Corrosion Behavior of Alumina-Forming Austenitic Steel in Supercritical Carbon Dioxide Conditions: Effects of Nb Content and Temperature.

The corrosion behavior of alumina-forming austenitic (AFA) stainless steels with different Nb additions in a supercritical carbon dioxide environment at 500 °C, 600 °C, and 20 MPa was investigated. The steels with low Nb content were found to have a novel structure with a double oxide as an outer Cr2O3 oxide film and an inner Al2O3 oxide layer with discontinuous Fe-rich spinels on the outer surface and a transition layer consisting of Cr spinels and γ'-Ni3Al phases randomly distributed under the oxide layer. Oxidation resistance was improved by accelerating diffusion through refined grain boundaries after the addition of 0.6 wt.% Nb. However, the corrosion resistance decreased significantly at higher Nb content due to the formation of continuous thick outer Fe-rich nodules on the surface and an internal oxide zone, and Fe2(Mo, Nb) laves phases were also detected, which prevented the outward diffusion of Al ions and promoted the formation of cracks within the oxide layer, resulting in unfavorable effects on oxidation. After exposure at 500 °C, fewer spinels and thinner oxide scales were found. The specific mechanism was discussed.

Unravelling the Interplay between Cardiac Metabolism and Heart Regeneration.

Ischemic heart disease (IHD) is the leading cause of heart failure (HF) and is a significant cause of morbidity and mortality globally. An ischemic event induces cardiomyocyte death, and the ability for the adult heart to repair itself is challenged by the limited proliferative capacity of resident cardiomyocytes. Intriguingly, changes in metabolic substrate utilisation at birth coincide with the terminal differentiation and reduced proliferation of cardiomyocytes, which argues for a role of cardiac metabolism in heart regeneration. As such, strategies aimed at modulating this metabolism-proliferation axis could, in theory, promote heart regeneration in the setting of IHD. However, the lack of mechanistic understanding of these cellular processes has made it challenging to develop therapeutic modalities that can effectively promote regeneration. Here, we review the role of metabolic substrates and mitochondria in heart regeneration, and discuss potential targets aimed at promoting cardiomyocyte cell cycle re-entry. While advances in cardiovascular therapies have reduced IHD-related deaths, this has resulted in a substantial increase in HF cases. A comprehensive understanding of the interplay between cardiac metabolism and heart regeneration could facilitate the discovery of novel therapeutic targets to repair the damaged heart and reduce risk of HF in patients with IHD.

Insulin-Like Growth Factor-1 Promotes Human Uterine Leiomyoma Cell Proliferation via PI3K/AKT/mTOR Pathway.

The present research aimed to evaluate the expression of insulin-like growth factor-1 (IGF-1) in uterine leiomyoma, and explore its relationship with the occurrence and development of uterine leiomyoma and potential signal pathways. qRT-PCR and enzyme-linked immunosorbent assay were used for estimating the levels of IGF-1 in human uterine leiomyoma compared to myometrium. The expression of cell proliferation and PI3K/AKT/mTOR signaling pathway-related proteins in uterine leiomyoma cells was evaluated by western blot. Cell viability analysis was performed by CCK-8 assay. Lentivirus infection was used for IGF-1 overexpression and knockdown in uterine leiomyoma cells. The IGF-1 expression level was elevated in human uterine leiomyomas compared to myometrium. IGF-1 promoted the cell viability of human uterine leiomyoma cells. Overexpression of IGF-1 induced the expression of pro-proliferation markers including c-Myc, PCNA, and cyclin D1 in uterine leiomyoma cells. IGF-1 elevated the phosphorylation levels of PI3K, AKT, and mTOR, thus modifying PI3K/AKT/mTOR signaling in uterine leiomyoma cells. IGF-1 promotes proliferation of human uterine leiomyoma cells via PI3K/AKT/mTOR pathway.

Effects of short-term waterfall forest aerosol air exposure on rat lung proteomics.

