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The Hippo pathway was originally discovered to control tissue growth in Drosophila and includes the Hippo kinase (Hpo; MST1/2 in mammals), scaffold protein Salvador (Sav; SAV1 in mammals) and the Warts kinase (Wts; LATS1/2 in mammals). The Hpo kinase is activated by binding to Crumbs‐Expanded (Crb‐Ex) and/or Merlin‐Kibra (Mer‐Kib) proteins at the apical domain of epithelial cells. Here we show that activation of Hpo also involves the formation of supramolecular complexes with properties of a biomolecular condensate, including concentration dependence and sensitivity to starvation, macromolecular crowding, or 1,6‐hexanediol treatment. Overexpressing Ex or Kib induces formation of micron‐scale Hpo condensates in the cytoplasm, rather than at the apical membrane. Several Hippo pathway components contain unstructured low‐complexity domains and purified Hpo‐Sav complexes undergo phase separation in vitro. Formation of Hpo condensates is conserved in human cells. We propose that apical Hpo kinase activation occurs in phase separated "signalosomes" induced by clustering of upstream pathway components. Synopsis: The conserved Hippo signalling pathway regulates the activity of Yorkie (YAP/TAZ in mammals) transcriptional co‐activator via Hippo (MST1/2) and Warts (LATS1/2) kinases. This study shows that Hippo pathway components form large cytoplasmic punctae in epithelial cells through a process that involves the formation of biomolecular condensates. Formation of Hippo kinase condensates is promoted by apically localised upstream signalling components such as Kibra or Expanded.Mechanical strain at the apical domain of epithelial cells inhibits Hippo kinase condensate formation.Hippo kinase condensate formation is inhibited by growth factor signalling via the PI3K‐Akt pathway.The organisation of Hippo kinase complexes into condensates and their regulation is conserved between Drosophila and mammalian epithelia. [ABSTRACT FROM AUTHOR]

Simple Summary: Betaine is a healthy source of methyl and glycine and a widely used feed additive to promote animal growth. Previous studies mainly focused on its anti-osmotic pressure, anti-inflammatory, and growth-promoting effect in vitro. Still, poultry's growth-promoting mechanism and regulation of muscle cells remain unknown. In this study, we found that a low concentration of betaine could inhibit myoblast cell proliferation but promote myotube formation, suggesting that the growth-promoting effect of betaine was achieved through the differentiation and fusion of myotubes. In addition, RNA sequencing found a series of betaine-affected genes, which could provide a theoretical basis for explaining betaine's regulation on chicken myogenesis in vitro. Betaine is trimethylglycine and a universal methyl donor which could provide methyl and glycine for cells and animals. As a new star in epigenetics, N6-Methyladenosine has been reported to regulate multiple biological activities, but the regulatory mechanism of betaine on N6-Methyladenosine as well as myogenesis was little studied. In this study, we treated chicken primary myoblast cells with different concentrations of betaine (0, 10, 25, and 50 mmol/L) and found that myoblast cell proliferation was inhibited, although the cell cycle was promoted in the S phase by betaine, where the myotube area was increased as well as the differentiation marker genes MyoD, MyoG, MyHC, Myomarker, and Ckm. RNA sequencing obtained a total of 61 differentially expressed genes (DEGs); DEGs caused by 50 mmol/L betaine were mainly enriched in the regulation of skeletal muscle tissue regeneration and some amino acid metabolic processes. The gene expression pattern trends of all DEGs were mainly clustered into 2 profiles, with the increase in betaine concentration, the gene expression pattern either increased or decreased continuously. Overall, a low concentration betaine can increase the N6-Methyladenosine modification level and myotube area but depresses myoblast cell proliferation in vitro. [ABSTRACT FROM AUTHOR]

Ferroptosis is a unique iron-dependent form of regulated cell death. Recently, researchers found that ferroptosis was sensitive to cell density, regulated by Hippo signaling. This article summarizes the roles of the Hippo pathway effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in ferroptosis and the therapeutic potential of activating ferroptosis in cancer. [ABSTRACT FROM AUTHOR]

