Single-Anion Conductive Solid-State Electrolytes with Hierarchical Ionic Highways for Flexible Zinc-Air Battery.

Flexible zinc-air batteries are leading power sources for next-generation smart wearable electronics. However, flexible zinc-air batteries suffer from the highly-corrosive safety risk and limited lifespan due to the absence of reliable solid-state electrolytes (SSEs). Herein, a single-anion conductive SSE with high-safety is constructed by incorporating a highly amorphous dual-cation ionomer into a robust hybrid matrix of functional carbon nanotubes and polyacrylamide polymer. The as-fabricated SSE obtains dual-penetrating ionomer-polymer networks and hierarchical ionic highways, which contribute to mechanical robustness with 1200% stretchability, decent water uptake and retention, and superhigh ion conductivity of 245 mS·cm-1 and good Zn anode reversibility. Remarkably, the flexible solid-state zinc-air batteries delivers a high specific capacity of 764 mAh·g-1 and peak power density of 152 mW·cm-2 as well as sustains excellent cycling stability for 1050 cycles (350 hours. This work offers a new paradigm of OH- conductors and broadens the definition and scope of OH- conductors.

Cerebral pseudoinfarction due to venoarterial extracorporeal membrane oxygenation: A case report.

BACKGROUND: Neurological complications are common in the management of venoarterial extracorporeal membrane oxygenation (VA-ECMO), with most patients requiring sedation and intubation, limiting the assessment of neurological function. There-fore, we must rely on advanced neuroimaging techniques, such as computed tomography angiography (CTA) and computed tomography perfusion (CTP). Because ECMO changes the normal blood flow pattern, it may interfere with the contrast medium in some special cases, leading to artifacts and ultimately mis-leading clinical decisions. CASE SUMMARY: A 61-year-old man presented to a local hospital with chest tightness and pain 1 d prior to presentation. The patient was treated with VA-ECMO after sudden car-diac and respiratory arrest at a local hospital. For further treatment, the patient was transferred to our hospital. The initial consciousness assessment was not clear, and routine CTP was performed to understand the intracranial changes, which suggested a large area of cerebral infarction on the right side; however, the cerebral oxygen was not consistent with the CTP results, and the reexamination of CTA still suggested a right cerebral infarction. To identify this difference, bedside transcranial Doppler was performed, and the blood flow on both sides was different. By reducing the ECMO flow, CTP reexamination showed that the results were normal and consistent with the clinical results. On day 3, the patient was alert and showed good limb movements. CONCLUSION: In patients with peripheral VA-ECMO, cerebral perfusion confirmed by CTP and CTA may lead to false cerebral infarction.

Biomass Solid-State Electrolyte with Abundant Ion and Water Channels for Flexible Zinc-Air Batteries.

Flexible zinc-air batteries are the leading candidates as the next-generation power source for flexible/wearable electronics. However, constructing safe and high-performance solid-state electrolytes (SSEs) with intrinsic hydroxide ion (OH-) conduction remains a fundamental challenge. Herein, by adopting the natural and robust cellulose nanofibers (CNFs) as building blocks, the biomass SSEs with penetrating ion and water channels are constructed by knitting the OH--conductive CNFs and water-retentive CNFs together via an energy-efficient tape casting. Benefiting from the abundant ion and water channels with interconnected hydrated OH- wires for fast OH- conduction under a nanoconfined environment, the biomass SSEs reveal the high water-uptake, impressive OH- conductivity of 175 mS cm-1 and mechanical robustness simultaneously, which overcomes the commonly existed dilemma between ion conductivity and mechanical property. Remarkably, the flexible zinc-air batteries assemble with biomass SSEs deliver an exceptional cycle lifespan of 310 h and power density of 126 mW cm-2. The design methodology for water and ion channels opens a new avenue to design high-performance SSEs for batteries.

Characterization of Potting Epoxy Resins Performance Parameters Based on a Viscoelastic Constitutive Model.

