A fluorescent probe for ultrarapid H2O2 detection during reagent-stimulated oxidative stress in cells and zebrafish.

Hydrogen peroxide(H2O2), as a reliable signaling biomolecule for oxidative stress, its accurate detection during agent-stimulated oxidative stress plays a vital role in pathological and physiological mechanism exploration for disease theranostics. It's necessary to develop an efficient method for their detection. In view of the advantages of fluorescent probes, we rationally constructed a novel fluorescent probe Compound 2 based on 4-(Bromomethyl)benzeneboronic acid pinacol ester_Herein, a small molecule fluorescent probe was fabricated using isoflore nitrile as fluorescent group, phenylboronic acid pinacol ester as the response group, to detect H2O2. The probe Compound 2 has a strong fluorescence intensity at 575 nm, indicating that the structure of the probe molecule is reasonably designed, and the Stokes shift is up to 172 nm. While the detection time is as low as 30 s and the LOD of the probe for H2O2 is as low as 3.7 µmol/L,the quantum yield is Φ = 40.31 %. It has been successfully used for imaging detection of H2O2 in HepG2 cells and zebrafish for its low toxicity. It can be found that this small molecule fluorescent probe can identify H2O2 in tumor cells significantly and efficiently, which would realize the early diagnosis of tumor.

Development of Integrated Vectors with Strong Constitutive Promoters for High-Yield Antibiotic Production in Mangrove-Derived Streptomyces.

It is important to improve the production of bioactive secondary products for drug development. The Escherichia coli-Streptomyces shuttle vector pSET152 and its derived vector pIB139 containing a strong constitutive promoter ermEp* are commonly used as integrative vectors in actinomycetes. Four new integrative vectors carrying the strong constitutive promoter kasOp*, hrdBp, SCO5768p, and SP44, respectively, were constructed and proven to be functional in different mangrove-derived Streptomyces host strains by using kanamycin resistance gene neo as a reporter. Some biosynthetic genes of elaiophylins, azalomycin Fs, and armeniaspirols were selected and inserted into these vectors to overexpress in their producers including Streptomyces sp. 219807, Streptomyces sp. 211726, and S. armeniacus DSM 43125, resulting in an approximately 1.1-1.4-fold enhancement of the antibiotic yields.

Design, Synthesis of Hydrogen Peroxide Response AIE Fluorescence Probes Based on Imidazo [1,2-a] Pyridine.

Hydrogen peroxide (H2O2), a significant member of reactive oxygen species, plays a crucial role in oxidative stress and cell signaling. Abnormal levels of H2O2 in the body can induce damage or even impair body function, leading to the development of certain diseases. Therefore, real-time monitoring of H2O2 in living cells is very important. In this work, the aggregation-induced emission fluorescence probe 2-(2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzyl) oxy) phenyl) imidazo [1,2-a] pyridine (B2) was designed and synthesized, which enables the long-term tracing of H2O2 in living cells. The addition of H2O2 to probe B2 results in a dramatic fluorescence enhancement around 500 nm. Notably, B2 can visualize both exogenous and endogenous H2O2 in living cells. The synthesis method for B2 is simple, has a high yield, and utilizes readily available materials. It exhibits advantages such as low toxicity, photostability, and good biocompatibility. Consequently, the developed fluorescent probe in this study has great potential as a reliable tool for determining H2O2 in living cells.

MANF brakes TLR4 signaling by competitively binding S100A8 with S100A9 to regulate macrophage phenotypes in hepatic fibrosis.

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6Chigh macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl4-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

TGPred: efficient methods for predicting target genes of a transcription factor by integrating statistics, machine learning and optimization.