Individual aquaculture farmers in developing countries play an important role in ensuring food security. This study uses survey data from aquaculture households in Rongcheng and Xiangshan cities in China to explore the impact of cooperative participation on the benefits to the aquaculture households. The empirical results show that the participation of aquaculture farmers in cooperatives has effectively increased their net profit and output per unit area. On average, participating in cooperatives increased the net profit and output per unit area of farmers by approximately 15.55% and 11.47%, respectively. The test results of the mechanism show that the information services, technical training, and product sales guidance provided by the cooperatives have increased the net profit of the farmers. At the same time, the information services and product sales guidance provided by cooperatives are important reasons for the increase in the output per unit area. [ABSTRACT FROM AUTHOR]

Liquid–liquid phase separation (LLPS) has emerged in recent years as an important physicochemical process for organizing diverse processes within cells via the formation of membraneless organelles termed biomolecular condensates. Emerging evidence now suggests that the formation and regulation of biomolecular condensates are also intricately linked to cancer formation and progression. We review the most recent literature linking the existence and/or dissolution of biomolecular condensates to different hallmarks of cancer formation and progression. We then discuss the opportunities that this condensate perspective provides for cancer research and the development of novel therapeutic approaches, including the perturbation of condensates by small-molecule inhibitors. Membraneless organelles formed by LLPS, termed biomolecular condensates, are increasingly recognized to play important roles in cancer emergence and progression. Cancer-related biomolecular condensates can serve in cancer progression in many ways, ranging from being platforms for proliferative signaling to hubs for enhancer element-mediated transcription of cancer genes. Therapeutics that target specific components or biophysical properties of biomolecular condensates are a fruitful avenue for future cancer diagnostics and therapy. [ABSTRACT FROM AUTHOR]

Purpose: Social crowding refers to the extent of social presence and proximity to others. A large number of studies have explored the effect of social crowding on consumers' feelings and behaviours in real shopping scenes, whereas few studies have examined the potential marketing effect of social crowding on online mobile consumption behaviour despite mobile commerce's increasing popularity in recent years. The current intends to explore the effect of social crowding on online mobile purchase and its underlying neural basis. Methods: The current study employed a questionnaire survey and an implicit panic buying experiment, in which the participants were asked to press the button as soon as possible to buy the showed product. A 2-level social crowding (low vs high) × 2-level feedback of panic buying (success vs fail) design was employed to test the negative impact of social crowding on consumers' online mobile purchase intention by using electroencephalogram (EEG) recordings. Results: Behaviorally, participants showed higher purchase intention in low social crowding environment compared with the high crowding condition. The event-related potentials (ERPs) results indicated that consumers had a higher affective/motivational evaluation (reflected in a smaller feedback-related negativity (FRN) amplitude) regarding the successful rather than the failing feedback in the low social crowding condition. However, this difference was not detected in the high social crowding condition. Meanwhile, more attentional resources (reflected in a greater P300 amplitude) were directed toward processing the feedback outcomes in the low rather than the high social crowding condition. Conclusion: The current study provided neurophysiological response that social crowding negatively influences consumers' online purchase intention. Some implications for theory and practice were also discussed. [ABSTRACT FROM AUTHOR]

A smartphone-integrated multi-model thermal immunochromatographic assay has been constructed for the detection of histamine by using anti-histamine antibody coupled Cu 2−x Se nanoparticles (Cu 2−x Se@antibody) as photothermal nanoprobes. Base on a competitive format, the coated histamine antigen on T-line and histamine simultaneously competed for binding the lateral flow photothermal signal probes. With the increase of histamine concentration, the temperature of Cu 2−x Se@antibody on T-line was decreased under the 808 nm laser irradiation, which can be monitored via the smartphone-thermal imager combination device. In addition, the color on T-line from nanoprobes gradually disappeared, and the inhibition rate calculated from the obtained temperature on T-line was increased. The smartphone-integrated multi-model thermal immunochromatographic assay enables detection of histamine in the range of 0.1–10.0 μg/L with limit of detection as low as 0.09 μg/L. The histamine concentrations in crab, tuna, saury, mackerel, shrimp were 5.67 mg/kg, 83.73 mg/kg, 14.03 mg/kg, 21.30 mg/kg, 3.22 mg/kg detected by the developed thermal immunochromatographic assay, respectively. The developed multi-model strategy provided good sensitivity, simple operation, effectiveness and practicability for histamine in real samples compared to ultra-performance liquid chromatography-tandem mass spectrometry UPLC-MS/MS and ELISA. • A multi-model thermal immunochromatographic assay was constructed for histamine. • Smartphone integrated photothermal sensor device for histamine quantitative detection. • Cu 2−x Se@antibody as a multi-model signal for histamine detection in real samples. • The multi-model assay has good reliability, practicability for histamine detection. [ABSTRACT FROM AUTHOR]