To describe the evolution of residual stresses in epoxy resin during the curing process, a more detailed characterization of its viscoelastic properties is necessary. In this study, we have devised a simplified apparatus for assessing the viscoelastic properties of epoxy resin. This apparatus employs a confining cylinder to restrict the circumferential and radial deformations of the material. Following the application of load by the testing machine, the epoxy resin sample gradually reduces the gap between its surface and the inner wall of the confining cylinder, ultimately achieving full contact and establishing a continuous interface. By recording the circumferential stress-strain on the outer surface of the confining cylinder, we can deduce the variations in material bulk and shear moduli with time. This characterization spans eight temperature points surrounding the glass transition temperature, revealing the bulk and shear relaxation moduli of the epoxy resin. Throughout the experiments, the epoxy resin's viscoelastic response demonstrated a pronounced time-temperature dependency. Below the glass transition temperature, the stress relaxation response progressively accelerated with increasing temperature, while beyond the glass transition temperature, the stress relaxation time underwent a substantial reduction. By applying the time-temperature superposition principle, it is possible to construct the relaxation master curves for the bulk and shear moduli of the epoxy resin. By fitting the data, we can obtain expressions for the constitutive model describing the viscoelastic behavior of the epoxy resin. In order to validate the reliability of the test results, a uniaxial tensile relaxation test was conducted on the epoxy resin casting body. The results show good agreement between the obtained uniaxial relaxation modulus curves and those derived from the bulk and shear relaxation modulus equations, confirming the validity of both the device design and the testing methodology.

Steric-hindrance Effect Tuned Ion Solvation Enabling High Performance Aqueous Zinc Ion Batteries.

Despite many additives have been reported for aqueous zinc ion batteries, steric-hindrance effect of additives and its correlation with Zn2+ solvation structure have been rarely reported. Herein, large-sized sucrose biomolecule is selected as a paradigm additive, and steric-hindrance electrolytes (STEs) are developed to investigate the steric-hindrance effect for solvation structure regulation. Sucrose molecules do not participate in Zn2+ solvation shell, but significantly homogenize the distribution of solvated Zn2+ and enlarge Zn2+ solvation shell with weakened Zn2+-H2O interaction due to the steric-hindrance effect. More importantly, STEs afford the water-shielding electric double layer and in situ construct the organic and inorganic hybrid solid electrolyte interface, which effectively boost Zn anode reversibility. Remarkably, Zn//NVO battery presents high capacity of 3.9 mAh ⋅ cm-2 with long cycling stability for over 650 cycles at lean electrolyte of 4.5 µL ⋅ mg-1 and low N/P ratio of 1.5, and the stable operation at wide temperature (-20 °C~+40 °C).

The N6-methyladenosine demethylase FTO is required for odontoblast differentiation in vitro and dentine formation in mice by promoting RUNX2 exon 5 inclusion through RBM4.

AIM: Fat mass and obesity-associated (FTO) protein, the first discovered N6-methyladenine (m6A) demethylase, played positive roles in bone formation. In this study, the aim was to investigate the function and potential mechanism of Fto in dentine formation. METHODOLOGY: In vivo model, postnatal 12-day (PN12), 4-week-old (4 wk), 6-week-old (6 wk) healthy male C57BL/6J were randomly divided into Fto knockout (Fto-/- ) mice and wild-type (WT) littermates according to their genotypes, with 3-5 mice in each group. The mandibles of Fto-/- mice and WT control littermates were isolated for analysis by micro-computed tomography (micro-CT), 3-dimensional reconstruction and Haematoxylin-eosin (HE) staining. In vitro, mouse dental papilla cells (mDPCs) and human dental stem pulp cells (hDPSCs) were cultured with odontogenetic medium to evaluate differentiation capacity; expression levels of odontoblastic related genes were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). The inclusion levels of Runt-related transcription factor 2 (RUNX2) exon 5 in mDPCs and hDPSCs were detected by semiquantitative real-time polymerase chain reaction (RT-PCR). The RNA binding motif protein 4 (RBM4) m6A site was verified through m6A methylated RNA immunoprecipitation (MeRIP) and the stability of RBM4 mRNA influenced by FTO knockdown was measured by mRNA stability assay. Differences with p values < .05 were regarded as statistically significant. RESULTS: We discovered that Fto-/- mice showed significant dentine formation defects characterized by widened pulp cavity, enlarged pulp-tooth volume ratio, thinned dentine and pre-dentine layer of root (p < .05). Fto-/- mDPCs and FTO-silencing hDPSCs not only exhibited insufficient mineralization ability and decreased expression levels of odontoblastic mineralization related genes (p < .05), but showed significantly reduced Runx2 exon 5 inclusion level (p < .05). FTO knockdown increased the m6A level of RBM4 and destabilized the mRNA of RBM4, thus contributing to the reduced RBM4 expression level. Moreover, Rbm4 overexpression in Fto-/- mDPCs can partly restore Runx2 exon 5 inclusion level and the differentiation ability disrupted by Fto knockout. CONCLUSION: Thus, within the limitations of this study, the data suggest that FTO promotes odontoblastic differentiation during dentine formation by stabilizing RBM4 mRNA to promote RUNX2 exon 5 inclusion.

