Tribbles pseudokinase 3 promoted renal fibrosis by regulating the expression of DNA damage-inducible transcript 3 in diabetic nephropathy.

Diabetic nephropathy (DN) is a severe complication of prolonged diabetes, impacting millions worldwide with an increasing incidence. This study investigates the role of tribbles pseudokinase 3 (TRIB3), a protein implicated in the progression of DN, focusing on its mechanisms underlying glomerular damage. Through analysis of the Gene Expression Omnibus (GEO) database, we identified TRIB3 among differentially expressed genes in streptozotocin (STZ)-treated C57BL/6J mice. Both in vitro and in vivo experiments were conducted to examine the effects of TRIB3 inhibition on high glucose (HG)-induced damage in podocytes and DN mouse models. The results demonstrated that TRIB3 inhibition reduced inflammatory responses and extracellular matrix (ECM) production in MPC5 cells, mediated by the downregulation of DNA damage-inducible transcript 3 (DDIT3) - a critical regulator of proinflammatory cytokine secretion and ECM synthesis. Inhibiting TRIB3 decreased inflammatory factors and ECM deposition in diabetic mice in vivo, confirming its pivotal role in DN pathogenesis. These findings indicate that TRIB3 and its interaction with DDIT3 contribute significantly to DN by promoting inflammatory cascades and ECM accumulation, presenting potential therapeutic targets for managing the disease.

Inhibition of LSD1 via SP2509 attenuated the progression of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia, pannus formation, and cartilage and bone destruction. Lysine-specific demethylase 1 (LSD1), an enzyme involved in transcriptional regulation, has an unclear role in synovial inflammation, fibroblast-like synoviocytes migration, and invasion during RA pathogenesis. In this study, we observed increased LSD1 expression in RA synovial tissues and in TNF-α-stimulated MH7A cells. SP2509, an LSD1 antagonist, directly reduced LSD1 expression and reversed the elevated levels of proteins associated with inflammation, apoptosis, proliferation, and autophagy induced by TNF-α. Furthermore, SP2509 inhibited the migratory capacity of MH7A cells, which was enhanced by TNF-α. In CIA models, SP2509 treatment ameliorated RA development, reducing the expression of pro-inflammatory cytokines and alleviating joint pathological symptoms. These findings underscore the significance of LSD1 in RA and propose the therapeutic potential of SP2509.

Preparation of Spherical δ-MnO2 Nanoflowers by One-Step Coprecipitation Method as Electrode Material for Supercapacitor.

Spherical δ-MnO2 nanoflower materials were synthesized via a facile one-step coprecipitation method through adjusting the molar ratio of KMnO4 to MnSO4. The influence of the molar ratio of the reactants on the crystal structure, morphology, and electrochemical performances was investigated. At a molar ratio of 3.3 for KMnO4 to MnSO4, the spherical δ-MnO2 nanoflowers composed of nanosheets with the highest specific surface area (228.0 m2 g-1) were obtained as electrode materials. In the conventional three-electrode system using 1 M Na2SO4 as an electrolyte, the specific capacitance of the spherical δ-MnO2 nanoflowers reached 172.3 F g-1 at a current density of 1 A g-1. Moreover, even after 5000 cycles at a current density of 5 A g-1, the GCD curves remained essentially unchanged, and the specific capacitance still retained 86.50% of the maximum value. The kinetics of the electrode reaction were preliminarily studied through the linear potential sweep technique to observe diffusion-controlled contribution toward total capacitance. For the spherical δ-MnO2 nanoflower electrode material, diffusion-controlled contribution accounted for 65.1% at low scan rates and still remained significant at high scan rates (100 mV s-1), indicating excellent utilization efficiency of the bulk phase. The as-fabricated asymmetric supercapacitor HFC-7//MnO2-3.3-ASC presented a prominent specific energy of 16.5 Wh kg-1 at the specific power of 450 W kg-1. Even when the specific power reached 9.0 kW kg-1, the energy density still retained 9.5 Wh kg-1.

