Genome-wide analysis of the U-box E3 ligases gene family in potato (Solanum tuberosum L.) and overexpress StPUB25 enhance drought tolerance in transgenic Arabidopsis.

BACKGROUND: Plant U-box (PUB) E3 ubiquitin ligases have vital effects on various biological processes. Therefore, a comprehensive and systematic identification of the members of the U-box gene family in potato will help to understand the evolution and function of U-box E3 ubiquitin ligases in plants. RESULTS: This work identified altogether 74 PUBs in the potato (StPUBs) and examined their gene structures, chromosomal distributions, and conserved motifs. There were seventy-four StPUB genes on ten chromosomes with diverse densities. As revealed by phylogenetic analysis on PUBs within potato, Arabidopsis, tomato (Solanum lycopersicum), cabbage (Brassica oleracea), rice (Oryza sativa), and corn (Zea mays), were clustered into eight subclasses (C1-C8). According to synteny analysis, there were 40 orthologous StPUB genes to Arabidopsis, 58 to tomato, 28 to cabbage, 7 to rice, and 8 to corn. In addition, RNA-seq data downloaded from PGSC were utilized to reveal StPUBs' abiotic stress responses and tissue-specific expression in the doubled-monoploid potato (DM). Inaddition, we performed RNA-seq on the 'Atlantic' (drought-sensitive cultivar, DS) and the 'Qingshu NO.9' (drought-tolerant cultivar, DT) in early flowering, full-blooming, along with flower-falling stages to detect genes that might be involved in response to drought stress. Finally, quantitative real-time PCR (qPCR) was carried out to analyze three candidate genes for their expression levels within 100 mM NaCl- and 10% PEG 6000 (w/v)-treated potato plantlets for a 24-h period. Furthermore, we analyzed the drought tolerance of StPUB25 transgenic plants and found that overexpression of StPUB25 significantly increased peroxidase (POD) activity, reduced ROS (reactive oxygen species) and MDA (malondialdehyde) accumulation compared with wild-type (WT) plants, and enhancing drought tolerance of the transgenic plants. CONCLUSION: In this study, three candidate genes related to drought tolerance in potato were excavated, and the function of StPUB25 under drought stress was verified. These results should provide valuable information to understand the potato StPUB gene family and investigate the molecular mechanisms of StPUBs regulating potato drought tolerance.

RBBP7, regulated by SP1, enhances the Warburg effect to facilitate the proliferation of hepatocellular carcinoma cells via PI3K/AKT signaling.

BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by aggressive progression and elevated mortality rates. This study aimed to investigate the regulatory effects of RBBP7 on HCC pathogenesis and the underlying mechanisms. METHODS: The expression and clinical feature of RBBP7 were evaluated using bioinformatics analysis and the assessment of clinical HCC samples. CCK8 and colony formation were employed to estimate cell proliferation function of RBBP7. Aerobic glycolysis levels of RBBP7 were evaluated by measuring ATP levels, lactic acid production, glucose uptake capacity, and the expression of relevant enzymes (PFKM, PKM2, and LDHA). The phosphorylation levels in PI3K/AKT signaling were measured by western blotting. The regulatory effect of transcription factors of specificity protein 1 (SP1) on RBBP7 mRNA expression was confirmed in dual-luciferase reporter assays and chromatin immunoprecipitation experiments. The proliferation- and glycolysis-associated proteins were assessed using immunofluorescence staining in vivo. RESULTS: We found that RBBP7 is expressed at high levels in HCC and predicts poor survival. Functional assays showed that RBBP7 promoted HCC proliferation and glycolysis. Mechanistically, it was demonstrated that RBBP7 activates the PI3K/AKT pathway, a crucial pathway in glycolysis, contributing to the progression of HCC. The outcomes of the dual-luciferase assay further confirmed that SP1 is capable of activating the promoter of RBBP7. CONCLUSIONS: RBBP7, which is up-regulated by SP1, promotes HCC cell proliferation and glycolysis through the PI3K/AKT pathway. The findings of this study suggest that RBBP7 is a potential biomarker for HCC.

High-resolution myelin-water fraction and quantitative relaxation mapping using 3D ViSTa-MR fingerprinting.

