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Abstract Accurate lung nodule segmentation is fundamental for the early detection of lung cancer. With the rapid development of deep learning, lung nodule segmentation models based on the encoder-decoder structure have become the mainstream research approach. However, during the encoding process, most models have limitations in extracting edge and semantic information and in capturing long-range dependencies. To address these problems, we propose a new lung nodule segmentation model, abbreviated as MCAT-Net. In this model, we construct a multi-threshold feature separation module to capture edge and texture features from different levels and specified intensities of the input image. Secondly, we introduce the coordinate attention mechanism, which allows the model to better recognize and utilize spatial information when handling long-range dependencies, enabling the deep network to maintain its sensitivity to nodule positions. Thirdly, we use the transformer to fully capture the long-range dependencies, further enhancing the global information integration of the network. The proposed method was verified on the LIDC-IDRI and LNDb datasets. The Dice similarity coefficient (DSC) values achieved were 88.29% and 78.51%, and the sensitivities were 86.33% and 75.05%, respectively. The experimental results demonstrated its high practical value for the early diagnosis of lung cancer.

Highlights Elephant trunk-inspired anisotropic wrinkling structures were formed on a sandwich-like conductive film through a controlled shrinking method. The wrinkled conductive network could withstand up to 200% tensile strain and exhibits a strain-enhanced electromagnetic interference shielding effectiveness when stretching parallel to the electric field polarization direction.

Abstract Background Depression and anxiety are common comorbid diseases of constipation. Fecal microbiota transplantation (FMT) significantly relieves gastrointestinal-related symptoms, but its impact on psychiatric symptoms remains uncharted. Methods We collected fecal and serum samples before and after FMT from 4 functional constipation patients with psychiatric symptoms and corresponding donor stool samples. We categorized the samples into two groups: before FMT (Fb) and after FMT (Fa). Parameters associated with constipation, depression, and anxiety symptoms were evaluated. Metagenomics and targeted neurotransmitter metabolomics were performed to investigate the gut microbiota and metabolites. 5-hydroxytryptamine (5-HT) biosynthesis was detected in patients’ fecal supernatants exposed to the QGP-1 cell model in vitro. Results Our study demonstrated that patient’s constipation, depression, and anxiety were improved after FMT intervention. At the genus level, relative abundance of g_Bacteroides and g_Klebsiella decreased in the Fa group, while g_Lactobacillus, and g_Selenomonas content increased in the same group. These observations suggest a potential involvement of these genera in the pathogenesis of constipation with psychiatric symptoms. Metabolomics analysis showed that FMT intervention decreased serum 5-HT levels. Additionally, we found that species, including s_Klebsiella sp. 1_1_55, s_Odoribacter splanchnicus, and s_Ruminococcus gnavus CAG:126, were positively correlated with 5-HT levels. In contrast, s_Acetobacterium bakii, s_Enterococcus hermanniensis, s_Prevotella falsenii, s_Propionispira arboris, s_Schwartzia succinivorans, s_Selenomonas artemidis, and s_Selenomonas sp. FC4001 were negatively correlated with 5-HT levels. Furthermore, we observed that patients’ fecal supernatants increased 5-HT biosynthesis in QGP-1 cells. Conclusion FMT can relieve patients’ constipation, depression, and anxiety symptoms by reshaping gut microbiota. The 5-HT level was associated with an altered abundance of specific bacteria or metabolites. This study provides specific evidence for FMT intervention in constipation patients with psychiatric symptoms.

Sea fog is a common weather phenomenon at sea, which reduces visibility and causes tremendous hazards to marine transportation, marine fishing, and other maritime operations. Traditional sea fog monitoring methods have enormous difficulties in characterizing the diversity of sea fog and distinguishing sea fog from low-level clouds. Thus, we propose a cloud image retrieval method for sea fog recognition (CIR-SFR) in a deep learning (DL) framework by combining the advantages of metric learning. CIR-SFR includes the feature extraction module and the retrieval-based SFR module. The feature extraction module adopts the double branch residual neural network (DBRNN) to comprehensively extract the global and local features of cloud images. By introducing local branches and using activation masks, DBRNN can focus on regions of interest in cloud images. Moreover, cloud image features are projected into the semantic space by introducing multisimilarity loss, which effectively improves the discrimination ability of sea fog and low-level clouds. For the retrieval-based SFR module, similar cloud images are retrieved from the cloud image dataset according to the distance in the feature space, and accurate SFR results are obtained by counting the percentage of various cloud image types in the retrieval results. To evaluate the SFR system, we establish a dataset of 2544 cloud images including clear sky, low-level cloud, medium high cloud, and sea fog. Experimental results show that the proposed method outperforms the traditional methods in SFR, which provides a new way for SFR.

