Heart disease is the leading cause of death worldwide. A key pathogenic factor in the development of lethal heart failure is loss of terminally differentiated cardiomyocytes. However, mechanisms of ...cardiomyocyte death remain unclear. Here, we discovered and demonstrated that ferroptosis, a programmed iron-dependent cell death, as a mechanism in murine models of doxorubicin (DOX)- and ischemia/reperfusion (I/R)-induced cardiomyopathy. In canonical apoptosis and/or necroptosis-defective Ripk3−/−, Mlkl−/−, or Fadd−/−Mlkl−/− mice, DOX-treated cardiomyocytes showed features of typical ferroptotic cell death. Consistently, compared with dexrazoxane, the only FDA-approved drug for treating DOX-induced cardiotoxicity, inhibition of ferroptosis by ferrostatin-1 significantly reduced DOX cardiomyopathy. RNA-sequencing results revealed that heme oxygenase-1 (Hmox1) was significantly up-regulated in DOX-treated murine hearts. Administering DOX to mice induced cardiomyopathy with a rapid, systemic accumulation of nonheme iron via heme degradation by Nrf2-mediated upregulation of Hmox1, which effect was abolished in Nrf2-deficent mice. Conversely, zinc protoporphyrin IX, an Hmox1 antagonist, protected the DOX-treated mice, suggesting free iron released on heme degradation is necessary and sufficient to induce cardiac injury. Given that ferroptosis is driven by damage to lipid membranes, we further investigated and found that excess free iron accumulated inmitochondria and caused lipid peroxidation on its membrane. Mitochondria-targeted antioxidant MitoTEMPO significantly rescued DOX cardiomyopathy, supporting oxidative damage of mitochondria as a major mechanism in ferroptosis-induced heart damage. Importantly, ferrostatin-1 and iron chelation also ameliorated heart failure induced by both acute and chronic I/R in mice. These findings highlight that targeting ferroptosis serves as a cardioprotective strategy for cardiomyopathy prevention.
In recent years, deep learning has made remarkable breakthroughs in single-image super-resolution (SISR). However, the improvements often come with the increased network size, which is impractical ...for resource-constrained mobile devices. To alleviate this problem, an SISR method based on stepwise feedback training and multi-feature maps fusion (SFTMFM) is proposed in this paper, with fewer parameters amidst improved performance. Specifically, to better balance the performance and model parameters, a symmetrical CNN (SCNN) based on parameter sharing is constructed. In addition, to make up the deficiency of CNN module, the Swin Transformer layer (STL) is adopted to extract similar features over long distances. Lastly, to further improve the reconstruction ability of the model, a stepwise feedback training strategy is designed, which combines the cross-feature maps attention module as a feedback mechanism with the multi-feature maps fusion module to gradually reconstruct the model with higher-quality images. Under × 2 upscaling, our method achieves the PSNR(dB) of 38.10, 33.69, 32.25, 32.33, and 39.00 for SET5, SET14, BSD100, Urban100, and Managa109 datasets. Compared with the state-of-the-art lightweight SISR methods, our method shows better reconstruction performance and less computational cost.
Although studies have examined the association between dietary magnesium intake and health outcome, the results are inconclusive. Here, we conducted a dose-response meta-analysis of prospective ...cohort studies in order to investigate the correlation between magnesium intake and the risk of cardiovascular disease (CVD), type 2 diabetes (T2D), and all-cause mortality.
PubMed, EMBASE, and Web of Science were searched for articles that contained risk estimates for the outcomes of interest and were published through May 31, 2016. The pooled results were analyzed using a random-effects model.
