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Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4–1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.

Rural sustainable land use (RSLU) is important to China's implementation of the UN 2030 Agenda for Sustainable Development Goals and the goals of rural revitalization strategy in China. Research on RSLU is key to understanding the impact of human activities on rural sustainability. This paper explored the evaluation method of RSLU from a system perspective based on the ecosystem service value (ESV). Three systems were proposed for consideration when conducting this evaluation method. One was the sustainability of the land system, the other was the sustainability of the eco-economic system, and the rest was the sustainability of the land-eco-economy system. Indicators including (1) land use intensity and land system stability, (2) gross domestic production (GDP), ESV, and the eco-economic harmony degree (EEHD), and (3) coupling degree and coupling coordination degree were used to analyze the sustainability of the land, eco-economic, and land-eco-economic systems, respectively. An empirical research on Yanhe eco-village was conducted and the study period extended from 2008 to 2020. The results showed that forest land had always accounted for more than 81.20% of the total area in Yanhe eco-village from 2008 to 2020, which greatly influenced land system stability and restricted economic development. This feature contrasted with RSLU. The total ESV of Yanhe eco-village declined by 1.60 ​× ​106 CNY during 2008–2020 because of land use changes. The EEHD was −0.01, which presented that there was a very slight unharmonious between ecology and economy. The coupling degree and coupling coordination degree showed that the development between the land and eco-economic systems exhibited a coupling coordination relationship. The results indicated that ecology and economy in Yanhe eco-village will change significantly in response to land use changes in rural areas, which further revealed the dynamic linkage between human beings and nature. Moreover, opposite variation tendencies in land system stability and ESV revealed that the contradiction between the high stability of the land system and well development of the eco-economic system. The results of this study implied that it is necessary and useful to integrate ESV into land management to achieve RSLU.

Efficient lithium-ion transport is pivotal for the battery advancement, and the transference number plays a central role in achieving this efficiency. In the literature, significant discrepancies in transference number values are often observed. For instance, in polymer electrolytes, notable inconsistencies in transference numbers exist even when the electrolyte chemistry, such as salt concentration and polymer molecular weight, is held constant. Therefore, conventional wisdom focusing on the material chemistry cannot explain these inconsistent results. Herein, we report a long-standing overlooked aspect: the discrepant transference number results can stem from the misestimation of parameters in measurement methodologies. Our analysis leverages the transmission-line-model applied to a polyethylene oxide electrolyte, allowing us to reevaluate traditional measurement methods. Through this reassessment, we not only uncover how the determination of measurement parameters can exert a significant influence on the attained transference number but also suggest a method to accurately characterize the transference number. Furthermore, we explore the origins of anomalous transference number and elucidate the impact of transference number on electrochemical impedance and direct-current polarization experiments. This research contributes vital insights into addressing critical challenges associated with transference number measurements in electrolyte systems, promoting the development of more efficient lithium-ion transport in battery technology. • Inconsistent transference numbers often occur in traditional measurement methods. • Instructions for accurate determination of transference numbers are provided. • Impacts of improperly determined parameters on transference numbers are unveiled. • The proposed method is applicable to various types of electrolyte systems. [ABSTRACT FROM AUTHOR]

Abstract Sarcopenia is a progressive skeletal muscle disorder involving the loss of muscle mass and function, associated with an increased risk of disability and frailty. Though its prevalence in dementia has been studied, its occurrence in mild cognitive impairment (MCI) has not been well established. As MCI is often a prelude to dementia, our study aims to investigate the prevalence of MCI among individuals with sarcopenia and to also ascertain whether sarcopenia is independently associated with MCI. The Cochrane Library, PubMed, Ovid, Embase and Web of Science were systematically searched for articles on MCI and/or sarcopenia published from inception to 1 February 2022. We reviewed the available literature on the number of individuals with MCI and/or sarcopenia and calculated odds ratios (ORs) of sarcopenia in MCI and MCI in sarcopenia, respectively. Statistical analyses were performed using the meta package in Stata, Version 12.0. A total of 13 studies and 27 428 patients were included in our analysis. The pooled prevalence of MCI in participants with sarcopenia was 20.5% (95% confidence interval [CI]: 0.140–0.269) in a total sample of 2923 cases with a high level of heterogeneity (P

