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Asthma caused substantial economic and health care burden and is susceptible to air pollution. Particularly, when it comes to elder asthma patient (older than 65), the phenomenon is more significant. The aim of this study is to investigate the Markov-based acute effects of air pollution on elder asthma hospitalizations, in forms of transition probabilities.
Aluminum-ion batteries (AIBs) have been highlighted as a potential alternative to lithium-ion batteries for large-scale energy storage due to the abundant reserve, light weight, low cost, and good safety of Al. However, the development of AIBs faces challenges due to the usage of AlCl3-based ionic liquid electrolytes, which are expensive, corrosive, and sensitive to humidity. Here, we develop a low-cost, non-corrosive, and air-stable hydrated eutectic electrolyte composed of aluminum perchlorate nonahydrate and methylurea (MU) ligand. Through optimizing the molar ratio to achieve the unique solvation structure, the formed Al(ClO4)3·9H2O/MU hydrated deep eutectic electrolyte (AMHEE) with an average coordination number of 2.4 can facilely realize stable and reversible deposition/stripping of Al. When combining with vanadium oxide nanorods positive electrode, the Al-ion full battery delivers a high discharge capacity of 320 mAh g-1 with good capacity retention. The unique solvation structure with a low desolvation energy of the AMHEE enables Al3+ insertion/extraction during charge/discharge processes, which is evidenced by in situ synchrotron radiation X-ray diffraction. This work opens a new pathway of developing low-cost, safe, environmentally friendly and high-performance electrolytes for practical and sustainable AIBs.
Purple cabbage is one of the world's most widely consumed vegetables with high nutritional values containing the antioxidants and anti-inflammatory activity of anthocyanins, vitamins, and minerals. But due to rapid postharvest quality decay, novel processing techniques including drying are required. In order to determine the conditions of combined microwave and hot air drying for purple cabbage, factors affecting the drying process including microwave density, hot air temperature, and the dry base water content at conversion point were investigated using the anthocyanin content, DPPH antioxidant capacity, chewiness, △E, rehydration ratio, and average drying rate as responses. The combined drying conditions were optimized considering three independent variables at three different levels by response surface methodology. The results showed that the processing parameters of purple cabbage with combined microwave and hot air drying technology were microwave density at 2.5 W/g, moisture content of conversion point at 4.0 g/g, and hot air temperature at 55°C. Under these conditions, the anthocyanin content, DPPH antioxidant capacity, chewiness, △E, rehydration ratio, average drying rate, and overall score of the dried purple cabbage were 175.87 mg/100 g, 87.59%, 4,521.468 g, 26.5, 4.3, 0.76 g/min, and 0.785, respectively. Therefore, combined microwave and hot air drying technology is an effective, suitable method for drying purple cabbage.
Myocardial infarction (MI) is a coronary artery-related disease and ranks as the leading cause of sudden death globally. Resveratrol (Res) is a bioactive component and has presented antioxidant, anti-inflammatory and anti-microbial properties. However, the effect of Res on ferroptosis during MI progression remains elusive. Here, we aimed to explore the function of Res in the regulation of ferroptosis and myocardial injury in MI. We observed that the treatment of Res attenuated the MI-related myocardium injury and fibrosis in the rats. The expression of collagen 1 and α-SMA was induced in MI rats, in which the treatment of Res could decrease the expression. Treatment of Res suppressed the levels of IL-6 and IL-1β in MI rats. The GSH levels were inhibited and MDA, lipid ROS, and Fe2+ levels were induced in MI rats, in which the treatment of Res could reverse the phenotypes. Meanwhile, the expression of GPX4 and SLC7A11 was reduced in MI rats, while the treatment of Res could rescue the expression in the model. Meanwhile, Res relieved oxygen-glucose deprivation (OGD)-induced cardiomyocyte injury. Importantly, Res repressed OGD-induced cardiomyocyte ferroptosis in vitro. Mechanically, we identified that Res was able to enhance GPX4 expression by inducing KAT5 expression. We confirmed that KAT5 alleviated OGD-induced cardiomyocyte injury and ferroptosis. The depletion of KAT5 or GPX4 could reverse the effect of Res on OGD-induced cardiomyocyte injury. Thus, we concluded that Res attenuated myocardial injury by inhibiting ferroptosis via inducing KAT5/GPX4 in myocardial infarction. Our finding provides new evidence of the potential therapeutic effect of Res on MI by targeting ferroptosis.