Forty prospective cohort studies totaling more than 1 million participants were included in the analysis. During the follow-up periods (ranging from 4 to 30 years), 7678 cases of CVD, 6845 cases of coronary heart disease (CHD), 701 cases of heart failure, 14,755 cases of stroke, 26,299 cases of T2D, and 10,983 deaths were reported. No significant association was observed between increasing dietary magnesium intake (per 100 mg/day increment) and the risk of total CVD (RR: 0.99; 95% CI, 0.88-1.10) or CHD (RR: 0.92; 95% CI, 0.85-1.01). However, the same incremental increase in magnesium intake was associated with a 22% reduction in the risk of heart failure (RR: 0.78; 95% CI, 0.69-0.89) and a 7% reduction in the risk of stroke (RR: 0.93; 95% CI, 0.89-0.97). Moreover, the summary relative risks of T2D and mortality per 100 mg/day increment in magnesium intake were 0.81 (95% CI, 0.77-0.86) and 0.90 (95% CI, 0.81-0.99), respectively.
Increasing dietary magnesium intake is associated with a reduced risk of stroke, heart failure, diabetes, and all-cause mortality, but not CHD or total CVD. These findings support the notion that increasing dietary magnesium might provide health benefits.
Numerous studies have suggested that excess body weight is associated with increased cancer risk. To examine this putative association, we performed a systematic review and quantitative meta‐analysis ...of cohort studies reporting body mass index (BMI) and the risk of 23 cancer types. PubMed, Embase, and Web of Science were searched for cohort studies, yielding 325 articles with 1,525,052 cases. Strong positive associations were observed between BMI and endometrial cancer (RR: 1.48), esophageal adenocarcinoma (RR: 1.45), and kidney cancer (RR: 1.20); weaker associations (RR < 1.20) were also found for several other cancer types. Interestingly, we found significant inverse associations between BMI and oral cavity (RR: 0.93), lung (RR: 0.91), premenopausal breast (RR: 0.95), and localized prostate (RR: 0.97) cancers. A male‐specific association was found for colorectal cancer (p = 0.023), and a female‐specific association was found for cancer in brain (p = 0.025) or kidney (p = 0.035). With respect to geography, the strongest positive association was found for total cancer in North America (p = 0.038). This comprehensive meta‐analysis provides epidemiological evidence supporting the association between BMI and cancer risk. These findings can be used to drive public policies and to help guide personalized medicine in order to better manage body weight, thereby reducing the risk of developing obesity‐related cancer.
What's new?
Recent studies have uncovered a startling rise in global prevalence of overweight and obesity among adults since the 1980s, raising new concerns about associations between obesity and cancer risk. The authors of the present study reassessed associations between obesity and different cancers. Analyses revealed positive associations between body mass index (BMI) and multiple cancer types, with several gender‐specific and geography‐specific associations. Geographically, the strongest positive association between obesity and total cancer was in North America. The findings, which are relevant for public health, could also help guide personalized efforts to improve body weight management and thereby reduce cancer risk.
A mathematical model was developed to predict the self-heating and self-ignition processes of relatively dry biomass during storage, considering in detail the effects of moisture exchange behaviour, ...low-temperature oxidation reaction and associated heat and mass transfer. Basket heating tests on fir pellets and powder at temperatures of 180–200 °C were conducted to observe the heating process and determine the kinetics of low-temperature chemical oxidation for model validation. As a result, it was demonstrated that the developed model could reasonably represent the self-heating and spontaneous combustion processes of biomass storage. Furthermore, the numerical study and model sensitivity analysis revealed that reasonably describing the low-temperature oxidation and associated heat and mass transfer process with reliable estimations of kinetic and thermophysical parameters of the biomass material is necessary for predicting the self-ignition, considering the effect of water exchange behaviour is essential to predict the self-heating process even for relatively dry biomass, such as pellets, with the moisture content up to 15–20%.
