Downregulation of Wtap causes dilated cardiomyopathy and heart failure.

RNA binding proteins have been shown to regulate heart development and cardiac diseases. However, the detailed molecular mechanisms is not known. In this study, we identified Wilms' tumor 1-associating protein (WTAP, a key regulatory protein of the m6A RNA methyltransferase complex) as a key regulator of heart function and cardiac diseases. WTAP is associated with heart development, and its expression is downregulated in both human and mice with heart failure. Cardiomyocyte-specific knockout of Wtap (Wtap-CKO) induces dilated cardiomyopathy, heart failure and neonatal death. Although WTAP deficiency in the heart decreases METTL3 (methyltransferase-like 3) protein levels, cardiomyocyte-specific overexpression of Mettl3 in Wtap-CKO mice does not rescue the phenotypes of Wtap-CKO mice. Instead, WTAP deficiency in the heart decreases chromatin accessibility in the promoter regions of Mef2a (myocyte enhancer factor-2α) and Mef2c, leading to reduced mRNA and protein levels of these genes and lower expression of their target genes. Conversely, WTAP directly binds to the promoter of the Mef2c gene and increases its promoter luciferase activity and expression. These data demonstrate that WTAP plays a key role in heart development and cardiac function by maintaining the chromatin accessibility of cardiomyocyte specific genes.

Gsw-fi: a GLM model incorporating shrinkage and double-weighted strategies for identifying cancer driver genes with functional impact.

BACKGROUND: Cancer, a disease with high morbidity and mortality rates, poses a significant threat to human health. Driver genes, which harbor mutations accountable for the initiation and progression of tumors, play a crucial role in cancer development. Identifying driver genes stands as a paramount objective in cancer research and precision medicine. RESULTS: In the present work, we propose a method for identifying driver genes using a Generalized Linear Regression Model (GLM) with Shrinkage and double-Weighted strategies based on Functional Impact, which is named GSW-FI. Firstly, an estimating model is proposed for assessing the background functional impacts of genes based on GLM, utilizing gene features as predictors. Secondly, the shrinkage and double-weighted strategies as two revising approaches are integrated to ensure the rationality of the identified driver genes. Lastly, a statistical method of hypothesis testing is designed to identify driver genes by leveraging the estimated background function impacts. Experimental results conducted on 31 The Cancer Genome Altas datasets demonstrate that GSW-FI outperforms ten other prediction methods in terms of the overlap fraction with well-known databases and consensus predictions among different methods. CONCLUSIONS: GSW-FI presents a novel approach that efficiently identifies driver genes with functional impact mutations using computational methods, thereby advancing the development of precision medicine for cancer.

CfIRF8-like interacts with the TBK1/IKKε family protein and regulates host antiviral innate immunity.

The interferon regulatory factor (IRF) family, a class of transcription factors with key functions, are important in host innate immune defense and stress response. However, further research is required to determine the functions of IRFs in invertebrates. In this study, the coding sequence of an IRF gene was obtained from the Zhikong scallop (Chlamys farreri) and named CfIRF8-like. The open reading frame of CfIRF8-like was 1371 bp long and encoded 456 amino acids. Protein domain prediction revealed a typical IRF domain in the N-terminus of the CfIRF8-like protein and a typical IRF3 domain in the C-terminus. Multiple sequence alignment confirmed the conservation of the amino acid sequences of these two functional protein domains. Phylogenetic analysis showed that CfIRF8-like clustered with mollusk IRF8 proteins and then clustered with vertebrate IRF3, IRF4, and IRF5 subfamily proteins. Quantitative real-time PCR detected CfIRF8-like mRNA in all tested scallop tissues, with the highest expression in the gills. Simultaneously, the expression of CfIRF8-like transcripts in gills was significantly induced by polyinosinic-polycytidylic acid challenge. The results of protein interaction experiments showed that CfIRF8-like could directly bind the TBK1/IKKε family protein of scallop (CfIKK2) via its N-terminal IRF domain, revealing the presence of an ancient functional TBK1/IKKε-IRF signaling axis in scallops. Finally, dual-luciferase reporter assay results showed that the overexpression of CfIRF8-like in human embryonic kidney 293T cells could specifically activate the interferon ß promoter of mammals and the interferon-stimulated response element promoter in dose-dependent manners. The findings of this preliminary analysis of the signal transduction and immune functions of scallop CfIRF8-like protein lay a foundation for an in-depth understanding of the innate immune function of invertebrate IRFs and the development of comparative immunology. The experimental results also provide theoretical support for the breeding of scallop disease-resistant strains.