Bakuchiol (BAK), a monoterpene phenol reported to have exerted a variety of pharmacological effects, has been related to multiple diseases, including myocardial ischemia reperfusion injury, pressure overload-induced cardiac hypertrophy, diabetes, liver fibrosis, and cancer. However, the effects of BAK on hyperglycemia-caused diabetic cardiomyopathy and its underlying mechanisms remain unclear. In this study, streptozotocin-induced mouse model and high-glucose-treated cell model were conducted to investigate the protective roles of BAK on diabetic cardiomyopathy, in either the presence or absence of SIRT1-specific inhibitor EX527, SIRT1 siRNA, or Nrf2 siRNA. Our data demonstrated for the first time that BAK could significantly abate diabetic cardiomyopathy by alleviating the cardiac dysfunction, ameliorating the myocardial fibrosis, mitigating the cardiac hypertrophy, and reducing the cardiomyocyte apoptosis. Furthermore, BAK achieved its antifibrotic and antihypertrophic actions by inhibiting the TGF-β1/Smad3 pathway, as well as decreasing the expressions of fibrosis- and hypertrophy-related markers. Intriguingly, these above effects of BAK were largely attributed to the remarkable activation of SIRT1/Nrf2 signaling, which eventually strengthened cardiac antioxidative capacity by elevating the antioxidant production and reducing the reactive oxygen species generation. However, all the beneficial results were markedly abolished with the administration of EX527, SIRT1 siRNA, or Nrf2 siRNA. In summary, these novel findings indicate that BAK exhibits its therapeutic properties against hyperglycemia-caused diabetic cardiomyopathy by attenuating myocardial oxidative damage via activating the SIRT1/Nrf2 signaling.
Cyclic dimeric adenosine monophosphate (c-di-AMP) is a ubiquitous second messenger of bacteria involved in diverse physiological processes as well as host immune responses. MSMEG_2630 is a c-di-AMP phosphodiesterase (cnpB) of Mycobacterium smegmatis, which is homologous to Mycobacterium tuberculosis Rv2837c. In this study, cnpB-deleted (ΔcnpB), -complemented (ΔcnpB::C), and -overexpressed (ΔcnpB::O) strains of M. smegmatis were constructed to investigate the role of c-di-AMP in regulating mycobacterial physiology and immunogenicity. This study provides more precise evidence that elevated c-di-AMP level resulted in smaller colonies, shorter bacteria length, impaired growth, and inhibition of potassium transporter in M. smegmatis. This is the first study to report that elevated c-di-AMP level could inhibit biofilm formation and induce porphyrin accumulation in M. smegmatis by regulating associated gene expressions, which may have effects on drug resistance and virulence of mycobacterium. Moreover, the cnpB-deleted strain with an elevated c-di-AMP level could induce enhanced Th1 immune responses after M. tuberculosis infection. Further, the pathological changes and the bacteria burden in ΔcnpB group were comparable with the wild-type M. smegmatis group against M. tuberculosis venous infection in the mouse model. Our findings enhanced the understanding of the physiological role of c-di-AMP in mycobacterium, and M. smegmatis cnpB-deleted strain with elevated c-di-AMP level showed the potential for a vaccine against tuberculosis.
The sphingolipid metabolite sphingosine 1‑phosphate (S1P) has emerged as a potential cardioprotective molecule against ischemic heart disease. Moreover, S1P triggers mobilization and homing of bone marrow-derived stem/progenitor cells into the damaged heart. However, it remains elusive whether S1P promotes mesenchymal stem cells (MSCs)-mediated cardioprotection against ischemic heart diseases.
Drug resistance is a major obstacle in cancer treatment and recurrence prevention and leads to poor outcomes in patients suffering from osteosarcoma. Clarification of the mechanism of drug resistance and exploration of effective strategies to overcome this obstacle could lead to clinical benefits for these patients. The expression of far upstream element-binding protein 1 (FUBP1) was found to be markedly elevated in osteosarcoma cell lines and clinical specimens compared with osteoblast cells and normal bone specimens. High expression of FUBP1 was correlated with a more aggressive phenotype and a poor prognosis in osteosarcoma patients. We found that overexpression of FUBP1 confers lobaplatin resistance, whereas the inhibition of FUBP1 sensitizes osteosarcoma cells to lobaplatin-induced cytotoxicity both in vivo and in vitro. Chromatin immunoprecipitation-seq and RNA-seq were performed to explore the potential mechanism. It was revealed that FUBP1 could regulate the transcription of prostaglandin E synthase (PTGES) and subsequently activate the arachidonic acid (AA) metabolic pathway, which leads to resistance to lobaplatin. Our investigation provides evidence that FUBP1 is a potential therapeutic target for osteosarcoma patients. Targeting FUBP1, its downstream target PTGES and the AA metabolic pathway may be promising strategies for sensitizing chemoresistant osteosarcoma cells to lobaplatin.