In recent years, it has become increasingly clear that many nuclear membrane-less compartments have liquid-like properties and may form through the physicochemical process of phase separation. In this review, we will first discuss how various nuclear compartments, such as the genome, transcription compartments, and nuclear bodies are formed through phase separation. Then, we propose that inter-compartmental communications can also be prevalent and may be mediated by inter-compartmental diffusion of macromolecules, fusion among different compartments, and transient or stable contacts among nuclear compartments. Understanding how nuclear compartments communicate with each other represents an exciting new area of research and may reveal important insights about cellular functions and uncover previously under-appreciated disease mechanisms. [ABSTRACT FROM AUTHOR]

Transcription is the fundamental process of gene expression, which in eukaryotes occurs within the complex physicochemical environment of the nucleus. Decades of research have provided extreme detail in the molecular and functional mechanisms of transcription, but the spatial and genomic organization of transcription remains mysterious. Recent discoveries show that transcriptional components can undergo phase separation and create distinct compartments inside the nucleus, providing new models through which to view the transcription process in eukaryotes. In this review, we focus on transcriptional condensates and their phase separation-like behaviors. We suggest differentiation between physical descriptions of phase separation and the complex and dynamic biomolecular assemblies required for productive gene expression, and we discuss how transcriptional condensates are central to organizing the three-dimensional genome across spatial and temporal scales. Finally, we map approaches for therapeutic manipulation of transcriptional condensates and ask what technical advances are needed to understand transcriptional condensates more completely. [ABSTRACT FROM AUTHOR]

As an important epigenetic modification, DNA methylation is involved in many biological processes such as animal cell differentiation, embryonic development, genomic imprinting and sex chromosome inactivation. As DNA methylation sequencing becomes more sophisticated, it becomes possible to use it to solve more zoological problems. This paper reviews the characteristics of DNA methylation, with emphasis on the research and application of DNA methylation in poultry. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Liuwei Dihuang (LWDH), a classical traditional Chinese medicine prescription, has been widely used to prevent and to treat various diseases with symptoms of ‘Kidney-Yin’ deficiency syndrome for over 1000 years in China. It is commonly used to treat functional decline associated with senile disease and menopausal syndrome, especially memory decline, insomnia, diabetes and osteoporosis. Modern experimental pharmacological studies indicated that the mechanism of LWDH treatment of menopausal syndrome may be associated with enhanced estrogenic effects. However, little attention has been paid to the potential impact of LWDH on atherosclerosis (AS) associated with female menopause. The aim of this study was to evaluate the preventive effects of LWDH intake on an animal model of female menopause AS and to explore the underlying molecular mechanism. Materials and methods ApoE −/− mice were randomly divided into 4 groups, with C57BN/L6 mice as the control group. All ApoE −/− mice were ovariectomized (Ovx) one week prior to oral administration and initiation of high-fat diet. C57BL/6 mice were given sham operation and maintained on normal diet. The three administered groups were given simvastatin (4 mg/kg via i.g.) and LWDH (4.5, 9.0 g/kg via i.g.) every day for 14 weeks. Atherosclerotic lesions in the aortic root were determined by oil red O staining and hematoxylin-eosin staining. α-Actin and CD68 in atherosclerotic lesions were detected by immunohistological assay. Serum lipids and homocysteine (Hcy) levels were measured in the 14th week. The cleaved caspase-3, C/EBP homologous protein (CHOP) and G protein coupled estrogen receptor 30 (GPR30) expressions in the aortic arch endothelium were determined by immunohistochemistry and Western blot. The inhibitory effect of LWDH-medicated (20%, 12 h) on Hcy (20%, 24 h)-induced apoptosis of human umbilical vein endothelial cells (HUVECs) was examined by flow cytometry and Hoechst 33258 staining. Intracellular ROS production, nitric oxide release, and endothelial NO synthase (eNOS) activity were measured with or without LWDH-medicated serum pretreatment. In addition, CHOP, glucose-regulated protein GPR30, 78 (Grp78), Bcl-2, Bax and cleaved caspase-3 were analyzed by Western blot. Finally, the influence of G15, a specific antagonist of GPR30, on the protective effect of LWDH on endothelial cells was investigated. Results In vivo administration of LWDH prevented plaque formation and reduced plasma lipid and Hcy levels. LWDH inhibited CHOP and cleaved caspase-3 expression in vivo and in vitro while maintaining GPR30 expression. In vitro study showed that Hcy-induced HUVECs apoptosis was weakened by LWDH-medicated serum pretreatment. Treatment with LWDH-medicated serum significantly upregulated NO release and eNOS activity in HUVECs. In addition, LWDH-medicated serum treatment optimized the balance between Bax and Bcl-2, and attenuated intracellular ROS production. G15 reversed the protective effect of LWDH on endothelial cells and the changes of apoptosis-related proteins. Conclusions LWDH treatment can significantly reduce plaque formation in an animal model of menopausal AS. The mechanism may be inhibition of Hcy-induced endothelial cell apoptosis by modulating GPR30. Hence, LWDH can potentially be used to prevent AS-related vascular disease in menopausal women. [ABSTRACT FROM AUTHOR]