ADP Ribosylation Factor 6 Relieves Airway Inflammation and Remodeling by Inhibiting Ovalbumin Induced-Epithelial Mesenchymal Transition in Experimental Asthma, Possibly by Regulating of E2F Transcription Factor 8.

BACKGROUND: Childhood asthma is a major global health concern. ADP-ribosylation factor 6 (ARF6) is a low-molecular-weight GTPase; however, its role in childhood asthma remains unclear. METHODS: Ovalbumin (OVA)-challenged neonatal mice and transforming growth factor-ß1 (TGF-ß1)-induced BEAS-2B cells were used as in vivo and in vitro models of childhood asthma, respectively. RESULTS: Upon OVA stimulation, ARF6 expression was upregulated in the lung tissue. Neonatal mice administered SehinH3 (an ARF6 inhibitor) exhibited improved pulmonary pathological injury, along with reduced inflammatory cell infiltration in the lungs and cytokine release in bronchial alveolar lavage fluid and serum (interleukin [IL]-3, IL-5, IL-13, IgE, and OVA-specific IgE). SehinH3 treatment restrained epithelial - mesenchymal transition (EMT) in the lungs of asthmatic mice, as evidenced by increased E-cadherin and decreased N-cadherin and α-smooth muscle actin expression. Different TGF-ß1 exposures to BEAS-2B cells induced a time- and dose-dependent increase in ARF6 expression in vitro. Upon TGF-ß1 stimulation, ARF6 knockdown repressed EMT and SehinH3 treatment caused similar results in BEAS-2B cells. The transcription factor E2F8 is involved in diverse biological functions and its increased expression was confirmed in vivo and in vitro. Dual-luciferase assays confirmed that E2F8 binds to the ARF6 promoter and promotes its transcriptional activity. In vitro results revealed that E2F8 silencing suppressed EMT, whereas rescue experiments showed that ARF6 overexpression partly reversed these phenomena. CONCLUSION: Our study showed that ARF6 is associated with childhood asthma progression and may be positively regulated by E2F8. These results provide insight into the pathogenesis and treatment of childhood asthma.

Cerebral Neural Changes in Venous-Arterial Extracorporeal Membrane Oxygenation Survivors.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is used as temporary cardiorespiratory support in patients with critical ailments, but very little is known about the functional cerebral changes in ECMO survivors. Degree centrality (DC), a graph-based assessment of network organization, was performed to explore the neural connectivity changes in ECMO survivors compared to controls and their correlation with cognitive and neurological measures. METHODS: This exploratory observational study was conducted from August 2020 to May 2022. ECMO survivors and controls underwent functional magnetic resonance imaging (fMRI) of the brain. We performed DC analysis to identify voxels that showed changes in whole-brain functional connectivity with other voxels. DC was measured by the fMRI graph method and comparisons between the two groups were performed. All participants underwent neuropsychological assessment (Montreal Cognitive Assessment, MoCA). Blood serum neuron-specific enolase and the Glasgow Coma Scale (GCS) were assessed in ECMO survivors. RESULTS: DC values in the right insula and right precuneus gyrus were lower in ECMO survivors and higher in the right medial superior frontal gyrus compared to controls (all p < 0.001). Decreased connectivity in the right insular and right precuneus gyrus correlated with total MoCA scores, delayed recollection, and calculation (all p < 0.05). Increased serum NSE levels, GCS score, and GCS-motor response correlated with decreased connectivity in the right insular and right precuneus gyrus and increased connectivity in the right medial superior frontal gyrus (all p < 0.05). CONCLUSIONS: We showed that both functional impairment and adaptation were observed in survivors of ECMO, suggesting that neural connectivity changes may provide insights into the mechanisms that may potentially link ECMO survivors to neurological and cognitive disorders.