PURPOSE: This study aims to develop a high-resolution whole-brain multi-parametric quantitative MRI approach for simultaneous mapping of myelin-water fraction (MWF), T1, T2, and proton-density (PD), all within a clinically feasible scan time. METHODS: We developed 3D visualization of short transverse relaxation time component (ViSTa)-MRF, which combined ViSTa technique with MR fingerprinting (MRF), to achieve high-fidelity whole-brain MWF and T1/T2/PD mapping on a clinical 3T scanner. To achieve fast acquisition and memory-efficient reconstruction, the ViSTa-MRF sequence leverages an optimized 3D tiny-golden-angle-shuffling spiral-projection acquisition and joint spatial-temporal subspace reconstruction with optimized preconditioning algorithm. With the proposed ViSTa-MRF approach, high-fidelity direct MWF mapping was achieved without a need for multicompartment fitting that could introduce bias and/or noise from additional assumptions or priors. RESULTS: The in vivo results demonstrate the effectiveness of the proposed acquisition and reconstruction framework to provide fast multi-parametric mapping with high SNR and good quality. The in vivo results of 1 mm- and 0.66 mm-isotropic resolution datasets indicate that the MWF values measured by the proposed method are consistent with standard ViSTa results that are 30× slower with lower SNR. Furthermore, we applied the proposed method to enable 5-min whole-brain 1 mm-iso assessment of MWF and T1/T2/PD mappings for infant brain development and for post-mortem brain samples. CONCLUSIONS: In this work, we have developed a 3D ViSTa-MRF technique that enables the acquisition of whole-brain MWF, quantitative T1, T2, and PD maps at 1 and 0.66 mm isotropic resolution in 5 and 15 min, respectively. This advancement allows for quantitative investigations of myelination changes in the brain.

DTI-MR fingerprinting for rapid high-resolution whole-brain T1 , T2 , proton density, ADC, and fractional anisotropy mapping.

PURPOSE: This study aims to develop a high-efficiency and high-resolution 3D imaging approach for simultaneous mapping of multiple key tissue parameters for routine brain imaging, including T1 , T2 , proton density (PD), ADC, and fractional anisotropy (FA). The proposed method is intended for pushing routine clinical brain imaging from weighted imaging to quantitative imaging and can also be particularly useful for diffusion-relaxometry studies, which typically suffer from lengthy acquisition time. METHODS: To address challenges associated with diffusion weighting, such as shot-to-shot phase variation and low SNR, we integrated several innovative data acquisition and reconstruction techniques. Specifically, we used M1-compensated diffusion gradients, cardiac gating, and navigators to mitigate phase variations caused by cardiac motion. We also introduced a data-driven pre-pulse gradient to cancel out eddy currents induced by diffusion gradients. Additionally, to enhance image quality within a limited acquisition time, we proposed a data-sharing joint reconstruction approach coupled with a corresponding sequence design. RESULTS: The phantom and in vivo studies indicated that the T1 and T2 values measured by the proposed method are consistent with a conventional MR fingerprinting sequence and the diffusion results (including diffusivity, ADC, and FA) are consistent with the spin-echo EPI DWI sequence. CONCLUSION: The proposed method can achieve whole-brain T1 , T2 , diffusivity, ADC, and FA maps at 1-mm isotropic resolution within 10 min, providing a powerful tool for investigating the microstructural properties of brain tissue, with potential applications in clinical and research settings.

COG3 confers the chilling tolerance to mediate OsFtsH2-D1 module in rice.

The chilling stress induced by the global climate change harms rice production, especially at seedling and booting stage, which feed half the population of the world. Although there are key quantitative trait locus genes identified in the individual stage, few genes have been reported and functioned at both stages. Utilizing chromosome segment substitution lines (CSSLs) and a combination of map-based cloning and phenotypes of the mutants and overexpression lines, we identified the major gene Chilling-tolerance in Geng/japonica rice 3 (COG3) of q chilling-tolerance at the booting and seedling stage 11 (qCTBS11) conferred chilling tolerance at both seedling and booting stages. COG3 was significantly upregulated in Nipponbare under chilling treatment compared with its expression in 93-11. The loss-of-function mutants cog3 showed a reduced chilling tolerance. On the contrary, overexpression enhanced chilling tolerance. Genome evolution and genetic analysis suggested that COG3 may have undergone strong selection in temperate japonica during domestication. COG3, a putative calmodulin-binding protein, physically interacted with OsFtsH2 at chloroplast. In cog3-1, OsFtsH2-mediated D1 degradation was impaired under chilling treatment compared with wild-type. Our results suggest that COG3 is necessary for maintaining OsFtsH2 protease activity to regulate chilling tolerance at the booting and seedling stage.

