Real-time predictive model of extrauterine growth retardation in preterm infants with gestational age less than 32 weeks.

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0-95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

The differential virulence of Fusarium strains causing corneal infections and plant diseases is associated with accessory chromosome composition.

Fusarium oxysporum is a cross-kingdom pathogen. While some strains cause disseminated fusariosis and blinding corneal infections in humans, others are responsible for devastating vascular wilt diseases in plants. To better understand the distinct adaptations of F. oxysporum to animal or plant hosts, we conducted a comparative phenotypic and genetic analysis of two strains: MRL8996 (isolated from a keratitis patient) and Fol4287 (isolated from a wilted tomato [ Solanum lycopersicum ]). In vivo infection of mouse corneas and tomato plants revealed that, while both strains cause symptoms in both hosts, MRL8996 caused more severe corneal ulceration and perforation in mice, whereas Fol4287 induced more pronounced wilting symptoms in tomato. In vitro assays using abiotic stress treatments revealed that the human pathogen MRL8996 was better adapted to elevated temperatures, whereas the plant pathogen Fol4287 was more tolerant of osmotic and cell wall stresses. Both strains displayed broad resistance to antifungal treatment, with MRL8996 exhibiting the paradoxical effect of increased tolerance to higher concentrations of the antifungal caspofungin. We identified a set of accessory chromosomes (ACs) and protein-encoding genes with distinct transposon profiles and functions, respectively, between MRL8996 and Fol4287. Interestingly, ACs from both genomes also encode proteins with shared functions, such as chromatin remodeling and post-translational protein modifications. Our phenotypic assays and comparative genomics analyses lay the foundation for future studies correlating genotype with phenotype and for developing targeted antifungals for agricultural and clinical uses. Importance: Fusarium oxysporum is a cross-kingdom fungal pathogen that infects both plants and animals. In addition to causing many devastating wilt diseases, this group of organisms was recently recognized by the World Health Organization as a high-priority threat to human health. Climate change has increased the risk of Fusarium infections, as Fusarium strains are highly adaptable to changing environments. Deciphering fungal adaptation mechanisms is crucial to developing appropriate control strategies. We performed a comparative analysis of Fusarium strains using an animal (mouse) and plant (tomato) host and in vitro conditions that mimic abiotic stress. We also performed comparative genomics analyses to highlight the genetic differences between human and plant pathogens and correlate their phenotypic and genotypic variations. We uncovered important functional hubs shared by plant and human pathogens, such as chromatin modification, transcriptional regulation, and signal transduction, which could be used to identify novel antifungal targets.

Structure-activity relationships of the intramolecular disulphide bonds in LEAP2, an antimicrobial peptide from Acrossocheilus fasciatus.

BACKGROUND: The liver-expressed antimicrobial peptide 2 (LEAP2) plays a pivotal role in the host's immune response against pathogenic microorganisms. Numerous such antimicrobial peptides have recently been shown to mitigate infection risk in fish, and studying those harboured by the economically important fish Acrossocheilus fasciatus is imperative for enhancing its immune responses against pathogenic microorganisms. In this study, we cloned and sequenced LEAP2 cDNA from A. fasciatus to examine its expression in immune tissues and investigate the structure-activity relationships of its intramolecular disulphide bonds. RESULTS: The predicted amino acid sequence of A. fasciatus LEAP2 was found to include a signal peptide, pro-domain, and mature peptide. Sequence analysis indicated that A. fasciatus LEAP2 is a member of the fish LEAP2A cluster and is closely related to Cyprinus carpio LEAP2A. A. fasciatus LEAP2 transcripts were expressed in various tissues, with the head kidney exhibiting the highest mRNA levels. Upon exposure to Aeromonas hydrophila infection, LEAP2 expression was significantly upregulated in the liver, head kidney, and spleen. A mature peptide of A. fasciatus LEAP2, consisting of two disulphide bonds (Af-LEAP2-cys), and a linear form of the LEAP2 mature peptide (Af-LEAP2) were chemically synthesised. The circular dichroism spectroscopy result shows differences between the secondary structures of Af-LEAP2 and Af-LEAP2-cys, with a lower proportion of alpha helix and a higher proportion of random coil in Af-LEAP2. Af-LEAP2 exhibited potent antimicrobial activity against most tested bacteria, including Acinetobacter guillouiae, Pseudomonas aeruginosa, Staphylococcus saprophyticus, and Staphylococcus warneri. In contrast, Af-LEAP2-cys demonstrated weak or no antibacterial activity against the tested bacteria. Af-LEAP2 had a disruptive effect on bacterial cell membrane integrity, whereas Af-LEAP2-cys did not exhibit this effect. Additionally, neither Af-LEAP2 nor Af-LEAP2-cys displayed any observable ability to hydrolyse the genomic DNA of P. aeruginosa. CONCLUSIONS: Our study provides clear evidence that linear LEAP2 exhibits better antibacterial activity than oxidised LEAP2, thereby confirming, for the first time, this phenomenon in fish.

Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives.

Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.

Switchable selectivity to electrocatalytic reduction of furfural over Cu2O-derived nanowire arrays.

Electrocatalytic reduction of biomass-derived furan compounds provides a green and sustainable approach to produce value-added fuels and chemicals. Despite the achievements in unimolecular transformation, C-C coupling which holds great promise to yield precursors for high-density fuels has not received extensive attention. Herein, we report a Cu2O-derived nanowire array material with switchable selectivity to electrocatalytic reduction of furfural depending on the electrolyte pH. Besides a high selectivity of 98.4% to furfuryl alcohol via hydrogenation at pH 9.5, the Cu2O-derived array structure also exhibits a high selectivity of 83.5% to hydrofuroin via C-C coupling at pH 14. Upon control experiments and detailed characterization of the electrodes, the array architecture is proposed to decrease the diffusion of ketyl radicals which are the key intermediates for C-C coupling. The confined diffusion results in a high local concentration of the radicals in the array and facilitates their collision for enhancing the formation of hydrofuroin.

Delineating abnormal individual structural covariance brain network organization in pediatric epilepsy with unilateral resection of visual cortex.

Although several previous studies have used resting-state functional magnetic resonance imaging and diffusion tensor imaging to report topological changes in the brain in epilepsy, it remains unclear whether the individual structural covariance network (SCN) changes in epilepsy, especially in pediatric epilepsy with visual cortex resection but with normal functions. Herein, individual SCNs were mapped and analyzed for seven pediatric patients with epilepsy after surgery and 15 age-matched healthy controls. A whole-brain individual SCN was constructed based on an automated anatomical labeling template, and global and nodal network metrics were calculated for statistical analyses. Small-world properties were exhibited by pediatric patients after brain surgery and by healthy controls. After brain surgery, pediatric patients with epilepsy exhibited a higher shortest path length, lower global efficiency, and higher nodal efficiency in the cuneus than those in healthy controls. These results revealed that pediatric epilepsy after brain surgery, even with normal functions, showed altered topological organization of the individual SCNs, which revealed residual network topological abnormalities and may provide initial evidence for the underlying functional impairments in the brain of pediatric patients with epilepsy after surgery that can occur in the future.

Medications and "Risk" of Aneurysm Rupture Based on Presentation: Setting the Record Straight.

OBJECTIVES: Studies assessing aneurysm rupture "risk" based on comparative retrospective analyses of medications taken on presentation may be subject to presentation bias. Are patients with ruptured aneurysms simply less likely to be taking medications than those with unruptured aneurysms? METHODS: A retrospective chart review was conducted among patients with treated aneurysms from June 2016 to July 2023. A step-wise comparison of demographics, clinical characteristics (rupture status), and medications taken upon presentation was performed between ruptured and unruptured cases. RESULTS: 1311 patients with intracranial aneurysms were included. The majority of patients presenting with ruptured aneurysms took no medications (68%), in contrast to 22% with unruptured aneurysms (p < 0.001). The majority of patients with unruptured aneurysms took 2-5 medications (51%), in contrast to 15% of patients with ruptured aneurysms taking 2-5 medications (p < 0.001). Twelve percent of patients with unruptured aneurysms took more than 5 medications while only 1% with ruptured aneurysms did (p < 0.001). Thirty-five different medications were associated with unruptured presentation, including all evaluated antiplatelet agents, anti-hypertensives, antacids, pulmonary inhalers, and psychiatric medications (p < 0.05); no medications were associated with rupture on presentation. CONCLUSION: One cannot derive conclusions about medications and "risk" of rupture based on analyses at time of presentation. This study identifies 35 different medications that were statistically-significantly associated with unruptured presentation; it is doubtful each are "protective" against aneurysm rupture.

The novel HLA-DPB1*05:01:20 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DPB1*05:01:20 differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 3.

The novel HLA-B*15:659 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*15:659 differs from HLA-B*15:02:01:01 by one nucleotide in exon 2.

Ketogenic diet time-dependently prevents NAFLD through upregulating the expression of antioxidant protein metallothionein-2.