Background: Chronic exposure to airborne microparticles has been shown to increase the incidence of several chronic diseases. Previous studies have found that waterfall forest aerosols contribute to a diminished immune stress response in patients with asthma. However, the specific effects of short-term waterfall forest aerosol exposure on lung proteins have not been fully elucidated. Methods: This study used liquid chromatography-tandem mass spectrometry (LC-MS) to analyze changes in protein expression in the lungs of rats exposed to short-term waterfall forest aerosol environments. Specific protein markers were identified using bioconductivity analysis screening and validated using immunohistochemistry. Results: Waterfall forest aerosol environment exposure on day 5 downregulated the expression of the classical inflammatory pathway nuclear factor κB (NF-κB) signaling pathway. As the waterfall forest aerosol environment increased due to the duration of exposure, it was involved in oxidative phosphorylation and then hormone signaling in lung cells from the very beginning. In contrast, at day 15 of exposure, there is an effect on the regulation of the immune-related high-affinity IgE receptor pathway. In addition, iron-sulfur Rieske protein (Uqcrfs1), mitochondrial Tu translation elongation factor (Tufm) and ribosomal protein L4 (Rpl4) were identified as possible bioindicators for the evaluation of air quality. Conclusions: These results provide a comprehensive proteomic analysis that supports the positive contribution of a good air quality environment to lung health.

Mechanism of the Huangguoshu waterfall forest environment's promotive effect on human health in Guizhou, China.

Background: The aim of this study was to investigate the specific mechanisms underlying the human health-promoting effects of the forest environment at Huangguoshu Falls, Guizhou, China. Methods: Ninety-five participants were recruited and an eye tracker was used to record fixation and sweep indices. A questionnaire was also used to evaluate the effects of different subject environments on human emotions, perceived recovery and preferences. Thereafter, 24 participants with chronic fatigue syndrome (CFS) were recruited and the participants' fatigue and stress-related scale indices and inflammatory factor levels were examined. Serum metabolites of the participants under different time waterfall forest interventions were detected by ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q/TOF-MS). Results: Eye tracking paradigm analysis showed that the "waterfall" element was the most interesting element for participants and that the "charm" of the waterfall forest environment could be well perceived by participants. Scores on the Fatigue Scale, Anxiety Scale and Depression Scale decreased as the duration of treatment in the waterfall forest environment increased. Levels of inflammatory factors decreased after treatment in the waterfall forest environment. At the same time the level of antioxidants, represented by L-ascorbic acid, increased significantly. Conclusions: The charm of the Huangguoshu waterfall scenery could be perceived by the participants and have a positive modulating effect on mood and cognitive function. In addition, the unique mixture of negative oxygen ions in this environment can increase the content of endogenous antioxidants and balance the metabolism of choline and amino acids.

MiR-571 affects the development and progression of liver fibrosis by regulating the Notch3 pathway.

Exploring the expression of miR-571 in patients with liver fibrosis and its role in the progression of liver fibrosis. A total of 74 patients with liver fibrosis in our institution from September to December 2018 were collected for study, and the expression of miR-571, Notch3 and Jagged1 in patients with different progressions of liver fibrosis was determined by RT-PCR and Western blot analysis. Set up Notch3 up group and Notch3 down regulated group, RT-PCR and Western blot were used to determine the effect of Notch signaling on the expression of fibrogenic factors. CCK-8, cell scratch assays, Transwell assays, flow cytometry were used to determine the effect of miR-571 on LX-2 proliferation, migration, apoptosis in human stem stellate cells, and RT-PCR, Western blot assays were performed to determine the effect of miR-571 on the Notch3 signaling pathway and the expression of profibrogenic factors. miR-571, Notch3 and Jagged1 are up-regulated in patients with liver fibrosis and is associated with the progression of liver fibrosis. Notch3 signaling pathway can promote the expression of fibroblast in human hepatic stellate cells; miR-571 can inhibit the apoptosis of human hepatic stellate cells, promote cell proliferation and migration; up regulation of miR-571 can promote the expression of Notch3 and Jagged1, and up-regulation of miR-571 also promoted the expression of related fibroblasts. MiR-571 can promote the activation of human stem cell stellate cells and the expression of fibroblast related factors through Notch3 signaling pathway.

Waterfall Forest Environment Regulates Chronic Stress via the NOX4/ROS/NF-κB Signaling Pathway.