Abstract Background Strokes significantly impair quality of life and incur high economic and societal burdens. The triglyceride and glucose (TyG) index is a biochemical marker of insulin resistance (IR) and may have important value in the prediction of strokes, especially ischemic stroke (IS). Our study aims to investigate the relationship between TyG index and IS and ascertain whether TyG index is independently associated with IS adverse outcomes. Methods The Cochrane, Embase, Medline, Web of Science, PubMed, and other relevant English databases and related websites were systematically searched for articles on ‘‘TyG index’’ and "stroke" published from inception to April 4, 2022. We reviewed the available literature on the TyG index and its relation to predicting IS occurrence in the general population and adverse clinical outcomes. We calculated odds ratios (OR) of TyG index and its predictability of IS occurrence and adverse outcomes. Statistical analyses were performed using the Meta Package in STATA, version 12.0. Results A total of 18 studies and 592,635 patients were included in our analysis. The pooled effect values of all stroke types showed that higher TyG index was associated with increased the risk of IS in the general population (OR 1.37; 95% CI 1.22–1.54) in a total sample of 554,334 cases with a high level of heterogeneity (P = 0.000, I 2 = 74.10%). In addition, compared to IS patients with a lower TyG index, IS patients with a higher TyG index was associated with higher risk of stroke recurrence (OR: 1.50; 95% CI 1.19–1.89) and increased risk of mortality (OR 1.40 95% CI 1.14–1.71). No correlation was found in the effect value combinations of poor functional outcomes (OR 1.12; 95% CI 0.88–1.43) and neurological worsening (OR: 1.76; 95% CI 0.79–3.95) in a total sample of 38,301 cases with a high level of heterogeneity (P = 0.000; I 2 = 77.20%). Conclusions TyG index has potential value in optimizing risk stratification for IS in the general population. Furthermore, there is a significant association between high TyG index and many adverse outcomes of stroke, especially stroke recurrence and high mortality. Future studies should focus on multi-center and multi-regional designs in order to further explore the relationship between IS and TyG index.

The coregistration of optical and synthetic aperture radar (SAR) imageries is the bottleneck in exploring the complementary information from the two multimodal datasets. The difficulties lie in not only the complex radiometric relationship between them, but also the distinct geometrical models of the optical and SAR imaging systems, which cause it nontrivial to explicitly depict the spatial relationship between the corresponding image regions when elevation fluctuations exist. This article aims to investigate the optical flow technique for the pixelwise dense registration of the high-resolution optical and SAR images, so as to get rid of the outlier removal and geometric mapping procedures, which have to be conducted in the classical image registration approaches that are based on sparse feature point matching. Herein, a deep optical flow framework is designed. First, a dilated feature concatenation method is proposed to enhance the discriminability of the pixelwise features for similarity measurement. An effective network training strategy is used, based on a smoothed flow loss, and also a training dataset that contains simulated elevation fluctuations. Second, we propose a self-supervised optical flow fine-tuning strategy. It incorporates the strength of the blockwise matching approach, which produces better matching precision, into the proposed pixelwise matching procedure. In this way, the accuracy of the optical-SAR dense registration is substantially improved. Extensive experiments conducted on the 1-m resolution optical-SAR image pairs of different land-cover types and distinct topographic conditions indicate that the proposed optical-SAR optical flow network -Ft framework is quite robust, and has the potential to perform the optical-SAR image dense registration in practical applications. The Python code of the proposed deep optical flow network will be made available.