Functional constipation is a common functional gastrointestinal disease. In our previous study, we found that the gut microbiota structure was disordered and the level of phenylalanine (Phe) in serum was decreased in constipated women. We conducted the present study to elucidate the role of Phe in remodeling the composition of gut microbiota and the relationship between gut microbiota and serum metabolites. Here, we demonstrated that Phe treatment significantly enhanced intestinal motility, suppressed inflammatory responses, and prevented intestinal barrier damage in rats with loperamide (Lop)-induced constipation. By metagenomic sequencing, the disbalanced gut microbial profile was analyzed in constipated rats. Phe treatment reversed changes in the abundance of several gut bacteria at the phylum, genus, and species levels. Further, we observed distinct metabolic patterns in constipated rats through targeted metabolomics and identified constipation-related gut microbial species linked to changes in circulating neurotransmitter metabolites. The abundances of species s_Lactobacillus murinus, s_Enterococcus italicus, s_Lactobacillus animalis, s_Lactobacillus apodemi, s_Enterococcus faecalis, and s_Lactobacillus backii were positively correlated with L-asparagine, L-Glutamic acid, Putrescine, and Spermidine levels. The abundances of s_Lactobacillus johnsonii and s_Butyricimonas virosa were negatively correlated with L-asparagine, L-Glutamic acid, Putrescine, and Spermidine levels. Taken together, our findings suggest that Phe can ameliorate the development of Lop-induced constipation in rats by remodeling the gut microbial community structure and changing metabolite levels.

Despite a wealth of research on the interaction behavior patterns among team members from different angles, few studies focus on the combination of innovation management and innovation team. With the “Input-Process-Output” theoretical framework, this study takes the coding analysis to explore the differences in the interaction behavior patterns of members caused by the cognitive differences in the higher and lower innovative-performing teams. An innovation experiment was conducted in 12 innovation teams based on an experimental paradigm proposed for team innovation tasks. Subsequently, team members’ 1,754 behaviors were coded to analyze the similarities and differences in the interaction behavior patterns between higher and lower innovative-performing teams with lag sequential analysis. The results revealed that both higher and lower innovative-performing teams showed some same interaction behavior patterns. More specifically, the probability of idea facilitation behaviors being followed by team spirit facilitation behaviors was significantly higher than expected, while the probability of idea facilitation behaviors recurring was significantly lower than expected. However, in lower innovative-performing teams, there were some special interaction behavior patterns, such as “the probability of idea facilitation behaviors being followed by neutral interaction or idea inhibition behaviors was significantly lower than expected.” These phenomena may reflect some realistic situations in our life, such as “One echoes the other,” “Sitting on the sidelines” and “A gentleman is ready to die for his bosom friends” in the members’ interaction after cognitive differences happen. This paper provides opinions and suggestions for the research on the interaction behavior observation and coding analysis among members of innovation teams, as well as theoretical contributions to the research on the behavior observation of innovation teams.

High-current pulsed electron beam sources are the core components of high-power microwave systems. In order to meet the requirements of future applications, one needs to improve the performance of electron beam sources in terms of vacuum insulation, beam transportation, and thermal management. In this paper, we report about our recent progress in the development of high-current vacuum electron beam sources. In order to meet the vacuum maintenance requirements of high-power microwave tubes, a high-electric field ceramic vacuum interface is designed and fabricated based on the ceramic metal brazing technique. In our experiments, a stable operation of the ceramic vacuum interface is demonstrated in the 10 Hz repetition mode with withstand voltage of larger than 600 kV and pulse width of about 100 ns. Besides, a cold cathode is developed using SiC nanowires, and an average beam current density of 1.2 kA/cm2 is achieved under the electric field strength of 90 kV/cm. Compared with traditional velvet cathodes, the characteristics of the SiC nanowire cathode, such as macro-electrical stability, emission uniformity, and operating life have been significantly improved. Furthermore, a high-current electron beam collector has been developed for relativistic backward wave oscillator tubes. A spiral flume is designed in the collector to meet the requirement of both high specific energy and low flow rate. It shows that the withstand heat flow density is in the order of 1012 W/m2, which is suitable for the long pulse and repetitive operation of the system. These results represent a significant step towards the practical application of long-life high-power microwave systems.