In this study, six different treatments involving extracellular polymeric substances (EPS) from Enterobacter sp. FM-1 (FM-1) (no EPS (control), original bacterial cells (FM-1), FM-1 cells with EPS ...artificially removed (EPS-free cells, EPS-R), different forms of EPS (soluble EPS (S-EPS), loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS)) obtained from FM-1) and three types of soils (non-contaminated soil (NC soil), high-contamination soil (HC soil) and low-contamination soil (LC soil)) were used to investigate the impact of different EPS treatments on soil microbial community composition and their potential role in the remediation of heavy metal (HM)-contaminated soil. The results indicate that the EPS secreted by FM-1 played a vital role in changing soil pH and helped increase soil bio- HMs. In addition, EPS secretion by FM-1 helped increase the soil EPS-polysaccharide and EPS-nucleic acid contents; even in HC soil, where the HM content was relatively high, LB-EPS addition still increased the EPS-polysaccharide and EPS-nucleic acid contents in the soil by 1.18- and 15.54-fold, respectively. FM-1, LB-EPS and TB-EPS addition increased the soil invertase, urease and alkaline phosphatase activities and increased the soil organic matter (SOM), NH4+-N and available phosphorus (AP) contents, which helped regulate soil nutrient reserves. Moreover, the addition of different EPS fractions modified the soil microbial community composition to help microbes adapt to an HM-contaminated environment. In the HC and LC soils, where the HM content was relatively high, the soil bacteria were dominated by Protobacteria, while fungi in the soil were dominated by Ascomycota. Among the soil physicochemical properties, the soil SOM and NH4+-N contents and invertase activity significantly impacted the diversity and community composition of both bacteria and fungi in the soil.
•EPS secreted by FM-1 played a vital role in changing soil pH.•LB-EPS addition increased the EPS-polysaccharide and nucleic acid contents in HC soil.•Proteobacteria and Ascomycota were the dominant bacterial and fungal phyla, respectively.•SOM and NH4+-N play vital roles in impacting the diversity and structure of soil microbes.
Soil respiration (Rs) of forests plays an important role in the global carbon cycle. However, patchy remnant forests and their Rs characteristics are rarely studied. In this study, the diurnal and ...seasonal dynamics of the Rs of three patchy remnant forests and two urban green landscapes were determined using a portable soil carbon flux automatic analyzer in the urban fringe of Tianjin, China. Then, the effects of abiotic and biotic factors on the Rs of the patchy remnant forests and urban green landscapes were evaluated. Results showed that the patchy remnant forests had higher Rs than the urban green landscapes throughout the year. However, the Rs responses of the patchy remnant forests to soil temperature (ST) were more modest than those of the urban green landscapes, which indicated the higher resistant capacity to global warming of the former than the latter. In contrast to the pair traits of Rs-ST, fit lines of Rs and soil water content (SWC) showed an opposite trend in the growing and dormant periods. In the growing season, the slopes of Rs-SWC were similar between the patchy remnant forests and the urban green landscapes. The higher y-intercept of the patchy remnant forests indicated their larger water use efficiency than the urban green landscapes. In the dormant period, the higher slope of Rs-SWC for the patchy remnant forests suggested they were more sensitive to changes in SWC than the urban green landscapes. Meanwhile, the linear slopes of Rs and fine root biomass (FRB) were lower in the patchy remnant forests than in the urban green landscapes, which demonstrated that the Rs of the patchy remnant forests increased gently with increasing FRB. In addition, Rs was positively correlated with the amounts of bacteria and actinomycetes but negatively correlated with fungi. Results of canonical correlation analysis showed that the first two driving factors on the Rs of the patchy remnant forests were ST and FRB.