Integrating ecosystem service value (ESV) into the evaluation system for sustainable land use (SLU) in fast-growing cities is an effective way to implement Sustainable Development Goals (SDGs) 15 and 11 of the United Nations' 2030 Agenda for Sustainable Development. Taking ESV as the intermediate parameter, six sustainability indicators were developed to evaluate SLU from two dimensions: sustainable land ecosystem services and economic development. These indicators are the total supply and demand index (RT) of ecosystem services, the potential supply and demand index (RP) of ecosystem services, the ecological cost index per unit of GDP (RC), the eco-economic coordination index (RD), the eco-economic equilibrium index (RE), and the ESV-based sustainable land use index (RS). Empirical research was conducted in Qingdao, a fast-growing city in eastern China, to verify the validity of the indicators. Five sets of Landsat TM/ETM/OLI remote sensing images from 1996, 2005, 2010, 2015, and 2017 were used to analyze the land use and ESV changes in Qingdao. The results indicate that land use changes in fast-growing cities significantly affect the ESV. The decrease in the area of ecological land and the expansion of construction land caused by rapid urbanization reduced ESV. The RC and RD of Qingdao were sustainable, while the RT and RP were unsustainable, and the RE showed volatility, which reduced the evaluation level of SLU in Qingdao from extremely strongly sustainable (L1) to moderately sustainable (L3). Thus, it is necessary to improve the ESV of Qingdao. Optimization strategies for promoting SLU in Qingdao are proposed based on the results, confirming that the evaluation provides guidance for land use management.

Summary: Background: Smoking, alcohol consumption and overweight/obesity are key cancer risk factors contributing to the cancer burden in China. We aimed to quantify the cancer burden in China associated with smoking, alcohol consumption and overweight/obesity, and estimate the potential effect for cancer prevention interventions under different scenarios. Methods: We used a macro-simulation approach called Prevent Model to estimate for a 30-year study period (2021–2050) numbers and proportions of future avoidable cancer cases under different scenarios of reducing the prevalence of smoking, alcohol consumption and overweight/obesity in Chinese adults. Cancer incidence was predicted under three scenarios: elimination, ambitious target (between elimination and manageable target) and manageable target (from national policy or global action plan). Risk factor prevalence was obtained from China Chronic Disease and Risk Factor Surveillance, and cancer incidence data were derived from the China Cancer Registry Annual Report. Relative risks were obtained from several recent large-scale studies or high-quality meta-analysis. Population data were extracted from the China Population & Employment Statistical Yearbook, China Health Statistical Yearbook and World Population Prospects. Findings: Estimates of the avoidable cancer burden varied with different scenarios. In the theoretical maximum intervention scenario, where the prevalence of smoking, alcohol consumption and overweight/obesity would be eliminated, 9.17% (males: 13.50%; females: 1.47%) of smoking-related cancer cases, 7.06% (males: 11.49%; females: 1.00%) of cancer cases related to alcohol consumption and 8.22% (males: 7.91%; females: 8.52%) of overweight/obesity-related cancer cases were estimated to be avoidable during 2021–2050. Other scenarios, with more moderate goals in the exposure prevalence of smoking, alcohol use and overweight/obesity were also found to be associated with substantial reductions in the future cancer burden. Interpretation: Our results suggested that a substantial number of future cancer cases could be avoided in Chinese adults by reducing the prevalence of smoking, alcohol consumption and overweight/obesity. Funding: National Science & Technology Fundamental Resources Investigation Program of China; Sanming Project of Medicine in Shenzhen.

ABSTRACT: Duck Tembusu virus (DTMUV), belonging to the Flaviviridae family, is a major virus that affects duck health in China. MicroRNAs (miRNAs) play an important role in viral replication. However, little is known about the function of miRNAs during DTMUV infection. Here, the host miR-146b-5p was found to regulate DTMUV replication. When DTMUV infected duck embryo fibroblasts (DEFs), the expression levels of miR-146b-5p increased significantly over time. Moreover, the viral RNA copies, E protein expression levels and virus titers were all upregulated when miR-146b-5p was overexpressed in DEFs. The opposite results were also observed upon knockdown of miR-146b-5p in DEFs. To explore the mechanism by which miR-146b-5p promoted DTMUV replication, mass spectrometry, and RNA pull-down assays were employed. Ribosomal protein S14 (RPS14), a component of 40S ribosomal proteins, was identified to interact with miR-146b-5p. In addition, the relative mRNA expression levels of RPS14 gene were negatively modulated by miR-146b-5p. Subsequently, it was found that overexpression of RPS14 could decrease the replication of DTMUV, and the reverse results were also detected by knockdown of RPS14. In conclusion, this study revealed that miR-146b-5p promoted DTMUV replication by targeting RPS14, which provides a new mechanism by which DTMUV evades host defenses and a new direction for further antiviral strategies development.

