data in English from EconPapers, PubMed, PsycARTICLES, Cochrane Library, Web of Science and Scopus (Elsevier) and in Chinese from China National Knowledge Infrastructure, Wanfang Data and VIP Information. We conducted frequentist meta-analyses of aggregate data and estimated random-effects meta-regressions. Certainty of evidence was rated according to the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: We identified 19 observational studies on the prevalence of developmental delays and stimulating parenting practices for children under 5 years of age (n=19 762) and ten studies on the impact of parental training programmes on early child development (n=13 766). Children's risk of cognitive, language and social-emotional delays in the rural study sites (covering 14 provinces mostly in Central and Western China) was 45%, 46%, and 36%, respectively. Parental training programmes had a positive impact on child cognition, language and social-emotional development. CONCLUSION: There is evidence to suggest that early developmental delay and the absence of stimulating parenting practices (ie, reading, storytelling and singing with children) may be prevalent across rural, low-income and middle-income regions in Central and Western China. Results support the effectiveness of parental training programmes to improve early development by encouraging parental engagement. TRIAL REGISTRATION NUMBER: This study was registered with PROSPERO (CRD42020218852).

Cardiac senescence is alleviated by the natural flavone acacetin via enhancing mitophagy.

Cardiac senescence is associated with cardiomyopathy which is a degenerative disease in the aging process of the elderly. The present study investigates using multiple experimental approaches whether the natural flavone acacetin could attenuate myocardial senescence in C57/BL6 mice and H9C2 rat cardiac cells induced by D-galactose. We found that the impaired heart function in D-galactose-induced accelerated aging mice was improved by oral acacetin treatment in a dose-dependent manner. Acacetin significantly countered the increased serum advanced glycation end products, the myocardial telomere length shortening, the increased cellular senescence marker proteins p21 and p53, and the reduced mitophagy signaling proteins PINK1/Parkin and Sirt6 expression in aging mice. In H9C2 rat cardiac cells, acacetin alleviated cell senescence induced by D-galactose in a concentration-dependent manner. Acacetin decreased p21 and p53 expression, up-regulated PINK1/Parkin, LC3II/LC3I ratio, pLKB1, pAMPK and Sirt6, and reversed the depolarized mitochondrial membrane potential in aging cardiac cells. Mitophagy inhibition with 3-methyladenine or silencing Sirt6 abolished the protective effects of acacetin against cardiac senescence. Further analysis revealed that acacetin effect on Sirt6 was mediated by Sirt1 activation and increase of NAD+/NADH ratio. These results demonstrate that acacetin significantly inhibits in vivo and in vitro cardiac senescence induced by D-galactose via Sirt1-mediated activation of Sirt6/AMPK signaling pathway, thereby enhancing mitophagy and preserving mitochondrial function, which suggests that acacetin may be a drug candidate for treating cardiovascular disorders related to aging.

Skill levels and gains in university STEM education in China, India, Russia and the United States.

Universities contribute to economic growth and national competitiveness by equipping students with higher-order thinking and academic skills. Despite large investments in university science, technology, engineering and mathematics (STEM) education, little is known about how the skills of STEM undergraduates compare across countries and by institutional selectivity. Here, we provide direct evidence on these issues by collecting and analysing longitudinal data on tens of thousands of computer science and electrical engineering students in China, India, Russia and the United States. We find stark differences in skill levels and gains among countries and by institutional selectivity. Compared with the United States, students in China, India and Russia do not gain critical thinking skills over four years. Furthermore, while students in India and Russia gain academic skills during the first two years, students in China do not. These gaps in skill levels and gains provide insights into the global competitiveness of STEM university students across nations and institutional types.