Highly selective and sensitive immunoassays for flurogestone acetate analysis in goat milk: From rational hapten design and antibody production to assay development.

The preparation of high specificity and affinity antibodies is challenging due to limited information on characteristic groups of haptens in traditional design strategy. In this study, we first predicted characteristic groups of flurogestone acetate (FGA) using quantitative analysis of molecular surface combined with atomic charge distribution. Subsequently, FGA haptens were rationally designed to expose these identified characteristic groups fully. As a result, seven monoclonal antibodies were obtained with satisfactory performance, exhibiting IC50 values from 0.17 to 0.45 µg/L and negligible cross-reactivities below 1% to other 18 hormones. The antibody recognition mechanism further confirmed hydrogen bonds and hydrophobic interactions involving predicted FGA characteristic groups and specific amino acids in the antibodies contributed to their high specificity and affinity. Finally, one selective and sensitive ic-ELISA was developed for FGA determination with a detection limit as low as 0.12 µg/L, providing an efficient tool for timely monitoring of FGA in goat milk samples.

Microbial species pool-mediated diazotrophic community assembly in crop microbiomes during plant development.

Plant-associated diazotrophs strongly relate to plant nitrogen (N) supply and growth. However, our knowledge of diazotrophic community assembly and microbial N metabolism in plant microbiomes is largely limited. Here we examined the assembly and temporal dynamics of diazotrophic communities across multiple compartments (soils, epiphytic and endophytic niches of root and leaf, and grain) of three cereal crops (maize, wheat, and barley) and identified the potential N-cycling pathways in phylloplane microbiomes. Our results demonstrated that the microbial species pool, influenced by site-specific environmental factors (e.g., edaphic factors), had a stronger effect than host selection (i.e., plant species and developmental stage) in shaping diazotrophic communities across the soil-plant continuum. Crop diazotrophic communities were dominated by a few taxa (~0.7% of diazotrophic phylotypes) which were mainly affiliated with Methylobacterium, Azospirillum, Bradyrhizobium, and Rhizobium. Furthermore, eight dominant taxa belonging to Azospirillum and Methylobacterium were identified as keystone diazotrophic taxa for three crops and were potentially associated with microbial network stability and crop yields. Metagenomic binning recovered 58 metagenome-assembled genomes (MAGs) from the phylloplane, and the majority of them were identified as novel species (37 MAGs) and harbored genes potentially related to multiple N metabolism processes (e.g., nitrate reduction). Notably, for the first time, a high-quality MAG harboring genes involved in the complete denitrification process was recovered in the phylloplane and showed high identity to Pseudomonas mendocina. Overall, these findings significantly expand our understanding of ecological drivers of crop diazotrophs and provide new insights into the potential microbial N metabolism in the phyllosphere.IMPORTANCEPlants harbor diverse nitrogen-fixing microorganisms (i.e., diazotrophic communities) in both belowground and aboveground tissues, which play a vital role in plant nitrogen supply and growth promotion. Understanding the assembly and temporal dynamics of crop diazotrophic communities is a prerequisite for harnessing them to promote plant growth. In this study, we show that the site-specific microbial species pool largely shapes the structure of diazotrophic communities in the leaves and roots of three cereal crops. We further identify keystone diazotrophic taxa in crop microbiomes and characterize potential microbial N metabolism pathways in the phyllosphere, which provides essential information for developing microbiome-based tools in future sustainable agricultural production.

Generation of a highly specific recombinant full-length antibody for detecting ethirimol in fruit and environmental water.