Four statistical selection methods for inferring transcription factor (TF)-target gene (TG) pairs were developed by coupling mean squared error (MSE) or Huber loss function, with elastic net (ENET) or least absolute shrinkage and selection operator (Lasso) penalty. Two methods were also developed for inferring pathway gene regulatory networks (GRNs) by combining Huber or MSE loss function with a network (Net)-based penalty. To solve these regressions, we ameliorated an accelerated proximal gradient descent (APGD) algorithm to optimize parameter selection processes, resulting in an equally effective but much faster algorithm than the commonly used convex optimization solver. The synthetic data generated in a general setting was used to test four TF-TG identification methods, ENET-based methods performed better than Lasso-based methods. Synthetic data generated from two network settings was used to test Huber-Net and MSE-Net, which outperformed all other methods. The TF-TG identification methods were also tested with SND1 and gl3 overexpression transcriptomic data, Huber-ENET and MSE-ENET outperformed all other methods when genome-wide predictions were performed. The TF-TG identification methods fill the gap of lacking a method for genome-wide TG prediction of a TF, and potential for validating ChIP/DAP-seq results, while the two Net-based methods are instrumental for predicting pathway GRNs.

Effects of Systematic Pregnancy Management on Labor, Maternal, and Infant Outcomes in Gestational Diabetes Mellitus Patients.

Objective: To investigate the effects of systematic pregnancy management on labor and maternal and infant outcomes in gestational diabetes mellitus patients (GDM). Methods: From February 2020 to December 2021, 116 patients who were diagnosed with GDM at the first hospital of Hebei medical university were enrolled in this prospective study. According to the random number table, patients were divided into the control group (n = 58, routine nursing) and the intervention group (n = 58, systematic pregnancy management). Results: After treatment, the blood glucose levels of both groups decreased compared to that measured before treatment, and the blood glucose levels in the intervention group were lower than those in the control group (P < .05). After treatment, the lipid profile cholesterol levels of both groups decreased compared to those measured before treatment. However, the lipid profile cholesterol levels were lower in the intervention group than those in the control group (P < .05). The first, second, and third stages of labor and total labor time in the intervention group were lower than those in the control group (P < .05). The rate of natural delivery in the intervention group was higher than that in the control group, while the rate of cesarean section was lower than that in the control group (P < .05). Conclusion: Systematic pregnancy management can reduce the level of blood glucose and improve lipid metabolism in patients with GDM.

Genetic and transcriptomic dissection of host defense to Goss's bacterial wilt and leaf blight of maize.

Goss's wilt, caused by the Gram-positive actinobacterium Clavibacter nebraskensis, is an important bacterial disease of maize. The molecular and genetic mechanisms of resistance to the bacterium, or, in general, Gram-positive bacteria causing plant diseases, remain poorly understood. Here, we examined the genetic basis of Goss's wilt through differential gene expression, standard genome-wide association mapping (GWAS), extreme phenotype (XP) GWAS using highly resistant (R) and highly susceptible (S) lines, and quantitative trait locus (QTL) mapping using 3 bi-parental populations, identifying 11 disease association loci. Three loci were validated using near-isogenic lines or recombinant inbred lines. Our analysis indicates that Goss's wilt resistance is highly complex and major resistance genes are not commonly present. RNA sequencing of samples separately pooled from R and S lines with or without bacterial inoculation was performed, enabling identification of common and differential gene responses in R and S lines. Based on expression, in both R and S lines, the photosynthesis pathway was silenced upon infection, while stress-responsive pathways and phytohormone pathways, namely, abscisic acid, auxin, ethylene, jasmonate, and gibberellin, were markedly activated. In addition, 65 genes showed differential responses (up- or down-regulated) to infection in R and S lines. Combining genetic mapping and transcriptional data, individual candidate genes conferring Goss's wilt resistance were identified. Collectively, aspects of the genetic architecture of Goss's wilt resistance were revealed, providing foundational data for mechanistic studies.

The effectiveness of motivation-guided PDCA cycle nursing for self-management ability and outcomes of patients with gestational diabetes mellitus.

AIM: To explore the effectiveness of motivation-guided 'plan, do, check and action' cycle nursing for self-management ability and outcomes of patients with gestational diabetes mellitus (GDM). DESIGN: A pre- and post- comparison quasi experimental study. METHODS: Totally 108 pregnant women with GDM diagnosed and delivered in our hospital from January 2020 to April 2021 were included in this study. They were divided into study group (54 cases) and control group (54 cases). RESULTS: The score of self-management ability were significantly higher than those of control group (t-test, all p < 0.05), as well as themselves before interventions in both groups (t-test, all p < 0.05). Besides, scores of anxiety, depression, extraverted stimulus and intraverted stimulus all achieved significant reduction after interventions in study group compared with control one (t-test, all p < 0.05), as well as themselves before interventions in both groups (t-test, all p < 0.05). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Bacterium-enabled transient gene activation by artificial transcription factors for resolving gene regulation in maize.

