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This study aimed to investigate the effects of the polysaccharide of Atractylodes macrocephala Koidz (PAMK) on cyclophosphamide (CTX)-induced renal injury in mice and its potential underlying mechanisms. One hundred male C57BL/6 mice, aged 42~43 days, were randomly divided into four groups, with five repetitions in each group and five mice in each repetition. The PAMK group and PAMK+CTX group were orally administered 200 mg/kg PAMK once daily, while the control group and CTX group were given an equivalent amount of saline. From days 25~27 of the experiment, the CTX group and PAMK+CTX group were intraperitoneally injected with 100 mg/kg CTX once daily, while the control group and PAMK group were injected with an equivalent amount of saline. On day 35 of the experiment, the kidneys were collected for histological observation, oxidative stress detection, and transcriptome sequencing. The results showed that compared with the CTX group, the renal injury in the PAMK+CTX group was alleviated. The content of malondialdehyde (MDA) in the kidneys was significantly decreased (P

Objective Stocking density (SD) is an important issue in the poultry industry, which is related to the production performance, intestinal health and immune status. In the present study, the effects of SD on the metabolism and homeostasis of uric acid as well as the related functions of the liver and kidney in ducks were examined. Methods A total of 360 healthy 56-day-old Shan-ma ducks were randomly divided into the low stocking density (n = 60, density = 5 birds/m2), medium stocking density (n = 120, density = 10 birds/m2) and high stocking density groups (HSD; n = 180, density = 15 birds/m2). Samples were collected in the 3rd, 6th, and 9th weeks of the experiment for analysis. Results The serum levels of uric acid, lipopolysaccharide and inflammatory cytokines (interleukin-1β [IL-1β], IL-8, and tumor necrosis factor-α [TNF-α]) were increased significantly in the HSD group. Serious histopathological lesions could be seen in both the livers and kidneys in the HSD group in the 9th week. The mRNA expression levels of inflammatory cytokines (IL-8 and TNF-α) and related pathway components (toll-like receptor 4, myeloid differentiation primary response gene 88, and nuclear factor-κB) were increased significantly in both the livers and kidneys in the HSD group. The mRNA expression levels of enzymes (adenosine deaminase, xanthine oxidase, phosphoribosyl pyrophosphate amidotransferase, and phosphoribosyl pyrophosphate synthetase 1) related to the synthesis of uric acid increased significantly in the livers in the HSD group. However, the mRNA expression level of solute carrier family 2 member 9, which plays an important role in the excretion of uric acid by the kidney, was decreased significantly in the kidneys in the HSD group. Conclusion These results indicated that a higher SD could cause tissue inflammatory lesions in the liver and kidney and subsequently affect the metabolism and homeostasis of uric acid, and is helpful for guiding decisions related to the breeding and production of ducks.

Summary: Here, we present a protocol for the quantitative assessment of rat and mouse cardiomyocyte proliferation both in vitro and in vivo. For the in vivo approach, we describe steps for the isolation of neonatal rat cardiomyocytes and the employment of various indicators to quantify cell proliferation. We then detail in vivo procedures that incorporate comprehensive assays and a genetic lineage tracing strategy to evaluate endogenous cardiomyocyte proliferation. This protocol can be modified to investigate other mammalian cardiomyocyte proliferation.For complete details on the use and execution of this protocol, please refer to Ji et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Ulcerative colitis (UC) manifests clinically with chronic intestinal inflammation and microflora dysbiosis. Although biologics can effectively control inflammation, efficient delivery to the colon and colon epithelial cells remains challenging. Milk‐derived extracellular vesicles (EV) show promise as an oral delivery tool, however, the ability to load biologics into EV presents challenges to therapeutic applications. Here, we demonstrate that fusing cell‐penetrating peptide (TAT) to green fluorescent protein (GFP) enabled biologics loading into EV and protected against degradation in the gastrointestinal environment in vitro and in vivo after oral delivery. Oral administration of EV loaded with anti‐tumour necrosis factor‐α (TNF‐α) nanobody (VHHm3F) (EVVHH) via TAT significantly reduced tissue TNF‐α levels and alleviated pathologies in mice with acute UC, compared to VHH alone. In mice with chronic UC, simultaneously introducing VHH and an antimicrobial peptide LL37 into EV (EVLV), then administering orally improved intestinal barrier, inflammation and microbiota balance, resulted in relief of UC‐induced depression and anxiety. Collectively, we demonstrated that oral delivery of EVLV effectively alleviated UC in mice and TAT efficiently loaded biologics into EV to confer protection from degradation in the gastrointestinal tract. This therapeutic strategy is promising for UC and is a simple and generalizable approach towards drug‐loaded orally‐administrable EV treatment for other diseases.

Abstract Background Lipopolysaccharide (LPS) can induce systemic inflammation and affect the growth and development of poultry. As a kind of traditional Chinese medicine, polysaccharide of Atractylodes macrocephala Koidz (PAMK) can effectively improve the growth performance of animals and improve the immunity of animal bodies. Objectives The purpose of this study was to investigate the effects of PAMK on LPS‐induced inflammatory response, proliferation, differentiation and apoptosis of chicken embryonic myogenic cells. Methods We used chicken embryonic myogenic cells as a model by detecting EdU/MYHC immunofluorescence, the expression of inflammation, proliferation, differentiation‐related genes and proteins and the number of apoptotic cells in the condition of adding LPS, PAMK, belnacasan (an inhibitor of Caspase1) or their combinations. Results The results showed that LPS stimulation increased the expression of inflammatory factors, inhibited proliferation and differentiation, and excessive apoptosis in chicken embryonic myogenic cells, and PAMK alleviated these adverse effects induced by LPS. After the addition of belnacasan (inhibitor of Caspase1), apoptosis in myogenic cells was inhibited, and therefore, the number of apoptotic cells and the expression of pro‐apoptotic genes Caspase1 and Caspase3 were increased. In addition, belnacasan inhibited the increased expression of inflammatory factors, inhibited proliferation, differentiation and excessive apoptosis in chicken embryonic myogenic cells induced by LPS. Conclusions This study provides a theoretical basis for further exploring the mechanism of action of PAMK and exogenous LPS on chicken embryonic myogenic cells and lays the foundation for the development and application of green feed additives in animal husbandry industry.

Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent, but treatment options are limited. Previous studies have demonstrated the hepatoprotective effects of Polysaccharide of Atractylodes macrocephala Koidz (PAMK) against liver injury induced by various causes, but its potential in alleviating NAFLD remains unknown. This study aimed to investigate the potential of PAMK in improving NAFLD and its regulatory effects on gene transcription during the process. The results indicated that Highfatdiet (HFD) could induce NAFLD in mice, and PAMK was found to alleviate symptoms of NAFLD and mitigate liver injury caused by HFD. Transcriptome analysis revealed that PAMK affects both metabolic and inflammatory pathways, suggesting its dual impact on maintaining metabolic homeostasis and suppressing inflammation during NAFLD progression. The results of liver biochemical markers, key genes of the cholesterol pathway, glucose (GLU), and inflammatory factors further demonstrated the dual role of PAMK in metabolism and inflammation.