Calcipotriol abrogates cancer-associated fibroblast-derived IL-8-mediated oxaliplatin resistance in gastric cancer cells via blocking PI3K/Akt signaling.

Activation of vitamin D receptor (VDR) in cancer-associated fibroblasts (CAFs) has been implicated in hesitating tumor progression and chemoresistance of several human malignancies. Yet, the role of VDR in CAF-induced chemotherapy resistance of gastric cancer (GC) cells remains elusive. In this study we first conducted immunohistochemistry analysis on tissue microarrays including 88 pairs of GC and normal mucosa samples, and provided clinical evidence that VDR was mainly expressed in gastric mucous cells but almost invisible in CAFs, and VDR expression was negatively correlated with malignant clinical phenotype and advanced stages, low VDR expression confers to poor overall survival rate of patients with GC. In a co-culture system of primary CAFs and cancer cells, we showed that treatment of HGC-27 and AGS GC cells with VDR ligand calcipotriol (Cal, 500 nM) significantly inhibited CAF-induced oxaliplatin resistance. By using RNA-sequencing and Human Cytokine Antibody Array, we demonstrated that IL-8 secretion from CAFs induced oxaliplatin resistance via activating the PI3K/AKT pathway in GC, whereas Cal treatment greatly attenuated the tumor-supportive effect of CAF-derived IL-8 on GC cells. Taken together, this study verifies the specific localization of VDR in GC tissues and demonstrates that activation of VDR abrogates CAF-derived IL-8-mediated oxaliplatin resistance in GC via blocking PI3K/Akt signaling, suggesting vitamin D supplementation as a potential strategy of enhancing the anti-tumor effect of chemotherapy in GC.

Dual-Scale Integration Design of Sn-ZnO Catalyst toward Efficient and Stable CO2 Electroreduction.

Electrochemical CO2 reduction to CO is a potential sustainable strategy for alleviating CO2 emission and producing valuable fuels. In the quest to resolve its current problems of low-energy efficiency and insufficient durability, a dual-scale design strategy is proposed by implanting a non-noble active Sn-ZnO heterointerface inside the nanopores of high-surface-area carbon nanospheres (Sn-ZnO@HC). The metal d-bandwidth tuning of Sn and ZnO alters the extent of substrate-molecule orbital mixing, facilitating the breaking of the *COOH intermediate and the yield of CO. Furthermore, the confinement effect of tailored nanopores results in a beneficial pH distribution in the local environment around the Sn-ZnO nanoparticles and protects them against leaching and aggregating. Through integrating electronic and nanopore-scale control, Sn-ZnO@HC achieves a quite low potential of -0.53 V vs reversible hydrogen electrode (RHE) with 91% Faradaic efficiency for CO and an ultralong stability of 240 h. This work provides proof of concept for the multiscale design of electrocatalysts.

Lightweight and Flexible Graphene Foam Composite with Improved Damping Properties.

As an elastomer, PDMS can effectively suppress vibration in various fields in a certain temperature range by its viscoelastic behavior in the vitrification transition region, but the vibration isolation effect is poor at high temperature. In this paper, a three-dimensional graphene oxide (GO) foam is fabricated by solution processing method and freeze-drying techniques. After sequential infiltration synthesis, a GO-foam-reinforced PDMS nanocomposite (GO/PDMS) is fabricated with improved damping ability. By adjusting the content of GO, the micros-tructure of GO foam can be sensitively changed, which is crucial to the damping properties of composites. In this paper, by the dynamic mechanical analysis (DMA) of pure PDMS and five kinds of GO/PDMS composites, it is proved that the GO/PDMS composites developed in this work have reliable elasticity and viscoelasticity at 25 °C, which is 100 °C higher than the applicable temperature of pure PDMS. The storage modulus can reach 3.58 MPa, and the loss modulus can reach 0.45 MPa, which are 1.87 times and 2.0 times of pure PDMS, respectively. This GO-based nanocomposite is an ideal candidate for damping materials in passive vibration isolation devices.

[The Role and Mechanism of Tfh and B Cell in Human Chronic Graft-Versus-Host-Disease].

