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FilaminC (Flnc) is a member of the actin binding protein family, which is preferentially expressed in the cardiac and skeletal muscle tissues. Although it is known to interact with proteins associated with myofibrillar myopathy, its unique role in skeletal muscle remains largely unknown. In this study, we identify the biological functions of Flnc in vitro and in vivo using chicken primary myoblast cells and animal models, respectively. From the results, we observe that the growth rate and mass of the skeletal muscle of fast-growing chickens (broilers) were significantly higher than those in slow-growing chickens (layers). Furthermore, we find that the expression of Flnc in the skeletal muscle of broilers was higher than that in the layers. Our results indicated that Flnc was highly expressed in the skeletal muscle, especially in the skeletal muscle of broilers than in layers. This suggests that Flnc plays a positive regulatory role in myoblast development. Flnc knockdown resulted in muscle atrophy, whereas the overexpression of Flnc promotes muscle hypertrophy in vivo in an animal model. We also found that Flnc interacted with dishevelled-2 (Dvl2), activated the wnt/β-catenin signaling pathway, and controlled skeletal muscle development. Flnc also antagonized the LC3-mediated autophagy system by decreasing Dvl2 ubiquitination. Moreover, Flnc knockdown activated and significantly increased mitophagy. In summary, these results indicate that the absence of Flnc induces autophagy or mitophagy and regulates muscle atrophy., Graphical Abstract, Filamin C (Flnc) interacts with dishevelled-2 (Dvl2) to activate wnt/β-catenin signaling, consequently regulating skeletal muscle development. Furthermore, Flnc stabilizes Dvl2 by reducing the level of LC3-labeled Dvl2 and preventing cells from undergoing autophagy. In addition, Flnc silence-induced autophagy mediates muscle atrophy by mitochondrial clearance.

Background Traditional Chinese Medicine (TCM) is distinguished by Syndrome differentiation, which prescribes various formulae for different Syndromes of same disease. This study aims to investigate the underlying mechanism. Methods Using a strategy which integrated proteomics, metabolomics study for clinic samples and network pharmacology for six classic TCM formulae, we systemically explored the biological basis of TCM Syndrome differentiation for two typical Syndromes of CHD: Cold Congealing and Qi Stagnation (CCQS), and Qi Stagnation and Blood Stasis (QSBS). Results Our study revealed that CHD patients with CCQS Syndrome were characterized with alteration in pantothenate and CoA biosynthesis, while more extensively altered pathways including D-glutamine and D-glutamate metabolism; alanine, aspartate and glutamate metabolism, and glyoxylate and dicarboxylate metabolism, were present in QSBS patients. Furthermore, our results suggested that the down-expressed PON1 and ADIPOQ might be potential biomarkers for CCQS Syndrome, while the down-expressed APOE and APOA1 for QSBS Syndrome in CHD patients. In addition, network pharmacology and integrated analysis indicated possible comorbidity differences between the two Syndromes, that is, CCQS or QSBS Syndrome was strongly linked to diabetes or ischemic stroke, respectively, which is consistent with the complication disparity between the enrolled patients with two different Syndromes. These results confirmed our assumption that the molecules and biological processes regulated by the Syndrome-specific formulae could be associated with dysfunctional objects caused by the Syndrome of the disease. Conclusion This study provided evidence-based strategy for exploring the biological basis of Syndrome differentiation in TCM, which sheds light on the translation of TCM theory in the practice of precision medicine. Supplementary Information The online version contains supplementary material available at 10.1186/s13020-021-00521-3., Highlights 1. Our work was based on clinical samples rather than pure data analysis or animal models. 2. We conducted multiple omics studies. Especially, as for metabolomics study, we performed both untargeted and targeted metabolomics experiments. 3. We performed network pharmacological study to cross-validated the results of multi-omics study. Although the data sources of network pharmacology were completely unrelated with our omics data, they came to the same conclusion about the difference of the two Syndromes. 4. In the network pharmacological study, we made efforts to collect and screen high-quality data. We collected data from multiple TCM databases and conducted drug likeness screening. Especially, we added quality markers of each herb, whose pharmacological relevance had been validated. To enhance the reliability of targets, for each Syndrome, we only studied common targets of 3 different TCM formulae prescribed for this Syndrome. Supplementary Information The online version contains supplementary material available at 10.1186/s13020-021-00521-3.