Monosaccharide transporter OsMST6 is activated by transcription factor OsERF120 to enhance chilling tolerance in rice seedlings.

Chilling stress caused by extreme weather is threatening global rice (Oryza sativa L.) production. Identifying components of the signal transduction pathways underlying chilling tolerance in rice would advance molecular breeding. Here, we report that OsMST6, which encodes a monosaccharide transporter, positively regulates the chilling tolerance of rice seedlings. The mst6 mutants showed hypersensitivity to chilling, while the OsMST6 overexpression lines were tolerant. During chilling stress, OsMST6 transported more glucose into cells to modulate sugar and ABA signal pathways. We showed that the transcription factor OsERF120 could bind to the DRE/CRT element of the OsMST6 promoter and activate the expression of OsMST6 to positively regulate chilling tolerance. Genetically, OsERF120 was functionally dependent on OsMST6 when promoting chilling tolerance. In summary, OsERF120 and OsMST6 form a new downstream chilling regulatory pathway in rice in response to chilling stress, providing valuable findings for molecular breeding aimed at achieving global food security.

Prokaryotic expression of soluble IFN-λ1 recombinant protein with cold-shock system.

Interferon (IFN)-λ1, a member of type III IFN, possesses unique antiviral, anti-tumor, and immune modulation properties. IFN-λ alone or combined with other drugs is considered an essential therapeutic regimen in the clinic. Obtaining high-quality, biologically-active recombinant human IFN-λ1 (rhIFN-λ1) is of great practical significance. In this study, pCold-II-IFN-λ1 expression plasmid was correctly constructed, the rhIFN-λ1 was expressed in BL21(DE3) E.coli and reached the highest level under the optimal condition of 15 °C culture temperature and at 1 µg/L IPTG induction for 12 h. The soluble rhIFN-λ1 was purified by Ni-NTA affinity chromatography. The purified rhIFN-λ1 can effectively activate the JAK1-STAT1 signaling pathway and induce the expression of a large number of interferon-stimulated genes (ISG) including ISG15, ISG54, ISG56, TRAIL, OAS1, MX1, IRF7 and IRF9. In addition, rhIFN-λ1 can effectively inhibit the growth/proliferation of cervical cancer HeLa cells in a dose-dependent pattern. Collectively, the soluble rhIFN-λ1 was successfully expressed in BL21(DE3) E.coli with the cold-shock system, and the purified rhIFN-λ1 demonstrated excellent biological activity. This study lays a solid basis for acquiring high-quality rhIFN-λ1 and its clinical application.

Optimization of welan gum extraction and purification using lysozyme and alkaline protease.

Welan gum, a natural polysaccharide produced by Sphingomonas sp. ATCC 31555, has attracted considerable attention in the scientific community due to its desirable properties. However, challenges, such as high viscosity, residual bacterial cells, carotenoids, and protein complexation, hinder the widespread application of welan gum. In this study, we established a method for the extraction and purification of welan gum using a synergistic approach with lysozyme and alkaline protease. Lysozyme hydrolysis conditions were optimized by applying response surface methodology, and the best results for bacterial cell removal were achieved at 11 000 U/g, 44 °C, and pH 9 after 3 h of treatment. Subsequently, we evaluated protein hydrolysis through computer simulation and identified alkaline protease as the most suitable enzyme. Through experimental investigations, we found that the optimal conditions for alkaline protease hydrolysis were 7500 U/g, 50 °C, pH 10, and 600 rpm. These conditions resulted in a sugar recovery rate of 76.1%, carotenoid removal rate of 89.5%, bacterial removal rate of 95.2%, and protein removal rate of 87.3% after 3 h of hydrolysis. The purified welan gum exhibited high transparency and purity. Structural characterization and antioxidant activity evaluation revealed that enzymatically purified welan gum has potential application prospects. Our study provides valuable insights into the optimal method for the enzymatic extraction and purification of welan gum. Such a method is conducive to the development of the multiple potential applications of welan gum. KEY POINTS: • A novel process for the synergistic purification of welan gum using lysozyme and alkaline protease was established. • In silico virtual digestion was employed to select the purification enzyme. • Welan gum with high transparency and purity was obtained.