Background: Forest therapy has been proven to have beneficial effects on people with depression and anxiety. However, it remains unknown whether the waterfall forest environment (WF) affects the physical and psychological health of patients with chronic fatigue and how the WF regulates chronic stress. Methods: Twenty-four patients with chronic fatigue were randomly divided into two groups: the WF group and the urban (U) group. Scores on the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Fatigue Scale-14 (FS-14) were evaluated before and after environmental intervention. Detection of physiological indexes and inflammatory factor levels and immunological analysis were also performed. In addition, the chronic stress rat model was constructed, and the effects of the WF on hopelessness and liver damage of rats were investigated. Results: Patients with chronic fatigue in the WF group showed a significant decrease in FS-14, HAMA, and HAMD scores compared with the U group. The expression levels of glutathione peroxidase and superoxide dismutase were remarkably higher in the WF group than in the U group. However, the expression levels of malondialdehyde and inflammatory factors (IL-1ß, TNF-α, IL-6, and IL-10) were remarkably decreased after the intervention of the WF. In addition, animal experiments confirmed that the WF improved hopelessness, liver damage, and excitability of neurons of chronic stress rats. Mechanistically, the WF reduced the liver damage caused by chronic stress in rats by inhibiting the NOX4/ROS/NF-κB signaling pathway. Conclusions: Collectively, the WF had a positive effect on immune enhancement and physical and psychological health in patients with chronic fatigue and might inhibit chronic stress by regulating the NOX4/ROS/NF-κB signaling pathway.

Experimental Investigation on Floating Solar-Driven Membrane Distillation Desalination Modules.

Membrane distillation (MD) processes need a relatively mild temperature gradient as the driving force for desalination. In the field, it is reasonable to utilize solar energy as the heat source for the feed, and seawater as the infinite cold source for condensation. Solar-driven MD provides a route for the practical application of seawater desalination at a small scale. In this work, we focus on floating MD modules with a solar heating bag as the power source, and perform proof-of-principle experiments on the MD performance under various conditioning parameters, including feed flow rate, feed temperature, salinity, air gap, and sea waves. The results indicate that floating solar-driven MD modules are feasible in terms of permeate flux and salt rejection ratio, and the upward evaporation MD configuration leads to a better performance in terms of permeate flux. The simulation and experiments also show that the natural sea waves disturb the heating bag and the MD module floating on the surface of seawater, and effectively enhance the feed circulation and transport in the system.

Mass Transfer Analysis of Air-Cooled Membrane Distillation Configuration for Desalination.

It has been proposed that the air-cooled configuration for air gap membrane distillation is an effective way to simplify the system design and energy source requirement. This offers potential for the practical applications of membrane distillation on an industrial scale. In this work, membrane distillation tests were performed using a typical water-cooled membrane distillation (WCMD) configuration and an air-cooled membrane distillation (ACMD) configuration with various condensing plates and operating conditions. To increase the permeate flux of an ACMD system, the condensing plate in the permeate side should transfer heat to the atmosphere more effectively, such as using a more thermally conductive plate, adding fins, or introducing forced convection air flow. Importantly, a practical mass transfer model was proposed to describe the ACMD performance in terms of permeate flux. This model can be simplified by introducing specific correction values to the mass transfer coefficient of a WCMD process under the same conditions. The two factors relate to the capacity (B) and the efficiency (σ), which can be considered as the characteristic factors of a membrane distillation (MD) system. The experimental results are consistent with the theoretical estimations based on this model, which can be used to describe the performance of an MD process.