BACKGROUND & AIMS: The past few decades have witnessed a rapid growth in the prevalence of nonalcoholic fatty liver disease (NAFLD). While the ketogenic diet (KD) is considered for managing NAFLD, the safety and efficacy of the KD on NAFLD has been a controversial topic. Here, we aimed to investigate the effect of KD of different durations on metabolic endpoints in mice with NAFLD and explore the underlying mechanisms. METHODS: NAFLD mice were fed with KD for 1, 2, 4 and 6 weeks, respectively. The blood biochemical indexes (blood lipids, AST, ALT and etc.) and liver fat were measured. The LC-MS/MS based proteomic analysis was performed on liver tissues. Metallothionein-2 (MT2) was knocked down with adeno-associated virus (AAV) or small interfering RNA (siRNA) in NAFLD mice and AML-12 cells, respectively. H&E, BODIPY and ROS staining were performed to examine lipid deposition and oxidative stress. Furthermore, MT2 protein levels, nucleus/cytoplasm distribution and DNA binding activity of peroxisome proliferators-activated receptors α (PPARα) were evaluated. RESULTS: KD feeding for 2 weeks showed the best improvement on NAFLD phenotype. Proteomic analysis revealed that MT2 was a key candidate for different metabolic endpoints of NAFLD affected by different durations of KD feeding. MT2 knockdown in NAFLD mice blocked the effects of 2 weeks of KD feeding on HFD-induced steatosis. In mouse primary hepatocytes and AML-12 cells, MT2 protein levels were induced by ß-hydroxybutyric acid (ß-OHB). MT2 Knockdown blunted the effects of ß-OHB on alleviating PA-induced lipid deposition. Mechanistically, 2 weeks of KD or ß-OHB treatment reduced oxidative stress and upregulated the protein levels of MT2 in nucleus, which subsequently increased its DNA binding activity and PPARα protein expression. CONCLUSIONS: Collectively, these findings indicated that KD feeding prevented NAFLD in a time dependent manner and MT2 is a potential target contributing to KD improvement on steatosis.

Functional analysis of nuclear receptor genes in molting and metamorphosis of the cigarette beetle, Lasioderma serricorne.

Nuclear receptors (NRs) are ligand-regulated transcription factors that are important for the normal growth and development of insects. However, systematic function analysis of NRs in the molting process of Lasioderma serricorne has not been reported. In this study, we identified and characterized 16 NR genes from L. serricorne. Spatiotemporal expression analysis revealed that six NRs were mainly expressed in 3-d-old 4th-instar larvae; five NRs were primarily expressed in 5-d-old adults and four NRs were predominately expressed in prepupae. All the NRs were highly expressed in epidermis, fat body and foregut. RNA interference (RNAi) experiments revealed that knockdown of 15 NRs disrupted the larva-pupa-adult transitions and caused 64.44-100 % mortality. Hematoxylin-eosin staining showed that depletion of 12 NRs prevented the formation of new cuticle and disrupted apolysis of old cuticle. Silencing of LsHR96, LsSVP and LsE78 led to newly formed cuticle that was thinner than the controls. The 20E titer and chitin content significantly decreased by 17.67-95.12 % after 15 NR dsRNA injection and the gene expression levels of 20E synthesis genes and chitin metabolism genes were significantly reduced. These results demonstrated that 15 NR genes are essential for normal molting and metamorphosis of L. serricorne by regulating 20E synthesis and chitin metabolism.

Comparative Analysis of Post-Translational Modifications of Human Serum Albumin Derived from Human Plasma and Recombinant Sources in China.