Identification of a Hypoxia-Related Signature as Candidate Detector for Schizophrenia Based on Genome-Wide Gene Expression.

INTRODUCTION: Schizophrenia (SCZ), a severe neuropsychiatric disorder with high genetic susceptibility, has high rates of misdiagnosis due to the unavoidably subjective factors and heterogeneous clinical presentations. Hypoxia has been identified as an importantly risk factor that participates in the development of SCZ. Therefore, development of a hypoxia-related biomarker for SCZ diagnosis is promising. Therefore, we dedicated to develop a biomarker that could contribute to distinguishing healthy controls and SCZ patients. METHODS: GSE17612, GSE21935, and GSE53987 datasets, consisting of 97 control samples and 99 SCZ samples, were involved in our study. The hypoxia score was calculated based on the single-sample gene-set enrichment analysis using the hypoxia-related differentially expressed genes to quantify the expression levels of these genes for each SCZ patient. Patients in high-score groups were defined if their hypoxia score was in the upper half of all hypoxia scores and patients in low-score groups if their hypoxia score was in the lower half. GSEA was applied to detect the functional pathway of these differently expressed genes. CIBERSORT algorithm was utilized to evaluate the tumor-infiltrating immune cells of SCZ patients. RESULTS: In this study, we developed and validated a biomarker consisting of 12 hypoxia-related genes that could distinguish healthy controls and SCZ patients robustly. We found that the metabolism reprogramming might be activated in the patient with high hypoxia score. Finally, CIBERSORT analysis illustrated that lower composition of naive B cells and higher composition of memory B cells might be observed in low-score groups of SCZ patients. CONCLUSION: These findings revealed that the hypoxia-related signature was acceptable as a detector for SCZ, providing further insight into effective diagnosis and treatment strategies for SCZ.

Genome-Wide Identification of LOX Gene Family and Its Expression Analysis under Abiotic Stress in Potato (Solanum tuberosum L.).

The lipoxygenases (LOXs) are non-heme iron-containing dioxygenases that play an important role in plant growth and defense responses. There is scarce knowledge regarding the LOX gene family members and their involvement in biotic and abiotic stresses in potato. In this study, a total of 17 gene family members (StLOXs) in potato were identified and clustered into three subfamilies: 9-LOX type I, 13-LOX type I, and 13-LOX type II, with eleven, one, and five members in each subfamily based on phylogenetic analysis. By exploiting the RNA-seq data in the Potato Genome Sequencing Consortium (PGSC) database, the tissue-specific expressed and stress-responsive StLOX genes in double-monoploid (DM) potato were obtained. Furthermore, six candidate StLOX genes that might participate in drought and salt response were determined via qPCR analysis in tetraploid potato cultivars under NaCl and PEG treatment. Finally, the involvement in salt stress response of two StLOX genes, which were significantly up-regulated in both DM and tetraploid potato under NaCl and PEG treatment, was confirmed via heterologous expression in yeast under salt treatment. Our comprehensive analysis of the StLOX family provides a theoretical basis for the potential biological functions of StLOXs in the adaptation mechanisms of potato to stress conditions.

Comprehensive Characterization of the C3HC4 RING Finger Gene Family in Potato (Solanum tuberosum L.): Insights into Their Involvement in Anthocyanin Biosynthesis.