Transcriptional expression analysis reveals multiple effects of nonylphenol exposure on scallop immune system.

Nonylphenol (NP) is an endocrine disruptor and environmental hormone representing alkylphenol compounds. Marine mollusks are an important source of protein for people worldwide. Many researchers have begun to study the effect of NP on marine mollusks immune system in view of its toxicity; however, the underlying molecular mechanisms require in-depth analysis. In this study, we focused on the transcriptional expression change of immune-related genes and antioxidant enzymes activities variation after NP exposure in a marine bivalve mollusk, Chlamys farreri, to explore the immunomodulatory capacity of NP in marine mollusks. We identified MAVS (Mitochondrial antiviral signaling protein), a key adaptor molecule in the RLR (RIG-I like receptor) pathway, and studied the expression of multiple immune-related genes in response to different concentrations of NP. The key genes involved in RLR/TLR (Toll like receptor) innate immune pathway, apoptosis, and cellular antioxidation mechanism were investigated. Changes in the enzymatic activities of scallop antioxidant enzymes after NP exposure were also examined. The results revealed that the genes expression and the antioxidant enzymes activities show significant changes, thus proving that NP stimulation affects the scallop immune system. Our research results demonstrate the immunomodulatory capacity of NP in marine bivalve mollusks and lay the foundation for further in-depth analysis of the molecular mechanism of NP toxicity.

Comparison of four different immunoassays and a rapid isotope-dilution liquid chromatography-tandem mass spectrometry assay for serum folate.

OBJECTIVES: Accurate measurement of serum folate is essential for the diagnosis and management of various disorders. This study aims to investigate the between-method differences of four immunoassays and a rapid isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method. METHODS: Roche Cobas (USA), Abbott Alinity i2000 (USA), Beckman Coulter Access (USA), Mindray CL-6000i (China), and the ID-LC-MS/MS method were compared using 46 human serum samples. The results were analysed by Passing-Bablok regressions and Bland-Altman plots. A bias of 13.31% based on biological variation was used as the bias criterion. RESULTS: All the within-run and total coefficients of variation (CVs) met the specification. The folate concentrations determined by all the assays were significantly different (p=0.0028). All assays had correlation coefficients over 0.97 with each other. The 95% confidence intervals (CIs) for the slope seldom contained 1 and few 95% CIs for the intercept contained 0 in the regression equations. Compared to ID-LC-MS/MS, the biases of all assays ranged from -20.91 to 13.56 nmol/L, and the mean relative biases ranged from -9.85 to 40.33%. The predicted mean relative biases at the medical decision levels rarely met the criterion. CONCLUSIONS: Assays for serum folate had good correlations with each other but lacked good agreement. The accuracy and consistency of assays for serum folate should be measured and assessed routinely. Standardization work to improve the accuracy of serum folate assays, such as the extension of traceability to reference methods or materials, calibration standardization efforts, and assay-adjusted cut-offs should be promoted.

Regulation of Tyrosinase Gene Expression by Retinoic Acid Pathway in the Pacific Oyster Crassostrea gigas.

Retinoic acid (RA) plays important roles in various biological processes in animals. RA signaling is mediated by two types of nuclear receptors, namely retinoic acid receptor (RAR) and retinoid x receptor (RXR), which regulate gene expression by binding to retinoic acid response elements (RAREs) in the promoters of target genes. Here, we explored the effect of all-trans retinoic acid (ATRA) on the Pacific oyster Crassostera gigas at the transcriptome level. A total of 586 differentially expressed genes (DEGs) were identified in C. gigas upon ATRA treatment, with 309 upregulated and 277 downregulated genes. Bioinformatic analysis revealed that ATRA affects the development, metabolism, reproduction, and immunity of C. gigas. Four tyrosinase genes, including Tyr-6 (LOC105331209), Tyr-9 (LOC105346503), Tyr-20 (LOC105330910), and Tyr-12 (LOC105320007), were upregulated by ATRA according to the transcriptome data and these results were verified by real-time quantitative polymerase chain reaction (RT-qPCR) analysis. In addition, increased expression of Tyr (a melanin-related TYR gene in C. gigas) and Tyr-2 were detected after ATRA treatment. The yeast one-hybrid assay revealed the DNA-binding activity of the RA receptors CgRAR and CgRXR, and the interaction of CgRAR with RARE present in the Tyr-2 promoter. These results provide evidence for the further studies on the role of ATRA and the mechanism of RA receptors in mollusks.