Egg production performance plays an important role in the poultry industry across the world. Previous studies have shown a great difference in egg production performance between pendulous-comb (PC) and upright-comb (UC) chickens. However, there are no reports to identify potential candidate genes for egg production in PC and UC chickens. In the present study, 1,606 laying chickens were raised, and the egg laid by individual chicken was collected for 100 d. Moreover, the expression level of estrogen and progesterone hormones was measured at the start-laying and peak-laying periods of hens. Besides, 4 PC and 4 UC chickens were selected at 217 d of age to perform transcriptome sequencing (RNA-seq) and whole genome resequencing (WGS) to screen the potential candidate genes of egg production. The results showed that PC chicken demonstrated better egg production performance (P < 0.05) and higher estrogen and progesterone hormone expression levels than UC chicken (P < 0.05). RNA-seq analysis showed that 341 upregulated and 1,036 downregulated differentially expressed genes (DEGs) were identified in the ovary tissues of PC and UC chickens. These DEGs were mainly enriched in protein-related, lipid-related, and nucleic acids-related biological processes including ribosome, peptide biosynthetic process, lipid transport terms, and catalytic activity acting on RNA which can significantly affect egg production in chicken. The enrichment results of WGS analysis were consistent with RNA-seq. Further, joint analysis of WGS and RNA-seq data was utilized to screen 30 genes and CAMK1D, CLSTN2, MAST2, PIK3C2G, TBC1D1, STK3, ADGRB3, and PPARGC1A were identified as potential candidate genes for egg production in PC and UC chickens. In summary, our study provides a wealth of information for a better understanding of the genetic and molecular mechanism for the future breeding of PC and UC chickens for egg production. [ABSTRACT FROM AUTHOR]

Carcass traits play important roles in the broiler industry and single nucleotide polymorphism (SNP) can be efficient molecular markers for marker-assisted breeding of chicken carcass traits. Based on our previous RNA-seq data (accession number GSE58755), cysteine rich with epidermal growth factor like domains 1 ( CRELD1 ) and DnaJ heat shock protein family member C30 ( DNAJC30 ) are differentially expressed in breast muscle between white recessive rock chicken (WRR) and Xinghua chicken (XH). In this study, we further characterize the potential function and SNP mutation of CRELD1 and DNAJC30 in chicken for the first time. According to protein interaction network and enrichment analysis, CRELD1 and DNAJC30 may play some roles in chicken muscle development and fat deposition. In WRR and XH, the results of the relative tissue expression pattern demonstrated that CRELD1 and DNAJC30 are not only differentially expressed in breast muscle but also leg muscle and abdominal fat. Therefore, we identified 5 SNP sites of CRELD1 and 7 SNP sites of DNAJC30 and genotyped them in an F 2 chicken population. There are 4 sites of CRELD1 and 3 sites of DNAJC30 are associated with chicken carcass traits like breast muscle weight, body weight, dressed weight, leg weight percentage, eviscerated weight with giblet percentage, intermuscular adipose width, shank length, and girth. These results suggest that the SNP sites of CRELD1 and DNAJC30 can be potential molecular markers to improve the chicken carcass traits and lay the foundation for marker-assisted selection. [ABSTRACT FROM AUTHOR]