Abstract Cardiac fibrosis is a pathological response characterized by excessive deposition of fibrous connective tissue within the heart. It typically occurs following cardiac injuries or diseases. However, the lack of suitable models for disease modeling and high-throughput drug discovery has hindered the establishment of an effective treatments for cardiac fibrosis. The emergence and rapid progress of stem-cell and lineage reprogramming technology offer an unprecedented opportunity to develop an improved humanized and patient-specific model for studying cardiac fibrosis, providing a platform for screening potential drugs and synchronously elucidating the underlying molecular mechanisms. Furthermore, reprogramming cardiac fibroblasts into cardiomyocyte-like cells to reduce scar volume and induce myocardial tissue regeneration is a promising approach in treating cardiac fibrosis. In this review, we summarize the current advancements in stem cell technologies applied to study cardiac fibrosis and provide insights for future investigations into its mechanisms, drug discovery as well as therapy method.

ABSTRACT: Geese evolved from migratory birds, and when they consume excessive high-energy feed, glucose is converted into triglycerides. A large amount of triglyceride deposition can induce incomplete oxidation of fatty acids, leading to lipid accumulation in the liver and the subsequent formation of fatty liver. In the Chaoshan region of Guangdong, China, Shitou geese develop a unique form of fatty liver through 24 h overfeeding of brown rice. To investigate the mechanisms underlying the formation of fatty liver in Shitou geese, we collected liver samples from normally fed and overfed geese. The results showed that the liver size in the treatment group was significantly larger, weighing 3.5 times more than that in the control group. Extensive infiltration of lipid droplets was observed in the liver upon staining of tissue sections. Biochemical analysis revealed that compared to the control group, the treatment group showed significantly elevated levels of total cholesterol (T-CHO), triglycerides (TG), and glycogen in the liver. However, no significant differences were observed in the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which are common indicators of liver damage. Furthermore, we performed a combined transcriptomic and lipidomic analysis of the liver samples and identified 1,510 differentially expressed genes (DEGs) and 1,559 significantly differentially abundant metabolites (SDMs). The enrichment analysis of the DEGs revealed their enrichment in metabolic pathways, cellular process-related signaling pathways, and specific lipid metabolism pathways. We also conducted KEGG enrichment analysis of the SDMs and compared them with the enriched signaling pathways obtained from the DEGs. In this study, we identified 3 key signaling pathways involved in the formation of fatty liver in Shitou geese, namely, the biosynthesis of unsaturated fatty acids, glycerol lipid metabolism, and glycerophospholipid metabolism. In these pathways, genes such as glycerol-3-phosphate acyltransferase, mitochondrial (GPAM), 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2), diacylglycerol O-acyltransferase 2 (DGAT2), lipase, endothelial (LIPG), lipoprotein lipase (LPL), phospholipase D family member 4 (PLD4), and phospholipase A2 group IVF (PLA2G4F) may regulate the synthesis of metabolites, including triacylglycerol (TG), phosphatidate (PA), 1,2-diglyceride (DG), phosphatidylethanolamine (PE), and phosphatidylcholine (PC). These genes and metabolites may play a predominant role in the development of fatty liver, ultimately promoting the accumulation of TG in the liver and leading to the progression of fatty liver.

Abstract Background Cardiomyocyte growth and differentiation rely on precise gene expression regulation, with epigenetic modifications emerging as key players in this intricate process. Among these modifications, N6-methyladenosine (m6A) stands out as one of the most prevalent modifications on mRNA, exerting influence over mRNA metabolism and gene expression. However, the specific function of m6A in cardiomyocyte differentiation remains poorly understood. Results We investigated the relationship between m6A modification and cardiomyocyte differentiation by conducting a comprehensive profiling of m6A dynamics during the transition from pluripotent stem cells to cardiomyocytes. Our findings reveal that while the overall m6A modification level remains relatively stable, the m6A levels of individual genes undergo significant changes throughout cardiomyocyte differentiation. We discovered the correlation between alterations in chromatin accessibility and the binding capabilities of m6A writers, erasers, and readers. The changes in chromatin accessibility influence the recruitment and activity of m6A regulatory proteins, thereby impacting the levels of m6A modification on specific mRNA transcripts. Conclusion Our data demonstrate that the coordinated dynamics of m6A modification and chromatin accessibility are prominent during the cardiomyocyte differentiation.

Cotton photosynthetic efficiency and the root–shoot relationship are two important physiological indexes affecting the final yield, but the interactive effects of plastic film mulching and planting density on the cotton photosynthetic efficiency and root–shoot relationship have rarely been reported. We aimed to investigate the optimal plant density with or without plastic film mulching for improved seed cotton yield in southern Xinjiang. Therefore, a two-year field experiment was conducted to investigate the effects of plastic film mulching (with or without plastic film mulching) and planting density (D1: 9 × 104 plants ha−1; D2: 18 × 104 plants ha−1; D3, 22 × 104 plants ha−1, local conventional planting density; D4, 27 × 104 plants ha−1) on the cotton root–shoot relationship, photosynthetic parameters, and seed cotton yield. Our results showed that the seed cotton yield was improved under plastic film mulching at all planting densities, but economic income was significantly lower in comparison to without plastic film mulching in 2023. Compared with D3, seed cotton yield and economic income at D2 increased by 6.9% and 12.2%, either with or without plastic film mulching, respectively. The highest increase in the seed cotton yield in D2 under plastic film mulching was due to the greatest improvements in the root production capacity and photosynthesis. The boll capacity of the root system (BCR) and boll loading of the root system (BLR) in D2 were the highest among all treatments with film mulching, being 9.0% and 16.9% higher than that in D3 in 2022 and 2023. However, the root–shoot ratio (R/S) was 7.1% and 6.9% lower in D2 than D3, under film mulching, in 2022 and 2023. Moreover, moderate plant density (D2) improved the SPAD value, chlorophyll fluorescence (Fv/Fm and PIabs), and photosynthetic parameter (Pn, Tr, and Gs) and decreased Ci compared with other planting density treatments in both years. Further analyses with correlation analysis showed that the seed cotton yield was highly positive correlated with BLR, BCR, and the photosynthetic parameter. In summary, suitable planting density (18 × 104 plants ha−1) combined with plastic film mulching has the potential to obtain high yields by enhancing the efficiency of photosynthetic assimilates, improving the capacity of cotton root production, providing a reference for suitable planting density under plastic film mulching.

The Sichuan Basin located in the intersection of the Tethys−Himalaya and Pacific domains is a multicycle sedimentary basin surrounded by orogenic belts. The geothermal resources are good, but with complex geological structures. Geothermal conditions and heat generation models are different in different tectonic zones in the basin, which seriously restrict the geothermal exploration, development and utilization of geothermal resources. In this paper, the distribution of geothermal resources, characteristics of geothermal fluids, heat flow and geothermal gradients in the Sichuan Basin are comprehensively analyzed by collecting the existing geothermal and petroleum exploration and development data. The geothermal reservoirs and caprocks, the burial depth and the resource conditions of different types of the basin-mountain structure areas in the Sichuan Basin are analyzed. The suggested exploration target for exploration and development are proposed in different tectonic units of the Sichuan Basin. The results show (1) the terrestrial heat flow values in the Sichuan Basin and its surrounding areas are from medium to low, and the geothermal gradient varies between 16 °C/km and 30 °C/km. The terrestrial heat source is obviously controlled by active faults and basement structure, and the hydrothermal systems are conductive and belong to the low-moderate temperature geothermal resources in the Sichuan Basin. (2) The distribution of geothermal resources in the Sichuan Basin is mainly controlled by basin structure, stratigraphic distribution and hydrologic conditions. (4) There are at least 4 karst-type geothermal reservoirs in the marine strata, and 1 − 2 glutenite-type geothermal reservoirs in clastic strata. Geothermal water is of SO4—Ca type and is brackish. The Middle-Lower Triassic and Middle Permian carbonate rocks are considered as the best marine reservoirs, especially in the eastern and western basin. Secondly, other marine karst-type geothermal reservoirs are selected for exploration. The continental clastic rocks should be cautious because their caprocks, groundwater recharge and heat source are worse than the geothermal conditions of the marine carbonate rocks. This study may provide important guidance for further promoting geothermal exploration, exploitation and utilization in the Sichuan Basin.