Ambient ultraviolet B radiation induced valve behavioral acclimation of Pacific oyster which resulted from the different response strategies of smooth and striated adductor muscles.

Light not only conveys image-forming vision but also has an impact on various physiological functions. In particular, ultraviolet B (UVB) radiation has the closest relationship with living organisms. For Pacific oysters (Crassostrea gigas), alteration of valve behavior is one of the most important ways responding to ambient UVB. In the present study, the response of adult C. gigas to sunlight (especially UVB) was evaluated by monitoring valve activity and further elucidated at the physiological and metabolomic levels. After exposure, the valve activity of C. gigas demonstrated flexible acclimation to the ambient conditions. The potential adjustment of osmoregulation and oxidative stress might be related to ambient UVB radiation. Mycosporine-like amino acids might contribute to the protection of C. gigas against UVB, while precursors of ß-alanine and degradation products of 5-hydroxytryptamine might adjust the contraction of the adductor muscles. The different responses of the adductor muscles (smooth and striated) were manifested in signal transduction and metabolisms of energy and nucleotide. This study not only indicated the correlation between the valve behavioral changes in oysters and light radiation, especially UVB, but illustrated the acclimation strategies of oysters to ambient light (UVB) environment.

Molecular characterization and functional analysis of a Rel gene in the Pacific oyster.

The nuclear factor-κB (NF-κB) signaling pathway plays a crucial role in regulating many physiological processes such as development, inflammation, apoptosis, cell proliferation, differentiation and immune responses. And the NF-κB/Rel family members were considered as the most important transcription factors in the NF-κB signaling pathway. In this study, we cloned a Rel homolog gene (named as CgRel2) from the Pacific oyster, Crassostrea gigas. The 2115-bp open reading frame (ORF) encodes 704 amino acids and CgRel2 possesses a conserved Rel Homology Domain (RHD) at the N-terminus. Phylogenetic analysis revealed that CgRel2 is most closely related to Pinctada fucata dorsal protein. CgRel2 transcripts are widely expressed in all tested tissues, with the highest expression observed in the labial palp and the gill. Moreover, the expression of CgRel2 is significantly upregulated after lipopolysaccharide (LPS), peptidoglycan (PGN), and polyinosinic-polycytidylic acid [poly(I:C)] challenge. CgRel2 transfection into human cell lines activated NF-κB, TNFα and oyster IL-17 (CgIL-17) reporter genes in a dose-dependent manner, while CgRel2 overexpression cannot induce ISRE (Interferon stimulation response element) reporter gene's transcriptional activity. Additionally, the results of co-immunoprecipitation showed that CgRel2 or CgRel1 could interact with oyster IκB1, IκB2 and IκB3 proteins strongly, which may be critical for the immune signaling transduction and the regulation of its immune functions. Together, these results suggest that CgRel2 could respond to pathogenic infection, participate in the immune signal transduction and activate NF-κB, TNFα and CgIL-17 reporter genes. Thus, CgRel2 could play an important role in the oyster immune system.

Systematic identification and validation of the reference genes from 60 RNA-Seq libraries in the scallop Mizuhopecten yessoensis.