In the booming electric vehicle market, the demand for refined cobalt is showing a blowout growth. China is the largest cobalt-refiner and cobalt-importer in the world. However, the life cycle inventory and potential environmental impact from cobalt refining in China have not been clearly illustrated. This paper builds a comprehensive inventory to support the data needs of downstream users of cobalt sulfate. A “cradle-to-gate” life cycle assessment was conducted to provide theoretical support to stakeholders. A life cycle assessment was performed based on ISO 14040 to evaluate the potential environmental impact and recognize the key processes. The system boundary of this study contains four stages of cobalt sulfate production: mining, beneficiation, primary extraction, and refining. Except for the experimental data used in the primary extraction stage, all relevant data are actual operating data. The normalization value was calculated based on the latest released global emission and extraction data. Normalization results show that the potential impacts of cobalt refining were mainly concentrated in the fossil depletion and freshwater ecotoxicity categories. The beneficiation stage and the refining stage account for 72% and 26% of the total normalization value, respectively. The beneficiation stage needs to consume a lot of chemicals and energy to increase the cobalt content, due to the low grade of cobalt ore in China. Compared with cobalt concentrate, the use of cobalt-containing waste (e.g., cobalt waste from EV batteries) can ease endpoint impact by up to 73%. With the application of the target electricity structure in 2050, the potential impact of China’s cobalt sulfate production on global warming, fossil depletion, and particulates formation can be reduced by 24%, 22%, and 26%, respectively. Findings indicate that the chemical inputs and electricity consumption are primary sources of potential environmental impact in China’s cobalt sulfate production. Promoting the development of urban mines can reduce excessive consumption of chemicals and energy in the beneficiation stage. The environmental benefits of transforming the electricity structure and using more renewable energy to reduce dependence on coal-based power in the cobalt refining industry were revealed.

In untargeted liquid chromatography‒mass spectrometry (LC‒MS) metabolomics studies, data preprocessing and metabolic pathway recognition are crucial for screening important pathways that are disturbed by diseases or restored by drugs. Here, we collected high-resolution mass spectrometry data of serum samples from 221 coronary heart disease (CHD) patients under two different chromatographic columns (BEH amide and C

Introduction: The expression levels of signal transducer and activator of transcription 3 (STAT3) protein and Fascin-1 were inhibited using the STAT3 inhibitor BP-1-102 and RNA interference, respectively, to investigate the expression of AtT20 in mouse pituitary cells. The proliferative capacity and related molecular mechanisms of pituitary tumor cells were then analyzed.Methods: Mouse AtT20 pituitary adenoma cells were divided into a control group (Pa group), a STAT3 inhibitor vehicle group (PA + DMSO group), a STAT3 inhibitor group (PA + BP-1-102 group), a Fascin-1 negative control group (PA + neg-siRNA group) and a Fascin-1 silenced group (PA + Fascin-siRNA group). The related protein expression and cell proliferation of the five groups were measured using immunofluorescence, Western blot and real-time RT-PCR, whereas their apoptosis and cell cycle were evaluated using CCK-8 and flow cytometry.Results: Proliferation of AtT20 cells is inhibited with BP-1-102 enhanced apoptosis, at the same time reduced the expression of Fascin-1 and N-cadherin, and increased the expression of E-cadherin. After inhibiting Fascin-1, the expression of STAT3 decreased, the expression of N-cadherin decreased and the expression of E-cadherin increased.Conclusions: BP-1-102 is a novel drug with a great potential in pituitary tumors. Given their important roles in the growth of pituitary adenomas, STAT3 and Fascin-1 can be used as new treatment targets.