The C3HC4 RING finger gene (RING-HC) family is a zinc finger protein crucial to plant growth. However, there have been no studies on the RING-HC gene family in potato. In this study, 77 putative StRING-HCs were identified in the potato genome and grouped into three clusters based on phylogenetic relationships, the chromosome distribution, gene structure, conserved motif, gene duplication events, and synteny relationships, and cis-acting elements were systematically analyzed. By analyzing RNA-seq data of potato cultivars, the candidate StRING-HC genes that might participate in tissue development, abiotic stress, especially drought stress, and anthocyanin biosynthesis were further determined. Finally, a StRING-HC gene (Soltu.DM.09G017280 annotated as StRNF4-like), which was highly expressed in pigmented potato tubers was focused on. StRNF4-like localized in the nucleus, and Y2H assays showed that it could interact with the anthocyanin-regulating transcription factors (TFs) StbHLH1 of potato tubers, which is localized in the nucleus and membrane. Transient assays showed that StRNF4-like repressed anthocyanin accumulation in the leaves of Nicotiana tabacum and Nicotiana benthamiana by directly suppressing the activity of the dihydroflavonol reductase (DFR) promoter activated by StAN1 and StbHLH1. The results suggest that StRNF4-like might repress anthocyanin accumulation in potato tubers by interacting with StbHLH1. Our comprehensive analysis of the potato StRING-HCs family contributes valuable knowledge to the understanding of their functions in potato development, abiotic stress, hormone signaling, and anthocyanin biosynthesis.

COG2 negatively regulates chilling tolerance through cell wall components altered in rice.

KEY MESSAGE: Chilling-tolerant QTL gene COG2 encoded an extensin and repressed chilling tolerance by affecting the compositions of cell wall. Rice as a major crop is susceptible to chilling stress. Chilling tolerance is a complex trait controlled by multiple quantitative trait loci (QTLs). Here, we identify a QTL gene, COG2, that negatively regulates cold tolerance at seedling stage in rice. COG2 overexpression transgenic plants are sensitive to cold, whereas knockout transgenic lines enhance chilling tolerance. Natural variation analysis shows that Hap1 is a specific haplotype in japonica/Geng rice and correlates with chilling tolerance. The SNP1 in COG2 promoter is a specific divergency and leads to the difference in the expression level of COG2 between japonica/Geng and indica/Xian cultivars. COG2 encodes a cell wall-localized extensin and affects the compositions of cell wall, including pectin and cellulose, to defense the chilling stress. The results extend the understanding of the adaptation to the environment and provide an editing target for molecular design breeding of cold tolerance in rice.

Short sleep duration associated with the incidence of cardio-cerebral vascular disease: a prospective cohort study in Shanghai, China.

IMPORTANCE: Sleep duration plays an important role in predicting CCVD incidence, and have implications for reducing the burden of CCVD. However, the association between sleep duration and predicted cardio-cerebral vascular diseases (CCVD) risk remains to be fully understood. OBJECTIVE: To investigate the effects of sleep duration on the development of CCVD among Chinese community residents. DESIGN: A prospective cohort study. The baseline survey was conducted from January 2013 to July 2013. The cohort has been followed until December 31, 2016 using a combination of in-person interviews and record linkages with the vital registry of Pudong New Area, Shanghai, China. SUBJECTS: A total of 8245 Chinese community residents were initially enrolled in the cohort. Of those, 6298 underwent the follow-up examination. EXPOSURE: Self-reported sleep duration and sleep quality were obtained via the questionnaire. Sleep duration was divided into five categories: ≤5, 6, 7, 8, or ≥ 9 h per day. MAIN OUTCOME(S) AND MEASURE(S): CCVD, Coronary heart disease (CHD) and Stroke occurrence, Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Fine-Gray proportional subdistribution hazards models. RESULTS: During a median follow-up of 3.00 years (IQR 2.92-3.08), we observed 370 participants have had incident CCVD events, of whom 230 had CHDs, 169 had strokes, and 29 had both. After adjustment for relevant confounders, short sleepers (≤ 5 h) had 83% higher risk of total CCVD incidence (HR: 1.83; 95% CI: 1.32-2.54), 82% higher risk of CHD incidence (HR: 1.82; 95% CI: 1.21-2.75), and 82% higher risk of stroke incidence (HR: 1.82; 95% CI: 1.12-2.98) in contrast to the reference group (7 h). Some of these U-shaped relationships varied by age, and were more pronounced in individuals aged < 65 years. Individuals who slept ≤ 5 h per day with baseline hypertension had the highest risk of CCVD incidence (HR: 3.38, 95% CI 2.08-5.48), CHD incidence (HR: 3.11, 95% CI 1.75-5.53), and stroke incidence (HR: 4.33, 95% CI 1.90-9.86), compared with those sleep 7 h and without baseline hypertension. CONCLUSIONS: Short sleep duration is independently associated with greater incidence of CCVD, CHD and stroke.