BACKGROUND: Reverse transcription quantitative PCR (RT-qPCR) is widely used for gene expression analysis in various organisms. Its accuracy largely relies on the stability of reference genes, making reference gene selection a vital step in RT-qPCR experiments. However, previous studies in mollusks only focused on the reference genes widely used in vertebrates. RESULTS: In this study, we conducted the transcriptome-wide identification of reference genes in the bivalve mollusk Mizuhopecten yessoensis based on 60 transcriptomes covering early development, adult tissues and gonadal development. A total of 964, 1210 and 2097 candidate reference genes were identified, respectively, resulting in a core set of 568 genes. Functional enrichment analysis showed that these genes are significantly overrepresented in Gene Ontology (GO) terms or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to ribosomes, energy production, etc. Six genes (RS23, EF1A, NDUS4, SELR1, EIF3F, and OLA1) were selected from the candidate genes for RT-qPCR validation, together with 6 commonly used reference genes (ACT, CYTC, HEL, EF1B, GAPDH and RPL16). Stability analyses using geNorm, NormFinder and the comparative delta-Ct method revealed that the new candidate reference genes are more stable than the traditionally used genes, and ACT and CYTC are not recommended under either of the three circumstances. There was a significant correlation between the Ct of RT-qPCR and the log2(TPM) of RNA-Seq data (Ct = - 0.94 log2(TPM) + 29.67, R2 = 0.73), making it easy to estimate the Ct values from transcriptome data prior to RT-qPCR experiments. CONCLUSION: Our study represents the first transcriptome-wide identification of reference genes for early development, adult tissues, and gonadal development in the Yesso scallop and will benefit gene expression studies in other bivalve mollusks.

Expression of Cathepsin F in response to bacterial challenges in Yesso scallop Patinopecten yessoensis.

Cathepsin F is a unique papain cysteine proteinase with highly conserved structures: catalytic triad and a cystatin domain contained in the elongated N-terminal pro-region. It has been reported that cathepsin F is associated with the establishment of innate immune in several vertebrate including fish in aquaculture, but not known in bivalves. In this study, we firstly identified and characterized cathepsin F in the Yesso scallop (Patinopecten yessoensis). The protein structural and phylogenetic analyses were then conducted to determine its identity and evolutionary position. We've also investigated the expression levels of cathepsin F gene at different embryonic developmental stages, in healthy adult tissues and especially in the hemocytes and hepatopancreas after Gram-positive (Micrococcus luteus) and negative (Vibrio anguillarum) challenges using quantitative real-time PCR (qPCR). Cathepsin F was significantly up-regulated 3 h after infection of V. anguillarum in hemocytes, suggesting its participation in immune response. Our findings have provided strong evidence that cathepsin F may be a good target for enhancing the immune activity in Yesso scallop.

Characterization of three mitogen-activated protein kinases (MAPK) genes reveals involvement of ERK and JNK, not p38 in defense against bacterial infection in Yesso scallop Patinopecten yessoensis.

Mitogen-activated protein kinases (MAPKs) are protein Ser/Thr kinases that play a vital role in innate immune responses by converting extracellular stimuli into a wide range of cellular responses. Although MAPKs have been extensively studied in various vertebrates and invertebrates, our current understanding of MAPK signaling cascade in scallop is in its infancy. In this study, three MAPK genes (PyERK, PyJNK, and Pyp38) were identified from Yesso scallop Patinopecten yessoensis. The open reading frame of PyERK, PyJNK, and Pyp38 was 1104, 1227, and 1104 bp, encoding 367, 408, and 367 amino acids, respectively. Conservation in some splicing sites was revealed across the three PyMAPKs, suggesting the common descent of MAPKs genes. The expression profiles of PyMAPKs over the course of ten different developmental stages showed that they had different expression patterns. In adult scallops, PyMAPKs were primarily expressed in muscles, hemocytes, gill, and mantle. To gain insights into their role in innate immunity, we investigated their expression profiles after infection with Gram-positive bacteria (Micrococcus luteus) and Gram-negative bacteria (Vibrio anguillarum). Significant difference in gene expression was only found in PyERK and PyJNK, but not Pyp38, suggesting Pyp38 may not participate in immune response to bacterial infection. Besides, PyERK and PyJNK exhibited more drastic change against the invasion of V. anguillarum than M. luteus, suggesting they could be more sensitive to Gram-negative bacteria than Gram-positive bacteria. This study provides valuable resource for elucidating the role of MAPK signal pathway in bivalve innate immune response.

Genome-wide identification and characterization of TRAF genes in the Yesso scallop (Patinopecten yessoensis) and their distinct expression patterns in response to bacterial challenge.