Galvanized sheet is the most widely used coated steel plate globally in the industry of construction, automobile, electronics manufacturing, etc. Large amounts of resources and energy are used in galvanized sheet production, which likewise generates vast amounts of pollutant emissions. In the face of the rapid growth of the production and demand of galvanized sheet in China, it is very important to find out the key factors of the environment impact in the production of galvanized sheet. An evaluation of the environmental impact of galvanized sheet production in China was conducted by using the framework of life cycle assessment to improve resource saving and environmental protection in the galvanized sheet industry, and update the life cycle inventory database of galvanized sheet production. The environmental impact assessment was carried out based on the life cycle assessment framework by the use of ReCiPe 2016 method which was applicable on a global scale to evaluate the environmental impact of galvanized sheet production. Methods of uncertainty analysis and sensitivity analysis were adopted to provide credible support. The midpoint categories of global warming and fossil resource scarcity, as well as the endpoint categories of human health contributed most to environmental burden, which were mainly caused by carbon dioxide emissions and coal consumption. Environmental impact was dominated by the key process of continuous casting billet production, followed by electrolytic zinc production and electricity generation. Additional CO2-reducing measures should be implemented in galvanized sheet production to slow the effect of global warming. Moreover, biomass char reducing agents, rather than coal-based reducing agents, should be utilized in steelmaking to reduce fossil resource consumption. Furthermore, renewable energy, rather than coal-based electricity, should be used in galvanized sheet production to reduce carbon emissions and fossil resource consumption. Increasing the recycling rate of scrap steel and zinc waste can save resources and reduce environmental burden. The results of this study can provide guidance in the reduction of resource consumption and environmental burden of galvanized sheet production to the maximum extent.

Circular RNA (circRNA) is a class of endogenous non-coding RNAs without 5′ and 3′ ends; an increasing number of studies show that circRNA is involved in skeletal muscle development. From our previous sequencing data, the circRNAome in breast muscle of two chicken lines with a distinct rate of muscle development, which included a fast muscle growing broiler (FMGB) and a slow muscle growing layer (SMGL), we found a novel differentially expressed circRNA generated by intersectin 2 (ITSN2) gene (named circITSN2). We verified that circITSN2 is a skeletal muscle-enriched circRNA that promotes chicken primary myoblast (CPM) proliferation and differentiation. Further molecular mechanism analysis of circITSN2 in chicken myogenesis was performed, and we found circITSN2 directly targeting miR-218-5p. Besides, miR-218-5p inhibits CPM proliferation and differentiation, which is contrary to circITSN2. Commonly, circRNAs act as a miRNA sponge to alleviate the inhibition of miRNAs on mRNAs. Thus, we also identified that a downstream gene LIM domain 7 (LMO7) was inhibited by miR-218-5p, while circITSN2 could block the inhibitory effect of miR-218-5p by targeting it. Functional analysis revealed that LMO7 also accelerates CPM proliferation and differentiation, which was similar to circITSN2 but contrary to miR-218-5p. Taken together, these results suggested that circITSN2 promotes chicken embryonic skeletal muscle development via relieving the inhibition of miR-218-5p on LMO7. Our findings revealed a novel circITSN2/miR-218-5p/LMO7 axis in chicken embryonic skeletal muscle development, which expands our understanding of the complex muscle development regulatory network.

Some randomized controlled trials have compared the effectiveness and safety outcomes between early initiation of Sacubitril/Valsartan and angiotensin‐converting enzyme inhibitors (ACEIs) in patients after acute myocardial infarction. Therefore, our current meta‐analysis aimed to clarify the confusion. Four Databases and relevant grey literature were searched for studies from inception to July 2, 2021. Two reviewers independently screened literature, extracted data, and assessed the risk of bias. Four studies involving 6154 patients were included to perform meta‐analysis. The results of meta‐analysis showed that the left ventricular ejection fraction in the Sacubitril/Valsartan group was higher than the ACEI group (SMD: 0.37, 95% CI: 0.19–0.55, P = .000), the incidence of major adverse cardiac events in the Sacubitril/Valsartan group was lower than the ACEI group (RR: 0.61, 95% CI: 0.46–0.82, P = .001), while the incidences of cardiac death (RR: 1.00, 95% CI: 0.81–1.24, P = 1.000) and the heart failure hospitalization (RR: 0.62, 95% CI: 0.37–1.03, P = .065) showed no difference. For the incidences of myocardial infarction and the adverse side effects, there was no obvious advantage of the Sacubitril/Valsartan group over the ACEI group, because the meta‐analysis was not performed due to the limited trials. This study indicated that early initiation of Sacubitril/Valsartan in patients after acute myocardial infarction was superior to ACEI in reducing the risks of major adverse cardiac events and left ventricular ejection fraction increasing. As for the other outcomes (the incidences of cardiac death, the heart failure hospitalization, the myocardial infarction and the adverse side effects), Sacubitril/Valsartan showed no obvious advantage than ACEI.