Skeletal muscle is a critical component of goose meat and a significant economic trait of geese. The regulatory roles of miRNAs and lncRNAs in the maturation stage of goose skeletal muscle are still unclear. Therefore, this study conducted experiments on the leg muscles of Magang geese at two stages: 3-day post-hatch (P3) and 3 months (M3). Morphological observations revealed that from P3 to M3, muscle fibers mainly underwent hypertrophy and maturation. The muscle fibers became thicker, nuclear density decreased, and nuclei moved towards the fiber edges. Additionally, this study analyzed the expression profiles of lncRNAs, miRNAs, and mRNAs during the skeletal muscle fiber maturation stage, identifying 1,949 differentially expressed mRNAs (DEMs), 21 differentially expressed miRNAs (DEMIs), and 172 differentially expressed lncRNAs (DELs). Furthermore, we performed enrichment analyses on DEMs, cis-regulatory genes of DELs, and target DEMs of DEMIs, revealing significant enrichment of signaling pathways including MAPK, PPAR, and mTOR signaling pathways. Among these, the MAPK signaling pathway was the only pathway enriched across all three types of differentially expressed RNAs, indicating its potentially more significant role in skeletal muscle maturation. Finally, this study integrated the targeting relationships between DELs, DEMs, and DEMIs from these two stages to construct a ceRNA regulatory network. These findings unveil the potential functions and mechanisms of lncRNAs and miRNAs in the growth and development of goose skeletal muscle and provide valuable references for further exploration of the mechanism underlying the maturation of Magang geese leg muscle.

Abstract Cardiac development involves large‐scale rearrangements of the proteome. How the developing cardiac cells maintain the integrity of the proteome during the rapid lineage transition remains unclear. Here it is shown that proteotoxic stress visualized by the misfolded and/or aggregated proteins appears during early cardiac differentiation of human pluripotent stem cells and is resolved by activation of the PERK branch of unfolded protein response (UPR). PERK depletion increases misfolded and/or aggregated protein accumulation, leading to pluripotency exit defect and impaired mesendoderm specification of human pluripotent stem cells. Mechanistically, it is found that PERK safeguards mesendoderm specification through its conserved downstream effector ATF4, which subsequently activates a novel transcriptional target WARS1, to cope with the differentiation‐induced proteotoxic stress. The results indicate that protein quality control represents a previously unrecognized core component of the cardiogenic regulatory network. Broadly, these findings provide a framework for understanding how UPR is integrated into the developmental program by activating the PERK‐ATF4‐WARS1 axis.

Ferroptosis is a distinctive form of iron-dependent cell death characterized by significant ultrastructural changes in mitochondria. Given the crucial involvement of mitochondria in various cellular processes such as reactive oxygen species production, energy metabolism, redox status, and iron metabolism, mounting evidence suggests a vital role of mitochondria in the regulation and execution of ferroptosis. Furthermore, there exists a strong correlation between ferroptosis and various diseases. In this review, we aim to summarize the mechanisms underlying the induction and defense of ferroptosis, emphasizing the influence of mitochondria on this intricate process. Additionally, we provide an overview of the role of ferroptosis in disease, particularly cancer, and elucidate the mechanisms by which drugs targeting mitochondria impact ferroptosis. By presenting a theoretical foundation and reference point, this review aims to contribute to both basic cell biology research and the investigation of clinically relevant diseases.

Enetriynes, which belong to the enyne family, are characterized by a distinct electron-rich carbon-bonding scheme. Here, the authors report the formation of enetriynes with high selectivity by tetramerization of terminal alkynes on Ag(100).

Almost all of the wear debris generated during the operation of the machine is suspended in the circulating lubricating oil. The analysis of the wear debris in the lubricating oil can effectively monitor the wear state of the machine and provide early warning of failures. An overview on inductive sensors for measuring wear debris in lubrication is introduced. To begin with, the significance of analyzing the wear debris in lubricating oil is explained and the working principle of the inductive wear sensors is illustrated. Furthermore, the development of inductive wear sensors and the key limitations are summarized. Finally, some rest factors affecting the sensor and the processing method of the induction signal aliasing are discussed, and the future development trend is prospected. It is pointed out that developing high sensitivity wear debris inductive sensors, increasing sensor throughput, and solving the problem of aliasing of detection signals are the following issues that should be further studied in the future.

The safety of spike-based adenovirus type-5 vectored COVID-19 vaccine is evaluated, showing it neither affects the survival and function of human cardiac cells and engineered heart tissues nor aggravates heart damage in mice after ischemic injury.

ABSTRACT: Lipopolysaccharide (LPS) can affect the immune system of geese by inducing liver injury. The polysaccharide of Atractylodes macrocephala Koidz (PAMK) have obvious immune-enhancing effects. Accordingly, this experiment investigated the effect of PAMK on LPS-induced liver injury in goslings. Two hundred 1-day-old goslings were randomly divided into the control group, LPS group, PAMK group, and PAMK+ LPS group, and the PAMK and PAMK+ LPS groups were fed the basal diet with 400 mg/kg PAMK, while the control and LPS groups were fed the basal diet. On D 21, 23, and 25 of the formal trial, the goslings in the LPS and PAMK+LPS groups were injected intraperitoneally with 2 mg/kg LPS, and goslings in the control and PAMK groups were injected intraperitoneally with the same amount of saline. Livers were collected on D 25. HE-stained sections showed that PAMK could effectively alleviate the LPS-induced indistinct hepatic cord structure, loss of cytoplasmic contents of hepatocytes, and dilatation of hepatic sinusoids. The biochemical parameters of liver tissues showed that PAMK could alleviate the LPS-induced upregulation of alanine aminotransferase and aspartate aminotransferase. To further investigate the mechanism of the mitigating effect of PAMK on LPS-induced injury, livers from the LPS and PAMK+LPS groups were selected for transcriptome sequencing. The sequencing results showed that there were 406 differentially expressed genes (DEGs) in the livers of LPS and PAMK+LPS goslings, of which 242 upregulated and 164 downregulated. The Kyoto Encyclopedia of Genes and Genome (KEGG) analysis showed that DEGs were significantly enriched in immune signal transduction, cell cycle, and cell metabolism. Besides, protein‒protein interaction analysis showed that 129 DEGs were associated with each other, including 7 DEGs enriched in the p53 and FOXO signaling pathway. In conclusion, PAMK may alleviate LPS-induced liver injury in gosling through the p53 and FOXO signaling pathway. These results provide a basis for further development of PAMK as an immunomodulator.