Understanding gene regulatory networks is essential to elucidate developmental processes and environmental responses. Here, we studied regulation of a maize (Zea mays) transcription factor gene using designer transcription activator-like effectors (dTALes), which are synthetic Type III TALes of the bacterial genus Xanthomonas and serve as inducers of disease susceptibility gene transcription in host cells. The maize pathogen Xanthomonas vasicola pv. vasculorum was used to introduce 2 independent dTALes into maize cells to induced expression of the gene glossy3 (gl3), which encodes a MYB transcription factor involved in biosynthesis of cuticular wax. RNA-seq analysis of leaf samples identified, in addition to gl3, 146 genes altered in expression by the 2 dTALes. Nine of the 10 genes known to be involved in cuticular wax biosynthesis were upregulated by at least 1 of the 2 dTALes. A gene previously unknown to be associated with gl3, Zm00001d017418, which encodes aldehyde dehydrogenase, was also expressed in a dTALe-dependent manner. A chemically induced mutant and a CRISPR-Cas9 mutant of Zm00001d017418 both exhibited glossy leaf phenotypes, indicating that Zm00001d017418 is involved in biosynthesis of cuticular waxes. Bacterial protein delivery of dTALes proved to be a straightforward and practical approach for the analysis and discovery of pathway-specific genes in maize.

Click Triazole as a Linker for Pretargeting Strategies: Synthesis, Docking Investigations, Fluorescence Diagnosis, and Antibacterial Action Studies.

In this study, three compounds A1, A2, and A3 and fluorescent probes T1, T2, T3, and T4 were designed and synthesized. 1H NMR, 13C NMR, and MS characterization and elemental analysis were used to confirm A1-A3 and T1-T4. A1-A3 and T1-T4 formed diagnostic molecules by "click" reactions. A1-A3 and T1-T4 did not significantly increase cell death at concentrations of 80 µmol/L. Preliminary screening of the compounds for antibacterial activity revealed that A2 has better antibacterial activity against Agrobacterium tumefaciens. The synthesized compounds and fluorescent probes can be targeted and combined in the physiological condition to form diagnostic molecules for fluorescence detection of Agrobacterium tumefaciens. The binding sites of A1-A3 were deduced theoretically using the AutoDock Vina software docking tool. Further study of the mechanism of the antibacterial action of these compounds is likely to identify new agents against resistant bacterial strains.

Effects of preventive nursing based on quantitative evaluation on psychological state and maternal-infant outcome in patients with gestational diabetes mellitus.

OBJECTIVE: To explore the effects of preventive nursing based on quantitative evaluation on psychological state and maternal-infant outcome in patients with gestational diabetes mellitus (GDM), further, to provide a theoretical basis for the effective management of GDM patients in clinical work. METHODS: From 1 February 2020 to 1 January 2021, 118 patients with GDM presenting to our hospital were included in this retrospective cohort study. According to the type of nursing care, patients were divided into study group and control groups. The study group consisted of 59 GDM patients who were given quantitative evaluation-based preventive nursing care. The control group included 59 GDM patients who were given routine nursing care. Outcome indicators included blood glucose level, degree of social support, resilience, coping style, and maternal-infant outcomes. RESULTS: There was no significant difference between two groups in other baseline clinical characteristics (p > .05). After the intervention, fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and 2 h postprandial blood glucose (2hPBG) levels were significantly lower in the study group than that in the control group (p < .05). The scores of objective support, subjective support, and social support utilization in the study group were significantly higher than those in the control group after intervention (p < .05). The scores of optimisms, self-strengthening and tenacity in the study group were significantly less than those in the control group (p < .05). The study group confrontation score was significantly higher, and the avoidance and acceptance scores were significantly lower, compared with the control group (p < .05). The maternal-infant outcome showed that the proportions of cesarean delivery, pregnancy-induced hypertension, polyhydramnios, premature delivery, hyperbilirubinemia, and neonatal hypoglycemia in the study group were significantly lower than those in the control group (p < .05). There was no significant difference in the incidence of postpartum hemorrhage and neonatal 5-min Apgar score between the two groups (p > .05). CONCLUSIONS: In conclusion, preventive nursing based on quantitative assessment can effectively control the blood glucose level of GDM patients, improve their degree of social support, resilience, coping style, and maternal-infant outcomes, which is worthy of clinical application.