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Abstract Background This study focused on the aging mechanism and degradation of mechanical and structural features of elastodontic appliances (EA) under artificial and intraoral aging to achieve oral myofunctional therapy with particular removable silicone elastomer devices. Materials and methods EAs artificially aged in saliva with different pH values were investigated through cyclic compression testing along with characterization techniques (Scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy), and characterization analysis was also performed on clinically retrieved EAs. Results Artificial aging was found to have minimal effect on the structural properties of EAs, and intraorally aged samples showed perceptible micro-morphology. The Mullins index and peak stress decreased (P

Academicians with a pro-environmental attitude can play a pivotal role in developing curricula and new programs aimed at education for sustainable development. Therefore, it is of utmost importance to identify the factors that influence academicians’ positive attitude toward the environment. This study attempts to investigate the effects of environmental consciousness, environmental knowledge, and biospheric values, as well as the moderating effects of social influence, on the attitude toward the environment among the faculty members of higher education institutions (HIEs) in Southern Pakistan. The data were collected from six universities in the district of Vehari, Punjab, Pakistan. After checking for reliability and validity, the study used the structural equation modeling technique to examine the aforementioned association. The results reveal that environmental consciousness and biospheric values significantly influence the attitude of faculty members toward the environment. Furthermore, social influence positively moderates the relationship only between biospheric values and attitudes toward the environment. Overall, this study contributes original insights into the factors influencing pro-environmental attitudes among faculty in a specific cultural and educational context. Its findings can inform targeted strategies to enhance environmental education and engagement in higher education, making it a valuable addition to the literature on education for sustainable development. The findings could guide policymakers of higher education institutions in promoting a pro-environmental attitude among faculty members by implementing awareness programs that increase environmental consciousness and integrate biospheric values into their core mission. Furthermore, HEIs should also establish “green teams” to induce a positive environmental attitude through social influence.

BackgroundHigh-grade serous ovarian cancer (HGSOC), the predominant subtype of epithelial ovarian cancer, is frequently diagnosed at an advanced stage due to its nonspecific early symptoms. Despite standard treatments, including cytoreductive surgery and platinum-based chemotherapy, significant improvements in survival have been limited. Understanding the molecular mechanisms, immune landscape, and drug sensitivity of HGSOC is crucial for developing more effective and personalized therapies. This study integrates insights from cancer immunology, molecular profiling, and drug sensitivity analysis to identify novel therapeutic targets and improve treatment outcomes. Utilizing single-cell RNA sequencing (scRNA-seq), the study systematically examines tumor heterogeneity and immune microenvironment, focusing on biomarkers influencing drug response and immune activity, aiming to enhance patient outcomes and quality of life.MethodsscRNA-seq data was obtained from the GEO database in this study. Differential gene expression was analyzed using gene ontology and gene set enrichment methods. InferCNV identified malignant epithelial cells, while Monocle, Cytotrace, and Slingshot software inferred subtype differentiation trajectories. The CellChat software package predicted cellular communication between malignant cell subtypes and other cells, while pySCENIC analysis was utilized to identify transcription factor regulatory networks within malignant cell subtypes. Finally, the analysis results were validated through functional experiments, and a prognostic model was developed to assess prognosis, immune infiltration, and drug sensitivity across various risk groups.ResultsThis study investigated the cellular heterogeneity of HGSOC using scRNA-seq, focusing on tumor cell subtypes and their interactions within the tumor microenvironment. We confirmed the key role of the C2 IGF2+ tumor cell subtype in HGSOC, which was significantly associated with poor prognosis and high levels of chromosomal copy number variations. This subtype was located at the terminal differentiation of the tumor, displaying a higher degree of malignancy and close association with stage IIIC tissue types. The C2 subtype was also associated with various metabolic pathways, such as glycolysis and riboflavin metabolism, as well as programmed cell death processes. The study highlighted the complex interactions between the C2 subtype and fibroblasts through the MK signaling pathway, which may be closely related to tumor-associated fibroblasts and tumor progression. Elevated expression of PRRX1 was significantly connected to the C2 subtype and may impact disease progression by modulating gene transcription. A prognostic model based on the C2 subtype demonstrated its association with adverse prognosis outcomes, emphasizing the importance of immune infiltration and drug sensitivity analysis in clinical intervention strategies.ConclusionThis study integrates molecular oncology, immunotherapy, and drug sensitivity analysis to reveal the mechanisms driving HGSOC progression and treatment resistance. The C2 IGF2+ tumor subtype, linked to poor prognosis, offers a promising target for future therapies. Emphasizing immune infiltration and drug sensitivity, the research highlights personalized strategies to improve survival and quality of life for HGSOC patients.

