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Introduction: Myocardial injury is a serious complication in sepsis with high mortality. Zero-valent iron nanoparticles (nanoFe) displayed novel roles in cecal ligation and puncture (CLP)-induced septic mouse model. Nonetheless, its high reactivity makes it difficult for long-term storage. Objectives: To overcome the obstacle and improve therapeutic efficiency, a surface passivation of nanoFe was designed using sodium sulfide. Methods: We prepared iron sulfide nanoclusters and constructed CLP mouse models. Then the effect of sulfide-modified nanoscale zero-valent iron (S-nanoFe) on the survival rate, blood routine parameters, blood biochemical parameters, cardiac function, and pathological indicators of myocardium was observed. RNA-seq was used to further explore the comprehensive protective mechanisms of S-nanoFe. Finally, the stability of S-nanoFe-1d and S-nanoFe-30 d, together with the therapeutic efficacy of sepsis between S-nanoFe and nanoFe was compared. Results: The results revealed that S-nanoFe significantly inhibited the growth of bacteria and exerted a protective role against septic myocardial injury. S-nanoFe treatment activated AMPK signaling and ameliorated several CLP-induced pathological processes including myocardial inflammation, oxidative stress, mitochondrial dysfunction. RNA-seq analysis further clarified the comprehensive myocardial protective mechanisms of S-nanoFe against septic injury. Importantly, S-nanoFe had a good stability and a comparable protective efficacy to nanoFe. Conclusions: The surface vulcanization strategy for nanoFe has a significant protective role against sepsis and septic myocardial injury. This study provides an alternative strategy for overcoming sepsis and septic myocardial injury and opens up possibilities for the development of nanoparticle in infectious diseases.

Abstract Background Depressive symptoms associated with schizophrenia are closely related to stigma and quality of life(QOL). There is, however, no thorough research on the connection between the three. This study sought to investigate the possible factors influencing depressive symptoms in people with schizophrenia (PWS) in rural Chaohu, China, and to further explore the role of depression severity in stigma and lifestyle quality. Methods Eight hundred twenty-one schizophrenia patients accomplished the entire scale, including the 9-item Patient Health Questionnaire (PHQ-9), the Social Impact Scale (SIS), and the World Health Organization on Quality of Life Brief Scale(WHOQOL—BREF). A straightforward mediation model was employed to determine if the intensity of the depression could act as a mediator between stigma and QOL. Results Two hundred seventy-nine schizophrenia patients (34%) had depressive symptoms (PHQ ≥ 10), and 542 patients (66%) did not (PHQ

Abstract Background Heart failure is a common complication of sepsis with a high mortality rate. It has been reported that melatonin can attenuate septic injury due to various properties. On the basis of previous reports, this study will further explore the effects and mechanisms of melatonin pretreatment, posttreatment, and combination with antibiotics in the treatment of sepsis and septic myocardial injury. Methods and results Our results showed that melatonin pretreatment showed an obvious protective effect on sepsis and septic myocardial injury, which was related to the attenuation of inflammation and oxidative stress, the improvement of mitochondrial function, the regulation of endoplasmic reticulum stress (ERS), and the activation of the AMPK signaling pathway. In particular, AMPK serves as a key effector for melatonin-initiated myocardial benefits. In addition, melatonin posttreatment also had a certain degree of protection, while its effect was not as remarkable as that of pretreatment. The combination of melatonin and classical antibiotics had a slight but limited effect. RNA-seq detection clarified the cardioprotective mechanism of melatonin. Conclusion Altogether, this study provides a theoretical basis for the application strategy and combination of melatonin in septic myocardial injury.

Abstract Background Septic heart failure accounts for high mortality rates globally. With a strong reducing capacity, zero-valent iron nanoparticles (nanoFe) have been applied in many fields. However, the precise roles and mechanisms of nanoFe in septic cardiomyopathy remain unknown. Results NanoFe was prepared via the liquid-phase reduction method and functionalized with the biocompatible polymer sodium carboxymethylcellulose (CMC). We then successfully constructed a mouse model of septic myocardial injury by challenging with cecal ligation and puncture (CLP). Our findings demonstrated that nanoFe has a significant protective effect on CLP-induced septic myocardial injury. This may be achieved by attenuating inflammation and oxidative stress, improving mitochondrial function, regulating endoplasmic reticulum stress, and activating the AMPK pathway. The RNA-seq results supported the role of nanoFe treatment in regulating a transcriptional profile consistent with its role in response to sepsis. Conclusions The results provide a theoretical basis for the application strategy and combination of nanoFe in sepsis and septic myocardial injury. Graphical Abstract