High-performance antibodies are core reagents for highly sensitive immunoassays. Herein, based on a novel hapten, a hybridoma secreting the high-affinity anti-ethirimol monoclonal antibody (mAb-14G5F6) was isolated with an IC50 value of 1.35 µg/L and cross-reactivity below 0.20% for 13 analogs. To further address the challenge of hybridoma preservation and antibody immortalization, a recombinant full-length antibody (rAb-14G5F6) was expressed using the HEK293(F) expression system based on the mAb-14G5F6 gene. The affinity, specificity, and tolerance of rAb-14G5F6, as characterized by indirect competitive enzyme-linked immunosorbent assay and noncompetitive surface plasmon resonance, exhibited high concordance with those of mAb-14G5F6. Further immunoassays based on rAb-14G5F6 were developed for irrigation water and strawberry fruit with limits of detection of 0.0066 and 0.036 mg/kg, respectively, recoveries of 80100%, and coefficients of variation below 10%. Furthermore, homology simulation and molecular docking revealed that GLU(L40), GLY(L107), GLY(H108), and ASP(H114) play important roles in forming hydrogen bonds and pi-anion ionic bonds between rAb-14G5F6 and ethirimol, resulting in the high specificity and affinity of rAb-14G5F6 for ethirimol, with a KD of 5.71 × 10-10 mol/L. Overall, a rAb specific for ethirimol was expressed successfully in this study, laying the groundwork for rAb-based immunoassays for monitoring fungicide residues in agricultural products and the environment.

Twenty years of Gendicine® rAd-p53 cancer gene therapy: The first-in-class human cancer gene therapy in the era of personalized oncology.

Genetic mutations in TP53 contribute to human malignancies through various means. To date, there have been a variety of therapeutic strategies targeting p53, including gene therapy to restore normal p53 function, mutant p53 rescue, inhibiting the MDM2-p53 interaction, p53-based vaccines, and a number of other approaches. This review focuses on the functions of TP53 and discusses the aberrant roles of mutant p53 in various types of cancer. Recombinant human p53 adenovirus, trademarked as Gendicine, which is the first anti-tumor gene therapy drug, has made tremendous progress in cancer gene therapy. We herein discuss the biological mechanisms by which Gendicine exerts its effects and describe the clinical responses reported in clinical trials. Notably, the clinical studies suggest that the combination of Gendicine with chemotherapy and/or radiotherapy may produce more pronounced efficacy in slowing tumor growth and progression than gene therapy/chemotherapy alone. Finally, we summarize the methods of administration of recombinant human p53 adenovirus for different cancer types to provide a reference for future clinical trials.

Patient-derived pathogenic microbe deposition enhances exposure risk in pediatric clinics.

Healthcare-associated infections (HAIs) pose significant risks to pediatric patients in outpatient settings. To prevent HAIs, understanding the sources and transmission routes of pathogenic microorganisms is crucial. This study aimed to identify the sources of opportunistic bacterial pathogens (OBPs) in pediatric outpatient settings and determine their transmission routes. Furthermore, assessing the public health risks associated with the core OBPs is important. We collected 310 samples from various sites in pediatric outpatient areas and quantified the bacteria using qPCR and CFU counting. We also performed 16S rRNA gene and single-bacterial whole-genome sequencing to profile the transmission routes and antibiotic resistance characteristics of OBPs. We observed significant variations in microbial diversity and composition among sampling sites in pediatric outpatient settings, with active communication of the microbiota between linked areas. We found that the primary source of OBPs in multi-person contact areas was the hand surface, particularly in pediatric patients. Five core OBPs, Staphylococcus epidermidis, Acinetobacter baumannii, Pseudomonas aeruginosa, Streptococcus mitis, and Streptococcus oralis, were mainly derived from pediatric patients and spread into the environment. These OBPs accumulated at multi-person contact sites, resulting in high microbial diversity in these areas. Transmission tests confirmed the challenging spread of these pathogens, with S. epidermidis transferring from the patient's hand to the environment, leading to an increased abundance and emergence of related strains. More importantly, S. epidermidis isolated from pediatric patients carried more antibiotic-resistance genes. In addition, two strains of multidrug-resistant A. baumannii were isolated from both a child and a parent, confirming the transmission of the five core OBPs centered around pediatric patients and multi-person contact areas. Our results demonstrate that pediatric patients serve as a significant source of OBPs in pediatric outpatient settings. OBPs carried by pediatric patients pose a high public health risk. To effectively control HAIs, increasing hand hygiene measures in pediatric patients and enhancing the frequency of disinfection in multi-person contact areas remains crucial. By targeting these preventive measures, the spread of OBPs can be reduced, thereby mitigating the risk of HAIs in pediatric outpatient settings.