Effectiveness of multidisciplinary intervention for gestational diabetes mellitus.

OBJECTIVE: To explore the effectiveness of multidisciplinary intervention for patients with gestational diabetes mellitus (GDM). METHODS: A total of 126 patients diagnosed with GDM from January 2020 to December 2021 in our hospital were enrolled in this retrospective study. Patients were divided into the control group (conventional treatment) and the study group (adding multidisciplinary intervention). Glucose index, self-management ability, psychological status, and delivery outcomes were evaluated. RESULTS: Fasting plasma glucose (4.32 ± 0.81 mmol/L), glycosylated hemoglobin (5.47 ± 1.09%), and postprandial blood glucose (6.02 ± 1.47 mmol/L) after intervention in study group were significantly lower than those in control group (p < 0.05), as well as those before intervention (p < 0.05). The score of GDM knowledge (38.03 ± 2.76), self-management (38.93 ± 2.32), social support (17.84 ± 1.23), and belief (17.93 ± 1.09) were all significantly higher than those of control group (p < 0.05), as well as those before intervention (p < 0.05). Besides, anxiety (7.83 ± 1.59) and depression (10.29 ± 1.82) evaluation scores showed that emotional relief were significantly achieved after intervention in study group compared with control group (p < 0.05). Moreover, the incidence of postpartum hemorrhage, cesarean delivery, premature delivery, macrosomia, and neonatal hypoglycemia was also significantly improved after intervention in study group compared with control group (p < 0.05). CONCLUSIONS: Multidisciplinary intervention can effectively control blood glucose levels, adjust self-management behavior, relieve psychological disorder, reduce complications, and improve delivery outcomes of GDM patients.

Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics.

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

Chromosome-level genome assembly of a regenerable maize inbred line A188.

BACKGROUND: The maize inbred line A188 is an attractive model for elucidation of gene function and improvement due to its high embryogenic capacity and many contrasting traits to the first maize reference genome, B73, and other elite lines. The lack of a genome assembly of A188 limits its use as a model for functional studies. RESULTS: Here, we present a chromosome-level genome assembly of A188 using long reads and optical maps. Comparison of A188 with B73 using both whole-genome alignments and read depths from sequencing reads identify approximately 1.1 Gb of syntenic sequences as well as extensive structural variation, including a 1.8-Mb duplication containing the Gametophyte factor1 locus for unilateral cross-incompatibility, and six inversions of 0.7 Mb or greater. Increased copy number of carotenoid cleavage dioxygenase 1 (ccd1) in A188 is associated with elevated expression during seed development. High ccd1 expression in seeds together with low expression of yellow endosperm 1 (y1) reduces carotenoid accumulation, accounting for the white seed phenotype of A188. Furthermore, transcriptome and epigenome analyses reveal enhanced expression of defense pathways and altered DNA methylation patterns of the embryonic callus. CONCLUSIONS: The A188 genome assembly provides a high-resolution sequence for a complex genome species and a foundational resource for analyses of genome variation and gene function in maize. The genome, in comparison to B73, contains extensive intra-species structural variations and other genetic differences. Expression and network analyses identify discrete profiles for embryonic callus and other tissues.

Characterization, Genetic Analyses, and Identification of QTLs Conferring Metabolic Resistance to a 4-Hydroxyphenylpyruvate Dioxygenase Inhibitor in Sorghum (Sorghum bicolor).