Introduction: Adriamycin (ADR) is an efficient and common broad-spectrum anticancer drug. However, the cumulative and dose-dependent toxicity induced by ADR severely limits its application in the clinic. Previous studies found that psoralidin (PSO) exhibits remarkable therapeutic effects against multiple cancers. Objectives: The aim of this study was to determine if PSO has beneficial effects on ADR-induced cardiotoxicity and to investigate the underlying mechanisms. Methods: ADR-induced cardiotoxicity models were established in BALB/c mice and HL-1 cardiomyocytes. A series of experimental methods were used to evaluate the effects of PSO on cardiac function indicators, blood biochemical parameters, histopathology, oxidative stress, apoptosis, mitochondrial function, fibrosis, and SIRT1/PPARγ signaling. Results: PSO significantly improved cardiac function indicators, blood biochemical parameters, and mitochondrial function and reduced the degree of myocardial fibrosis, oxidative stress, and apoptosis in ADR-injured mice. PSO significantly increased cell viability, inhibited the release of LDH, reduced oxidative stress and apoptosis, and improved mitochondrial function in ADR-injured HL-1 cells. Moreover, we also demonstrated there was cross-talk between SIRT1 and PPARγ, as shown by SIRT1 siRNA significantly decreasing the expression of PPARγ and GW9662 (a PPARγ antagonist), which remarkably reduced the expression of SIRT1. Conclusion: In summary, this study proved for the first time the beneficial effect of PSO on ADR-induced cardiotoxicity through activation of the SIRT1/PPARγ signaling pathway. Therefore, these findings may favor PSO as a potential cardioprotective drug candidate to alleviate ADR-induced cardiotoxicity in the clinic and improve the application of ADR in oncotherapy.

Abstract Cytochrome c oxidase subunit VIc (COX6c) is one of the most important subunits of the terminal enzyme of the respiratory chain in mitochondria. Numerous studies have demonstrated that COX6c plays a critical role in the regulation of oxidative phosphorylation (OXPHOS) and energy production. The release of COX6c from the mitochondria may be a hallmark of the intrinsic apoptosis pathway. Moreover, The changes in COX6c expression are widespread in a variety of diseases and can be chosen as a potential biomarker for diagnosis and treatment. In light of its exclusive effects, we present the elaborate roles that COX6c plays in various diseases. In this review, we first introduced basic knowledge regarding COX6c and its functions in the OXPHOS and apoptosis pathways. Subsequently, we described the regulation of COX6c expression and activity in both positive and negative ways. Furthermore, we summarized the elaborate roles that COX6c plays in various diseases, including cardiovascular disease, kidney disease, brain injury, skeletal muscle injury, and tumors. This review highlights recent advances and provides a comprehensive summary of COX6c in the regulation of OXPHOS in multiple diseases and may be helpful for drug design and the prediction, diagnosis, treatment, and prognosis of diseases.

Hydrogen energy has the advantages of high energy density,green and sustainability,which make it an ideal energy source for human society.Hydrogen generation by seawater electrocatalysis becomes the strategic direction of hydrogen energy industry in the future.The activity and stability of cathode hydrogen evolution catalyst are vital to this hydrogen energy strategy.Although the precious metal Pt-based electrocatalysts have shown excellent catalytic performance on hydrogen evolution,the high price and scarce resources limit their large-scale application.Therefore,nonprecious metal electrocatalysts have attracted much research attention.Starting from the principle of hydrogen evolution reaction,important parameters of overpotential,Tafel slope,Faraday efficiency,specific activity and mass activity,etc.were introduced to evaluate catalytic performances.The review summarized recent progress on multiple nonprecious metal electrocatalysts for cathode hydrogen generation by seawater electrocatalysis,and the problems of current research was clarified.Additionally,the future research of nonprecious metal electrocatalysts in cathode for large-scale hydrogen generation by seawater electrocatalysis was prospected from the following aspects:1) Designing nonprecious metal catalysts with high activity and stability;2) Optimizing production and preparation process of nonprecious metal catalyst;3) Using advanced test and characterization to construct reaction models;4) Deepening theoretical calculation for the mechanism research.