Joint associations among non-essential heavy metal mixtures and nutritional factors on glucose metabolism indexes in US adults: evidence from the NHANES 2011-2016.

Dietary intake can modify the impact of metals on human health, and is also closely related to glucose metabolism in human bodies. However, research on their interaction is limited. We used data based on 1738 adults aged ≥20 years from the National Health and Nutrition Examination Survey 2011-2016. We combined linear regression and restricted cubic splines with Bayesian kernel machine regression (BKMR) to identify metals associated with each glucose metabolism index (P < 0.05 and the posterior inclusion probabilities of BKMR >0.5) in eight non-essential heavy metals (barium, cadmium, antimony, tungsten, uranium, arsenic, lead, and thallium) and glucose metabolism indexes [fasting plasma glucose (FPG), blood hemoglobin A1c (HbA1c) and homeostatic model assessment of insulin resistance (HOMA-IR)]. We identified two pairs of metals associated with glucose metabolism indexes: cadmium and tungsten to HbA1c and barium and thallium to HOMA-IR. Then, the cross-validated kernel ensemble (CVEK) approach was applied to identify the specific nutrient group (nutrients) that interacted with the association. By using the CVEK model, we identified significant interactions between the energy-adjusted diet inflammatory index (E-DII) and cadmium, tungsten and barium (all P < 0.05); macro-nutrients and cadmium, tungsten and barium (all P < 0.05); minerals and cadmium, tungsten, barium and thallium (all P < 0.05); and A vitamins and thallium (P = 0.043). Furthermore, a lower E-DII, a lower intake of carbohydrates and phosphorus, and a higher consumption of magnesium seem to attenuate the positive association between metals and glucose metabolism indexes. Our finding identifying the nutrients that interact with non-essential heavy metals could provide a feasible nutritional guideline for the general population to protect against the adverse effects of non-essential heavy metals on glucose metabolism.

Malignant cell receptor-ligand subtypes guide the prediction of prognosis and personalized immunotherapy of liver cancer.

OBJECTIVE: Liver cancer is a prevalent disease with a dismal prognosis. The aim of the research is to identify subgroups based on malignant cell receptor ligand gene from single-cell RNA, which might lead to customized immunotherapy for patients with liver cancer. METHODS: Based on scRNA-seq data, we identified the receptor-ligand genes associated with prognosis and classify patients into molecular subtypes by univariate Cox regression and consensus clustering. LASSO regression was performed to construct a prognostic model, which was validated in TCGA and ICGC datasets. Immune infiltration and prediction of immunotherapy response were analyzed using ssGSEA, ESTIMATE, TIDE, and TRS score calculation. Finally, qPCR and Western blot validation of key genes and protein levels in cell lines. RESULTS: A risk model using 16-gene expression levels predicted liver cancer patients' prognosis. The RiskScore associated significantly with tumor clinical characteristics and immunity, integrated with clinicopathological features for survival prediction. Differential expression of SRXN1 was verified in hepatocellular carcinoma and normal liver cells. CONCLUSION: Our study utilizes single-cell analysis to investigate the communication between malignant cells and other cell types, identifying molecular subtypes based on malignant cell receptor ligand genes, offering new insights for the development of personalized immunotherapy and prognostic prediction models.

Immunoassays and Emerging Analytical Techniques of Fipronil and its Metabolites for Food Safety: A Review.

Fipronil, classified as a phenylpyrazole insecticide, is utilized to control agricultural, public health, and veterinary pests. Notably, its unique ecological fate involves degradation to toxic metabolites, which poses the risk of contamination in water and foodstuffs and potential human exposure through the food chain. In response to these concerns, there is a pressing need to develop analytical methodologies for detecting fipronil and its metabolites. This review provides a concise overview of the mode of action, metabolism, and toxicology of fipronil. Additionally, various detection strategies, encompassing antibody-based immunoassays and emerging analytical techniques, such as fluorescence assays based on aptamer/molecularly imprinted polymer/fluorescent probes, electrochemical sensors, and Raman spectroscopy, are thoroughly reviewed and discussed. The focus extends to detecting fipronil and its metabolites in crops, fruits, vegetables, animal-derived foods, water, and bodily fluids. This comprehensive exploration contributes valuable insights into the field, aiming to foster the development and innovation of more sensitive, rapid, and applicable analytical methods.