DNA methylation has been found to regulate microRNAs (miRNAs) expression, but the prognostic value of miRNA-related DNA methylation aberration remained largely elusive in cancers including glioblastomas (GBMs). This study aimed to investigate the clinical and biological feature of miRNA methylation in GBMs of non-glioma-CpG island methylator phenotype (non-G-CIMP).
Myocardial ischemia-reperfusion (MI/R) injury is a common and serious complication following reperfusion treatment for myocardial infarction (MI). Increasing evidence has verified the crucial role of circular RNAs (circRNAs) in the MI/R injury processes. The objective of this study was to investigate the effects and potential regulatory mechanisms of circHMGA2 on MI/R injury. Hypoxia/reoxygenation (H/R) models were established using human cardiac myocytes (HCMs) and mice models were induced by MI/R. The level of circHMGA2 was detected by RT-qPCR. Myocardial function was evaluated by the hemodynamic parameters, the activity of serum myocardial enzymes, HE staining and TUNEL assays. Cell proliferation was measured by CCK-8 assay. The ferrous ion (Fe2+) level was determined with an iron assay kit. Ferroptosis- and pyroptosis-related proteins were determined using western blotting. The levels of oxidative stress and inflammatory factors were analyzed using DCFH-DA staining or ELISA assays. CircHMGA2 was upregulated in H/R-induced HCMs and myocardial tissues of MI/R mice. In vitro, circHMGA2 knockdown attenuated the proliferation inhibition, restrained the ferroptosis and pyroptosis in H/R-induced HCMs. This regulatory mechanism may be associated with the suppression of NLRP3 pathway. In vivo, circHMGA2 depletion attenuated myocardial tissue damage of MI/R mice through inhibiting the oxidative stress and pyroptosis. Taken together, CircHMGA2 enhanced MI/R injury via promoting ferroptosis and pyroptosis, providing new insights into the treatment of MI/R injury.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains the most common cause of death from a single infectious disease. More safe and effective vaccines are necessary for preventing the prevalence of TB. In this study, a subunit vaccine of ESAT-6 formulated with c-di-AMP (ESAT-6:c-di-AMP) promoted mucosal and systemic immune responses in spleen and lung. ESAT-6:c-di-AMP inhibited the differentiations of CD8+ T cells as well as macrophages, but promoted the differentiations of ILCs in lung. The co-stimulation also enhanced inflammatory cytokines production in MH-S cells. It was first revealed that ESAT-6 and c-di-AMP regulated autophagy of macrophages in different stages, which together resulted in the inhibition of Mtb growth in macrophages during early infection. After Mtb infection, the level of ESAT-6-specific immune responses induced by ESAT-6:c-di-AMP dropped sharply. Finally, inoculation of ESAT-6:c-di-AMP led to significant reduction of bacterial burdens in lungs and spleens of immunized mice. Our results demonstrated that subunit vaccine ESAT-6:c-di-AMP could elicit innate and adaptive immune responses which provided protection against Mtb challenge, and c-di-AMP as a mucosal adjuvant could enhance immunogenicity of antigen, especially for innate immunity, which might be used for new mucosal vaccine against TB.
With the decreasing regional-transported levels, the health risk assessment derived from fine particulate matter (PM2.5) has become insufficient to reflect the contribution of local source heterogeneity to the exposure differences. Here, we combined the both ultra-high-resolution PM2.5 concentration with population distribution to provide the personal daily PM2.5 internal dose considering the indoor/outdoor exposure difference. A 30-m PM2.5 assimilating method was developed fusing multiple auxiliary predictors, achieving higher accuracy (R2 = 0.78-0.82) than the chemical transport model outputs without any post-simulation data-oriented enhancement (R2 = 0.31-0.64). Weekly difference was identified from hourly mobile signaling data in 30-m resolution population distribution. The population-weighted ambient PM2.5 concentrations range among districts but fail to reflect exposure differences. Derived from the indoor/outdoor ratio, the average indoor PM2.5 concentration was 26.5 μg/m3. The internal dose based on the assimilated indoor/outdoor PM2.5 concentration shows high exposure diversity among sub-groups, and the attributed mortality increased by 24.0% than the coarser unassimilated model.