The primary purpose of this study is to assess the policies that affect the ethics of business and draw recommendations for an ethical and sustainable policy for the improvement of Business Sustainability in Bangladesh’s RMG sector. The RMG sector is crucial to Bangladesh’s economy, being the backbone and providing the highest export earnings. A PST (Purposive Sampling Technique) was used to collect the data by conducting self-administered surveys completed by 279 participants from 20 RMG companies situated in five different areas. The potentials and perspectives given in the feedback are practical in terms of ethics and the present tendencies in the field. The research shows a strong positive link between an ECC (Ethical Code of Conduct) and BS (Business Sustainability) (r = 0. 256) and an even more substantial correlation for CSR (Corporate Social Responsibility) (r = 0. 355). Ethical leadership also demonstrates a positive relationship with business sustainability (r = 0.282). Additionally, there is a weaker but still positive connection exists between BS and NG (New Governance) (r = 0. 168). Such findings highlight the importance of ethical business regulation since it can be instrumental in enhancing Bangladesh RMG firms’ sustainability. Managers, who play a critical role in this process, are particularly important in retaining experienced employees and promoting ethical practices. This study underscores the need for robust ethical frameworks to ensure the long-term sustainability and competitiveness of the RMG industry in Bangladesh. Bangladeshi enterprises participating in such RMG industry must imitate sustainable studies in their operations to gain a competitive benefit in the market and develop sustainable value propositions.

ABSTRACT: Myocyte enhancer factor 2A (MEF2A) is a transcription factor that plays a critical role in cell proliferation, differentiation and apoptosis. In contrast to the wide characterization of its regulation mechanism in mammalian skeletal muscle, its role in chickens is limited. Especially, its wide target genes remain to be identified. Therefore, we utilized Cleavage Under Targets and Tagmentation (CUT&Tag) technology to reveal the genome-wide binding profile of MEF2A in chicken primary myoblasts thus gaining insights into its potential role in muscle development. Our results revealed that MEF2A binding sites were primarily distributed in intergenic and intronic regions. Within the promoter region, although only 8.87% of MEF2A binding sites were found, these binding sites were concentrated around the transcription start site (TSS). Following peak annotation, a total of 1903 genes were identified as potential targets of MEF2A. Gene Ontology (GO) enrichment analysis further revealed that MEF2A target genes may be involved in the regulation of embryonic development in multiple organ systems, including muscle development, gland development, and visual system development. Moreover, a comparison of the MEF2A target genes identified in chicken primary myoblasts with those in mouse C2C12 cells revealed 388 target genes are conserved across species, 1515 target genes are chicken specific. Among these conserved genes, ankyrin repeat and SOCS box containing 5 (ASB5), transmembrane protein 182 (TMEM182), myomesin 2 (MYOM2), leucyl and cystinyl aminopeptidase (LNPEP), actinin alpha 2 (ACTN2), sorbin and SH3 domain containing 1 (SORBS1), ankyrin 3 (ANK3), sarcoglycan delta (SGCD), and ORAI calcium release-activated calcium modulator 1 (ORAI1) exhibited consistent expression patterns with MEF2A during embryonic muscle development. Finally, TMEM182, as an important negative regulator of muscle development, has been validated to be regulated by MEF2A by dual-luciferase and quantitative real-time PCR (qPCR) assays. In summary, our study for the first time provides a wide landscape of MEF2A target genes in chicken primary myoblasts, which supports the active role of MEF2A in chicken muscle development.