Skeletal muscle is a heterogeneous tissue that is essential for initiating movement and maintaining homeostasis. The genesis of skeletal muscle is an integrative process that lasts from embryonic development to postnatal stages, which is carried out under the modulation of many factors. Recent studies have shown that circular RNAs (circRNAs), a class of non-coding RNAs, are involved in myogenesis. However, more circRNAs and their mechanisms that may regulate skeletal muscle development remain to be explored. Through in-depth analysis of our previous RNA-Seq data, circFNDC3AL was found to be a potentially functional circRNA highly expressed during embryonic development of chicken skeletal muscle. Therefore, in this study, we investigated the effect of circFNDC3AL on skeletal muscle development in chickens and found that circFNDC3AL promoted chicken skeletal muscle satellite cell (SMSC) proliferation and differentiation. To gain a thorough understanding of the exact modulatory mechanisms of circFNDC3AL in chicken skeletal muscle development, we performed target miRNA analysis of circFNDC3AL and found that circFNDC3AL has a binding site for miR-204. Subsequently, we demonstrated that miR-204 inhibited chicken SMSC proliferation and differentiation, which showed the opposite functions of circFNDC3AL. Furthermore, we identified the miR-204 target gene B-cell CLL/lymphoma 9 (BCL9) and validated that miR-204 had an inhibitory effect on BCL9, while the negative effect could be relieved by circFNDC3AL. In addition, we verified that BCL9 performed the same positive functions on chicken SMSC proliferation and differentiation as circFNDC3AL, as opposed to miR-204. In conclusion, our study identified a circRNA circFNDC3AL that upregulates BCL9 expression to promote the proliferation and differentiation of chicken SMSCs by binding to miR-204.

Water consumption and pollution in wheat production, which are worth paying attention in agricultural countries and arid regions, need to be assessed systematically and comprehensively. China, one of the largest wheat-producing country in the world, should be concerned about this issue. Thus, an impact-oriented water footprint assessment of wheat production in China was conducted based on the ISO 14046 standard to quantify water-related environmental impacts. We quantified the environmental impacts on human health and ecosystem quality categories of wheat production from 2009 to 2016 and evaluated the spatial variation of these categories in 2016. Results showed that the environmental impacts on human health and ecosystem quality categories in 2016 were 5.15 × 10−4 DALY/t and 37.17 PDF·m2·yr/t, respectively. Key factor analysis showed that the overall environmental impacts were primarily derived from fertilizer production, diesel production, and direct water consumption and emission. The dynamic analysis results revealed that the temporal variations in impacts were associated with water and fertilizer consumption. Areas with high potential impacts were mainly congregated in the North China Plain and Xinjiang Province due to their high wheat yields. Ecosystem quality was negatively correlated with wheat yield, and human health was positively correlated with crop water requirement. Therefore, on the basis of ensuring grain production, improving the utilization efficiency of irrigation water and reducing fertilizer and diesel consumption are the priorities for the management of agricultural water resources.

Four and a half LIM domain protein 1 (FHL1) belongs to the FHL protein family and is predominantly expressed in skeletal and cardiac muscle. FHL1 acts as a scaffold during sarcomere assembly and plays a vital role in muscle growth and development. Autophagy is key to skeletal muscle development and regeneration, with its dysfunction associated with a range of muscular pathologies and disorders. In this study, we constructed FHL1-silenced or FHL1-overexpressed myoblasts to investigate its role in autophagy during the differentiation of chicken myoblasts into myotubules. Our data showed that FHL1 contributes to myoblast differentiation as measured through MyoG, MyoD, Myh3, and Mb mRNA expression, MyoG and MyHC protein expression and the morphological characteristics of myoblasts. The results showed that FHL1 silencing inhibited the expression of ATG5 and ATG7, meanwhile, immunofluorescence and immunoprecipitation showed that FHL1 and LC3 interacted to regulate the correct formation of autophagosomes. FHL1 inhibition increased cleaved caspase-3 and PARP abundance and promoted myoblast apoptosis. Furthermore, FHL1 rescued skeletal muscle atrophy through regulating the expression of Atrogin-1 and MuRF1. Taken together, these data suggested that FHL1 regulates chicken myoblast differentiation through its interaction with LC3.