AbstractObjective: To investigate the role and mechanism of circulating follicular helper T cells (cTfh), extrafollicular helper T cells, B cells and their subsets in chronic graft-versus-host disease (cGVHD) after transplantation. METHODS: Peripheral blood of cGVHD 64 patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital of Soochow University from 2016 to 2019 were collected. The percentage of cTfh cells, extrafollicular helper T cells, B cells and subsets were detected by flow cytometry. The healthy donors were detected as control. Percentage of each cell subpopulation between the two groups were compared by the two-tailed Students' T test. RESULTS: The percentage of circulating follicular helper T cells (cTfh, CD4+CXCR5+) was markedly decreased in patients with cGVHD as compared with that in the healthy donors (0.53%±0.10% vs 3.91%±0.60%, P<0.001). The percentage of extrafollicular helper T cells (CD44hiCD62LloPSGL-1loCD4+T) of the patients in cGVHD and the healthy donors were 8.86%±0.45% and 5.38%±0.79% (P=0.003). A significant change in B cell subsets was found in the patients with cGVHD. The two types of antigen-stimulate CD27+ B cell: the percentages of pre-GC B cells (CD19+IgD+CD38hiCD27+) and plasmablast/plasma cells (PB/PC, CD19+IgD-CD38hiCD27+) of patients with cGVHD were 20.91%±2.70% and 41.05%±5.00%, respectively, which were significantly higher than those in healthy donors (P=0.005, P=0.014). Meanwhile, the percentage of unstimulated CD27- B cells in patients with cGVHD was significantly reduced, especially the naive B cells (CD19+IgD+CD38loCD27-, 12.59%±2.63%, P=0.025). There was a positive correlation between the percentage of extrafollicular helper T cells and plasmablast/ plasma cells (PB/PC) in cGVHD patients (r=0.43). CONCLUSION: Compared with healthy donor, cTfh cells, extrafollicular helper T cells and B cell subsets in the peripheral blood of patients with cGVHD after transplantation changed in varying degress.

Molecular signatures of tumor progression in pancreatic adenocarcinoma identified by energy metabolism characteristics.

BACKGROUND: In this study, we performed a molecular evaluation of primary pancreatic adenocarcinoma (PAAD) based on the comprehensive analysis of energy metabolism-related gene (EMRG) expression profiles. METHODS: Molecular subtypes were identified by nonnegative matrix clustering of 565 EMRGs. An overall survival (OS) predictive gene signature was developed and internally and externally validated based on three online PAAD datasets. Hub genes were identified in molecular subtypes by weighted gene correlation network analysis (WGCNA) coexpression algorithm analysis and considered as prognostic genes. LASSO cox regression was conducted to establish a robust prognostic gene model, a four-gene signature, which performed better in survival prediction than four previously reported models. In addition, a novel nomogram constructed by combining clinical features and the 4-gene signature showed high-confidence clinical utility. According to gene set enrichment analysis (GSEA), gene sets related to the high-risk group participate in the neuroactive ligand receptor interaction pathway. CONCLUSIONS: In summary, EMRG-based molecular subtypes and prognostic gene models may provide a novel research direction for patient stratification and trials of targeted therapies.

Hierarchically Nanostructured Solid-State Electrolyte for Flexible Rechargeable Zinc-Air Batteries.

The construction of safe and environmentally-benign solid-state electrolytes (SSEs) with intrinsic hydroxide ion-conduction for flexible zinc-air batteries is highly desirable yet extremely challenging. Herein, hierarchically nanostructured CCNF-PDIL SSEs with reinforced concrete architecture are constructed by nanoconfined polymerization of dual-cation ionic liquid (PDIL, concrete) within a robust three-dimensional porous cationic cellulose nanofiber matrix (CCNF, reinforcing steel), where plenty of penetrating ion-conductive channels are formed and undergo dynamic self-rearrangement under different hydrated levels. The CCNF-PDIL SSEs synchronously exhibit good flexibility, mechanical robustness, superhigh ion conductivity of 286.5 mS cm-1 , and decent water uptake. The resultant flexible solid-state zinc-air batteries deliver a high-power density of 135 mW cm-2 , a specific capacity of 775 mAh g-1 and an ultralong cycling stability with continuous operation of 240 hours for 720 cycles, far outperforming those of the state-of-the-art solid-state batteries. The marriage of biomaterials with the diversity of ionic liquids creates enormous opportunities to construct advanced SSEs for solid-state batteries.

Population pharmacokinetics of polymyxin B: a systematic review.