Integrative proteomic and lipidomic analysis of Kaili Sour Soup-mediated attenuation of high-fat diet-induced nonalcoholic fatty liver disease in a rat model.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease and is characterized by excessive fat accumulation. Kaili Sour Soup, a food typical of Guizhou Province, is believed to have significant health benefits. Thus, we aimed to identify and assess the impact of Kaili Sour Soup on NAFLD and its underlying mechanism using integrative proteomic and lipidomic analysis. METHODS: A high-fat diet and male Wistar rats were used to construct a NAFLD rat model. Haematoxylin and eosin (HE) and Oil Red O staining analyses were used to perform the histologic examination. Proteomic analysis was utilized to systematically identify the global protein profile in NAFLD with and without Kaili Sour Soup treatment. Western blot assays were used to verify the expression of proteins screened by proteomic analysis. Lipidomic analysis was performed to screen lipid metabolism in NAFLD with and without Kaili Sour Soup treatment. RESULTS: Kaili Sour Soup alleviated high-fat diet (HFD)-induced fatty liver and had a normalizing effect on physiological and biochemical indicators of NAFLD, including body weight, liver weight, liver index, total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and insulin resistance level of homeostasis model assessment (HOMA-IR). Kaili Sour Soup decreased the levels of 13 proteins (Tmem44, Rnaseh2b, Gstm6l, LOC100910877, Rufy4, Slc12a2, Pcif1, P4503A1, Sult1e1, Nop53, AABR07065656.4, AABR07065789.3) that were upregulated by HFD and increased the levels of 3 proteins (Sult1c2, Sult1c2a, Snrnp48) that were downregulated by HFD. Kaili Sour Soup attenuated the HFD-induced increase in acyl carnitine (AcCa) and enhanced the HFD-induced decreases in gangliosides (GM3) and lysophosphatidylserine (LPS) in the NAFLD rat model. CONCLUSIONS: Altogether, this study revealed that Kaili Sour Soup attenuated HFD-induced fatty liver and systematically identified abnormal proteins and lipids involved in the role of Kaili Sour Soup in a NAFLD rat model.

Oxidative stress in cardiac hypertrophy: From molecular mechanisms to novel therapeutic targets.

When faced with increased workload the heart undergoes remodelling, where it increases its muscle mass in an attempt to preserve normal function. This is referred to as cardiac hypertrophy and if sustained, can lead to impaired contractile function. Experimental evidence supports oxidative stress as a critical inducer of both genetic and acquired forms of cardiac hypertrophy, a finding which is reinforced by elevated levels of circulating oxidative stress markers in patients with cardiac hypertrophy. These observations formed the basis for using antioxidants as a therapeutic means to attenuate cardiac hypertrophy and improve clinical outcomes. However, the use of antioxidant therapies in the clinical setting has been associated with inconsistent results, despite antioxidants having been shown to exert protection in several animal models of cardiac hypertrophy. This has forced us to revaluate the mechanisms, both upstream and downstream of oxidative stress, where recent studies demonstrate that apart from conventional mediators of oxidative stress, metabolic disturbances, mitochondrial dysfunction and inflammation as well as dysregulated autophagy and protein homeostasis contribute to disease pathophysiology through mechanisms involving oxidative stress. Importantly, novel therapeutic targets have been identified to counteract oxidative stress and attenuate cardiac hypertrophy but more interestingly, the repurposing of drugs commonly used to treat metabolic disorders, hypertension, peripheral vascular disease, sleep disorders and arthritis have also been shown to improve cardiac function through suppression of oxidative stress. Here, we review the latest literature on these novel mechanisms and intervention strategies with the aim of better understanding the complexities of oxidative stress for more precise targeted therapeutic approaches to prevent cardiac hypertrophy.

Fecal transplantation alleviates acute liver injury in mice through regulating Treg/Th17 cytokines balance.

Changes in intestinal microecology during acute liver failure (ALF) directly affect the occurrence and development of the disease. The study aimed to investigate the relationship between the intestinal microbiota and the key immune cells. Fecal microbiota transplantation (FMT) was used to determine whether ALF can balance Th17/Treg cytokines. The relationship between gut microbiota and clinical indicators was analyzed. BALB/c mice were treated with D-galactosamine (D-GalN) to induce a murine ALF model. FMT to D-GalN mice was conducted to test for liver function indicators. Results showed that the proportions of Lachnospiraceae, Prevotella, S24-7, Odoribacter and Rikenellaceae in D-GalN mice with intestinal microbiota disorder were restored after FMT. Further, CIA analysis showed that bacteria had a covariant relationship with clinical indicators. Microbiota could account for changes in 49.9% of the overall clinical indicators. Adonis analysis showed that Ruminococcus, and Enterococcus have a greater impact on clinical indicators. FMT down-regulated the expression of IL-17A, TNF-α, and TGF-ß, while up-regulated IL-10 and IL-22. Transplantation of feces from Saccharomyces boulardii donor mice improved GalN-induced liver damage. These findings indicate that FMT attenuates D-GalN-induced liver damage in mice, and a clinical trial is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with ALF.