The tumor necrosis factor (TNF) receptor associated factors (TRAFs) are the major signal transducers for the TNF receptor superfamily and the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) superfamily, which regulate a variety of cellular activities and innate immune responses. TRAF genes have been extensively studied in various species, including vertebrates and invertebrates. However, as one of the key component of NF-κB pathway, TRAF genes have not been systematically characterized in marine invertebrates. In this study, we identified and characterized five TRAF genes, PyTRAF2, PyTRAF3, PyTRAF4, PyTRAF6 and PyTRAF7, in the Yesso scallop (Patinopecten yessoensis). Phylogenetic and protein structural analyses were conducted to determine their identities and evolutionary relationships. In comparison with the TRAF genes from vertebrate species, the structural features were all relatively conserved in the PyTRAF genes. To gain insights into the roles of TRAF genes during scallop innate immune responses, quantitative real-time PCR was used to investigate the expression profiles in the different stages of scallop development, in the healthy adult tissues, and in the hemocytes after bacterial infection with Micrococcus luteus and Vibrio anguillarum. Based on the qRT-PCR analysis, the expression of most of the PyTRAFs was significantly induced in the acute phases (3-6 h) after infection with Gram-positive (M. luteus) and Gram-negative (V. anguillarum) bacteria, and many more dramatic changes in PyTRAFs expression were observed after V. anguillarum challenge. Notably, the strong response in the up-regulation of PyTRAF6 post-bacterial challenge was distinct from that previously reported in scallops and crabs but was similar to that of other shellfish, Echinodermata and even teleost fish. The high level expressions of PyTRAFs in the hemocytes and the gill, and their specific expression patterns after challenges provide insights into the versatile roles and responses of TRAFs in the innate immune system against Gram-negative bacterial pathogens in bivalves.

A feature-aware multimodal framework with auto-fusion for Alzheimer's disease diagnosis.

Alzheimer's disease (AD), one of the most common dementias, has about 4.6 million new cases yearly worldwide. Due to the significant amount of suspected AD patients, early screening for the disease has become particularly important. There are diversified types of AD diagnosis data, such as cognitive tests, images, and risk factors, many prior investigations have primarily concentrated on integrating only high-dimensional features and simple fusion concatenation, resulting in less-than-optimal outcomes for AD diagnosis. Therefore, We propose an enhanced multimodal AD diagnostic framework comprising a feature-aware module and an automatic model fusion strategy (AMFS). To preserve the correlation and significance features within a low-dimensional space, the feature-aware module employs a low-dimensional SHapley Additive exPlanation (SHAP) boosting feature selection as the initial step, following this analysis, diverse tiers of low-dimensional features are extracted from patients' biological data. Besides, in the high-dimensional stage, the feature-aware module integrates cross-modal attention mechanisms to capture subtle relationships among different cognitive domains, neuroimaging modalities, and risk factors. Subsequently, we integrate the aforementioned feature-aware module with graph convolutional networks (GCN) to address heterogeneous data in multimodal AD, while also possessing the capability to perceive relationships between different modalities. Lastly, our proposed AMFS autonomously learns optimal parameters for aligning two sub-models. The validation tests using two ADNI datasets show the high accuracies of 95.9% and 91.9% respectively, in AD diagnosis. The methods efficiently select features from multimodal AD data, optimizing model fusion for potential clinical assistance in diagnostics.

A novel automated multi-cycle magnetic solid-phase extraction coupled to LC-MS/MS to study the disorders of six functional B vitamins in patients with gastroenterology and hyperhomocysteinemia.

B vitamins are essential for human life and their disorders can cause a variety of diseases. Solid-phase extraction (SPE) coupled to LC-MS/MS is a preferred technique for determining multiple B vitamins, however, their complexity in real biological matrices makes it hard to achieve satisfactory recovery and accuracy when simultaneous detection. In this study, a novel automated multi-cycle magnetic SPE (MSPE) coupled to the LC-MS/MS method was established using a mixed-mode anion exchange magnetic adsorbent for the simultaneous extraction of six functional B vitamins, including methylmalonic acid, riboflavin, pantothenic acid, 4-pyridoxic acid, folic acid, and 5-methyltetrahydrofolate. After three consecutive MSPE cycles, the recoveries of all analytes were between 51.5% and 89.6%. The method exhibited excellent sensitivity and linearity, with a dynamic range of 200-fold (R > 0.99 for all analytes), exceptional accuracy (ranging between 95.4% and 105.6%) and precision (with RSDs ≤ 6.2%) without significant matrix effects or interferences. Compared to manual SPE method, the automated multi-cycle MSPE method has better feasibility and greater vitamin coverage. It shows a high correlation with the manual method for the detection of 5-methyltetrahydrofolate and folate (R > 0.99). A study of patients from the gastroenterology department showed that those undergoing surgery and those with malignancies may be at risk of folate deficiency. In addition, patients with hyperhomocystinemia had higher levels of methylmalonic acid and lower levels of 5-methyltetrahydrofolate, which correlated with homocysteine levels (R = 0.404 and -0.311, respectively) and showed dose-response relationships. This method is highly automated and cost-effective, with minimal systematic error, making it suitable for the analysis of clinical samples.