Both drought and high temperature can influence the antioxidant metabolism of crop reproductive organs in different ways, affecting the fertility of reproductive organs and yield formation. However, the combined effects of drought stress and high temperature on the crop reproductive physiology have not yet been widely considered. In order to broaden our understanding of this mechanism of influence, a pond experiment was conducted using a cotton variety Yuzaomian 9110 divided into four treatment groups: control (CK), drought stress (DS), high temperature (HT), and drought stress coupled with high temperature (DS+HT). Results showed a significant negative correlation between pollen viability and superoxide anion (O2−) content, as well as hydrogen peroxide (H2O2). Compared with CK, DS did not alter O2− content in anthers, but HT treatment resulted in higher anther O2−. Compared with single-stress groups, DS+HT further promoted the formation of O2− in anthers, leading to more malondialdehyde in anthers. Moreover, a higher H2O2 content in anthers was found in DS and HT than in CK. DS+HT did not show altered H2O2 content relative to HT treatment, although its H2O2 was higher than in DS. Further analyses of the antioxidant enzyme system showed that DS had no significant effect on superoxide dismutase gene (GhCu/ZnSOD) expression, but HT and DS+HT significantly downregulated its expression. The expression of GhCu/ZnSOD was lower under DS+HT than HT, which might be why O2− content was not altered under DS treatment compared with CK and was higher in DS+HT than HT. DS and HT significantly downregulated the expression of the peroxidase gene (GhPOD) and catalase gene (GhCAT), which should be the main reason for the larger accumulation of H2O2 under drought stress and high-temperature conditions. Compared with single-stress groups, DS+HT had lower expression of GhCAT, resulting in a larger H2O2 content. Regarding the ascorbic acid–glutathione (AsA–GSH) cycle, DS and HT significantly downregulated the expression of monodehydroascorbate reductase gene (GhMDHAR) to hinder the production of AsA and upregulated the expression of ascorbate oxidase gene (GhAAO) to promote the oxidation of AsA, which was theoretically detrimental to AsA accumulation. However, HT downregulated the expression of the ascorbate peroxidase gene (GhAPX), hindering the reduction of H2O2 by AsA, which was the reason for AsA and H2O2 accumulation. Moreover, DS also significantly upregulated the expression of the dehydroascorbate reductase gene (GhDHAR2) to enhance the reduction of dehydroascorbate to form AsA, leading to a higher content of AsA under DS than HT. The combined stress significantly downregulated the expression of GhAAO to inhibit the oxidation of AsA but significantly upregulated the expression of GhMDHAR and GhDHAR2, promoting the AsA production, and downregulated the expression of GhAPX, hindering the reduction of H2O2 by AsA. All these resulted in increased AsA content under combined stresses. In addition, HT significantly downregulated the glutathione reductase gene (GhGR) expression, hindering the reduction of oxidized glutathione (GSSG), which led to the reduction of GSH. However, DS and DS+HT significantly downregulated the glutathione peroxidase gene (GhGPX) expression, resulting in the accumulation of GSH. Overall, compared with single-stress treatments, the effects of DS+HT on cotton pollen fertility and peroxide accumulation were more significant. The effects of DS+HT on the antioxidant enzyme system were mainly caused by high temperature, while the mechanism of abnormal accumulation of AsA and GSH caused by DS+HT was different from those of single-stress groups.

In light of advancements in big data analysis and artificial intelligence (AI), there are emerging opportunities to harness these technologies to address perceptive biases. This study examines the potential perceptive biases that may arise when construction mediation is quasi-imposed on the disputing parties. This can happen when mediation attempts are stipulated in the construction contract or court-directed. It is argued that, under such circumstances, a negative perception might arise over whether a bona fide mediation can be realised. Concerns include the fairness and timeliness of the process, as well as the practice of opportunistic mediating behaviours. With data collected from practising construction mediation practitioners in Hong Kong, the constructs of Perceptions of Bona Fide Mediation, Quasi-Imposition, and Positive Mediation Outcomes were first developed. Applying partial least square structural equation modelling to the relationship frameworks of the constructs, it was found that quasi-imposition is not as damaging as envisaged as far as having a bona fide mediation and attaining positive mediation outcomes are concerned. Moreover, a negative perception of the fairness and timeliness of the quasi-imposed mediation would jeopardise the integrity of a bona fide mediation. In this regard, utilizing NLP and machine learning algorithms offers a pioneering AI-driven approach to informing mediating parties, as well as reminding mediators to uphold the fairness and timeliness of the process for the purposes of reaching positive mediation outcomes.

Datamation is designed to animate an analysis pipeline step by step, serving as an intuitive and efficient method for interpreting data analysis outcomes and facilitating easy sharing with others. However, the creation of a datamation is a difficult task that demands expertise in diverse skills. To simplify this task, we introduce Datamator, a language-oriented authoring tool developed to support datamation generation. In this system, we develop a data query analyzer that enables users to generate an initial datamation effortlessly by inputting a data question in natural language. Then, the datamation is displayed in an interactive editor that affords users the ability to both edit the analysis progression and delve into the specifics of each step undertaken. Notably, the Datamator incorporates a novel calibration network that is able to optimize the outputs of the query decomposition network using a small amount of user feedback. To demonstrate the effectiveness of Datamator, we conduct a series of evaluations including performance validation, a controlled user study, and expert interviews.

N6-methyladenosine (m6A) plays important role in lineage specifications of embryonic stem cells, but its role at specific sites has not been assessed. Here the authors develop an adenine editor-based strategy, and systematically identify functional m6A sites that control lineage decisions in human embryonic stem cells.

ABSTRACT: Lipopolysaccharide (LPS) infection could cause severe liver inflammation and lead to liver damage, even death. Previous studies have shown that polysaccharide of Atractylodes macrocephala Koidz (PAMK) could protect liver from inflammation caused by LPS in mice. However, whether PAMK could alleviate liver inflammatory injury in other animals with LPS is still unknown. For evaluating whether PAMK could alleviate liver inflammatory injury in goslings with LPS, a total of 80 healthy 1-day old Magang goslings were randomly divided into 4 groups (control group, PAMK group, LPS group, and PAMK+LPS group). Goslings in control group and LPS group were fed with basal diet, and goslings in PAMK group and PAMK+LPS group were fed basal diet supplemented with 400 mg/kg PAMK to the end of trial. On 24 d of age, goslings in the control group and PAMK group were intraperitoneal injected 0.5 mL normal saline, and goslings in LPS and PAMK+LPS groups were intraperitoneal injected with LPS at 5 mg/kg BW. The serum and liver samples were collected for further analysis after treatment of LPS at 6, 12, 24, and 48 h. Furthermore, the hepatocytes were extracted from goose embryo to measure the expression of the key genes of miR-223/NLRP3 axis. The results showed that PAMK pretreatment could maintain normal cell morphology of liver, alleviate the enhanced levels of biochemical indexes ALT and AST, decrease the levels of IL-1β and IL-18, increase the relative mRNA expression of miR-223, and decrease the expression of NLRP3, Caspase-1, and cleaved Caspase-1 in liver and hepatocytes of goslings induced by LPS. These results indicated that PAMK could relieve inflammatory liver tissue damage after LPS treatment and downregulate the level of inflammation factors via miR-223/NLRP3 axis, thus playing a liver protective role in liver inflammation injury in goslings.

Active enhancers are still understudied in colorectal cancers (CRC). Here the authors analyse active enhancers in CRC patients using genomics, transcriptomics, and epigenomics, identifying and validating variant super-enhancer loci as well as KLF3 as a relevant transcription factor.

Mitochondria are important organelles involved in cell metabolism and programmed cell death in eukaryotic cells and are closely related to the innate immunity of host cells against viruses. Mitophagy is a process in which phagosomes selectively phagocytize damaged or dysfunctional mitochondria to form autophagosomes and is degraded by lysosomes, which control mitochondrial mass and maintain mitochondrial dynamics and cellular homeostasis. Innate immunity is an important part of the immune system and plays a vital role in eliminating viruses. Viral infection causes many physiological and pathological alterations in host cells, including mitophagy and innate immune pathways. Accumulating evidence suggests that some virus promote self-replication through regulating mitophagy-mediated innate immunity. Clarifying the regulatory relationships among mitochondria, mitophagy, innate immunity, and viral infection will shed new insight for pathogenic mechanisms and antiviral strategies. This review systemically summarizes the activation pathways of mitophagy and the relationship between mitochondria and innate immune signaling pathways, and then discusses the mechanisms of viruses on mitophagy and innate immunity and how viruses promote self-replication by regulating mitophagy-mediated innate immunity.