"One stone, two birds": engineering 2-D ultrathin heterostructure nanosheet BiNS@NaLnF4 for dual-modal computed tomography/magnetic resonance imaging guided, photonic synergetic theranostics.

It is interesting yet challenging to design theranostic nanoplatforms for the accurate diagnosis and therapy of diseases; these nanoplatforms consist of single contrast-enhanced imaging or therapeutic agents, and they possess their own unique shortcomings that limit their widespread bio-medical applications. Therefore, designing a potential theranostic agent is an emerging approach for the synergistic diagnosis and therapeutics in bio-medical applications. Herein, a lanthanide-loaded (NaLnF4) heterostructure BiOCl ultrathin nanosheet (BiNS@NaLnF4) as a theranostic agent was synthesized facilely by a solvothermal protocol. BiNS@NaLnF4 was employed as a multi-modal contrast agent for computed tomography (CT) and magnetic resonance imaging (MRI), showing a high-performance X-ray absorption contrast effect, an outstanding T1-weighted imaging function result, good cytocompatibility and favorable in vivo effective imaging for CT. Notably, BiNS@NaLnF4 was applied to achieve a satisfactory photon-thermal conversion efficiency (35.3%). Moreover, the special heterostructure barrier achieved increased utilization of electrons/holes, enhancing the generation of reactive oxygen species (ROS) under visible-light irradiation to further expand the therapeutic effect. Dramatically, visible light emission with the up-conversion law was employed to stimulate ROS after irradiation with a 980 nm laser. Simultaneously, the as-prepared BiNS@NaLnF4 can be applied in photothermal/photodynamic therapy (PTT/PDT) investigation for tumor ablation. In summary, the results reveal that BiNS@NaLnF4 is a potential multi-modal theranostic candidate, providing new insights for synergistic theranostics of tumors.

Human-induced pluripotent stem cells for modelling metabolic perturbations and impaired bioenergetics underlying cardiomyopathies.

Normal cardiac contractile and relaxation functions are critically dependent on a continuous energy supply. Accordingly, metabolic perturbations and impaired mitochondrial bioenergetics with subsequent disruption of ATP production underpin a wide variety of cardiac diseases, including diabetic cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, anthracycline cardiomyopathy, peripartum cardiomyopathy, and mitochondrial cardiomyopathies. Crucially, there are no specific treatments for preventing the onset or progression of these cardiomyopathies to heart failure, one of the leading causes of death and disability worldwide. Therefore, new treatments are needed to target the metabolic disturbances and impaired mitochondrial bioenergetics underlying these cardiomyopathies in order to improve health outcomes in these patients. However, investigation of the underlying mechanisms and the identification of novel therapeutic targets have been hampered by the lack of appropriate animal disease models. Furthermore, interspecies variation precludes the use of animal models for studying certain disorders, whereas patient-derived primary cell lines have limited lifespan and availability. Fortunately, the discovery of human-induced pluripotent stem cells has provided a promising tool for modelling cardiomyopathies via human heart tissue in a dish. In this review article, we highlight the use of patient-derived iPSCs for studying the pathogenesis underlying cardiomyopathies associated with metabolic perturbations and impaired mitochondrial bioenergetics, as the ability of iPSCs for self-renewal and differentiation makes them an ideal platform for investigating disease pathogenesis in a controlled in vitro environment. Continuing progress will help elucidate novel mechanistic pathways, and discover novel therapies for preventing the onset and progression of heart failure, thereby advancing a new era of personalized therapeutics for improving health outcomes in patients with cardiomyopathy.

Investigation of Microstructure and Nanoindentation Hardness of C+ & He+ Irradiated Nanocrystal SiC Coatings during Annealing and Corrosion.

The microstructure and nanoindentation hardness of unirradiated, irradiated, annealed and corroded SiC coatings were characterized. Irradiation of 400 keV C+ and 200 keV He+ with approximately 10 dpa did not cause obvious amorphous transformation to nanocrystal SiC coatings and induced helium bubbles with 2-3 nm dimension distributed uniformly in the SiC matrix. High temperature annealing resulted in the transformation of SiC nanocrystals into columnar crystals in the irradiated region. Line-shaped bubble bands formed at the columnar crystal boundaries and their stacking fault planes and made the formation of microcracks of hundreds of nanometers in length. Meanwhile, some isolated helium bubbles distributed in SiC grains still maintained a size of 2-3 nm, despite annealing at 1200 °C for 5 h. The SiC coating showed excellent corrosion resistance under high-temperature, high-pressure water. The weight of the sample decreased with the increase of corrosion time. The nanoindentation hardness and the elastic modulus increased significantly with C+ and He+ irradiation, while their values decreased with high-temperature annealing. An increase in the annealing temperature led to an increased reduction in the values. Corrosion caused the decrease of nanoindentation hardness and the elastic modulus in the whole test depth range, whether the samples were irradiated or unirradiated.