Comparison of the prognostic value of a comprehensive set of predictors in identifying risk of metabolic-associated fatty liver disease among employed adults.

OBJECTIVE: Metabolic-associated fatty liver disease (MAFLD) is of concern in employed adults, while the crucial indicators in predicting MAFLD are understudied in this population. We aimed to investigate and compare the prediction performance of a set of indicators for MAFLD in employed adults. METHODS: A cross-sectional study recruiting 7968 employed adults was conducted in southwest China. MAFLD was assessed by abdominal ultrasonography and physical examination. Comprehensive indicators of demographics, anthropometric, lifestyle, psychological, and biochemical indicators were collected by questionnaire or physical examination. All indicators were evaluated for importance in predicting MAFLD by random forest. A prognostic model based on multivariate regression model was constructed to obtain a prognostic index. All indicators and prognostic index were compared to evaluate their prediction performance in predicting MAFLD by the receiver operating characteristic (ROC) curve, calibration plot, and Decision curve analysis (DCA). RESULTS: Triglyceride Glucose-Body Mass Index (TyG-BMI), BMI, TyG, triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C), and TG ranked the top five important indicators, and TyG-BMI performed the most accurate prediction of MAFLD according to the ROC curve, calibration plot and DCA. The area under the ROC curves (AUCs) of the five indicators were all over 0.7, with TyG-BMI (cut-off value: 218.284, sensitivity: 81.7%, specificity: 78.3%) suggesting the most sensitive and specific indicator. All five indicators showed higher prediction performance and net benefit than the prognostic model. CONCLUSION: This epidemiological study firstly compared a set of indicators to evaluate their prediction performance in predicting MAFLD risk among employed adults. Intervention targeting powerful predictors can be helpful to reduce the MAFLD risk among employed adults.

Electroencephalogram-Based Brain Connectivity Analysis in Prolonged Disorders of Consciousness.

Background: Prolonged disorders of consciousness (pDOC) are common in neurology and place a heavy burden on families and society. This study is aimed at investigating the characteristics of brain connectivity in patients with pDOC based on quantitative EEG (qEEG) and extending a new direction for the evaluation of pDOC. Methods: Participants were divided into a control group (CG) and a DOC group by the presence or absence of pDOC. Participants underwent magnetic resonance imaging (MRI) T1 three-dimensional magnetization with a prepared rapid acquisition gradient echo (3D-T1-MPRAGE) sequence, and video EEG data were collected. After calculating the power spectrum by EEG data analysis tool, DTABR ((δ + θ)/(α + ß) ratio), Pearson's correlation coefficient (Pearson r), Granger's causality, and phase transfer entropy (PTE), we performed statistical analysis between two groups. Finally, receiver operating characteristic (ROC) curves of connectivity metrics were made. Results: The proportion of power in frontal, central, parietal, and temporal regions in the DOC group was lower than that in the CG. The percentage of delta power in the DOC group was significantly higher than that in the CG, the DTABR in the DOC group was higher than that in the CG, and the value was inverted. The Pearson r of the DOC group was higher than that of CG. The Pearson r of the delta band (Z = -6.71, P < 0.01), theta band (Z = -15.06, P < 0.01), and alpha band (Z = -28.45, P < 0.01) were statistically significant. Granger causality showed that the intensity of directed connections between the two hemispheres in the DOC group at the same threshold was significantly reduced (Z = -82.43, P < 0.01). The PTE of each frequency band in the DOC group was lower than that in the CG. The PTE of the delta band (Z = -42.68, P < 0.01), theta band (Z = -56.79, P < 0.01), the alpha band (Z = -35.11, P < 0.01), and beta band (Z = -63.74, P < 0.01) had statistical significance. Conclusion: Brain connectivity analysis based on EEG has the advantages of being noninvasive, convenient, and bedside. The Pearson r of DTABR, delta, theta, and alpha bands, Granger's causality, and PTE of the delta, theta, alpha, and beta bands can be used as biological markers to distinguish between pDOC and healthy people, especially when behavior evaluation is difficult or ambiguous; it can supplement clinical diagnosis.