Motion-Aware Memory Network for Fast Video Salient Object Detection.

Previous methods based on 3DCNN, convLSTM, or optical flow have achieved great success in video salient object detection (VSOD). However, these methods still suffer from high computational costs or poor quality of the generated saliency maps. To address this, we design a space-time memory (STM)-based network that employs a standard encoder-decoder architecture. During the encoding stage, we extract high-level temporal features from the current frame and its adjacent frames, which is more efficient and practical than methods reliant on optical flow. During the decoding stage, we introduce an effective fusion strategy for both spatial and temporal branches. The semantic information of the high-level features is used to improve the object details in the low-level features. Subsequently, spatiotemporal features are methodically derived step by step to reconstruct the saliency maps. Moreover, inspired by the boundary supervision prevalent in image salient object detection (ISOD), we design a motion-aware loss that predicts object boundary motion, and simultaneously perform multitask learning for VSOD and object motion prediction. This can further enhance the model's capability to accurately extract spatiotemporal features while maintaining object integrity. Extensive experiments on several datasets demonstrate the effectiveness of our method and can achieve state-of-the-art metrics on some datasets. Our proposed model does not require optical flow or additional preprocessing, and can reach an impressive inference speed of nearly 100 FPS.

Allergenicity of alternative proteins: research hotspots, new findings, evaluation strategies, regulatory status, and future trends: a bibliometric analysis.

As the world population rises, the demand for protein increases, leading to a widening gap in protein supply. There is an unprecedented interest in the development of alternative proteins, but their allergenicity has raised consumer concerns. This review aims to highlight and correlate the current research status of allergenicity studies on alternative proteins based on previously published studies. Current research keywords, hotspots and trends in alternative protein sensitization were analyzed using a mixed-method approach that combined bibliometric analysis and literature review. According to the bibliometric analysis, current research is primarily focused on food science, agriculture, and immunology. There are significant variations in the type and amount of allergens found in alternative proteins. A significant amount of research has been focused on studying plant-based proteins and the cross-reactivity of insect proteins. The allergenicity of alternative proteins has not been studied extensively or in depth. The allergenicity of other alternative proteins and the underlying mechanisms warrant further study. In addition, the lack of a standardized allergy assessment strategy calls for additional efforts by international organizations and collaborations among different countries. This review provides new research and regulatory perspectives for the safe utilization of alternative proteins in human food systems.

The transplant rejection response involves neutrophil and macrophage adhesion-mediated trogocytosis and is regulated by NFATc3.

The anti-foreign tissue (transplant rejection) response, mediated by the immune system, has been the biggest obstacle to successful organ transplantation. There are still many enigmas regarding this process and some aspects of the underlying mechanisms driving the immune response against foreign tissues remain poorly understood. Here, we found that a large number of neutrophils and macrophages were attached to the graft during skin transplantation. Furthermore, both types of cells could autonomously adhere to and damage neonatal rat cardiomyocyte mass (NRCM) in vitro. We have demonstrated that Complement C3 and the receptor CR3 participated in neutrophils/macrophages-mediated adhesion and damage this foreign tissue (NRCM or skin grafts). We have provided direct evidence that the damage to these tissues occurs by a process referred to as trogocytosis, a damage mode that has never previously been reported to directly destroy grafts. We further demonstrated that this process can be regulated by NFAT, in particular, NFATc3. This study not only enriches an understanding of host-donor interaction in transplant rejection, but also provides new avenues for exploring the development of novel immunosuppressive drugs which prevent rejection during transplant therapy.

Undrained shear behavior of silty sand with a constant state parameter considering initial stress anisotropy effect.