Summary: Here, we present a protocol to reprogram mouse and human fibroblasts into expandable cardiovascular progenitor cells (CPCs) via a defined small-molecule treatment. We describe steps to prepare fibroblasts and generate the chemically induced CPCs (ciCPCs), followed by expansion and differentiation of the ciCPCs. These cells can self-renew in the long term, faithfully retaining the CPC phenotype and cardiovascular differentiation capacity. This protocol provides an autologous and expandable cardiovascular cell source, which may find uses in cardiovascular disease modelling, drug discovery, and cardiac cell therapy.For complete details on the use and execution of this protocol, please refer to Wang et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Coronavirus disease 2019 continues to spread worldwide. Given the urgent need for effective treatments, many clinical trials are ongoing through repurposing approved drugs. However, clinical data regarding the cardiotoxicity of these drugs are limited. Human pluripotent stem cell‐derived cardiomyocytes (hCMs) represent a powerful tool for assessing drug‐induced cardiotoxicity. Here, by using hCMs, it is demonstrated that four antiviral drugs, namely, apilimod, remdesivir, ritonavir, and lopinavir, exhibit cardiotoxicity in terms of inducing cell death, sarcomere disarray, and dysregulation of calcium handling and contraction, at clinically relevant concentrations. Human engineered heart tissue (hEHT) model is used to further evaluate the cardiotoxic effects of these drugs and it is found that they weaken hEHT contractile function. RNA‐seq analysis reveals that the expression of genes that regulate cardiomyocyte function, such as sarcomere organization (TNNT2, MYH6) and ion homeostasis (ATP2A2, HCN4), is significantly altered after drug treatments. Using high‐throughput screening of approved drugs, it is found that ceftiofur hydrochloride, astaxanthin, and quetiapine fumarate can ameliorate the cardiotoxicity of remdesivir, with astaxanthin being the most prominent one. These results warrant caution and careful monitoring when prescribing these therapies in patients and provide drug candidates to limit remdesivir‐induced cardiotoxicity.

Aim: The purpose of this study was to investigate the mechanical and electrophysiological effects of emodin on BK channels in the IRASMCs, of the rat. Methods: Isolated interlobar renal artery was used for vascular reactivity measurements using a pressure myograph system. Electrophysiological measurements of single vascular smooth muscle cells were conducted using whole-cell and cell-attached patch-clamp recording. Laser scanning confocal microscope technology was used to measure cytosolic calcium ion signals. Key results: Emodin relaxed the interlobar renal artery and enhanced the outward currents amplitude of IRASMCs in a concentration-dependent manner, and IbTX inhibited these emodin-induced outward currents. Incubation of IRASMCs in a calcium ion free medium for 30 min decreased the observed effects of emodin on IRASMCs membrane currents. Furthermore, the application of nimodipine, an L-Type calcium ion channel blocker, ryanodine, a ryanodine receptor modifier, and heparin, an IP3 receptor blocker, decreased the emodin-induced BK channel currents, respectively. BAPTA-AM, a selective calcium ion chelator, abolished the emodin-induced BK channel currents. Emodin repolarized cytomembrane and enhanced BK channel open probabilities and elevated cytosolic calcium ion concentration. Conclusion: The vasorelaxant effect of emodin on vessels is mediated through the activation of BK channels.

Slope cutting is becoming more common in engineering construction to obtain a large floor area. Slope cutting disrupts a slope’s inherent stability, causing instability and sliding. To solve the problem of geological disasters caused by artificial slope cutting, Cangxi County is used as an example to analyze the cutting slope and the height of different slope structures in the county, to study the disaster mode and disaster factors caused by slope cutting, and to analyze the influence of slope cutting height and slope cutting gradient on the disaster process. This study demonstrates that the stability of cutting on different types of slopes is weakened to different degrees, with mixed rocky-soil slopes having the strongest resistance to weakening, thick-soil slopes the second strongest, and thin-soil slopes the weakest. Slope cutting is the main factor of disaster, and rainwater infiltration promotes landslide formation. Numerical simulation is employed to determine the proximities of the slope cutting height and slope cutting gradient, and 75% of the critical value is taken as the proposed threshold value of slope cutting. The recommended cut slope threshold value corresponds to the real stable cut slope gradient on site, and the research findings can be used to guide engineering cut slope decisions in Cangxi County and other red-layer areas.

The innate immune pathway serves as the first line of defense against viral infections and plays a crucial role in the host’s immune response in clearing viruses. Prior research has indicated that the influenza A virus has developed various strategies to avoid host immune responses. Nevertheless, the role of the NS1 protein of the canine influenza virus (CIV) in the innate immune pathway remains unclear. In this study, eukaryotic plasmids of NS1, NP, PA, PB1, and PB2 were constructed, and it was found that these proteins interact with melanoma differentiation-associated gene 5 (MDA5) and antagonize the activation of IFN-β promoters by MDA5. We selected the NS1 protein for further study and found that NS1 does not affect the interaction between the viral ribonucleoprotein (RNP) subunit and MDA5, but that it downregulates the expression of the laboratory of genetics and physiology 2 (LGP2) and retinoic acid-inducible gene-I (RIG-I) receptors in the RIG-I pathway. Additionally, NS1 was found to inhibit the expression of several antiviral proteins and cytokines, including MX dynamin like GTPase 1 (MX1), 2′-5′oligoadenylate synthetase (OAS), Signal Transducers and Activators of Transcription (STAT1), tripartite motif 25 (TRIM25), interleukin-2 (IL-2), IFN, IL-8, and IL-1β. To further investigate the role of NS1, a recombinant H3N2 virus strain (rH3N2) and an NS1-null virus (rH3N2ΔNS1) were rescued using reverse-genetic technology. The rH3N2ΔNS1 virus exhibited lower viral titers compared to rH3N2, but had a stronger activation effect on the receptors LGP2 and RIG-I. Furthermore, when compared to rH3N2, rH3N2ΔNS1 exhibited a more pronounced activation of antiviral proteins such as MX1, OAS, STAT1, and TRIM25, as well as antiviral cytokines such as IL-6, IFN-β, and IL-1β. These findings suggest a new mechanism by which NS1, a nonstructural protein of CIV, facilitates innate immune signaling and provides new avenues for the development of antiviral strategies.

Abstract Background Canonical nonsense-mediated decay (NMD) is an important splicing-dependent process for mRNA surveillance in mammals. However, processed pseudogenes are not able to trigger NMD due to their lack of introns. It is largely unknown whether they have evolved other surveillance mechanisms. Results Here, we find that the RNAs of pseudogenes, especially processed pseudogenes, have dramatically higher m6A levels than their cognate protein-coding genes, associated with de novo m6A peaks and motifs in human cells. Furthermore, pseudogenes have rapidly accumulated m6A motifs during evolution. The m6A sites of pseudogenes are evolutionarily younger than neutral sites and their m6A levels are increasing, supporting the idea that m6A on the RNAs of pseudogenes is under positive selection. We then find that the m6A RNA modification of processed, rather than unprocessed, pseudogenes promotes cytosolic RNA degradation and attenuates interference with the RNAs of their cognate protein-coding genes. We experimentally validate the m6A RNA modification of two processed pseudogenes, DSTNP2 and NAP1L4P1, which promotes the RNA degradation of both pseudogenes and their cognate protein-coding genes DSTN and NAP1L4. In addition, the m6A of DSTNP2 regulation of DSTN is partially dependent on the miRNA miR-362-5p. Conclusions Our discovery reveals a novel evolutionary role of m6A RNA modification in cleaning up the unnecessary processed pseudogene transcripts to attenuate their interference with the regulatory network of protein-coding genes.