Straw pulp in China, which is the world's largest producer of this material, suffers from water and energy shortages during its entire life cycle. However, limited systematic studies have focused on these issues, and decision makers need be provided with improvement methods for the environmental performance. Thus, an impact-oriented energy and carbon coupled water footprint analysis was conducted in this study based on ISO standards. Results showed that the impact of energy consumption and carbon emissions exceeded that of water footprint. Carcinogens, non-carcinogens, and freshwater ecotoxicity also played effective roles in improving the environmental performance. Optimizing key indirect processes, including chemicals production, steam preparation, electricity generation, wood pulping, and fertilizer recovery, dominated the reduction in environmental burdens. Direct freshwater consumption and wastewater disposal played additional effective roles in controlling water footprint. The water network was thus optimized by a water pinch analysis to decrease the freshwater consumption and pollutant emissions by maximum values of 91.5% and 99.7% after optimization, respectively. Meanwhile, carbon dioxide, methane, chromium, arsenic, mercury, titanium, copper, strontium, total nitrogen, total phosphorus, BOD5, and COD were the main pollutants. Overall, the environmental impact can be further reduced by diminishing coal power ratio in national energy structure, adopting recovered steam, and considering multistage regeneration water network to cope with different water use demands.

Objective To investigate the effectiveness and safety of corticosteroids therapy in adult critical ill patients with septic shock. Methods The PUBMED, EMBASE, Web of Science, Cochrane Library databases were systematically searched from the inception dates to March 24, 2018. To identify randomized controlled trials that evaluating the role of corticosteroids therapy in adult critical ill patients with septic shock. The primary outcome was 28-day mortality. The second outcomes included 90-day mortality, intensive care unit (ICU) mortality, in-hospital mortality, length of stay in ICU, length of stay in hospital, reversal of shock, and superinfection. Results A total of 18 randomized controlled trials involving 8,128 adult critical ill patients with septic shock fulfilled the inclusion criteria. The outcomes of this meta-analysis showed that corticosteroids therapy did not significantly reduce the 28-day mortality [RR = 0.94; 95% CI, 0.84-1.05; Z = 1.07 (P = 0.285)]. However, corticosteroids therapy was associated with a significantly shorter length of stay in ICU [WMD = -1.55; 95% CI, -2.19 to -0.91; Z = 4.74 (P = 0.000)]. 90-day mortality, ICU mortality, in-hospital mortality, length of stay in hospital, reversal of shock, and superinfection had no significant difference between the corticosteroids therapy and placebo therapy (P > 0.05). Similar results were obtained in subgroups of trials stratified according to the dose of corticosteroids (high dose or low does). Conclusions Based on the results of this meta-analysis, corticosteroids therapy was associated with a significantly shorter length of stay in ICU among adult critical ill patients with septic shock. The mortality was similar between the corticosteroids therapy and placebo.