Winter supplemental feeding (SF) is commonly used to improve the survival of captive wildlife. To investigate the impact of winter supplementation on the gut microbiota of wildlife, we assessed changes in the gut microbiota of red deer (Cervus elaphus) during the supplementary and non-supplementary feeding (NSF) groups using 16S rRNA sequencing technology. We found no significant differences in the diversity of the gut microbiota between SF and NSF except for the Simpson’s index. However, the relative abundance of Bacteroidetes, Lentisphaerae, and Proteobacteria in the gut microbiota was significantly higher during SF. Further, genera such as Intestinimonas, Rikenella, Lawsonibacter, Muribaculum, and Papillibacter were more abundant during SF. Beta diversity analysis showed significant differences between SF and NSF. The microbes detected during SF were primarily associated with lipid metabolism, whereas those detected during NSF were linked to fiber catabolism. High-energy feed affects the gut microbial composition and function in red deer. During SF, the gut microbes in red deer were enriched in microorganisms associated with butyrate and lipid metabolism, such as R. microfusus, M. intestinale, and Papillibacter cinnamivorans. These gut microbes may be involved in ameliorating obesity associated with high-energy diets. In summary, SF is a reasonable and effective management strategy.

Abstract Background Intracerebral hemorrhage (ICH) is a devastating disease, its mortality and disability rate are high. In China, hypertensive intracerebral hemorrhage (HICH) is responsible for 75% of all the cases of primary ICH. A lot of randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) for treating HICH have been carried out. However, these RCTs have a lot of problems, such as heterogeneous outcomes, non-uniform point of measurement. These lead to systematic review/meta-analysis only can include a small number of studies. And outcome measures did not take the wishes of patients and other stakeholders into account. The aim of this study is to establish the core outcome set (COS) for future TCM clinical trials of HICH. Methods and analysis First, we will develop a long list of general outcomes by making systematic literature review and semi-structured interviews. Then healthcare professionals and patients with HICH will be invited to participate in two rounds of the Delphi survey to determine the importance of the outcome. Finally, a face-to-face consensus meeting will be conducted to determine the final COS of HICH, including what outcomes should be measured and when and how to measure the outcomes. Results We aim to develop a COS that includes TCM core syndrome for HICH to determine what outcomes should be reported and when and how to measure them. Conclusion By doing this, we can increase the reporting consistency and reduce the reporting bias in the outcome, which leads to the reuse of research data in meta-analysis and the making of informed healthcare decisions. Ethics and dissemination The entire project has received approval from the Ethics Committee of Xiyuan Hospital, China Academy of Chinese Medical Sciences. The final COS will be published and reported at the national and international conferences. Trial registration This study is registered with the Core Outcome Measures in Effectiveness Trials database as study 1475 . Registered on December 2019.