Quantifying the learning curve of emergent total arch replacement in acute type A aortic dissection.

BACKGROUND: Acute type A aortic dissection with arch involvement is a life-threatening condition, which requires immediate surgical attention. Emergent total arch replacement and root reconstruction is a technically demanding operation with varying outcomes based on surgeon experience. The human factors in total arch replacement in the emergent setting have never been systematically investigated. The ability of surgeons with low volumes to achieve acceptable results in their start-up period is not known. METHODS: From January 2013 to December 2016, patients with acute type A aortic dissection who underwent emergent total arch replacement with three surgeons were enrolled. Basic characteristics, procedural and postoperative outcomes were collected. The time of critical surgical steps and operative mortality were calculated using descriptive statistics and cumulative SUM (CUSUM) analysis. RESULTS: A total of 300 patients (age 53.8±11.5 years, female 63, 21.0%) with acute type A aortic dissection underwent emergent total arch replacement. A total of 219 patients (73.0%) had root reinforcement, 295 patients (98.3%) underwent frozen elephant trunk repair. Mean circulatory arrest and cross-clamp times were 29.8±9.8 and 112.3±32.1 min, respectively. The operative mortality was 6.7%, the stroke rate was 4.0%. The mean length of postoperative ICU and hospital stays were 8.4±10.6 and 18.0±12.2 days, respectively. By CUSUM depictions, surgeons appeared to have different learning curves with regards to operative time. By CUSUM failure analysis on operative mortality, two newly appointed surgeons in their start-up period stayed in an acceptable range, while one senior surgeon with higher volumes experienced superior outcomes and better performance. CONCLUSIONS: Although emergent total arch replacement for acute type A dissection is a complex scenario, surgeons well-trained in adult cardiac surgery are able to achieve acceptable results in their start-up period.

Platycodin D alleviates liver fibrosis and activation of hepatic stellate cells by regulating JNK/c-JUN signal pathway.

Liver fibrosis is involved in the progression of most chronic liver diseases. Even though we have made a huge progress in order to understand the pathogenesis of liver fibrosis, however, there is still a lack of productive treatments. Being a traditional Chinese medicine, Platycodin D (PD), an oleanane kind of triterpenoid saponin has been put to extensive use for treating different kinds of illnesses that include not just anti-nociceptive, but also antiviral, anti-inflammatory, and anti-cancer for thousands of years. Nonetheless, there has been no clarification made for its effects on the progression of liver fibrosis. In this manner, we carried out in vitro studies for the purpose of investigating the anti-fibrosis impact of PD. Activation of hepatic stellate cells was evaluated by means of the detection of the proliferation of HSCs and the expression of specific proteins. We discovered the fact that PD had the potential of activating HSCs. Thereafter, we detected the apoptosis and autophagy of the HSCs; as the results suggested, PD induced apoptosis and autophagy of the HSCs. It augmented the expression level of apoptotic proteins that included Bax, Cytochrome C (cyto-c), cleaved caspase3 and cleaved caspase9, in addition to the autophagy relevant proteins, for instance, LC3II, beclin1, Atg5 and Atg9. Further research was carried out for the investigation of the underlying molecular mechanism, and discovered that PD promoted the phosphorylation of JNK and c-Jun. Treating the JNK inhibitor P600125 inhibited the effect of PD, confirming the impact of PD on the regulation of JNK/c-Jun pathway. Thus, we speculated that PD alleviates liver fibrosis and activation of hepatic stellate via promoting phosphorylation of JNK and c-Jun and further altering the autophagy along with apoptosis of HSCs.

Mechanisms underlying diabetic cardiomyopathy: From pathophysiology to novel therapeutic targets.