N6-Methyladenosine (m6A) has been reported to involve and play an important role in various biological activities but seldom in poultry myogenesis. Cycloleucine usually functions as a nucleic acid methylation inhibitor, the inhibition efficiency of cycloleucine at the m6A level and corresponding dynamic changes of poultry muscle cells remain unknown. In this study, we aim to find out the effect of cycloleucine on the total N6-Methyladenosine level and its molecular mechanism for regulating myogenesis. A total of 745 differentially expressed genes (DEG s) were obtained by 10 mM, 20 mM, and 30 mM of cycloleucine treatment compared with 0 mM treatment. DEGs in 10 mM cycloleucine were significantly enriched in the biological process of skeletal muscle and satellite cell proliferation and differentiation, DEGs in 20 and 30 mM cycloleucine were enriched in some metabolic and biosynthetic processes. The trend analysis showed that 85% of all DEGs were significantly clustered into 4 files, among them 59% DEGs were dose-dependent and 26% were dose-independent, 52% DEGs were in downtrend and 33% DEGs were in uptrend. Also, the cycloleucine treatment could trigger cell cycle arrest in the G1 phase and depress myoblast cell proliferation and inhibit myotube formation. In conclusion, cycloleucine could continuously reduce the m6A level of myoblast cells, depress myoblast cell proliferation and inhibit myotube formation. [ABSTRACT FROM AUTHOR]

The traditional view of directional cell migration within a tissue is that it requires a gradient of a soluble attractive chemical that is stable in space and time due to the presence of a source and a sink. However, advances in live imaging technology and the ability to study cell migration in vivo have revealed that endogenous sources and sinks are typically far more varied and complex. Both sources and sinks can be made up of multiple tissues. During long-range migrations, cells tend to divide up their trajectories and follow different source signals in each segment. When a single source signal is used repeatedly in each segment, its expression is dynamically controlled. Source signals can also originate locally from neighboring migrating cells. Sinks are important in some cases but not all, to sculpt a permissive migratory path or allow cells to move from one intermediate target to another. Migrating cells themselves can function as sinks to create a gradient out of an initially uniform chemoattractant. These diverse ways of building sources and sinks allow different cell types to navigate distinct trajectories through the same embryo even as the whole embryo undergoes the dramatic changes in cell number, position, arrangement and fate that are the essence of development. [ABSTRACT FROM AUTHOR]

Summary: E-cadherin is a major homophilic cell-cell adhesion molecule that inhibits motility of individual cells on matrix. However, its contribution to migration of cells through cell-rich tissues is less clear. We developed an in vivo sensor of mechanical tension across E-cadherin molecules, which we combined with cell-type-specific RNAi, photoactivatable Rac, and morphodynamic profiling, to interrogate how E-cadherin contributes to collective migration of cells between other cells. Using the Drosophila ovary as a model, we found that adhesion between border cells and their substrate, the nurse cells, functions in a positive feedback loop with Rac and actin assembly to stabilize forward-directed protrusion and directionally persistent movement. Adhesion between individual border cells communicates direction from the lead cell to the followers. Adhesion between motile cells and polar cells holds the cluster together and polarizes each individual cell. Thus, E-cadherin is an integral component of the guidance mechanisms that orchestrate collective chemotaxis in vivo. [ABSTRACT FROM AUTHOR]

In a previous study, the laying pattern of Muscovy duck was explored by macro-fitting the laying curve of Muscovy duck, and transcriptome sequencing technique of the ovarian tissues was used to screen the egg-related gene "TAT." Moreover, recent results have shown that TAT is expressed in organs such as oviduct, ovary, and testis. The objective of this study is to examine the effect of TAT gene on egg production traits of Muscovy ducks. First, the expression levels of TAT gene in highest producing (HP) and lowest producing (LP) in 3 tissues related to reproduction were examined, and the results indicated that the expression of TAT gene in hypothalamus was significantly different between HP and LP groups. Then, 6 SNP loci (g. 120G>T, g, 122G>A, g, 254G> A, g. 270C >T, g, 312G>A, and g. 341C>A) were detected in TAT gene. Further, association analysis between the six SNP loci of TAT gene and egg production traits of 652 individual Muscovy ducks was done. The results showed that g. 254G>A and g. 270C>T were significantly correlated (P < 0.05 or 0.001) with the egg production traits of Muscovy ducks. This study elucidated the molecular mechanism that TAT gene might be regulating the egg production traits of Muscovy ducks. [ABSTRACT FROM AUTHOR]