Background: Polymyxin B (PMB) is a basic cyclic polypeptide antibiotic produced by Bacillus polymyxa, and is one of the last options for treating multi-drug-resistant negative bacterial infections in clinical practice. In recent years, many population pharmacokinetic studies of PMB have been conducted. This paper sought to comprehensively summarize the characteristics of population pharmacokinetic models of PMB and provide a theoretical basis for the individualized use of PMB. Methods: In this review, we systematically searched the PubMed and Embase databases to find articles on population pharmacokinetic models published from database establishment to August 2021. Results: A total of 10 studies were included in this review, including studies on various types of severe infections caused by multi-drug-resistant bacteria, hospital-acquired infections with fibrosis and other male and female populations, and a study of 2 continuous renal replacement therapy (CRRT) patients, aged 16-94 years, who received PMB doses of 10-360 mg/day (0.13-3.45 mg/kg/day), at an administration time of 0.5-6 hours. First-order linear elimination was used in all the studies; a 1-compartment model was used in 5 studies, and a 2-compartment model was used in 5 studies. The most common covariates were creatinine clearance (CrCL) and body weight. Discussion: Although these studies included several covariates and total clearance (CL) was close, but the external validation of some models was poorly correlated between the actual and predicted value. Novel or potential covariates represent important directions for further study.

Bioinspired Tough Solid-State Electrolyte for Flexible Ultralong-Life Zinc-Air Battery.

Manufacturing advanced solid-state electrolytes (SSEs) for flexible rechargeable batteries becomes increasingly important but remains grand challenge. The sophisticated structure of robust animal dermis and good water-retention of plant cell in nature grant germane inspirations for designing high-performance SSEs. Herein, tough bioinspired SSEs with intrinsic hydroxide ion (OH- ) conduction are constructed by in situ formation of OH- conductive ionomer network within a hollow-polymeric-microcapsule-decorated hydrogel polymer network. By virtue of the bioinspired design and dynamic dual-penetrating network structure, the bioinspired SSEs simultaneously obtain mechanical robustness with 1800% stretchability, good water uptake of 107 g g-1 and water retention, and superhigh ion conductivity of 215 mS cm-1 . The nanostructure of bioinspired SSE and related ion-conduction mechanism are revealed and visualized by molecular dynamics simulation, where plenty of compact and superfast ion-transport channels are constructed, contributing to superhigh ion conductivity. As a result, the flexible solid-state zinc-air batteries assembled with bioinspired SSEs witness high power density of 148 mW cm-2 , specific capacity of 758 mAh g-1 and ultralong cycling stability of 320 h as well as outstanding flexibility. The bioinspired methodology and deep insight of ion-conduction mechanism will shed light on the design of advanced SSEs for flexible energy conversion and storage systems.

Comprehensive molecular characterization and identification of prognostic signature in stomach adenocarcinoma on the basis of energy-metabolism-related genes.

BACKGROUND: Stomach adenocarcinoma (STAD) is a leading cause of cancer deaths, but its molecular and prognostic characteristics has never been fully illustrated. AIM: To describe a molecular evaluation of primary STAD and develop new therapies and identify promising prognostic signatures. METHODS: We describe a comprehensive molecular evaluation of primary STAD based on comprehensive analysis of energy-metabolism-related gene (EMRG) expression profiles. RESULTS: On the basis of 86 EMRGs that were significantly associated to patients' progression-free survival (PFS), we propose a molecular classification dividing gastric cancer into two subtypes: Cluster 1, most of which are young patients and display more immune and stromal cell components in tumor microenvironment and lower tumor priority; and Cluster 2, which show early stages and better PFS. Moreover, we construct a 6-gene signature that can classify the prognostic risk of patients after a three-phase training test and validation process. Compared with patients with low-risk score, patients with high-risk score had shorter overall survival. Furthermore, calibration and DCA analysis plots indicate the excellent predictive performance of the 6-gene signature, and which present higher robustness and clinical usability compared with three previous reported prognostic gene signatures. According to gene set enrichment analysis, gene sets related to the high-risk group were participated in the ECM receptor interaction and hedgehog signaling pathway. CONCLUSION: Identification of the EMRG-based molecular subtypes and prognostic gene model provides a roadmap for patient stratification and trials of targeted therapies.

A Lipid Metabolism-Based Seven-Gene Signature Correlates with the Clinical Outcome of Lung Adenocarcinoma.