ABSRACT: Ferroptosis is a newly discovered form of cell death due to iron-dependent lipid peroxidation. In animal breeding, many environmental factors could lead to oxidative stress, which in turn reduce animal immunity and production performance. Polysaccharide of Atractylodes macrocephala Koidz (PAMK) has antioxidation, immunomodulatory, and inflammatory modulating effects. For investigating the effect of PAMK on splenic ferroptosis in gosling caused by lipopolysaccharide (LPS), 40 one-day-old Magang goslings were randomly divided into 4 groups (CON group, LPS group, PAMK group, and LPS+PAMK group). The protein expression of the ferroptosis marker Glutathione Peroxidase 4 (GPX4), the relative mRNA expression of ferroptosis-related genes and cytokines, and the oxidative stress and iron content of spleen tissues were examined. The correlation between ferroptosis and inflammatory factors was further analyzed by principal component analysis. The results showed that, compared with CON group, LPS caused alterations in the expression of the ferroptosis pathway genes and cytokines, which could upregulate levels of ferroptosis and inflammation. However, after treated with PAMK, the inflammation and ferroptosis was alleviated. Meanwhile, PAMK restored the expression and distribution of GPX4. In addition, PAMK alleviated the oxidative stress caused by LPS and reduced the iron content in spleen. Principal component analysis showed that cytokines were more closely related to antioxidant indexes. The CON, PAMK and LPS+PAMK groups had similar effects on the four components, with the LPS and PAMK groups showing the furthest difference in results. The result indicated that PAMK could reduce the level of oxidative stress and inflammatory cytokines in spleen of gosling caused by LPS, and jointly alleviate ferroptosis by regulating genes related to the ferroptosis pathway.

Corneal epithelium shares similar molecular signatures to other stratified epithelia. Here, the authors map super-enhancers and accessible chromatin in corneal epithelium, identifying a transcription regulatory circuit, including RUNX1, PAX6, and SMAD3, required for corneal epithelial identity and homeostasis.

Summary: As a biological pump, the heart needs to consume a substantial amount of energy to maintain sustained beating. Myocardial energy metabolism was recently reported to be related to the loss of proliferative capacity in cardiomyocytes (CMs). However, the intrinsic relationship between beating rate and proliferation in CMs and whether energy metabolism can regulate this relationship remains unclear. In this study, we find that moderate heart rate reduction (HRR) induces CM proliferation under physiological conditions and promotes cardiac regenerative repair after myocardial injury. Mechanistically, moderate HRR induces G1/S transition and increases the expression of glycolytic enzymes in CMs. Furthermore, moderate HRR induces a metabolic pattern switch, activating glucose metabolism and increasing the relative proportion of ATP production by the glycolytic pathway for biosynthesis of substrates needed for proliferative CMs. These results highlight the potential therapeutic role of HRR in not only acute myocardial protection but also long-term CM restoration.

As companion animals, felines play an important role in human's family life, and their healthcare has attracted great attention. Viruses such as feline calicivirus (FCV), feline herpesvirus 1 (FHV-1), and feline parvovirus virus (FPV) are the most common pathogens that cause severe infectious disease in baby cats. Thus, preclinical detection and intervention of these three viruses is an effective means to prevent diseases and minimize their danger condition. In this study, a triplex TaqMan quantitative real-time polymerase chain reaction (qRT-PCR) assay was developed to detect these three viruses simultaneously. The detection limit of FPV, FCV, and FHV-1 was 5 × 101 copies/assay, which exhibited higher sensitivity (about 10- to100-fold) than conventional PCR. The coefficients of variation (CVs) of the intra-assay variability were lower than 1.86%, and that of inter-assay variability were lower than 3.19%, indicating the excellent repeatability and reproducibility of the triplex assay. Additionally, the assay showed good specificity. Finally, samples from 48 cats were analyzed using the established assay and commercial kits. As a result, the total positive rates for these viruses were 70.83 or 62.5%, respectively, which demonstrated that the developed qRT-PCR assay was more accurate than the commercial kits and could be used in clinical diagnosis.

Abstract Heart diseases (HDs) are the leading cause of morbidity and mortality worldwide. Despite remarkable clinical progress made, current therapies cannot restore the lost myocardium, and the correlation of genotype to phenotype of many HDs is poorly modeled. In the past two decades, with the rapid developments of human pluripotent stem cell (hPSC) biology and technology that allow the efficient preparation of cardiomyocytes from individual patients, tremendous efforts have been made for using hPSC‐derived cardiomyocytes in preclinical and clinical cardiac therapy as well as in dissection of HD mechanisms to develop new methods for disease prediction and treatment. However, their applications have been hampered by several obstacles. Here, we discuss recent advances, remaining challenges, and the potential solutions to advance this field.

Optimal strategy, one of the main transit assignment models, can better demonstrate the flexibility for passengers using routes in a transit network. According to the basic optimal strategy model, passengers can board trains based on their frequency without any capacity limitation. In the metropolitan cities such as Beijing, Shanghai, and Hong Kong, morning commuters face huge transit problems. Especially for the metro system, there is heavy rush in metro stations. Owing to the limited train capacity, some passengers cannot board the first coming train and need to wait for the next one. To better demonstrate the behavior of passengers pertaining to the limited train capacity, we consider capacity constraints for the basic optimal strategy model to represent the real situation. We have proposed a simulation-based algorithm to solve the model and apply it to the Beijing Subway to demonstrate the feasibility of the model. The application of the proposed approach has been demonstrated using the computational results for transit networks originating from practice.

In the coastal saline soils, moisture and salinity are the functions of groundwater depth affecting crop growth and yield. Accordingly, the objectives of this study were to: 1) investigate the combined effects of moisture and salinity stresses on wheat growth as affected by groundwater depth, and 2) find the optimal groundwater depth for wheat growth in coastal saline soils. The groundwater depths (0.7, 1.1, 1.5, 1.9, 2.3, and 2.7 m during 2013–2014 (Y1) and 0.6, 1.0, 1.4, 1.8, 2.2, and 2.6 m during 2014–2015 (Y2)) of the field experiment were maintained by soil columns. There was a positive correlation between soil moisture and salinity. Water logging with high salinity (groundwater depth at 0.7 m in Y1 and 0.6 m in Y2) showed a greater decline towards wheat growth than that of slight drought with medium (2.3 m in Y1) or low salinity (2.7 m in Y1, 2.2 and 2.6 m in Y2). The booting stage was the most sensitive stage of wheat crop under moisture and salinity stresses. Data showed the most optimal rate of photosynthesis, grain yield, and flour quality were obtained under the groundwater depth (ditch depth) of 1.9 m (standard soil moisture with medium salinity) and 2.3 m (slight drought with medium salinity) in Y1 and 1.8 m (standard soil moisture with medium salinity) and 2.2 m (slight drought with low salinity) in Y2. The corresponding optimal soil relative moisture content and conductivity with the 1:5 distilled water/soil dilution, in the depth of 0–20 cm and 20–40 cm in coastal saline soils, were equal to 58.67–63.07% and 65.51–72.66% in Y1, 63.09–66.70% and 69.75–74.72% in Y2; 0.86–1.01 dS m–1 and 0.63–0.77 dS m–1 in Y1, 0.57–0.93 dS m–1 and 0.40–0.63 dS m–1 in Y2, respectively.