Repeatability and robustness of MP-GRASP T1 mapping.

PURPOSE: To demonstrate the repeatability of fast 3D T1 mapping using Magnetization-Prepared Golden-angle RAdial Sparse Parallel (MP-GRASP) MRI and its robustness to variation of imaging parameters including flip angle and spatial resolution in phantoms and the brain. THEORY AND METHODS: Multiple imaging experiments were performed to (1) assess the robustness of MP-GRASP T1 mapping to B1 inhomogeneity using a single tube phantom filled with uniform MnCl2 liquid; (2) compare the repeatability of T1 mapping between MP-GRASP and inversion recovery-based spin-echo (IR-SE; over 12 scans), using a commercial T1MES phantom; (3) evaluate the longitudinal variation of T1 estimation using MP-GRASP with varying imaging parameters, including spatial resolution, flip angle, TR/TE, and acceleration rate, using the T1MES phantom (106 scans performed over a period of 12 months); and (4) evaluate the variation of T1 estimation using MP-GRASP with varying imaging parameters in the brain (24 scans in a single visit). In addition, the accuracy of MP-GRASP T1 mapping was also validated against IR-SE by performing linear correlation and calculating the Lin's concordance correlation coefficient (CCC). RESULTS: MP-GRASP demonstrates good robustness to B1 inhomogeneity, with intra-slice variability below 1% in the single tube phantom experiment. The longitudinal variability is good both in the phantom (below 2.5%) and in the brain (below 2%) with varying imaging parameters. The T1 values estimated from MP-GRASP are accurate compared to that from the IR-SE imaging (R2 = 0.997, Lin's CCC = 0.996). CONCLUSION: MP-GRASP shows excellent repeatability of T1 estimation over time, and it is also robust to variation of different imaging parameters evaluated in this study.

ETS-1 facilitates Th1 cell-mediated mucosal inflammation in inflammatory bowel diseases through upregulating CIRBP.

BACKGROUND & AIMS: As a susceptibility gene for human inflammatory bowel diseases (IBD), how avian erythroblastosis virus E26 oncogene homolog-1 (ETS-1) modulates intestinal mucosal immune response remains unclear. Here we studied the potential roles of ETS-1 in the pathogenesis of IBD. METHODS: ETS-1 expression was examined in IBD patients. CD45RBhighCD4+ T cell-transfer colitis, dextran sulfate sodium (DSS)-induced colitis, and azomethane (AOM)/DSS-induced colitis-associated cancer (CAC) models were constructed to probe the function of ETS-1 in vivo. RNA-sequencing of CD4+ T cells from Ets-1 transgenic (Tg) mice was performed to decipher the key differentially expressed genes. Adenovirus transduction was conducted to verify the therapeutic potentials of ETS-1 in vivo. RESULTS: ETS-1 expression was significantly increased in CD4+ T cells from active IBD patients compared with healthy controls, which was upregulated by TNF-α but markedly suppressed by anti-TNF-α mAb therapy. More severe colitis was observed in Rag1-/- mice reconstituted with Ets-1TgCD45RBhighCD4+ T cells or in Ets-1 Tg mice after DSS exposure compared with controls, characterized by higher TNF-α and IFN-γ expression in inflamed colon. Ets-1 Tg mice were more prone to develop AOM/DSS-induced CAC, and bone marrow chimeras further proved that lamina propria immune cells but not intestinal epithelial cells contributed to the development of colitis. RNA-sequencing and luciferase analysis revealed cold-inducible RNA-binding protein (CIRBP) as a functional target of ETS-1 to promote Th1 cell-driven immune response. Consistently, intraperitoneal administration of adenovirus-m-cirbp-shRNA ameliorated trinitrobenzene sulfonic acid (TNBS)-induced colitis of Ets-1 Tg mice. CONCLUSIONS: Our data identify that ETS-1 is highly expressed in IBD patients and promotes Th1-driven mucosal inflammation through CIRBP. CIRBP may serve as a novel therapeutic target for treatment of human IBD.