Postemergence grass weed control continues to be a major challenge in grain sorghum [Sorghum bicolor (L.) Moench], primarily due to lack of herbicide options registered for use in this crop. The development of herbicide-resistant sorghum technology to facilitate broad-spectrum postemergence weed control can be an economical and viable solution. The 4-hydroxyphenylpyruvate dioxygenase-inhibitor herbicides (e.g., mesotrione or tembotrione) can control a broad spectrum of weeds including grasses, which, however, are not registered for postemergence application in sorghum due to crop injury. In this study, we identified two tembotrione-resistant sorghum genotypes (G-200, G-350) and one susceptible genotype (S-1) by screening 317 sorghum lines from a sorghum association panel (SAP). These tembotrione-resistant and tembotrione-susceptible genotypes were evaluated in a tembotrione dose-response [0, 5.75, 11.5, 23, 46, 92 (label recommended dose), 184, 368, and 736 g ai ha-1] assay. Compared with S-1, the genotypes G-200 and G-350 exhibited 10- and seven fold more resistance to tembotrione, respectively. To understand the inheritance of tembotrione-resistant trait, crosses were performed using S-1 and G-200 or G-350 to generate F1 and F2 progeny. The F1 and F2 progeny were assessed for their response to tembotrione treatment. Genetic analyses of the F1 and F2 progeny demonstrated that the tembotrione resistance in G-200 and G-350 is a partially dominant polygenic trait. Furthermore, cytochrome P450 (CYP)-inhibitor assay using malathion and piperonyl butoxide suggested possible CYP-mediated metabolism of tembotrione in G-200 and G-350. Genotype-by-sequencing based quantitative trait loci (QTL) mapping revealed QTLs associated with tembotrione resistance in G-200 and G-350 genotypes. Overall, the genotypes G-200 and G-350 confer a high level of metabolic resistance to tembotrione and controlled by a polygenic trait. There is an enormous potential to introgress the tembotrione resistance into breeding lines to develop agronomically desirable sorghum hybrids.

Physicochemical Properties, Antioxidant and Antidiabetic Activities of Polysaccharides from Quinoa (Chenopodium quinoa Willd.) Seeds.

Quinoa is known for its rich nutrients and bioactive compounds. In order to elucidate the preliminary structural characteristics and biological activity of polysaccharides from quinoa (QPs), five crude polysaccharides (QPE50, QPE60, QPE70, QPE80 and QPE90) were successively fractionated by gradient ethanol, and their physicochemical properties, antioxidant and antidiabetic activities were analyzed. The results implied that their total sugar contents were 52.82%, 63.69%, 67.15%, 44.56%, and 41.01%, and their weight-average molecular weights were 13,785 Da, 6489 Da, 4732 Da, 3318 Da, and 1960 Da, respectively. Glucose was a predominantly monosaccharide in these QPs, which together in QPE50, QPE60, QPE70, QPE80, and QPE90, respectively, made up 94.37%, 87.92%, 92.21%, 100%, and 100% of the total polysaccharide. Congo red test showed that all five QPs contained triple-helix structure. The Fourier transform-infrared spectroscopy (FT-IR) and X-ray diffractometry (XRD) results suggest that the QPs form a semi-crystalline polymer constituted typical functional groups of polysaccharide including CO, CH and OH. The thermogravimetric analysis (TGA) of QPs showed that weight loss was at about 200 °C and 320 °C. The observation from scanning electron microscope (SEM) and atomic force microscope (AFM) image indicated that the morphology of QPs exhibited spherical shape. Antioxidant and antidiabetic assay exhibited that all five QPs samples had certain antioxidant and antidiabetic activities, and QPE90 showed the best antioxidant and antidiabetic activity. Overall, QPs present a promising natural source of food antioxidants and antidiabetic agents.

The Effects of Dietary Nutrition on Sleep and Sleep Disorders.

Sleep disorder significantly affects the life quality of a large number of people but is still an underrecognized disease. Dietary nutrition is believed to play a significant impact on sleeping wellness. Many nutritional supplements have been used trying to benefit sleep wellness. However, the relationship between nutritional components and sleep is complicated. Nutritional factors vary dramatically with different diet patterns and depend significantly on the digestive and metabiotic functions of each individual. Moreover, nutrition can profoundly affect the hormones and inflammation status which directly or indirectly contribute to insomnia. In this review, we summarized the role of major nutritional factors, carbohydrates, lipids, amino acids, and vitamins on sleep and sleep disorders and discussed the potential mechanisms.