Recent studies found that mutations in the human SLC30A10 gene, which encodes a manganese (Mn) efflux transporter, are associated with hypermanganesemia with dystonia, polycythemia, and cirrhosis ...(HMDPC). However, the relationship between Mn metabolism and HMDPC is poorly understood, and no specific treatments are available for this disorder. Here, we generated two zebrafish slc30a10 mutant lines using the CRISPR/Cas9 system. Compared to wild-type animals, mutant adult animals developed significantly higher systemic Mn levels, and Mn accumulated in the brain and liver of mutant embryos in response to exogenous Mn. Interestingly, slc30a10 mutants developed neurological deficits in adulthood, as well as environmental Mn-induced manganism in the embryonic stage; moreover, mutant animals had impaired dopaminergic and GABAergic signaling. Finally, mutant animals developed steatosis, liver fibrosis, and polycythemia accompanied by increased epo expression. This phenotype was rescued partially by EDTA- CaNa2 chelation therapy and iron supplementation. Interestingly, prior to the onset of slc30a10 expression, expressing ATP2C1 (ATPase secretory pathway Ca2+ transporting 1) protected mutant embryos from Mn exposure, suggesting a compensatory role for Atp2c1 in the absence of Slc30a10. Notably, expressing either wild-type or mutant forms of SLC30A10 was sufficient to inhibit the effect of ATP2C1 in response to Mn challenge in both zebrafish embryos and HeLa cells. These findings suggest that either activating ATP2C1 or restoring the Mn-induced trafficking of ATP2C1 can reduce Mn accumulation, providing a possible target for treating HMDPC.
In medical validation experiments, such as drug testing and clinical trials, 3D bioprinted biomimetic tissues, especially those containing blood vessels, can be used to replace animal models. The ...difficulty in the viability of printed biomimetic tissues, in general, lies in the provision of adequate oxygen and nutrients to the internal regions. This is to ensure normal cellular metabolic activity. The construction of a flow channel network in the tissue is an effective way to address this challenge by both allowing nutrients to diffuse and providing sufficient nutrients for internal cell growth and by removing metabolic waste in a timely manner. In this paper, a three-dimensional TPMS vascular flow channel network model was developed and simulated to analyse the effect of perfusion pressure on blood flow rate and vascular-like flow channel wall pressure when the perfusion pressure varies. Based on the simulation results, the in vitro perfusion culture parameters were optimised to improve the structure of the porous structure model of the vascular-like flow channel, avoiding perfusion failure due to unreasonable perfusion pressure settings or necrosis of cells without sufficient nutrients due to the lack of fluid passing through some of the channels, and the research work promotes the development of tissue engineering in vitro culture.
Introduction
Given the new ideas on wound care offered by the eCASH (early Comfort using Analgesia, minimal Sedatives, and maximal Humane care) and the substantial differences in clinical treatment ...between acute and chronic wounds, we aimed to investigate the effect of comfort therapy under the eCASH concept on analgesic sedation and accelerated wound healing in patients with acute or chronic wounds.
Methods
This randomized clinical study was conducted in two parts: acute wounds and chronic wounds. Patients with acute wounds were allocated into the acute wound control group (AWCG) and the acute wound experimental group (AWEG). Patients with chronic wounds were allocated into the chronic wound control group (CWCG) and two experimental groups, in which they received intermittent negative pressure therapy (IPTEG) and continuous negative pressure therapy (CPTEG). On the basis of the standard treatment for patients in the control group, eCASH therapy was used in the experimental groups. In addition, pain intensity and procedural anxiety were evaluated using the visual analogue score (VAS) and the Hamilton Anxiety Scale (HAM-A). In addition, clinical effects were assessed on the basis of the size of the surface area, rate of healing, and concentration of pro-inflammatory factors (IL-1, IL-6, TNF-α) and growth factors (VEGF, bFGF, TGF-β1).
Results
Compared with the control group, the VAS score and HAM-A score in the experimental groups were significantly decreased after intervention (
P
< 0.05). After intervention, the levels of IL-1β, IL-6, and TNF-α in AWEG, IPTEG, and CPTEG were significantly lower than those in AWCG. In addition, the levels of VEGF, bFGF, and TGF-β1 in IPTEG and CPTEG were significantly higher than those in CWCG (
P
< 0.05).
Conclusion
These results indicated that comfort therapy under the eCASH concept has a significant effect on ameliorating the pain and anxiety of patients, reducing the inflammatory reaction during the period of wound healing in the treatment of acute and chronic wounds.
Clinical Trial Registry
The trial has been registered in the Chinese Clinical Trial Registry (ChiCTR2200057981).
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