ABSTRACT: Sustained lipolysis and insulin resistance increase the risk of metabolic dysfunction in dairy cows during the transition period. Proinflammatory cytokines are key regulators of adipose tissue metabolism in nonruminants, but biological functions of these molecules in ruminants are not well known. Thus, the objective of this study was to investigate whether tumor necrosis factor-α (TNF-α) could affect insulin sensitivity and lipolysis in bovine adipocytes as well as the underlying mechanisms. Bovine adipocytes (obtained from the omental and mesenteric adipose depots) isolated from 5 Holstein female calves (1 d old) with similar body weight (median: 36.9 kg, range: 35.5–41.2 kg) were differentiated and used for (1) treatment with different concentrations of TNF-α (0, 0.1, 1, or 10 ng/mL) for 12 h; (2) pretreatment with 10 μM lipolytic agonist isoproterenol (ISO) for 3 h, followed by treatment with or without 10 ng/mL TNF-α for 12 h; and (3) pretreatment with the c-Jun N-terminal kinase (JNK) inhibitor SP600125 (20 μM for 2 h) and nuclear factor kappa B (NF-κB) inhibitor BAY 11–7082 (10 μM for 1 h) followed by treatment with or without 10 ng/mL TNF-α for 12 h. The TNF-α increased glycerol content in supernatant, decreased triglyceride content and insulin-stimulated phosphorylation of protein kinase B suggesting activation of lipolysis and impairment of insulin sensitivity. The TNF-α reduced cell viability, upregulated mRNA abundance of Caspase 3 (CASP3), an apoptosis marker, and increased activity of Caspase 3. In addition, increased phosphorylation of NF-κB and JNK, upregulation of mRNA abundance of interleukin-6 (IL-6), TNFA, and suppressor of cytokine signaling 3 (SOCS3) suggested that TNF-α activated NF-κB and JNK signaling pathways. Furthermore, ISO plus TNF-α-activated NF-κB and JNK signaling pathway to a greater extent than TNF-α alone. Combining TNF-α and ISO aggravated TNF-α-induced apoptosis, insulin insensitivity and lipolysis. In the absence of TNF-α, inhibition of NF-κB and JNK did not alter glycerol content in supernatant, triglyceride content or insulin-stimulated phosphorylation of protein kinase B. In the presence of TNF-α, inhibition of NF-κB and JNK alleviated TNF-α-induced apoptosis, insulin insensitivity and lipolysis. Overall, TNF-α impairs insulin sensitivity and induces lipolysis and apoptosis in bovine adipocytes, which may be partly mediated by activation of NF-κB and JNK. Thus, the data suggested that NF-κB and JNK are potential therapeutic targets for alleviating lipolysis dysregulation and insulin resistance in adipocytes.

Abstract Background The prognosis of thymic epithelial tumors (TETs) currently relies on the commonly adopted WHO classification and Masaoka staging system, which cannot reflect the undefined biological behaviors limiting them as prognostic factors. Methods In this study, we first identified 40 genes and 179 genes, respectively that were epigenetically upregulated and silenced, corresponding to a total of 509 functionally methylated CpG sites between thymomas and thymic carcinomas by using the TCGA dataset. Results The methylation β‐values of cg20068620 in MAPK4 and cg18770944 in USP51 were significantly associated with recurrence‐free survival (RFS). In the independent validation cohort, only WHO classification and methylation β‐values of cg20068620 in MAPK4 were independent prognostic factors for RFS in Chinese patients with TETs. A linear weighted model including these two factors was used to calculate the recurrence risk score (RRS). Time‐dependent ROC curve analysis revealed that RRS was overwhelmingly superior to WHO classification for predicting 3‐, 5‐, and 10‐year RFS and Masaoka stage for 3‐ and 5‐year RFS. Conclusions These results suggested that the methylation site cg20068620 in MAPK4 can improve the accuracy of the WHO classification alone regarding the prognostic value of TETs recurrence.