The Roles of Monocyte and Monocyte-Derived Macrophages in Common Brain Disorders.

The brain is the most important and complex organ in most living creatures which serves as the center of the nervous system. The function of human brain includes controlling of the motion of the body and different organs and maintaining basic homeostasis. The disorders of the brain caused by a variety of reasons often severely impact the patients' normal life or lead to death in extreme cases. Monocyte is an important immune cell which is often recruited to the brain in a number of brain disorders. However, the role of monocytes may not be simply described as beneficial or detrimental. It significantly depends on the disease models and the stages of disease progression. In this review, we summarized the current knowledge about the role of monocytes and monocyte-derived macrophages during several common brain disorders. Major focuses include ischemic stroke, Alzheimer's disease, multiple sclerosis, intracerebral hemorrhage, and insomnia. The recruitment, differentiation, and function of monocyte in these diseases are reviewed.

Effect of two different colloid priming strategies in infants weighing less than 5 kg undergoing on-pump cardiac surgeries.

Our aim was to explore the effect of two different priming strategies (artificial colloid only vs. artificial colloid combined with human serum albumin) on the prognosis of children weighing less than 5 kg undergoing on-pump congenital heart disease (CHD) surgery. A total of 65 children weighing less than 5 kg who underwent on-pump CHD surgery in our hospital from September 2016 to December 2017 were enrolled in this study. The children were randomly divided into two groups: artificial colloid priming group (AC group, n = 33) and artificial colloid combined albumin priming group (ACA group, n = 32). The primary clinical endpoint was the peri-CPB colloid osmotic pressure (COP). Secondary clinical endpoints included perioperative blood product and hemostatic drug consumption, postoperative renal function, coagulation function, postoperative renal function, and postoperative recovery parameters. COP values were not significant in the priming system as well as peri-CPB time points between the two groups (P > .05). Platelet consumption in the AC group was significantly lower than that in the ACA group (P < .05). There were no significant differences in the use of other blood products and hemostatic drugs as well as perioperative coagulation parameters between the two groups (P > .05). Postoperative length of stay in the AC group was significantly lower than that in the ACA group (P < .05). There were no significant differences in mortality, postoperative mechanical ventilation time, ICU time, and perioperative adverse events (including postoperative AKI) occurrences between the two groups (P > .05). In the on-pump cardiac surgeries of patients weighing less than 5 kg, total colloidal priming would not affect peri-CPB COP values, postoperative coagulation function, and blood products consumption. Total artificial colloidal priming strategy is feasible in low-weight patients.

Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis.

Impairment of glucose (Glu) uptake and storage by skeletal muscle is a prime risk factor for the development of metabolic diseases. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a highly abundant RNA-binding protein that has been implicated in diverse cellular functions. The aim of this study was to investigate the function of hnRNP A1 on muscle tissue insulin sensitivity and systemic Glu homeostasis. Our results showed that conditional deletion of hnRNP A1 in the muscle gave rise to a severe insulin resistance phenotype in mice fed a high-fat diet (HFD). Conditional knockout mice fed a HFD showed exacerbated obesity, insulin resistance, and hepatic steatosis. In vitro interference of hnRNP A1 in C2C12 myotubes impaired insulin signal transduction and inhibited Glu uptake, whereas hnRNP A1 overexpression in C2C12 myotubes protected against insulin resistance induced by supraphysiological concentrations of insulin. The expression and stability of glycogen synthase (gys1) mRNA were also decreased in the absence of hnRNP A1. Mechanistically, hnRNP A1 interacted with gys1 and stabilized its mRNA, thereby promoting glycogen synthesis and maintaining the insulin sensitivity in muscle tissue. Taken together, our findings are the first to show that reduced expression of hnRNP A1 in skeletal muscle affects the metabolic properties and systemic insulin sensitivity by inhibiting glycogen synthesis.