Abstract Most sepsis deaths are due to the development of multiple organ failure, in which heart failure is a recognized manifestation of sepsis. To date, the role of liver X receptors α (NR1H3) in sepsis is still uncertain. Here, we hypothesized that NR1H3 mediates multiple essential sepsis‐related signalings to attenuate septic heart failure. Adult male C57BL/6 or Balbc mice and HL‐1 myocardial cell line were performed for in vivo and in vitro experiments, respectively. NR1H3 knockout mice or NR1H3 agonist T0901317 was applied to evaluate the impact of NR1H3 on septic heart failure. We found decreased myocardial expression levels of NR1H3‐related molecules while increased NLRP3 level in septic mice. NR1H3 knockout worsensed cardiac dysfunction and injury in mice subjected to cecal ligation and puncture (CLP), in association with exacerbated NLRP3‐mediated inflammation, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis‐related markers. The administration of T0901317 reduced systemic infection and improve cardiac dysfunction in septic mice. Moreover, Co‐IP assays, luciferase reporter assays, and chromatin immunoprecipitation analysis, confirmed that NR1H3 directly repressed NLRP3 activity. Finally, RNA‐seq detection further clarified an overview of the roles of NR1H3 in sepsis. In general, our findings indicate that NR1H3 had a significant protective effect against sepsis and sepsis‐induced heart failure.

Abstract Sepsis causes multiple organ injuries, among which the heart is one most severely damaged organ. Melatonin (MEL) alleviates septic myocardial injury, although a systematic and comprehensive approach is still lacking to understand the precise protective machinery of MEL. This study aimed to examine the underlying mechanisms of MEL on improvement of septic myocardial injury at a systematic level. This study integrated three analytic modalities including database investigations, RNA‐seq analysis, and weighted gene co‐expression network analysis (WCGNA), in order to acquire a set of genes associated with the pathogenesis of sepsis. The Drugbank database was employed to predict genes that may serve as pharmacological targets for MEL‐elicited benefits, if any. A pharmacological protein–protein interaction network was subsequently constructed, and 66 hub genes were captured which were enriched in a variety of immune response pathways. Notably, PIK3CG, one of the hub genes, displayed high topological characteristic values, strongly suggesting its promise as a novel target for MEL‐evoked treatment of septic myocardial injury. Importantly, molecular docking simulation experiments as well as in vitro and in vivo studies supported an essential role for PIK3CG in MEL‐elicited effect on septic myocardial injury. This study systematically clarified the mechanisms of MEL intervention in septic myocardial injury involved multiple targets and multiple pathways. Moreover, PIK3CG‐governed signaling cascade plays an important role in the etiology of sepsis and septic myocardial injury. Findings from our study provide valuable information on novel intervention targets for the management of septic myocardial injury. More importantly, this study has indicated the utility of combining a series of techniques for disease target discovery and exploration of possible drug targets, which should shed some light on elucidation of experimental and clinical drug action mechanisms systematically.

The nucleosome-binding proteins HMGN1 and HMGN2 prefer acetylated nucleosomes at H3K27ac and the loss of this interaction alters binding of transcription factors to chromatin.

The photosynthetic tetrapyrroles share a common structural feature comprised of a β-ketoester motif embedded in an exocyclic ring (ring E). As part of a total synthesis program aimed at preparing native structures and analogues, 3-(3-methoxy-1,3-dioxopropyl)pyrrole was sought. The pyrrole is a precursor to analogues of ring C and the external framework of ring E. Four routes were developed. Routes 1–3 entail a Pd-mediated coupling process of a 3-iodopyrrole with potassium methyl malonate, whereas route 4 relies on electrophilic substitution of TIPS-pyrrole with methyl malonyl chloride. Together, the four routes afford considerable latitude. A long-term objective is to gain the capacity to create chlorophylls and bacteriochlorophylls and analogues thereof by facile de novo means for diverse studies across the photosynthetic sciences.

Ischemic stroke is characterized by insufficient blood supply to brain tissue and is associated with increased morbidity and mortality in adults worldwide. Growth arrest-specific protein 6 (GAS6) is a vitamin K-dependent protein and is widely expressed in the central nervous system. The biological functions of GAS6 are mediated by the interaction with TAM (Tyro3, Axl and Mertk) receptors, including cell survival and proliferation, immune regulation and apoptosis. Omentin-1, also known as intelectin-1 (ITLN-1), is a novel adipocytokine that is involved in a variety of biological events, such as insulin resistance, endothelial dysfunction, programmed cell death and metabolic disorders. Our previous study has found that omentin-1 act as a novel regulator of vascular and anti-apoptotic response in cerebral ischemia. However, the specific molecular mechanism of omentin-1’s protective effect on cerebral ischemia-reperfusion injury (IRI) is still unclear. First, the toxicity of recombinant human omentin-1 (rh-omentin) was assessed and a safe concentration was chosen for the next experiments. Then, rh-omentin exerted neuroprotection against hypoxia/reoxygenation (H/R) injury in N2a cells, indicated by increased cell viability, decreased LDH, ROS generation, and cell apoptotic rate. Furthermore, the similar protective effect was observed in omentin-1 overexpression cells constructed by lentivirus transfection. Rh-omentin could also inhibit H/R-induced apoptotic molecules, oxidative stress molecules, and GAS6/Axl signaling molecules which as evidence by increased omentin-1, GAS6, Axl, p-Axl, NQO1, HO-1, Nrf2, Bcl2 and decreased Bax expressions. However, GAS6 siRNA could reverse rh-omentin-induced neuroprotection and the levels of these molecules mentioned above. In conclusion, these findings suggest that omentin-1 treatment exerts neuroprotection against H/R injury partly via activating GAS6/Axl signaling at least. Therefore, these finding may favor omentin-1 a potential neuroprotective drug candidate to alleviate ischemia-reperfusion injury in clinic.