Meat production performance is the most important economic trait in broilers, and skeletal muscle, as the largest organ in animals, is directly related to meat production during embryonic and postnatal growth and development. N6-Methyladenosine (m6A) is a chemical modification occurs on RNA adenosine that has been reported to participate in a variety of biological processes in all species. However, there are still few reports on the regulatory role of muscle growth and development in poultry after birth. This study aims to reveal the distribution of m6A modification sites in chicken pectoralis major muscle after birth and find out the regulatory relationship between m6A and muscle development. As representatives of leaner (Xinghua chicken [ XH ]) and hypertrophic (White Recessive Rock chicken [ WRR ]) broilers, there are significant differences in body weight, muscle fiber diameter, and muscle fiber cross-sectional area between XH and WRR chickens. RNA sequencing detected a total of 397 differentially expressed genes (DEG) in the pectoralis major muscle of XH and WRR chicken, and these DEGs were mainly enriched in catalytic activity and metabolic pathways. MeRIP sequencing results showed that among all 6,476 differentially modified m6A peaks, about 90% peaks (5,823) were differentially down regulated in XH chickens. The joint analysis of the mRNA and MeRIP sequencing data found 145 DEGs with differential m6A peak, ALKBH5 as a m6A demethylase, was also included. The highly expression of ALKBH5 in the muscle tissue of poultry and differential expression between XH and WRR chickens suggest that ALKBH5 may play a crucial role in regulating muscle development. Our results revealed that there were significant differences in growth rate, body weight, muscle fiber diameter, and fiber cross-section area between WRR and XH chicken, as well as significant differences in m6A methylation level and muscle metabolism level. [ABSTRACT FROM AUTHOR]

Qingyuan partridge chicken (QYM) is a highly regarded native breed in China, highly esteemed for its exceptional breeding characteristics. However, the investigation into the selection signatures and its strains remains largely unexplored. In this study, blood sampling, DNA extracting, and high-depth resequencing were performed in 27 QYMs. Integrating the genomic data of 14 chicken (70 individuals) breeds from other researches, to analyze the genetic structure, selection signatures, and effects of selective breeding within QYM and its 3 strains (QYMA, QYMB, and QYMC). Population structure analysis revealed an independent QYM cluster, which exhibited distinct from other breeds, with each of its 3 strains displaying distinct clustering patterns. Linkage disequilibrium analysis highlighted QYMB's notably slower decay rate, potentially influenced by selection pressure from various production indicators. Examination of selection signatures uncovered genes and genetic mechanisms associated with genomic changes resulting from extensive selective breeding within the QYM and its strains. Intriguingly, diacylglycerol kinase beta ( DGKB ) and catenin alpha 2 ( CTNNA2 ) were identified as commonly selected genes across the 3 QYM strains, linked to energy metabolism, muscle development, and fat metabolism. Our research validates the substantial impact of selective breeding on QYM and its strains, concurrently identifying genomic regions and signaling pathways associated with their distinctive characters. This research also establishes a fundamental framework for advancing yellow-feathered broiler breeding strategies. [ABSTRACT FROM AUTHOR]

There is ample experimental evidence showing that the proposers' social role is related to individuals' fairness perception in the Ultimatum Game (UG). However, various social roles, e.g., degree of economic neediness, have different influences on fairness perception, yet it has not been well studied. In this study, we adapted the UG paradigm and recorded electroencephalography (EEG) to probe the neural signatures of whether and how the degree of neediness influences fairness perception. Behavioral results showed that responders are prone to accept unfair offers from proposers in need more than those who are not in need. At the brain level, MFN (medial frontal negativity) was more negative-going in response to unfair than fair offers for not-in-need proposers. In contrast, we found a reversed MFN difference response to unfair and fair offers for in-need proposers, showing a strongly pure altruistic phenomenon. Moreover, we found smaller P300 amplitude was induced in the proposer-in-need condition, compared with its counterpart, while a negative correlation between empathy rating and P300 amplitude in the proposer-in-need condition regardless of the offers' fairness. The current results indicate that the degree of neediness might reduce fairness perception by promoting the empathic concern toward the in-need proposers rather than decreasing the empathic concern for the not-in-need proposers. [ABSTRACT FROM AUTHOR]