Diabetic cardiomyopathy (DC) is defined as a clinical condition of cardiac dysfunction that occurs in the absence of coronary atherosclerosis, valvular disease, and hypertension in patients with diabetes mellitus (DM). Despite the increasing worldwide prevalence of DC, due to the global epidemic of DM, the underlying pathophysiology of DC has not been fully elucidated. In addition, the clinical criteria for diagnosing DC have not been established, and specific therapeutic options are not currently available. The current paradigm suggests the impaired cardiomyocyte function arises due to a number of DM-related metabolic disturbances including hyperglycemia, hyperinsulinemia, and hyperlipidemia, which lead to diastolic dysfunction and signs and symptoms of heart failure. Other factors, which have been implicated in the progression of DC, include mitochondrial dysfunction, increased oxidative stress, impaired calcium handling, inflammation, and cardiomyocyte apoptosis. Herein, we review the current theories surrounding the occurrence and progression of DC, and discuss the recent advances in diagnostic methodologies and therapeutic strategies. Moreover, apart from conventional animal DC models, we highlight alternative disease models for studying DC such as the use of patient-derived human induced pluripotent stem cells (hiPSCs) for studying the mechanisms underlying DC. The ability to obtain hiPSC-derived cardiomyocytes from DM patients with a DC phenotype could help identify novel therapeutic targets for preventing and delaying the progression of DC, and for improving clinical outcomes in DM patients.

Postoperative hypothermia after total aortic arch replacement in acute type A aortic dissection-multivariate analysis and risk identification for postoperative hypothermia occurrence.

BACKGROUND: Postoperative hypothermia (PH) is a common physiological abnormality associated with increased morbidity and mortality after non-cardiac surgery. The incidence, risk factors of PH and its impact on early outcomes after total aortic arch replacement are not clear. METHODS: We conducted a retrospective cohort study in patients with acute type A aortic dissection who underwent total arch replacement from January 2013 to December 2016 at our institution. Basic variables, procedural and postoperative early outcomes were collected. Univariate and multivariate statistical analysis were performed for statistical interpretation. The early outcomes were compared between patients with or without PH. RESULTS: A total of 300 patients (age 53.8±11.5 years, female 63, 21.0%) with acute type A aortic dissection underwent total arch replacement. Forty-four patients (14.7%) developed PH. The independent risk factors of PH are age and the intraoperative lowest bladder temperature. There is no significant difference in major postoperative morbidity and mortality between patients with or without PH. CONCLUSIONS: The incidence of PH after total arch replacement in acute type A aortic dissection is relatively low. The independent risk factors of PH in this population include age and the intraoperative lowest bladder temperature. With comprehensive rewarming strategy upon arrival at the ICU, the PH is easy to be corrected, and the adverse effect of transient PH on early outcomes after arch surgery is minimal.

Myeloperoxidase As a Multifaceted Target for Cardiovascular Protection.

Significance: Myeloperoxidase (MPO) is a heme peroxidase that is primarily expressed by neutrophils. It has the capacity to generate several reactive species, essential for its inherent antimicrobial activity and innate host defense. Dysregulated MPO release, however, can lead to tissue damage, as seen in several diseases. Increased MPO levels in circulation are therefore widely associated with conditions of increased oxidative stress and inflammation. Recent Advances: Several studies have shown a strong correlation between MPO and cardiovascular disease (CVD), through which elevated levels of circulating MPO are linked to poor prognosis with increased risk of CVD-related mortality. Accordingly, circulating MPO is considered a "high-risk" biomarker for patients with acute coronary syndrome, atherosclerosis, heart failure, hypertension, and stroke, thereby implicating MPO as a multifaceted target for cardiovascular protection. Consistently, recent studies that target MPO in animal models of CVD have demonstrated favorable outcomes with regard to disease progression. Critical Issues: Although most of these studies have established a critical link between circulating MPO and worsening cardiac outcomes, the mechanisms by which MPO exerts its detrimental effects in CVD remain unclear. Future Directions: Elucidating the mechanisms by which elevated MPO leads to poor prognosis and, conversely, investigating the beneficial effects of therapeutic MPO inhibition on alleviating disease phenotype will facilitate future MPO-targeted clinical trials for improving CVD-related outcomes.