ABSTRACT: Mitochondria are the main site of fatty acid oxidation and reactive oxygen species (ROS) formation. Damaged or dysfunctional mitochondria induce oxidative stress and increase the risk of lipid accumulation. During the process of mitophagy, PTEN induced kinase 1 (PINK1) accumulates on damaged mitochondria and recruits cytoplasmic Parkin to mitochondria. As an autophagy receptor protein, sequestosome-1 (p62) binds Parkin-ubiquitinated outer mitochondrial membrane proteins and microtubule-associated protein 1 light chain 3 (LC3) to facilitate degradation of damaged mitochondria. In nonruminants, clearance of dysfunctional mitochondria through the PINK1/Parkin-mediated mitophagy pathway contributes to reducing ROS production and maintaining metabolic homeostasis. Whether PINK1/Parkin-mediated mitophagy plays a similar role in dairy cow liver is not well known. Thus, the objective of this study was to investigate mitophagy status in dairy cows with fatty liver and its role in free fatty acid (FFA)-induced oxidative stress and lipid accumulation. Liver and blood samples were collected from healthy dairy cows (n = 10) and cows with fatty liver (n = 10) that had a similar number of lactations (median = 3, range = 2 to 4) and days in milk (median = 6 d, range = 3 to 9 d). Calf hepatocytes were isolated from 5 healthy newborn female Holstein calves (1 d of age, 30–40 kg). Hepatocytes were transfected with small interfering RNA targeted against PRKN for 48 h or transfected with PRKN overexpression plasmid for 36 h, followed by treatment with FFA (0.3 or 1.2 mM) for 12 h. Mitochondria were isolated from fresh liver tissue or calf hepatocytes. Serum concentrations of β-hydroxybutyrate were higher in dairy cows with fatty liver. Hepatic malondialdehyde (MDA) and hydrogen peroxide (H2O2) were greater in cows with fatty liver. The lower protein abundance of PINK1, Parkin, p62, and LC3-II in hepatic mitochondrial fraction of dairy cows with fatty liver indicated the mitophagy was impaired. In hepatocytes, knockdown of PRKN decreased protein abundance of p62 and LC3-II in the mitochondrial fraction, and increased contents of triacylglycerol (TG), MDA, and H2O2. In addition, protein abundances of PINK1, Parkin, p62, and LC3-II were lower in the mitochondrial fraction from hepatocytes treated with 1.2 mM FFA than the hepatocytes treated with 0.3 mM FFA, whereas the content of TG, MDA, and H2O2 increased. In 1.2 mM FFA-treated hepatocytes, PRKN overexpression increased protein abundance of p62 and LC3-II in the mitochondrial fraction and decreased contents of TG, MDA, and H2O2. Together, our data demonstrate that low abundance of mitophagy markers is associated with ROS overproduction in dairy cows with fatty liver and impaired mitophagy induced by a high concentration of FFA promotes ROS production and lipid accumulation in female calf hepatocytes.

Summary: While insulin resistance (IR) is associated with inflammation in white adipose tissue, we report a non-inflammatory adipose mechanism of high fat-induced IR mediated by loss of Pref-1. Pref-1, released from adipose Pref-1+ cells with characteristics of M2 macrophages, endothelial cells or progenitors, inhibits MIF release from both Pref-1+ cells and adipocytes by binding with integrin β1 and inhibiting the mobilization of p115. High palmitic acid induces PAR2 expression in Pref-1+ cells, downregulating Pref-1 expression and release in an AMPK-dependent manner. The loss of Pref-1 increases adipose MIF secretion contributing to non-inflammatory IR in obesity. Treatment with Pref-1 blunts the increase in circulating plasma MIF levels and subsequent IR induced by a high palmitic acid diet. Thus, high levels of fatty acids suppress Pref-1 expression and secretion, through increased activation of PAR2, resulting in an increase in MIF secretion and a non-inflammatory adipose mechanism of IR.

Oxidative dehydrogenation of ethane (ODE) is limited by the facile deep oxidation and potential safety hazards. Now, electrochemical ODE reaction is incorporated into the anode of a solid oxide electrolysis cell, utilizing the oxygen species generated at anode to catalytically convert ethane. By infiltrating γ‐Al2O3 onto the surface of La0.6Sr0.4Co0.2Fe0.8O3‐δ‐Sm0.2Ce0.8O2‐δ (LSCF‐SDC) anode, the ethylene selectivity reaches as high as 92.5 %, while the highest ethane conversion is up to 29.1 % at 600 °C with optimized current and ethane flow rate. Density functional theory calculations and in situ X‐ray photoelectron spectroscopy characterizations reveal that the Al2O3/LSCF interfaces effectively reduce the amount of adsorbed oxygen species, leading to improved ethylene selectivity and stability, and that the formation of Al‐O‐Fe alters the electronic structure of interfacial Fe center with increased density of state around Fermi level and downshift of the empty band, which enhances ethane adsorption and conversion. [ABSTRACT FROM AUTHOR]