Rapid fat-water separated T1 mapping using a single-shot radial inversion-recovery spoiled gradient recalled pulse sequence.

T1 mapping is increasingly used in clinical practice and research studies. With limited scan time, existing techniques often have limited spatial resolution, contrast resolution and slice coverage. High fat concentrations yield complex errors in Look-Locker T1 methods. In this study, a dual-echo 2D radial inversion-recovery T1 (DEradIR-T1) technique was developed for fast fat-water separated T1 mapping. The DEradIR-T1 technique was tested in phantoms, 5 volunteers and 28 patients using a 3 T clinical MRI scanner. In our study, simulations were performed to analyze the composite (fat + water) and water-only T1 under different echo times (TE). In standardized phantoms, an inversion-recovery spin echo (IR-SE) sequence with and without fat saturation pulses served as a T1 reference. Parameter mapping with DEradIR-T1 was also assessed in vivo, and values were compared with modified Look-Locker inversion recovery (MOLLI). Bland-Altman analysis and two-tailed paired t-tests were used to compare the parameter maps from DEradIR-T1 with the references. Simulations of the composite and water-only T1 under different TE values and levels of fat matched the in vivo studies. T1 maps from DEradIR-T1 on a NIST phantom (Pcomp = 0.97) and a Calimetrix fat-water phantom (Pwater = 0.56) matched with the references. In vivo T1 was compared with that of MOLLI: R comp 2 = 0.77 ; R water 2 = 0.72 . In this work, intravoxel fat is found to have a variable, echo-time-dependent effect on measured T1 values, and this effect may be mitigated using the proposed DRradIR-T1.

Malto-oligosaccharides as critical functional ingredient: a review of their properties, preparation, and versatile applications.

Malto-oligosaccharides (MOS) are α-1,4 glycosidic linked linear oligosaccharides of glucose, which have a diverse range of functional applications in the food, pharmaceutical, and other industries. They can be used to modify the physicochemical properties of foods thereby improving their quality attributes, or they can be included as prebiotics to improve their nutritional attributes. The degree of polymerization of MOS can be controlled by using specific enzymes, which means their functionality can be tuned for specific applications. In this article, we review the chemical structure, physicochemical properties, preparation, and functional applications of MOS in the food, health care, and other industries. Besides, we offer an overview for this saccharide from the perspective of prospect functional ingredient, which we feel lacks in the current literature. MOS could be expected to provide a novel promising substitute for functional oligosaccharides.

Pentraxin-3 as a predictive marker of mortality in sepsis: an updated systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to clarify the prognostic value of Pentraxin-3 (PTX3) on the mortality of patients with sepsis. METHODS: Publications published up to January 2021 were retrieved from PubMed, EMBASE, and the Cochrane library. Data from eligible cohort and case-control studies were extracted for the meta-analysis. Multivariate regression analysis was used to evaluate the correlation of the outcomes with sample size and male proportion. RESULTS: A total of 17 studies covering 3658 sepsis patients were included. PTX3 level was significantly higher in non-survivor compared to survivor patients (SMD (95% CI): -1.06 (-1.43, -0.69), P < 0.001). Increased PTX3 level was significantly associated with mortality (HR (95% CI): 2.09 (1.55, 2.81), P < 0.001). PTX3 showed good predictive capability for mortality (AUC:ES (95% CI): 0.73 (0.70, 0.77), P < 0.001). The outcome comparing PTX3 level in non-survivors vs. survivors and the outcome of the association between PTX3 and mortality were associated with sample size but not male proportion. AUC was associated with both sample size and male proportion. CONCLUSIONS: PTX3 level was significantly higher in non-survivor compared to survivor patients with sepsis. Elevated PTX3 level was significantly associated with mortality. Furthermore, the level of PTX3 might predict patient mortality.