Field observations in sedimentation and erosion-prone areas indicate that most natural sand deposits may contain a certain amount of non-plastic fines and are often under anisotropic stress conditions. A series of triaxial compression tests were performed on clean and silty sand with fines content fc ranging from 0 to 20% at an initial mean effective stress of p0' = 100 kPa and varying consolidation conditions to understand the impact of initial stress anisotropy on undrained shear behavior. The results indicate that the state parameter ψ is a superior predictor for characterizing the responses of sand-fines mixtures compared to the global void ratio and relative density. A comparison of the behavior of clean and silty sand with a constant ψ (= - 0.03) confirms that the sample with 10% fc exhibits the strongest dilation and greatest shear resistance, irrespective of the consolidation conditions. It is also demonstrated that the initial stress anisotropy with a comparably higher static stress ratio ηs typically diminishes the shear strength of mixtures. However, the influence of initial stress anisotropy on soil stiffness is not unilateral. The sample consolidated to a negative ηs is stiffer than that under isotropic consolidation, while the presence of a positive ηs leads to a decrease in the secant Young's modulus.

Analysis of Factors Influencing the Duration of Early Enteral Nutrition Support in Patients Diagnosed with Acute Pancreatitis.

Objective: This study aimed to assess the current status of early enteral nutrition (EN) support among patients diagnosed with acute pancreatitis (AP) and analyze the factors influencing its duration. The findings aimed to provide guidance for the development of tailored EN support protocols for pancreatitis patients. Methods: A convenience sampling method was employed, and 51 patients diagnosed with acute pancreatitis (AP) were enrolled from the Gastroenterology Department of Zhoushan Hospital between May 2020 and June 2021. Data analysis included the categorization of patients based on their early enteral nutrition (EN) support duration, followed by thorough statistical analysis, including logistic regression, to identify the factors impacting EN duration. Results: The mean duration of early EN support among AP patients was (93.57 ± 43.29) hours. A mere 13.73% of patients initiated EN within 48 hours of admission. Upon categorizing patients by the median duration of EN support, multiple logistic regression analysis revealed several significant risk factors influencing the duration of EN in AP patients, including patient age, underlying medical conditions, severity of pancreatitis, nutritional status, and blood lipase levels (P < .05). Conclusion: The study highlights the significant influence of disease severity and patients' functional status on the duration of early EN support in AP cases. It emphasizes the importance of a comprehensive patient assessment by medical professionals to determine the optimal timing for initiating EN support.

Mitochondrial Regulation of Macrophages in Innate Immunity and Diverse Roles of Macrophages During Cochlear Inflammation.

Macrophages are essential components of the innate immune system and constitute a non-specific first line of host defense against pathogens and inflammation. Mitochondria regulate macrophage activation and innate immune responses in various inflammatory diseases, including cochlear inflammation. The distribution, number, and morphological characteristics of cochlear macrophages change significantly across different inner ear regions under various pathological conditions, including noise exposure, ototoxicity, and age-related degeneration. However, the exact mechanism underlying the role of mitochondria in macrophages in auditory function remains unclear. Here, we summarize the major factors and mitochondrial signaling pathways (e.g., metabolism, mitochondrial reactive oxygen species, mitochondrial DNA, and the inflammasome) that influence macrophage activation in the innate immune response. In particular, we focus on the properties of cochlear macrophages, activated signaling pathways, and the secretion of inflammatory cytokines after acoustic injury. We hope this review will provide new perspectives and a basis for future research on cochlear inflammation.

Clinical features and demographic characteristics of gestational trophoblastic neoplasia: Single center experience and the SEER database.