The electrophysiological signal can reflect the basic activity of cardiomyocytes, which is often used to study the working mechanism of heart. Intracellular recording is a powerful technique for studying transmembrane potential, proving a favorable strategy for electrophysiological research. To obtain high-quality and high-throughput intracellular electrical signals, an integrated electrical signal recording and electrical pulse regulating system based on nanopatterned microelectrode array (NPMEA) is developed in this work. Due to the large impedance of the electrode, a high-input impedance preamplifier is required. The high-frequency noise of the circuit and the baseline drift of the sensor are suppressed by a band-pass filter. After amplifying the signal, the data acquisition card (DAQ) is used to collect the signal. Meanwhile, the DAQ is utilized to generate pulses, achieving the electroporation of cells by NPMEA. Each channel uses a voltage follower to improve the pulse driving ability and isolates each electrode. The corresponding recording control software based on LabVIEW is developed to control the DAQ to collect, display and record electrical signals, and generate pulses. This integrated system can achieve high-throughput detection of intracellular electrical signals and provide a reliable recording tool for cell electro-physiological investigation.

Lipopolysaccharide (LPS) is one of the main virulence factors of Gram-negative bacteria. In the process of waterfowl breeding, an inflammatory reaction due to LPS infection is easily produced, which leads to a decline in waterfowl performance. The liver plays a vital role in the immune response and the removal of toxic components. Therefore, it is necessary to study the mechanism of liver injury induced by LPS in goose. In this study, a total of 100 1-day-old goslings were randomly divided into a control group and LPS group after 3 days of pre-feeding. On days 21, 23, and 25 of the formal experiment, the control group was intraperitoneally injected with 0.5 mL normal saline, and the LPS group was intraperitoneally injected with LPS 2 mg/(kg body weight) once a day. On day 25 of the experiment, liver samples were collected 3 h after the injection of saline and LPS. The results of histopathology and biochemical indexes showed that the livers of the LPS group had liver morphological structure destruction and inflammatory cell infiltration, and the levels of ALT and AST were increased. Next, RNA sequencing analysis was used to determine the abundances and characteristics of the transcripts, as well as the associated somatic mutations and alternative splicing. We screened 727 differentially expressed genes (DEGs) with p < 0.05 and |log2(Fold Change)| ≥ 1, as the thresholds; GO and KEGG enrichment analysis showed that LPS-induced liver injury may be involved in the Toll-like receptor signaling pathway, MAPK signaling pathway, NOD-like receptor signaling pathway, FoxO, and PPAR signaling pathway. Finally, we intersected the genes enriched in the key pathway of LPS-induced liver injury with the top 50 key genes in protein–protein interaction networks to obtain 28 more critical genes. Among them, 17 genes were enriched in Toll-like signaling pathway and MAPK signaling pathway. Therefore, these results suggest that LPS-induced liver injury in geese may be the result of the joint action of Toll-like receptor, MAPK, NOD-like receptor, FoxO, and PPAR signaling pathway. Among them, the TLR7-mediated MAPK signaling pathway plays a major role.

The present study aimed to explore the mechanism by which PAMK alleviates cyclophosphamide (CTX)-induced ferroptosis in thymocytes. One-day-old goslings were divided into four groups (10 goslings/group). The CON and CTX groups were fed a basic diet. The PAMK and CTX + PAMK groups were fed the basic diet mixed with PAMK (400 mg/kg). Moreover, the CTX and CTX + PAMK groups were given a daily injection of 40 mg/kg BW of CTX (at 19, 20, and 21 days of age). On the other hand, the CON and PAMK groups were given 0.5 mL of sterilized saline into the leg muscle (at 19, 20, and 21 days of age). The goslings were fed for 28 days. The ferroptosis pathway was enriched in transcriptome sequencing. Compared to the CON group, the thymus in the CTX group underwent injury, and the mitochondria of thymocytes showed features of ferroptosis. PAMK treatment alleviated ferroptosis in thymocytes and thymus injury, and CTX-induced elevated levels of oxidative stress and iron content restored GPX4 protein expression (p < 0.05) and inhibited the CTX-induced activation of the ferroptosis pathway (p < 0.05). Conclusively, PAMK could reduce thymus injury by alleviating CTX-induced thymocyte ferroptosis in gosling to alleviate the immunosuppression caused by CTX in the organism.

Lipopolysaccharide (LPS) can trigger a series of immune reactions, leading to the occurrence of disease and a decrease in the growth performance of geese. However, the mechanisms of LPS in geese muscle development have not been reported. This study aimed to investigate the effects and mechanisms of LPS on proliferation and differentiation of goose embryonic myoblasts. Embelin and belnacasan combined with LPS were used to explore these effects. Our results demonstrated that LPS significantly induced inflammatory cytokine production in both proliferation and differentiation stages. LPS and embelin treatment significantly improved the proliferation ability (p < 0.05), while LPS reduced the differentiation ability of goose embryonic myoblasts. By adding embelin, the differentiation ability of myoblasts was enhanced, while by adding belnacasan, LPS treatment led to a lower differentiation ability. Combined with the correlation of the expression levels of myogenic, cell cycle, and inflammatory-related genes and proteins, it is speculated that one of the reason for the decrease of differentiation ability of goose embryo myoblasts induced by LPS is the increase of the expression levels of pro-inflammatory factors. Moreover, LPS, embelin and belnacasan, and LPS treatments could significantly increase the apoptosis rate of goose embryonic myoblasts. Taken together, these findings suggest that LPS promotes the proliferation and differentiation of goose embryonic myoblasts by promoting cytokine expression and appropriate apoptosis processes. These findings lay a foundation for the study of the mechanisms of LPS in goose muscle development.

Photocatalytic technology has been considered as an efficient protocol to drive chemical reactions in a sustainable and green way. With the assistance of semiconductor-based materials, heterogeneous photocatalysis converts solar energy directly into chemical energy that can be readily stored. It has been employed in several fields including CO2 reduction, H2O splitting, and organic synthesis. Given that near-infrared (NIR) light occupies 47% of sunlight, photocatalytic systems with a NIR response are gaining more and more attention. To enhance the solar-to-chemical conversion efficiency, precise regulation of the symmetric/asymmetric nanostructures and band structures of NIR-response photocatalysts is indispensable. Under the irradiation of NIR light, the symmetric nano-morphologies (e.g., rod-like core-shell shape), asymmetric electronic structures (e.g., defect levels in band gap) and asymmetric heterojunctions (e.g., PN junctions, semiconductor-metal or semiconductor-dye composites) of designed photocatalytic systems play key roles in promoting the light absorption, the separation of electron/hole pairs, the transport of charge carriers to the surface, or the rate of surface photocatalytic reactions. This review will comprehensively analyze the four main synthesis protocols for the fabrication of NIR-response photocatalysts with improved reaction performance. The design methods involve bandgap engineering for the direct utilization of NIR photoenergy, the up-conversion of NIR light into ultraviolet/visible light, and the photothermal effect by converting NIR photons into local heat. Additionally, challenges and perspectives for the further development of heterogeneous photocatalysts with NIR response are also discussed based on their potential applications.