ABSTRACT: The laying hen is the spontaneous model of ovarian tumor. A comprehensive comparison based on RNA-seq from hens and women may shed light on the molecular mechanisms of ovarian cancer. We performed next-generation sequencing of microRNA and mRNA expression profiles in 9 chicken ovarian cancers and 4 normal ovaries, which has been deposited in GSE246604. Together with 6 public datasets (GSE21706, GSE40376, GSE18520, GSE27651, GSE66957, TCGA-OV), we conducted a comparative transcriptomics study between chicken and human. In the present study, miR-451, miR-2188-5p, and miR-10b-5p were differentially expressed in normal ovaries, early- and late-stage ovarian cancers. We also disclosed 499 up-regulated genes and 1,061 down-regulated genes in chicken ovarian cancer. The molecular signals from 9 cancer hallmarks, 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and 369 Gene Ontology (GO) pathways exhibited abnormalities in ovarian cancer compared to normal ovaries via Gene Set Enrichment Analysis (GSEA). In the comparative analysis across species, we have uncovered the conservation of 5 KEGG and 76 GO pathways between chicken and human including the mismatch repair and ECM receptor interaction pathways. Moreover, a total of 174 genes contributed to the core enrichment for these KEGG and GO pathways were identified. Among these genes, the 22 genes were found to be associated with overall survival in patients with ovarian cancer. In general, we revealed the microRNA profiles of ovarian cancers in hens and updated the mRNA profiles previously derived from microarrays. And we also disclosed the molecular pathways and core genes of ovarian cancer shared between hens and women, which informs model animal studies and gene-targeted drug development.

Objective To investigate the efficacy and safety of Venetoclax combined with Azacitidine in the treatment of high-risk myelodysplastic syndrome. Methods A total of 56 patients with high-risk myelodysplastic syndrome were enrolled from June 2019 to June 2022 in the Second Affiliated Hospital of Qiqihar Medical University.The patients were divided into a control group(n=30) and a study group(n=26) by simple random sampling.The control group received Azacitidine chemotherapy.The study group received Venetoclax combined with Azacitidine chemotherapy.The efficacy, adverse reactions, lactate dehydrogenase, β2 microglobulin, and folic acid were compared between the two groups. Results The overall response rate in the study group was higher than that in the control group(P0.05).After treatment, the serum levels of lactate dehydrogenase, β2 microglobulin and folic acid in the study group were all lower than those in the control group(P

BackgroundCervical cancer (CC) is the fourth most common malignancy among women globally and serves as the main cause of cancer-related deaths among women in developing countries. The early symptoms of CC are often not apparent, with diagnoses typically made at advanced stages, which lead to poor clinical prognoses. In recent years, numerous studies have shown that there is a close relationship between mast cells (MCs) and tumor development. However, research on the role MCs played in CC is still very limited at that time. Thus, the study conducted a single-cell multi-omics analysis on human CC cells, aiming to explore the mechanisms by which MCs interact with the tumor microenvironment in CC. The goal was to provide a scientific basis for the prevention, diagnosis, and treatment of CC, with the hope of improving patients’ prognoses and quality of life.MethodThe present study acquired single-cell RNA sequencing data from ten CC tumor samples in the ArrayExpress database. Slingshot and AUCcell were utilized to infer and assess the differentiation trajectory and cell plasticity of MCs subpopulations. Differential expression analysis of MCs subpopulations in CC was performed, employing Gene Ontology, gene set enrichment analysis, and gene set variation analysis. CellChat software package was applied to predict cell communication between MCs subpopulations and CC cells. Cellular functional experiments validated the functionality of TNFRSF12A in HeLa and Caski cell lines. Additionally, a risk scoring model was constructed to evaluate the differences in clinical features, prognosis, immune infiltration, immune checkpoint, and functional enrichment across various risk scores. Copy number variation levels were computed using inference of copy number variations.ResultThe obtained 93,524 high-quality cells were classified into ten cell types, including T_NK cells, endothelial cells, fibroblasts, smooth muscle cells, epithelial cells, B cells, plasma cells, MCs, neutrophils, and myeloid cells. Furthermore, a total of 1,392 MCs were subdivided into seven subpopulations: C0 CTSG+ MCs, C1 CALR+ MCs, C2 ALOX5+ MCs, C3 ANXA2+ MCs, C4 MGP+ MCs, C5 IL32+ MCs, and C6 ADGRL4+ MCs. Notably, the C2 subpopulation showed close associations with tumor-related MCs, with Slingshot results indicating that C2 subpopulation resided at the intermediate-to-late stage of differentiation, potentially representing a crucial transition point in the benign-to-malignant transformation of CC. CNVscore and bulk analysis results further confirmed the transforming state of the C2 subpopulation. CellChat analysis revealed TNFRSF12A as a key receptor involved in the actions of C2 ALOX5+ MCs. Moreover, in vitro experiments indicated that downregulating the TNFRSF12A gene may partially inhibit the development of CC. Additionally, a prognosis model and immune infiltration analysis based on the marker genes of the C2 subpopulation provided valuable guidance for patient prognosis and clinical intervention strategies.ConclusionsWe first identified the transformative tumor-associated MCs subpopulation C2 ALOX5+ MCs within CC, which was at a critical stage of tumor differentiation and impacted the progression of CC. In vitro experiments confirmed the inhibitory effect of knocking down the TNFRSF12A gene on the development of CC. The prognostic model constructed based on the C2 ALOX5+MCs subset demonstrated excellent predictive value. These findings offer a fresh perspective for clinical decision-making in CC.