A Fully Automated Mini-Mental State Examination Assessment Model Using Computer Algorithms for Cognitive Screening.

Background: Rapidly growing healthcare demand associated with global population aging has spurred the development of new digital tools for the assessment of cognitive performance in older adults. Objective: To develop a fully automated Mini-Mental State Examination (MMSE) assessment model and validate the model's rating consistency. Methods: The Automated Assessment Model for MMSE (AAM-MMSE) was an about 10-min computerized cognitive screening tool containing the same questions as the traditional paper-based Chinese MMSE. The validity of the AAM-MMSE was assessed in term of the consistency between the AAM-MMSE rating and physician rating. Results: A total of 427 participants were recruited for this study. The average age of these participants was 60.6 years old (ranging from 19 to 104 years old). According to the intraclass correlation coefficient (ICC), the interrater reliability between physicians and the AAM-MMSE for the full MMSE scale AAM-MMSE was high [ICC (2,1)=0.952; with its 95% CI of (0.883,0.974)]. According to the weighted kappa coefficients results the interrater agreement level for audio-related items showed high, but for items "Reading and obey", "Three-stage command", and "Writing complete sentence" were slight to fair. The AAM-MMSE rating accuracy was 87%. A Bland-Altman plot showed that the bias between the two total scores was 1.48 points with the upper and lower limits of agreement equal to 6.23 points and -3.26 points. Conclusions: Our work offers a promising fully automated MMSE assessment system for cognitive screening with pretty good accuracy.

DriverGenePathway: Identifying driver genes and driver pathways in cancer based on MutSigCV and statistical methods.

Although computational methods for driver gene identification have progressed rapidly, it is far from the goal of obtaining widely recognized driver genes for all cancer types. The driver gene lists predicted by these methods often lack consistency and stability across different studies or datasets. In addition to analytical performance, some tools may require further improvement regarding operability and system compatibility. Here, we developed a user-friendly R package (DriverGenePathway) integrating MutSigCV and statistical methods to identify cancer driver genes and pathways. The theoretical basis of the MutSigCV program is elaborated and integrated into DriverGenePathway, such as mutation categories discovery based on information entropy. Five methods of hypothesis testing, including the beta-binomial test, Fisher combined p-value test, likelihood ratio test, convolution test, and projection test, are used to identify the minimal core driver genes. Moreover, de novo methods, which can effectively overcome mutational heterogeneity, are introduced to identify driver pathways. Herein, we describe the computational structure and statistical fundamentals of the DriverGenePathway pipeline and demonstrate its performance using eight types of cancer from TCGA. DriverGenePathway correctly confirms many expected driver genes with high overlap with the Cancer Gene Census list and driver pathways associated with cancer development. The DriverGenePathway R package is freely available on GitHub: https://github.com/bioinformatics-xu/DriverGenePathway.

Lipid accumulation product is an effective predictor of metabolic syndrome in non-obese women with polycystic ovary syndrome.

Objective: To explore the correlation of lipid accumulation product (LAP) with metabolic syndrome (MS) and to assess the predictive value of LAP for MS risk in polycystic ovary syndrome (PCOS) with different body mass index (BMI). Methods: A total of 242 PCOS patients and 150 controls were recruited and divided into normal-weight, overweight, and obese groups, then further divided into MS and without MS subgroups. Clinical and anthropometric variables and laboratory results were recorded. LAP was calculated from waist circumference (WC) and triglyceride using sex-specific formulae. Logistic regression analysis and receiver operating characteristic (ROC) curve were applied to determine and analyze the predictive value of LAP for MS. Results: The prevalence of MS among PCOS patients was 45.04%, which was significantly higher than that of the controls (10%). Stratified by BMI, the incidence of MS in the normal-weight, overweight, and obese PCOS groups were 15.58%, 41.43%, and 71.58%, respectively. Logistic regression analysis indicated that LAP was an independent risk factor for MS in both normal-weight and overweight groups; however, the results were not significant in the obese group. ROC curve analysis showed that LAP had an outstanding discrimination index for MS in normal-weight (AUC=0.960, cut-off value=42.5) and overweight (AUC=0.937, cut-off value=47.93) PCOS patients, with a sensitivity of 0.917/0.931 (normal-weight/overweight) and a specificity of 0.969/0.854 (normal-weight/overweight), respectively. Conclusion: Normal-weight and overweight PCOS patients also have a fairly high incidence of MS and should receive as much attention as obese patients. Compared to applying multiple clinical indicators, LAP is more convenient and facilitates acquiring early and accurate diagnoses of MS among non-obese PCOS patients using fewer MS markers.