ABSTRACT: Polysaccharide Of Atractylodes Macrocephala Koidz (PAMK) has been proved to have anti-cancer, antitumor, anti-inflammation function and improve the immune level of the organism. The miRNA plays a very important role in regulating the immune function by negatively regulate the expression of target genes. To explore the molecular mechanism of PAMK active the lymphocytes, thirty 61-d-old geese were randomly divided into 4 groups (C, CTX, PAMK, PAMK+CTX). The thymus morphology, the level of serum granulocyte-macrophage colony-stimulating factor (GMC-SF), IL-1β, IL-3, IL-5, the relative mRNA expression of CD25, novel_mir2, CTLA4 and CD28 signal pathway were measured. Further more, the lymphocytes was extracted from thymus to measure the relative mRNA expression of CD28 signal pathway. The results showed that PAMK could significantly maintain normal cell morphology of thymus, alleviate the decrease level of GMC-SF, IL-1β, IL-5, IL-6, TGF-β, the increase level of IL-4, IL-10, and the decrease relative mRNA expression of novel_mir2, CD25 and CD28 signal pathway in thymus and lymphocytes induced by cyclophosphamide (CTX). In conclusion, PAMK alleviated the decreased T lymphocytes activation levels induced by CTX through novel_mir2/CTLA4/CD28/AP-1 signal pathway.

Abstract Deficiency of the N6‐methyladenosine (m6A) methyltransferase complex results in global reduction of m6A abundance and defective cell development in embryonic stem cells (ESCs). However, it's unclear whether regional m6A methylation affects cell fate decisions due to the inability to modulate individual m6A modification in ESCs with precise temporal control. Here, a targeted RNA m6A erasure (TRME) system is developed to achieve site‐specific demethylation of RNAs in human ESCs (hESCs). TRME, in which a stably transfected, doxycycline‐inducible dCas13a is fused to the catalytic domain of ALKBH5, can precisely and reversibly demethylate the targeted m6A site of mRNA and increase mRNA stability with limited off‐target effects. It is further demonstrated that temporal m6A erasure on a single site of SOX2 is sufficient to control the differentiation of hESCs. This study provides a versatile toolbox to reveal the function of individual m6A modification in hESCs, enabling cell fate control studies at the epitranscriptional level.

Background Our aim was to investigate the effects of the protein expression and the function of sodium, potassium, and chloride co-transporter (NKCC1) in the dorsal root ganglion (DRG) after activation of transient receptor potential vanilloid 1 receptor (TRPV1) in capsaicin-induced acute inflammatory pain and the possible mechanism of action.Methods Male Sprague–Dawley rats were randomly divided into control, capsaicin, and inhibitor groups. The expression and distribution of TRPV1 and NKCC1 in rat DRG were observed by immunofluorescence. Thermal radiation and acetone test were used to detect the pain threshold of heat and cold noxious stimulation in each group. The expressions of NKCC1 mRNA, NKCC1 protein, and p-NKCC1 in the DRG were detected by PCR and western blotting (WB). Patch clamp and chloride fluorescent probe were used to observe the changes of GABA activation current and intracellular chloride concentration. After intrathecal injection of protein kinase C (PKC) inhibitor (GF109203X) or MEK/extracellular signal-regulated kinase (ERK) inhibitor (U0126), the behavioral changes and the expression of NKCC1 and p-ERK protein in L4–6 DRG were observed.Result: TRPV1 and NKCC1 were co-expressed in the DRG. Compared with the control group, the immunofluorescence intensity of NKCC1 and p-NKCC1 in the capsaicin group was significantly higher, and the expression of NKCC1 in the nuclear membrane was significantly higher than that in the control group. The expression of NKCC1 mRNA and protein of NKCC1 and p-NKCC1 in the capsaicin group were higher than those in the control group. After capsaicin injection, GF109203X inhibited the protein expression of NKCC1 and p-ERK, while U0126 inhibited the protein expression of NKCC1. In the capsaicin group, paw withdrawal thermal latency (WTL) was decreased, while cold withdrawal latency (CWL) was prolonged. Bumetanide, GF109203X, or U0126 could reverse the effect. GABA activation current significantly increased in the DRG cells of the capsaicin group, which could be reversed by bumetanide. The concentration of chloride in the DRG cells of the capsaicin group increased, but decreased after bumetanide, GF109203X, and U0126 were administered.Conclusion Activation of TRPV1 by exogenous agonists can increase the expression and function of NKCC1 protein in DRG, which is mediated by activation of PKC/p-ERK signaling pathway. These results suggest that DRG NKCC1 may participate in the inflammatory pain induced by TRPV1.

Humans perceive and discriminate high-frequency tactile vibrations based on the intensity and envelope of the stimuli. However, no studies have investigated exactly how the envelope and intensity each affect the ability to discriminate. The objectives of this paper are to identify the boundary at which the envelope begins not to strongly affect the ability to discriminate vibrations and to investigate the effects of the carrier frequency and intensity on the discrimination ability. The results of our testing showed that the ability to discriminate was dependent on the envelope frequency and that the ability to discriminate sinusoidal and amplitude-modulated (AM) vibrations in which the envelope frequency ranged from 12 to 50 Hz was higher than that required to discriminate sinusoidal and AM vibrations in which the envelope frequency was above 80 Hz. When the envelope frequency of an AM vibration was 125 Hz, the ability to discriminate sinusoidal and AM vibrations was found to be low and no significant difference was noted in comparison to discriminating AM vibrations with the same envelope frequency. These results suggest that the boundary for envelope perception was at an envelope frequency of around 80-125 Hz at low intensities and that the carrier frequency had little effect on the discrimination, although the discrimination ability tended to increase as the intensity increased.

A novel gout disease, characterized by visceral urate deposition with high-mortality, with outbreaks in goslings in China since 2016 was caused by a novel goose astrovirus (GoAstV) and resulted in serious economic loss. However, the epidemiology and variation of the GoAstV in goslings in southern China and its evolutionary history as well as the classification of the GoAstV are unclear. In the present study, systematic molecular epidemiology, and phylogenetic analyses of the GoAstV were conducted to address these issues. Our results showed that the GoAstV is widespread in goslings in southern China, and the genomes of six GoAstV strains were obtained. Two amino acid mutations (Y36H and E456D) were identified in capsid proteins in this study, which is the dominant antigen for the GoAstV. In addition, the GoAstV could be divided into two distinct clades, GoAstV-1 and GoAstV-2, and GoAstV-2 is responsible for gout outbreaks in goslings and could be classified into Avastrovirus 3 (AAstV-3), while GoAstV-1 belongs to Avastrovirus 1 (AAstV-1). Moreover, the emergence of GoAstV-2 in geese was estimated to have occurred in January 2010, approximately 12 years ago, while GoAstV-1 emerged earlier than GoAstV-2 and was estimated to have emerged in April 1985 based on Bayesian analysis. The mean evolutionary rate for the GoAstV was also calculated to be approximately 1.42 × 10−3 nucleotide substitutions per site per year. In conclusion, this study provides insight into the epidemiology of the GoAstV in goslings in southern China and is helpful for understanding the origin and evolutionary history as well as the classification of the GoAstV in geese.

Data quality management, especially data cleansing, has been extensively studied for many years in the areas of data management and visual analytics. In the paper, we first review and explore the relevant work from the research areas of data management, visual analytics and human-computer interaction. Then for different types of data such as multimedia data, textual data, trajectory data, and graph data, we summarize the common methods for improving data quality by leveraging data cleansing techniques at different analysis stages. Based on a thorough analysis, we propose a general visual analytics framework for interactively cleansing data. Finally, the challenges and opportunities are analyzed and discussed in the context of data and humans. MSC: 00-01, 99-00, Keywords: Data quality management, Visual analytics, Data cleansing