ObjectiveThe aim of this research was to gain a thorough understanding of the processes involved in cell communication and discover potential indicators for treating multiple myeloma (MM) through the use of single-cell RNA sequencing (scRNA-seq). And explored the expression of multiple myeloma-related subgroups on metal ion-related pathways to explore the relationship between MM and metal ions.MethodsWe performed a fair examination using single-cell RNA sequencing on 32 bone marrow specimens collected from 22 individuals at different points of MM advancement and 9 individuals without any health issues. To analyze the scRNA-seq data, we employed advanced computational algorithms, including Slingshot, Monocle2, and other methodologies. Specifically, Slingshot and Monocle2 enabled us to simulate the biological functionalities of different cell populations and map trajectories of cell developmental pathways. Additionally, we utilized the UMAP algorithm, a powerful dimension reduction technique, to cluster cells and identify genes that were differentially expressed across clusters.ResultsOur study revealed distinct gene expression patterns and molecular pathways within each patient, which exhibited associations with disease progression. The analysis provided insights into the tumor microenvironment (TME), intra- and inter-patient heterogeneity, and cell-cell interactions mediated by ligand-receptor signaling. And found that multiple myeloma-related subgroups were expressed higher levels in MMP and TIMP pathways, there were some associations.ConclusionOur study presents a fresh perspective for future research endeavors and clinical interventions in the field of MM. The identified gene expression patterns and molecular pathways hold immense potential as therapeutic targets for the treatment of multiple myeloma. The utilization of scRNA-seq technology has significantly contributed to a more precise understanding of the complex cellular processes and interactions within MM. Through these advancements, we are now better equipped to unravel the underlying mechanisms driving the development and progression of this complex disease.

Highlights 1. MET is a direct target of miR-27b. 2. Low expression of miR-27b is correlated with the growth activity of DLBCL cells. 3. miR-27b inhibits the proliferation and invasiveness of DLBCL cells, and promotes the apoptosis of the cells by targeting MET and inhibiting the activity of the MET/PI3K/AKT pathway.

Somatostatin shows an anti-lipolytic effect in both chickens and ducks. However, its molecular mediator remains to be identified. Here, we report that somatostatin type 2 receptor (SSTR2) is expressed at a high level in chicken adipose tissue. In cultured chicken adipose tissue, the inhibition of glucagon-stimulated lipolysis by somatostatin was blocked by an SSTR2 antagonist (CYN-154086), supporting an SSTR2-mediated anti-lipolytic effect. Furthermore, a significant pro-proliferative effect was detected in SST28-treated immortalized chicken preadipocytes (ICP-1), and this cell proliferative effect may be mediated through the MAPK/ERK signaling pathway activated by SSTR2. In summary, our results demonstrate that SSTR2 may regulate adipose tissue development by affecting the number and volume of adipocytes in chickens.

Calcitonin (CT) and calcitonin gene-related peptide (CGRP) are critical regulators of calcium balance and have extensive implications for vertebrate physiological processes. This study explores the CT and CGRP signaling systems in chickens through cloning and characterization of the chicken calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR), together with three receptor activity-modifying proteins (RAMPs). We illuminated the functional roles for chickens between the receptors examined alone and in RAMP-associated complexes using luciferase reporter assays. Chicken CTRs and CLRs stimulated the cAMP/PKA and MAPK/ERK signaling pathways, signifying their functional receptor status, with CT showing appreciable ligand activity at nanomolar concentrations across receptor combinations. Notably, it is revealed that chicken CLR can act as a functional receptor for CT without or with RAMPs. Furthermore, we uncovered a tissue-specific expression profile for CT, CGRP, CTR, CLR, and RAMPs in chickens, indicating the different physiological roles across various tissues. In conclusion, our data establish a clear molecular basis to reveal information on CT, CGRP, CTR, CLR, and RAMPs in chickens and contribute to understanding the conserved or divergent functions of this family in vertebrates.