• A colorimetric-based dual-mode nanoplatform was constructed for POCT histamine. • The high peroxidase-like activity of SU-Pt@Au NPs had been researched. • An easy-to-use immunoassay nanoplatform was employed to quantify histamine. • Smartphone integrated portable device for the quantification of histamine. Rapid detection of histamine remains a challenge due to the complexity of food matrices. Based on the high peroxidase-like activity of sea urchin-shaped Pt@Au NPs (SU-Pt@Au NPs), a novel dual-mode nanoplatform is developed for the sensitive detection of histamine utilizing an indirect competitive enzyme-linked immunosorbent assay. According to the colorimetric-based UV–vis nanoplatform, histamine is sensitively detected with a liner range from 0.5 to 100 ng/mL and a limit of detection (LOD) as low as 0.3 ng/mL. Then, a smartphone-loaded color picker APP can intelligently detect histamine in point-of-care testing (POCT) based on the R/B ratio of the color channels, with a detection range of 0.5 to 1000 ng/mL and a LOD as low as 0.15 ng/mL, significantly expanding the detection range. Such an easy-to-use and sensitive detection system is employed to quantify histamine in Pacific saury, crab, and pork samples, indicating outstanding application potential in protein-rich meat food safety. [ABSTRACT FROM AUTHOR]

The C9orf72 hexanucleotide repeat expansion (HRE) is the most frequent genetic cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we describe the pathogenic cascades that are initiated by the C9orf72 HRE DNA. The HRE DNA binds to its protein partner DAXX and promotes its liquid-liquid phase separation, which is capable of reorganizing genomic structures. An HRE-dependent nuclear accumulation of DAXX drives chromatin remodeling and epigenetic changes such as histone hypermethylation and hypoacetylation in patient cells. While regulating global gene expression, DAXX plays a key role in the suppression of basal and stress-inducible expression of C9orf72 via chromatin remodeling and epigenetic modifications of the promoter of the major C9orf72 transcript. Downregulation of DAXX or rebalancing the epigenetic modifications mitigates the stress-induced sensitivity of C9orf72-patient-derived motor neurons. These studies reveal a C9orf72 HRE DNA-dependent regulatory mechanism for both local and genomic architectural changes in the relevant diseases. [Display omitted] • G4C2 repeat DNA binds to DAXX and promotes its condensation and nuclear enrichment • LLPS of DAXX reprograms chromatin structures at the C9orf72 locus and in the genome • DAXX suppresses stress-related C9orf72 induction and changes global gene expression • Rebalancing DAXX alleviates stress-induced toxicity in C9orf72 HRE motor neurons This study has revealed pathogenic cascades initiated by C9orf72 hexanucleotide repeat DNA that influence genomic structures and gene expression. DAXX, a G4C2 repeat DNA-binding protein, regulates stress-dependent C9orf72 induction and global gene expression through chromatin remodeling and epigenetic changes as a key player mediating C9orf72 haploinsufficiency and DNA-dependent gain-of-function toxicities. [ABSTRACT FROM AUTHOR]

The risk of atherosclerosis (AS) ascends among post-menopausal women, while current hormone replacement therapy exerts several adverse effects. Alisol B 23-acetate (AB23A), a tetracyclic triterpenoid isolated from the rhizome of Alisma orientale , was reported to show multiple physiological activities, including regulating lipid metabolism. According to molecular docking analysis, it was predicted to bind with estrogen receptor α (ERα). In this study, we aimed to observe the effect of AB23A on preventing post-menopausal AS and explore whether the mechanism was mediated by ERα. In vitro, free fatty acid (FFA) was applied to induce the abnormal lipid metabolism of L02 cells. In vivo, the ApoE−/− mice were ovariectomized to mimic the cessation of estrogen. The high-fat diet was also given to induce post-menopausal AS. We demonstrated AB23A attenuated the accumulation of total cholesterol and triglyceride induced by free fatty acids in hepatocytes. In high-fat diet-ovariectomy-treated ApoE−/− mice, AB23A eliminated lipids in blood and liver. AB23A not only reduced the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) through sterol-regulatory element binding proteins (SREBPs) but also suppressed the secretion of PCSK9 through silent information regulator 1 (SIRT1). Notably, AB23A promoted the expression of ERα in vivo and in vitro. The both ERα inhibitor and ERα siRNA were also applied in confirming whether the hepatic protective effect of AB23A was mediated by ERα. We found that AB23A significantly promoted the expression of ERα. AB23A could inhibit the synthesis and secretion of PCSK9 through ERα, lower the accumulation of triglyceride and cholesterol, and prevent post-menopausal AS. Unlabelled Image [ABSTRACT FROM AUTHOR]