The aim of this study was to analyze the clinical features and demographic characteristics of gestational trophoblastic neoplasia (GTN) patients, specifically choriocarcinoma (CC), placental site trophoblastic tumour (PSTT), and epithelioid trophoblastic tumor (ETT). We utilized data from a local hospital and the SEER database, as well as survival outcomes of CC in SEER database. Additionally, we used multiple risk factors to create a prognostic nomogram model for CC patients. The study included GTN patients from the SEER database between 1975 and 2016 as well as those from the First Affiliated Hospital of Xi 'an Jiaotong University between January 2005 and May 2022. Related factors of patients were compared using the chi-square (χ2) or Fisher's exact test. For assessing overall survival we employed the Kaplan-Meier method and log-rank test. To construct the nomogram, we used Cox regression. Statistically significant differences were found between CC and PSTT/ETT patients in terms of surgery in local hospital, as well as age and year of diagnosis in the SEER database. Moreover, significant differences were observed between low and high (HR) /ultra-high risk (UHR) groups regarding FIGO stage, surgery and chief complaint at the local hospital, and FIGO stage, surgery and unemployment in the SEER database. The Cox regression analysis confirmed that age, race, surgery, marital status, FIGO stage, and unemployment were correlated with CC prognosis. Furthermore, the analysis showed that patients aged 40 years or older and those with FIGO Ⅲ/Ⅳ were independent prognostic factors of CC. The study indicates that atypical symptoms or signs may be the main reasons for HR /UHR patients to seek medical treatment. Therefore, providing multidisciplinary care is recommended for CC patients experiencing psychological distress due to unfavorable marital status or unemployment.

Effect of hypoglycemia on cognitive performance in older patients with diabetes: A meta-analysis.

GOALS: The goal of this study was to use meta-analysis to compile information from various studies to investigate the existence and severity of cognitive impairment in elderly diabetes patients who have hypoglycemic episodes. MATERIALS AND TECHNIQUES: For research studies on the relationship between hypoglycemia and cognitive decline or dementia in persons older than 45 years, we searched the PubMed, EMBASE, Cochrane Library, CNKI, WanFang, CBM and VIP databases for the period 1989 to 2022. We conducted random effects inverse variance on the meta-analysis and used the I2 statistic to assess heterogeneity. RESULT: We selected 44 of the 518 studies we retrieved, 7 being appropriate for meta-analysis. Six thousand and forty-five individuals were involved in total. Both types of older diabetic patients with hypoglycemia performed considerably worse on tests of general intelligence than control participants (standardized mean difference, 0.58; 95% CI, 0.88-0.28). Also, elderly type-2 diabetes patients with hypoglycemic episodes had significantly worse memory performance (standardized mean difference, 0.19; 95% CI, 0.29-0.09). Additionally, we found that older type-2 diabetes patients with hypoglycemia had significantly poorer psychomotor function than those without hypoglycemia (standardized mean difference, 0.51; 95% CI, 0.38-0.63).

A novel short-type peptidoglycan recognition protein with unique polysaccharide recognition specificity in sea cucumber, Apostichopus japonicus.

Pattern recognition receptors (PRRs) are the first line of immune defense in invertebrates against pathogen infection; they recognize pathogens and transmit signals to downstream immune pathways. Among these, peptidoglycan recognition proteins (PGRPs) are an important family in invertebrates that generally comprise of complicated isoforms. A comprehensive understanding of PGRPs in evolutionarily and economically important marine invertebrates, such as the sea cucumber, Apostichopus japonicus, is crucial. Previous studies have identified two PGRPs in sea cucumber, AjPGRP-S and AjPGRP-S1, and another novel short-type PGRP, AjPGRP-S3, was additionally identified here. The full-length cDNA sequence of AjPGRP-S3 was obtained here by PCR-RACE, followed by which showed its gene expression analyses by in situ hybridization that showed it to be relatively highly expressed in coelomocytes and tube feet. Based on an analysis of the recombinant protein, rAjPGRP-S3, a board-spectrum pathogen recognition ability was noted that covered diverse Gram-negative and -positive bacteria, and fungi. Moreover, according to the results of yeast two-hybridization, it was suggested that rAJPGRP-S3 interacted with multiple immune-related factors, including proteins involved in the complement system, extracellular matrix, vesicle trafficking, and antioxidant system. These findings prove the important functions of AjPGRP-S3 in the transduction of pathogen signals to downstream immune effectors and help explore the functional differences in the AjPGRP isoforms.