Solid oxide electrolysis cells (SOECs) have attracted increasing attention as a promising device for the electrochemical CO2 reduction reaction (CO2RR) due to their high efficiency and fast kinetics. Exploring active cathode catalysts for the CO2RR is highly desirable for the research and development of SOECs. Herein, in situ exsolved FeNi3 nanoparticles on a Sr2Fe1.35Mo0.45Ni0.2O6−δ (SFMN) double perovskite substrate (FeNi3@SFMN) is developed to efficiently catalyze the CO2RR in SOECs. The SOEC with the FeNi3@SFMN–GDC (Gd0.2Ce0.8O1.9) cathode shows a current density of 0.934 A cm−2 at 1.6 V and 800 °C, as well as high stability and no coke deposition for 40 h at 1.2 V. CO2-temperature programmed desorption and quasi in situ Fourier-transform infrared spectroscopy measurements verify the intensive adsorption of CO2 on the FeNi3@SFMN–GDC cathode. Distribution of relaxation time analysis combined with density functional theory calculations discloses the stimulative activation of CO2 at the interface between the exsolved FeNi3 nanoparticles and the SFMN substrate with abundant oxygen vacancies, which improves the CO2RR performance at the FeNi3@SFMN–GDC cathode. [ABSTRACT FROM AUTHOR]

ABSTRACT: Endoplasmic reticulum (ER) stress can be induced by various stimuli and triggers the unfolded protein response to activate intracellular signaling pathways that are mediated by 3 ER-resident sensors: inositol requiring protein-1α (IRE1α), PKR-like ER kinase (PERK), and activating transcription factor-6 (ATF6). In nonruminants, ER stress plays a critical role in hepatic insulin resistance. However, whether ER stress plays a role in nonesterified fatty acid (NEFA)-induced hepatic insulin resistance in dairy cows is still unknown. Experiments were conducted using primary bovine hepatocytes isolated from 5 healthy calves (body weight: 30–40 kg; 1 d old). First, hepatocytes were treated with NEFA (1.2 mM) for 0.5, 1, 2, 3, 5, 7, 9, or 12 h. Treatment with NEFA elevated abundance of phosphorylated IRE1α and PERK, and cleavage of ATF6, along with the ER stress-associated genes XBP1, ATF4, and DNAJC3, resulting in both linear and quadratic effects. Furthermore, ER Tracker red staining and transmission electron microscopy results indicated that ER was dilated and degranulated in response to NEFA treatment, suggesting that ER stress was induced by NEFA treatment in bovine hepatocytes. Second, to assess the effect of ER stress on NEFA-induced insulin resistance, hepatocytes were treated with different concentrations of NEFA (0, 0.6, 1.2, or 2.4 mM) for 5 h with or without tauroursodeoxycholic acid (TUDCA, a canonical inhibitor of ER stress). Here, NEFA induced insulin resistance by increasing the abundance of insulin receptor substrate-1 (IRS1) phosphorylation at the inhibitory residue Ser 307 (S307) and decreasing the abundance of phosphorylated protein kinase B (AKT) and glycogen synthase kinase-3β (GSK3β) in a dose-dependent manner. This was accompanied by upregulation of an abundance of gluconeogenic genes [phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6-Pase)]. These detrimental effects of NEFA on insulin signaling could be reversed with TUDCA treatment, indicating a mechanistic link between ER stress and NEFA-induced insulin resistance. In a third experiment, pGPU6/GFP/Neo vectors containing short hairpin RNA targeting IRE1α were used to silence IRE1α transcription, and GSK2656157 (PERK phosphorylation inhibitor) and 4-(2-aminoethyl) benzenesulfonyl fluoride (AEBSF; an inhibitor of ATF6) were used to block PERK and ATF6 branches, respectively. Notably, the silencing of the IRE1α branch improved NEFA-induced insulin resistance by decreasing phosphorylation of IRS1 (S307) and increasing phosphorylation of AKT and GSK3β, and reducing PEPCK and G6-Pase mRNA abundance, which was likely dependent on IRE1α kinase activity. Similarly, blockage of the PERK branch increased phosphorylation of AKT and GSK3β, and reduced PEPCK and G6-Pase mRNA abundance, but had no effect on phosphorylation of IRS1 (S307). However, results showed that inhibition of the ATF6 branch had no effects on phosphorylation of IRS1, AKT, and GSK3β, and instead found increasing PEPCK and G6-Pase mRNA abundance. Taken together, data in the present study found that impeding IRE1α and PERK signaling might aid in relieving hepatic insulin resistance. However, the more detailed mechanisms of how IRE1α and PERK signaling contribute to hepatic insulin resistance in dairy cows remain to be determined.