The lumbar fusion is an important surgery for the orthopedic diseases. The rehabilitation might improve the outcome of patients with lumbar fusion surgery. The rehabilitation-related effects can be revealed by a systemic review and meta-analysis of randomized clinical trials (RCTs). The purpose of this study is to clarify the rehabilitation effects in the patients with lumbar fusion surgery.
Airborne particulate matter (PM) is causing more and more serious air pollution and threatening the public health. However, existing air filter technologies with the easy-to-block manner can rarely meet the requirements of high-performance PM filters. Here we propose a conceptually new type of inertial impaction filters for rapidly high-efficiency PM removal. Under the airflow velocity of 8.0 m/s, the real inertial impaction filters show high PM removal efficiencies of up to 97.77 ± 1.53% and 99.47 ± 0.45% for PM2.5 and PM10, respectively. Compared with the traditional air filters reported previously, the inertia impaction filters exhibit extremely low pressure drop of 5-10 Pa and high quality factor (QF) values of 0.380 Pa-1 and 0.524 Pa-1 for PM2.5 and PM10, respectively. These greatly improved QF values are achieved through a series of inertial separation processes. The feature dimension of filtration channel is dozens of times larger than PM average size, which greatly decreases airflow resistance. Particularly, this inertial structure can be made of various types of materials, which shows great potential for low-cost fabrication of large-area devices. As a stand-alone device or incorporated with the existing PM air filter, this inertial impaction filter will bring great benefits to the public health.
Peri-implant epithelial sealing is the first line of defense against external pathogens or stimuli; hence, an essential process to prevent peri-implantitis. Laminin 332 (LN332) is the main component of the internal basal lamina and participates in peri-implant epithelial sealing by forming hemidesmosomes (HDs) with integrin α6β4. In this work, poly (D, L-lactide) (PDLLA)-LN332 composite coating was successfully constructed by a method similar to layer-by-layer assembly, displaying staged LN332 release for as long as 28 days. The PDLLA-LN332 composite coating can activate the intracellular PI3K-Akt pathway via binding to cellular integrin α6β4, which can promote adhesion, migration and proliferation of HaCaT cells and further enhance the expression of keratinocyte HD-related molecules, including integrin α6β4, LN332 and plectin. Furthermore, the PDLLA-LN332 composite coating can promote the adhesion, spreading and proliferation of gingival mesenchymal stem cells and accelerate their epithelial differentiation. Therefore, the PDLLA-LN332 composite coating can enhance implant soft tissue sealing, warranting further in vivo study.
Chromatin-modifying enzymes, especially protein arginine methyltransferases (PRMTs), have been identified as candidate targets for cancer. Cellular or animal-based evidence has suggested an association between coactivator-linked arginine methyltransferase 1 (CARM1) and cancer progression. However, the relationship between CARM1 and patient prognosis and immune infiltration in pancancer patients is unknown. On the basis of the GEO and TCGA databases, we first investigated the possible oncogenic functions of CARM1 in thirty-three tumor types. CARM1 expression was elevated in many types of tumors. In addition, there was a significant association between CARM1 expression and the survival rate of tumor patients. Uterine corpus endometrial carcinoma (UCES) samples had the highest CARM1 mutation frequency of all cancer types. In head and neck squamous cell carcinoma (HNSC) and lung squamous cell carcinoma (LUSC), CARM1 expression was associated with the level of CD8+ T cell infiltration, and cancer-associated fibroblast infiltration was also observed in other tumors including kidney renal papillary cell carcinoma (KIRC) and prostate adenocarcinoma (PRAD). CARM1 was involved in immune modulation and played an important role in the tumor microenvironment (TME). Furthermore, activities associated with RNA transport and its metabolism were included in the possible mechanisms of CARM1. Herein, our first pancancer research explores the oncogenic role of CARM1 in various tumors. CARM1 is associated with immune infiltrates and can be employed as a predictive biomarker in pancancer.
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