BACKGROUND: Herein, we tried to develop a prognostic prediction model for patients with LUAD based on the expression profiles of lipid metabolism-related genes (LMRGs). METHODS: Molecular subtypes were identified by non-negative matrix factorization (NMF) clustering. The overall survival (OS) predictive gene signature was developed and validated internally and externally based on online data sets. Time-dependent receiver operating characteristic (ROC) curve, Kaplan-Meier curve, nomogram, restricted mean survival time (EMST), and decision curve analysis (DCA) were used to assess the performance of the gene signature. RESULTS: We identified three molecular subtypes in LUAD with distinct characteristics on immune cells infiltration and clinical outcomes. Moreover, we confirmed a seven-gene signature as an independent prognostic factor for patients with LUAD. Calibration and DCA analysis plots indicated the excellent predictive performance of the prognostic nomogram constructed based on the gene signature. In addition, the nomogram showed higher robustness and clinical usability compared with four previously reported prognostic gene signatures. CONCLUSIONS: Findings in the present study shed new light on the characteristics of lipid metabolism within LUAD, and the established seven-gene signature can be utilized as a new prognostic marker for predicting survival in patients with LUAD.

DUBR suppresses migration and invasion of human lung adenocarcinoma cells via ZBTB11-mediated inhibition of oxidative phosphorylation.

Long noncoding RNAs (lncRNAs) are involved in a variety of cancers, but the role of LncRNA DUBR in lung adenocarcinoma (LUAD), the most prevalent form of lung cancer, remains unclear. In this study we investigated the expression of DUBR in LUAD to ascertain its association with the clinical pathology and prognosis of LUAD. Analysis of mRNA expression in The Cancer Genome Atlas (TCGA) LUAD database and in-house LUAD cohort (n = 94) showed that DUBR was significantly downregulated in LUAD, and was associated with poor prognosis. In LUAD cell lines (H1975, A549), overexpression of DUBR significantly suppressed the migration and invasion of the LUAD cells. We demonstrated that c-Myc could bind to the promoter of DUBR, and transcriptionally suppressed its expression. Knockdown of c-Myc almost completely blocked the invasion and migration of LUAD cells, whereas knockdown of DUBR partially rescued c-Myc-knockdown suppressed cell migration and invasion. Furthermore, DUBR overexpression significantly increased the expression of a downstream protein of DUBR, zinc finger, and BTB domain containing 11 (ZBTB11), in H1975 and A549 cells; knockdown of ZBTB11 partially rescued the DUBR-overexpression suppressed cell migration and invasion; knockdown of c-Myc significantly upregulated the expression of ZBTB11 in LUAD cells. Finally, we revealed that DUBR/ZBTB11 axis suppressed oxidative phosphorylation in LUAD cells. In short, we demonstrate that c-Myc/DUBR/ZBTB11 axis suppresses migration and invasion of LUAD by attenuating cell oxidative phosphorylation, which provides new insights into the regulatory mechanism of DUBR.

Tempering governs the milk fat crystallisation and viscoelastic behaviour of unprocessed and homogenised creams.

The crystallisation behaviour of milk fat plays an important role in the functionality and sensory properties of fat-rich dairy products. In this study, we investigated the impact of tempering to 25 °C on the viscoelastic properties, particle size and thermal behaviour of 20% w/w unprocessed and homogenised creams prepared from bovine milk. The crystallisation properties were examined by synchrotron X-ray diffraction (XRD) at small (SAXS) and wide angle (WAXS) and differential scanning calorimetry (DSC). Oscillation rheology was performed to characterise the cream's viscoelastic properties. Homogenisation (35 MPa) reduced the average droplet size from 4.4 to 1.3 µm. After 24 h storage at 4 °C, milk fat structures showed triacylglycerol (TAG) 2L and 3L(001, 002, 003, 005) lamellar stacking orders associated predominantly with the α and ß' polymorphic forms. Tempering to 25 °C induced the complete melting of the 3L crystals and led to an irreversible loss in the elastic modulus (G') and a reduction in the viscous modulus (G'') once returned to refrigerated conditions, due to changes in the particle-particle interactions and structure of the reformed milk fat crystals. The results demonstrate that crystallisation behaviour of milk fat is influenced by droplet size and the rearrangement of triacylglycerol (TAG) upon tempering, and lead to changes in the viscoelastic behaviour of dairy products containing a high level of milk fat.