Cancer has become the most common cause of death in China. Owing to rapid economic development, improved livelihood, and shifts in risk factors, cancer epidemiology has experienced substantial changes during the past several decades. In this review, we aim to describe the current cancer epidemiology of the main types of cancer in China, report major risk factors associated with cancer development, and summarize the contributions of the Chinese government to controlling the cancer burden. A total of 4,064,000 new cases were diagnosed in China in 2016. The most frequent types are lung cancer (828,100; 20.4%), colorectal cancer (408,000; 10.0%), and gastric cancer (396,500; 9.8%). Lung (657,000; 27.2%), liver (336,400, 13.9%), and stomach (288,500; 12.0%) cancers are the 3 most deadly cancers in the general population. The 5-year survival rate for cancer has dramatically increased in recent decades. However, liver and particularly pancreatic cancers still have the poorest prognosis. The main modifiable risk factors associated with cancer development include infectious agents, smoking, alcohol consumption, obesity, unhealthful dietary habits, and inadequate physical activity. The Chinese government has made unremitting efforts to decrease the cancer burden, including cancer education and investment in cancer screening programs.

ABSTRACT: When ketosis occurs, supraphysiological levels of free fatty acids (FFA) can cause oxidative injury to the mammary gland and autophagy can regulate the cellular oxidative status. The aim of this study was to investigate the autophagy status of mammary tissue and its associations with oxidative stress in healthy and clinically ketotic dairy cows. Mammary tissue and blood samples were collected from healthy cows [n = 15, β-hydroxybutyrate (BHB) 3.0 mM) at 3 to 15 (average = 7) days in milk. For in vitro study, bovine mammary epithelial cells (BMEC) isolated from healthy cows were treated with 0, 0.3, 0.6, or 1.2 mM FFA for 24 h. Furthermore, BMEC were pretreated with 100 nM rapamycin, an autophagy activator, for 4 h or 50 mM 3-methyladenine (3-MA), an autophagy inhibitor, for 1 h, followed by treatment with or without FFA (1.2 mM) for another 24 h. Oxidation indicators and autophagy-related protein abundance were measured. Compared with healthy cows, serum concentrations of FFA, BHB, and malondialdehyde were greater in clinically ketotic cows, but milk production (kg/d), milk protein (kg/d), activities of superoxide dismutase, catalase, and glutathione peroxidase were lower. Abundances of mRNA and protein of autophagy-related gene 5 (ATG5) and 7 (ATG7) were lower, but sequestosome-1 (SQSTM1, also called p62) greater in mammary tissue of clinically ketotic cows. The mRNA abundance of microtubule-associated protein 1 light chain 3 (MAP1LC3, also called LC3) and protein abundance of LC3-II were lower in mammary tissue of clinically ketotic cows. In vitro, exogenous FFA increased the content of malondialdehyde and reactive oxygen species, but decreased the activities of superoxide dismutase, catalase, and plasma glutathione peroxidase. Compared with the 0 mM FFA group, abundance of ATG5, ATG7, LC3-II was greater, but p62 was lower in the 0.6 mM FFA-treated cells. Similarly, abundance of ATG5, ATG7, and LC3-II was lower, but p62 greater in the 1.2 mM FFA-treated cells relative to 0 mM FFA group. Culture with rapamycin alleviated oxidative stress induced by 1.2 mM FFA, whereas 3-MA aggravated it. Overall, results indicated that a low concentration (0.6 mM) of FFA can induce oxidative stress and activate autophagy in BMEC. At higher concentrations of FFA (1.2 mM), autophagy is impaired and oxidative stress is aggravated. Autophagy is a mechanism for BMEC to counteract FFA-induced stress. As such, it could serve as a potential target for further development of novel strategies against oxidative stress.