A novel NHC-catalyzed regiodivergent reaction of ynones with trifluoromethyl ketones consisting of Aldol reactions and intermolecular [3 + 2] annulations has been developed. Employing two different NHC catalysts, various tertiary alcohols and dihyrofuranones containing trifluoromethyl can be obtained in moderate to good yields (35 examples, up to 91% yield). This protocol features mild reaction conditions, high efficiency and broad substrates scope, promoting the development of NHC catalysis and transformations of ynones.

BackgroundGrowing evidence has shown that the antioxidant diet is a protective factor against depression. However, the relationship between the Composite Dietary Antioxidant Index (CDAI), an important measure of antioxidant diet, and depression has received little attention. Therefore, we investigated the relationship between CDAI and depression through a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018.MethodsThe association between CDAI and depression was investigated using a weighted multiple logistic regression model with subgroup analysis. Non-linear correlations were explored using fitted smoothing curves. And we used a recursive method to figure out the turning point and build a weighted two-piece linear regression model.ResultsIn the multivariate logistic regression model with full adjustment for confounding variables, the ORs (95% CI) for the association between CDAI and depression were 0.83 (0.78, 0.88). Moreover, a non-linear association was found, with 0.16 being the inflection point. Before the inflection point, each unit increase in CDAI was associated with a 30% decrease in the risk of depression. After the inflection point, the risk of depression was found to be reduced by 11% for each unit increase. None of the interactions in all subgroup analyses were statistically significant.ConclusionsOur study highlighted a negative non-linear association between CDAI and depression in a nationally representative sample of US adults. Further clinical and basic research is needed to explore their association better.

PurposeAs depression in patients with pelvic inflammatory diseases (PID) has received increasing attention in recent years, this study aims to investigate the relationship between depression severity and risk factors for pelvic inflammatory disease, and to provide new perspectives in the treatment of PID.Patients and methodsMultivariate regression was used to evaluate the association between pelvic inflammatory disease and the severity of depression. Females who participated in the United States National Health and Nutrition Examination Survey (NHANES) from 2013 to 2018 were included. In addition, risk factors for PID and depression were also included in the analysis as adjustment factors.ResultsThe risk of developing PID was associated with depressive status (odds ratio, OR 1.10, 95% confidence interval, CI 1.08–1.12), especially in people with severe depression (odds ratio, OR 6.34, 95% confidence interval, CI 3.72–10.79). Subgroup analysis showed differences in the risk of PID among people with different characteristics.ConclusionThis study showed that there may be a potential positive association between depressive status and the prevalence of PID in the United States adult female population. Depression should be actively looked for in all patients with PID and treated appropriately

Melanocortin receptors (MC1R-MC5R) and their accessory proteins (MRAPs) are involved in a variety of physiological processes, including pigmentation, lipolysis, adrenal steroidogenesis, and immunology. However, the physiological roles of MC5R are rarely characterized in vertebrates, particularly in birds. In this work, we cloned the full-length cDNA of chicken MC5R and identified its core promoter region. Functional studies revealed that cMC5R was more sensitive to ACTH/α-MSH than β-MSH/γ-MSH, and was coupled to the cAMP/PKA signaling pathway. We demonstrated that MRAP2 decreased MC5R sensitivity to α-MSH, whereas MRAP1 did not have a similar effect, and that both MRAPs significantly reduced MC5R expression on the cell membrane surface. Transcriptome and qPCR data showed that both MRAP1 and MC5R were highly expressed in chicken liver. Additionally, we observed that ACTH might increase hepatic glucose production and decrease lipogenesis in primary hepatocytes, and dose-dependently downregulated the expression levels of ELOVL6 and THRSPA genes. These findings indicated that ACTH may act directly on hepatocytes to regulate glucolipid metabolism, which will help to understand the function of MC5R in avian.

AMP-activated protein kinase (AMPK) is an evolutionarily conserved energy sensor. Activation of AMPK leads to a number of metabolic benefits, including improved mitochondrial function in skeletal muscle and lowering of serum glucose levels in type-2 diabetes models. However, direct activation of AMPK leads to cardiac enlargement, and an alternative strategy that activates AMPK without affecting the heart is needed. Inhibition of phosphodiesterase 4 (PDE4), which is poorly expressed in the human heart, activates AMPK in other tissues. In a screen to identify novel PDE4 inhibitors, we discovered compound CBU91, which is 5-10 fold more potent than rolipram, the best characterized PDE4 inhibitor. CBU91, like rolipram, is able to activate AMPK and Sirt1 and increase mitochondrial function in myotubes. These findings suggest that activation of AMPK in myotubes is a general property of PDE4 inhibition and that PDE4 inhibition may activate AMPK in metabolically relevant tissues without affecting the heart.