FOXO3, which encodes the transcription factor forkhead box O-3 (FoxO3), is a member of the FOXO subfamily of the forkhead box (FOX) family. FOXO3 can be negatively regulated by its phosphorylation by the PI3K/Akt signaling pathway and ultimately drives apoptosis when activated. In mammalian ovaries, the FOXO3 protein regulates atresia and follicle growth by promoting apoptosis of ovarian granulosa cells. Nonetheless, the specific effects of the FOXO3 protein on granulosa apoptosis of avian ovaries have not been elucidated. Therefore, we studiedFOXO3expression in follicles with different organization and at all hierarchical levels of chicken follicles. Via an immunofluorescence assay, the chicken follicular theca at all hierarchical levels were found to be strongly stained with an anti-FOXO3 antibody. In chicken primary ovarian granulosa cells, mRNA levels of proapoptotic factors BNIP3 and BCL2L11 decreased in the absence of FOXO3, and so did PARP-1 and cleaved caspase 3 protein levels. After treatment with a recombinant FOXO3 protein, PARP-1 and caspase 3 protein levels increased, along with mRNA levels of Bnip3 and BCL2L11 (significantly,pFOXO3was downregulated in chicken granulosa cells when different estradiol or FSH concentrations were applied. In conclusion,FOXO3is expressed in chicken reproductive tissues, including follicles and ovarian granulosa cells, and promotes apoptosis of chicken ovarian granulosa cells.

Water footprint (WF) is an indicator of the volume of freshwater resource consumption that incorporates direct and indirect water use. Global freshwater resources are prone to detriment due to water consumption in agriculture. Wheat production contributes considerably to the global water consumption burden. A life cycle assessment-based WF analysis of wheat production was conducted to quantify the water consumption during the entire life cycle of wheat systematically and scientifically. We quantified the temporal distribution of WF of wheat production in Shandong Province, China, from 2009 to 2015 and analyzed the spatial distribution of direct WF of wheat production in 2015. Soil testing and an on-site survey were conducted to examine fertilization overuse. Results showed that gray WF accounted for the largest proportion (nearly 46%), followed by green and blue WFs. Gray WF was mainly from aquatic eutrophication (over 96%), and its key substances were chemical oxygen demand and total phosphorus. Direct water consumption, direct emissions, fertilizer use, and diesel consumption exhibited high potential impacts. This study indicated that rational fertilization on the basis of the soil testing, improving the diesel consumption efficiency, and wheat straw returning to fields have great potential for intensifying water resource management.

Ferronickel is irreplaceable in modern infrastructure construction because of its use in stainless steel production. This study explored the cost-combined environmental impacts of ferronickel production in China which is the largest producer and consumer of ferronickel in the world. Life cycle impact assessment was combined with life cycle costing analysis to assess the environmental and economic performance of ferronickel production in China. Both internal cost (e.g., raw materials, energy, transport, infrastructure, tax, and labor) and external cost (i.e., human health, ecosystem quality, and environmental emission) were considered. The environmental burden of ferronickel production in this study was mainly attributed to the damage on resources and human health as endpoints caused by indirect processes, such as electricity supply, transportation, coke production, lateritic nickel ore acquisition, and coal mining. Carbon dioxide, mercury, particulates, methane, sulfur dioxide, nitrogen oxides, coal, and nickel ores were the substances pivotal for optimizing environmental performance. The total economic cost was 2734.8 $/t, of which 2333.3 $/t was internal cost and 401.5 $/t was external cost. Lateritic nickel ore, electricity, human health cost, and transport contributed 44.9%, 20.6%, 14.2%, and 4.8% to the total economic cost, respectively. The remaining economic burden was mainly divided to coke, coal, argon, labor, equipment, and tax. A win-win case for the environment and economy can be achieved by optimizing electricity and lateritic nickel ore quality, including its transport. Application of other power types (e.g., hydro, wind, and solar electricity) as a substitute for thermal power can also reduce environmental impacts considerably. Sites with high steel yield, low thermal power ratio, and high port proximity, such as Fujian Province, are the primary choices for ferronickel production. Finally, although the economic benefits of coke and coal are minimal, their efficiency in environmental improvement is crucial.