BACKGROUND: The variations in sequence, three-dimensional structure, and post-translational modifications (PTMs) of human serum albumin (HSA) are crucial for its physiological functions. This study aims to analyze and compare the disparities in PTMs between HSA derived from human plasma and genetically recombinant sources for clinical treatments in China. METHODS: Six distinct PTMs, namely acetylation, succinylation, crotonylation, phosphorylation, beta-hydroxybutyrylation, and lactylation, were identified using pan-specific antibodies via Western blot analysis. The samples, comprising human plasma-derived HSA (pHSA) from six different manufacturers and recombinant HSA (rHSA) expressed in yeast and Oryza sativa, underwent detection for various types of PTMs. Additionally, a 4D label-free quantitative proteomic analysis was performed to identify N-glycosylation and the aforementioned PTMs in both pHSA and rHSA samples. This analysis aimed to discern disparities in modification sites and levels. RESULTS: Through Western blot analysis, all six pHSA and two rHSA samples displayed positive bands for albumin (66.5 kDa) across the six PTMs. Subsequent analysis using 4D label-free quantitative proteomics revealed 25 (29) acetylated, 30 (32) succinylated, 41 (50) malonylated, 15 (23) phosphorylated, 36 (30) beta-hydroxybutyrylated, and 27 (34) lactylated modification sites in pHSA and rHSA samples, with no N-glycosylation modification sites detected. The analysis identified 1 acetylation (ALB_K160), 2 beta-hydroxybutyrylation (ALB_K569, ALB_K426), and 3 crotonylation (ALB_K264, ALB_K581, ALB_K560) specific modification sites in pHSA, as well as 3 crotonylation (ALB_K560, ALB_K562, ALB_K75), 1 succinylation (ALB_K490), and 23 phosphorylation specific modification sites in rHSA. In pHSA (rHSA), 2 (6) acetylation, 10 (12) succinylation, 0 (9) crotonylation, 1 (9) phosphorylation, 6 (0) beta-hydroxybutyrylation, and 0 (7) lactylation specific modification sites were found. Moreover, in the shared modification sites between pHSA and rHSA, pHSA exhibited up-regulation of amberylation (16:1) and beta-hydroxybutyrylation (12:2) in more sites, and up-regulation of acetylation (7:11), crotonylation (2:11), phosphorylation (1:8), and lactylation (1:14) in fewer sites compared to rHSA. CONCLUSION: In clinical practice, both pHSA and rHSA utilized in China commonly display acetylation, succinylation, crotonylation, phosphorylation, beta-hydroxybutyrylation, and lactylation. Notably, there exist distinctions in the site characteristics and modification levels of these alterations between pHSA and rHSA. Further experimental inquiries are imperative to delve into the implications of these disparities in PTMs on the biological functionality, effectiveness, and safety of pHSA and rHSA.

NSUN2 mediates distinct pathways to regulate enterovirus 71 replication.

Increasing evidences suggest that the methyltransferase NSUN2 catalyzes 5-methylcytosine (m5C) modifications on viral RNAs, which are essential for the replication of various viruses. Despite the function of m5C deposition is well characterized, other potential roles of NSUN2 in regulating viral replication remain largely unknown. In this study, the m5C modified residues catalyzed by NSUN2 on enterovirus 71 (EV71) RNAs were mapped. NSUN2, along with m5C modifications, played multiple roles during the EV71 life cycle. Functional m5C modified nucleotides increased the translational efficiency and stability of EV71 RNAs. Additionally, NSUN2 was found to target the viral protein VP1 for binding and promote its stability by inhibiting the ubiquitination. Furthermore, both viral replication and pathogenicity in mice were largely attenuated when functional m5C residues were mutated. Taken together, this study characterizes distinct pathways mediated by NSUN2 in regulating EV71 replication, and highlights the importance of its catalyzed m5C modifications on EV71 RNAs for the viral replication and pathogenicity.

Factors Influencing Seed Dormancy and Germination and Advances in Seed Priming Technology.

Seed dormancy and germination play pivotal roles in the agronomic traits of plants, and the degree of dormancy intuitively affects the yield and quality of crops in agricultural production. Seed priming is a pre-sowing seed treatment that enhances and accelerates germination, leading to improved seedling establishment. Seed priming technologies, which are designed to partially activate germination, while preventing full seed germination, have exerted a profound impact on agricultural production. Conventional seed priming relies on external priming agents, which often yield unstable results. What works for one variety might not be effective for another. Therefore, it is necessary to explore the internal factors within the metabolic pathways that influence seed physiology and germination. This review unveils the underlying mechanisms of seed metabolism and germination, the factors affecting seed dormancy and germination, as well as the current seed priming technologies that can result in stable and better germination.

Bacterial-fungal interactions and response to heavy metal contamination of soil in agricultural areas.