Differentiating Alzheimer's disease from mild cognitive impairment: a quick screening tool based on machine learning.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterised by cognitive decline, behavioural and psychological symptoms of dementia (BPSD) and impairment of activities of daily living (ADL). Early differentiation of AD from mild cognitive impairment (MCI) is necessary. METHODS: A total of 458 patients newly diagnosed with AD and MCI were included. Eleven batteries were used to evaluate ADL, BPSD and cognitive function (ABC). Machine learning approaches including XGboost, classification and regression tree, Bayes, support vector machines and logical regression were used to build and verify the new tool. RESULTS: The Alzheimer's Disease Assessment Scale (ADAS-cog) word recognition task showed the best importance in judging AD and MCI, followed by correct numbers of auditory verbal learning test delay recall and ADAS-cog orientation. We also provided a selected ABC-Scale that covered ADL, BPSD and cognitive function with an estimated completion time of 18 min. The sensitivity was improved in the four models. CONCLUSION: The quick screen ABC-Scale covers three dimensions of ADL, BPSD and cognitive function with good efficiency in differentiating AD from MCI.

Identification and characterization of gonadotropin-releasing hormone (GnRH) in Zhikong scallop Chlamys farreri during gonadal development.

Gonadotropin-releasing hormone (GnRH) controls synthesis of sex steroid hormones through hypothalamic-pituitary-gonadal (HPG) axis in vertebrates. But in mollusks, research on neuroendocrine control of gonadal function, such as the function of GnRH during gonadal development is limited. In this study, we investigated the morphology and structure of the nerve ganglia of Zhikong scallop Chlamys farreri by physiological and histological observations. We also cloned the ORF and studied the expression patterns of GnRH in the scallop. Tissue expression analysis showed that GnRH was highly expressed in parietovisceral ganglion (PVG). The in situ hybridization result further confirmed that GnRH mRNA only distributed in some good-sized neurons in the posterior lobe (PL) and some pint-sized neurons in the lateral lobe (LL). In addition, by examining the expression of GnRH during gonadal development in ganglia, we found GnRH displayed higher expression in the female scallops, and showed significant high expression at the growing stage of female scallops in PVG. This study would contribute to gaining insight into the mechanism underlying reproduction regulation by GnRH in the scallop and help to provide a better understanding of reproductive neuroendocrine in mollusks.

Outer fold is sole effective tissue among three mantle folds with regard to oyster shell colour.

Molluscs constitute the second largest phylum of animals in the world, and shell colour is one of their most important phenotypic characteristics. In this study, we found among three folds on the mantle edge of oyster, only the outer fold had the same colour as the shell. Transcriptome and mantle cutting experiment indicated that the outer fold may be mainly reflected in chitin framework formation and biomineralisation. There were obvious differences in SEM structure and protein composition between the black and white shell periostraca. The black shell periostraca had more proteins related to melanin biosynthesis and chitin binding. Additionally, we identified an uncharacterized protein gene (named as CgCBP) ultra-highly expressed only in the black outer fold and confirmed its function of chitin-binding and CaCO3 precipitation promoting. RNAi also indicated that CgCBP knockdown could change the structure of shell periostracum and reduce shell pigmentation. All these results suggest that the mantle outer fold plays multiple key roles in shell periostraca bioprocessing, and shell periostracum structure affected by chitin-binding protein is functionally correlated with shell pigmentation. The investigation of oyster shell periostracum structure and shell colour will provide a better understanding in pigmentation during biological mineralisation in molluscs.