China is currently facing water scarcity due to its large national population and rapid economic development. Lead is a typical non-ferrous metal. The lead industry is one of the top 10 water-consuming industries in China and suffers from the heavy burden of properly managing discharged wastewater containing heavy metals and organic pollutants. Accordingly, a water footprint analysis of lead refining was conducted in this study to enhance the water management in China’s lead industry. This study is part 2 of the environmental improvement for lead-refining series. In accordance with the ISO 14046 standard, life cycle assessment-based water footprint analysis was applied to a lead-refining enterprise in Jiangxi Province, China. Five midpoint (i.e., water scarcity, aquatic eutrophication, carcinogens, non-carcinogens, and freshwater ecotoxicity) and two endpoint (i.e., human health and ecosystem quality) indicators are utilized to assess the water footprint impact results. Direct pollutant emissions are a major contributor to ecosystem quality and freshwater ecotoxicity, whereas indirect processes (i.e., industrial hazardous waste landfill, transport, and chemicals) contribute considerably to human health, aquatic eutrophication, and carcinogen categories. Chromium, copper, arsenic, and zinc were the key substances in the lead production chain, and their emissions exerted a significant impact on human health and ecosystem quality. Reducing direct copper emission was the most important key to minimizing ecosystem quality decline in China’s lead industry, and optimizing indirect processes was effective in mitigating the impact on human health. Enhancing wastewater treatment, increasing chemical consumption efficiency, optimizing transport and industrial hazardous waste disposal, improving supervision, issuing relevant governmental regulations, and adopting advanced wastewater treatment technologies are urgently needed to control the water footprint.

Scope: As DNA methylation is one of the key epigenetic mechanisms involved in embryonic muscle development, elucidating its relationship with non-coding RNAs and genes is essential for understanding early muscle development. The methylome profiles of pre-hatching chicken across multiple developmental stages remain incomplete although several related studies have been reported. Methods: In this study, we performed single-base-resolution bisulfite sequencing together with RNA-seq of broilers and layers in different embryonic development points (E10, E13, E16 and E19) to explore the genetic basis of embryonic muscle development in chicken. The differential methylated regions and novel lncRNAs were identified for association analyses. Through genomic position and correlation analysis between DMRs and lncRNAs, the target lncRNAs were detected to participate in the embryonic muscle formation and the results were then verified in vitro experiments. Results: Comparison of methylome profiles between two chicken lines revealed that lower methylation in broilers might contribute to muscle development in embryonic period. Differential methylated region analysis showed that the majority of differential methylated regions were hypo-DMRs for broilers. Differential methylated genes were significantly enriched in muscle development-related terms at E13 and E19. Furthermore, we identified a long non-coding RNA MyH1-AS that potentially regulated embryonic muscle development, proved by the regulatory network construction and further in vitro experiments. Conclusion: Our study revealed an integrative landscape of middle- to late-stage of embryonic myogenesis in chicken, gave rise to a comprehensive understanding of epigenetic and transcriptional regulation in muscle development. Moreover, we provided a reliable data resource for further embryonic muscle development studies.

Shexiang Baoxin Pill (SBP) and Suxiao Jiuxin Pill (SJP) are traditional Chinese medicines used to treat cardiovascular disease (CVD) in China. However, the mechanism of their therapeutic effect on CVD has not been clearly elucidated yet.The aim of this study is to investigate the cardioprotective effect of SBP and SJP in the treatment of acute myocardial infarction (AMI) model rats by applying serum proteomic approach.The rat model of AMI was generated by ligating the left anterior descending coronary artery. 42 rats were randomly divided into four groups: sham-operating (Sham, n = 10) group, model (Mod, n = 8) group, Shexiang Baoxin pills pretreatment (SBP, n = 12) group and Suxiao Jiuxin pills pretreatment (SJP, n = 12) group. Data Independent Acquisition (DIA) proteomic approach was utilized to investigate the serum proteome from the rat individuals. The differentially expressed proteins were subsequently obtained with bioinformatic analysis.DIA-MS identified 415 proteins within 42 samples, and 84 differentially expressed proteins may contribute to the therapeutic effects of SBP and SJP. GOBP and KEGG pathway analysis of 84 differentially expressed proteins revealed that the proteins were mainly involved in platelet activation and adhesion processes. All 84 differentially expressed proteins presented the same changing tendency in the SBP and SJP groups when compared with the Mod group. Among these 84 proteins, 25 proteins were found to be related to CVD. Among these 25 proteins, ACTB, ACTG1, FGA, FGB, FGG, PF4 and VWF were found to be involved in platelet aggregation and activation. FN1, HSPA5 and YWHAZ were associated with adhesion.The results of our study suggest that the cardioprotective effects of SBP and SJP are achieved through the modulation of focal adhesion, platelet activation pathways.