Introduction: Long-term heavy metal contamination of soil affects the structure and function of microbial communities. The aim of our study was to investigate the effect of soil heavy metal contamination on microorganisms and the impact of different heavy metal pollution levels on the microbial interactions. Methods: We collected soil samples and determined soil properties. Microbial diversity was analyzed in two groups of samples using high-throughput sequencing technology. Additionally, we constructed microbial networks to analyze microbial interactions. Results: The pollution load index (PLI) < 1 indicates that the area is not polluted. 1 < PLI < 2 represents moderate pollution. PLI was 1.05 and 0.14 for the heavy metal contaminated area and the uncontaminated area, respectively. Cd, Hg, Pb, Zn, and Cu were identified as the major contaminants in the contaminated area, with the contamination factors were 30.35, 11.26, 5.46, 5.19, and 2.46, respectively. The diversities and compositions of the bacterial community varied significantly between the two groups. Compared to the uncontaminated area, the co-occurrence network between bacterial and fungal species in the contaminated area was more complex. The keystone taxa of the co-occurrence network in the contaminated area were more than those in the uncontaminated area and were completely different from it. Discussion: Heavy metal concentrations played a crucial role in shaping the difference in microbial community compositions. Microorganisms adapt to long-term and moderate levels of heavy metal contamination through enhanced interactions. Bacteria resistant to heavy metal concentrations may play an important role in soils contaminated with moderate levels of heavy metals over long periods of time.

Potentially functional genetic variants in interferon regulatory factor family genes are associated with colorectal cancer survival.

Interferon regulatory factor (IRF) family genes play a critical role in colorectal cancer (CRC) development and impact patient survival. This study evaluated the influence of functional single nucleotide polymorphisms (SNPs) in IRF genes on CRC survival, including functional predictions and experimental validations. Multivariate Cox regression analysis identified three linked SNPs as significant survival predictors, with the rs141112353 T/T genotype in the 3'UTR region of IRF6 significantly associated with decreased survival (HR = 1.60, P = 6E-04). Expression quantitative trait loci (eQTL) analysis indicated that the rs141112353 TA > T alteration reduced IRF6 expression. Dual luciferase assays showed lower activity for the T allele in the presence of hsa-miR-548ap-3p. Data from The Cancer Genome Atlas (TCGA) and other databases confirmed lower IRF6 levels in CRC tissues, correlating with worse survival and inversely with M2 macrophage infiltration. In vitro, IRF6 overexpression inhibited CRC cell proliferation and M2 macrophage polarization by downregulating MIF expression. These findings suggest that the IRF6 rs141112353 TA > T variant significantly affects CRC survival, potentially by enhancing miR-548-ap-3p binding affinity.

The novel HLA-C*03:652 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*03:652 differs from the HLA-C*03:04:01:01 by one nucleotide in exon 3.

AKR1B10 expression characteristics in hepatocellular carcinoma and its correlation with clinicopathological features and immune microenvironment.

Hepatocellular carcinoma (HCC) represents a major global health threat with diverse and complex pathogenesis. Aldo-keto reductase family 1 member B10 (AKR1B10), a tumor-associated enzyme, exhibits abnormal expression in various cancers. However, a comprehensive understanding of AKR1B10's role in HCC is lacking. This study aims to explore the expression characteristics of AKR1B10 in HCC and its correlation with clinicopathological features, survival prognosis, and tumor immune microenvironment, further investigating its role and potential regulatory mechanisms in HCC. This study conducted comprehensive analyses using various bioinformatics tools and databases. Initially, differentially expressed genes related to HCC were identified from the GEO database, and the expression of AKR1B10 in HCC and other cancers was compared using TIMER and GEPIA databases, with validation of its specificity in HCC tissue samples using the HPA database. Furthermore, the relationship of AKR1B10 expression with clinicopathological features (age, gender, tumor size, staging, etc.) of HCC patients was analyzed using the TCGA database's LIHC dataset. The impact of AKR1B10 expression levels on patient prognosis was evaluated using Kaplan-Meier survival analysis and the Cox proportional hazards model. Additionally, the correlation of AKR1B10 expression with tumor biology-related signaling pathways and tumor immune microenvironment was studied using databases like GSEA, Targetscan, and others, identifying microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate AKR1B10 expression to explore potential regulatory mechanisms. Elevated AKR1B10 expression was significantly associated with gender, primary tumor size, and fibrosis stage in HCC tissues. High AKR1B10 expression indicated poor prognosis and served as an independent predictor for patient outcomes. Detailed mechanism analysis revealed a positive correlation between high AKR1B10 expression, immune cell infiltration, and pro-inflammatory cytokines, suggesting a potential DANCR-miR-216a-5p-AKR1B10 axis regulating the tumor microenvironment and impacting HCC development and prognosis. The heightened expression of AKR1B10 in HCC is not only related to significant clinical-pathological traits but may also influence HCC progression and prognosis by activating key signaling pathways and altering the tumor immune microenvironment. These findings provide new insights into the role of AKR1B10 in HCC pathogenesis and highlight its potential as a biomarker and therapeutic target.