The objectives of flood control, power generation, water supply and ecology for reservoir operation are neither completely coordinated nor completely opposed, and its optimal operation and decision-making is very complicated. This study proposed a method of multi-objective optimization and multi-attribute decision making for reservoir operation (MODRO). The correlation analysis method was used to analyze the competitive relationship among the extracted objectives, and the multi-objective optimal operation model was constructed. The NSGA-II-SEABODE algorithm was applied to solve the MODRO problem. The objective extraction, model construction, optimization solution and scheme selection were coupled to form a multi-objective optimization and multi-attribute decision making method with the whole process of “Objective-Modeling-Optimization-Selection”. Huangjinxia Reservoir, which is located in Shaanxi, China, was selected as the case study. The results show that: (1) Quantifying the degree of conflict among objectives makes the construction of the multi-objective optimal operation model more reasonable. (2) The NSGA-II-SEABODE algorithm are used to obtain the decision-making scheme, which provides decision-making basis for managers. (3) For Huangjinxia Reservoir, water diversion is negatively related to power generation and ecology, and power generation is positively related to ecology. The results can promote the efficient utilization of water resources, improve the comprehensive benefits of reservoirs, and provide decision-making support for actual reservoir operation.

HMGN1 and HMGN2 are ubiquitous nucleosome binding proteins. Here the authors provide evidence that HMGN proteins preferentially localize to chromatin regulatory sites to modulate the plasticity of the epigenetic landscape, proposing that HGMNs stabilize, rather than determine, cell identity.

The authors have investigated the impact of nanowire geometry on the carrier transport in axial indium gallium nitride and gallium nitride (InGaN/GaN) nanowire light-emitting diodes (LEDs). The results reveal that hole transport depends critically on the nanowire geometry. With identical material parameters, the carrier transport process can be varied with different nanowire geometry designs, which lead to different overall device performance. This study offers important insight into the design and epitaxial growth of high-performance nanowire LEDs.

The optical performance of top-down etched InGaN/GaN nanorod light emitting diodes (LEDs) was studied using temperature variable photoluminescence spectroscopy with a 405 nm pump laser. Efficiency droop is measured from such nanorod structures, which is further enhanced with decreasing temperature. Through detailed rate equation analysis of the temperature-dependent carrier distribution and modeling of the quantum efficiency, this unique phenomenon can be largely explained by the interplay and dynamics between carrier radiative recombination in localized states and nonradiative recombination via surface states/defects.

Archaea are an important component of the gut microbiomes of animals and play a key role in animal health. However, they have been neglected in previous microbial studies, particularly those involving migratory waterbirds. Here, we investigated the gut archaeal communities of Anser erythropus wintering at Shengjin and Caizi Lakes in China using metagenomic analysis of 20 fecal samples (ten samples per lake). The operational taxonomic units (OTUs) in the gut archaea of geese wintering in the two lakes represented 16 phyla, 16 classes, 24 orders, 27 families, and 45 genera, with Euryarchaeota, Thaumarchaeota, and Bathyarchaeota being the dominant gut archaeal phyla. The results of alpha diversity analysis showed a significant difference in composition between the Shengjin and Caizi Lake samples, and orthogonal partial least squares-discriminant analysis (OPLS-DA) analysis indicated that geese were well-matched with their lakes of origin. Stamp analysis revealed a difference of 27 gut archaeal species between A. erythropus wintering at Shengjin Lake and those at Caizi Lake. Archaeal network analysis results fell into four major modules, with Methanolobus psychrotolerans and Thaumarchaeota archaeon as the hub modules. The abundances of several bacterial and fungal genera were significantly correlated with abundances of archaeal genera in pairwise populations, and a positive correlation was observed between archaeal, bacterial, and fungal diversities in the guts of A. erythropus wintering at both Shengjin and Caizi Lakes (R=0.4, p=2.2×10-16; R=0.86, p=2.2×10-16, respectively). This suggests that fecal bacteria and fungi may cooperate with archaea to perform crucial roles in the gut. However, because of the small sample size in this study, further studies are needed to fully investigate the altered archaea in the guts of these geese. [ABSTRACT FROM AUTHOR]