The classical and traditional Chinese medicine prescription, Liuwei Dihuang (LWDH), has been commonly used to treat the menopausal syndrome. It has been reported that LWDH could improve estrogen receptor α (ERα) expression to prevent atherosclerosis (AS), while the mechanism of LWDH on regulating ERα expression was still unknown. To reveal the mechanism of LWDH on regulating the ERα expression. The protective effect of LWDH on Hcy-induced apoptosis of human umbilical vein endothelial cells (HUVECs) was examined. The expression of ERα and DNA methyltransferases 1 (DNMT1) were detected by Western blot and real-time polymerase chain reaction (RT-PCR). The methylation rate of the ERα gene was assayed by the bisulfite sequencing PCR (BSP). High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) was applied to determine the level of S-Adenosyl methionine (SAM) and S-Adenosyl homocysteine (SAH). In vivo, the ApoE−/- mice were ovariectomized to establish postmenopausal atherosclerosis (AS) model. In vitro study showed that LWDH protects HUVECs from Hcy-induced apoptosis. Treatment with LWDH significantly increased the ERα expression and reduced the methylation rate of the ERα gene by inhibiting the DNMT1 expression. The level of main methyl donor SAM and the ration of SAM/SAH were reduced by LWDH. In vivo, LWDH prevented the formation of plaque and reduced the concentration of Hcy. In addition, LWDH upregulated the ERα expression, as well as inhibiting the expression of DNMT1 in atherosclerotic mice. LWDH exerted protective effects on postmenopausal AS mice, and HUVECs treated with Hcy. LWDH increased of ERα expression via inhibiting DNMT1-dependent ERα methylation. Image 1 [ABSTRACT FROM AUTHOR]

Liuwei Dihuang (LWDH) is a classic prescription that has been used as a traditional medicinal formula for more than 1000 years in China. In clinical, LWDF is used for treating functional decline associated with senile disease and menopausal syndrome. Studies have demonstrated that LWDH could significantly improve estrogen level and ER expression, and suspend the process of atherosclerosis. However, the under mechanism of how LWDH suppressing VSMCs phenotypic conversion and proliferation through ER is still unknown. This study was to reveal the under mechanism of how LWDH inhibits the phenotypic conversion of VSMCs. 24 ApoE−/− mice were divided into 4 groups: sham group, model group, E 2 group, and LWDH group, and 6 C57BN/L6 mice were used as control group. The primary VSMCs were divided into control group, model group, E 2 group, LWDH group, LWDH + MPP group, and LWDH + PHTPP group with or without control siRNA, ERα siRNA, ERβ siRNA, and myocardin siRNA. Oil red staining was used to evaluate the lipid deposition in the cardiac aorta. Serum chemistry analysis to test serum TG, TC, LDL, and HDL. Immunofluorescence staining was used to test α-SMA, osteopontin and F-actin. Immunohistochemical staining was performed to check out the myocardin in the cardiac aorta. The mRNA levels of α-SMA, osteopontin, ERα, ERβ, SRC3 and myocardin were detected by Real Time-PCR, and the protein expression levels of them were detected by Western blotting. Co-immunoprecipitation was proceed to test the interaction between ERα and SRC3 and SRC3 and myocardin. Flow cytometry was used to check out the cell cycle. Wound healing assay and Transwell were managed to evaluate the migration capacity of VSMCs. In vivo administration of LWDH suppressed AS symptoms, decreases phenotypic marker of vascular endothelial cell, and increases phenotypic marker of VSMC in ovariectomized ApoE−/− female mice. Moreover, LWDH significantly increased the mRNA and protein expression levels of ERα, ERβ, SRC3 and myocardin in the cardiac aorta of ovariectomized ApoE−/− female mice. In vitro, LWDH altered cell cycle and reduced the elevated cyclinD protein expression migration capacity and in the model VSMCs. In addition, LWDH inhibited phenotypic conversion and promoted the expression of ER, SRC3, and myocardin of the primary VSMC phenotypic conversion model. Inhibition of ERα almost completely eliminated the impacts of LWDH on α- SMA and osteopontin. Furthermore, LWDH promoted the interaction between ERα and SRC3 and up-regulated the co-activation of SRC3 and myocardin. LWDH could inhibit the phenotypic conversion of VSMCs in vitro and in vivo by increasing the activity of myocardin through up-regulating the expression of ERα and promoting the interaction between ERα and SRC3. Our research reveals the under mechanism of how LWDH inhibits the phenotypic conversion of VSMCs. Image 1 [ABSTRACT FROM AUTHOR]