BackgroundAcute myeloid leukemia (AML) is a clonal malignant disease with poor prognosis and a low overall survival rate. Although many studies on the treatment and detection of AML have been conducted, the molecular mechanism of AML development and progression has not been fully elucidated. The present study was designed to pursuit the molecular mechanism of AML using a comprehensive bioinformatics analysis, and build an applicable model to predict the survival probability of AML patients in clinical use.MethodsTo simplify the complicated regulatory networks, we performed the gene co-expression and PPI network based on WGCNA and STRING database using modularization design. Two machine learning methods, A least absolute shrinkage and selector operation (LASSO) algorithm and support vector machine-recursive feature elimination (SVM-RFE), were used to filter the common hub genes by five-fold cross-validation. The candidate hub genes were used to build the predictive model of AML by the cox-proportional hazards analysis, and validated in The Cancer Genome Atlas (TCGA) cohort and ohsu cohort, which were reliable in the experimental verification by qRT-PCR and western blotting in mRNA and protein levels.ResultsThree hub genes, FLT3, CD177 and TTPAL were used to build a clinically applicable model to predict the survival probability of AML patients and divided them into high and low groups. To compare the survival ability of the model with the classical clinical features, we generated the nomogram. The model displayed the most risk points contrast to other clinical characteristics, which was compatible with the data of cox multivariate regression.ConclusionThis study reveal the novel molecular mechanism of AML, and construct a clinical model significantly related to AML patient prognosis. We showed the integrated roles of critical pathways, hub genes associated, which provide potential targets and new research ideas for the treatment and early detection of AML.

The high alkali content of alkaline accelerators has a negative influence on the late strength and durability of concrete. Further, their corrosive nature is harmful to the skin of construction personnel, posing safety concerns. Therefore, the development of alkali-free accelerators has gained interest, especially in shotcrete-based constructions. The production process of aluminum-sulfate-based alkali-free accelerators is simple and less exothermic, with no negative impact on the later strength of concrete, aspects that are widely recognized and very important in construction. However, their high sulfate content may have a significant impact on the durability of concrete; therefore, reducing the sulfate content plays an important role in enhancing the durability of concrete. In this study, an alkali-free liquid accelerator was synthesized by replacing aluminum sulfate with aluminum formate, which effectively reduced the sulfate content. Experiments were performed on concrete samples in which aluminum sulfate was replaced with aluminum formate at different levels. The results showed that the formate and 3CaO·Al _2 O _3 (C _3 A) of the alkali-free liquid accelerator prepared from aluminum formate form calcium aluminate, similar to the ettringite phase. The formate promoted the dissolution of Ca _3 SiO _5 (C _3 S), thus accelerating the hydration of concrete. Meanwhile, aluminum ions hydrolyzed by aluminum formate also participated in the reaction, resulting in the dual participation of cations and anions in hydration, leading to a synergistic effect with aluminum sulfate.

Although numerous recent studies have shown the importance of polymeric microfibrous extracellular matrices (ECMs) in maintaining cell behaviors and functions, the mechanistic nexus between ECMs and intracellular activities is largely unknown. Nevertheless, this knowledge will be critical in understanding and treating diseases with ECM remodeling. Therefore, we present our findings that ECM microstructures could regulate intracellular amino acid levels in liver cells mechanistically through integrin β1. Amino acids were studied because they are the fundamental blocks for protein synthesis and metabolism, two vital functions of liver cells. Two ECM conditions, flat and microfibrous, were prepared and studied. In addition to characterizing cell growth, albumin production, urea synthesis, and cytochrome p450 activity, we found that the microfibrous ECM generally upregulated the intracellular amino acid levels. Further explorations showed that cells on the flat substrate expressed more integrin β1 than cells on the microfibers. Moreover, after partially blocking integrin β1 in cells on the flat substrate, the intracellular amino acid levels were restored, strongly supporting integrin β1 as the linking mechanism. This is the first study to report that a non-biological polymer matrix could regulate intracellular amino acid patterns through integrin. The results will help with future therapy development for liver diseases with ECM changes (e.g., fibrosis).